Risk Of Infection-related Hospitalization Research Articles

#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.

Adverse Events Associated With Disease-Modifying Drugs for Multiple Sclerosis: A Multiregional Population-Based Study

It is not possible to fully establish the safety of a disease-modifying drug (DMD) for multiple sclerosis (MS) from randomized controlled trials as only very common adverse events occurring over the short-term can be captured, and the quality of reporting has been variable. We examined the relationship between the DMDs for MS and potential adverse events in a multiregion population-based study. We identified people with MS using linked administrative health data from 4 Canadian provinces. MS cases were followed from the most recent of first MS or related demyelinating disease event on January 1, 1996, until the earliest of emigration, death, or December 31, 2017. DMD exposure primarily comprised β-interferon, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, and alemtuzumab. We examined associations between DMD exposure and infection-related hospitalizations and physician visits using recurrent events proportional means models and between DMD exposure and 15 broad categories of incident adverse events using stratified multivariate Cox proportional hazard models. We identified 35,894 people with MS. While virtually all DMDs were associated with a 42%-61% lower risk of infection-related hospitalizations, there was a modest increase in infection-related physician visits by 10%-33% for select DMDs. For incident adverse events, most elevated risks involved a second-generation DMD, with alemtuzumab's hazard of thyroid disorders being 19.42 (95% CI 9.29-36.51), hypertension 4.96 (95% CI 1.78-13.84), and cardiovascular disease 3.72 (95% CI 2.12-6.53). Natalizumab's highest risk was for cardiovascular disease (adjusted hazard ratio [aHR] 1.61; 95% CI 1.24-2.10). For the oral DMDs, fingolimod was associated with higher hazards of cerebrovascular (aHR 2.04; 95% CI 1.27-3.30) and ischemic heart diseases (aHR 1.64; 95% CI 1.10-2.44) and hypertension (aHR 1.73; 95% CI 1.30-2.31); teriflunomide with higher hazards of thyroid disorders (aHR 2.30; 95% CI 1.11-4.74), chronic liver disease (aHR 1.94; 95% CI 1.19-3.18), hypertension (aHR 1.76; 95% CI 1.32-2.37), and hyperlipidemia (aHR 1.61; 95% CI 1.07-2.44); and from complementary analyses (in 1 province), dimethyl fumarate with acute liver injury (aHR 6.55; 95% CI 1.96-21.87). Our study provides an extensive safety profile of several different DMDs used to treat MS in the real-world setting. Our findings not only complement those observed in short-term clinical trials but also provide new insights that help inform the risk-benefit profile of the DMDs used to treat MS in clinical practice. The results of this study highlight the continued need for long-term, independent safety studies of the DMDs used to treat MS. This study provides Class III evidence that for patients with MS, while DMD exposure reduces the risk of infection-related hospitalizations, there are increased risks of infection-related physician visits and incident adverse events for select DMDs.

Primary Care Antibiotic Prescribing and Infection-Related Hospitalisation.

Inappropriate prescribing of antibiotics has been widely recognised as a leading cause of antimicrobial resistance, which in turn has become one of the most significant threats to global health. Given that most antibiotic prescriptions are issued in primary care settings, investigating the associations between primary care prescribing of antibiotics and subsequent infection-related hospitalisations affords a valuable opportunity to understand the long-term health implications of primary care antibiotic intervention. A narrative review of the scientific literature studying associations between primary care antibiotic prescribing and subsequent infection-related hospitalisation was conducted. The Web of Science database was used to retrieve 252 potentially relevant studies, with 23 of these studies included in this review (stratified by patient age and infection type). The majority of studies (n = 18) were published in the United Kingdom, while the remainder were conducted in Germany, Spain, Denmark, New Zealand, and the United States. While some of the reviewed studies demonstrated that appropriate and timely antibiotic prescribing in primary care could help reduce the need for hospitalisation, excessive antibiotic prescribing can lead to antimicrobial resistance, subsequently increasing the risk of infection-related hospitalisation. Few studies reported no association between primary care antibiotic prescriptions and subsequent infection-related hospitalisation. Overall, the disparate results in the extant literature attest to the conflicting factors influencing the decision-making regarding antibiotic prescribing and highlight the necessity of adopting a more patient-focussed perspective in stewardship programmes and the need for increased use of rapid diagnostic testing in primary care.

