Pneumonia is the most common indication for antibiotics in the ICU. Better diagnostic tools are needed to target therapy. We evaluated the impact of the BIOFIRE Pneumonia Panel (PNP) coupled with aggressive stewardship interventions in the ICU.The PNP was implemented 5/2020 with interpretation guidance, provider education, and intermittent stewardship feedback. From 2/21 to 7/21 (Intervention) stewardship personnel reviewed all ICU PNP and provided structured feedback. We compared this group to patients with a respiratory tract culture in the ICU 9/19-2/20 (Control). We evaluated only first PNP/culture and excluded age < 19 years and expired < 24 hours after PNP/culture. Antibiotic use for 7 days after PNP/culture was compared between groups with time to de-escalation as the primary outcome. Times were measured from PNP/culture collection.Table 1). PNP results were available 4 hours after collection and positive in 56.9% (culture positive 38.3%) with the most common pathogens detected being S. aureus , H. influnezae (32), respiratory viruses (30), and P. aeruginosa (24). Use of urine antigens and respiratory pathogen panel testing was less common in the Intervention group (Table 1) while stewardship interventions were more common (82% vs. 13%) and occurred 23 hours earlier (Table 2). Intervention period antibiotic de-escalation occurred 18 hours earlier (P< 0.0001) and time to stopping anti-MRSA and anti-Pseudomonal therapy was shorter . Median antibiotic days were decreased  and days of vancomycin, metronidazole, azithromycin, and Anti-Pseudomonal therapy significantly decreased during the intervention.A total of 313 intervention patients and 315 controls were compared with differences noted in ICU location and LOS, COVID detection, specimen type, and mortality (PNP detected more pathogens and when coupled with an aggressive stewardship intervention resulted in faster pathogen detection, decreased urine antigen testing, faster de-escalation of antibiotics, and less antibiotic use. Clinical characteristics and outcomes were different between the groups which may be due to differences in the populations including the presence of COVID.Trevor C. Van Schooneveld, MD, FSHEA, FACP, AN2 Therapeutics: Grant/Research Support|Biomeriuex: Advisor/Consultant|Biomeriuex: Grant/Research Support|Insmed: Grant/Research Support|Thermo-Fischer: Honoraria Scott J. Bergman, PharmD, bioMerieux, Inc.: Honoraria Erica J. Stohs, MD, MPH, bioMerieux: Grant/Research Support|Merck: Grant/Research Support


Respiratory syncytial virus (RSV) is an important cause of severe lower respiratory tract illness in older adults. RSV and influenza are both typically seasonal diseases, with peaks during winter in temperate climates. Annual vaccination with high-dose or adjuvanted influenza vaccine formulations is recommended to prevent influenza illness in older adults. Therefore, in a Phase 3 study in older adults, the safety and immunogenicity of coadministration of Pfizer’s investigational bivalent, stabilized RSV prefusion F subunit vaccine (RSVpreF) and adjuvanted quadrivalent seasonal inactivated influenza vaccine (SIIV) was compared with SIIV alone or RSVpreF alone.The primary immunogenicity objective of this Phase 3, 1:1 randomized, parallel-group, double-blind, placebo-controlled study with 1471 healthy adults ≥65 years of age in Australia was to demonstrate noninferiority of coadministration of RSVpreF 120 µg with SIIV compared with sequential administration of SIIV followed by RSVpreF one month later, using a 1.5-fold equivalence margin.The safety profile of coadministration of RSVpreF with SIIV was evaluated by collection of reactogenicity and adverse events.Study Design SchemaA total of 1403 participants were randomized, with 1399 participants who received vaccination at a median age of 70 years (range 65-91 years) included in the safety population. Local reactions and systemic events were mostly mild or moderate when RSVpreF was coadministered with SIIV. There were no vaccine related serious adverse events reported.The primary immunogenicity objective was met. The geometric mean ratios (GMRs) ranged from 0.85 to 0.86 for RSVpreF and 0.77 to 0.90 for SIIV, for RSV neutralizing titers and strain-specific hemagglutination inhibition assay (HAI) titers at 1 month after vaccination, achieving the 1.5-fold prespecified non-inferiority margin (lower bound CI > 0.667).Geometric Mean Titer (GMT) Ratios for RSV Neutralizing Titers (NT) and Influenza HAI titers with 95% Confidence Intervals (CI)The primary objectives of the study were met demonstrating noninferiority of the RSVpreF and SIIV immune responses when RSVpreF was coadministered with SIIV, and that RSVpreF had an acceptable safety profile when coadministered with SIIV. The results of this study support the coadministration of RSVpreF and SIIV in an older adult population.James A. Baber, MBChB, MPH, Pfizer: Salary|Pfizer: Stocks/Bonds Karen Quan, BSc, MBBS, DPM, Pfizer: Employee|Pfizer: Stocks/Bonds Anna Jaques, MPH, Pfizer: Salary|Pfizer: Stocks/Bonds Qin Jiang, PhD, Pfizer: Employee|Pfizer: Employee|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds Wen Li, PhD, Pfizer: Stocks/Bonds David Cooper, PhD, Pfizer, Inc.: Stocks/Bonds Mark W. Cutler, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Elena Kalinina, PhD, Pfizer: Pfizer employee|Pfizer: Stocks/Bonds Annaliesa S. Anderson, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Kena A. Swanson, Ph.D., Pfizer: Employee|Pfizer: Stocks/Bonds William C. Gruber, MD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Alejandra C. Gurtman, M.D, Pfizer: Employee|Pfizer: Stocks/Bonds Beate Schmoele-Thoma, MD, Pfizer: Stocks/Bonds


SMARCB1 (95%) or SMARCA4 (5%) genes [ASCL1, with additional sub-entities recently reported), TYR , and MYC (overexpressing MYC and HOXC clusters). These subgroups seem to be associated with distinct genetic and clinical features [Atypical Teratoid/Rhabdoid Tumors (AT/RT) are malignant pediatric tumors of the Central Nervous System (CNS) and are molecularly characterized by a biallelic alteration of the features  but theiSMARCB1-deficient) to evaluate the sensitivity/specificity of various combinations of immunohistochemical (IHC) markers to predict the molecular subgrouping. Using previously reported results and in-house datasets [https://www.molecularneuropathology.org/mnp/). Consistently, 42/51 were assigned to a subgroup of AT/RT with a calibrated score (≥ 0.9) . The nine remaining cases were classified as AT/RT-TYR (n = 4), AT/RT-MYC (n = 4), and control tissue (n = 1) but with a low calibrated score and were thus excluded from subsequent analyses. Their overall distribution within subgroups is depicted by the specificity of t-Distributed Stochastic Neighbor Embedding (t-SNE) analysis , ASCL1 was excluded from our analyses. Next, nineteen different combinations of five different antibodies were tested to evaluate the accuracy of AT/RT subgrouping using the IHC markers we selected ; AT/RT, SHH , AT/RT, TYR , CNS NB, FOXR2 , CNS tumor, BCOR ITD ; CTRL, HEMI ; ETMR, C19MC ; ETMR, DICER1 ; MB, non-WNT/ non-SHH ; MB, SHH ; MB, WNT . Cohort cases are designated by their numberSupplementary Material 1: Fig. S1. t-distributed stochastic neighbor embedding (t-SNE) analysis of the DNA methylation profiles of the 51 investigated tumors alongside selected reference samples of the DKFZ classifier (v12.5). Reference DNA methylation classes: AT/RT, Supplementary Material 2: Fig. S2. Additional immunohistochemical results.A: Comparison of results for molecular subtyping using nineteen different immunohistochemical panels . NEC: Not Elsewhere Classified. *designate the panels with the highest accuracy for subtyping. B: Discrepant cases with immunohistochemical findings (magnification x400). Black scale bars represent 50 μmSupplementary Material 3: Detailed data of the cohort and synthesis


Empiric antibiotic selection in outpatient care often relies on inpatient antibiograms which may not accurately reflect ambulatory susceptibility rates. To address this, Novant Health (NH) and Labcorp analyzed urine culture results from North Carolina (NC) to create an ambulatory antibiogram and assess temporal and regional differences.Cross-sectional study of urine culture data collected 1/1/20-12/31/21 from ambulatory sites in NC. Testing and antibiogram preparation were performed at Labcorp  based on CLSI guidelines (M100 S28). Pediatric and adult data were compiled separately. NH and state-wide data were analyzed using the chi-square or Fisher exact test with Bonferroni correction for multiple comparisons.Escherichia coli was the most common isolate for NH  and state-wide . E. coli was ≥ 80% susceptible to all tested antibiotics except ampicillin; Klebsiella pneumoniae was ≥ 80% susceptible to all except nitrofurantoin; and Proteus mirabilis/penneri was ≥ 80% susceptible to all antibiotics tested. Susceptibility rates were similar between NH and state-wide data except for lower susceptibility to ceftriaxone . Compared to 2020, state-wide adult E. coli isolates from 2021 had increased susceptibility for amoxicillin/clavulanic acid (86% vs 85%), ampicillin (60% vs 59%), cephalosporins (84-93% vs 82-92%), and quinolones (87% vs 86%) . NH isolates did not show significant changes. Susceptibility rates by region were similar, except for lower susceptibility to cefuroxime among adult E. coli isolates in the Triad region relative to state-wide . No significant temporal or regional differences in susceptibility were observed for K. pneumoniae, Proteus spp., P. aeruginosa, and among pediatric samples.In 2021, Susceptibility data were largely similar in NH vs. state-wide data, and between regions. Small but statistically significant temporal changes were found in state-wide data. Overall, our results support use of a state-wide antibiogram to inform treatment choices across all regions and within specific healthcare systems.Dusica Curanovic, PhD, Labcorp: employed by labcorp during study|Labcorp: Stocks/Bonds Chris Garcia, MD, Labcorp: Prior employee|Labcorp: Stocks/Bonds Catherine Wright, PhD, Labcorp: Employee|Labcorp: Stocks/Bonds Rita Stainback, MS, MT (ASCP) SM, DLM, Labcorp: Employee|Labcorp: Stocks/Bonds Melissa Martin, BS, Labcorp: Employee Samia Naccache, PhD, D(ABMM), Labcorp: Employee|Labcorp: Stocks/Bonds Kristen Smith, PhD, bioMerieux: Employee|Labcorp: Stocks/Bonds Howard Engler, PhD, D(ABMM), Labcorp: Employee|Labcorp: Stocks/Bonds


