A New Species of the Anastrepha pseudoparallela Group (Diptera: Tephritidae) with a Synopsis of the Group in Brazil.

The genus Anastrepha contains some of the most important fruit pests in the Americas. It comprises more than 300 species, of which 129 occur in Brazil. The genus is divided into 26 species groups, including the pseudoparallela group with 31 species, whose known host plants are primarily fruits of the genus Passiflora (Passifloraceae). Fourteen species are recorded in Brazil. Here, a new species of Anastrepha reared from fruits of Passiflora actinia Hook. and Passiflora elegans Mast. from southern Brazil is described and illustrated. In addition, a synopsis of the Brazilian species of the pseudoparallela group is provided.

Rickettsia asembonensis Isolated from Four Human Cases with Acute Undifferentiated Febrile Illness in Peru.

Rickettsioses, often underreported, pose public health challenges. Rickettsia asembonensis is a potential emerging pathogen that was previously detected in humans, animals, and a variety of arthropods. While its pathogenicity in humans remains unclear, it poses a potential public health threat. Here, we present an extended epidemiological, diagnostic, and genetic analysis of the information provided in a preliminary report on the investigation of rickettsiae in Peru. In particular, we report the detection of R. asembonensis in blood specimens collected from four human patients with an acute undifferentiated fever of a seven- to nine-day duration, all of whom tested negative for other vector-borne pathogens. Additionally, we describe the replicative capacity of the R. asembonensis isolates in cell cultures.

Intraoperative Ultrasound for the Management of Oral Tongue Cancer: a Systematic Review and Meta-Analysis.

Objective: To evaluate for correlation between intraoperative ultrasound (IOUS)-measured tumor thickness (TT) (uTT) and histopathological TT (hTT), and to compare IOUS-assisted resection with conventional resection in patients with oral tongue cancers. Data Sources: Ovid MEDLINE (1946-2023), Embase.com (1947-2023), and Web of Science (All Databases 1900-2023). Review Methods: Inclusion criteria were the use of IOUS for the management of oral tongue cancer. Studies that did not report quantitative data were excluded. Additionally, studies that were not contributory to meta-analysis, or a narrative analysis of pooled results were excluded. Selection was carried out by 2 reviewers. A total of 2417 studies were initially identified, with 12 ultimately being included in this review, and 7 included in the meta-analysis. Data were extracted by 2 investigators and were pooled using a random-effects model. Results: Our meta-analysis reveals a pooled correlation coefficient of 0.92 (95% confidence interval: 0.80-0.96) for studies comparing uTT to hTT. Studies comparing IOUS-assisted resection to conventional resection found IOUS-assisted resection yielded wider nearest margins in all studies reporting this outcome. Conclusion: IOUS reliably measures TT, similarly to that of histopathology measurement. IOUS-assisted resection, which allows the surgeon to view the deep extent of tumor invasion, may increase closest radial margin distance compared to conventional resection. IOUS-assisted resection may represent a more reliable approach to achieving clear margins than conventional resection.

Using Separate Single-Outcome Risk Presentations Instead of Integrated Multioutcome Formats Improves Comprehension in Discrete Choice Experiments.

INTRODUCTION: Despite decades of research on risk-communication approaches, questions remain about the optimal methods for conveying risks for different outcomes across multiple time points, which can be necessary in applications such as discrete choice experiments (DCEs). We sought to compare the effects of 3 design factors: 1) separated versus integrated presentations of the risks for different outcomes, 2) use or omission of icon arrays, and 3) vertical versus horizontal orientation of the time dimension. METHODS: We conducted a randomized study among a demographically diverse sample of 2,242 US adults recruited from an online panel (mean age 59.8 y, s = 10.4 y; 21.9% African American) that compared risk-communication approaches that varied in the 3 factors noted above. The primary outcome was the number of correct responses to 12 multiple-choice questions asking survey respondents to identify specific numbers, contrast options to recognize dominance (larger v. smaller risks), and compute differences. We used linear regression to test the effects of the 3 design factors, controlling for health literacy, graph literacy, and numeracy. We also measured choice consistency in a subsequent DCE choice module. RESULTS: Mean comprehension varied significantly across versions (P < 0.001), with higher comprehension in the 3 versions that provided separated risk information for each risk. In the multivariable regression, separated risk presentation was associated with 0.58 more correct responses (P < 0.001; 95% confidence interval: 0.39, 0.77) compared with integrated risk information. Neither providing icon arrays nor using vertical versus horizontal time formats affected comprehension rates, although participant understanding did correlate with DCE choice consistency. CONCLUSIONS: In presentations of multiple risks over multiple time points, presenting risk information separately for each health outcome appears to increase understanding. HIGHLIGHTS: When conveying information about risks of different outcomes at multiple time points, separate presentations of single-outcome risks resulted in higher comprehension than presentations that combined risk information for different outcomes.We also observed benefits of presenting single-outcome risks separately among respondents with lower numeracy and graph literacy.Study participants who scored higher on risk understanding were more internally consistent in their responses to a discrete choice experiment.

