How I manage infection risk and prevention in patients with lymphoid cancer.

Infections are a common cause of morbidity and mortality in patients with lymphoid cancer. Because cancer therapeutics, including new targeted therapies and immunotherapies, are evolving, clinicians need to be aware of additional risk factors and infections that may arise in patients treated with these agents. This article highlights fundamental issues in treating patients with lymphoid cancer, including risk factors for infection, screening for infectious diseases, and recommendations for antimicrobial prophylaxis in patients with lymphoid cancers. We present 4 scenarios of patients with lymphoid cancers who have various infections, and we describe a treatment approach based on a combination of evidence-based data and experience because objective data are limited regarding infections, especially with newer agents. The goal of this discussion is to provide a framework for institutions and health care providers to help them develop their own approach to preventing and treating infections in patients with lymphoid cancer.

Vaccine response after pneumococcal vaccination in allogeneic hematopoietic stem cell transplant recipients.

Current guidelines for vaccination in allogeneic hematopoietic stem cell transplant (HCT) recipients recommend initiation of pneumococcal vaccination series three to six months post-HCT, with most data supporting initiation at six months due to a more robust immune response. This single-center, retrospective, observational chart review aimed to evaluate the impact of initiating the pneumococcal vaccine series at three months post-HCT compared to six months post-HCT. The primary endpoints were defined as a percentage of patients with a serologic response of >1 and >1.3 µg/mL for over 50% of the defined serotypes. Outcomes showed no difference in immunologic response between the two groups.

Development of Host Immune Response to Bacteriophage in a Lung Transplant Recipient on Adjunctive Phage Therapy for a Multidrug-Resistant Pneumonia.

Bacteriophage therapy is the use of viruses to kill bacteria for the treatment of antibiotic-resistant infections. Little is known about the human immune response following phage therapy. We report the development of phage-specific CD4 T cells alongside rising phage-specific immunoglobulin G and neutralizing antibodies in response to adjunctive bacteriophage therapy used to treat a multidrug-resistant Pseudomonas aeruginosa pneumonia in a lung transplant recipient. Clinically, treatment was considered a success despite the development phage-specific immune responses.

Donor call simulation: A novel medical education tool to evaluate trainees' clinical decision-making in transplant infectious disease.

BACKGROUND: Evaluating organ suitability for transplantation based on infection risk is a core competency in transplant infectious disease (TID). It is unclear if trainees have opportunities to practice during training. We created a simulation curriculum to develop and evaluate this skill among infectious disease (ID) trainees. METHODS: We created six simulation questions about organ suitability for transplant based on infection risk. During trainees' TID rotations, faculty texted or paged the simulation cases posing as the transplant coordinator. Trainees had 15 min to ask questions before deciding the suitability of the organ and explained their clinical reasoning in a survey. Trainees completed a post-simulation survey to evaluate its effectiveness. RESULTS: ID trainees, including residents and fellows on rotation, from seven centers participated. Eighty-seven percent (13/15) of trainees felt the simulation was effective in teaching them this concept, and 80% (12/15) felt prepared for clinical practice. The proportion of correct responses was generally high among the six different cases (43%-100%); correct responses increased for some cases in the post-activity survey. Of the 100 clinical reasoning decisions made during the activity, 19% were discordant, where the trainee correctly identified suitable organs for incorrect reasons. CONCLUSION: Our simulation was effective in teaching when to accept or reject an organ for transplant and was a valuable educational tool. By evaluating clinical reasoning for decisions our simulation provides educators with nuanced insight and allows for targeted coaching. This study demonstrates a critical need for further educational tools in TID.

Post-transplant survey to assess patient experiences with donor-derived HCV infection.

