Use Of Intravenous Immune Globulin Research Articles

Effect of intravenous immunoglobulin on the outcome of children with septic shock in a PICU: a retrospective cohort study.

In children with septic shock, the use of intravenous immunoglobulin as an adjuvant therapy does not reduce in-hospital mortality. • Guidelines suggest against the routine use of intravenous immuneglobulin in children with septic shock. Some small observational studies have reported conflicting result. • The use of intravenous immunoglobulin as an adjuvant therapy does not reduce in-hospital mortality in children with septic shock.

Stevens-Johnson Syndrome – clinical symptoms, etiology, pathophysiology and medical treatment - a review of the literature

Stevens-Johnson syndrome (SJS) is a rare disease of the skin and mucous membrane. It develops as a result of a sudden skin reaction, which is most often triggered by the use of certain drugs. It is characterized by acute epidermal necrosis. The syndrome can lead to many complications and death. Currently, there are no guidelines and management schematics for this disease. Treatment has changed over the years due to the discovery of the possible pathomechanism of SJS. Nevertheless, because of the rarity of the disease, there is a lack of adequate prospective randomized studies that could provide valuable information on treatment. Objective: The purpose of this study was to present Stevens-Johnson syndrome, including clinical features, etiology, pathomechanism, complications and treatment. Methods: A literature search was performed in the PubMed medical publication database using the following keywords: Stevens-Johnson syndrome, acute drug-induced skin reaction, cutaneous adverse drug reactions. Results: Stevens-Johnson syndrome is an example of an acute cutaneous reaction to certain medicinal substances. The pathomechanism is not fully understood. There is an association of genetics with the risk of developing symptoms of the syndrome in selected populations. Treatment formerly was based on glucocorticosteroids, but now IVIG (intravenous immune globulin) is used. Dehydration, pneumonia or sepsis may develop as a complication of the syndrome. Conclusions: The discovery of a genetic predisposition to develop Stevens-Johnson syndrome offers the possibility of future effective disease prevention. It is necessary to create medical procedure schemes for the diagnosis and treatment of this disorder. The discovery of the possible pathomechanism has allowed the use of IVIG in the treatment of the syndrome. Effective and prompt diagnosis and treatment can prevent life-threatening complications and death from SJS.

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents

To summarize the epidemiology and clinical characteristics of multisystem inflammatory syndrome in children (MIS-C) cases in 26 states.A total of 186 pediatric patients admitted to 38 sites in 26 states that were participating health centers in the Overcoming COVID-19 study and members of the Pediatric Acute Lung Injury and Sepsis Investigators Pediatric Intensive Care Influenza and Emerging Pathogens Subgroup. The case definition of MIS-C included 6 criteria: serious illness leading to hospitalization, an age of <21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), antibody testing, or exposure to persons with SARS-CoV-2.Prospective and retrospective surveillance was used. Statistical analysis was performed to report the frequency of clinical features, laboratory findings, and treatments among patients stratified by SARS-CoV-2 test results, age, and clinical presentation.A total of 186 patients were included on the basis of case definition. The median age was 8.3 years old, 62% were male, and 73% had previously been healthy. Overall, 70% were positive for SARS-CoV-2 by reverse transcription polymerase chain reaction or antibody testing. The most common system involvement included the gastrointestinal, cardiovascular, hematologic, mucocutaneous, and respiratory. In terms of clinical management, 80% received intensive care, 20% received mechanical ventilation, and 48% received vasoactive support. Treatment included the use of intravenous immune globulin in 77%, glucocorticoids in 49%, and interleukin 6 or 1RA inhibitors in 20%. Kawasaki disease–like features were documented in 40%.MIS-C affects previously healthy children and adolescents and includes multiple organ system involvement.The pathogenesis of MIS-C is still being investigated. Cardiac involvement appears common in MIS-C, and coronary artery dilation has been noted. The long-term cardiac sequelae of MIS-C is still unknown.

Red blood cell distribution width and tumor necrosis factor-α for the early prediction of coronary artery lesion in Kawasaki disease: a retrospective study.