Measles, mumps, and rubella vaccine at age 6 months and hospitalisation for infection before age 12 months: randomised controlled trial

ObjectiveTo test for potential non-specific effects of an additional, early measles, mumps, and rubella (MMR) vaccine at age 5-7 months on risk of infection related hospitalisation before age 12 months.DesignRandomised,...

Maternal Inflammatory Bowel Disease During Pregnancy and Infectious Disease in Offspring Younger Than 5 Years: A Population-Based Cohort Study.

Maternal inflammatory bowel disease (IBD) during pregnancy may be associated with increased susceptibility to infection in offspring. We aimed to assess this association, taking into consideration the mediating role of anti-tumor necrosis factor α (anti-TNFα) agents and adverse birth outcomes. This population-based cohort study included all live-born singletons born in Denmark during 1995-2016 (n = 1,343,960). The exposure was maternal IBD. Main outcome of interest was offspring infection younger than 5 years, defined by either infection-related hospitalization or systemic antibiotic prescription, whose corresponding risk estimates were hazard ratios (HRs) and incidence rate ratios (IRRs), respectively. We applied an inverse probability-weighted marginal structural model for mediation analysis. Offspring born to mothers with Crohn's disease (CD) had an 18% increased risk of infection-related hospitalization (HR 1.18, 95% confidence interval 1.10-1.26) and a 16% increased frequency of prescribed antibiotics (IRR 1.16, 95% confidence interval 1.11-1.21). Anti-TNFα agents could explain 10% and 3% of the 2 estimated total associations, respectively, while a composite of preterm birth, low birth weight, and small for gestational age could explain 4% and 0%, respectively. The association between prenatal anti-TNFα and frequency of antibiotics attenuated after additional adjustment for maternal CD (IRR from 1.23 [0.98-1.55] to 1.10 [0.87-1.40]). Maternal ulcerative colitis, however, was not associated with offspring infection. Maternal CD, but not ulcerative colitis, was associated with an increased risk of infection in offspring younger than 5 years, of which adverse birth outcomes and anti-TNFα had a minor role. The association between anti-TNFα agents and pediatric infection could be partially explained by maternal CD.

Frailty and the risk of infection-related hospitalizations in older age: Differences by sex

ObjectivesTo investigate the extent to which frailty is associated with infection-related hospitalizations in older men and women, and to explore whether, among women, previous exposure to endogenous estrogens in terms of age at menopause and number of pregnancies modify such a relationship. Study designThe sample comprised 2784 participants in the Progetto Veneto Anziani aged ≥65 years. At baseline and after 4.4 years, frailty was identified according to the presence of three or more of the following: weakness, exhaustion, weight loss, low physical activity, and low walking speed. A passive follow-up on infection-related hospitalizations and mortality was performed for 10 years of observation through linkage with regional registers. Main outcome measuresThe association between frailty and infection-related hospitalizations was assessed through mixed-effects Cox regressions. ResultsFrailty was significantly associated with a 78 % higher risk of infection-related hospitalization, with stronger results in men (hazard ratio = 2.32, 95 % confidence interval 1.63–3.30) than in women (hazard ratio = 1.54, 95 % confidence interval 1.18–2.02). Focusing on women, we found a possible modifying effect for the number of pregnancies but not menopausal age. Women who had experienced one or no pregnancy demonstrated a higher hazard of infection-related hospitalization as a function of frailty (hazard ratio = 3.00, 95 % confidence interval 1.58–5.71) than women who had experienced two or more pregnancies (hazard ratio = 1.68, 95 % confidence interval 1.18–2.39). ConclusionFrailty in older age increases the risk of infection-related hospitalizations, especially in men. The “immunologic advantage” of the female sex in younger age seems to persist also after menopause as a function of the number of pregnancies a woman has experienced.

Higher Soluble ACE2 Levels and Increased Risk of Infection-Related Hospitalization in Patients on Maintenance Hemodialysis.