BACKGROUND: Despite increased utilization of hepatitis C virus-infected (HCV+) organs for transplantation into HCV-uninfected recipients, there is lack of standardization in HCV-related patient education/consent and limited data on financial and social impact on patients. METHODS: We conducted a survey on patients with donor-derived HCV infection at our center transplanted between 4/1/2017 and 11/1/2019 to assess: why patients chose to accept HCV+ organ(s), the adequacy of their pre-transplant HCV education and informed consent process, financial issues related to copays after discharge, and social challenges they faced. RESULTS: Among 49 patients surveyed, transplanted organs included heart (n = 19), lung (n = 9), kidney (n = 11), liver (n = 4), heart/kidney (n = 4), and liver/kidney (n = 2). Many recipients accepted an HCV-viremic (HCV-V) organ due to perceived reduction in waitlist time (n = 33) and/or trust in their physician's recommendation (n = 29). Almost all (n = 47) felt that pre-transplant education and consent was appropriate. Thirty patients had no copay for direct-acting antivirals (DAA) for HCV, including 21 with household income <$20 000; seven had copays of <$100 and one had a copay >$1000. Two patients reported feeling isolated due to HCV infection and eight reported higher than anticipated medication costs. Patients' biggest concern was potential HCV transmission to partners (n = 18) and family/friends (n = 15). Overall almost all (n = 47) patients reported a positive experience with HCV-V organ transplantation. CONCLUSION: We demonstrate that real-world patient experiences surrounding HCV-V organ transplantation have been favorable. Almost all patients report comprehensive HCV-related pre-transplant consent and education. Additionally, medication costs and social isolation/exclusion were not barriers to the use of these organs.

Early clinical experience of bacteriophage therapy in 3 lung transplant recipients.

Bacteriophage therapy (BT) uses bacteriophages to treat pathogenic bacteria and is an emerging strategy against multidrug-resistant (MDR) infections. Experience in solid organ transplant is limited. We describe BT in 3 lung transplant recipients (LTR) with life-threatening MDR infections caused by Pseudomonas aeruginosa (n = 2) and Burkholderia dolosa (n = 1). For each patient, lytic bacteriophages were selected against their bacterial isolates. BT was administered for variable durations under emergency Investigational New Drug applications and with patient informed consent. Safety was assessed using clinical/laboratory parameters and observed clinical improvements described, as appropriate. All patients received concurrent antibiotics. Two ventilator-dependent LTR with large airway complications and refractory MDR P. aeruginosa pneumonia received BT. Both responded clinically and were discharged from the hospital off ventilator support. A third patient had recurrent B. dolosa infection following transplant. Following BT initiation, consolidative opacities improved and ventilator weaning was begun. However, infection relapsed on BT and the patient died. No BT-related adverse events were identified in the 3 cases. BT was well tolerated and associated with clinical improvement in LTRs with MDR bacterial infection not responsive to antibiotics alone. BT may be a viable adjunct to antibiotics for patients with MDR infections.

Successful adjunctive use of bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa infection in a cystic fibrosis patient.

INTRODUCTION: We describe the use of bacteriophage therapy in a 26-year-old cystic fibrosis (CF) patient awaiting lung transplantation. HOSPITAL COURSE: The patient developed multidrug resistant (MDR) Pseudomonas aeruginosa pneumonia, persistent respiratory failure, and colistin-induced renal failure. We describe the use of intravenous bacteriophage therapy (BT) along with systemic antibiotics in this patient, lack of adverse events, and clinical resolution of infection with this approach. She did not have recurrence of pseudomonal pneumonia and CF exacerbation within 100 days following the end of BT and underwent successful bilateral lung transplantation 9 months later. CONCLUSION: Given the concern for MDR P. aeruginosa infections in CF patients, BT may offer a viable anti-infective adjunct to traditional antibiotic therapy.

Clinical and economic burden of infections in hospitalized solid organ transplant recipients compared with the general population in Canada - a retrospective cohort study.

