Infection-related Outcomes Research Articles

Pre-infection anticoagulant exposure and SARS-CoV-2 infection outcomes - Differential mortality by age.

The risk of thrombosis increases after SARS-CoV-2 infection. This study aimed to assess associations between pre-infection anticoagulant exposure and SARS-CoV-2 infection-related outcomes in a population-based cohort. Members of the "Meuhedet" health maintenance organization aged >45years who tested positive for SARS-CoV-2 infection (03/2020-04/2022) were followed. Pre-infection anticoagulant exposure (PAE) was defined as any anticoagulant therapy prescribed ≥1month prior to SARS-CoV-2 testing. Univariate analyses, multivariable models adjusting for confounders, propensity-score matching, and an age-stratified analysis were performed to assess associations between PAE and hospitalization, intensive care unit (ICU) admission, 30-day and one-year mortality. Of the 127,801 patients included, 2951(2.3%) had PAE. Comorbidities including ischemic heart disease, diabetes mellitus, hypertension, heart failure, and atrial fibrillation were more common among anticoagulant-exposed than unexposed individuals (p<0.001). Patients with PAE experienced higher hospitalization (22.7% vs 5.6%), ICU admissions (1.9% vs 0.5%), 30-day and 1-year mortality rates (4.8% vs. 0.6, and 8.8% vs. 1.1%, respectively), than unexposed individuals, but similar lengths-of-stay. In the multivariable analysis, PAE was independently associated only with hospitalizations (adjusted odds ratio (aOR)=1.29 [95% confidence interval (CI): 1.13-1.47]), whereas in the propensity-matched analysis, none of the outcomes differed significantly between the groups. However, in the stratum aged >75years, 30-day and one-year mortality were significantly reduced in those with PAE (aOR=0.68 [CI:0.48-0.97], and aOR=0.73 [CI:0.55-0.97], respectively). SARS-CoV-2-infected individuals with prior exposure to anticoagulants have more comorbidities and experienced a higher incidence of hospitalization but not mortality compared to unexposed patients. Paradoxically, mortality risks decreased in the oldest stratum of anticoagulant-exposed individuals. Further research is required to assess mechanisms for this apparent protective effect.

Fungal infection-related conditions and outcomes in severe COVID-19: a nationwide case-control study

BackgroundFungal infections are significant complications of severe coronavirus disease 2019 (COVID-19). Although various risk factors for poor outcomes in patients with COVID-19 have been identified, clinical and treatment factors associated with fungal infections in patients with severe COVID-19 remain unclear. This study aimed to elucidate clinical factors associated with fungal infections during severe COVID-19 treatment.MethodsThis was a post hoc analysis of the J-RECOVER study, a multicenter retrospective observational study involving patients with COVID-19 who required admission at 66 hospitals between January and September 2020. Inclusion criteria were ages ≥ 18 years, COVID-19 diagnosis with reverse-transcription polymerase chain reaction, and treatment with mechanical ventilation (MV). Patients who received antifungal drugs before MV were excluded. Potential predictors were identified through univariate analysis of patient and treatment characteristics between patients with- and those without fungal infection, which was defined as antifungal agent use for ≥ 5 days. To account for facility-specific data clustering, generalized estimating equations (GEE) were employed as adjusted analyses to calculate the relative risks of potentially associated factors. Two sensitivity analyses were performed with modified definitions for the two groups: patients who received antifungal drugs for ≤ 4 days were excluded, and fungal infection was re-defined as antifungal drug use for ≥ 14 days.ResultsAmong 4,915 patients in the J-RECOVER study, 559 adults with COVID-19 who required MV were included. Fungal infections occurred in 57 (10.2%) patients. Univariate analyses identified age, age ≥ 65 years, D-dimer level, remdesivir use, steroid use, and duration of steroid therapy as potential predictors of fungal infections. Multivariate analysis using GEE on these six factors revealed that only the duration of steroid use was significantly associated with an increased risk of fungal infection (odds ratio [OR] for a day increase: 1.01; 95% confidence interval [CI]: 1.00–1.01; p < 0.001). The two sensitivity analyses similarly showed that the duration of steroid use was associated with fungal infection (odds ratio for a day increase: 1.01; 95% CI: 1.00–1.01; p < 0.001 for both).ConclusionsIn patients with severe COVID-19 requiring MV, each additional day of steroid use was associated with prolonged use of antifungal medications for ≥ 5 days.

Machine learning-based infection diagnostic and prognostic models in post-acute care settings: a systematic review.