BackgroundAngiotensin-converting enzyme 2 (ACE2) works as an endogenous counter-regulator of the renin-angiotensin system, which has pivotal roles in preventing both cardiovascular disease (CVD) and inflammation. In general populations, higher plasma soluble ACE2 levels were reported to be associated with increased risks of all-cause death and major CVD. Because infections are fatal in patients on maintenance hemodialysis, we aimed to explore whether soluble ACE2 levels are associated with an increased risk of infection-related hospitalization in these patients.MethodsUsing data from a prospective, multicenter, cohort study conducted in Tokyo, Japan, we performed a post-hoc analyses of 724 clinically stable patients on maintenance hemodialysis. We measured baseline serum soluble ACE2 levels and assessed potential determinants of its with infection-related hospitalization as a primary outcome as well as all-cause death and CVD as secondary outcomes using a Cox proportional hazards model.ResultsThe soluble ACE2 level (median, 0.16 ng/ml; interquartile range, 0.07–0.57 ng/ml) showed a weak negative association with age. During a median follow-up of 39 months, 106 patients (14.6%) were hospitalized with infectious diseases. Compared with the lower half of soluble ACE2 levels, the higher half was associated with an increased risk of infection-related hospitalization (hazard ratio, 1.57; 95% confidence interval, 1.02–2.41) with adjustment by other risk factors. On the other hand, there were no significant associations between soluble ACE2 and risks of all-cause death and CVD.ConclusionHigher soluble ACE2 levels may associate with an increased risk of infection-related hospitalization in patients on maintenance hemodialysis.

Higher Hospitalization Rates in Children Born HIV-exposed Uninfected in British Columbia, Canada, Between 1990 and 2012.

Compared with children who are HIV-unexposed and uninfected (CHUU), children who are HIV-exposed and uninfected (CHEU) experience more clinical complications. We investigated hospitalizations among CHEU by antenatal antiretroviral therapy (ART) exposure, in British Columbia, Canada. This retrospective controlled cohort study used administrative health data from 1990 to 2012. CHEU and CHUU were matched 1:3 for age, sex and maternal geographical area of residence. We determined adjusted odds ratios (aORs) via conditional logistic regression, adjusting for maternal risk factors. A total of 446 CHEU and 1333 CHUU were included. Compared with CHUU, more CHEU experienced one or more lifetime hospitalization (47.3% vs. 29.8%), one or more neonatal hospitalization (40.4% vs. 27.6%), and any intensive care unit admission (28.5% vs. 9.2%). In adjusted analyses, CHEU experienced higher odds of any lifetime hospitalization (aOR 2.30, 95% confidence interval 1.81-2.91) and neonatal hospitalization (aOR 2.14, 95% confidence interval 1.68-2.73), compared with CHUU. There was, however, no difference in infection-related hospitalizations (9.0% vs. 7.5%), which were primarily respiratory tract infections among both CHEU and CHUU. CHEU whose mothers-initiated ART preconception showed lower odds of infection-related hospitalizations than children whose mothers initiated ART during pregnancy or received no ART. CHEU experienced increased odds of hospitalization relative to CHUU. A substantial number of CHEU hospitalizations occurred within the neonatal period and were ICU admissions. Initiating ART preconception may reduce the risk of infection-related hospitalizations. These findings reinforce the benefit of ART in pregnancy and the need for ongoing pediatric care to reduce hospitalizations.

Vedolizumab Is Associated With a Lower Risk of Serious Infections Than Anti-Tumor Necrosis Factor Agents in Older Adults

Despite the increased numbers of older adults with inflammatory bowel diseases (IBDs), there are few studies regarding the safety and effectiveness of IBD treatments in older adults. The aim of this study was to compare the safety and effectiveness of anti-tumor necrosis factor (TNF)-α agents and vedolizumab in older adults with IBD. We conducted a retrospective cohort study using an active comparator, new-user design for adults age 65 years and older with IBD initiating anti-TNF-α agents and vedolizumab in the Medicare claims database from 2014 to 2017. The primary safety outcome was infection-related hospitalization (excluding intra-abdominal and perianal abscesses). Co-primary outcomes to estimate effectiveness were IBD-related hospitalization, IBD-related surgery, and new corticosteroid use 60 days or more after biologic initiation. We performed propensity score weighting to control for confounding and estimated adjusted hazard ratios and 95% confidence intervals using standardized morbidity ratio-weighted variables. We identified 1152 anti-TNF-α new users and 480 vedolizumab new users. The median age was 71 years in both cohorts and 11% were age 80 years or older. Crohn's disease patients comprised 54% of the anti-TNF-α cohort and 57% of the vedolizumab cohort. There was no significant difference in demographics, health care utilization, or frailty in both cohorts. More than half of both cohorts had a Charlson comorbidity index of 2 or higher. Vedolizumab users had a decreased risk of infection-related hospitalization (adjusted hazard ratio, 0.47; 95% confidence interval, 0.25-0.86). There was no significant difference in the outcomes approximating effectiveness. Older IBD patients treated with vedolizumab had a lower risk of infection-related hospitalization compared with those initiating anti-TNFs. We observed no difference in effectiveness defined by hospitalizations, surgery, or new corticosteroid use.

