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1.
Pediatr Hematol Oncol ; : 1-10, 2022 Sep 20.
Article in English | MEDLINE | ID: covidwho-2317645

ABSTRACT

During COVID-19, public health measures including masks and social distancing decreased viral upper respiratory infections (URI). Upper respiratory infections are the most common infectious etiology for low-risk pediatric febrile neutropenia (FN). This single-center, quasi-experimental, pre-post study was designed to understand the impact of public health measures on FN admissions and outcomes in the general pediatric oncology population during the COVID (March 2020-February 2021) vs. pre-COVID era (January 2018-February 2020) and their respective respiratory seasons (November-February). Episodes were risk-stratified using a tool recommended by the Children's Oncology Group. Descriptive and bivariate statistics were used to compare admission characteristics and outcomes. Comparing respiratory seasons, the Covid-era season had 60% fewer URI diagnoses (5/12), while high-risk episodes (63.6% [28/44] vs. 44.2% [23/52]) and intensive care admissions (18.2% [8/44] vs. 3.8% [2/52]) increased. Between eras, URIs were lower in the COVID-era (10.8% [16/148] vs. 19.9% [67/336]; p = 0.01), but admission characteristics and severe outcomes were not different. The impact of public health measures was most prominent during the respiratory season. Despite decreased incidence of URIs, the overall admission characteristics and severe outcomes were minimally impacted due to the brevity of respiratory seasons, but larger studies are warranted.

2.
PLoS One ; 17(11): e0276806, 2022.
Article in English | MEDLINE | ID: covidwho-2098761

ABSTRACT

BACKGROUND: Racial and ethnic disparities in COVID-19 outcomes exist, but whether in-hospital care explains this difference is not known. We sought to determine racial and ethnic differences in demographics, comorbidities, in-hospital treatments, and in-hospital outcomes of patients hospitalized with COVID-19. METHODS AND FINDINGS: This was a cohort study using MiCOVID-19, a multi-center, retrospective, collaborative quality improvement registry, which included data on patients hospitalized with COVID-19 across 38 hospitals in the State of Michigan. 2,639 adult patients with COVID-19 hospitalized at a site participating in the MiCOVID-19 Registry were randomly selected. Outcomes included in-hospital mortality, age at death, intensive care unit admission, and need for invasive mechanical ventilation by race and ethnicity. Baseline comorbidities differed by race and ethnicity. In addition, Black patients had higher lactate dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, creatine phosphokinase, and ferritin levels. Black patients were less likely to receive dexamethasone and remdesivir compared with White patients (4.2% vs 14.3% and 2.2% vs. 11.8%, p < 0.001 for each). Black (18.7%) and White (19.6%) patients experienced greater mortality compared with Asian (13.0%) and Latino (5.9%) patients (p < 0.01). The mean age at death was significantly lower by 8 years for Black patients (69.4 ± 13.3 years) compared with White (77.9 ± 12.6), Asian (77.6 ± 6.6), and Latino patients (77.4 ± 15.5) (p < 0.001). CONCLUSIONS: COVID-19 mortality appears to be driven by both pre-hospitalization clinical and social factors and potentially in-hospital care. Policies aimed at population health and equitable application of evidence-based medical therapy are needed to alleviate the burden of COVID-19.


Subject(s)
COVID-19 , Adult , Humans , Child , Ethnicity , Retrospective Studies , Cohort Studies , White People , Hospitalization , Registries
3.
BMJ Qual Saf ; 31(9): 652-661, 2022 09.
Article in English | MEDLINE | ID: covidwho-2001861