Correction to: BMC Nursing (2022) 21:37510.1186/s12912-022-01165-wFollowing publication of the original article , the autThe original author names were:2, Negesu Gizaw Demssie3Zewdu BayeTezeraThe correct author names are:2, Negesu Gizaw Demissie3Zewdu Baye TezeraThe correct author names have been provided in this Correction. The original article  has been


HSV reactivation (HSVr) is frequent in HM and SOM patients while oropharyngeal/ mucocutaneous infections (OP-MCI) and especially HSV pneumonitis (HSVP) are uncommon. BALF-HSV-PCR can identify shedding or disease, however, may result in inappropriate high dose antiviral usage in non-HSVP situations. We report a cohort of patients with positive BALF-HSV-PCR, its impact on antiviral usage and role of IDC on antiviral use.Retrospective chart review of BALF-HSV-PCR positive patients who had IDC between 1/1/2018 and 8/31/2022. Exclusion criteria: No chest imaging (CT scan or chest X-ray imaging within ±7 days of positive test) and no malignancy. Data collection: demographics, laboratory and clinical findings, and antiviral medication dosing before and after each positive BALF-HSV-PCR preceding the IDC. Clinical diagnosis and treatment of HSVP versus non-HSVP was based on IDC. Kruskal-Wallis tests was used for continuous variables and Fisher’s exact test for categorical variables, and p-values reported were 2-sided at significance level of 0.05.One-hundred-nine patients met inclusion criteria. Nineteen (17.4%) had HSVP, 90 (82.6%) non-HSVP. In non-HSVP; 83 (92%) had oropharyngeal shedding (HM >SOM), 6 (6%) OP-MCI and 1 (1%) immunotherapy related pneumonitis (IrP). Tables 1-3 provide details on demographics and baseline characteristics, antiviral use, and statistical analysis. HSV shedding/ disease (HSVP and OP-MCI) was more common in HM patients. All HSVP patients received high dose antiviral agents. Of ninety patients determined as non-HSVP, 42% were overtreated with antivirals with a positive test that preceded IDC. Positive PCR led to change in antiviral dose (p < 0.05) with highly significant impact on the dose of acyclovir used (prophylaxis vs. OP-MCI vs. HSPV doses) (p< 0.0001). IDC led to modification of HSVP dosing to either prophylaxis or complete discontinuation in 84.2% of patients (p=0.008).BALF-HSV-PCR positive test without HSVP led to overtreatment in both HM and SOM patients that is preventable by IDC, underscoring its value in antiviral stewardship. Diagnostic stewardship can further limit inappropriate use of antivirals.Randy Taplitz, MD, Karius: Advisor/Consultant|Merck: Advisor/Consultant|SNIPR biome: Advisor/Consultant Sanjeet S. Dadwal, MD, FACP, FIDSA, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|Aseptiscope, Inc: Stocks/Bonds|Astellas: Honoraria|Karius: Grant/Research Support|Matinas Biopharma: Stocks/Bonds|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer/Amplyx: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Honoraria|Viracor: Honoraria


Respiratory syncytial virus (RSV) can cause severe disease in older adults (≥65 years) or those with comorbidities. Understanding the risk of hospitalization after RSV diagnosis through current real-world data analyses is limited by estimates combining cases identified in inpatient and outpatient settings. To address this gap and to better understand opportunities for intervention to prevent such hospitalizations, we quantified the crude 28-day risk of all-cause hospitalizations following RSV infections initially managed in an outpatient setting.This retrospective observational study identified outpatient RSV episodes (clinics and emergency departments [ED]) for RSV between 01Sep2016-31Oct2022 using Optum’s de-identified Integrated Claims-Clinical data set, which contains linked person-level claims and electronic health record (EHR) data. RSV diagnosis was defined using positive test results  and ICD-10-CM diagnosis codes. Comorbidities were identified using diagnosis, procedure, and medication codes. Only the first eligible episode (index date) for each study-defined RSV season (01Oct–30Sep) was included . Episodes hospitalized on the index date or with an RSV-related hospitalization 14 days prior to the index date were excluded. Crude risk of all-cause hospitalization was assessed over a 28-day follow-up period.Study schematic for the retrospective observational cohort study designThe schematic depicts how eligible RSV outpatient episodes were identified and the inclusion/exclusion criteria that were applied to generate the final sample.Of 2,792 included episodes, 62% occurred among females, 55% occurred among patients aged ≥65, and 21% received ED care on the index date. Between 2016-2018, the 28-day risk of hospitalization ranged from 6-9% and declined to 3% in 2019/20 . The risk of hospitalization also varied by age or the presence of comorbidities (Table 1).This table summarizes the crude 28-day risk of all-cause hospitalization for adults overall and stratified by clinical conditions and age groups.This figure displays the crude 28-day risk of all-cause hospitalization following an outpatient episode of RSV, stratified by season and displayed for adults with high-risk conditions.A meaningful risk of all-cause hospitalization following outpatient RSV episodes was observed using a US integrated database that captures a patient’s longitudinal healthcare journey. Risk of hospitalization varied across seasons and was influenced by age and comorbidities. Results include diagnosed cases, and RSV infections may have been underreported due to infrequent standard-of-care testing.Suzanne Landi, PhD, Pfizer, Inc: Employment|Pfizer, Inc: Stocks/Bonds Diana Garofalo, PhD MPH, Pfizer: Stocks/Bonds Amie Scott, MPH, Pfizer, Inc: Employee|Pfizer, Inc: Stocks/Bonds Jill McCarthy, PhD, Pfizer: Contractor Margaret Tawadrous, MD, MS, Pfizer: Full time employee|Pfizer: Full-time employee|Pfizer: Full-time employee|Pfizer: Full -time employee|Pfizer: Ownership Interest|Pfizer: Ownership Interest|Pfizer: Ownership Interest|Pfizer: Ownership Interest|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds Glenn Pixton, MS, Abbott: Stocks/Bonds|Abbvie: Stocks/Bonds|Pfizer: employee|Pfizer: Stocks/Bonds|Viatris: Stocks/Bonds Niki Alami, MD, Pfizer: Employee|Pfizer: Stocks/Bonds Scott P. Kelly, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Joshua T. Swan, PharmD, MPH, BCPS, FCCM, CareDx: Grant/Research Support|Genentech: Grant/Research Support|Grifols Share Services North America: Grant/Research Support|Heron Therapeutics: Grant/Research Support|Kedrion Biopharma: Advisor/Consultant|Kedrion Biopharma: Grant/Research Support|Pacira Pharmaceuticals: Grant/Research Support|Pfizer: Grant/Research Support|Pfizer: Employee|Pfizer: Stocks/Bonds|VigiLanz Corporation: Grant/Research Support


The cerebellum has been implicated in cognitive, affective and motor functions, including emotion regulation, executive control and sensorimotor processing. In schizophrenia, cerebellar dysfunction has been associated with treatment resistance and clinical features. However, few studies have been focused on delusional disorder (DD).Our main purpose was to review the evidence available on cerebellum abnormalities and dysfunctions in patients with DD.A systematic review was conducted through PubMed, Scopus and ClinicalTrials.gov (inception-June 2022) according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) directives. The following search terms were used: cerebellum OR cerebellar AND . Reference lists from included studies were hand-checked to find other potential relevant papers.Six studies were included from a total of 119 retrieved records . Study 1:Patients with DD somatic type (n=14) presented a decreased gray matter volume in cerebellar lobules compared to healthy controls (HC)  and non-somatic DD . Cerebellar volumes did not seem to differ between HC and non-somatic DD. Study 2:Abnormalities of voluntary saccadic eye movements, linking frontal and cerebellar functions, were found in DD patients (n=34) compared to HC (n=40). Study 3: Abnormal smooth pursuit eye movements in DD (n=15) compared with HC (n=40) and similar to schizophrenia (n=40). Case reports (n=3): DD associated with Dandy-Walker variant , unruptured intracerebral aneurysm of basilar artery, and megacisterna magna.Cerebellar deficits in patients with DD has been reported, particularly in those presenting somatic delusional contents.None Declared


Telehealth (TH) offers valuable opportunities to improve healthcare delivery that may translate to better health outcomes. Utilization of TH by pediatric subspecialty programs has been successful in inpatient settings. Limited data is available on its applicability to outpatient Pediatric Infectious Diseases during the pandemic. We aim to assess the differences between in person vs TH services in a pediatric infectious disease practice.This retrospective cohort study included patients aged 0 to 21 evaluated in a pediatric infectious disease clinic from 1/1/2019 – 12/31/2022 across 5 locations in Southwest Florida. Data was collected for new or established unduplicated patients seen in consultation for an acute, subacute, or chronic pediatric infectious disease condition. All encounters were characterized by in-person or TH modality. Clinic encounters related to research were excluded.Altogether, 2,207 patients made 6,905 appointments. Of those appointments, 1,034 (15%) were TH visits, and 5,871 (85%) were in-person visits. New patient TH visits represented 17% vs 22% for in-person. There was a significant difference between the TH and in-person groups in mean age , race , ethnicity , and type of insurance . There was no significant difference in gender . The most frequent diagnoses are described in Figure 1. Physicians provided 77% of the TH visits vs 44% for the in-person visits. Cancellation/no-show rate was significantly lower for TH vs in-person visits . Mean traveled distance for in-person visits was 21 miles vs 30 miles avoided for TH encounters.TH offered a valuable option for pediatric infectious diseases patients during the COVID-19 pandemic. Availability of mobile connectivity, distance to appointment, and type of diagnosis may play a role in the selection of the appointment modality. TH holds promise for improving access to pediatric subspecialty services, allowing patient convenience and potential better health outcomes while delivering comparable care.Claudia M. Espinosa, MD, MSc, AstraZeneca: Grant/Research Support|Enanta: Grant/Research Support|Jansen and Jansen: Advisor/Consultant|Kentucky Rural Health Association: Honoraria|Merck: Grant/Research Support|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|Sanofi: Honoraria|Sobi: Dinner Amol Purandare, MD, Caribou: Stocks/Bonds|Intellia: Stocks/Bonds|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Carina A. Rodriguez, MD, Gilead: Grant/Research Support|Moderna: Grant/Research Support|Novavax: Grant/Research Support


The correct name is: Ololade G. Adewole. The correct citation is: Adewol OG, Babalola BI, Omotoso KO, Oyelade OO, Ibrahim EA (2023) Linkages between men’s wealth status and the ideal number of children: A trend and multilevel analysis of survey data in Nigeria. PLOS Glob Public Health 3(3): e0001036.