This study aims to (1) review machine learning (ML)-based models for early infection diagnostic and prognosis prediction in post-acute care (PAC) settings, (2) identify key risk predictors influencing infection-related outcomes, and (3) examine the quality and limitations of these models. PubMed, Web of Science, Scopus, IEEE Xplore, CINAHL, and ACM digital library were searched in February 2024. Eligible studies leveraged PAC data to develop and evaluate ML models for infection-related risks. Data extraction followed the CHARMS checklist. Quality appraisal followed the PROBAST tool. Data synthesis was guided by the socio-ecological conceptual framework. Thirteen studies were included, mainly focusing on respiratory infections and nursing homes. Most used regression models with structured electronic health record data. Since 2020, there has been a shift toward advanced ML algorithms and multimodal data, biosensors, and clinical notes being significant sources of unstructured data. Despite these advances, there is insufficient evidence to support performance improvements over traditional models. Individual-level risk predictors, like impaired cognition, declined function, and tachycardia, were commonly used, while contextual-level predictors were barely utilized, consequently limiting model fairness. Major sources of bias included lack of external validation, inadequate model calibration, and insufficient consideration of data complexity. Despite the growth of advanced modeling approaches in infection-related models in PAC settings, evidence supporting their superiority remains limited. Future research should leverage a socio-ecological lens for predictor selection and model construction, exploring optimal data modalities and ML model usage in PAC, while ensuring rigorous methodologies and fairness considerations.

The Efficacy of Calcium Sulfate/Hydroxyapatite (CaS/HA) Gentamicin in Osteomyelitis Treatment: A Case Series.

Osteomyelitis is a challenging condition caused by infection and inflammation of the bone, presenting a significant economic burden to healthcare systems. Calcium sulfate/hydroxyapatite (CaS/HA) is a bone void filler composed of 60% calcium sulfate and 40% hydroxyapatite. This case series aimed to report the efficacy and infection-related outcomes of CaS/HA combined with Gentamicin (CaS/HA-G) in treating osteomyelitis. Patients aged 18 and older diagnosed with osteomyelitis requiring surgical intervention and treated with CaS/HA-G during their procedure were included in the study, with a median (Q1-Q3) = 10 (7-16)-month follow-up period of time. Data collected included demographic, surgical, and outcome information. Infection eradication was determined by the normalization of the C-reactive protein, erythrocyte sedimentation rate levels, or the absence of clinical infection symptoms. The case series involved 21 patients (twelve male, nine female) with a mean (SD) age of 54.8 (16.6) years. Vancomycin or/and Tobramycin were used as an additional antibiotic in 17 patients. At the last follow-up, 20 out of 21 patients (95.2%) had eradicated the infection, with a median (Q1-Q3) eradication time of 128 (71.8-233.5) days. In conclusion, this study demonstrates that CaS/HA-G is effective in controlling osseous infection in osteomyelitis while acting as an absorbable bone void filler.

Assessing Long-Term Adverse Outcomes in Older Kidney Transplant Recipients: A Propensity Score-Matched Comparison of Early Steroid Withdrawal Versus Continuous Steroid Immunosuppression Using a Large Real-World Database.

Steroids are widely used in maintenance immunosuppression treatment in kidney transplant recipients. Older individuals undergo age-related immunosenescence that consequently decreases their ability to process and evoke a response to foreign antigens. Thus, steroids may not be necessary in preventing allograft rejection and may consequently increase older recipients' risk of long-term steroid-related adverse effects. The objective of this study was to analyze the adverse outcomes of long-term steroid immunosuppression in older kidney transplant recipients using real-world electronic medical record data. The TriNetX database "US Collaborative Network" was utilized to perform a propensity score-matched case-control study comparing 1-year, 3-year, and 5-year adverse effects of steroid immunosuppression in older adults (aged ≥65 years) kidney transplant recipients who underwent either an early-steroid withdrawal (ESW) maintenance regimen or a steroid continuous immunosuppression (SCI) regimen between 31 December, 2010 and 31 December, 2020. Early-steroid withdrawal was defined as tacrolimus plus mycophenolate mofetil maintenance with no prednisone after the seventh day post-transplant. Steroid continuous immunosuppression was defined as tacrolimus plus mycophenolate mofetil plus prednisone maintenance. Cohorts were matched on age, race/ethnicity, and risk factors for adverse steroid-related outcomes and rejection. Outcomes included post-transplant diabetes mellitus, dyslipidemia osteoporosis/fractures, myocardial infarction, glaucoma/cataract, stroke, pulmonary embolism, and malignancy. Secondary outcomes analyzed incidences of infection-related outcomes, graft-related outcomes, and recipient mortality. After matching, there were 304 recipients in each group (ESW, SCI). Mean age at the time of transplant was 69.2±3.7 years (ESW) and 69.2±3.4 years (SCI, p=0.96). The Kaplan-Meier analysis showed recipients who underwent SCI had increased incidences of post-transplant diabetes mellitus at 1 year (22.36% vs 30.37%, p=0.01) and 3 years (34.89% vs 44.29%, p=0.01), but this became non-significant at 5 years post-transplant (41.97% vs 42.6%, p=0.34). Incidences of acute pancreatitis were higher for the SCI cohort at 3 years (p=0.02) as well as incidences of acute myocardial infarction at 5 years post-kidney transplant (6.75% vs 14.39%, p<0.01). No difference was found for other adverse outcomes. Early-steroid withdrawal recipients experienced significantly fewer infection-related outcomes, such as cytomegalovirus, BK virus, sepsis/bacteremia, and fungal infections, compared with SCI recipients. Last, recipients who underwent ESW experienced fewer incidences of rejection and death-censored graft failure at 5 years post-transplant. There is currently no standard maintenance immunosuppression protocol for older kidney transplant recipients. Death-censored graft survival, rejection, and patient survival were improved with ESW. Steroid minimization may be beneficial in this population given that it lowers the risk of drug-induced adverse effects.

