Association of comorbid obstructive sleep apnea and insomnia with risk of major adverse cardiovascular events in sleep medicine center patients.

OBJECTIVES: To investigate the association between comorbid obstructive sleep apnea and insomnia and major adverse cardiovascular events, including myocardial infarction, unstable angina, congestive heart failure, and stroke, in adults with suspected sleep disorders who underwent sleep apnea testing. METHODS: We conducted a retrospective analysis of electronic medical records data from patients with clinical encounters at sleep medicine centers to identify patients with comorbid obstructive sleep apnea and insomnia, obstructive sleep apnea only, insomnia only, and patients without a diagnosis of obstructive sleep apnea or insomnia (i.e., controls). Obstructive sleep apnea, insomnia, comorbidities, and new-onset major adverse cardiovascular events were ascertained by ICD-9-CM and ICD-10-CM codes. Multivariable adjusted Cox proportional regression models evaluated the risk of major adverse cardiovascular events over a 10-year follow-up period. RESULTS: A total of 3951 patients, 226 controls, 2107 with obstructive sleep apnea only, 276 with insomnia only, and 1342 with comorbid obstructive sleep apnea and insomnia, were included in the analysis. Compared to controls, comorbid obstructive sleep apnea and insomnia were associated with a significantly higher risk of developing major adverse cardiovascular events (hazard ratio 3.60, 95 CI%: 2.33-5.91) in unadjusted analyses. The relationship between comorbid obstructive sleep apnea and insomnia and major adverse cardiovascular events remained after adjustment for demographic and behavioral factors, but not after further adjustment for comorbidities. The greatest risk of major adverse cardiovascular events was found among younger adults with comorbid obstructive sleep apnea and insomnia. Obstructive sleep apnea only was associated with greater risk of major adverse cardiovascular events in unadjusted analyses only (hazard ratio 2.77, 95% CI: 1.80-4.54). Insomnia only was not significantly associated with increased risk of major adverse cardiovascular events. CONCLUSIONS: Comorbid obstructive sleep apnea and insomnia may be a high-risk group for major adverse cardiovascular events, particularly younger adults. Further research is needed to better understand the association between comorbid obstructive sleep apnea and insomnia and major adverse cardiovascular events risk.

Burnout, job satisfaction, and turnover intention among primary care nurse practitioners with their own patient panels.

BACKGROUND: Nurse practitioners (NPs) can enhance NP care and improve access to care by autonomously managing their patient panels. Yet, its impact on workforce outcomes such as burnout, job satisfaction, and turnover intention remains unexplored. PURPOSE: To estimate the impact of NP panel management on workforce outcomes. METHODS: Structural equation modeling was conducted using survey data from 1,244 primary care NPs. NP panel management was categorized into co-managing patients with other providers, both co-managing and autonomously managing, and fully autonomous management. DISCUSSION: Fully autonomous management led to more burnout than co-managing (B = 0.089, bias-corrected 95% bootstrap confidence interval [0.028, 0.151]). Work hours partially (27%) mediated this relationship. This findings indicate that greater autonomy in panel management among NPs may lead to increased burnout, partially due to longer work hours. CONCLUSION: Interventions to reduce work hours could help NPs deliver quality care without burnout.

Clinical, molecular, and drug resistance epidemiology of HIV in Jordan, 2019-2021: A national study.