ABSTRACT

BACKGROUND: Little is known about peripherally inserted central catheter (PICC) use, appropriateness and device outcomes in Brazil. METHODS: We conducted an observational, prospective, cohort study spanning 16 Brazilian hospitals from October 2018 to August 2020. Patients ≥18 years receiving a PICC were included. PICC placement variables were abstracted from medical records. PICC-related major (deep vein thrombosis (DVT), central line-associated bloodstream infection (CLABSI) and catheter occlusion) and minor complications were collected. Appropriateness was evaluated using the Michigan Appropriateness Guide for Intravenous Catheters (MAGIC). Devices were considered inappropriate if they were in place for <5 days, were multi-lumen, and/or were placed in patients with a creatinine >2.0 mg/dL. PICCs considered appropriate met none of these criteria. Mixed-effects logistic regression models adjusting for patient-level and hospital-level characteristics assessed the association between appropriateness and major complications. RESULTS: Data from 12 725 PICCs were included. Mean patient age was 66.4±19 years and 51.0% were female. The most common indications for PICCs were intravenous antibiotics (81.1%) and difficult access (62.7%). Most PICCs (72.2%) were placed under ultrasound guidance. The prevalence of complications was low: CLABSI (0.9%); catheter-related DVT (1.0%) and reversible occlusion (2.5%). Of the 12 725 devices included, a total of 7935 (62.3%) PICCs were inappropriate according to MAGIC. With respect to individual metrics for appropriateness, 17.0% were placed for <5 days, 60.8% were multi-lumen and 11.3% were in patients with creatinine >2.0 mg/dL. After adjusting for patient and hospital-level characteristics, multi-lumen PICCs considered inappropriate were associated with greater odds of major complications (OR 2.54, 95% CI 1.61 to 4.02). CONCLUSIONS: Use of PICCs in Brazilian hospitals appears to be safe and comparable with North America. However, opportunities to improve appropriateness remain. Future studies examining barriers and facilitators to improving device use in Brazil would be welcomed.


Subject(s)
Catheter-Related Infections , Catheterization, Central Venous , Catheterization, Peripheral , Central Venous Catheters , Aged , Aged, 80 and over , Brazil/epidemiology , Catheter-Related Infections/epidemiology , Catheterization, Central Venous/methods , Catheterization, Peripheral/adverse effects , Catheters , Central Venous Catheters/adverse effects , Cohort Studies , Creatinine , Female , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , Risk Factors
4.
Ann Intern Med ; 175(8): 1195-1196, 2022 08.
Article in English | MEDLINE | ID: covidwho-1994461
5.
6.
Ann Intern Med ; 175(4): 505-512, 2022 04.
Article in English | MEDLINE | ID: covidwho-1818638

ABSTRACT

BACKGROUND: Although disparities in COVID-19 outcomes have been observed, factors contributing to these differences are not well understood. OBJECTIVE: To determine whether COVID-19 hospitalization outcomes are related to neighborhood-level social vulnerability, independent of patient-level clinical factors. DESIGN: Pooled cross-sectional study of prospectively collected data. SETTING: 38 Michigan hospitals. PATIENTS: Adults older than 18 years hospitalized for COVID-19 in a participating site between March and December 2020. MEASUREMENTS: COVID-19 outcomes included acute organ dysfunction, organ failure, invasive mechanical ventilation, intensive care unit stay, death, and discharge disposition. Social vulnerability was measured by the social vulnerability index (SVI), a composite measure of social disadvantage. RESULTS: Compared with patients in low-vulnerability ZIP codes, those living in high-vulnerability ZIP codes were more frequently treated in the intensive care unit (29.0% vs. 24.5%); more frequently received mechanical ventilation (19.3% vs. 14.2%); and experienced higher rates of organ dysfunction (51.9% vs. 48.6%), organ failure (54.7% vs. 51.6%), and in-hospital death (19.4% vs. 16.7%). In mixed-effects regression analyses accounting for age, sex, and comorbid conditions, an increase in a patient's neighborhood SVI by 0.25 (1 quartile) was associated with greater likelihood of mechanical ventilation (increase of 2.1 percentage points), acute organ dysfunction (increase of 2.8 percentage points), and acute organ failure (increase of 2.8 percentage points) but was not associated with intensive care unit stay, mortality, or discharge disposition. LIMITATION: Observational data focused on hospitalizations in a single state. CONCLUSION: Hospitalized patients with COVID-19 from socially vulnerable neighborhoods presented with greater illness severity and required more intensive treatment, but once hospitalized they did not experience differences in hospital mortality or discharge disposition. Policies that target socially vulnerable neighborhoods and access to COVID-19 care may help ameliorate health disparities. PRIMARY FUNDING SOURCE: Blue Cross Blue Shield of Michigan (BCBSM) and Blue Care Network as part of the BCBSM Value Partnerships Program, the Michigan Public Health Institute, and the Michigan Department of Health & Human Services.


