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

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

Hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: The ADVANCE-CIDP 1 randomized controlled trial.

BACKGROUND AND AIMS: ADVANCE-CIDP 1 evaluated facilitated subcutaneous immunoglobulin (fSCIG; human immunoglobulin G 10% with recombinant human hyaluronidase) efficacy and safety in preventing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse. METHODS: ADVANCE-CIDP 1 was a phase 3, double-blind, placebo-controlled trial conducted at 54 sites in 21 countries. Eligible adults had definite or probable CIDP and adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores of 0-7 (inclusive), and received stable intravenous immunoglobulin (IVIG) for ≥12 weeks before screening. After stopping IVIG, patients were randomized 1:1 to fSCIG 10% or placebo for 6 months or until relapse/discontinuation. fSCIG 10% was administered at the same dose (or matching placebo volume) and interval as pre-randomization IVIG. The primary outcome was patient proportion experiencing CIDP relapse (≥1-point increase in adjusted INCAT score from pre-subcutaneous treatment baseline) in the modified intention-to-treat population. Secondary outcomes included time to relapse and safety endpoints. RESULTS: Overall, 132 patients (mean age 54.4 years, 56.1% male) received fSCIG 10% (n = 62) or placebo (n = 70). CIDP relapse was reduced with fSCIG 10% versus placebo (n = 6 [9.7%; 95% confidence interval 4.5%, 19.6%] vs n = 22 [31.4%; 21.8%, 43.0%], respectively; absolute difference: -21.8% [-34.5%, -7.9%], p = .0045). Relapse probability was higher with placebo versus fSCIG 10% over time (p = .002). Adverse events (AEs) were more frequent with fSCIG 10% (79.0% of patients) than placebo (57.1%), but severe (1.6% vs 8.6%) and serious AEs (3.2% vs 7.1%) were less common. INTERPRETATION: fSCIG 10% more effectively prevented CIDP relapse than placebo, supporting its potential use as maintenance CIDP treatment.

Intravenous Immunoglobulin Initiation in Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A US Claims-based Cohort Study.

INTRODUCTION: Intravenous immunoglobulin (IVIG) is recommended as first-line therapy for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), an immune-mediated neuropathy. The clinical profile of patients with CIDP newly initiating IVIG is poorly characterized. This claims-based cohort study describes characteristics of US patients with CIDP initiating IVIG treatment. METHODS: Adult immunoglobulin (IG)-naïve patients with CIDP diagnosed between 2008 and 2018 and a subgroup of patients subsequently initiating IVIG were identified in the Merative MarketScan Research Databases. Demographics, clinical characteristics, and diagnostic procedures were described for patients initiating IVIG. RESULTS: Of 32,090 patients with CIDP identified, 3975 (mean age 57 years) subsequently initiated IVIG. In the 6 months prior to IVIG initiation, diagnoses of comorbidities including neuropathy (75%), hypertension (62%), and diabetes (33%) were frequent, as were CIDP features/symptoms/markers of functional status including chronic pain (80%), difficulty walking (30%), and weakness (30%). CIDP-related laboratory/diagnostic procedures were performed in approximately 20- > 40% of patients in the 3 months prior to IVIG initiation (63.7% underwent electrodiagnostic/nerve conduction testing in the 6 months prior to IVIG initiation). Patient characteristics by initial IVIG product differed only in IVIG initiation year, US geographic region, and insurance type. Comorbidities, CIDP severity or functional status markers, and other clinical variables were generally well balanced across initial IVIG product groups. CONCLUSION: A heavy burden of symptoms, comorbidities, and diagnostic testing exists in patients with CIDP initiating IVIG. Characteristics of patients with CIDP initiating different IVIG products are well balanced, suggesting an absence of clinical or demographic determinants underlying IVIG selection.

Intravenous immunoglobulin, also called IVIG, involves giving antibodies through a drip into a vein. IVIG is recommended as one of the first treatments that patients receive if they have chronic inflammatory demyelinating polyradiculoneuropathy, also called CIDP, which is a rare disease that causes the body's immune system to attack its nerves. Our study described the characteristics of patients with CIDP who received IVIG in the USA. Information was collected from a large health insurance database and included records of patients aged ≥ 18 years who were diagnosed with CIDP between 2008 and 2018. Overall, 3975 patients with CIDP who received IVIG were included in the study. In the 6 months before starting IVIG, patients frequently had diagnoses of other diseases in addition to their CIDP; these included neuropathy (75% of patients), hypertension (62%), and diabetes (33%). CIDP features and symptoms that affected patients' daily lives were also frequently reported in these 6 months, including long-lasting pain (80%), difficulty walking (30%), and weakness (30%). In the 3 months before starting IVIG treatment, 20% to > 40% of patients underwent diagnostic procedures related to their CIDP. Different IVIG products were used similarly, but the year of IVIG initiation, geographic region, and insurance type all differed by IVIG product. In conclusion, patients with CIDP who receive IVIG experience a heavy burden caused by their symptoms, other diseases, and CIDP-related procedures. Patient characteristics were generally similar between patients receiving different IVIG products, suggesting that no specific characteristics are factored in when doctors select an IVIG product.