High caregiver adverse childhood experiences are associated with increased pediatric infection-related healthcare utilization and antibiotic use

Abstract Background Higher caregiver adverse childhood experiences (ACEs) have been associated with a range of pediatric outcomes, including hospitalizations. We recently found that higher caregiver ACEs are associated with higher rates of influenza vaccine uptake. However, to our knowledge, no studies have examined links between caregiver ACEs and specific infections or infection-related outcomes, such as antibiotics prescribed. We sought to evaluate associations between caregiver ACEs and pediatric infection-related outcomes. Methods We conducted a retrospective cohort study of two pediatric primary care sites, each serving a predominantly non-Hispanic Black, publicly insured population. At one primary care site (Clinic A), routine screenings for caregiver ACEs began in 2019 at the 1-month well-child check and were retrieved from the electronic health record. For the other primary care site (Clinic B), a prior research study surveyed caregiver ACEs of 283 children. Focusing on children 0-4 years of age in both primary care sites, we retrieved data from the electronic health record, including patient infection-related outcomes, demographic characteristics, and social risk screen results for those who had caregiver ACEs systematically recorded. The number of reported caregiver ACEs was our exposure variable, dichotomized as high (≥4) or low (≤3). Patient demographic characteristics, results of the overall social risk and maternal depression screen, and area deprivation index scores linked to patients’ geocoded home addresses were also collected. Bivariate analyses were pursued using chi square test statistics. Results A total of 1,442 children 0-4 years of age were included in the study, and 50.0% were female, 74.7% Black, and 2.6% Hispanic. Fifteen percent of caregivers had high (≥4) ACEs. Differences in infection-related outcomes, and relevant covariates, based on high and low caregiver ACEs are depicted in Table 1. Children of caregivers with high ACEs had more outpatient infection-related visits (80% versus 72.6%, p = 0.03), including more diagnoses of streptococcal pharyngitis (10.1% versus 4.1%, p = 0.0004). They also had more prescriptions for any oral antibiotic (30.9% versus 23.2%, p = 0.02). In bivariate analyses, high caregiver ACEs (31.3% versus 23.7%, p = 0.03), lower area deprivation index score (mean (SD) of 0.47 (0.16) versus 0.50 (0.16), p &amp;lt; 0.01), older patient age (mean (SD) of 2.73 (1.10) versus 1.73 (1.00) years, p &amp;lt; 0.0001), and any outpatient (35.9% versus 2.2%, p &amp;lt; 0.0001), emergent (40.0% versus 10.9%, p &amp;lt; 0.0001), or inpatient visit (42.7% versus 23.0%, p &amp;lt; 0.0001) were each associated with the presence of antibiotic use. Race, ethnicity, a positive social risk screen, and positive depression screen were not associated with antibiotic use. Conclusion High caregiver ACEs appear to be associated with some types of pediatric infectious diagnoses, antibiotic use and increased infection-related outpatient healthcare utilization. Future adjusted analyses assessing for potential links between ACEs and infection-related outcomes, independent of variables like insurance status, social risk, and area-level deprivation, are warranted and planned.

Visible damp in a child’s bedroom is associated with increased respiratory morbidity in early life: a multicentre cohort study

ObjectiveHousehold damp exposure is an important public health issue. We aimed to assess the impact of the location of household damp on respiratory outcomes during early life.MethodsHousehold damp exposure was...

Caregiver Adverse Childhood Experiences and Pediatric Infection-Related Outcomes.

Higher caregiver-adverse childhood experiences (ACEs) have been associated with multiple adverse pediatric outcomes. However, no studies have examined links between caregiver ACEs and infectious outcomes like antibiotic prescriptions or infection-related clinical encounters. We conducted a retrospective cohort study including patients from 2 pediatric primary care sites, serving predominantly non-Hispanic Black, publicly insured populations. Our outcomes were antibiotic prescriptions and infection-related ambulatory clinical encounters for children 0-3 years old. We captured these outcomes and additional covariates (demographics, health-related social risk screen results, and Socioeconomic Deprivation Index scores linked to geocoded street addresses) from the electronic health record. High (≥4) or low (≤3) caregiver ACEs, and individual ACE question answers, were our exposures. Multivariable logistic regression was used to determine associations with any antibiotic use. Cox proportional hazards regression was used to assess the time to first antibiotic exposure and first infection-related visit. A total of 1465 children 0-3 years were included (50.0% female, 75.0% Black, and 2.6% Hispanic). High caregiver ACEs were not associated with pediatric antibiotic exposure. The presence of caregiver-witnessed parental abuse was associated with a higher likelihood of any antibiotic exposure (odds ratio [OR 1.90]; 95% confidence interval [CI] 1.2, 3.2) and time to first antibiotic exposure (hazard ratio [HR] 1.77; 95% CI 1.23, 2.56). Sexual abuse of the caregiver was associated with time to first infection-related clinical visit (HR 1.27; 95% CI 1.05, 1.53). Certain caregiver ACEs were associated with pediatric antibiotic use and infection-related visits. Future studies need to evaluate underlying mechanisms and test effective clinical responses.