Infections continue to be a major cause of post-transplant morbidity and mortality, requiring increased health services utilization. Estimates on the magnitude of this impact are relatively unknown. Using national administrative databases, we compared mortality, acute care health services utilization, and costs in solid organ transplant (SOT) recipients to nontransplant patients using a retrospective cohort of hospitalizations in Canada (excluding Manitoba/Quebec) between April-2009 and March-2014, with a diagnosis of pneumonia, urinary tract infection (UTI), or sepsis. Costs were analyzed using multivariable linear regression. We examined 816 324 admissions in total: 408 352 pneumonia; 328 066 UTI's; and 128 275 sepsis. Unadjusted mean costs were greater in SOT compared to non-SOT patients with pneumonia [(C$14 923 ± C$29 147) vs. (C$11 274 ± C$18 284)] and sepsis [(C$23 434 ± C$39 685) vs. (C$20 849 ± C$36 257)]. Mortality (7.6% vs. 12.5%; P < 0.001), long-term care transfer (5.3% vs. 16.5%; P < 0.001), and mean length of stay (11.0 ± 17.7 days vs. 13.1 ± 24.9 days; P < 0.001) were lower in SOT. More SOT patients could be discharged home (63.2% vs. 44.3%; P < 0.001), but required more specialized care (23.5% vs. 16.1%; P < 0.001). Adjusting for age and comorbidities, hospitalization costs for SOT patients were 10% (95% CI: 8-12%) lower compared to non-SOT patients. Increased absolute hospitalization costs for these infections are tempered by lower adjusted costs and favorable clinical outcomes.

Molecular characterization of ß-lactamase genes in clinical isolates of carbapenem-resistant Acinetobacter baumannii.

BACKGROUND: Acinetobacter baumannii is a nosocomial pathogen which is establishing as a major cause of morbidity and mortality within the healthcare community. The success of this pathogen is largely due to its ability to rapidly gain resistance to antimicrobial therapies and its capability to persist in an abiotic environment through the production of a biofilm. Our tertiary-care hospital has showed high incidence of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. METHODS: In this study we explore both genotypic and phenotypic properties of 26 CRAB isolates: 16 isolates were collected from January 2010 to March 2011, and 10 were collected between February and May 2015. RESULTS: We determined that all 26 CRAB isolates possessed multiple ß-lactamase genes, including genes from Groups A, C, and D. Specifically, 42% of the isolates possesses the potentially plasmid-borne genes of OXA-23-like or OXA-40-like ß-lactamase. The presence of mobile gene element integron cassettes and/or integrases in 88% of the isolates suggests a possible mechanism of dissemination of antibiotic resistance genes. Additionally, the location of insertion sequence (IS) ISAba1 in promotor region of of the OXA-51-like, ADC-7, and ampC genes was confirmed. Multilocus sequence typing (MLST) demonstrated that all 26 CRAB isolates were either sequence type (ST)-229 or ST-2. Interestingly, ST-2 went from being the minority CRAB strain in the 2010-2011 isolates to the predominant strain in the 2015 isolates (from 32 to 90%). We show that the ST-2 strains have an enhanced ability to produce biofilms in comparison to the ST-229 strains, and this fact has potentially led to more successful colonization of the clinical environment over time. CONCLUSIONS: This study provides a longitudinal genetic and phenotypic survey of two CRAB sequence types, and suggests how their differing phenotypes may interact with the selective pressures of a hospital setting effecting strain dominance over a 5-year period.

Digital Technology Use and Adolescent Mental Health Before and During the COVID-19 Pandemic: The Roles of Internet Addiction and Digital Competence.

This study examined whether Internet addiction (IA) and digital competence (DC) mediated the association between digital technology use and mental health problems in adolescents before and during the COVID-19 pandemic, when digital device use increased dramatically. Repeated cross-sectional data from a 3-year cross-cohort study adopting stratified random sampling were analyzed. In 2019, 569 adolescents (female = 312) from 14 secondary schools completed a DC assessment and an online survey on their digital technology use, IA, and mental health. In 2021, 775 adolescents (female = 397) from 11 of those 14 schools completed both instruments. Results showed that adolescents in 2021 spent more time using digital devices, were more digitally competent, and reported more mental health problems than adolescents in 2019. The prevalence of IA was 8 percent in 2019 and 12.4 percent in 2021. In both years, more frequent digital technology use predicted a higher risk of IA, which was associated with more mental health problems (indirect ß = 0.08, p < 0.001 for 2019 and ß = 0.05, p < 0.001 for 2021). In addition, in 2021, DC was positively associated with digital technology use and negatively with IA, which indirectly related to fewer mental health problems (indirect ß = -0.01, p = 0.03). In conclusion, DC is a protective factor alleviating the positive associations of digital technology use and IA with mental health problems in adolescents when the ecological context requires high levels of digital device use.

Understanding the Symptom Burden and Impact of Myasthenia Gravis from the Patient's Perspective: A Qualitative Study.