Utility of bioselection with neoadjuvant chemotherapy for organ preservation in patients with T4 laryngeal cancer.

BACKGROUND: Neoadjuvant chemotherapy for induction selection of definitive treatment (IS) protocols have shown excellent outcomes for organ preservation and survival in patients with T3 laryngeal squamous cell carcinoma (LSCC). We seek to evaluate survival and organ preservation outcomes in T4 LSCC patients treated with IS protocols. METHODS: Retrospective cohort of advanced T3 and T4 LSCC patients who underwent IS protocols based upon potential for preserving a functional larynx. Patients received one neoadjuvant cycle of platinum-based chemotherapy with either 5-fluorouracil or docetaxel or with two cycles of platinum-based chemotherapy with docetaxel and a Bcl-2 inhibitor. Patients who achieved ≥ 50 % response as determined by radiographic review and/or endoscopic evaluation received definitive chemoradiation. Patients who had < 50 % response after IS underwent total laryngectomy (TL) followed by post-operative radiation +/- chemotherapy. RESULTS: Amongst T4 patients, 114 met inclusion criteria including 89 who underwent IS protocols and 25 who received an upfront TL. In total, 76.0 % of T3 patients and 71.9 % of T4 patients responded to IS and underwent definitive chemoradiation. There was no significant difference in hazard of death between T4 IS and T4 TL patients (HR: 0.9, p = 0.86). Among responders, there was no significant difference in 5-year laryngectomy-free survival (T3 - 59.6 %, T4 44.3 %, p = 0.15) or laryngeal preservation by T stage (T3 - 72.8 %, T4 - 73.0 %, p = 0.84). CONCLUSIONS: Select T4 patients may benefit from organ preservation using IS protocols with similar response rates to patients with T3 tumors, without compromising survival when compared to upfront TL.

Characterization of the MSAP Flap in Head and Neck Surgical Oncology: A 3D Cadaveric Study.

OBJECTIVES: The medial sural artery (MSA) perforator flap is a versatile free flap. However, the cutaneous perforators are not well characterized. The objectives of this pilot anatomical study were to: (1) visualize in three-dimensions, as in-situ, the origin, course, and distribution of the cutaneous perforators, (2) characterize the number and frequency of the perforators, and (3) quantify mean pedicle length. METHODS: Thirteen cadaveric specimens were dissected, digitized, and modeled in 3D. Three-dimensional models and dissection photographs were used to determine the origin, course, number, distribution, and pedicle length of MSA perforators. RESULTS: The most common pattern consisted of three perforators (39% of specimens). The maximum number of perforators identified was four (23%). The majority of specimens (92%) had a cutaneous perforator originating from the lateral branch of the MSA and coursed most frequently in the second (43%) and third (37%) quartiles of the length of the tibia. Mean pedicle length was 19.1 ± 6.9 cm. Perforators originating from the medial branch of the MSA were significantly (p < 0.05) shorter than those from the lateral branch and were found to course only in the first quartile. CONCLUSION: The 3D models constructed in this study provide a comprehensive overview of the location and course of the perforators, enabling measurement of parameters in 3D-space. Anatomical characterization of the MSA perforator flap using 3D analysis can assist reconstructive surgeons in understanding the relevant anatomy and optimizing the surgical technique for flap harvest. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Stronger interspecific sexual differences may be favored when females search for mates in the presence of congeners.