We aimed to identify novel risk factors for the early prediction of coronary artery lesion (CAL) in children with Kawasaki disease (KD). We retrospectively analyzed data from hospitalized children newly diagnosed with KD between January 1, 2018, and December 31, 2020, with the following inclusion criteria: (1) diagnosis of KD, (2) first onset of CAL after admission, (3) with complete clinical records. Demographic and laboratory data were collected and analyzed. The independent risk factors of KD combined with CAL were identified by multivariate logistic regression analysis, followed by receiver operating characteristic (ROC) curve analysis to calculate the efficacy of identified risk factors in predicting KD combined with CAL. Among 241 initially recruited patients, 226 were eligible to be included in the study. Based on echocardiographic indications of CAL, 104 patients (46%) were assigned to the CAL (KD-CAL) group and 122 (54%) patients were assigned to the non-CAL (KD-nCAL) group. The levels of red blood cell count, red blood cell distribution width (RDW), C-reactive protein, tumor necrosis factor-α (TNF-α), and interleukin-6 were significantly higher in the KD-CAL group than those in the KD-nCAL group (all p < 0.05). RDW and TNF-α were found as independent risk factors of CAL occurrence. The sensitivity and specificity of RDW, TNF-α, and RDW + TNF-α in predicting KD with CAL were 67.31% and 79.51%, 74.04% and 73.77%, and 79.81% and 80.33%, respectively.Conclusion: In conclusion, alterations in RDW and TNF-α levels can be used as novel biomarkers for early prediction of CAL in KD patients, although the differences in their absolute values were small and might not give any added value to echocardiography. What is Known: •Known risk factors of CAL in children with KD include male gender and delayed use of intravenous immune globulin. What is New: •Our current study identified that red blood cell distribution width (RDW) and tumor necrosis factor-α (TNF-α) are novel independent risk factors for predicting CAL combined with KD among patients. •The combination of these RDW and TNF-α together shows higher sensitivity and specificity than either one used alone.

Sodium Levels Predict Disability at Discharge in Guillain-Barré Syndrome: A Retrospective Cohort Study.

Guillain-Barré syndrome (GBS) is an inflammatory polyradiculopathy with potentially severe complications. Clinical tools for risk stratification have been developed, but no definitive prognostic biomarker has been reported. Hyponatremia is frequent in GBS patients, but the impact of serum sodium levels on clinical outcomes is still ill-defined. In this retrospective cohort study, we included all adult patients diagnosed with GBS spectrum disorders at our center from January 2010 to July 2020. Disability at discharge was assessed with the GBS Disability Score (GDS), and all clinical and laboratory data was retrieved from medical charts. Thirty (58.8%) of the 51 subjects included in the study were discharged with severe residual disability (GDS ≥ 3). After accounting for relevant confounders, the odds of experiencing severe disability decreased by 27% (p = 0.027) for each unitary increase in serum sodium concentration. Thirteen (25.5%) patients were diagnosed with mild to moderate hyponatremia; the use of intravenous immune globulin (IVIG) independently increased the odds of developing hyponatremia. In conclusion, we found a significant, independent association between baseline serum sodium levels and severe disability at discharge in GBS patients. In our cohort, hyponatremia was more frequently observed after treatment with IVIG, suggesting dilutional pseudohyponatremia as a probable cause.

Epidemiology of intravenous immune globulin in septic shock: a retrospective cohort analysis of the Premier Healthcare Database.

Intravenous immune globulin (IVIG) may improve survival in people with septic shock. Current utilization patterns of IVIG are unknown. We sought to characterize adult patients with septic shock requiring vasopressors who received IVIG, describes IVIG regimens, and evaluate determinants of IVIG use in patients with septic shock. We conducted a retrospective database study of adult patients with septic shock admitted to US hospitals in the Premier Healthcare Database (from July 2010 to June 2013). We described the proportion of patients with septic shock receiving IVIG, examined IVIG regimens across sites and employed random-effects multivariable regression techniques to identify predictors of IVIG use. Intravenous immune globulin was administered to 0.3% (n = 685) of patients with septic shock; with a median [interquartile range (IQR)] dose of 1 [0.5-1.8] g·kg-1 for a median [IQR] of 1 [1-2] day. Receipt of IVIG was less likely for Black patients (odds ratio [OR], 0.54; 95% confidence interval [CI] 0.41 to 0.72) and patients without private insurance (Medicare OR, 0.73; 95% CI 0.59 to 0.90; Medicaid OR, 0.41; 95% CI 0.30 to 0.57) and more likely for patients with immunocompromise (OR, 6.83; 95% CI 5.47 to 8.53), necrotizing fasciitis (OR, 9.78; 95% CI 6.97 to 13.72), and toxic shock (OR, 56.9; 95% CI 38.7 to 83.7). Intravenous immune globulin is used infrequently across the US in patients with septic shock. Regimens of IVIG in septic shock may be less intensive than those associated with a survival benefit in meta-analyses. Observed infrequent use supports apparent clinical equipoise, perhaps secondary to limitations of the primary literature. A clinical trial evaluating the role of IVIG in septic shock is needed.