INTRODUCTION: Patients with generalized myasthenia gravis (gMG) experience functional impairment due to MG symptoms. This study aimed to assess, from the patient perspective, the symptoms, impacts, and treatment goals of individuals diagnosed with gMG. METHODS: Semi-structured, in-depth concept-elicitation interviews were conducted with 28 individuals diagnosed with gMG in the United States. RESULTS: Participants reported gMG symptoms that affected many body regions and functions, with an average of 16 symptoms per participant. The most frequently reported symptoms were eyelid drooping (93%), physical fatigue (89%), symptoms affecting the legs (82%), difficulty breathing (82%), and difficulty holding head up (82%). Nearly all participants (96%) reported fluctuations in symptoms and severity. Participants' most bothersome symptoms were blurry/double vision (43%), breathing difficulties (36%), all-over fatigue (36%), and swallowing problems (29%). Impacts on physical functioning included an inability to participate in hobbies/sports, need for increased planning, and difficulties performing activities of daily living. All participants reported emotional impacts and impacts on their work and finances. Their treatment goals included reduced fatigue and weakness, improved symptom stability, and minimization of the impact of symptoms, in particular the emotional impact. CONCLUSIONS: The fluctuating and unpredictable nature of gMG symptoms was found to have a substantial impact on patients' emotional, social, and economic well-being. Participants' goals for symptom management suggest that greater focus is needed to help them quickly resume a normal lifestyle by achieving symptom stability. Impacts of fluctuating and unpredictable symptoms are difficult to measure, but it is important to consider symptom fluctuation as well as ongoing symptomatology when making treatment decisions, and to recognize the impact of uncontrolled symptoms on patients, their partners/caregivers, and family/friends. These factors are often not reflected in burden/cost-of-illness studies.

The aim of this study was to understand­from the patient's point of view­the range of generalized myasthenia gravis (gMG) symptoms that they experience, which symptoms bother them most, and which symptoms have the greatest impact on everyday life, as well as patients' treatment goals. Researchers asked these questions in one-on-one interviews with 28 people in the US who have gMG. Study participants reported living with symptoms that come and go, and are sometimes severe, making it difficult to lead a normal life. The most frequently reported symptoms were eyelid drooping (reported by 93% of study participants), physical fatigue (89%), symptoms affecting the legs (82%), difficulty breathing (82%), and difficulty holding head up (82%). The symptoms that bothered patients most were difficulties with vision (43%), problems breathing (36%), all-over fatigue (36%), and trouble swallowing (29%). Participants reported that gMG symptoms affected physical functioning, making it hard to participate in hobbies/sports, increasing the amount of planning needed to conduct their daily lives, and hindering their ability to do day-to-day activities (like driving, eating, and bathing). All participants reported that they were affected emotionally, and that the symptoms of gMG impacted their ability to work and their financial well-being. Participants' treatment goals included reducing fatigue and weakness, making symptoms more stable, and reducing the impact of symptoms, particularly emotional impacts. These responses reveal the extensive effects of gMG symptoms on patients' daily lives and highlight that symptom stability is especially important to people with gMG.

Real world effectiveness of tixagevimab/cilgavimab (Evusheld) in the Omicron era.