Characterization of the Elderly Patients Admitted with Infection to a Tertiary Hospital in Bangladesh

Background: The proportion of hospitalizations attributable to infectious diseases is high, and likely to increase further in the future as a result of the expected aging of the population and the increasing prevalence of comorbid conditions among the elderly. The present study aimed to investigate the clinical characteristics and outcomes of elderly patients admitted due to infection in a tertiary-level hospital in Chattogram, Bangladesh. Materials and methods: This prospective observational study was conducted in Chittagong Medical College Hospital (CMCH) Chattogram. Two hundred and six patients aged ≥60 admitted with a diagnosis of infectious aetiology in the medicine department were enrolled according to set inclusion criteria. Patients were followed up for in-hospital outcomes after admission. Results: Age ranges from 60-90 years with a mean age of 65.82 (±5.56) years) and 51.5% were male. Pre-hospital antibiotic was received by 108 (52.4%) patients and 7.4% had antibiotic prescribed by registered physicians The most frequent infections were respiratory tract infections (47.6%) and urinary tract infections (43.2%). Sixty-four (31.1%) patients developed sepsis and 17 (8.3%) required ICU support. Eleven patients expired in-hospital, indicating a mortality rate of 5.3%. Length of hospitalization ranged from 2 to 17 days, with a median of 6 days. Conclusion: This study result suggests that infection-related hospitalization and outcomes of elderly individuals were high and their health seeking behaviour was poor. IAHS Medical Journal Vol 6(2), December 2023; 31-34

Infection prophylaxis among patients with antineutrophil cytoplasmic antibody (ANCA) vasculitis: a scoping review.

Severe infections associated with the use of strong immunosuppressive medication are a leading cause of morbidity and mortality in patients with ANCA vasculitis (AV). While guidelines conditionally recommend trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis for Pneumocystis jirovecii pneumonia in AV patients, robust evidence on prophylaxis strategies is lacking. This scoping review aimed to assess the existing evidence on infection prophylaxis in AV patients, identify knowledge gaps, and guide future study design. A comprehensive search of six databases and relevant references identified original studies in English from January 1, 2000, to July 31, 2020. Inclusion criteria encompassed studies evaluating the impact of any antimicrobial prophylaxis strategy on infection-related outcomes in AV patients receiving immunosuppressive treatment. Studies were screened by four researchers using a blinded approach. Data was extracted by two reviewers, with differences resolved via consensus in consultation with a third reviewer. Nineteen studies met inclusion criteria, including two randomized trials and 17 cohort studies, with TMP-SMX being the most commonly assessed prophylactic strategy. The studies varied in sample sizes, outcomes measured, prophylactic strategies employed, and proportion of patients who received the regimen. Most cohort studies included no or limited control of potential confounding factors. This scoping review suggests significant variation in AV patients' receipt of TMP-SMX and alternative infection prophylaxis approaches. Observational studies using large secondary healthcare databases with rigorous designs are needed to provide high-quality evidence of the real-world effectiveness of antimicrobial prophylactic regimens, to improve clinical decision-making and quality of care for AV patients receiving immunosuppressive treatment.

Reduction of peritoneal dialysis associated infections using a novel exit-site care practice.

Peritoneal dialysis (PD) related infections are a significant obstacle leading to PD discontinuation. Since catheter related infections (CRI), defined as exit site infections and/or tunnel infection, can progress to peritonitis, vigorous efforts are implemented in CRI prevention. Following an increased CRI rate in our institution, partially related to environmental organisms found in water distribution systems, we hypothesized that exit site care that includes prevention of water exposure-related pathogens may reduce CRI. In this prospective single center study, we compared a contemporary cohort consisting of PD patients who implemented the modified exit-site care protocol, mainly including water avoidance during shower with stoma bag usage and local Mupirocin ointment against a historical control group before the protocol implementation. The historical cohort was allowed water exposure and used local gentamicin ointment. The primary outcome was the development of a CRI. Secondary outcomes were PD associated peritonitis and infection related outcomes. There were 55 patients in contemporary cohort and 58 in historical group. The CRI rate was significantly lower in study group (0.11/episodes per patient year [EPP]) compared to control group (0.71 EPP), p < 0.001. A multivariate Cox regression analysis demonstrated a protective effect of being in the contemporary cohort compared to historical group (HR for first CRI = 12.0 95%CI: 4.0-35.7, p < 0.001). Peritonitis rate was significantly lower in contemporary cohort (0.19/EPP) compared to the historical group (0.40/EPP), p = 0.011. Transfer to hemodialysis was significantly lower in contemporary cohort than historical group (7.3% vs 31.0% in contemporary and historical group respectively, HR = 0.2, 95%CI; 0.05-0.6, p = 0.001). An exit site care protocol that includes water avoidance and local Mupirocin use reduced substantially both CRI and peritonitis rate in patients treated with PD.