Anti-CD20 Monoclonal Antibody Therapy for Immune Modulation Across a Range of Autoimmune Diseases

Background: Intravenous immune globulin (IVIG) is a plasma-derived blood product that is used as a treatment for various autoimmune diseases. The anti-CD20 monoclonal antibody rituximab has similar immunomodulatory properties and mechanisms of action. We did a systematic review and meta-analysis to determine the efficacy and safety of rituximab across a broad range of autoimmune diseases with a view to investigate this agent as an alternative to IVIG.Study design: Systematic review and meta-analysis.Methods: We identified the most common indications for IVIG (besides immune replacement therapy) from a recent Ontario audit based on total amount of IVIG used. Starting with the highest users, these were: chronic inflammatory demyelinating polyneuropathy (CIDP); immune thrombocytopenia (ITP); myasthenia gravis (MG); multifocal motor neuropathy (MMN); Guillain-Barre syndrome (GBS); systemic lupus erythematosus (SLE); Sjogren's syndrome (SS); and pemphigus vulgaris (PV). Next, we did a systematic review of rituximab for each of these conditions by searching MEDLINE, EMBASE and the Cochrane Library until July 2016. Randomized controlled trials (RCT) and observational studies of ≥10 adult patients were included. The primary outcome was clinical response at 6 months from RCTs across all conditions. Secondary outcomes were clinical response for each condition and adverse events. Pooled relative risk (RCTs) or pooled proportions (observational studies) were calculated using fixed and random effects models. Risk of bias was assessed for each study using the Cochrane Collaboration tool.Results: We identified 108 studies for the target conditions (n=3536 patients) including 10 RCTs (n=1044). Most studies were in ITP (n=1543), SLE (n=1192), PV (n=504) and SS (n=200). There were 4 studies in MG (n=66), 2 studies in CIDP (n=31) and none in GBS or MMN. Risk of bias in 9 of 10 RCTs was low. Response to rituximab was 30% higher than controls (RR=1.30, 95% CI 1.01, 1.67) based on pooled results of 10 RCTs in ITP, SLE, PV and SS. Pooled proportions for disease-specific responses ranged from 48% (95%CI 30% -66%) for CIDP to 94% (95% CI 88% -98%) for PV. Adverse events were mild.Conclusion: Rituximab is an effective immune-modulating treatment and may represent an alternative to IVIG for some conditions. Few studies have been done in the rare autoimmune neurological disorders despite these being among the most frequent indications for current IVIG use. [Display omitted] DisclosuresArnold:Bristol Myers Squibb: Research Funding; Novartis: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; UCB: Consultancy; Dova: Consultancy; Rigel: Consultancy.

English

BACKGROUND Neonatal sepsis refers to systemic infections affecting infants within 28 days of life, 1 characterised by invasion of bloodstream by pathogens and possible involvement of multiple organ systems. Neonatal sepsis can present as bloodstream infections (BSI) or septicaemia, pneumonia, meningitis, urinary tract, and bone / joint infections but does not as superficial infections. We wanted to evaluate the rationale of administering intravenous immune globulin (IVIG) with antimicrobials to improve the therapeutic significance of sepsis in preterm neonates. METHODS One hundred preterm neonates with sepsis were randomly assigned into study and control categories at SNCU, Department of Paediatrics, Darbhanga Medical College and Hospital, Laheriasarai, Darbhanga, Bihar, India. Study-category was given IVIG in addition to standard treatment. RESULTS Total 100 sick new-borns were registered, 50 in study, and 50 in control categories. There were no differences in sex ratio (male 50 %, female 50 %) of sick new-borns who were registered. This was also apparent in the study (males 47.7 %, females 52.3 %) and control category (males 52.3 %, females 47.7 %). CONCLUSIONS The cause of increased morbidity and mortality in severe infection of preterm neonates was the low level of immunity. IVIG use in conjunction with the antimicrobials and other sympathetic therapy can change the end result. KEY WORDS IVIG, Neonatal Sepsis, Preterm Babies

Intravenous immune globulin in septic shock: a Canadian national survey of critical care medicine and infectious disease specialist physicians.