BACKGROUND: Pre-exposure prophylaxis for COVID-19 with tixagevimab/cilgavimab (T/C) received Emergency Use Authorization (EUA) based on results of a clinical trial conducted prior to the emergence of the Omicron variant. The clinical effectiveness of T/C has not been well described in the Omicron era. We examined the incidence of symptomatic illness and hospitalizations among T/C recipients when Omicron accounted for virtually all local cases. METHODS: Through retrospective electronic medical record chart review, we identified patients who received T/C between January 1 -July 31, 2022 within our quaternary referral health system. We determined the incidence of symptomatic COVID-19 infections and hospitalizations due to or presumed to be caused by early Omicron variants before and after receiving T/C (pre-T/C and post-T/C). Chi square and Mann-Whitney Wilcoxon two-sample tests were used to examine differences between the characteristics of those who got COVID-19 before or after T/C prophylaxis, and rate ratios (RR) and 95% confidence intervals (CI) were calculated to assess differences in hospitalization rates for the two groups. RESULTS: Of 1295 T/C recipients, 105 (8.1%) developed symptomatic COVID-19 infection before receiving T/C, and 102 (7.9%) developed symptomatic disease after receiving it. Of the 105 patients who developed symptomatic infection pre-T/C, 26 (24.8%) were hospitalized, compared with six of the 102 patients (5.9%) who were diagnosed with COVID-19 post-T/C (RR = 0.24; 95% CI = 0.10-0.55; p = 0.0002). Seven of the 105 (6.7%) patients infected pre-T/C, but none of the 102 infected post-T/C required ICU care. No COVID-related deaths occurred in either group. The majority of COVID-19 cases among those infected pre-T/C treatment occurred during the Omicron BA.1 surge, while the majority of post-T/C cases occurred when Omicron BA.5 was predominant. In both groups, having at least one dose of vaccine strongly protected against hospitalization (pre-T/C group RR = 0.31, 95% CI = 0.17-0.57, p = 0.02; post-T/C group RR = 0.15; 95% CI = 0.03-0.94; p = 0.04). CONCLUSION: We identified COVID-19 infections after T/C prophylaxis. Among patients who received T/C at our institution, COVID-19 Omicron cases occurring after T/C were one-fourth as likely to require hospitalization compared to those with Omicron prior to T/C. However, due to the presence of changing vaccine coverage, multiple therapies, and changing variants, the effectiveness of T/C in the Omicron era remains difficult to assess.

Evolution of Clinical Care in COVID-Infected Solid Organ Transplant Recipients.

Purpose of Review: In this review, we aim to summarize the evolution of care for the solid organ transplant recipient (SOTR) with COVID-19 disease, based on the current published guidelines and our center's experience. Recent Findings: Oral antiviral medications and monoclonal antibodies are now used with the goal to prevent severe disease. Immunomodulating drugs in addition to antivirals have been used in the treatment of severe COVID-19. Summary: With the ongoing pandemic and unique challenges posed by the SOTR, understanding the risk and advancing management and treatment of COVID-19 infections are imperative to the successful care of a transplant recipient. There are many ongoing clinical trials being conducted in hopes of developing novel therapeutics towards COVID-19.

Digital Technology Use and Cyberbullying Among Primary School Children: Digital Literacy and Parental Mediation as Moderators.

Cyberbullying has become a critical issue in many parts of the world. Children affected by bullying in cyberspace may also experience various other problems in their daily lives, such as emotional and behavioral issues. Despite the well-documented positive correlation between digital technology use and cyberbullying experiences in adolescents, a paucity of research has explored the association between digital technology use and cyberbullying, and the extent to which digital literacy (DL) and parental mediation moderate these relationships among primary school-aged children. This study addressed these research gaps. A total of 736 children (third grade, female = 52 percent) in Hong Kong, selected through stratified random sampling, reported on their digital technology use, parental mediation of technology use (i.e., active mediation and restriction), and cyberbullying experiences. A performance-based assessment measured children's DL. Results showed a positive association between children's digital technology use (both for leisure activities and for schoolwork) and cyberbullying experiences (both as perpetrator and victim). These positive associations were more pronounced among children with low levels of DL (only victims) as well as among children with highly restrictive parents (both perpetrators and victims). Implications for digital citizenship education and parental intervention are discussed.

Parental Home Monitoring and Support and Students' Online Learning and Socioemotional Well-Being During COVID-19 School Suspension in Hong Kong.

Contextualized in the prolonged period of COVID-19-related school suspension in Hong Kong, the present study unravels relationships among socioeconomic status (SES), parental involvement, and learning outcomes for a matched sample of 186 primary and 932 secondary school students and their parents who participated in the eCitizen Education 360 survey. Three-step latent profile analysis (LPA) revealed different types of parental involvement at home and in school. For the primary school sample, students' SES did not predict membership in the parental involvement typology, but students whose parents provided more home monitoring and support had the highest level of online self-efficacy. As for the secondary student sample, students whose parents provided more home monitoring and support tended to have access to more home learning resources. Students whose parents provided home monitoring and support had the highest levels of online self-efficacy, acquisition of digital skills, and cognitive-emotional regulation, and were the least worried about school resumption. The study underscores complex patterns of parental involvement and identifies effective parental involvement practices that contribute to students' home online learning during the school suspension.