Why are some species sexually dimorphic while other closely related species are not? While all females in genus Strauzia share a multiply-banded wing pattern typical of many other true fruit flies, males of four species have noticeably elongated wings with banding patterns "coalesced" into a continuous dark streak across much of the wing. We take an integrative phylogenetic approach to explore the evolution of this dimorphism and develop general hypotheses underlying the evolution of wing dimorphism in flies. We find that the origin of coalesced and other darkened male wing patterns correlate with the inferred origin of host plant sharing in Strauzia. While wing shape among non-host-sharing species tended to be conserved across the phylogeny, shapes of male wings for Strauzia species sharing the same host plant were more different from one another than expected under Brownian models of evolution and overall rates of wing shape change differed between non-host-sharing species and host-sharing species. A survey of North American Tephritidae finds just three other genera with specialist species that share host plants. Host-sharing species in these genera also have wing patterns unusual for each genus. Only genus Eutreta is like Strauzia in having the unusual wing patterns only in males, and of genera that have multiple species sharing hosts, only in Eutreta and Strauzia do males hold territories while females search for mates. We hypothesize that in species that share host plants, those where females actively search for males in the presence of congeners may be more likely to evolve sexually dimorphic wing patterns.

Understanding pathways from implementation to sustainment: a longitudinal, mixed methods analysis of promising practices implemented in the Veterans Health Administration.

BACKGROUND: The Veterans Health Administration (VHA) is the United States largest learning health system. The Diffusion of Excellence (DoE) program is a large-scale model of diffusion that identifies and diffuses evidence-informed practices across VHA. During the period of 2016-2021, 57 evidence-informed practices were implemented across 82 VHA facilities. This setting provides a unique opportunity to understand sustainment determinants and pathways. Our objective was to characterize the longitudinal pathways of practices as they transition from initial implementation to long-term sustainment at each facility. METHODS: A longitudinal, mixed-methods evaluation of 82 VHA facilities. Eighty-two facility representatives, chosen by leadership as points-of-contact for 57 DoE practices, were eligible for post-implementation interviews and annual sustainment surveys. Primary outcomes (implementation, sustainment), and secondary outcomes (institutionalization, effectiveness, anticipated sustainment) at four time-points were collected. We performed descriptive statistics and directed content analysis using Hailemariam et al.'s factors influencing sustainment. RESULTS: After approximately five years post-implementation (e.g., 2021 sustainment outcomes), of the 82 facilities, about one-third fully sustained their practice compared to one-third that did not fully sustain their practice because it was in a "liminal" stage (neither sustained nor discontinued) or permanently discontinued. The remaining one-third of facilities had missing 2021 sustainment outcomes. A higher percentage of facilities (70%) had inconsistent primary outcomes (changing over time) compared to facilities (30%) with consistent primary outcomes (same over time). Thirty-four percent of facilities with sustained practices reported resilience since they overcame implementation and sustainment barriers. Facilities with sustained practices reported more positive secondary outcomes compared to those that did not sustain their practice. Key factors facilitating practice sustainment included: demonstrating practice effectiveness/benefit, sufficient organizational leadership, sufficient workforce, and adaptation/alignment with local context. Key factors hindering practice sustainment included: insufficient workforce, not able to maintain practice fidelity/integrity, critical incidents related to the COVID-19 pandemic, organizational leadership did not support sustainment of practice, and no ongoing support. CONCLUSIONS: We identified diverse pathways from implementation to sustainment, and our data underscore that initial implementation outcomes may not determine long-term sustainment outcomes. This longitudinal evaluation contributes to understanding impacts of the DoE program, including return on investment, achieving learning health system goals, and insights into achieving high-quality healthcare in VHA.

Height Restrictions for Dual-energy X-ray Absorptiometry: What Are Our Options for Body Composition and Bone Health Precision?