The familial risk of infection-related hospitalization in children: A population-based sibling study.

To assess the risk of severe childhood infections within families, we conducted a sibling analysis in a population-based cohort study with genealogical linkage. We investigated the sibling risk of hospitalization with common infections, a marker of severity. We hypothesized that having siblings hospitalized for infection would increase the proband's risk of admission with infection. We used population data on Western Australian live-born singletons and their siblings between 1980 and 2014. Measures of infection were infection-related hospitalizations from discharge diagnostic codes. Exposure was having a sibling who had an infection-related hospitalization. Outcomes were infection-related hospitalizations in the child/proband. Probands were followed until an infection-related hospitalization admission (up to the first three), death, 18th birthday, or end of 2014, whichever occurred first. Infection risks were estimated by adjusted Cox proportional hazard models for multiple events. Of 512,279 probands, 142,915 (27.9%) had infection-related hospitalizations; 133,322 (26.0%) had a sibling with a previous infection-related hospitalization (i.e. exposed). Median interval between sibling and proband infection-related hospitalizations was 1.4 years (inter-quartile range 0.5-3.7). Probands had a dose-dependent increase in risk if sibling/s had 1, 2, or 3+ infection-related hospitalizations (adjusted hazard ratio, aHR 1.41, 95% CI 1.39-1.43; aHR 1.65, 1.61-1.69; aHR 1.83, 1.77-1.90, respectively). Among siblings with the same clinical infection type, highest sibling risks were for genitourinary (aHR 2.06, 1.68-2.53), gastrointestinal (aHR 2.07, 1.94-2.19), and skin/soft tissue infections (aHR 2.34, 2.15-2.54). Overall risk of infection-related hospitalization was higher in children with more siblings and with older siblings. In this population-based study, we observed an increased risk of infection-related hospitalization in children whose siblings were previously hospitalized for infection. Public health interventions may be particularly relevant in families of children hospitalized with infection.

Infection-related morbidity and mortality among older patients with DLBCL treated with full- or attenuated-dose R-CHOP

Infection-related morbidity and mortality are increased in older patients with diffuse large B-cell lymphoma (DLBCL) compared with population-matched controls. Key predictive factors for infection-related hospitalization during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and deaths as a result of infection in older patients during and after treatment with R-CHOP remain incompletely understood. For this study, 690 consecutively treated patients age 70 years or older who received full-dose or attenuated-dose R-CHOP treatment were analyzed for risk of infection-related hospitalization and infection-related death. Median age was 77 years, and 34.4% were 80 years old or older. Median follow-up was 2.8 years (range, 0.4-8.9 years). Patient and baseline disease characteristics were assessed in addition to intended dose intensity (IDI). Of all patients, 72% were not hospitalized with infection. In 331 patients receiving an IDI ≥80%, 33% were hospitalized with ≥1 infections compared with 23.3% of 355 patients receiving an IDI of <80% (odds ratio, 1.61; 95% confidence interval, 1.15-2.25; P = .006). An increased risk of infection-related admission was independently associated with IDI >80% across the whole cohort. Primary quinolone prophylaxis independently reduced infection-related admission. A total of 51 patients died as a result of infection. The 6-month, 12-month, 2-year, and 5-year cumulative incidences of infection-related death were 3.3%, 5.0%, 7.2%, and 11.1%, respectively. Key independent factors associated with infection-related death were an International Prognostic Index (IPI) score of 3 to 5, Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score ≥6, and low albumin, which enabled us to generate a predictive risk score. We defined a smaller group (15%) of patients (IPI score of 0-2, albumin >36 g/L, CIRS-G score <6) in which no cases of infection-related deaths occurred at 5 years of follow-up. Whether patients at higher risk of infection-related death could be targeted with enhanced antimicrobial prophylaxis remains unknown and will require a randomized trial.