Intravenous Immunoglobulin Treatment Patterns and Outcomes in Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A US Claims Database Analysis.

INTRODUCTION: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare progressive or relapsing inflammatory disease. Intravenous immunoglobulin (IVIG) is recommended as a first-line therapy. The aim of this study was to describe real-world treatment patterns and outcomes of patients with CIDP in the Define initiating IVIG treatment. METHODS: This cohort study used health insurance claims data from the Merative MarketScan Research Databases (2008-2018). Adult patients (≥ 18 years old) with CIDP without prior immunoglobulin treatment were identified using International Statistical Classification of Diseases and Related Health Problems (ICD) codes, and patients subsequently initiating IVIG were included in the analysis. Real-world IVIG treatment patterns and treatment and safety outcomes (assessed via ICD codes) were described. RESULTS: In total, 3975 patients (median age 58 years) with CIDP who initiated IVIG were identified. After the initial IVIG loading period, patients received IVIG at a median dosing interval of 21 days (quartile [Q]1, Q3: 7, 28), and continued treatment for a median of 129 days (Q1, Q3: 85, 271). After the 2-year follow-up period, 55% of patients had discontinued all IVIG treatment; more than one-half of these discontinuations occurred within 4 months. Diagnoses of impaired functional status were evident in more than 30% of patients at baseline, but at lower rates during follow-up. Rates of new-onset safety outcomes after IVIG treatment were low. CONCLUSION: This real-world analysis of IVIG treatment patterns and treatment and safety outcomes of patients with CIDP who initiated IVIG highlights the unmet need for improved long-term management. Further research is needed to evaluate the use of functional status measures as endpoints for immunoglobulin treatment effectiveness.

Chronic inflammatory demyelinating polyradiculoneuropathy, also called CIDP, is a rare disease that causes the body's immune system to attack its nerves. Treatments for CIDP include antibodies, which are also called immunoglobulins. Immunoglobulins may be given intravenously, meaning they are administered into a vein. Intravenous immunoglobulin, also called IVIG, is recommended as one of the first treatments that patients with CIDP receive in their therapy and involves giving antibodies through a drip into a vein. This study aimed to gather information on the day-to-day use of IVIG by patients with CIDP. Information from 2008 to 2018 was collected from a large health insurance database in the USA. Information was taken from the records of patients aged 18 years or older who had received IVIG during the information collection period. In total, records from 3975 patients with an average age of 58 years were included in the study. On average, patients received IVIG every 21 days for 129 days. By 2 years, 55% of patients had stopped receiving IVIG; most of those patients had stopped within 4 months of first receiving the treatment. In the 6 months before receiving IVIG, over 30% of patients experienced limitations owing to their CIDP that affected their daily lives, although this percentage became smaller once patients started to receive IVIG. In addition, a low number of patients experienced side effects because of their IVIG treatment. This study highlights that improved long-term care for patients with CIDP is needed. Further research into ways of measuring the impact of CIDP on patients' daily lives is required, which may help doctors to work out how effective IVIG is at treating CIDP.

Early Diagnosis of Primary Immunodeficiency Disease Using Clinical Data and Machine Learning.

BACKGROUND: Primary immunodeficiency diseases (PIDD) are a group of immune-related disorders that have a current median delay of diagnosis between 6 and 9 years. Early diagnosis and treatment of PIDD has been associated with improved patient outcomes. OBJECTIVE: To develop a machine learning model using elements within the electronic health record data that are related to prior symptomatic treatment to predict PIDD. METHODS: We conducted a retrospective study of patients with PIDD identified using inclusion criteria of PIDD-related diagnoses, immunodeficiency-specific medications, and low immunoglobulin levels. We constructed a control group of age-, sex-, and race-matched patients with asthma. The primary outcome was the diagnosis of PIDD. We considered comorbidities, laboratory tests, medications, and radiological orders as features, all before diagnosis and indicative of symptom-related treatment. Features were presented sequentially to logistic regression, elastic net, and random forest classifiers, which were trained using a nested cross-validation approach. RESULTS: Our cohort consisted of 6422 patients, of whom 247 (4%) were diagnosed with PIDD. Our logistic regression model with comorbidities demonstrated good discrimination between patients with PIDD and those with asthma (c-statistic: 0.62 [0.58-0.65]). Adding laboratory results, medications, and radiological orders improved discrimination (c-statistic: 0.70 vs 0.62, P < .001), sensitivity, and specificity. Extending to the advanced machine learning models did not improve performance. CONCLUSIONS: We developed a prediction model for early diagnosis of PIDD using historical data that are related to symptomatic care, which has potential to fill an important need in reducing the time to diagnose PIDD, leading to better outcomes for immunodeficient patients.

Subcutaneous immunoglobulin use in immunoglobulin-naive patients with primary immunodeficiency: a systematic review.