ABSTRACT: Redinger, AL, Russell, JL, Allen, SMF, and Baker, BS. Height restrictions for dual-energy X-ray absorptiometry: what are our options for body composition and bone health precision? J Strength Cond Res 38(7): e359-e365, 2024-Dual-energy X-ray absorptiometry (DXA) is commonly used for testing athlete's body composition, but many athletes are too tall. The first aim was to assess the viability of combining upper- and lower-body regions of interest (ROI), creating a combined scan for tall athletes who do not fit on the table and second, to provide practical solutions to DXA users who routinely scan tall athletes. Sixty subjects (34.8 ± 11.9 years; 171 ± 9 cm) completed 2 total-body DXA scans for baseline precision testing, using GE Lunar Prodigy (LP) or Hologic Horizon A (HA) models. Next, an upper body ROI from the skull to the distal femoral condyles was combined with a flipped scan (feet-to-head) ROI encompassing the proximal tibial plateau to the distal foot. Soft and bone tissue coefficient of variance (CV%) were calculated between the baseline scans and for the newly combined ROI scan. The combined ROI scan added 0.25-0.63% and 0.01-4.35% error rates for the LP and HA, respectively. An exploratory assessment of a GE Lunar iDXA demonstrated results similar to the HA with 4%+ error. The combined ROI scan is a user-friendly and precise method for older LP systems adding less than 1% error; however, newer DXA systems cannot use the stitched scan technique. Coaches and practitioners who use newer DXAs must prioritize consistently using the same boney landmarks (head, jaw, or feet) and ROI heights to provide precise longitudinal assessments of tall athletes' bone and body composition, until larger DXA tables become available.

A proof of concept for a targeted enrichment approach to the simultaneous detection and characterization of rickettsial pathogens from clinical specimens.

Infection with either Rickettsia prowazekii or Orientia tsutsugamushi is common, yet diagnostic capabilities are limited due to the short window for positive identification. Until now, although targeted enrichment had been applied to increase sensitivity of sequencing-based detection for various microorganisms, it had not been applied to sequencing of R. prowazekii in clinical samples. Additionally, hybridization-based targeted enrichment strategies had only scarcely been applied to qPCR of any pathogens in clinical samples. Therefore, we tested a targeted enrichment technique as a proof of concept and found that it dramatically reduced the limits of detection of these organisms by both qPCR and high throughput sequencing. The enrichment methodology was first tested in contrived clinical samples with known spiked-in concentrations of R. prowazekii and O. tsutsugamushi DNA. This method was also evaluated using clinical samples, resulting in the simultaneous identification and characterization of O. tsutsugamushi directly from clinical specimens taken from sepsis patients. We demonstrated that the targeted enrichment technique is helpful by lowering the limit of detection, not only when applied to sequencing, but also when applied to qPCR, suggesting the technique could be applied more broadly to include other assays and/or microbes for which there are limited diagnostic or detection modalities.

Correlation research demonstrates that an inflammatory diet is a risk factor for calcium oxalate renal stone formation.

BACKGROUND AND AIMS: Previous studies have demonstrated associations between the Dietary Inflammatory Index (DII®), an analytical tool which evaluates the inflammatory potential of the diet according to the pro- and anti-inflammatory properties of its components, and renal stone formation. However, these have not comprehensively addressed important parameters such as stone type, gender, DII scores in stone formers (SFs) and healthy controls (Cs) and associations of DII with urine and blood chemistries. These were adopted as the survey parameters for the present study, the purpose of which was to test whether the contributory role of an inflammatory diet on stone formation could be further confirmed. METHODS: 97 calcium oxalate (CaOx) SFs and 63 Cs, matched for age and gender each completed a semi-quantitative food frequency questionnaire from which nutrient composition was computed. These data were used to calculate the DII® score. To control the effect of energy intake, energy-adjusted DII scores were calculated per 1000 kcal consumed (E-DII™). A single blood sample and two consecutive overnight (8h) urine samples were collected from a subset (n = 59 SFs and n = 54 Cs) of the overall number of particpants (n = 160). These were analysed for renal stone risk factors. Data were analysed using regression models fit in R software. RESULTS: E-DII scores were found to fit the data better than DII, so they were used throughout. E-DII scores were significantly more positive (more pro-inflammatory) in SFs than in controls in the combined gender group (-0.34 vs. -1.73, p < 0.0001) and separately in males (-0.43 vs. -1.78, p = 0.01) and females (-0.26 vs. - 1.61, p = 0.05). In blood, a significant negative correlation was seen between E-DII and HDL cholesterol. In urine significant positive correlations were seen between E-DII and each of calcium (ρ = 0.25, p = 0.02), phosphate (ρ = 0.48, p < 0.001), magnesium (ρ = 0.33, p < 0.0001) and uric acid (ρ = 0.27, p = 0.004) concentrations. A significant negative correlation was seen between E-DII and urinary volume ρ = -0.27, p = 0.003). There was no correlation between E-DII scores and the relative supersaturations of urinary CaOx, calcium phosphate (brushite) and uric acid. CONCLUSIONS: Our findings provide hitherto unreported quantitative evidence in support of the notion that the diet of calcium oxalate renal stone patients is significantly more pro-inflammatory than that of healthy controls.