Low Serum Zinc Concentration Is Associated With Infection Particularly in Patients With Stage 5 Chronic Kidney Disease Medicated with Proton Pump Inhibitors

Zinc (Zn) plays an important role in immune function. Several studies have identified an association between a Zn deficiency and infection. Infectious diseases are major complications of chronic kidney disease (CKD). We investigated whether serum Zn concentrations are associated with risk of infection in patients with advanced CKD. We retrospectively analyzed data from 299 patients with CKD whose serum Zn values were measured to evaluate anemia between January 2013 and December 2016. Among them, 9 who were supplemented with Zn and 67 who had started urgent dialysis at the time of measurement were excluded. We analyzed infection events, length of infection-related hospitalization and infection-related and all-cause mortality in the remaining 223 patients during a median follow-up of 36months. We assigned the patients to groups with low or high Zn values (≤50 and>50μg/dL, respectively) based on a median value of 50μg/dL. Data were analyzed using Kaplan-Meier curves and Cox hazards models. During a median follow-up of 36months, 40 patients were hospitalized with infections. The rate of infection-related and long-term hospitalization (>10days) due to infection was higher for patients with low, than high, Zn values (23.3% vs. 12.6%; P=.042 and 26.2% vs. 12.4%; P=.007, respectively). After adjustment in Cox hazards models, low serum Zn values remained an independent risk factor for infection-related hospitalization (Hazard ratio [HR], 1.93; 95% confidence interval [CI], 1.01-3.71; P=.048), especially for patients on proton pump inhibitor (PPI) medications (HR, 2.66, 95%; CI, 1.22-5.81; P=.014). Patients with advanced CKD accompanied by low serum Zn concentration, and particularly those medicated with PPI, are at high risk of infection-related hospitalization, which results in long-term hospitalization.

Shorter and Longer Courses of Antibiotics for Common Infections and the Association With Reductions of Infection-Related Complications Including Hospital Admissions

BackgroundAntimicrobial resistance is a serious global health concern that emphasizes completing treatment course. Recently, the effectiveness of short versus longer antibiotic courses has been questioned. This study investigated the duration of prescribed antibiotics, their effectiveness, and associated risk of infection-related complications.MethodsClinical Practice Research Datalink identified 4 million acute infection episodes prescribed an antibiotic in primary care between January 2014—June 2014, England. Prescriptions were categorized by duration. Risk of infection-related hospitalizations within 30 days was modelled overall and by infection type. Risk was assessed immediately after or within 30 days follow-up to measure confounders given similar and varying exposure, respectively. An interaction term with follow-up time assessed whether hazard ratios (HRs) remained parallel with different antibiotic durations.ResultsThe duration of antibiotic courses increased over the study period (5.2–19.1%); 6–7 days were most common (66.9%). Most infection-related hospitalizations occurred with prescriptions of 8–15 days (0.21%), accompanied by greater risk of infection-related complications compared to patients who received a short prescription (HR: 1.75 [95% CI: 1.54–2.00]). Comparing HRs in the first 5 days versus remaining follow-up showed longer antibiotic courses were no more effective than shorter courses (1.02 [95% CI: 0.90–1.16] and 0.92 [95% CI: 0.75–1.12]). No variation by infection-type was observed.ConclusionsEqual effectiveness was found between shorter and longer antibiotic courses and the reduction of infection-related hospitalizations. Stewardship programs should recommend shorter courses of antibiotics for acute infections. Further research is required for treating patients with a complex medical history.SummaryPrescribing of longer courses increased over the study period. The majority of hospitalizations occurred for patients receiving longer courses. Risk of developing a complication (immediate vs remaining follow-up) found longer courses were no more effective than shorter courses.

Mode of birth and risk of infection-related hospitalisation in childhood: A population cohort study of 7.17 million births from 4 high-income countries.