Cisgender women account for approximately 20% of incident HIV diagnoses in the US. However, only 10% of women who could benefit from HIV pre-exposure prophylaxis (PrEP) have been prescribed PrEP. US women face several challenges that may affect their seeking HIV prevention services, such as lack of PrEP awareness. Understanding these challenges may improve PrEP uptake, especially as innovative PrEP options, such as long-acting (LA) injectable PrEP, become available. This study explored interest in using LA-PrEP by factors that may increase risk of HIV acquisition.Cisgender women were recruited between November 2021 – March 2022 though targeted social media ads on Facebook, Instagram, and Tinder to complete an online, self-administered survey. Eligible participants were cisgender women who were: 18+ years, current US residents, reported penetrative sex in the past six months, and reported an unknown or negative HIV status. The survey included questions on demographics, sexual health and behavior, LA-PrEP awareness, and LA-PrEP interest. Descriptive statistics were calculated using SAS v9.4.1,834 eligible women completed the survey ; Geography: South – 65%, West – 21%, Northeast – 7.3%, Midwest – 6.8%; Race: Black, non-Hispanic – 34%, White, non-Hispanic – 25%, Hispanic – 27%, Another race – 14%). Women were more likely to have heard of LA-PrEP if they had reported injection drug use in the past year (71%), had an STI diagnosis (70%) or HIV test (66%) in the past two years, and were currently using contraception (65%). Interest in using LA-PrEP was consistently high; the difference between LA-PrEP awareness and interest was greatest among women with non-private health insurance and those with perceived likelihood of future HIV acquisition.Although interest in using LA-PrEP is high among US women, these results demonstrate the large gap between LA-PrEP awareness and interest in using it.Tonia Poteat, PhD, MPH, PAC, Viiv Healthcare: Advisor/Consultant Supriya Sarkar, PhD, MPH, GlaxoSmithKline: Stocks/Bonds|Viiv Healthcare: Employee Leigh Ragone, MS, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Danielle Bogan, BSN, MPH,DrPH, ViiV Healthcare: Contract worker Keith Rawlings, MD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Alex R. Rinehart, PhD, ViiV Healthcare: Employee Vani Vannappagari, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee


The neurobiology of gambling disorder (GD) is not yet fully understood. Although dysfunctional signalling involved in energy homeostasis has been studied in substance use disorders, it should be examined in detail in GD.To compare different endocrine and neuropsychological factors between individuals with GD and healthy controls (HC), and to explore endocrine interactions with neuropsychological and clinical variables.A case-control design was performed in 297 individuals with GD and 41 HC, assessed through a semi-structured clinical interview and a psychometric battery, adding 38 HC in the evaluation of endocrine and anthropometric variables.Individuals with GD presented higher fasting plasma ghrelin (p<.001) and lower LEAP2 and adiponectin concentrations (p<.001) than HC adjusting for body mass index (BMI). The GD group reported higher cognitive impairment regarding cognitive flexibility and decision-making strategies, a worse psychological state, higher impulsivity levels, and a more dysfunctional personality profile. Despite failing to find significant associations between endocrine factors and either neuropsychological or clinical aspects in GD, some impaired cognitive dimensions and lower LEAP2 concentrations significantly predicted GD presence.This study suggests distinctive neuropsychological and endocrine dysfunctions may operate in individuals with GD, predicting GD presence. Further exploration of endophenotypic vulnerability pathways in GD appear warranted, especially with respect to etiological and therapeutic potentials.F. Fernandez-Aranda Consultant of: Novo Nordisk , Employee of: editorial honoraria as EIC from Wiley, I. Baenas: None Declared, M. Etxandi : None Declared, B. Mora-Maltas: None Declared, R. Granero : None Declared, S. Tovar : None Declared, C. Diéguez: None Declared, M. Potenza Grant / Research support from: Mohegan Sun Casino and Connecticut Council on Problem Gambling, Consultant of: Opiant Pharmaceuticals, Idorsia Pharmaceuticals, Baria-Tek, AXA, Game Day Data and the Addiction Policy Forum; has participated in surveys, mailings or telephone consultations related to drug addiction, impulse control disorders or other health topics; and has consulted for law offices and gambling entities on issues related to impulse control or addictive disorders, Employee of: patent application in Yale University and Novartis, S. Jiménez-Murcia: None Declared.


Invasive fungal infections (IFI) are a major threat for patients under immunosuppression or with viral respiratory infections, like influenza or coronavirus disease 2019 (COVID-19). Access to appropriate tools is vital for early diagnosis and clinical management. The European Confederation of Medical Mycology (ECMM) survey on laboratory capacities in Europe aims to decipher the current diagnostic capacity and availability of treatments for IFIs in order to guide health professionals, patients, and policymakers.www.clinicalsurveys.net/uc/IFI_management_capacity/. A campaign seeking for mycologist feedback was launched. The survey was disseminated to all European mycologists affiliated with the ECMM and via social media  and email. Collected variables were a) institution profile, b) perceptions on invasive fungal disease in the respective institution, c) microscopy, d) culture and fungal identification, e) serology, f) antigen detection, g) molecular tests and h) therapeutic drug monitoring.The ECMM IFI diagnostic capacity survey is online accessible at Candida spp. (95.0%) and Aspergillus spp. (89.9%) were considered the most relevant pathogens. All the institutions had access (on site or outsourced) to cultures . Regarding availability of other diagnostic tests, 84.5% could also utilize microscopy, 83.7% antigen detection tests , 73.3% molecular tests (mainly PCR), and 62.4% to serology. At least one triazole was available for prescribing in 93.0% of the institutions, whereas at least one echinocandin in 90.3% and liposomal amphotericin B in 80.2%.258 centers from 41 countries have participated in the survey . Germany (n=30), France (n=28), Italy, Spain  and Turkey (n=21) were the origin country of almost half of the respondents. Incidence of IFI was considered as very low or low in 46.9% of the institutions, and moderate in 38.0%. Europe is generally well prepared to diagnose and treat invasive fungal infections. However, some institutions miss access to certain diagnostic tools and antifungal drugs.Martin Hoenigl, n/a, Astellas: Grant/Research Support|Euroimmun: Grant/Research Support|F2G: Grant/Research Support|Gilead: Grant/Research Support|Immy: Grant/Research Support|MSD: Grant/Research Support|Mundipharma: Grant/Research Support|Pfizer: Grant/Research Support|Pulmocide: Grant/Research Support|Scynexis: Grant/Research Support Oliver A. Cornely, MD PhD, DZIF: Advisor/Consultant|DZIF: Board Member|DZIF: Grant/Research Support|DZIF: Honoraria|DZIF: Stocks/Bonds


Integrase inhibitor (INI)–based antiretroviral (ARV) therapies are associated with greater weight gain than non-nucleoside reverse transcriptase inhibitor– or boosted protease inhibitor–based regimens, disproportionately affecting Black and Hispanic individuals and women. The mechanisms underlying this weight gain are unknown, and there are no prospective, randomized data exploring the impact of switching ARV classes to mitigate or reverse ARV-related weight gain.DEFINE  is a randomized (1:1), prospective, 48-week, active-controlled, open-label, multicenter phase 4 study evaluating switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) versus continuing INI+TAF/emtricitabine (FTC) in virologically-suppressed HIV-1–infected adults who had ≥10% weight gain while on the INI-based regimen. The primary objective was to assess percent change in body weight from baseline to Week 24 in both arms. The primary endpoint was analyzed using a mixed model for repeated measures in the intent-to-treat set of randomized participants who had received ≥1 dose of study drug. Secondary endpoints included change in body mass index (BMI), waist circumference (WC), efficacy, and safety. Data through Week 24 are reported.Table 1). Discontinuation rates were low and similar between arms. At Week 24, there was no significant difference in percent change in body weight from baseline between the D/C/F/TAF and INI+TAF/FTC arms . Most participants in each arm had body weight changes of ≤±3% and remained within baseline BMI and WC categories. Percent body weight changes for key subgroups are shown in Table 2. Switching to D/C/F/TAF was safe and well tolerated, and efficacy was maintained.Overall, 103 adults were randomized to D/C/F/TAF (n=53) or continued INI+TAF/FTC (n=50); 30% were female and 61% were Black/African American, with median 27.0 months virologic suppression on INI+TAF/FTC (Percent Change From Baseline in Body Weight Over Time for Participants Who Switched to D/C/F/TAF and Those Who Continued Their Current INI+TAF/FTC Regimen (ITT Set)D/C/F/TAF, darunavir/cobicistat/emtricitabine/tenofovir alafenamide; FTC, emtricitabine; INI, integrase inhibitor; ITT, intent-to-treat; LS, least-squares; TAF, tenofovir alafenamide. LS means percent changes in body weight were calculated in the ITT set of randomized participants who had received ≥1 dose of study drug using a mixed model for repeated measures, in which the dependent variable was percent change from baseline in body weight; independent variables were treatment, baseline body mass index, sex, and race (Black/African American vs non–Black/African American); and visits were repeated measures. Participants in the ITT set with baseline records and ≥1 postbaseline record were included.There was no significant difference in weight change through 24 weeks after switching from an INI-based regimen to D/C/F/TAF in adults with INI-related weight gain. Additional analyses are ongoing, including follow up through Week 48 and evaluation of changes in biomarkers and body composition (DEXA).William R. Short, MD, Gilead Sciences: Advisor/Consultant|ViiV: Advisor/Consultant|ViiV: Honoraria Moti Ramgopal, MD, FACP, FIDSA, AbbVie: Honoraria|Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Honoraria|Janssen Pharmaceuticals: Advisor/Consultant|Janssen Pharmaceuticals: Honoraria|Merck: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Debbie P. Hagins, MD, FAPCR, AAHIVS, Janssen Pharmaceuticals: Advisor/Consultant Johnnie Lee, MD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Richard Bruce Simonson, BS, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Tien-Huei Hsu, PhD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Ping Xu, PhD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds David Anderson, MD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds


Highly Resistant (including ceftriaxone-resistant and carbapenem-resistant) Enterobacterales (HRE) are a major and growing public health threat. Community spread of HRE is poorly understood.Monthly stool samples were obtained from patients who were discharged home after a hospitalization at one of 6 participating US medical centers with a clinical culture positive for HRE based on local laboratory antimicrobial susceptibility testing. Stool samples were also collected from community and household contacts they referred, and any contacts referred by those contacts. Samples were screened by culture on selective media for HRE, and with PCR for presence of extended-spectrum β-lactamase (ESBL), AmpC, and carbapenemase genes. Whole genome sequencing was performed on selected isolates.blaSHV and blaCTX-M-15 carrying K. pneumoniae isolates in a cluster of 4 participants, which included secondary transmission between a contact of the index patient and one of their contacts over a period of 555 days.Of 1,923 patients with positive HRE cultures from healthcare settings, 943/1,923 (49%) were discharged home. 65/943 (7%) were consented into the study, and 31/65 (48%) returned at least one sample . The index HRE species was isolated from stool samples from 19/31 (61%) participants; the median duration of detected carriage was 391 days (range 84-662 days). Screening for resistance genes was performed on 477 sample-derived isolates (Table 1); ESBL/AmpC and carbapenemase genes were present in 221/447 (49%) and 17/447 (4%), respectively. Stool samples  were collected from 11 contacts of 9 participants, and 1 contact of a contact. Index HRE were isolated from samples from 10/12 contacts (83%); the median duration from date of positive index culture to last positive sample in a contact was 400 days (range 146-588). Whole genome analysis confirmed genetic similarity (< 21 single nucleotide polymorphism difference) between ceftriaxone-resistant Patients with a clinical culture positive for HRE are at risk for prolonged intestinal HRE carriage after hospitalization. Upon returning home, community spread of HRE was very common in this cohort.Robert A. Bonomo, MD, Entasis: Grant/Research Support|Merck: Grant/Research Support|venatorax: Grant/Research Support|Wockhardt: Grant/Research Support David van Duin, MD, PhD, Entasis: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Union: Advisor/Consultant|Utility: Advisor/Consultant


Severe manifestations of human parechovirus (HPeV) infection, including meningoencephalitis and sepsis, can occur in neonates and young infants. Death has rarely been reported. Rates of HPeV infection fluctuate from year to year in the community. After the home isolation during the initial COVID-19 era in 2020, waves of respiratory viral outbreaks at unusual times of the year were identified in the pediatric community in 2021 and 2022, including increased number of cases of severe HPeV infection in young infants. This study characterizes the U.S. outbreak of HPeV infections that occurred in newborns and young infants in 2022.A multi-site, retrospective and prospective observational study identified hospitalized infants < =6 months, with a body fluid specimen positive for HPeV. IRB approval of a single protocol was obtained at each site. Data obtained included hospital summary, maternal and birth history, medications, bacterial and viral testing, and radiology results. Analysis included infants with hospitalizations from January 1 through December 31, 2022.13 academic sites were enrolled, which included 8 sites achieving full IRB approval/activation and completed data collection, and 5 sites pending activation [Fig 1A]. Interim analysis shows 112 infants across eleven states hospitalized with HPeV infection with a median hospital duration of 3 days (range 0-178 d), peaking in May 2022 [Fig 1B], with a spectrum of biochemical markers [Table 1]. The median age at hospitalization was 21.5 days of life . All but five infants received antibiotics during the admission, and more than half (54%) received acyclovir. Other pathogens were rarely reported [Table 2]. 45 (38%) infants received MRI brain imaging during hospitalization of which 29 were abnormal; 10 reports directly mentioning HPeV in the interpretation. A total of 51 EEGs were completed in 31 infants; 20 infants (18%) had seizures reported. 17 infants required anticonvulsants. Two infants died.We report the first multi-site, clinical description of the 2022 U.S. outbreak of HPeV among neonates and young infants. This is the first large series of infants with HPeV to report mortality. Further development of a multi-site U.S. collaboration to improve surveillance for HPeV is needed.Laura Filkins, PhD, Avsana Labs: Board Member|Avsana Labs: Stocks/Bonds|Biofire Diagnostics: Grant/Research Support Claudia M. Espinosa, MD, MSc, AstraZeneca: Grant/Research Support|Enanta: Grant/Research Support|Jansen and Jansen: Advisor/Consultant|Kentucky Rural Health Association: Honoraria|Merck: Grant/Research Support|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|Sanofi: Honoraria|Sobi: Dinner Joseph A. Bocchini, Jr., MD, Avalere: Advisor/Consultant|Enanta: Site PI on multicenter clinical trials, contract with employer|Moderna: Advisor/Consultant|Novavax: Sub-I on multicenter clinical trials, contract with employer|Pfizer: Advisor/Consultant|Pfizer: Site PI on multicenter clinical trials, contract with employer|Regeneron: Site PI on multicenter clinical trials, contract with employer|Sobi: Advisor/Consultant|Valneva: Advisor/Consultant Roberto P. Santos, MD, MSCS, Eli Lilly  - Site Open for Enrollment on March 8, 2023: Industry-sponsored clinical trials with research contract awarded to the University of Mississippi Medical Center with RPS as site PI|Eli Lilly  - study discontinuation on January 3, 2022: Industry-sponsored clinical trials with research contract awarded to the University of Mississippi Medical Center with RPS as site PI|JNJ  - study discontinuation on March 1, 2022: Industry-sponsored clinical trials with research contract awarded to the University of Mississippi Medical Center with RPS as site PI|MSD  - study discontinuation on December 6, 2022: Industry-sponsored clinical trials with research contract awarded to the University of Mississippi Medical Center with RPS as site PI Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, FAAM, Abbott: Honoraria|Altona Diagnostics: Grant/Research Support|Baebies Inc: Advisor/Consultant|BioMerieux: Advisor/Consultant|BioMerieux: Grant/Research Support|Bio-Rad: Grant/Research Support|Cepheid: Grant/Research Support|GSK: Advisor/Consultant|Hologic: Grant/Research Support|Lab Simply: Advisor/Consultant|Luminex: Grant/Research Support David W. Kimberlin, MD, Gilead: Grant/Research Support|Gilead: I served as site PI on Gilead's study of remdesivir in pediatric patients. All monies went directly to my university and not to me.


Integrated HIV, mental health, and substance use (SU) treatment strategies to improve health outcomes among women living with HIV (WWH) are limited. We described co-utilization of HIV, SU, and mental health treatment services among women enrolled in the Women’s Interagency HIV Study (WIHS) who report current SU.We included data from participants enrolled in 10 WIHS sites during their last study visit from 2013-2020. Current SU was defined as self-reported, non-medical use of drugs in the past year, excluding use of only marijuana. We described utilization of each treatment service  by subgroups of participants with current SU and either HIV, depressive symptoms (Center for Epidemiologic Studies–Depression score ≥ 16), heavy alcohol use ( > 7 drinks/week), or current tobacco use. We then compared utilization of services by those who did or did not utilize SU treatment using Chi-square/Fisher exact tests.Table) and 82.7% receiving any health care. Among women with current SU+HIV (n=233), 86.3% had an HIV healthcare provider visit since last study visit; among current SU+depressive symptoms (n=204), 39.2% had a mental health provider visit since last visit; among current SU+heavy alcohol use (n=87), 23.0% utilized alcohol treatment in the past year; and among current SU+current tobacco use (n=296), 10.1% utilized tobacco cessation treatment in the past year. Among subgroups of women with current SU who were eligible for another service, utilization of other services was significantly higher among those who utilized SU treatment for alcohol and tobacco cessation treatment, but not for any healthcare provider, HIV care, or mental health care provider .Among women with current SU (n=377), 41.9% reported utilizing SU treatment  high engagement in SU treatment, and high engagement in health care and HIV care regardless of SU treatment, but 2) low engagement in alcohol and tobacco cessation treatments. Integrated drug, alcohol, and tobacco treatment programs should not be missed opportunities for WWH with concurrent SU, alcohol or tobacco use.Cyra Christina Mehta, PhD, MSPH, Merck: Grant/Research Support Ellen Eaton, MD, MPH, Gilead: Grant/Research Support|Gilead: Honoraria


Understanding the transmissibility of respiratory viruses by symptoms is important for public health.Persons who tested positive for SARS-CoV-2 and their household contacts (HHC) were recruited from 7 US sentinel sites or by remote invitation nationwide during Sep. 2021—Mar. 2023. The household primary case was the person with the earliest symptom onset or positive test. Starting ≤6 days after primary case onset, primary cases and HHC completed symptom logs  and collected nasal or saliva specimens (daily for 10 days) that were tested by RT-PCR. Infected individuals were counted as having developed fever, lower respiratory symptoms , other symptoms , or as being asymptomatic based on all logs. Risk of secondary infection (any PCR positivity) among eligible, tested HHC (Methods 1) by symptoms of primary cases was estimated using Poisson regression with generalized estimating equations. We estimated days from onset to last PCR positive in a survival model.Methods upload 1. Enrolled and analytically included household members in case-ascertained studies of household transmission of SARS-CoV-2, United States, Sept 2021 - Mar 2023.This analysis included 842 households . Most primary cases (99%) and infected HHC (81%) were symptomatic (Results 1). Primary cases had higher frequencies of fever or LRS than infected HHC (Results 2). HHC exposed to primary cases who developed fever or LRS were more likely to become infected than HHC exposed to primary cases who did not have fever or LRS (Results 3). Post-hoc comparisons by individual symptoms supported this for fever and all LRS but chest pain . Primary cases with fever or LRS were PCR positive for a median of 14 days (95% CI: 14 – 15) post-onset, compared to 10 days (95% CI: 9 – 11) for cases who did not have fever or LRS.Results upload 1. Characteristics of included household members in case-ascertained studies of household transmission of SARS-CoV-2, United States, Sep 2021 - Mar 2023.Results upload 2. Proportion of primary cases and infected household contacts who experienced individual symptoms.Results upload 3. Unadjusted and adjusted risk of household contacts becoming infected with SARS-CoV-2, by symptoms in the primary case.Contacts of primary cases with fever or lower respiratory symptoms may have been more likely to become infected than contacts of primary cases without, suggesting higher transmissibility.Joshua Petrie, PhD, CSL Seqirus: Grant/Research Support Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member Suchitra Rao, MBBS, MSCS, Sequiris: Advisor/Consultant Edward Belongia, MD, Seqirus: Grant/Research Support Huong McLean, PhD, MPH, Seqirus: Grant/Research Support Edwin J. Asturias, MD, Hillevax: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support