Modified FOLFOX6 plus bevacizumab with and without nivolumab for first-line treatment of metastatic colorectal cancer: phase 2 results from the CheckMate 9X8 randomized clinical trial.

BACKGROUND: Standard first-line therapies for metastatic colorectal cancer (mCRC) include fluoropyrimidine-containing regimens with oxaliplatin and/or irinotecan and a biologic agent. Immunotherapy may enhance antitumor activity in combination with standard therapies in patients with mCRC. Here, we present phase 2 results of nivolumab plus standard-of-care therapy (SOC; 5-fluorouracil/leucovorin/oxaliplatin/bevacizumab) versus SOC in the first-line treatment of patients with mCRC (CheckMate 9X8). METHODS: CheckMate 9X8 was a multicenter, open-label, randomized, phase 2/3 trial. Eligible patients were at least 18 years of age with unresectable mCRC and no prior chemotherapy for metastatic disease. Patients were randomized 2:1 to receive nivolumab 240 mg plus SOC or SOC alone every 2 weeks. The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors V.1.1. Secondary endpoints included PFS by investigator assessment; objective response rate (ORR), disease control rate, duration of response, and time to response, all by BICR and investigator assessments; overall survival; and safety. Preplanned exploratory biomarker analyses were also performed. RESULTS: From February 2018 through April 2019, 310 patients were enrolled, of which 195 patients were randomized to nivolumab plus SOC (n=127) or SOC (n=68). At 21.5-month minimum follow-up, PFS with nivolumab plus SOC versus SOC did not meet the prespecified threshold for statistical significance; median PFS by BICR was 11.9 months in both arms (HR, 0.81 (95% CI, 0.53 to 1.23); p=0.30). Higher PFS rates after 12 months (18 months: 28% vs 9%), higher ORR (60% vs 46%), and durable responses (median 12.9 vs 9.3 months) were observed with nivolumab plus SOC versus SOC. Grade 3-4 treatment-related adverse events were reported in 75% versus 48% of patients; no new safety signals were identified. CONCLUSIONS: The CheckMate 9X8 trial investigating first-line nivolumab plus SOC versus SOC in patients with mCRC did not meet its primary endpoint of PFS by BICR. Nivolumab plus SOC showed numerically higher PFS rates after 12 months, a higher response rate, and more durable responses compared with SOC alone, with acceptable safety. Further investigation to identify subgroups of patients with mCRC that may benefit from nivolumab plus SOC versus SOC in the first-line setting is warranted. TRIAL REGISTRATION NUMBER: NCT03414983.

Use of the spider limb positioner for fibular free flap reconstruction of head and neck bony defects.

BACKGROUND: Osseous and osteocutaneous fibular free flaps are the workhorse of maxillomandibular reconstruction over 30 years after the initial description. Since 2019, we have routinely used the Spider Limb Positioner, adapted from its use in shoulder orthopedic procedures, for fibular free flap harvest. Herein, we describe this novel technique in our cohort. METHODS: We describe our intraoperative setup and endorse the versatility and utility of this technique in comparison to other reported fibular free flap harvest techniques. RESULTS: The Spider Limb Positioner was used 61 times in 60 different patients to harvest osseous or osteocutaneous fibular free flaps. Median (range) tourniquet time for flap harvest was 90 (40-124) minutes. No iatrogenic nerve compression injuries or complications related to lower extremity positioning occurred. CONCLUSION: We describe a novel approach to fibular free flap harvest utilizing the Spider Limb Positioner, which affords optimal ergonomics, visibility, and patient repositioning. There were no nerve injuries or complications related to positioning in our series.