BACKGROUND: Limited epidemiologic studies have been conducted in Jordan describing the HIV epidemic. This study aimed to address this gap to inform HIV prevention and control. METHODS: A nationally-representative cross-sectional study was conducted among adults living with HIV in Jordan. Laboratory testing included HIV viral load and next-generation-sequencing-based clinical genotype. Log-binomial regression estimated risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Among 231 (70%) participants, most were male (184/80%), and from Jordan (217/94%). Among 188 treatment-experienced-participants (>6 months), 165 (88%) were virally suppressed. High-level resistance was most frequent against nucleoside reverse transcriptase inhibitor (13/81%), and integrase-strand transfer inhibitor (INSTI) (10/62%) drugs among viremic (≥1000 HIV copies/mL) treatment-experienced participants with drug-resistant mutations (DRMs, n = 16). Common HIV subtypes (n = 43) were B (6/14%), A1 (5/12%), and CRF01_AE (5/12%); additionally, novel recombinant forms were detected. In multivariate analysis, independently higher risk for late diagnosis (n = 49) was observed with diagnosis through blood donation (vs check-up: RR 2.20, 95%CI 1.16-4.17) and earlier time-period of diagnosis (1986-2014 vs 2015-2021: RR 2.87, 95%CI 1.46-5.62). CONCLUSIONS: Late diagnosis and INSTI resistance endanger national HIV prevention and treatment in Jordan-high-level resistance to INSTI suggests therapeutic drug monitoring is needed for treatment efficacy and conservation of treatment options.

SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21: a phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial.

BACKGROUND: A self-assembling SARS-CoV-2 WA-1 recombinant spike ferritin nanoparticle (SpFN) vaccine co-formulated with Army Liposomal Formulation (ALFQ) adjuvant containing monophosphoryl lipid A and QS-21 (SpFN/ALFQ) has shown protective efficacy in animal challenge models. This trial aims to assess the safety and immunogenicity of SpFN/ALFQ in a first-in-human clinical trial. METHODS: In this phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial, adults were randomly assigned (5:5:2) to receive 25 µg or 50 µg of SpFN/ALFQ or saline placebo intramuscularly at day 1 and day 29, with an optional open-label third vaccination at day 181. Enrolment and randomisation occurred sequentially by group; randomisation was done by an interactive web-based randomisation system and only designated unmasked study personnel had access to the randomisation code. Adults were required to be seronegative and unvaccinated for inclusion. Local and systemic reactogenicity, adverse events, binding and neutralising antibodies, and antigen-specific T-cell responses were quantified. For safety analyses, exact 95% Clopper-Pearson CIs for the probability of any incidence of an unsolicited adverse event was computed for each group. For immunogenicity results, CIs for binary variables were computed using the exact Clopper-Pearson methodology, while CIs for geometric mean titres were based on 10 000 empirical bootstrap samples. Post-hoc, paired one-sample t tests were used to assess the increase in mean log-10 neutralising antibody titres between day 29 and day 43 (after the second vaccination) for the primary SARS-CoV-2 targets of interest. This trial is registered at ClinicalTrials.gov, NCT04784767, and is closed to new participants. FINDINGS: Between April 7, and June 29, 2021, 29 participants were enrolled in the study. 20 individuals were assigned to receive 25 µg SpFN/ALFQ, four to 50 µg SpFN/ALFQ, and five to placebo. Neutralising antibody responses peaked at day 43, 2 weeks after the second dose. Neutralisation activity against multiple omicron subvariants decayed more slowly than against the D614G or beta variants until 5 months after second vaccination for both dose groups. CD4+ T-cell responses were elicited 4 weeks after the first dose and were boosted after a second dose of SpFN/ALFQ for both dose groups. Neutralising antibody titres against early omicron subvariants and clade 1 sarbecoviruses were detectable after two immunisations and peaked after the third immunisation for both dose groups. Neutralising antibody titres against XBB.1.5 were detected after three vaccinations. Passive IgG transfer from vaccinated volunteers into Syrian golden hamsters controlled replication of SARS-CoV-1 after challenge. INTERPRETATION: SpFN/ALFQ was well tolerated and elicited robust and durable binding antibody and neutralising antibody titres against a broad panel of SARS-CoV-2 variants and other sarbecoviruses. FUNDING: US Department of Defense, Defense Health Agency.

Development of an opportunistic diagnostic prediction algorithm for osteoporosis and fragility fracture risk estimates from forearm radiographs (The OFFER1 Study).