This national survey evaluated the perceived efficacy and safety of intravenous immune globulin (IVIG) in septic shock, self-reported utilization patterns, barriers to use, the population of interest for further trials and willingness to participate in future research of IVIG in septic shock. We conducted a cross-sectional survey of critical care and infectious diseases physicians across Canada. We summarized categorical item responses as counts and proportions. We developed a multivariable logistic regression model to identify physician-level predictors of IVIG use in septic shock. Our survey was disseminated to 674 eligible respondents with a final response rate of 60%. Most (91%) respondents reported having prescribed IVIG to patients with septic shock at least once, 86% for septic shock due to necrotizing fasciitis, 52% for other bacterial toxin-mediated causes of septic shock, and 5% for undifferentiated septic shock. The majority of respondents expressed uncertainty regarding the impact of IVIG on mortality (97%) and safety (95%) in septic shock. Respondents were willing to participate in further IVIG research with 98% stating they would consider enrolling their patients into a trial of IVIG in septic shock. Familiarity with published evidence was the single greatest predictor of IVIG use in septic shock (odds ratio, 10.2; 95% confidence interval, 3.4 to 30.5; P < 0.001). Most Canadian critical care and infectious diseases specialist physicians reported previous experience using IVIG in septic shock. Respondents identified inadequacy of existing research as the greatest barrier to routine use of IVIG in septic shock. Most respondents support the need for further studies on IVIG in septic shock, and would consider enrolling their own patients into a trial of IVIG in septic shock.

Administration of intravenous immunoglobulin in the treatment of COVID-19: A review of available evidence.

Since December 31, 2019, unknown causes of pneumonia have been reported in Wuhan, China. This special pneumonia associated with a novel coronavirus was named 2019-nCoV by the World Health Organization (WHO) in January 2020. From the beginning of this infectious disease, clinicians and researchers have been endeavoring to discover an effective and suitable treatment for affected patients. To date, there is no definitive and specific treatments for coronavirus disease-19 (COVID-19) infection while drugs introduced are still in the clinical trial phase. Intravenous immune globulin (IVIG) is a biological product prepared from the serum and an optional treatment for patients with antibody deficiencies. In many countries, much attention has been paid to the use of IVIG in the treatment of patients with COVID-19. Due to the therapeutic importance of IVIG in virus infections, in the current study, we reviewed the possible effect of IVIG in viral infections and potential evidence of IVIG therapy in patients with COVID-19 virus.

Intravenous Immune Globulin Uses in the Fetus and Neonate: A Review.

Intravenous immune globulin (IVIG) is made after processing plasma from healthy donors. It is composed mainly of pooled immunoglobulin and has clinical evidence-based applications in adult and pediatric populations. Recently, several clinical applications have been proposed for managing conditions in the neonatal population, such as hemolytic disease of the newborn, treatment, and prophylaxis for sepsis in high-risk neonates, enterovirus parvovirus and COVID-19 related neonatal infections, fetal and neonatal immune-induced thrombocytopenia, neonatal hemochromatosis, neonatal Kawasaki disease, and some types of immunodeficiency. The dosing, mechanism of action, effectiveness, side effects, and adverse reactions of IVIG have been relatively well studied in adults but are not well described in the neonatal population. This review aims to provide the most recent evidence and consensus guidelines about the use of IVIG in the fetus and neonate.

Therapeutic plasma exchange and intravenous immune globulin in the treatment of heparin-induced thrombocytopenia: A systematic review.

Immunomodulatory strategies in heparin-induced thrombocytopenia (HIT) include the use of intravenous immune globulin (IVIG) and therapeutic plasma exchange (TPE). The optimal application of these therapies is unknown and outcomes data are limited. We investigated treatment categories and laboratory and clinical outcomes of IVIG and/or TPE in HIT with a systematic literature review. We searched MEDLINE, Embase, and Web of Science through December 2019 for studies combining controlled vocabulary and keywords related to thrombocytopenia, heparin, TPE, and IVIG. The primary outcome was treatment indication. Secondary outcomes were platelet recovery, HIT laboratory parameters, heparin re-exposure, and post-treatment course. Case-level data were analyzed by qualitative synthesis. After 4241 references were screened, we identified 60 studies with four main categories of IVIG and/or TPE use as follows: (a) treatment of refractory HIT (n = 35; 31%); (b) initial therapy (n = 45; 40%); (c) cardiopulmonary bypass surgery (CPB; n = 30; 27%); and (d) other (n = 2; 2%). IVIG was most commonly used for the treatment of refractory HIT while TPE was primarily used to facilitate heparin exposure during CPB. Both IVIG and TPE were equally used as initial therapy. Heparin re-exposure occurred without thrombotic event in 29 TPE-treated patients and three IVIG-treated patients. In patients with HIT, both TPE and IVIG are used for initial therapy or treatment of refractory HIT. However, TPE is more commonly used in patients undergoing CPB. Prospective studies may help clarify which treatment is indicated in HIT population subsets.