Factors associated with infection-related severe maternal outcomes in pregnant and recently pregnant women: Asecondary analysis of the WHO global maternal sepsis study.

The aim of the present study was to identify the risk factors for severe maternal outcomes (SMO) of women with suspected or confirmed infections using the data from the WHO global maternal sepsis study (GLOSS). We conducted a secondary analysis of the GLOSS cohort study, which involved pregnant or recently pregnant women with suspected or confirmed infection around 713 health facilities in 52 low- and middle-income countries, and high-income countries. A nested case-control study was conducted within the GLOSS cohort. Cases included infection-related maternal deaths or near misses, while controls represented non-SMO. Logistic mixed models, adjusting for country variations, were employed. Using univariate analysis, we calculated crude odds ratios (crude OR) and their 95% confidence interval (95% CI). Variables were identified with less than 16% missing data, and P values less than 0.20 were used to perform the multivariate logistic model multilevel. A total of 2558 women were included in the analysis. As for the cases, 134 patients were found in the pregnant in labor or not in labor group and 246 patients in the postpartum or postabortion group. Pregnant women with prior childbirths faced a 64% increased risk of SMO. Ante- or intrapartum hemorrhage increased risk by 4.45 times, while trauma during pregnancy increased it by 4.81 times. Pre-existing medical conditions elevated risk five-fold, while hospital-acquired infections increased it by 53%. Secondary infections raised risk six-fold. Postpartum/postabortion women with prior childbirths had a 45% elevated risk, and pre-existing medical conditions raised it by 2.84 times. Hospital-acquired infections increased risk by 93%. Postpartum hemorrhage increased risk approximately five-fold, while abortion-related bleeding doubled it. Previous cesarean, abortion, and stillbirth also elevated risk. Key risk factors for SMO include prior childbirths, hemorrhage, trauma, pre-existing conditions, and hospital-acquired or secondary infections. Implementing effective alert systems and targeted interventions is essential to mitigate these risks and improve maternal health outcomes, especially in resource-limited settings.

History of childhood maltreatment associated with hospitalization or death due to COVID-19: a cohort study

BackgroundChildhood maltreatment (CM) has been indicated in adverse health outcomes across the lifespan, including severe infection-related outcomes. Yet, data are scarce on the potential role of CM in severe COVID-19-related outcomes as well as on mechanisms underlying this association.MethodsWe included 151,427 individuals in the UK Biobank who responded to questions on the history of CM in 2016 and 2017 and were alive on January 31, 2020. Binomial logistic regression models were performed to estimate the association between a history of CM and severe COVID-19 outcomes (i.e. hospitalization or death due to COVID-19), as well as COVID-19 diagnosis and vaccination as secondary outcomes. We then explored the potential mediating roles of socio-economic status, lifestyle and pre-pandemic comorbidities, and the effect modification by polygenic risk score for severe COVID-19 outcomes.ResultsThe mean age of the study population at the start of the pandemic was 67.7 (SD = 7.72) years, and 56.5% were female. We found the number of CM types was associated with the risk of severe COVID-19 outcomes in a graded manner (pfor trend < 0.01). Compared to individuals with no history of CM, individuals exposed to any CM were more likely to be hospitalized or die due to COVID-19 (odds ratio [OR] = 1.54 [95%CI 1.31–1.81]), particularly after physical neglect (2.04 [1.57–2.62]). Largely comparable risk patterns were observed across groups of high vs. low genetic risks for severe COVID-19 outcomes (pfor difference > 0.05). Mediation analysis revealed that 50.9% of the association between CM and severe COVID-19 outcomes was explained by suboptimal socio-economic status, lifestyle, and pre-pandemic diagnosis of psychiatric disorders or other chronic medical conditions. In contrast, any CM exposure was only weakly associated with COVID-19 diagnosis (1.06 [1.01–1.12]) while significantly associated with not being vaccinated for COVID-19 (1.21 [1.13–1.29]).ConclusionsOur results add to the growing knowledge base indicating the role of childhood maltreatment in negative health outcomes across the lifespan, including severe COVID-19-related outcomes. The identified factors underlying this association represent potential intervention targets for mitigating the harmful effects of childhood maltreatment in COVID-19 and similar future pandemics.