Osteoporosis and associated fractures are an increasingly prevalent concern with an ageing population. This study reports testing of IBEX Bone Health (IBEX BH) software, applied following acquisition of forearm radiographs. IBEX Bone Health analyses the radiograph to measure areal bone mineral density (aBMD) at the examination site. A non-randomized cross-sectional study design was performed involving 261 (254 after exclusions) participants (112/142 m/f; mean age 70.8 years (SD+/-9.0); 53 with osteoporosis). They underwent posterior-anterior distal forearm radiographs; dual X-ray absorptiometry (DXA) of the wrists, hips, and lumbar spine; and questionnaires exploring clinical risk factors. IBEX Bone Health automatically identifies regions of interest (ROI) at the ultra-distal (UD) and distal third (TD) regions of the radius. Analysis investigated area under the receiver operating characteristics curve performance of IBEX BH for prediction of (i) osteoporosis (based on clinical reporting of the hip and spine DXA) and (ii) treatment recommendations by Fracture Risk Assessment Tool (FRAX) inclusive of neck of femur (NoF) areal bone mineral density (aBMD) results following National Osteoporosis Guideline Group (NOGG) guidelines. Area under the receiver operating characteristics curve for osteoporosis prediction at the UD and TD ROIs were 0.86 (99% confidence interval (CI) [0.80, 0.91]) and 0.81 (99% CI [0.75, 0.88]), respectively. Area under the receiver operating characteristics curve for treatment recommendation using FRAX inclusive of NoF aBMD at the UD and TD ROIs were 0.95 (99% CI [0.91, 1.00]) and 0.97 (99% CI [0.93,1.00]), respectively. With a matched sensitivity to FRAX (without NoF aBMD) 0.93 (99% CI [0.78, 0.99]), IBEX BH predicted at the UD and TD ROIs recommended treatment outcomes by NOGG guidelines using FRAX (with NoF aBMD) with specificity 0.89 (99% CI 0.83, 0.94]) and 0.93 (99% CI [0.87, 0.97]), respectively. This is compared with 0.60 (99% CI [0.51, 0.69]) for FRAX (without NoF aBMD). Results demonstrate the potential clinical utility of IBEX BH as an opportunistic screening tool.

Current treatment and immunomodulation strategies in Acute Myocarditis.

Myocarditis is an inflammatory disease of the myocardium characterized by a great heterogeneity of presentation and evolution. Treatment of myocarditis is often supportive and the evidence for immunosuppression is scarce and debated. Conventional treatment is based on clinical presentation, ranging from conservative to advanced mechanical assist devices. In this setting, immunosuppression and immunomodulation therapies are mostly reserved for patients presenting with major clinical syndromes. In this review, we will summarise the current evidence and strategies for conventional and immunosuppressive treatments for patients presenting with acute myocarditis.

Factors Associated With Sleep Quality Among Undergraduate Nursing Students During Clinical Practicums.

BACKGROUND: Limited evidence exists on factors influencing nursing students' sleep quality during clinical practicums. PURPOSE: This study examined the sleep quality of nursing students and factors that affect sleep quality during clinical practicums. METHODS: Undergraduate nursing students (n = 135) enrolled in clinical practicums in 3 universities completed questionnaires including sociodemographics and the Pittsburgh Sleep Quality Index (PSQI). Stepwise linear regression evaluated factors predicating sleep quality. RESULTS: Seventy percent of nursing students reported poor sleep quality. Weekly work hours and clinical hours were significant factors in predicting global PSQI scores, subjective sleep quality, sleep duration, sleep efficiency, and daytime dysfunctions. The race was related to sleep latency and sleeping medication. Clinical hours and living on campus were associated with sleep disturbances. CONCLUSION: Knowing the factors that influence nursing students' sleep during clinical practicums, nurse educators can help students improve sleep health and clinical experience.

High Prevalence of New Clinically Significant Findings in Patients With Embolic Stroke of Unknown Source Evaluated by Cardiac Magnetic Resonance Imaging.