Intravenous Immune Globulin (IVIG) for Treatment of Autoimmune Heparin-Induced Thrombocytopenia: A Systematic Review.

To evaluate intravenous immune globulin (IVIG) for autoimmune heparin-induced thrombocytopenia (aHIT), including platelet recovery, IVIG dose, dosing weight, IVIG product used, and complications reported. PubMed and EMBASE were searched from inception through June 21, 2020. Search terms included heparin-induced thrombocytopenia, HIT, intravenous immune globulin, IVIG, autoimmune HIT, aHIT, and immune globulin. Patients administered IVIG for HIT and diagnosed by immunoassay (optical density ≥2) or positive activation assay were included. Twenty-four cases were reviewed; 92% had persistent aHIT. Time to IVIG administration post-nonheparin anticoagulant initiation was 9 days (median). Most common IVIG cumulative dose was 2 g/kg (dosed as 1 g/kg/d for 2 consecutive days); 75% had a favorable platelet increase (≥50 × 109/L) within 5 days of initial IVIG dosing. aHIT is characterized by critically low platelets, thrombosis, and a persistent delay in platelet recovery despite treatment with a nonheparin anticoagulant. An immunoassay and subsequent confirmatory activation assay (at low, high, and 0 IU/mL unfractionated heparin levels) is recommended to confirm diagnosis. Patients nonresponsive to nonheparin anticoagulants within 5 days of initiation should be evaluated for IVIG treatment (2 g/kg cumulative dose). More data are needed to clarify appropriate IVIG dosing weight, although based on current published literature, it is recommended to use actual body weight. Data reported support use of IVIG as adjunctive therapy for patients with aHIT. Judicious IVIG use based on key clinical and laboratory findings is critical.

Optimization of intravenous immune globulin use at a comprehensive cancer center

Intravenous immune globulin (IVIG) is a high-cost medication used in a diverse range of settings. At many institutions, IVIG is dosed using total body weight (TBW). Recent evidence suggests that alternative dosing weights reduce waste without compromising clinical outcomes. The objective of this study was to quantify the waste reduction potential generated through the use of alternative IVIG dosing weights. We performed a retrospective analysis of all IVIG doses administered from January 2011 through January 2016 to adults (≥18 years). TBW and height at the time of administration were used to calculate prescribed dose (g/kg), ideal body weight (IBW), and adjusted body weight (AdjBW). Three dosing methods were analyzed, as follows: use of AdjBW if TBW is >120% IBW (method 1), AdjBW for all doses (method 2), and IBW for all doses (method 3). Outcomes included potential IVIG use averted, direct drug cost savings, and reductions in outpatient infusion times for each method. A total of 9,918 doses were administered to 2,564 patients over 5 years, representing an average usage of 75,994 g/year. If dosing methods 1, 2, and 3 had been used, the annual use of IVIG would have decreased by 21.9% (16,658 g/year, p < 0.001), 24.2% (18,371 g/year, p < 0.001), and 35.9% (27,252 g/year, p < 0.001), respectively. This translates into average annual cost differences of $2.37 million, $2.62 million, and $3.89 million and average annual outpatient infusion time savings of 841 hours, 920 hours, and 1,366 hours, respectively. IVIG dosing optimization through use of alternative dosing weights represents a significant source of waste reduction and cost reduction.