Multi-strain probiotic improves subjective sleep quality with no impact on body composition, hemodynamics, and physical activity.

The objective of the study was to examine the impact of a multi-strain probiotic (MSP) on sleep, physical activity, and body composition changes. We used a randomised, double-blind, placebo-controlled approach with 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented daily with MSP (4 × 109 live cells Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04; Probiotical S.p.A., Novara, Italy) or placebo (PLA). In response to supplementation (after 0, 2, 4, and 6 weeks of supplementation) and 3 weeks after stopping supplementation, participants had subjective (Pittsburgh Sleep Quality Index, PSQI) and objective sleep indicators, body composition, daily physical activity and resting hemodynamics assessed. Subjective sleep quality indicators using the PSQI (sleep latency, sleep disturbance, and global PSQI score) improved ( P < 0.05) at various time points with MSP supplementation. Systolic blood pressure in PLA increased ( P < 0.05) after 6 weeks of supplementation with no change in MSP. No changes ( P > 0.05) in sleep (hours asleep, minutes awake, number of times awake) or physical activity (step count, minutes of sedentary activity, total active minutes) metrics assessed by the wearable device were observed. Additionally, no changes in resting heart rate, diastolic blood pressure, and body composition were discerned. In conclusion, MSP supplementation improved the subjective ability to fall asleep faster and disturbances experienced during sleep, which resulted in improved overall sleep quality as assessed by the PSQI. No differences in other sleep indicators, physical activity, hemodynamics, and body composition were observed during or following MSP supplementation. Registered at clinicaltrials.gov: NCT05343533.

The association between influenza vaccination uptake and influenza and pneumonia-associated deaths in the United States.

BACKGROUND: The influenza mortality burden has remained substantial in the United States (US) despite relatively high levels of influenza vaccine uptake. This has led to questions regarding the effectiveness of the program against this outcome, particularly in the elderly. The aim of this evaluation was to develop and explore a new approach to estimating the population-level effect of influenza vaccination uptake on pneumonia and influenza (P&I) associated deaths. METHODS: Using publicly available data we examined the association between state-level influenza vaccination and all-age P&I associated deaths in the US from the 2013-2014 influenza season to the 2018-2019 season. In the main model, we evaluated influenza vaccine uptake in all those age 6 months and older. We used a mixed-effects regression analysis with generalised least squares estimation to account for within state correlation in P&I mortality. RESULTS: From 2013-2014 through 2018-2019, the total number of all-age P&I related deaths during the influenza seasons was 480,111. The mean overall cumulative influenza vaccine uptake (age 6 months and older) across the states and years considered was 46.7%, with higher uptake (64.8%) observed in those aged ≥ 65 years. We found that overall influenza vaccine uptake (6 months and older) had a statistically significant protective association with the P&I death rate. This translated to a 0.33 (95% CI: 0.20, 0.47) per 100,000 population reduction in P&I deaths in the influenza season per 1% increase in overall influenza vaccine uptake. DISCUSSION: These results using a population-level statistical approach provide additional support for the overall effectiveness of the US influenza vaccination program. This reassurance is critical given the importance of ensuring confidence in this life saving program. Future research is needed to expand on our approach using more refined data.

A 13.2 mg epinephrine intranasal spray demonstrates comparable pharmacokinetics, pharmacodynamics, and safety to a 0.3 mg epinephrine autoinjector.