How to protect long-term care facilities from pandemic-like events? - A systematic review on the effectiveness of non-pharmacological measures to prevent viral respiratory infections

BackgroundThe SARS-CoV-2 pandemic underscored the need for pandemic preparedness, with respiratory-transmitted viruses considered as a substantial risk. In pandemics, long‐term care facilities (LTCFs) are a high-risk setting with severe outbreaks and burden of disease. Non‐pharmacological interventions (NPIs) constitute the primary defence mechanism when pharmacological interventions are not available. However, evidence on the effectiveness of NPIs implemented in LTCFs remains unclear.MethodsWe conducted a systematic review assessing the effectiveness of NPIs implemented in LTCFs to protect residents and staff from viral respiratory pathogens with pandemic potential. We searched Medline, Embase, CINAHL, and two COVID-19 registries in 09/2022. Screening and data extraction was conducted independently by two experienced researchers. We included randomized controlled trials and non-randomized observational studies of intervention effects. Quality appraisal was conducted using ROBINS-I and RoB2. Primary outcomes encompassed number of outbreaks, infections, hospitalizations, and deaths. We synthesized findings narratively, focusing on the direction of effect. Certainty of evidence (CoE) was assessed using GRADE.ResultsWe analysed 13 observational studies and three (cluster) randomized controlled trials. All studies were conducted in high-income countries, all but three focused on SARS-CoV-2 with the rest focusing on influenza or upper-respiratory tract infections. The evidence indicates that a combination of different measures and hand hygiene interventions can be effective in protecting residents and staff from infection-related outcomes (moderate CoE). Self-confinement of staff with residents, compartmentalization of staff in the LTCF, and the routine testing of residents and/or staff in LTCFs, among others, may be effective (low CoE). Other measures, such as restricting shared spaces, serving meals in room, cohorting infected and non-infected residents may be effective (very low CoE). An evidence gap map highlights the lack of evidence on important interventions, encompassing visiting restrictions, pre-entry testing, and air filtration systems.ConclusionsAlthough CoE of interventions was low or very low for most outcomes, the implementation of NPIs identified as potentially effective in this review often constitutes the sole viable option, particularly prior to the availability of vaccinations. Our evidence-gap map underscores the imperative for further research on several interventions. These gaps need to be addressed to prepare LTCFs for future pandemics.Trial registrationCRD42022344149.

#1798 Infection-related outcomes in CKD patients with lupus nephritis: a nationwide cohort study

Abstract Background and Aims Although absolute risks of infection in patients with lupus nephritis (LN) are believed high, it is not known whether they differ from those of patients with other etiologies of moderate and advanced chronic kidney disease (CKD). The aim of this study was to compare infection outcomes between patients with LN-CKD and other forms of CKD. Method Using data from the Swedish Renal Registry (2006-2021), we compared infection-related outcomes between LN-patients with moderate and advanced, non-dialysis, CKD and patients with 1) diabetic kidney disease (DKD), 2) primary glomerular diseases (PGD, i.e. IgA nephropathy, focal segmental glomerulosclerosis, membranous nephropathy), and 3) autosomal dominant polycystic kidney disease (ADPKD). Cause-specific Cox proportional hazard models were used to estimate the adjusted hazard ratios of death due to infection, first all-cause infection-related hospitalization and first cause-specific infection-related hospitalization (sepsis, pulmonary, gastrointestinal, genitourinary, and other infections). Results We identified 317 patients with LN (61 years, 76% women, median eGFR 30 mL/min per 1.73 m²), 8877 patients with DKD (71 years, 33% women, eGFR 24 mL/min per 1.73 m²), 2296 patients with PGD (57 years, 30% women, eGFR 29 mL/min per 1.73 m²) and 1855 patients with ADPKD (59 years, 45% women, eGFR 26 mL/min per 1.73 m²). Over a median follow-up of 2.8 [1.2; 5.0] years, 667 (5%) deaths due to infection and 4034 (30%), infection-related (first-time) hospitalizations occurred, including 2127 (16%) pulmonary, 1507 (11%) genitourinary, 1130 (8%) gastrointestinal, 615 (5%) other infections, and 450 (3%) sepsis. In multivariable analyses, and when compared to DKD, patients with LN had a similar risk of death due to infection (adjusted HR 1.15 [95% CI: 0.62-2.11]) and sepsis (HR 1.24 [0.64-2.4]), but a higher risk of all infection-related hospitalization (HR 1.31 [1.04-1.65]), the latter being mainly driven by pulmonary, gastrointestinal, and other infections (Figure panel A). The risks of death due to infection (HR LN vs PGD 2.78 [1.62-4.77], HR LN vs ADPKD 2.34 [1.31-4.19]), of infection-related hospitalization (HR 1.87 [1.52-2.31], HR 1.43 [1.16-1.77]), and of cause-specific infection-related hospitalization were higher in LN than in PGD and ADKPD, respectively, except for the risk of sepsis which was similar between LN and ADPKD. The risk of genitourinary infection tended to be lower in LN than in ADPKD, although the 95% CI slightly overlapped (Figure panels B-C). Conclusion LN patients had higher risk of infection-related hospitalization than all other investigated CKD etiologies, and a higher risk of death due to infections than patients with PGD and ADPKD. Our findings highlight the need for improvements in infection prevention in patients with LN. Whether a more tailored immunosuppressive treatment approach could further improve outcomes in this high-risk population remains to be investigated.