There is a range of conditions for which long-term antibiotics are prescribed, most of which lack high quality evidence. Apart from promoting antimicrobial resistance, long-term antibiotics also impact the individual patient, disrupting the normal microbiome, and increasing the risk of infection with multi-resistant organisms (MROs). Previous work conducted at Monash Health, in Victoria, Australia, in 2014 noted great heterogeneity in both indications for prolonged antibiotic courses and the antimicrobial agents used.st January 2019 – 30th June 2019, and 1st January 2021 – 30th June 2021.The current study aimed to reassess prescribing trends within the same health network, across two time periods in 2019 and 2021. Outpatient prescriptions were extracted from the Monash Health pharmaceutical database at two time points, from 1Pneumocystis jirovecii pneumonia, and 83 (12%) post splenectomy. Trimethoprim/sulfamethoxazole was predominantly prescribed for PJP prophylaxis (n = 583), followed by dapsone (n = 21). Prosthetic joint infections made up 57 (73%) of those on suppressive antibiotics for infections deemed incurable. An array of antibiotics was utilised to treat them, as seen in Figure 1. The “Other” category included those on antibiotics for difficult to treat infections, such as mycobacterial infections (n = 43), chronic airways disease (n = 38), spontaneous bacterial peritonitis (n = 23) and recurrent urinary tract infections (n = 12). Data on comorbidities, hospitalisations and MROs between groups can be viewed in Table 1.From 4,704 outpatient prescriptions, 929 patients were identified as being on either one or more antibiotics for an intended duration of ≥ 12 months. There were a total 536 (57.7%) males and 393 females (42.3%), with a mean age of 58.20 years. Sixty-eight patients died between the two follow-up periods. Data was separated into 3 groups: primary prophylaxis in the setting of immunosuppression (n = 687), secondary prophylaxis for infections deemed incurable (n = 78), and “Other” (n = 164). Six hundred and four patients (88%) on primary prophylaxis were for Further research is needed. Prospective data examining long-term patient outcomes, and patterns of prescribing across different health networks would be of benefit.Jillian Lau, MBBS, FRACP, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|MSD: Grant/Research Support|Viiv Healthcare: Advisor/Consultant Ian Woolley, MBBS, FRACP, DTM&H, MD, Gilead: Educational support, investigator for Gilead supported trial|MSD: educational support, participation in a clinical trial|Pfizer: Educational support|ViiV: Educational Programs, Advisory Board member, ViiV sponsored trials


Despite extensive lab testing, infectious agents were not detected in ∼50% of patients hospitalized for acute undifferentiated febrile illness (AUFI) at Siriraj Hospital, Bangkok, Thailand. Unbiased metagenomic Next Generation Sequencing (mNGS) enables detection of many microbes present in patient samples. Target enrichment for viruses in these libraries represents a highly sensitive and cost-effective approach for overcoming host background present in clinical specimens. Plasma collected from 440 patients with AUFI between 2014-2021 were analyzed by both viral target enrichment and mNGS to determine their diagnostic values for the identification of human pathogens.m2000 instrument. mNGS libraries were prepared from ds-cDNA and hybridized to CVRP probes (Twist Biosciences) covering > 15,000 strains of vertebrate viruses. Target enriched libraries were run on a MiSeq; mNGS libraries were sequenced on a NextSeq. Reads were processed by the SURPI or DiVir pipelines and viral reads were mapped in the CLC Bio Genomics Workbench.Benzonase-treated plasma was extracted on an Abbott Rickettsia typhi, R. felis and Capnocytophaga canimorsus. Identification of parasites P. falciparum and P. vivax was consistent with clinical presentations. mNGS failed to detect blood-culture positive patients with Klebsiella pneumoniae, Pseudomonas aeruginosa, and Streptococcus gallolyticus septicemia.We identified viruses in 23% of our AUFI population using CVRP. mNGS increased viral detection to 26.8% and overall pathogen detection to 41.8%. Both methods identified relatively prevalent viruses such as Dengue, HIV-1, HBV, HAV and CHIKV, less common viruses such as Measles, HHV-6B, CMV, and PARV and emerging viruses such as SFTS virus with a high degree of correlation between NGS and clinical data. Bacterial pathogens identified by mNGS included CVRP and mNGS demonstrated that viral and rickettsial infections were important etiologies for AUFI in Thailand. This data supports the current recommendation of empirical therapy with ceftriaxone and doxycycline or azithromycin in severe or hospitalized AUFI. Implications for proper management of AUFI include lower rates of unnecessary testing and antimicrobial use.Julie Yamaguchi, BS, Abbott Labs: Patents|Abbott Labs: Employee|Abbott Labs: Stocks/Bonds Michael G. Berg, PhD, Abbott Laboratories: employee|Abbott Laboratories: Stocks/Bonds Sonja Weiss, BS, Abbott Laboratories: Employee|Abbott Laboratories: Stocks/Bonds Pakpoom Phoompoung, MD, Abbott Labs: Grant/Research Support|Abbott Labs: Mahidol University is a partner in the Abbott Pandemic Defense Coalition Gavin Cloherty, PhD, Abbott Labs: Patents|Abbott Labs: Employee|Abbott Labs: Stocks/Bonds Yupin Suputtamongkol, MD, Abbott Labs: Grant/Research Support|Abbott Labs: Mahidol University is partner in the Abbott Pandemic Defense Coalition


In “Evaluating the Acceptance and Usability of an App Promoting Weight Gain Prevention and Healthy Behaviors Among Young Women With a Family History of Breast Cancer: Protocol for an Observational Study” :e41246) the authors noted one error.Reference 15 originally appeared as:Cacciamani GE, Aron M, Gill I, Desai M. Re: oncological outcome according to attainment of pentafecta after robot-assisted radical cystectomy in patients with bladder cancer in the multicentre KORARC database. BJU Int 2020 Nov;126(5):644-645. [doi: 10.1111/bju.15222] [Medline: 32870582]This has been changed to:Michie S, Johnston M, Francis J, Hardeman W, Eccles M. From Theory to Intervention: Mapping Theoretically Derived Behavioural Determinants to Behaviour Change Techniques. Applied Psychology 2008 July;57(4):660-680. [doi: 10.1111/j.1464-0597.2008.00341]The correction will appear in the online version of the paper on the JMIR Publications website on April 4, 2023 together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories.


Oral sulopenem is a bilayer tablet composed of sulopenem etzadroxil and probenecid, an organic anion transport inhibitor that delays renal excretion of sulopenem. The goal of these studies was to determine whether the chosen clinical PO dosing regimen of 500 mg q12h, based on murine thigh models, would induce resistance amplification in a hollow-fiber Escherichia coli clinical isolates , at an initial burden of 106 CFU/mL, were subjected to sulopenem concentration-time profiles simulating total-drug urine concentrations following a 500 mg PO q12h regimen in a hollow-fiber in vitro infection model. Each isolate was additionally exposed to negative (levofloxacin 750 mg) and positive (meropenem 2 g) control regimens simulating free-drug plasma concentrations following intravenous (IV) dosing every 24 and 8 hours, respectively. Samples were collected for the enumeration of bacterial burdens and evaluation of the simulated pharmacokinetic profiles over the five-day study period. Each sample for bacterial enumeration was suspended onto agar plates, with and without supplementation of the respective antibiotic, to observe the density of the total and drug-resistant subpopulations over five days.Four 6 CFU/mL to those below 1 log10 CFU/mL, and prevented amplification of drug-resistant subpopulations over the five-day period for each isolate . The activity observed for the sulopenem 500 mg q12h regimen simulating urine concentrations was similar to that of the meropenem positive control regimen, while the levofloxacin negative control failed to provide any antimicrobial activity.The sulopenem 500 mg q12h regimen repeatedly reduced the bacterial density of the total population from the initial burden of 1.0 x 10These data support the selection of sulopenem etzadroxil/probenecid 500 mg/500 mg PO q12h, which minimized the potential for on-therapy drug-resistance amplification.Brian D. VanScoy, B.S., Adagio Therapeutics, Inc.: Grant/Research Support|Albany Medical Center: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|BioFire Diagnostics LLC: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Genentech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Employee|Inotrem: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|Theravance: Grant/Research Support|tranScrip Partners: Grant/Research Support|University of Wisconsin: Grant/Research Support|Utility Therapeutics: Grant/Research Support|ValanBio Therapeutics Inc.: Grant/Research Support|VenatoRx: Grant/Research Support Haley Conde, B.S., Adagio Therapeutics, Inc.: Grant/Research Support|Albany Medical Center: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|BioFire Diagnostics LLC: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Genentech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Employee|Inotrem: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|Theravance: Grant/Research Support|tranScrip Partners: Grant/Research Support|University of Wisconsin: Grant/Research Support|Utility Therapeutics: Grant/Research Support|ValanBio Therapeutics Inc.: Grant/Research Support|VenatoRx: Grant/Research Support Catherine E. Vincent, Ph.D., Adagio Therapeutics, Inc.: Grant/Research Support|Albany Medical Center: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|BioFire Diagnostics LLC: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Genentech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Employee|Inotrem: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|Theravance: Grant/Research Support|tranScrip Partners: Grant/Research Support|University of Wisconsin: Grant/Research Support|Utility Therapeutics: Grant/Research Support|ValanBio Therapeutics Inc.: Grant/Research Support|VenatoRx: Grant/Research Support Sujata M. Bhavnani, PharmD; MS; FIDSA, Adagio Therapeutics, Inc.: Grant/Research Support|Albany Medical Center: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|BioFire Diagnostics LLC: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Genentech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|Inotrem: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|Theravance: Grant/Research Support|tranScrip Partners: Grant/Research Support|University of Wisconsin: Grant/Research Support|Utility Therapeutics: Grant/Research Support|ValanBio Therapeutics Inc.: Grant/Research Support|VenatoRx: Grant/Research Support Steven I. Aronin, MD, Iterum Therapeutics Limited: Stocks/Bonds Sailaja Puttagunta, MD, Iterum Therapeutics Limited: Full time employee|Iterum Therapeutics Limited: Stocks/Bonds Paul G. Ambrose, PharmD; MS; FIDSA, Adagio Therapeutics, Inc.: Grant/Research Support|Albany Medical Center: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|BioFire Diagnostics LLC: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Genentech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|Inotrem: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|Theravance: Grant/Research Support|tranScrip Partners: Grant/Research Support|University of Wisconsin: Grant/Research Support|Utility Therapeutics: Grant/Research Support|ValanBio Therapeutics Inc.: Grant/Research Support|VenatoRx: Grant/Research Support