Serologic problems associated with administration of intravenous immune globulin (IVIg)

Intravenous immune globulin (IVIg) is manufactured from large pools of donor plasma and contains a high diversity of antibodies, primarily IgG. For this reason, IVIg is routinely used as antibody replacement therapy for patients having primary immunodeficiencies. In 1981, IVIg was also found to be a strong immunomodulator of various inflammatory and autoimmune conditions. This observation has led to the exponential increase in the use of IVIg throughout the world, with the United States and Canada being the biggest users of IVIg. Although relatively rare, adverse events, such as hemolytic anemia and thrombosis, can complicate the administration of IVIg. More frequently, the administration of IVIg can cause serologic challenges for the transfusion service including ABO discrepancies, positive direct antiglobulin tests, positive antibody detection tests, and incompatible crossmatches. This article will review each of the potential transfusion service challenges associated with IVIg administration.

Using Chargemaster Data to Understand Childhood Leukemia Costs

Introduction: Recent changes in health care financing have increased the out-of-pocket costs borne by families. The potential "financial toxicity" can pose challenges for families beyond those encountered in the treatment of cancer. Several families of children diagnosed with leukemia at our center have recently requested information on the expected costs of the planned treatment. There is little published information on the patient's cost (that is, the health system patient charges) for childhood cancer treatment, and costs can be expected to vary between patients and institutions. To better understand the cost of leukemia treatment at our center, the charges accumulated over the course of therapy for a cohort of children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were analyzed.Methods: A sample of children who successfully completed treatment at our institution in 2014 using the current Children's Oncology Group (COG) treatment protocols for standard risk ALL (AALL0932) and AML (AAML0531) was chosen. All inpatient and outpatient charges for the entire course of therapy for each child were used to determine total charges for treatment and types of charges (room and board, medications, laboratory, radiology, professional fees). Using our health system's chargemaster data, the expected charges for ALL therapy based upon protocol requirements was estimated and compared to actual charges. We analyzed high frequency and high cost items to identify potential drivers of charges to suggest areas for potential cost reduction.Results: Charges for 11 patients with ALL and 7 with AML were assessed. The average charges for ALL therapy were $311,000 (range $182,000-634,000) and for AML were $1.05 million (range $733,000-$1,346,000). For ALL, room and board, medications, and laboratory accounted for 37%, 16%, and 19% of charges respectively. For AML, room and board medications and laboratory accounted 66%, 14%, and 14% of charges respectively. (Figure 1) Low risk ALL treatment had higher overall charges driven by increased inpatient chemotherapy. Expected charges for low risk ALL treatment were $245,000 compared to $165,000 for average risk standard therapy. Actual charges however did not differ greatly between low risk and average risk ALL subtypes. (Figure 2) The highest charges for items in ALL therapy were for intravenous immune globulin (IVIG), asparaginase, and inpatient stays (intensive care and oncology ward). For AML, the most expensive items were inpatient stays (intensive care and oncology ward), blood products, and complete blood counts (CBC).Conclusion: AML therapy is more expensive than ALL therapy, driven primarily by the prolonged hospitalizations awaiting count recovery after each cycle. ALL treatment charges were highly variable depending upon experienced toxicities and arm of therapy. Low risk therapy for ALL has the potential to be the most expensive ALL therapy due to six inpatient courses of intermediate dose methotrexate. Estimates for ALL therapy charges did not capture medical toxicity expense or other supportive care related charges. Many drivers of cost cannot be altered without affecting quality of care, but increasing outpatient therapy has the potential to provide the largest reduction in charges. The use of IVIG in some ALL patients and the frequency of CBCs in AML patients highlighted areas where clinical interventions could be implemented without obvious decrements to care quality and with potential cost savings. Understanding data on patient charges can provide an expected range of charges for families and may inform areas to target for cost savings. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Trends in Outcomes and Hospitalization Charges of Infant Botulism in the United States: A Comparative Analysis Between Kids' Inpatient Database and National Inpatient Sample