#831 Associations of quality of life with hospitalization for infection and subsequent death in hemodialysis patients: Osaka Dialysis Complication Study

Abstract Background and Aims Health-related quality of life (HRQOL) as self-reported health status is known to predict mortality in hemodialysis (HD) patients. Infection is one of the major causes for death in those patients, although limited studies have examined possible associations of HRQOL with infection-related outcomes. In the present study, we examined the associations of HRQOL scores with all-cause mortality, hospitalization for infection, and subsequent death in HD patients. Method Patients for this study were selected from the Osaka Dialysis Complication Study (ODCS) which is a prospective cohort study from 2012 to 2017 including a total of 1696 HD patients. HRQOL was assessed by Medical Outcomes Study short form 36 (SF-36) questionnaire to determine scores of the physical component summary (PCS) and the mental component summary (MCS) at baseline, and patients were divided into tertiles of them. The key outcomes were all-cause mortality, hospitalization for infection, and subsequent death after infection. Association was analyzed with Cox proportional hazards models or Fine-Gray models to estimate hazard ratios (HRs) with the highest tertile of PCS or MCS (T3) as referent. Models were unadjusted and adjusted for potential confounders including major demographic factors, traditional cardiovascular risk factors, and the factors related to chronic kidney disease-mineral and bone disorder (CKD-MBD), protein energy wasting and inflammation, and renal anemia. Results We analyzed data from 1464 patients, and we identified 384 all-cause deaths, 321 hospitalizations for infections, and 143 subsequent deaths following infection. Risk of all-cause death was the highest in the lowest PCS tertile in unadjusted model, and this association remained significant in multivariable-adjusted models. In addition, a lower PCS was significantly predictive of a higher risk of both hospitalization for infection in models unadjusted and adjusted for demographic variables, but not significant in a model adjusted for all confounders. However, risk of death after hospitalization for infection was significantly higher in the lowest PCS tertile in unadjusted and in multivariable-adjusted models, compared with the highest PCS tertile. In contrast, MCS was not associated with all-cause mortality, hospitalization for infection, or death following hospitalization for infection. Conclusion A low PCS was associated with both hospitalization for infection and subsequent death after infection in HD patients, but it was more closely associated with the latter. This study revealed that HRQOL, particularly its physical component, is an independent predictor of infection-related outcomes in this population.

Infection-related severe maternal outcomes and case fatality rates in 43 low and middle-income countries across the WHO regions: Results from the Global Maternal Sepsis Study (GLOSS).

The highest toll of maternal mortality due to infections is reported in low and middle-income countries (LMICs). However, more evidence is needed to understand the differences in infection-related severe maternal outcomes (SMO) and fatality rates across the WHO regions. This study aimed to compare the burden of infection-related SMO and case fatality rates across the WHO regions using the Global Maternal Sepsis Study (GLOSS) data. GLOSS was a hospital-based one-week inception prospective cohort study of pregnant or recently pregnant women admitted with suspected or confirmed infection in 2017. Four hundred and eight (408) hospitals from 43 LMICs in the six WHO regions were considered in this analysis. We used a logistic regression model to compare the odds of infection-related SMOs by region. We then calculated the fatality rate as the proportion of deaths over the total number of SMOs, defined as maternal deaths and near-misses. The proportion of SMO was 19.6% (n = 141) in Africa, compared to 18%(n = 22), 15.9%(n = 50), 14.7%(n = 48), 12.1%(n = 95), and 10.8%(n = 21) in the Western Pacific, European, Eastern Meditteranean, Americas, and South-Eastern Asian regions, respectively. Women in Africa were more likely to experience SMO than those in the Americas (aOR = 2.41, 95%CI: [1.78 to 2.83]), in South-East Asia (aOR = 2.60, 95%CI: [1.57 to 4.32]), and the Eastern Mediterranean region (aOR = 1.58, 95%CI: [1.08 to 2.32]). The case fatality rate was 14.3%[3.05% to 36.34%] (n/N = 3/21) and 11.4%[6.63% to 17.77%] (n/N = 16/141) in the South-East Asia and Africa, respectively. Infection-related SMOs and case fatality rates were highest in Africa and Southeast Asia. Specific attention and actions are needed to prevent infection-related maternal deaths and severe morbidity in these two regions.

COVID-19 Vaccine Effectiveness among Patients with Psoriatic Disease: A Population-Based Study.