BACKGROUND: Embolic stroke of unknown source (ESUS) accounts for 1 in 6 ischemic strokes. Current guidelines do not recommend routine cardiac magnetic resonance (CMR) imaging in ESUS, and beyond the identification of cardioembolic sources, there are no data assessing new clinical findings from CMR in ESUS. This study aimed to assess the prevalence of new cardiac and noncardiac findings and to determine their impact on clinical care in patients with ESUS. METHODS AND RESULTS: In this prospective, multicenter, observational study, CMR imaging was performed within 3 months of ESUS. All scans were reported according to standard clinical practice. A new clinical finding was defined as one not previously identified through prior clinical evaluation. A clinically significant finding was defined as one resulting in further investigation, follow-up, or treatment. A change in patient care was defined as initiation of medical, interventional, surgical, or palliative care. From 102 patients recruited, 96 underwent CMR imaging. One or more new clinical findings were observed in 59 patients (61%). New findings were clinically significant in 48 (81%) of these patients. Of 40 patients with a new clinically significant cardiac finding, 21 (53%) experienced a change in care (medical therapy, n=15; interventional/surgical procedure, n=6). In 12 patients with a new clinically significant extracardiac finding, 6 (50%) experienced a change in care (medical therapy, n=4; palliative care, n=2). CONCLUSIONS: CMR imaging identifies new clinically significant cardiac and noncardiac findings in half of patients with recent ESUS. Advanced cardiovascular screening should be considered in patients with ESUS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04555538.

Impact of lifestyle-based interventions on absolute cardiovascular disease risk: a systematic review and meta-analysis.

OBJECTIVE: The objective of the review was to synthesize the evidence of the effectiveness of lifestyle-based interventions for mitigating absolute cardiovascular disease (CVD) risk. INTRODUCTION: Evidence-based guidelines recommend employing an absolute CVD risk score to inform the selection and intensity of preventive interventions. However, studies employing this strategy have reported mixed results, hence the need for a systematic review of the current evidence. INCLUSION CRITERIA: Studies published in English that included a lifestyle-based intervention to mitigate CVD risk were considered. Studies were eligible if they enrolled individuals aged ≥18 years, with no history of CVD at baseline. The primary outcome was change in absolute CVD risk score post-intervention. METHODS: PubMed, Embase, and CINAHL searches were conducted from database inception to February 2022. The trial registers searched included Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov. Searches for unpublished studies/gray literature were conducted in ProQuest Dissertations and Theses Global, GreyLit Report, and OCLC First Search Proceedings. Two independent reviewers selected the studies and critically appraised them for methodological quality using JBI tools. Data extraction was performed for main outcome variables. Data were presented using separate pooled statistical meta-analysis for quasi-experimental and randomized clinical trials. Random effects models were employed in the analyses. Effect sizes (Cohen's d) were expressed as standardized mean difference at 95% CI. Heterogeneity was assessed via Cochran's Q statistic, and the inconsistency index ( I2 ) was used to describe variability in effect estimates due to heterogeneity rather than sampling error. RESULTS: Twenty-nine studies with a total sample of 5490 adults with no CVD at baseline were included. Fifteen were randomized controlled trials (RCTs; n=3605) and 14 were quasi-experimental studies (n=1885). The studies were conducted in Europe (n=18), the United States (n = 5), Asia (n=3), Mexico (n=1), Canada (n = 1), and Australia (n=1) and included the following lifestyle interventions: diet, physical activity, motivational interviewing, problem-solving, psychological counseling, cardiovascular risk assessment and feedback, health self-management education, and peer support. Six validated absolute CVD risk assessment tools were used to measure the study outcomes, including Framingham, SCORE, Heart Health Risk Assessment Score, Dundee, ASSIGN, and The UK Prospective Diabetes Study risk score. Overall, the methodological rigor of the RCTs and quasi-experimental studies was high. Of the 15 RCTs included in the meta-analysis, lifestyle intervention was favored over control in reducing absolute CVD risk score (Cohen's d = -0.39; P =0.032; Z= -2.14; I2 = 96). Similarly, in the 14 quasi-experimental studies, the absolute CVD risk score after lifestyle intervention was significantly lower compared to baseline (Cohen's d = -0.39; P <0.001; Z= -3.54; I2= 88). RCTs that combined diet and physical activity reported no significant impact on absolute CVD risk score, but those that used either intervention independently reported significant improvement in the absolute CVD risk score. CONCLUSIONS: There is evidence supporting the positive impact of lifestyle modification on absolute CVD risk score in adult populations without CVD. Our analysis further suggests that diet and physical activity had significant impact on absolute CVD risk, and a variety of validated screening tools can be used to monitor, evaluate, and communicate changes in absolute risk score after lifestyle modification. SUPPLEMENTAL DIGITAL CONTENT: A Spanish-language version of the abstract of this review is available [ http://links.lww.com/SRX/A29 ].