Background: Recent acute anaphylaxis guideline updates have identified remaining unmet needs based on currently available therapeutic options as a critical focus. Objective: We compared the pharmacokinetic, pharmacodynamic, safety, and tolerability profiles of intranasal epinephrine with intramuscular epinephrine administered by autoinjector and manual syringe. Methods: An open-label, 3-period crossover study was conducted in 116 healthy adult volunteers to assess the bioavailability of a single 13.2 mg intranasal dose of epinephrine compared to a 0.3 mg intramuscular autoinjector and a 0.5 mg manual syringe. Patients with epinephrine concentrations of 50, 100, and 200 pg/mL at 10, 20, 30, and 60 minutes after dosing were also evaluated. Results: Pharmacokinetic parameters for the 13.2 mg intranasal dose exceeded those of the 0.3 mg autoinjector with a rapid and higher maximum observed concentration (intranasal, 429.4 pg/mL; autoinjector, 328.6 pg/mL) and greater systemic exposure (AUC0-360; intranasal, 39,060 pg∙min/mL; autoinjector, 17,440 pg∙min/mL). Similar results were observed compared to the 0.5 mg manual syringe. Pharmacokinetic parameters for opposite-nostril and same-nostril dosing were higher than both intramuscular doses, except time to reach maximum observed concentration, which was bracketed between the 2 intramuscular doses (intranasal opposite and same nostril, 20 minutes; autoinjector, 14.9 minutes; manual syringe, 45 minutes). Similar effects on blood pressure and heart rate were observed for intranasal and autoinjector administration. Intranasal epinephrine was safe and well tolerated. No serious or unexpected adverse events were reported, confirming results from earlier clinical studies. Conclusions: Bidose epinephrine spray addresses the unmet medical and patient needs for a needle-free, convenient, and effective dose-delivery system for self-administration of epinephrine that is as good as or better than the 0.3 mg autoinjector.

First Molecular Identification of Rickettsia aeschlimannii and Rickettsia africae in Ticks from Ghana.

The threats from vector-borne pathogens transmitted by ticks place people (including deployed troops) at increased risk for infection, frequently contributing to undifferentiated febrile illness syndromes. Wild and domesticated animals are critical to the transmission cycle of many tick-borne diseases. Livestock can be infected by ticks, and serve as hosts to tick-borne diseases such as rickettsiosis. Thus, it is necessary to identify the tick species and determine their potential to transmit pathogens. A total of 1,493 adult ticks from three genera-Amblyomma, Hyalomma, and Rhipicephalus-were identified using available morphological keys and were pooled (n = 541) by sex and species. Rickettsia species were detected in 308 of 541 (56.9%) pools by genus-specific quantitative polymerase chain reaction assay (Rick17b). Furthermore, sequencing of the outer membrane protein A and B genes (ompA and ompB) of random samples of Rickettsia-positive samples led to the identification of Rickettsia aeschlimannii and Rickettsia africae with most R. africae DNA (80.2%) detected in pools of Amblyomma variegatum. We report the first molecular detection and identification of the rickettsial pathogens R. africae and R. aeschlimannii in ticks from Ghana. Our findings suggest there is a need to use control measures to prevent infections from occurring among human populations in endemic areas in Ghana. This study underscores the importance of determining which vector-borne pathogens are in circulation in Ghana. Further clinical and prevalence studies are needed to understand more comprehensively the clinical impact of these rickettsial pathogens contributing to human disease and morbidity in Ghana.

Evaluation of potential biomarkers for lenvatinib plus pembrolizumab among patients with advanced endometrial cancer: results from Study 111/KEYNOTE-146.

BACKGROUND: Lenvatinib plus pembrolizumab demonstrated clinically meaningful benefit in patients with previously treated advanced endometrial carcinoma in Study 111/KEYNOTE-146 (NCT02501096). In these exploratory analyses from this study, we evaluated the associations between clinical outcomes and gene expression signature scores and descriptively summarized response in biomarker subpopulations defined by tumor mutational burden (TMB) and DNA variants for individual genes of interest. METHODS: Patients with histologically confirmed metastatic endometrial carcinoma received oral lenvatinib 20 mg once daily plus intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles. Archived formalin-fixed paraffin-embedded tissue was obtained from all patients. T-cell-inflamed gene expression profile (TcellinfGEP) and 11 other gene signatures were evaluated by RNA sequencing. TMB, hotspot mutations in PIK3CA (oncogene), and deleterious mutations in PTEN and TP53 (tumor suppressor genes) were evaluated by whole-exome sequencing (WES). RESULTS: 93 and 79 patients were included in the RNA-sequencing-evaluable and WES-evaluable populations, respectively. No statistically significant associations were observed between any of the RNA-sequencing signature scores and objective response rate or progression-free survival. Area under the receiver operating characteristic curve values for response ranged from 0.39 to 0.54; all 95% CIs included 0.50. Responses were seen regardless of TMB (≥175 or <175 mutations/exome) and mutation status. There were no correlations between TcellinfGEP and TMB, TcellinfGEP and microvessel density (MVD), or MVD and TMB. CONCLUSIONS: This analysis demonstrated efficacy for lenvatinib plus pembrolizumab regardless of biomarker status. Results from this study do not support clinical utility of the evaluated biomarkers. Further investigation of biomarkers for this regimen is warranted. TRIAL REGISTRATION NUMBER: NCT02501096.