The proportion of births via cesarean section (CS) varies worldwide and in many countries exceeds WHO-recommended rates. Long-term health outcomes for children born by CS are poorly understood, but limited data suggest that CS is associated with increased infection-related hospitalisation. We investigated the relationship between mode of birth and childhood infection-related hospitalisation in high-income countries with varying CS rates. We conducted a multicountry population-based cohort study of all recorded singleton live births from January 1, 1996 to December 31, 2015 using record-linked birth and hospitalisation data from Denmark, Scotland, England, and Australia (New South Wales and Western Australia). Birth years within the date range varied by site, but data were available from at least 2001 to 2010 for each site. Mode of birth was categorised as vaginal or CS (emergency/elective). Infection-related hospitalisations (overall and by clinical type) occurring after the birth-related discharge date were identified in children until 5 years of age by primary/secondary International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes. Analysis used Cox regression models, adjusting for maternal factors, birth parameters, and socioeconomic status, with results pooled using meta-analysis. In total, 7,174,787 live recorded births were included. Of these, 1,681,966 (23%, range by jurisdiction 17%-29%) were by CS, of which 727,755 (43%, range 38%-57%) were elective. A total of 1,502,537 offspring (21%) had at least 1 infection-related hospitalisation. Compared to vaginally born children, risk of infection was greater among CS-born children (hazard ratio (HR) from random effects model, HR 1.10, 95% confidence interval (CI) 1.09-1.12, p < 0.001). The risk was higher following both elective (HR 1.13, 95% CI 1.12-1.13, p < 0.001) and emergency CS (HR 1.09, 95% CI 1.06-1.12, p < 0.001). Increased risks persisted to 5 years and were highest for respiratory, gastrointestinal, and viral infections. Findings were comparable in prespecified subanalyses of children born to mothers at low obstetric risk and unchanged in sensitivity analyses. Limitations include site-specific and longitudinal variations in clinical practice and in the definition and availability of some data. Data on postnatal factors were not available. In this study, we observed a consistent association between birth by CS and infection-related hospitalisation in early childhood. Notwithstanding the limitations of observational data, the associations may reflect differences in early microbial exposure by mode of birth, which should be investigated by mechanistic studies. If our findings are confirmed, they could inform efforts to reduce elective CS rates that are not clinically indicated.

Clinical outcomes of infection-related hospitalization in incident peritoneal dialysis patients.

BackgroundInfection is the second leading cause of death in patients undergoing long-term dialysis. Peritoneal dialysis (PD) is associated with an increased risk of infection-related hospitalization (IRH) when compared with hemodialysis. In this study, we investigated the influence of IRH on clinical outcomes in incident PD patients.MethodsIn total, 583 incident PD patients were selected from the Clinical Research Center Registry for End-Stage Renal Disease, a nationwide multicenter prospective observational cohort study in Korea. Incident PD patients who had been hospitalized for infection-related diseases were defined as the IRH group. The primary outcome was all-cause mortality and the secondary outcome was technical failure. The median follow-up period was 29 months.ResultsSeventy-three PD patients (12.5%) were categorized in the IRH group. Multivariable logistic regression analysis showed that diabetes mellitus was a significant independent predictor for IRH (odds ratio, 2.43; 95% confidence interval [CI], 1.12 to 5.29; P = 0.007). The most common causes of IRH were peritonitis (63.0%) and respiratory tract infection (9.6%). Multivariable Cox proportional hazard model analysis showed that IRH was a significant independent risk factor for all-cause mortality (hazard ratio [HR], 2.51; 95% CI, 1.12 to 5.62; P = 0.026) and for the technical failure of PD (HR, 3.23; 95% CI, 1.90 to 5.51; P < 0.001).ConclusionOur data showed that after initiation of PD, IRH was significantly associated with higher risk of all-cause mortality and technical failure.

Association of FGF23 with Incident Sepsis in Community-Dwelling Adults: A Cohort Study.