Transplant recipients with CMV infection have a high risk of complications and mortality. This study aimed to better understand patient and CP knowledge of post-transplant CMV and identify how it can be improved.Fig 1). We report results from Phase 2 (September 2022–March 2023), which included an educational webinar with a pre- and post-webinar assessment comprising 4 questions on the risk, symptoms, treatment, and complications of CMV; participants (pts) self-reported their confidence rating pre- and post-webinar. Transplant recipients and CPs also completed a quantitative survey on CMV management and patient/CP burden. Pts were recruited via the PatientsLikeMe (PLM) website, email, or social media.The study included 2 research phases (Table 1). Patients primarily contacted their surgeon about CMV and sought information on the internet.The webinar was completed by 33 pts. There was a total of 86 and 121 correct responses to the 4 pre- and post-survey questions, respectively, indicating a significant improvement in understanding of CMV post-webinar as compared with before . Almost half (n=16 [48%]) of pts reported feeling “not at all confident” in recognizing CMV symptoms post-transplant pre-webinar; post-webinar, this was 0 pts. Twenty-eight transplant recipients  and 1 CP completed the quantitative survey. Half of recipients received a CMV diagnosis post-transplant and 16/28 reported having no awareness of their or their donor’s CMV status prior to transplant. Most (27/28) recipients reported a positive experience with their care team post-transplant. Half of recipients set goals with their care team or were provided resources to track them post-transplant. Recipients reported CMV medication changes and challenges with treatment (Although transplant recipients reported positive experiences with their healthcare team, the post-transplant care journey could be improved by better educating patients about CMV and CMV management. Aggregate-level learnings from the study with be shared on the PLM platform to reinforce the value of participation in research.Funding: Collaborative research study; primary funding from Takeda Pharmaceuticals U.S.A., Inc.Deepshikha Singh, MPH, PatientsLikeMe: Employee|PatientsLikeMe: Ownership Interest Mary C. Burke, MHA, PatientsLikeMe: Employee|PatientsLikeMe: Ownership Interest Subhara Raveendran, PhD, Ascendis Pharma: Employee|PatientsLikeMe: Ownership Interest Erlyn Rachelle Macarayan, PhD, PatientsLikeMe: Employee|PatientsLikeMe: Ownership Interest Maisha Razzaque, MS, PatientsLikeMe: Employee|PatientsLikeMe: Ownership Interest Genovefa Papanicolaou, MD, Allovir: Advisor/Consultant|Amplyx: Advisor/Consultant|Astellas: Advisor/Consultant|Cidara: Advisor/Consultant|CSL Behring: Advisor/Consultant|DSMC: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: institutional research support for clinical trials|MSD: Advisor/Consultant|Octapharma: Advisor/Consultant|Partners Rx: Advisor/Consultant|Shire/Takeda: institutional research support for clinical trials|Symbio: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Advisor/Consultant|Vera Pharma: Advisor/Consultant Macey L. Levan, PhD, Takeda Pharmaceuticals: Advisor/Consultant Maggie McCue, MS, RD, Takeda Pharmaceuticals U.S.A., Inc.: Employee Megan Gower, PharmD, Takeda Pharmaceuticals U.S.A., Inc.: Employee|Takeda Pharmaceuticals U.S.A., Inc.: Ownership Interest Daniele K. Gelone, PharmD, Abbott Laboratories: Ownership Interest|Ionis Pharmaceuticals: Ownership Interest|Johnson & Johnson: Ownership Interest|NovoNordisk: Ownership Interest|Pfizer: Ownership Interest|Regenxbio: Ownership Interest|Takeda Pharmaceuticals U.S.A., Inc.: Employee|Takeda Pharmaceuticals U.S.A., Inc.: Ownership Interest|Vertex Pharmaceuticals: Ownership Interest


Acinetobacter baumannii (ACB), P. aeruginosa (PSA) and Enterobacterales are needed. Sulbactam-durlobactam (SUL-DUR) has potent, selective activity against ACB. Cefepime (FEP) is a common first-line therapy for hospital/ventilator associated pneumonia caused by non-ACB Gram-negative pathogens, but resistance to FEP is increasing. This study investigated the in vitro synergy of SUL-DUR + FEP against relevant pathogens.Due to the incidence of polymicrobial nosocomial infections, effective therapies with activity against ACB, n=4; PSA, n=4; E. coli, n=3; K. pneumoniae, n=3). One wild type K. pneumoniae isolate was included. Antibiotic concentrations simulated the free-steady state average concentration of clinically administered doses in patients .Static time-kills were performed in duplicate against fourteen FEP-resistant isolates (10 reduction in CFU/mL relative to 0h control). SUL-DUR plus FEP showed synergy  against one ACB isolate with an elevated MIC to SUL-DUR (32 mg/L). SUL-DUR plus FEP showed synergy vs. all PSA isolates . Against Enterobacterales, combination therapy was indifferent due to significant kill from SUL-DUR  with ∼ 4 log10 kill relative to 0h. SUL-DUR plus FEP was synergistic  vs. one E. coli isolate with an elevated MIC to SUL-DUR ( >128 mg/L). SUL-DUR plus FEP showed synergy against one of the K. pneumoniae with 2.97 log10 CFU/mL reduction relative to SUL-DUR and an additive effect against the other two K. pneumoniae tested . No antagonism was observed in any isolates.SUL-DUR alone showed significant activity against ACB consistent with the MIC for isolates at 8 mg/L and lower (range: 0.91-2.14 login vivo to verify these results are warranted.Synergy and no antagonism was observed with the combination of SUL-DUR and FEP. Further pharmacokinetic/pharmacodynamic studies conducted David P. Nicolau, PharmD, Allergan: Advisor/Consultant|Allergan: Grant/Research Support|Cepheid: Advisor/Consultant|Cepheid: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Tetraphase: Advisor/Consultant|Tetraphase: Grant/Research Support|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support|Wockhardt: Advisor/Consultant|Wockhardt: Grant/Research Support Christian M. Gill, PharmD, Cepheid: Grant/Research Support|Entasis therapeutics: Grant/Research Support|Everest Medicines: Grant/Research Support|Shionogi: Grant/Research Support


Cytomegalovirus (CMV) commonly affects solid organ transplant (SOT) recipients, with increased risks of rejection, graft failure, and other infections. While valganciclovir (vGCV) prophylaxis is effective in preventing CMV, its use is sometimes hindered by toxicity. We examined the association between vGCV exposure and adverse outcomes in SOT recipients.We performed a retrospective cohort study in two large academic transplant centers in Boston, with 1650 sequential adult (≥ 18 years of age) lung (343), heart (200), and kidney (1107) transplant recipients from 2010-2016. CMV D+ and/or CMV R+ SOT recipients generally received 3-12 months of vGCV prophylaxis. We used Fisher’s exact tests, Wilcoxon rank-sum tests, and Cox models to examine the relationship between vGCV exposure and adverse events potentially related to vGCV exposure.2, 594 (36%) were CMV D+R-, 397 (24%) D+R+, 333 (20%) D-R+, and 319 (19%) D-R-. Total vGCV exposure in patients receiving prophylaxis was 182  days. Patients receiving vGCV prophylaxis were significantly more likely to develop incident leukopenia with a white blood cell (WBC) count < 4000 cells/μL , severe leukopenia with a WBC < 1500 cells/μL (logrank p< 0.001), and incident thrombocytopenia < 150,000/μL (< 0.001) compared to patients not receiving vGCV. Early vGCV discontinuation, treatment interruption, reductions of vGCV below the dose appropriate for their renal function, and discontinuation or interruption of trimethoprim-sulfamethoxazole (TMP-SMZ) and mycophenolate due to myelosuppression were common, and patients exposed to vGCV were more likely to require G-CSF (Table 1). Opportunistic infections during holding of TMP-SMZ or vGCV, incident CMV resistance mutations, and rejection events occurring when mycophenolate was held for myelosuppression were extremely rare. After adjusting for age, BMI, and SOT type, vGCV exposure remained strongly associated with the risk of incident leukopenia (Table 2).Median age was 56  years, 1040 (63%) were male, median BMI was 26.8  kg/mExposure to vGCV prophylaxis in SOT recipients is associated with high rates of hematologic toxicities, although downstream clinical consequences of these toxicities are relatively rare.Sarah P. Hammond, MD, F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Grant/Research Support|Pfizer: Advisor/Consultant|Scynexis: Grant/Research Support|Seres therapeutics: Advisor/Consultant Sophia Koo, MD, SM, Aerium Therapeutics: Advisor/Consultant|GSK: Grant/Research Support|Merck: Grant/Research Support|Scynexis: Grant/Research Support


Posaconazole is a potent broad spectrum mould-active triazole that is increasingly used in children for treatment of aspergillosis, mucormycosis, and endemic mycoses. Although posaconazole has a favorable safety profile in pediatric patients, we recently observed an excess mineralocorticoid syndrome characterized by hypertension and hypokalemia within three weeks of treatment initiation in two patients. Both showed endocrinological evidence of posaconazole inhibition of 11-β-hydroxylase. As this condition is seldom reported in children, we conducted a systematic review of the literature for reports of this condition in pediatric cases.https://pubmed.ncbi.nlm.nih.gov/ and https://scholar.google.com/) was performed using key phrases of pediatrics (< 18 years) plus posaconazole plus hypertension, hypokalemia, mineralocorticoid excess, or 11-β-hydroxylase. Variables included age, sex, underlying condition, indication for posaconazole, blood pressure > 95th% for age and height, time from exposure to posaconazole to onset of hypertension, hypokalemia (≤3mEq/L), plasma aldosterone, serum 11- deoxycorticosterone, and serum 11-deoxycortisol.A systematic review of the literature . Four of 5 patients were male. Patients were treated for mucormycosis, histoplasmosis or ABPA. All patients developed hypertension within three weeks of starting posaconazole. Hypokalemia occurred in 4 out of 5 cases. Consistent with posaconazole inhibition of 11-β-hydroxylase, patients with available data had elevated serum 11- deoxycorticosterone, and/or elevated serum 11-deoxycortisol, and/or decreased or undetectable plasma aldosterone. All patients were managed with antihypertensive therapy.Children who develop hypertension and hypokalemia within 3 weeks of receiving posaconazole should be evaluated further for an excess mineralocorticoid syndrome and 11-β-hydroxylase inhibition. Management may consist of discontinuation of posaconazole and/or initiation of antihypertensive therapy.Jong Chung, MD, Cardinal Health: Advisor/Consultant|Dispersol Technologies: Advisor/Consultant|Forma Therapeutics: Advisor/Consultant|Global Blood Therapeutics: Advisor/Consultant|Jazz Pharmaceuticals: Advisor/Consultant Thomas J. Walsh, MD PhD, Abbott: Advisor/Consultant|Amplyx: Grant/Research Support|Astellas: Advisor/Consultant|Astellas: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Karyopharm: Advisor/Consultant|Lediant: Advisor/Consultant|Lediant: Grant/Research Support|Merck: Grant/Research Support|Omeros: Advisor/Consultant|Omeros: Grant/Research Support|Partner Therapeutics: Advisor/Consultant|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Statera: Advisor/Consultant|T2 Biosystems: Advisor/Consultant|T2 Biosystems: Grant/Research Support