Subject(s)
COVID-19 , Adult , COVID-19/epidemiology , COVID-19/therapy , Cross-Sectional Studies , Hospital Mortality , Hospitalization , Humans , Multiple Organ Failure , Retrospective Studies , SARS-CoV-2
7.
Infect Control Hosp Epidemiol ; 43(9): 1184-1193, 2022 09.
Article in English | MEDLINE | ID: covidwho-1764088

ABSTRACT

BACKGROUND: We sought to determine the incidence of community-onset and hospital-acquired coinfection in patients hospitalized with coronavirus disease 2019 (COVID-19) and to evaluate associated predictors and outcomes. METHODS: In this multicenter retrospective cohort study of patients hospitalized for COVID-19 from March 2020 to August 2020 across 38 Michigan hospitals, we assessed prevalence, predictors, and outcomes of community-onset and hospital-acquired coinfections. In-hospital and 60-day mortality, readmission, discharge to long-term care facility (LTCF), and mechanical ventilation duration were assessed for patients with versus without coinfection. RESULTS: Of 2,205 patients with COVID-19, 141 (6.4%) had a coinfection: 3.0% community onset and 3.4% hospital acquired. Of patients without coinfection, 64.9% received antibiotics. Community-onset coinfection predictors included admission from an LTCF (OR, 3.98; 95% CI, 2.34-6.76; P < .001) and admission to intensive care (OR, 4.34; 95% CI, 2.87-6.55; P < .001). Hospital-acquired coinfection predictors included fever (OR, 2.46; 95% CI, 1.15-5.27; P = .02) and advanced respiratory support (OR, 40.72; 95% CI, 13.49-122.93; P < .001). Patients with (vs without) community-onset coinfection had longer mechanical ventilation (OR, 3.31; 95% CI, 1.67-6.56; P = .001) and higher in-hospital mortality (OR, 1.90; 95% CI, 1.06-3.40; P = .03) and 60-day mortality (OR, 1.86; 95% CI, 1.05-3.29; P = .03). Patients with (vs without) hospital-acquired coinfection had higher discharge to LTCF (OR, 8.48; 95% CI, 3.30-21.76; P < .001), in-hospital mortality (OR, 4.17; 95% CI, 2.37-7.33; P ≤ .001), and 60-day mortality (OR, 3.66; 95% CI, 2.11-6.33; P ≤ .001). CONCLUSION: Despite community-onset and hospital-acquired coinfection being uncommon, most patients hospitalized with COVID-19 received antibiotics. Admission from LTCF and to ICU were associated with increased risk of community-onset coinfection. Future studies should prospectively validate predictors of COVID-19 coinfection to facilitate the reduction of antibiotic use.


Subject(s)
COVID-19 , Coinfection , Anti-Bacterial Agents/therapeutic use , COVID-19/epidemiology , Cohort Studies , Coinfection/drug therapy , Coinfection/epidemiology , Hospital Mortality , Hospitalization , Hospitals , Humans , Retrospective Studies , Risk Factors
8.
Obstet Gynecol ; 138(4): 603-615, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1591562

ABSTRACT

OBJECTIVE: To perform a literature review of key aspects of prenatal care delivery to inform new guidelines. DATA SOURCES: A comprehensive review of Ovid MEDLINE, Elsevier's Scopus, Google Scholar, and ClinicalTrials.gov. METHODS OF STUDY SELECTION: We included studies addressing components of prenatal care delivery (visit frequency, routine pregnancy assessments, and telemedicine) that assessed maternal and neonatal health outcomes, patient experience, or care utilization in pregnant individuals with and without medical conditions. Quality was assessed using the RAND/UCLA Appropriateness Methodology approach. Articles were independently reviewed by at least two members of the study team for inclusion and data abstraction. TABULATION, INTEGRATION, AND RESULTS: Of the 4,105 published abstracts identified, 53 studies met inclusion criteria, totaling 140,150 participants. There were no differences in maternal and neonatal outcomes among patients without medical conditions with reduced visit frequency schedules. For patients at risk of preterm birth, increased visit frequency with enhanced prenatal services was inconsistently associated with improved outcomes. Home monitoring of blood pressure and weight was feasible, but home monitoring of fetal heart tones and fundal height were not assessed. More frequent weight measurement did not lower rates of excessive weight gain. Home monitoring of blood pressure for individuals with medical conditions was feasible, accurate, and associated with lower clinic utilization. There were no differences in health outcomes for patients without medical conditions who received telemedicine visits for routine prenatal care, and patients had decreased care utilization. Telemedicine was a successful strategy for consultations among individuals with medical conditions; resulted in improved outcomes for patients with depression, diabetes, and hypertension; and had inconsistent results for patients with obesity and those at risk of preterm birth. CONCLUSION: Existing evidence for many components of prenatal care delivery, including visit frequency, routine pregnancy assessments, and telemedicine, is limited.