The female self-advocacy in Cancer Survivorship scale is a psychometrically sound measure of self-advocacy in male cancer survivors.

OBJECTIVE: To develop and psychometrically evaluate an adapted version of the Female Self-Advocacy in Cancer Survivorship (FSACS) Scale in men with a history of cancer. METHODS: This psychometric instrument development and validation study used a two-phase approach to first adapt the FSACS Scale items to reflect the experience of men with a history of cancer and then evaluate the psychometric properties of the adapted scale compared to the original FSACS Scale. The study was conducted from December 2018 through April 2022 through cancer clinics, patient registries, and national advocacy organizations. We evaluated scale reliability and validity using reliability coefficients, exploratory and confirmatory factor analyses, and item analyses to determine a final set of scale items. RESULTS: Item responses from N = 171 men with a history of cancer were evaluated to determine scale validity. After removing poor-performing items based on item-level analyses, factor analyses confirmed that a 3-factor structure of both the adapted and original FSACS Scale best fit the scale. The 10 new items did not outperform the original 20-item scale and were therefore excluded from the final scale. The final 20-item scale explained 87.94% of item variance and subscale's Cronbach α varied from 0.65 to 0.86. CONCLUSION: The SACS Scale can be used in research and clinical contexts to assess the propensity of men and women to get their needs, values, and priorities met in the face of a challenge.

Taking Action Against Clinician Burnout Through Reducing the Documentation Burden With an Operating Room Supply Scanning Approach.

Documenting surgical supply items in the operating room can be a burdensome task for circulating nurses because of manual input within the electronic medical record. This can lead to documentation fatigue and contribute to nursing burnout. The aim of this quality improvement project was to design and implement a supply item scanning process and evaluate the effect on intraoperative documentation completion time, room turnover time, picklist documentation accuracy, nurse satisfaction, and burnout. The sample included nine acute care hospitals throughout the United States, with 189 total circulating nurses and 31 718 procedures occurring during the study timeframe of 8 months. Results indicated that nurses were able to complete documentation on average 37.33 minutes sooner, and the operating room turnover time decreased by 1.88 minutes. Although nurses reported that their perceived picklist documentation accuracy did not improve, and the presence of new scanning technology did not influence their hospital employment decision, subjective feedback was mostly positive, with most responses citing the helpfulness of scanning for documentation. This study shows that an interdisciplinary team can effectively work to optimize documentation efficiency and performance improvement using a scanning intervention. Lessons learned through this process can translate into optimizations elsewhere in the electronic medical record.

Risk of sexually transmitted infections among U.S. military service members in the setting of HIV pre-exposure prophylaxis use.