Fibroblast growth factor 23 (FGF23) is a hormone that regulates vitamin D activity. Higher circulating FGF23 concentrations have been associated with an increased risk of infection-related hospitalization, but the association of FGF23 with risk of sepsis remains unclear. We examined the association of FGF23 with incident sepsis events in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national longitudinal cohort of black and white adults ≥45 years of age. Using a case-cohort design, we measured baseline FGF23 in 703 sepsis cases and in 991 participants randomly selected from the REGARDS cohort. We defined sepsis as the presence of a serious infection plus two or more Systemic Inflammatory Response Syndrome criteria. We identified first sepsis hospitalizations during 2003-2012 by adjudicated medical record review. Cox proportional hazards models were used to examine associations of FGF23 with incident sepsis, adjusting for age, sex, race, income, education, smoking, body mass index, physical activity, chronic pulmonary disease, eGFR, urine albumin-creatinine ratio, and high-sensitivity C-reactive protein. We also examined whether associations differed by age, race, sex, and CKD by testing interaction terms. Higher FG23 concentrations were associated with greater risk of sepsis (hazard ratio [HR] per doubling of FGF23, 1.37; 95% CI, 1.22 to 1.54) in models adjusted for sociodemographic and clinical variables. After further adjusting for eGFR, urine albumin-creatinine ratio, and high-sensitivity C-reactive protein, the association was attenuated and no longer statistically significant (HR per doubling, 1.01; 95% CI, 0.85 to 1.21). The results did not statistically differ by strata of age, sex, race, or CKD. In community-dwelling adults, higher FGF23 concentrations were not independently associated with higher risk of sepsis.

Comparison of infection-related hospitalization risk and costs in tumor necrosis factor inhibitor-experienced patients with rheumatoid arthritis (RA) treated with abatacept or other targeted disease-modifying anti-rheumatic drugs (tDMARDs)

Background: Evidence on the cost and risk of infection-related hospitalizations associated with targeted disease-modifying anti-rheumatic drugs (tDMARDs) in patients with RA previously treated with a tumor necrosis factor inhibitor (TNFi) is limited. This study compared the risk and cost of infection-related hospitalizations in commercially insured TNFi-experienced RA patients receiving abatacept, TNFi, or another non-TNFi.Methods: A retrospective observational study was conducted using 2 large insurance claims databases (1 January 2009–30 June 2017). Adult TNFi-experienced RA patients initiating a subsequent tDMARD (initiation date of tDMARD = index date) with 12 months of continuous enrollment pre-index date, and who had ≥1 inpatient or ≥2 outpatient medical RA claims on 2 different dates were included. Abatacept was compared to TNFis (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) and other non-TNFis (tocilizumab, rituximab, and tofacitinib). Cox proportional hazards models estimated the adjusted risk for infection-related hospitalization; costs were calculated on a per-member-per-month (PMPM) and per-patient-per-month (PPPM) basis using generalized linear models.Results: More patients in the abatacept cohort had an infection-related hospitalization at baseline (4.5%) vs TNFis (2.0%, p < .0001) and other non-TNFis (3.6%, p = .2619). However, during follow-up abatacept patients had fewer infection-related hospitalizations (abatacept: 2.8%, TNFi: 3.7% and other non-TNFis: 5.2%; p < .05). Regression results indicated that compared to patients on abatacept, patients receiving a TNFi [HR: 1.6 (95% CI: 1.1, 2.2)] and other non-TNFis [HR: 1.9 (95% CI: 1.3, 2.8)] had a significantly higher risk of infection-related hospitalization. Abatacept PMPM costs were lowest ($0.25 vs $0.39 and $0.43 for TNFi and other non-TNFi respectively). Mean PPPM (95% CI) cost in the follow-up was lower for abatacept compared to TNFi ($73 vs. $115; p = .042), and other non-TNFi ($73 vs. $125; p = .039).Conclusions: There were significantly lower infection-related hospitalizations and associated costs in TNF-experienced RA patients treated with abatacept than TNFis and other non-TNFis.

Stratified risks of infection-related hospitalization in patients with chronic kidney disease - A prospective cohort study

Patients with chronic kidney disease (CKD) are at high risk of infection, but whether the risks are attenuated in different patient groups remains unclear. This study enrolled participants with CKD stages 1–3 in the New Taipei City Health Screening Program between 2005 and 2008. A proportional hazard regression model was employed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for infection-related hospitalization and mortality in younger (<50-year-old) and older (≥50-year-old) CKD patients. Of 119,871 adults, there were 14,207 cases of first hospitalization for infection during a median follow-up of 8.14 years; 45.5% of these cases were younger patients. Unlike CKD stage 1 and 2 patients, the risk of infection-related hospitalization in younger CKD stage 3 patients is as high as for older CKD stage 3 patients. Proteinuria increases the risk of infection-related hospitalization independent of estimated glomerular filtration rate (eGFR) levels in older CKD patients but this relationship is weak in their younger counterparts. In conclusion, the risk of infection-related hospitalization is high in subgroups of CKD patients. Prevention and treatment of infections in these patients merit more attention.