Subject(s)
Delivery of Health Care/methods , Prenatal Care/methods , COVID-19/epidemiology , Diabetes, Gestational/epidemiology , Female , Humans , Hypertension, Pregnancy-Induced/epidemiology , Infant, Newborn , Michigan , Practice Guidelines as Topic , Pregnancy , Pregnancy Complications/epidemiology , Pregnancy Outcome/epidemiology , Premature Birth/epidemiology , Randomized Controlled Trials as Topic , SARS-CoV-2 , Telemedicine/methods
10.
Journal of the American Medical Directors Association ; 2021.
Article in English | EuropePMC | ID: covidwho-1451721

ABSTRACT

<h4>Objective</h4> To examine racial and ethnic disparities in clinical, financial, and mental health outcomes within a diverse sample of hospitalized COVID-19–positive patients in the 60 days postdischarge. <h4>Design</h4> A cross-sectional study. <h4>Setting and Participants</h4> A total of 2217 adult patients who were hospitalized with a COVID-19–positive diagnosis as evidenced by test (reverse-transcriptase polymerase chain reaction), a discharge diagnosis of COVID-19 (ICD-10 code U07.1), or strong documented clinical suspicion of COVID-19 but no testing completed or recorded owing to logistical constraints (n=24). <h4>Methods</h4> Patient records were abstracted for the Mi-COVID19 data registry, including the hospital and insurer data of patients discharged from one of 38 participating hospitals in Michigan between March 16, 2020, and July 1, 2020. Registry data also included patient responses to a brief telephone survey on postdischarge employment, mental and emotional health, persistence of COVID-19–related symptoms, and medical follow-up. Descriptive statistics were used to summarize data;analysis of variance and Pearson chi-squared test were used to evaluate racial and ethnic variances among patient outcomes and survey responses. <h4>Results</h4> Black patients experienced the lowest physician follow-up postdischarge (n = 65, 60.2%) and the longest delays in returning to work (average 35.5 days). More than half of hospital readmissions within the 60 days following discharge were among nonwhite patients (n = 144, 55%). The majority of postdischarge deaths were among white patients (n = 153, 21.5%), most of whom were discharged on palliative care (n = 103). Less than a quarter of patients discharged back to assisted living, skilled nursing facilities, or subacute rehabilitation facilities remained at those locations in the 60 days following discharge (n = 48). <h4>Conclusions and Implications</h4> Increased attention to postdischarge care coordination is critical to reducing negative health outcomes following a COVID-19–related hospitalization.

11.
J Thromb Thrombolysis ; 53(2): 257-263, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1432597

ABSTRACT

Venous thromboembolism (VTE) is an important complication of coronavirus disease 2019 (COVID-19). To date, few studies have described vascular access device use and VTE risk in this cohort. To examine the use of vascular access devices and incidence of VTE in patients hospitalized with COVID-19. We performed a retrospective, multi-center cohort study of patients hospitalized with COVID-19 who received a midline catheter, peripherally inserted central catheter (PICCs), tunneled or non-tunneled central venous catheter (CVC), hemodialysis (HD) catheter or a port during hospitalization. Mixed-effects multivariable logit models adjusting for VTE risk factors in the Caprini risk score were fit to understand the incremental risk of VTE in patients with vascular access devices vs. those that did not receive devices. Management of VTE was determined by examining anticoagulant use pre- vs. post-thrombosis. Results were expressed using odds ratios (ORs) and associated 95% confidence intervals (CI). A total of 1228 hospitalized COVID-19 patients in 40 hospitals, of which 261 (21.3%) received at least one vascular access device of interest, were included. The prevalence of acute, non-tunneled CVCs was 42.2%, acute HD catheters 18.4%, midline catheters 15.6%, PICCs 15.6%, tunneled CVCs 6.8%, and implanted ports 1.4%. The prevalence of VTE was 6.0% in the study cohort, and 10.0% among patients with vascular access devices. After adjusting for known VTE risk factors, patients that had a vascular access device placed were observed to have a four-fold greater odds of VTE than those that did not (OR 4.17, 95% CI 2.33-7.46). Patients who received multiple different catheters experienced more VTE events compared with patients that received only one type (21.5% vs. 6.1%, p < .001). Among the 26 patients with VTE, only 8 (30.8%) survived to discharge and among these, only 5 were discharged on therapeutic doses of anticoagulation. Hospitalized patients with COVID-19 that receive vascular access devices experienced higher rates of VTE than those that do not. Future studies to evaluate the nexus between COVID-19, vascular device use, and thrombosis appear are warranted.