Understanding protective and risk factors affecting adolescents' well-being during the COVID-19 pandemic.

This study investigated the factors affecting adolescents' well-being during the COVID-19 pandemic from the perspectives of their participation in digital activities, emotional regulation, self-regulated learning, and parental involvement. Using self-reported data from 932 pairs of adolescents and their parents, we performed multiple-group structural equation modeling, which revealed that self-efficacy in online learning during school suspension was a key factor influencing adolescents' perceived worries after schools resumed. During school suspension, boys' cognitive-emotional regulation played a protective role in their well-being, helping them to avoid cyberbullying incidents, while girls' participation in leisure-oriented digital activities compromised their self-efficacy in online learning and led to cyberbullying incidents. Furthermore, improvement in parent-child relationships during school suspension encouraged adolescents to use more positive emotional regulation strategies, enhanced their self-efficacy in online learning, and reduced their leisure-time digital activities. The findings indicate that the effective regulation of adolescents' online behaviors, emotions, and self-efficacy, especially when combined with an emotionally secure family relationship, can ensure adolescents' well-being.

Digital competence as a protective factor against gaming addiction in children and adolescents: A cross-sectional study in Hong Kong.

Background: Digital competence can help children and adolescents engage with technology for acquiring new knowledge and for broadening social contact and support, while reducing the risk of inappropriate media use. This study investigated the effects of digital competence on the risk of gaming addiction among children and adolescents. We explored whether students with good digital competence were protected from the adverse effects of media use and the risk of gaming addiction. Methods: 1956 students (690 primary and 1266 secondary) completed a digital competence assessment and a self-report questionnaire on their mental health status, use of digital devices, and experiences of cyberbullying. Multiple regression analyses with further mediation and moderation analyses were performed to investigate the association of digital competence with gaming addiction and mental health in children and adolescents. Findings: Regression analyses showed that children and adolescents with better digital competence were less likely to develop gaming addiction (ß = -0.144, p < 0.0001) and experienced less cyberbullying behaviour as perpetrators (ß = -0.169, p < 0.0001) and as victims (ß = -0.121, p < 0.0001). Digital competence was found to mediate the relationship between digital device usage time and gaming addiction. Interpretation: Digital competence is associated with less gaming addiction and could potentially lead to better mental wellbeing by reducing the risks of gaming addiction and cyberbullying. Education that promotes digital competence is essential to maximize the benefits of media use, while reducing the potential adverse effects from the inappropriate use of digital devices. Funding: This study was supported by a grant from the Research Grants Council of the HKSAR Government (#T44-707/16N) under the Theme-based Research Scheme.

The Lived Experience of Myasthenia Gravis: A Patient-Led Analysis.

INTRODUCTION: A greater understanding of the reality of living with myasthenia gravis (MG) may improve management and outcomes for patients. However, there is little published data on the patient perspective of how MG impacts life. Our objective was to reveal the lived experience of MG from the patient perspective. METHODS: This analysis was led by an international Patient Council comprising nine individuals living with MG who serve as local/national patient advocates in seven countries (Europe and the United States). Insights into the lived experience of MG were consolidated from three sources (a qualitative research study of 54 people with MG or their carers from seven countries; a previous Patient Council meeting [September 2019]; and a literature review). Insights were prioritised by the Patient Council, discussed during a virtual workshop (August 2020) and articulated in a series of statements organised into domains. Overarching themes that describe the lived experience of MG were identified by the patient authors. RESULTS: From 114 patient insights and supporting quotes, the Patient Council defined 44 summary statements organised into nine domains. Five overarching themes were identified that describe the lived experience of MG. These themes include living with fluctuating and unpredictable symptoms; a constant state of adaptation, continual assessment and trade-offs in all aspects of life; treatment inertia, often resulting in under-treatment; a sense of disconnect with healthcare professionals; and feelings of anxiety, frustration, guilt, anger, loneliness and depression. CONCLUSION: This patient-driven analysis enriches our understanding of the reality of living with MG from the patient perspective.