Infection-related hospitalization after intensive immunosuppressive therapy among lupus nephritis and ANCA glomerulonephritis patients

Introduction This study aimed to investigate the clinical characteristics, risk factors, and outcomes of infection-related hospitalization (IRH) in patients with lupus nephritis (LN) and ANCA glomerulonephritis after intensive immunosuppressive therapy. Methods Patients diagnosed with LN or ANCA glomerulonephritis who received intensive immunosuppressive therapy at the First Affiliated Hospital of Sun Yat-sen University from 2005 to 2014 were enrolled. Demographics, laboratory parameters, immunosuppressive agents, and IRH details were collected. Multivariable Cox regression was used, and hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. Results Totally, 872 patients with 806 LN and 66 ANCA glomerulonephritis were enrolled, and 304 (34.9%) patients with 433 episodes of IRH were recorded. ANCA glomerulonephritis patients were more vulnerable to IRH than LN patients (53.0% vs. 33.4%, p = .001). Multivariable Cox regression analysis showed that ANCA glomerulonephritis (HR = 1.62, 95% CI: 1.06–2.49, p = .027), diabetes (HR = 1.82, 95% CI: 1.03–3.22, p = .039) and a higher initial dose of prednisone (HR = 1.01, 95% CI: 1.00–1.02, p = .013) were associated with a higher likelihood of IRH. Higher albumin (HR = 0.96, 95% CI: 0.94–0.98, p < .001), globulin (HR = 0.98, 95% CI: 0.96–0.99, p = .008), and eGFR (HR = 0.99, 95% CI: 0.99–1.00, p < .001), were associated with a lower likelihood of IRH. The rates of transfer to ICU and mortality for ANCA glomerulonephritis patients were higher than those for LN patients (22.9% vs. 1.9%, p < .001, and 20.0% vs. 0.7%, p < .001, respectively). Conclusions ANCA glomerulonephritis patients had a higher risk of IRH and poorer outcome once infected after intensive immunosuppressive therapy than LN patients. More strict control for infection risks is required for ANCA glomerulonephritis patients who undergo intensive immunosuppressive therapy.

Proton Pump Inhibitors and Infection-Related Hospitalizations Among Residents of Long-Term Care Facilities: A Case-Control Study.

Our objective was to investigate associations between proton pump inhibitor (PPIs) use and infection-related hospitalizations among residents of long-term care facilities (LTCFs). This was a case-control study of residents aged ≥ 65years admitted to hospital between July 2013 and June 2015. Residents admitted for infections (cases) and falls or fall-related injuries (controls) were matched for age (± 2years), sex, and index date of admission (± 6months). Conditional logistic regression was used to estimate crude and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between PPI use and infection-related hospitalizations. Analyses were adjusted for age, sex, polypharmacy, diabetes, heart failure, chronic obstructive pulmonary disease, myocardial infarction, cerebrovascular accident, and concomitant use of cancer and immunosuppressant medications. Subgroup analyses were performed for high- and low/moderate-intensity PPIs and for respiratory and non-respiratory infections. Logistic regression was used to compare the odds of infection-related hospitalizations among users of high- and low/moderate-intensity PPIs. Overall, 181 cases were matched to 354 controls. Preadmission PPI use was associated with infection-related hospitalizations (aOR 1.66; 95% CI 1.11-2.48). In subgroup analyses, the association was apparent only for respiratory infections (aOR 2.26; 95% CI 1.37-3.73) and high-intensity PPIs (aOR 1.93; 95% CI 1.23-3.04). However, the risk of infection-related hospitalization was not significantly higher among users of high- versus low/moderate-intensity PPIs (aOR 1.25; 95% CI 0.74-2.13). Residents who use PPIs may be at increased risk of infection-related hospitalizations, particularly respiratory infections. Study findings provide further support for initiatives to minimize unnecessary PPI use in the LTCF setting.