Subject(s)
COVID-19 , Catheterization, Central Venous , Thrombosis , Vascular Access Devices , Venous Thromboembolism , COVID-19/complications , Catheterization, Central Venous/adverse effects , Hospitals , Humans , Michigan/epidemiology , Retrospective Studies , Risk Factors , SARS-CoV-2 , Thrombosis/epidemiology , Thrombosis/etiology , Vascular Access Devices/adverse effects , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology
12.
BMJ Open ; 11(7): e044921, 2021 07 23.
Article in English | MEDLINE | ID: covidwho-1322819

ABSTRACT

OBJECTIVE: To describe patient characteristics, symptoms, patterns of care and outcomes for patients hospitalised with COVID-19 in Michigan. DESIGN: Multicentre retrospective cohort study. SETTING: 32 acute care hospitals in the state of Michigan. PARTICIPANTS: Patients discharged (16 March-11 May 2020) with suspected or confirmed COVID-19 were identified. Trained abstractors collected demographic information on all patients and detailed clinical data on a subset of COVID-19-positive patients. PRIMARY OUTCOME MEASUREMENTS: Patient characteristics, treatment and outcomes including cardiopulmonary resuscitation, mortality and venous thromboembolism within and across hospitals. RESULTS: Demographic-only data from 1593 COVID-19-positive and 1259 persons under investigation discharges were collected. Among 1024 cases with detailed data, the median age was 63 years; median body mass index was 30.6; and 51.4% were black. Cough, fever and shortness of breath were the top symptoms. 37.2% reported a known COVID-19 contact; 7.0% were healthcare workers; and 16.1% presented from congregated living facilities.During hospitalisation, 232 (22.7%) patients were treated in an intensive care unit (ICU); 558 (54.9%) in a 'cohorted' unit; 161 (15.7%) received mechanical ventilation; and 90 (8.8%) received high-flow nasal cannula. ICU patients more often received hydroxychloroquine (66% vs 46%), corticosteroids (34% vs 18%) and antibiotic therapy (92% vs 71%) than general ward patients (p<0.05 for all). Overall, 219 (21.4%) patients died, with in-hospital mortality ranging from 7.9% to 45.7% across hospitals. 73% received at least one COVID-19-specific treatment, ranging from 32% to 96% across sites.Across 14 hospitals, the proportion of patients admitted directly to an ICU ranged from 0% to 43.8%; mechanical ventilation on admission from 0% to 12.8%; mortality from 7.9% to 45.7%. Use of at least one COVID-19-specific therapy varied from 32% to 96.3% across sites. CONCLUSIONS: During the early days of the Michigan outbreak of COVID-19, patient characteristics, treatment and outcomes varied widely within and across hospitals.