BackgroundNew therapeutic strategies, including immune globulin intravenous, have emerged in the past two decades for the management of botulism. However, impact on outcomes and hospitalization charges among infants (aged ≤1 year) with botulism in the United States is unknown. MethodsWe analyzed the Kids' Inpatient Database (KID) and National Inpatient Sample (NIS) for in-hospital outcomes and charges for infant botulism cases from 1997 to 2009. Demographics, discharge status, mortality, length of stay, and hospitalization charges were reported from the two databases and compared. ResultsBetween 1997 and 2009, 504 infant hospitalizations were captured in KID’, and 340 hospitalizations from NIS, for comparable years. A significant decrease was observed in mean length of stay for ’KID (P < 0.01); a similar decrease was observed for the NIS. The majority of patients were discharged to home. Despite an initial decrease after 1997, an increasing trend was observed for ’KID/NIS mean hospital charges from 2000 to 2009 (from $57,659/$56,309 to $143,171/$106,378; P < 0.001/P < 0.001). A linear increasing trend was evident when examining mean daily hospitalization charges for both databases. In conducting a subgroup analysis of the ’KID database, the youngest patients with infantile botulism (≤1.9 months) displayed the highest average number of procedures during their hospitalization (P < .001) and the highest rate of mechanical ventilation (P < .001), compared with their older counterparts. ConclusionInfant botulism cases have demonstrated a significant increase in hospitalization charges over the years despite reduced length of stay. Additionally, there were significantly higher daily adjusted hospital charges and an increased rate of routine discharges for immune globulin intravenous–treated patients. More controlled studies are needed to define the criteria for cost-effective use of intravenous immune globulin in the population with infant botulism.

Renal transplantation across the donor-specific antibody barrier: Graft outcome and cancer risk after desensitization therapy.

Desensitization regimens including use of intravenous immune globulin and rituximab have been reported to overcome renal transplant hyperacute rejection. A retrospective case-control study was performed to assess the results and complications of renal transplantation with desensitization therapy for donor-specific antibody (DSA) in a transplant center in Asia, where donor exchange was usually not allowed. Between January 2007 and December 2013, 22 patients with DSA received live-donor renal transplantation after desensitization (DSA group). During the same period, the DSA group was compared to the NSA group (152 renal transplants) who had no specific antibody to the donors (66 from deceased donors and 86 from living relatives). Rejection, renal function, graft and patient survival rates, infection, and cancer incidence were reviewed and analyzed from medical records. The DSA group (46.8%) had significantly higher acute rejection rates than the NSA group (13.7%) at the 1-year follow-up. The estimated renal function, 5-year graft, and patient survival rates were comparable between the groups. The DSA group (19.6%) had significantly higher 5-year de novo cancer incidence than the NSA group (8.5%; p=0.028); three patients of the DSA group developed urothelial carcinoma 17.0±3.0 months after transplantation. By using stepwise Cox regression analysis, desensitization therapy was identified as the sole independent risk factor for post-transplant urothelial carcinoma. When compared to renal transplantation without DSA, desensitization therapy for DSA resulted in equivalent renal transplant outcome but potentially increased risk of urothelial carcinoma after transplantation.

Role of intravenous immune globulin in streptococcal toxic shock syndrome and Clostridium difficile infection.

The use of intravenous immune globulin (IVIG) in the management of streptococcal toxic shock syndrome (STSS) and Clostridium difficile infection (CDI) is reviewed. IVIG has a wide range of uses in clinical practice, including STSS and CDI. It is an attractive option for these two infections because both infections are toxin mediated, and IVIG may contain antibodies that neutralize these toxins. For STSS and CDI, IVIG is often considered for use in critically ill patients who are not responding to traditional therapies. Several encouraging case reports and retrospective chart reviews have been published, highlighting the potential benefit of IVIG in such patients. However, its definitive role remains unclear, mainly due to the lack of high-level evidence. Data supporting its use have been extrapolated from retrospective chart reviews and case reports in which profound heterogeneity in patient populations and treatment modalities exist. The use of IVIG must be weighed carefully because it is not a benign product. As with the use of IVIG for STSS, the role of IVIG for CDI is unclear. Nonetheless, IVIG may serve as a useful adjunct therapy for patients suffering from severe complicated CDI (shock, ileus, or megacolon) who do not respond to conventional treatment. Adverse reactions to IVIG are mild and transitory and occur during or immediately after drug infusion. Although randomized, controlled trials supporting the use of IVIG for STSS and CDI are lacking, IVIG may be considered a last-line adjunct therapy in those patients for whom the clinical benefit outweighs the potential adverse effects of therapy.

Use of Intravenous immune globulin in Critically Ill Patients

Intravenous immune globulin (IVIG) preparations have been suggested for many years for the treatment of various conditions. It is apparent, through in vitro and in vivo studies, that IVIG exerts potent anti-inflammatory and immunomodulatory effects. However, the mechanism of action remains mostly unknown. The following article reviews the current literature and summarizes what is known about the mechanism of action of IVIG and the use of IVIG to treat certain conditions. Specifically, the use of IVIG for treatment of critically ill patients is outlined.