BACKGROUND: The evidence for an increased incidence of sexually transmitted infections (STIs) among patients utilizing HIV pre-exposure prophylaxis (PrEP) has been inconsistent. We assessed the risk of incident STI while on PrEP compared to periods off PrEP among military service members starting PrEP. METHODS: Incidence rates of chlamydia, gonorrhea, syphilis, hepatitis C virus, and HIV were determined among military service members without HIV prescribed daily oral tenofovir disoproxil fumarate and emtricitabine for HIV PrEP from February 1, 2014 through June 10, 2016. Hazard ratios for incident STIs were calculated using an Anderson-Gill recurrent event proportional hazard regression model. RESULTS: Among 755 male service members, 477 (63%) were diagnosed with incident STIs (overall incidence 21.4 per 100 person-years). Male service members had a significantly lower risk of any STIs (adjusted hazard ratio (aHR) 0.21, 95% CI 0.11-0.40) while using PrEP compared to periods off PrEP after adjustment for socio-demographic characteristics, reasons for initiating PrEP, surveillance period prior to PrEP initiation, and the effect of PrEP on site and type of infection in multivariate analysis. However, when stratifying for anatomical site and type of infection, the risk of extragenital gonorrhea infection (pharyngeal NG: aHR 1.84, 95% CI 0.82-4.13, p = 0.30; rectal NG: aHR 1.23, 95% CI 0.60-2.51, p = 1.00) and extragenital CT infection (pharyngeal CT: aHR 2.30, 95% CI 0.46-11.46, p = 0.81; rectal CT: aHR 1.36, 95% CI 0.81-2.31, p = 0.66) was greater on PrEP compared to off PrEP although these values did not reach statistical significance. CONCLUSIONS: The data suggest entry into PrEP care reduced the overall risk of STIs following adjustment for anatomical site of STI and treatment. Service members engaged in PrEP services also receive more STI prevention counseling, which might contribute to decreases in STI risk while on PrEP.

Diagnostic accuracy, clinical characteristics, and prognostic differences of patients with acute myocarditis according to inclusion criteria.

INTRODUCTION: The diagnosis of acute myocarditis (AM) is complex due to its heterogeneity and typically is defined by either Electronic Healthcare Records (EHRs) or advanced imaging and endomyocardial biopsy, but there is no consensus. We aimed to investigate the diagnostic accuracy of these approaches for AM. METHODS: Data on ICD 10th Revision(ICD-10) codes corresponding to AM were collected from two hospitals and compared to CMR-confirmed or clinically suspected(CS) AM cases with respect to diagnostic accuracy, clinical characteristics, and all-cause mortality. Next, we performed a review of published AM studies according to inclusion criteria. RESULTS: We identified 291 unique admissions with ICD-10 codes corresponding to AM in the first three diagnostic positions. The positive predictive value(PPV) of ICD-10 codes for CMR-confirmed or CS-AM was 36%, and patients with CMR-confirmed or CS AM had a lower all-cause mortality than those with a refuted diagnosis (P = 0.019). Using an unstructured approach, patients with CMR-confirmed and CS AM had similar demographics, comorbidity profiles and survival over a median follow-up of 52 months (P = 0.72). Our review of the literature confirmed our findings. Outcomes for patients included in studies using CMR-confirmed criteria were favourable compared to studies with EMB-confirmed AM cases. CONCLUSION: ICD-10 codes have poor accuracy in identification of AM cases and should be used with caution in clinical research. There are important differences in management and outcomes of patients according to the selection criteria used to diagnose AM. Potential selection biases must be considered when interpreting AM cohorts and requires standardisation of inclusion criteria for AM studies.

Patient-level factors associated with the self-report of trouble sleeping to healthcare providers in adults at high risk for obstructive sleep apnea.