Implementation of Direct-to-Patient Mobile Teledermatology in VA.

BACKGROUND: Innovative technology can enhance patient access to healthcare but must be successfully implemented to be effective. OBJECTIVE: We evaluated Department of Veterans Affairs' (VA's) implementation of My VA Images, a direct-to-patient asynchronous teledermatology mobile application enabling established dermatology patients to receive follow-up care remotely instead of in-person. DESIGN /PARTICIPANTS/APPROACH: Following pilot testing at 3 facilities, the app was introduced to 28 facilities (4 groups of 7) every 3 months using a stepped-wedge cluster-randomized design. Using the Organizational Theory of Implementation Effectiveness, we examined the app's implementation using qualitative and quantitative data consisting of encounter data from VA's corporate data warehouse; app usage from VA's Mobile Health database; bi-monthly reports from facility representatives; phone interviews with clinicians; and documented communications between the operational partner and facility staff. KEY RESULTS: Implementation policies and practices included VA's vision to expand home telehealth and marketing/communication strategies. The COVID-19 pandemic dominated the implementation climate by stressing staffing, introducing competing demands, and influencing stakeholder attitudes to the app, including its fit to their values. These factors were associated with mixed implementation effectiveness, defined as high quality consistent use. Nineteen of 31 exposed facilities prepared to use the app; 10 facilities used it for actual patient care, 7 as originally intended. Residents, nurse practitioners, and physician assistants were more likely than attendings to use the app. Facilities exposed to the app pre-pandemic were more likely to use and sustain the new process. CONCLUSIONS: Considerable heterogeneity existed in implementing mobile teledermatology, despite VA's common mission, integrated healthcare system, and stakeholders' broad interest. Identifying opportunities to target favorable facilities and user groups (such as teaching facilities and physician extenders, respectively) while addressing internal implementation barriers including incomplete integration with the electronic health record as well as inadequate staffing may help optimize the initial impact of direct-to-patient telehealth. The COVID pandemic was a notable extrinsic barrier. CLINICAL TRIALS REGISTRATION: NCT03241589.

Relationship Between Patient Portal Tool Use and Medication Adherence and Viral Load Among Patients Living with HIV.

BACKGROUND: Patient portals play an increasingly critical role in engaging patients in their health care. They have the potential to significantly impact the health of those living with chronic diseases, such as HIV, for whom consistent care engagement is both critical and complex. OBJECTIVE: The primary aim was to examine the longitudinal relationships between individual portal tool use and health-related outcomes in patients living with HIV. DESIGN: Retrospective cohort study using electronic health record data to examine the relationship between patient portal tool use and key HIV-specific, health-related outcomes in patients engaged in care in the Veterans Health Administration (VA) through the application of marginal structural models. PARTICIPANTS: A national sample of patients living with HIV (PLWH) active in VA care who were registered to use the VA's patient portal, My HealtheVet (MHV; n = 18,390) between 10/1/2012 and 4/1/2017. MAIN MEASURES: The MHV tools examined were prescription refill (including prescription refill of an antiretroviral (ART) medication and any medication), secure messaging, view appointments, and view labs. Primary outcomes were viral load test receipt, viral load suppression, and ART medication adherence (measured as proportion of days covered). KEY RESULTS: The use of prescription refill for any medication or for ART was positively associated with ART adherence. Secure messaging was positively associated with ART adherence but not with viral load test receipt or viral load suppression. The use of view appointments was positively associated with ART adherence and viral load test receipt but not viral load suppression. The use of view labs was positively associated with viral load suppression but not ART adherence or viral load test receipt. CONCLUSIONS: These findings highlight the valuable role patient portals may play in improving health-related outcomes among PLWH and have implications for patients living with other types of chronic disease.