Subject(s)
COVID-19 , Hospitals , Humans , Intensive Care Units , Michigan/epidemiology , Middle Aged , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
13.
Ann Intern Med ; 174(9): 1319-1320, 2021 09.
Article in English | MEDLINE | ID: covidwho-1296185
14.
Clin Infect Dis ; 72(10): e533-e541, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1232185

ABSTRACT

BACKGROUND: Antibacterials may be initiated out of concern for bacterial coinfection in coronavirus disease 2019 (COVID-19). We determined prevalence and predictors of empiric antibacterial therapy and community-onset bacterial coinfections in hospitalized patients with COVID-19. METHODS: A randomly sampled cohort of 1705 patients hospitalized with COVID-19 in 38 Michigan hospitals between 3/13/2020 and 6/18/2020. Data were collected on early (within 2 days of hospitalization) empiric antibacterial therapy and community-onset bacterial coinfections (positive microbiologic test ≤3 days). Poisson generalized estimating equation models were used to assess predictors. RESULTS: Of 1705 patients with COVID-19, 56.6% were prescribed early empiric antibacterial therapy; 3.5% (59/1705) had a confirmed community-onset bacterial infection. Across hospitals, early empiric antibacterial use varied from 27% to 84%. Patients were more likely to receive early empiric antibacterial therapy if they were older (adjusted rate ratio [ARR]: 1.04 [1.00-1.08] per 10 years); had a lower body mass index (ARR: 0.99 [0.99-1.00] per kg/m2), more severe illness (eg, severe sepsis; ARR: 1.16 [1.07-1.27]), a lobar infiltrate (ARR: 1.21 [1.04-1.42]); or were admitted to a for-profit hospital (ARR: 1.30 [1.15-1.47]). Over time, COVID-19 test turnaround time (returned ≤1 day in March [54.2%, 461/850] vs April [85.2%, 628/737], P < .001) and empiric antibacterial use (ARR: 0.71 [0.63-0.81] April vs March) decreased. CONCLUSIONS: The prevalence of confirmed community-onset bacterial coinfections was low. Despite this, half of patients received early empiric antibacterial therapy. Antibacterial use varied widely by hospital. Reducing COVID-19 test turnaround time and supporting stewardship could improve antibacterial use.


Subject(s)
COVID-19 , Coinfection , Anti-Bacterial Agents/therapeutic use , Cohort Studies , Coinfection/drug therapy , Coinfection/epidemiology , Hospitalization , Hospitals , Humans , Michigan , SARS-CoV-2
16.
BMJ Open ; 11(4): e042475, 2021 04 14.
Article in English | MEDLINE | ID: covidwho-1186290

ABSTRACT

INTRODUCTION: Peripherally inserted central catheters (PICCs) are vital for the delivery of medical therapies, but up to 30% of PICCs are associated with complications such as deep vein thrombosis or infection. The integration of antimicrobial and hydrophobic catheter materials, and pressure-activated valves, into polyurethane PICCs are innovations designed to prevent infective and/or thrombotic complications. METHODS AND ANALYSIS: A multicentre, parallel group, superiority randomised controlled trial with two experimental arms ((1) hydrophobic PICC (with pressure-activated valve); (2) chlorhexidine gluconate-impregnated PICC (with external clamp)) and one control group ((3) conventional polyurethane PICC (with external clamp)). Recruitment of 1098 adult and paediatric patients will take place over 2 years at three tertiary-referral hospitals in Queensland, Australia. Patients are eligible for inclusion if their PICC is to be inserted for medical treatment, with a vascular size sufficient to support a 4-Fr PICC or larger, and with informed consent. The primary outcome is PICC failure, a composite of thrombotic (venous thrombosis, breakage and occlusion) and infective complications (PICC-associated bloodstream infection and local infection). Secondary outcomes include: all-cause PICC complication; thrombotic complications; infective complications; adverse events (local or systemic reaction); PICC dwell time; patient/parent satisfaction; and healthcare costs. Differences between both intervention groups and the control group will be compared using Cox proportional hazards regression. Effect estimates will be presented as HRs with corresponding 95% CI. ETHICS AND DISSEMINATION: Ethical approval from Queensland Health (HREC/QCHQ/48682) and Griffith University (Ref. No. 2019/094). Results will be published. TRIAL REGISTRATION NUMBER: ACTRN12619000022167.


Subject(s)
Catheter-Related Infections , Catheterization, Central Venous , Catheterization, Peripheral , Central Venous Catheters , Adult , Australia , Catheter-Related Infections/prevention & control , Catheterization, Central Venous/adverse effects , Catheterization, Peripheral/adverse effects , Central Venous Catheters/adverse effects , Child , Humans , Multicenter Studies as Topic , Queensland , Randomized Controlled Trials as Topic , Risk Factors
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