Limited information is available on the effectiveness of COVID-19 vaccination in patients with psoriasis and psoriatic arthritis (psoriatic disease (PsD)). The objective of our research was to assess the effectiveness of mRNA COVID-19 vaccination in preventing SARS-CoV-2 positivity and severe infection in a cohort of patients with PsD and the association of immunosuppressants on SARS-CoV-2 infection-related outcomes from December 2020 to December 2021. Vaccine effectiveness was assessed in a matched nested case control study using conditional logistic regression adjusted for demographics, comorbidities and immunosuppressant use. Study outcomes included SARS-CoV-2 positivity and severe COVID-19 (moderate-to-severe COVID-19-related hospitalizations or death). At least one dose of mRNA COVID-19 vaccine was associated with reduced risk of SARS-CoV-2 positivity and severe COVID-19 (OR = 0.41 (95% CI, 0.38-0.43) and OR = 0.15 (95% CI, 0.11-0.20), respectively). A more significant effect was found among patients who received three vaccines doses compared with those who did not receive any (OR (for positive SARS-CoV-2) = 0.13 (95% CI, 0.12-0.15) and OR (for severe disease) = 0.02 (0.01-0.05)). Etanercept and methotrexate were associated with higher risk of SARS-CoV-2 positivity (1.58 (1.19-2.10), p = 0.001 and 1.25 (1.03-1.51), p = 0.03, respectively). In conclusion, our results show that mRNA COVID-19 vaccines are effective in reducing both infection and severe COVID-19-related outcomes.

Additive and Dose-Dependent Effect of Rituximab on Pediatric Patients’ Outcomes Concurrently Receiving Immunosuppressive Chemotherapy, A Prospective Cohort Study

Background: Rituximab (RTX) is approved for treating CD20-positive B-cell malignancies, including non-Hodgkin lymphoma, when used alongside chemotherapy. It has the potential to interact with and alter the host immune system, putting patients at a heightened risk of infection. Therefore, the use of RTX necessitates a meticulous assessment of infectious risks based on the latest evidence. Objectives: We conducted a prospective investigation into infectious complications and mortality among children undergoing RTX treatment over the observation period of the study. Methods: In this observational cohort study, we included 61 pediatric patients treated with RTX for malignancy and immune thrombocytopenic purpura (ITP), as well as 122 cancer patients who had never received RTX (the unexposed group). These patients were prospectively monitored for febrile neutropenia (FN), bloodstream infection (BSI), invasive fungal infection (IFI), and mortality. All infectious complications were documented starting from the initial dose of RTX and continuing for at least six months following the last dose. Logistic regression and Cox regression analyses, with consideration for the proportional hazards assumption, were utilized to evaluate the impact of covariates on mortality and infection-related outcomes. Results: Infectious complications were observed in 52.5% of children treated with RTX. These complications were notably more prevalent in children with malignancy compared to those with chronic ITP (89.5% versus 10.5%, respectively). RTX was found to be associated with an increased likelihood of mortality in children with malignancy (OR [95% CI]: 1.54 [0.41, 5.69]). According to Cox regression analysis, RTX was linked to a higher risk of IFIs, death, FN events, and BSIs over a 36-month observation period (4.33 [1.21, 15.52], 3.26 [1.008, 10.59], 1.68 [0.83, 3.41], and 1.59 [0.27, 9.17], respectively). The total dose of RTX administered was also associated with adverse patient outcomes, with the odds of infectious events and death increasing in the second, third, and fourth quartiles of the total RTX dose administered. Furthermore, the estimated one-year and two-year survival rates for cancer patients treated with RTX were 77% and 58%, respectively. Conclusions: RTX treatment, when used concurrently with immunosuppressive chemotherapy for hematologic malignancies in children, showed additive and dose-dependent effects on clinical outcomes.

Burden of Infection in Patients With and Without Secondary Immunodeficiency Disease Following Diagnosis of a Mature B Cell Malignancy

BackgroundThis retrospective cohort study compared patient characteristics and burden of infection in patients with mature B cell malignancies with and without secondary immunodeficiency disease (SID). Patients and MethodsData were extracted from the Humedica database (H-DB) and Guardian Research Network (GRN) database from October 1, 2015 to March 10, 2020, including a 6-month pre-index period (PIP) and 12-month follow-up. Patients aged ≥18 years diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma, multiple myeloma, or non-Hodgkin's lymphoma in the PIP were stratified into 2 cohorts: SID (hypogammaglobulinemia [using ICD-10-CM codes] or serum IgG levels <5.0 g/L, both with signs and symptoms of SID or at least 1 infection) and no-SID. Patients with SID or primary immunodeficiency diseases in the PIP were excluded. ResultsOverall, 2221 patients with SID (H-DB/GRN: n = 1959/262), and 19,141 patients without SID (n = 17,598/1543) were included. Baseline characteristics were similar across cohorts. At 12-month follow-up, significantly more patients with SID had experienced ≥1 infection and ≥1 severe bacterial infection than those without SID (both P < .001). H-DB/GRN mean (standard deviation) number of severe bacterial infections was 7.6 (9.9)/2.9 (2.7) for the SID cohort versus 5.2 (6.8)/2.4 (2.2) for the no-SID cohort. ConclusionThis study confirms that patients with mature B cell malignancies and SID face a significantly higher burden of infections than those without SID.