INTRODUCTION: In adults at risk for obstructive sleep apnea, it is unclear what patient-level factors and symptoms may influence communication with healthcare providers regarding sleep difficulties. This analysis examined associations between sociodemographic characteristics, comorbidities, and obstructive sleep apnea-related symptoms and whether adults at high risk for obstructive sleep apnea reported trouble sleeping to an healthcare provider. METHODS: The sample included participants from the 2015-2018 National Health and Nutrition Examination Survey determined by a modified STOP-Bang to be at high risk for obstructive sleep apnea (n = 2009). Participants were asked if they had ever reported trouble sleeping to an healthcare provider. Self-reported comorbidities and obstructive sleep apnea-related symptoms (ie, snoring, snorting, gasping, or breathing cessation during sleep, daytime sleepiness, fatigue, insomnia, and nocturia) were assessed. RESULTS: Half of the sample (50.8%) never reported trouble sleeping to an healthcare provider. Factors associated with an increased likelihood of reporting trouble sleeping included female sex, former smoker, and prediabetes or diabetes, obstructive lung disease, daytime sleepiness, insomnia, nocturia, and symptoms of snorting, gasping, and/or breathing cessation during sleep. Factors associated with a decreased likelihood of reporting trouble sleeping included Mexican American background or Asian race and having less than a high school education. CONCLUSION: Differences in sex, race, education, comorbidities, and obstructive sleep apnea-related symptoms exist between adults at high risk for obstructive sleep apnea who have and have not reported trouble sleeping to an healthcare provider. It is important for healthcare providers to ask all adults about sleep problems, recognizing that men, minorities, and persons with lower educational attainment may be less likely to report trouble sleeping.

Safety, tolerability, and immunogenicity of the Ebola Sudan chimpanzee adenovirus vector vaccine (cAd3-EBO S) in healthy Ugandan adults: a phase 1, open-label, dose-escalation clinical trial.

BACKGROUND: Sudan Ebola virus can cause severe viral disease, with an average case fatality rate of 54%. A recent outbreak of Sudan Ebola virus in Uganda caused 55 deaths among 164 confirmed cases in the second half of 2022. Although vaccines and therapeutics specific for Zaire Ebola virus have been approved for use during outbreak situations, Sudan Ebola virus is an antigenically distinct virus with no approved vaccines available. METHODS: In this phase 1, open-label, dose-escalation trial we evaluated the safety, tolerability, and immunogenicity of a monovalent chimpanzee adenovirus 3 vaccine against Sudan Ebola virus (cAd3-EBO S) at Makerere University Walter Reed Project in Kampala, Uganda. Study participants were recruited from the Kampala metropolitan area using International Review Board-approved written and electronic media explaining the trial intervention. Healthy adults without previous receipt of Ebola, Marburg, or cAd3 vectored-vaccines were enrolled to receive cAd3-EBO S at either 1 × 1010 or 1 × 1011 particle units (PU) in a single intramuscular vaccination and were followed up for 48 weeks. Primary safety and tolerability endpoints were assessed in all vaccine recipients by reactogenicity for the first 7 days, adverse events for the first 28 days, and serious adverse events throughout the study. Secondary immunogenicity endpoints included evaluation of binding antibody and T-cell responses against the Sudan Ebola virus glycoprotein, and neutralising antibody responses against the cAd3 vector at 4 weeks after vaccination. This study is registered with ClinicalTrials.gov, NCT04041570, and is completed. FINDINGS: 40 healthy adults were enrolled between July 22 and Oct 1, 2019, with 20 receiving 1 × 1010 PU and 20 receiving 1 × 1011 PU of cAd3-EBO S. 38 (95%) participants completed all follow-up visits. The cAd3-EBO S vaccine was well tolerated with no severe adverse events. The most common reactogenicity symptoms were pain or tenderness at the injection site (34 [85%] of 40), fatigue (29 [73%] of 40), and headache (26 [65%] of 40), and were mild to moderate in severity. Positive responses for glycoprotein-specific binding antibodies were induced by 2 weeks in 31 (78%) participants, increased to 34 (85%) participants by 4 weeks, and persisted to 48 weeks in 31 (82%) participants. Most participants developed glycoprotein-specific T-cell responses (20 [59%, 95% CI 41-75] of 34; six participants were removed from the T cell analysis after failing quality control parameters) by 4 weeks after vaccination, and neutralising titres against the cAd3 vector were also increased from baseline (90% inhibitory concentration of 47, 95% CI 30-73) to 4 weeks after vaccination (196, 125-308). INTERPRETATION: The cAd3-EBO S vaccine was safe at both doses, rapidly inducing immune responses in most participants after a single injection. The rapid onset and durability of the vaccine-induced antibodies make this vaccine a strong candidate for emergency deployment in Sudan Ebola virus outbreaks. FUNDING: National Institutes of Health via interagency agreement with Walter Reed Army Institute of Research.