Candida species are common colonizers in deceased donors managed in the intensive care environment, and transmission to the recipient through transplantation is a described phenomenon. We sought to characterize Candida transmission events in the US SOT population.Solid organ transplantation (SOT) is lifesaving, but donor-derived infections can be associated with significant morbidity and mortality. Candida occurred.Cases referred to Organ Procurement and Transplantation Network (OPTN) Disease Transmission Advisory Committee (DTAC) between 2012 and 2022 as potential donor disease transmission events (PDDTE) were adjudicated by DTAC based on consensus definitions. We included all recipients from any donor in which ≥1 proven or probable (P/P) or possible transmission of Candida in culture occurred in 24 of 40 donors and 63 of 124 recipients. Recipients were frequently bacteremic and had Candida growth at site of explanted kidney (Table 2). Mycotic aneurysm, bleed or hematoma occurred in 22 SOT recipients, 10 of which were P/P. Allograft explant was performed in 14 recipients (13 kidney and 1 other), 7 of which were P/P. Within 45 days of PDDTE reports, death occurred in 17 SOT recipients . Only 6 of the 17 recipients who died received antifungal therapy. Seven deaths occurred in the 49 mate recipients of the 24 P/P transmissions, though lack of culture results did not support escalating adjudications beyond possible.Forty deceased donors were identified . 124 SOT recipients received organs from these donors including 60 kidney, 27 liver, 15 heart, 14 lung, and 8 multivisceral or other. DTAC adjudications of recipients included 8 proven, 16 probable, 24 possible, 1 unlikely, 51 excluded, and 24 intervention without disease transmission (IWDT). Growth of Donor-derived Candida infections occur with significant associated morbidity, including graft loss, and mortality, especially in kidney recipients. Opportunity exists to further identify risks, improve communication across transplant centers, initiate appropriate antifungal therapy, and improve management of mycotic aneurysm due to candidiasis.Jason D. Goldman, MD, MPH, Adaptive Biotechnologies: Collaborative services agreements|Eli Lilly: Advisor/Consultant|Eli Lilly: Grant/Research Support|Eli Lilly: Honoraria|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|GSK: Advisor/Consultant|Karius, Inc.: Advisor/Consultant|Merck: Grant/Research Support|Monogram Biosciences / Labcorp: Collaborative services agreements|Regeneron: Grant/Research Support Anil J. Trindade, MD, CareDx, Inc.: Advisor/Consultant|CareDx, Inc.: Grant/Research Support|Veloxis Pharmaceuticals, Inc.: Grant/Research Support Ricardo M. La Hoz, MD, Takeda: Advisor/Consultant Lara A. Danziger-Isakov, MD, MPH, Aicuris: Contracted Clinical Research|Ansun Biopharma: Contracted Clinical Research|Astellas: Contracted Clinical Research|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Contracted Clinical Research|Pfizer: Contracted Clinical Research|Roche Diagnostics: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Contracted Clinical Research


Aging with HIV has unique challenges, including comorbidities and drug-drug interactions. TANDEM was a retrospective medical chart review conducted across 24 US sites. This subgroup analysis examines stable-switch PWH receiving dolutegravir/lamivudine by age.Eligible PWH were adults initiating dolutegravir/lamivudine prior to September 30, 2020, with ≥6 months of clinical follow-up . Stable-switch PWH were defined as having HIV-1 RNA < 50 copies/mL and on a stable antiretroviral regimen for ≥3 months upon dolutegravir/lamivudine initiation. Clinical characteristics, treatment history, and outcomes were analyzed for 3 age groups among dolutegravir/lamivudine stable-switch PWH. Analyses were descriptive.The number of dolutegravir/lamivudine stable-switch PWH in each age group was 86 (< 50 years), 106 (≥50 years), and 20 (≥65 years). A greater proportion of PWH in the older age groups were female sex at birth . More PWH in older age groups had reported comorbidity  and polypharmacy . Avoidance of long-term toxicities was the biggest driver for initiating dolutegravir/lamivudine in the older age groups  while simplification/streamlining of treatment was the most common (27.9%) primary reason for PWH to switch to dolutegravir/lamivudine in the < 50 years group . For PWH < 50 years, 95.3% remained virologically suppressed for the study period. Similarly, 96.2% of PWH ≥50 years and 95.0% of PWH ≥65 years remained virologically suppressed for the study period . Three PWH with nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance at baseline remained suppressed.Virological suppression rates were high and similar by age group among dolutegravir/lamivudine stable-switch PWH despite higher rates of comorbidities and polypharmacy in the older age groups. This real-world analysis is consistent with clinical study data supporting dolutegravir/lamivudine as an effective treatment strategy in older PWH.Andrew P. Brogan, PhD, ViiV Healthcare: Stocks/Bonds Jihad Slim, MD, FACP, ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support Gustavo Verdier, BSc, BPharm, MBA, ViiV Healthcare: Stocks/Bonds Gavin Harper, BA, ViiV Healthcare: Grant/Research Support Katie L. Mycock, MChem, ViiV Healthcare: Grant/Research Support Hannah Wallis, MS, ViiV Healthcare: Grant/Research Support Cynthia Donovan, PharmD, ViiV Healthcare: Stocks/Bonds


In the TACKLE phase 3 outpatient treatment study, 600-mg AZD7442 (tixagevimab/cilgavimab) in adults with mild to moderate COVID-19 significantly reduced progression to severe disease or death over 29 days and was well-tolerated at primary analysis. Here, we report final safety findings from TACKLE.In TACKLE (NCT04723394), non-hospitalized adults with mild to moderate COVID-19 were randomized 1:1 and dosed ≤7 days from symptom onset with 600-mg AZD7442 (N=452) or placebo (N=451). Results are reported from the January 22, 2023 final data cut-off. The primary safety endpoint was assessment of adverse events (AEs), serious adverse events (SAEs), and AEs of special interest (AESIs). A cardiovascular events adjudication committee independently evaluated 5 event types .Table). The most common AEs were COVID-19, post-acute COVID-19 syndrome, and COVID-19 pneumonia. Reinfection with COVID-19 within 6 months occurred in 1 (0.2%) and 2 (0.4%) participants in the AZD7442 and placebo groups, respectively . Most AEs were mild to moderate in severity; 33 (7.3%) and 51 (11.3%) of participants in the AZD7442 and placebo groups, respectively, reported an AE of grade 3 (severe) or 4 (life-threatening). SAEs occurred in 46 (10.2%) and 65 (14.4%) AZD7442 and placebo participants, and deaths in 8 (1.8%) and 8 (1.8%), respectively. AESIs occurred 4.2% and 3.8% of AZD7442 and placebo participants, respectively, including 0.4% and 0.2% with cardiovascular disorders categorized as AESIs. Cardiovascular events occurring in 4 (0.9%) participants in both groups were evaluated by an adjudication committee, with 1 (0.2%) participant in both groups having a positively adjudicated event.Across both the AZD7442 and placebo groups, 797 (87.6%) participants completed the study. Median follow-up was ∼15 months or 458.5 days in the AZD7442 group and 458.0 days in the placebo group. AEs occurred in 251 (55.5%) and 252 (55.9%) of participants administered AZD7442 and placebo, respectively (This analysis provides further evidence of the long-term safety of AZD7442 as treatment for COVID-19.F.D. Richard Hobbs, FMedSci, AstraZeneca: Grant/Research Support|National Institute for Health and Care Research: Grant/Research Support|UK Research and Innovation: Grant/Research Support Hugh Montgomery, MD, AstraZeneca: Advisor/Consultant|Millfield Medical Electronics Ltd: Advisor/Consultant Francisco Padilla, MD, Amgen: Grant/Research Support|AstraZeneca: Grant/Research Support|Boehringer Ingelheim: Grant/Research Support|Ferrer: Grant/Research Support|Kowa: Grant/Research Support|Medix: Grant/Research Support|Merck: Grant/Research Support|Merck Sharp and Dohme: Grant/Research Support|Novartis: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support|Servier: Grant/Research Support|Silanes: Grant/Research Support Jesus Abraham Simón Campos, MD, AstraZeneca: Expert Testimony|Atea: Advisor/Consultant|Eli Lilly: Advisor/Consultant|Pfizer: Expert Testimony|Regeneron: Expert Testimony|Roche: Expert Testimony Douglas Arbetter, MPH, AstraZeneca: Employement|AstraZeneca: Stocks/Bonds Seth Seegobin, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Alexandre Kiazand, MD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Katie Streicher, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Nuria Martinez-Alier, PhD, AstraZeneca: Employee|AstraZeneca: Employement|AstraZeneca: Stocks/Bonds|AstraZeneca: Stocks/Bonds Taylor Cohen, PhD, AstraZeneca: Employement|AstraZeneca: Stocks/Bonds Mark T. Esser, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds


MenACWY and MenB are commonly used vaccines to prevent invasive meningococcal disease (IMD), targeting serogroups A, B, C, W, Y. MenABCWY combination vaccines are under development and could provide increased vaccine coverage of serogroups. This qualitative study aimed to identify concepts affecting preferences in adolescents (Ado) and parents/caregivers (P/C) decision making towards combination vaccine in the US.Two focus group discussions (FGD), 90-minutes with Ado (16-23 years) and P/C of adolescents (16-18 years) were conducted (Table 1). Guides were developed based on a targeted literature review to investigate preferences for potential features of a combination vaccine. Participants were presented with IMD and vaccines information. Important/least important factors for decision-making were transcribed in response to open-ended/probes questions. FGDs were coded to apply thematic assessment. Results were synthesized separately by moderator-probed and spontaneously mentioned themes. Percentages were calculated on participant numbers contributing to a theme.Thirteen participants were included in FGDs . Ado preferred a combination vaccine which provided time saving (100%) and convenience (83%) by reducing the number of injections in the immunization series (100%) and number of visits (100%). P/C considered injection site discomfort (71%) as an important decision factor for a combination vaccine, however Ado considered this as least important (100%). Both groups considered impact on healthcare system and environment as least important for a combination vaccine (55%) (Table 3). Cross-protection against other infectious disease  and spontaneous themes  emerged (Table 4). These concepts were considered relevant for combination vaccine decision-making, although could be applicable to IMD vaccination more generally.The findings suggest vaccine-receivers preferred a combination vaccine covering serogroups A, B, C, W, Y, with simplified schedules (e.g. fewer visits and injections) and potential cross-protection against other infectious diseases.Shahina Begum, GSK: Employee Eliazar Sabater Cabrera, PhD, GSK: Employee|GSK: Stocks/Bonds Linda Hortobagyi, MSc, GSK: Contractor Twinkle Khera, Mtech, IQVIA: Advisor/Consultant Selene Camargo Correa, PhD, IQVIA: Advisor/Consultant Laurie Batchelder, PhD, IQVIA: Advisor/Consultant Zeki Kocaata, PhD, GSK: Stocks/Bonds


Although respiratory syncytial virus (RSV) is a common pathogen in older adults, little is known about the social risk factors for RSV hospitalization in this population. In this study, we sought to evaluate the social determinants of RSV-related hospitalizations in older adults.From October 2018 to March 2020, we enrolled patients ≥50 years of age who were admitted with an acute respiratory infection (ARI) or CHF/COPD exacerbation at two Emory University hospitals. Enrolled patients were interviewed regarding their medical and social history and their medical charts were abstracted. Nasopharyngeal and oropharyngeal swabs and standard-of-care specimens were obtained for BioFire® Respiratory Panel analysis. Demographic, interview responses, and selected comorbidities were compared with bivariate analysis and generated a stepwise logistic regression model with inclusion in the model set at 0.05. Statistical analysis was performed using SAS v.9.4.Of the 1429 enrolled participants, 78 (5.5%) were RSV-positive (Table 1). Compared to RSV-negative participants, those with RSV were more commonly female , immunocompromised  and particularly with HIV/AIDS , and had traveled > 100 miles in the prior 2 weeks . No significant differences were found between the groups by baseline health status or other comorbidities. Participants with RSV had higher frequency of low to moderate activity at baseline than those who were RSV-negative. No significant differences were identified for those living with children or performing childcare ≥ 6 hours a week. Adjusting for sex, activity frequency, travel, and immunocompromised status, those who were male , exercised 2-3 times per week , traveled , or were immunocompromised  had greater odds of RSV positivity compared to the reference groups (Table 2).Among ARI hospitalizations, RSV prevalence was higher for female sex, immunocompromised status, and those that travelled within the preceding two weeks. Understanding risk factors for severe RSV hospitalization may inform prevention recommendations.Elizabeth Begier, M.D., M.P.H., Pfizer: EB is an employee of Pfizer, the sponsor of this study|Pfizer: Stocks/Bonds Qing Liu, M.S., Pfizer Inc.: Stocks/Bonds Robin Hubler, MS, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Bradford J. Gessner, M.D., M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant|Hillevax, Inc: Advisor/Consultant Nadine Rouphael, MD, Icon, EMMES, Sanofi, Seqirus, Moderna: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc.: Safety Monitoring Board|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Currently an employee|Moderna: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Safety Monitoring Board|WCG/ACI Clinical: Data Adjudication Board Christina A. Rostad, MD, BioFire Inc.: Grant/Research Support|GlaxoSmithKline Biologicals: Grant/Research Support|Janssen: Grant/Research Support|MedImmune LLC: Grant/Research Support|Meissa Vaccines, Inc.: RSV vaccine technology|Merck & Co., Inc.: Grant/Research Support|Micron Technology, Inc.: Grant/Research Support|Moderna, Inc.: Grant/Research Support|Novavax: Grant/Research Support|PaxVax: Grant/Research Support|Pfizer, Inc.: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Grant/Research Support


Two independent placebo-controlled clinical trials conducted prior to SARS-CoV-2 Omicron demonstrated that sotrovimab and remdesivir reduced hospitalization among high-risk outpatients with mild to moderate COVID-19. However, their effectiveness have not been directly compared.This retrospective study examined all high-risk outpatients with mild to moderate COVID-19 who received either remdesivir or sotrovimab at Mayo Clinic during the Omicron BA.1 surge from January to March 2022. COVID-19-related hospitalization or death within 28 days were compared between the two treatment groups.Among 3,257 patients, 2,158 received sotrovimab and 1,099 received remdesivir. Patients treated with sotrovimab were younger  and had lower comorbidity , but were more likely to be immunocompromised (47.3% vs. 30.2%) than remdesivir-treated patients. The majority (89%) had received at least one dose of COVID-19 vaccine . COVID-19-related hospitalization  and mortality within 28 days  were similarly low. A propensity score weighted analysis demonstrated no significant difference in the rates of COVID-related hospitalization and death within 28 days between the two groups.This study demonstrated favorable outcomes that were not significantly different between patients treated with remdesivir or sotrovimab. As sotrovimab is no longer authorized, these results support the continued use of remdesivir for treating high-risk patients with COVID-19 during the current Omicron-predominant epoch.Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Maria Gonzalez Suarez, M.D., Ph.D., Gilead: Grant/Research Support Ravindra Ganesh, M.B.B.S., M.D., Alpaca Health: Advisor/Consultant Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support


When remdesivir was approved for non-hospitalized, high-risk patients with mild to moderate COVID-19, Texas Children’s Hospital (TCH) implemented an outpatient clinic for eligible patients to receive remdesivir infusions. There are limited data evaluating the use of outpatient remdesivir in pediatric patients. We describe the clinical characteristics and outcomes of the patients treated with outpatient remdesivir at TCH.Patients that were referred to receive outpatient remdesivir from June 7, 2022 to April 5, 2023 were included. Information collected includes demographics, comorbidities, refusal reason, adverse events, emergency center (EC) visit or admission within 14 days after final dose, and EC visit or admission within 14 days of referral if patients did not receive remdesivir. Chi-square was used to determine differences between the groups.There were 187 patients referred during the study period. The median age of all referred patients was 8.8 years (IQR 4.84-12.96 years). The median time from reported symptom onset to dose 1 of remdesivir was 2 days (IQR 1-4 days). The comorbidities of all patients are listed in Figure 1. Out of the 182 patients, 69 patients (37.9%) received remdesivir, 10 patients (5.5%) were admitted prior to receiving their first dose, and 107 (58.8%) were not treated. The most common refusal reason was improvement between the referral and treatment evaluation visit . Among those treated, 8 patients (11.6%) visited the EC resulting in 7 admissions (10.1%) within 14 days of their last dose of remdesivir, while 7 patients (6.5%) that were referred but did not receive remdesivir visited the EC resulting in 3 admissions (2.8%) within 14 days of their referral being placed (p=0.04). More serious underlying conditions  were more common among treated patients vs. untreated patients (p=0.00002).Outpatient remdesivir was well tolerated among pediatric patients. In our series, the majority of high- risk patients receiving outpatient remdesivir treatment did not require subsequent EC visit or hospitalization. More robust data are needed to determine the clinical efficacy of this treatment for pediatric patients in the outpatient setting.Lisa Forbes Satter, MD, ADMA: Advisor/Consultant|CsL Behring: Advisor/Consultant|Grifols: Advisor/Consultant|incyte: Advisor/Consultant|Pharming: Advisor/Consultant|Takeda: Advisor/Consultant Flor M. Munoz, MD, MSc, CDC respiratory virus surveillance: Grant/Research Support|Gilead: Grant/Research Support|Moderna, sanofi, aztra zeneca, Merck, GSK: Advisor/Consultant|NIH: DSMB|NIH COVID-19 vaccines in pregnancy: Grant/Research Support|Pfizer Pediatric COVID-19 vaccines: Grant/Research Support|Pfizer, Dynavax, Monderna, Meissa, NIH: DSMB


Antibiotic resistant infections commonly occur in healthcare settings, but the prevalence of antibiotic resistant genes (ARGs) in healthy individuals in the community is unknown. We provide an initial assessment of nasopharyngeal carriage of ARGs conferring resistance to macrolides and/or lincosamides, including erm, mph, ABC-F, and lnu genes.Nasopharyngeal swabs were systematically obtained at enrollment and weekly thereafter from children and adults enrolled in a household-based prospective cohort study in Lima, Peru. Samples were sequenced using the Illumina Respiratory Pathogen/ID AMR Panel to detect common respiratory bacteria and ARGs. We defined ‘any erm gene’ (erm) as the detection of any specific erm gene class, ‘any mph gene’ as detection of any specific mph gene class, ‘any ABC-F gene’ as any specific ABC-F gene class, and ‘any lnu gene’ as any specific lnu gene detection. We compared the prevalence of erm, mph, ABC-F and lnu gene colonization at enrollment among age groups  using the Fisher's exact test. We then compared the frequency of co-detection of two or more macrolide or lincosamide ARGs between both pediatric age groups (ages 0-17 years) and both adult age groups (18+ years).114 individuals were included in this analysis (Table 1). At least one macrolide or lincosamide ARG was detected in 61/114 (53.5%) individuals. The prevalence of erm, mph, ABC-F, or lnu gene detection was similar among age groups . Two or more genes were co-detected in 45/114 (39.4%) individuals. Co-detections with two or more erm, mph, ABC-F, or lnu genes were more frequent in children 0-17 years compared to adults 18+ years (p=0.013) .Conclusions: These preliminary results indicate that macrolide or lincosamide ARGs were commonly detected in healthy community-dwelling children and adults in Lima, Peru. The prevalence of erm, mph, ABC-F, and lnu genes was similar across age groups, and co-detection of ARGs was more common in children. Future studies will assess changes in ARG carriage over time, transmission among household members, and its clinical relevance.  Claudio Lanata, MD, MPH, CureVAc AG Germany: Grant/Research Support|HilleVac Inc.: Advisor/Consultant|HilleVac Inc.: Grant/Research Support Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support