Prophylactic Uterine Artery Embolization in Placenta Accreta Spectrum-An Active Intervention to Reduce Morbidity and Promote Uterine Preservation.

PURPOSE: To evaluate the feasibility and safety of early and proactive involvement of interventional radiology (IR) in the management of placenta accreta spectrum (PAS) by performing the cesarean operation and prophylactic uterine artery embolization in the IR angiography suite as a combined procedure. MATERIALS AND METHODS: This study evaluated the effectiveness and safety of prophylactic uterine artery embolization prior to placental separation in cases of antenatally proven or suspected abnormal placentation. Over a 5-year period, 16 consecutive patients with PAS underwent combined IR and obstetric intervention. In all cases, cesarean delivery was performed in the IR angiography suite. Vascular access was obtained prior to surgery with balloon placement into both internal iliac arteries. These balloons were inflated after delivery, followed by uterine artery embolization (14 of 16) if there was evidence of active postpartum bleeding or inability to deliver the placenta. RESULTS: There was no fetal or maternal mortality and no significant IR or surgical adverse events. Mean blood loss was 1900 mL. Seven patients (44%) underwent hysterectomy. CONCLUSIONS: In patients with PAS, cesarean section in the angiography suite preceded by prophylactic balloon placement and followed by uterine artery embolization was feasible, safe, and effective in preventing massive blood loss, with a 56% uterine sparing rate.

Cloning, purification and characterization of human dentine matrix protein 1(DMP1).

Introduction: Human teeth are composed mainly of dentin, formed by the odontoblasts. Dentin matrix protein 1 (DMP1) is one of odontoblast differentiation's most important growth factors. Human DMP1 has yet to be completely identified or studied. This study aimed to clone and characterize human DMP1. Materials and methods: The DMP1 gene sequence was prepared and cloned by transfection of human 293 cells. Results: The recombinant DMP1 was purified and characterized. Conclusion: The results suggested its future use in dental tissue regeneration and tissue engineering.

Analytical validation of quantitative SARS-CoV-2 subgenomic and viral load laboratory developed tests conducted on the Panther Fusion® (Hologic) with preliminary application to clinical samples.

OBJECTIVE: Validate the performance characteristics of two analyte specific, laboratory developed tests (LDTs) for the quantification of SARS-CoV-2 subgenomic RNA (sgRNA) and viral load on the Hologic Panther Fusion® using the Open Access functionality. METHODS: Custom-designed primers/probe sets targeting the SARS-CoV-2 Envelope gene (E) and subgenomic E were optimized. A 20-day performance validation following laboratory developed test requirements was conducted to assess assay precision, accuracy, analytical sensitivity/specificity, lower limit of detection and reportable range. RESULTS: Quantitative SARS-CoV-2 sgRNA (LDT-Quant sgRNA) assay, which measures intermediates of replication, and viral load (LDT-Quant VLCoV) assay demonstrated acceptable performance. Both assays were linear with an R2 and slope equal to 0.99 and 1.00, respectively. Assay precision was evaluated between 4-6 Log10 with a maximum CV of 2.6% and 2.5% for LDT-Quant sgRNA and LDT-Quant VLCoV respectively. Using negative or positive SARS-CoV-2 human nasopharyngeal swab samples, both assays were accurate (kappa coefficient of 1.00 and 0.92). Common respiratory flora and other viral pathogens were not detected and did not interfere with the detection or quantification by either assay. Based on 95% detection, the assay LLODs were 729 and 1206 Copies/mL for the sgRNA and VL load LDTs, respectively. CONCLUSION: The LDT-Quant sgRNA and LDT-Quant VLCoV demonstrated good analytical performance. These assays could be further investigated as alternative monitoring assays for viral replication; and thus, medical management in clinical settings which could inform isolation/quarantine requirements.