Aim: Identify and describe published literature on the use of subcutaneous immunoglobulin (SCIG) as initial immunoglobulin (IG)-replacement therapy for patients with primary immunodeficiency diseases (PID). Methods: We systematically identified and summarized literature in MEDLINE, Embase, BioSciences Information Service and Cochrane Library assessing efficacy/effectiveness, safety/tolerability, health-related quality-of-life (HRQoL) and dosing regimens of SCIG for IG-naive patients with PID. Results: Sixteen studies were included. In IG-naive patients, SCIG managed/reduced infections and demonstrated similar pharmacokinetic parameters to IG-experienced patients; adverse events were mostly minor injection-site pain or discomfort. Three studies reported improvements in HRQoL. Quality of studies was difficult to assess due to limited reporting. Conclusion: Although studies were lacking, available data suggest IG-naive and IG-experienced patients initiating SCIG likely have similar outcomes.

Update on real-world use of facilitated subcutaneous immunoglobulin and immune globulin subcutaneous (human) 20% solution in patients with immunodeficiencies: poster extracts from the 19th Biennial Meeting of the European Society for Immunodeficiencies.

Immunoglobulin replacement therapy has been shown in clinical trials to be an important therapeutic option for reducing the incidence of serious bacterial infections and improving the quality of life in patients with primary and secondary immunodeficiencies (PID and SID, respectively). This article summarizes a poster series presented at the 19th Biennial Meeting of the European Society for Immunodeficiencies (October 14-17, 2020) further evaluating real-world usage and patient/physician experience with Immune Globulin Subcutaneous (Human) 20% Solution (Ig20Gly) in patients with PID and facilitated subcutaneous immunoglobulin (fSCIG) in patients with PID or SID.

Coinfection rates and clinical outcome data for cytomegalovirus and Epstein-Barr virus in post-transplant patients: A systematic review of the literature.

BACKGROUND: In transplant recipients, cytomegalovirus (CMV) infection increases morbidity and mortality; furthermore, coinfection with other human herpesviruses like the Epstein-Barr virus (EBV) may complicate their management. This systematic literature review aimed to summarize rates of CMV-EBV coinfection and associated clinical outcomes among solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. METHODS: An electronic literature search was performed using pre-specified search strategies (January 1, 2010-October 31, 2018) and following established/best practice methodology. Of 316 publications identified, 294 did not report CMV-EBV coinfection and were excluded. Studies meeting the inclusion criteria were further analyzed. Due to limited reporting/heterogeneity, data were not meta-analyzable. RESULTS: Nine studies (six SOT; three HSCT) reported CMV-EBV coinfection; rates of coinfection post transplantation varied between 2.6% and 32.7%. Two studies indicated CMV reactivation to be an independent variable associated with EBV reactivation. Among SOT studies, higher rates of graft dysfunction (47.4% vs 22.9%), rejection episodes (20.0% vs 8.9%), or acute rejection (50.0% vs 31.0%) were reported for patients with coinfection than without. In HSCT studies, patients with graft-vs-host disease were not reported separately for coinfection. Two studies described cases of post-transplant lymphoproliferative disorder (PTLD) in patients with CMV-EBV coinfection and reported rates of PTLD of 92% and 100%. CONCLUSION: The CMV-EBV coinfection rate in HSCT and SOT recipients varied and was associated with increased graft rejection and PTLD compared with patients without coinfection. Further research may improve understanding of the burden of CMV-EBV coinfection among transplant recipients.

Complications associated with surgical treatment of sleep-disordered breathing among hospitalized U.S. adults.

The purpose of this cross-sectional study is to examine the relationship between surgical treatments for sleep-disordered breathing (SDB) and composite measure of surgical complications in a nationally representative sample of hospital discharges among U.S. adults. We performed secondary analyses of 33,679 hospital discharges from the 2002-2012 Nationwide Inpatient Sample that corresponded to U.S. adults (≥18 years) who were free of head-and-neck neoplasms, were diagnosed with SDB and had undergone at least one of seven procedures. Multivariate logistic regression models were constructed to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI), controlling for age, sex, race/ethnicity, obstructive sleep apnea (OSA) and obesity diagnoses. Positive associations were found between composite measure of surgical complications and specific procedures: palatal procedure (aOR = 12.69, 95% CI: 11.91,13.53), nasal surgery (aOR = 6.47, 95% CI: 5.99,6.99), transoral robotic assist (aOR = 5.06, 95% CI: 4.34-5.88), tongue base/hypopharynx (aOR = 4.24, 95% CI: 3.88,4.62), maxillomandibular advancement (MMA) (aOR = 3.24, 95% CI: 2.74,3.84), supraglottoplasty (aOR = 2.75, 95% CI: 1.81,4.19). By contrast, a negative association was found between composite measures of surgical complications and tracheostomy (aOR = 0.033, 95% CI: 0.031,0.035). In conclusion, most procedures for SDB, except tracheostomy, were positively associated with complications, whereby palatal procedures exhibited the strongest and supraglottoplasty exhibited the weakest association.

Predicting Successful Treatment of Intracranial Aneurysms with the Pipeline Embolization Device Through Meta-Regression.

OBJECTIVE: To conduct meta-regression for the identification of clinically meaningful characteristics that can predict successful treatment of intracranial aneurysms with the Pipeline Embolization Device (PED). METHODS: Using the key word "Pipeline Embolization Device" and prespecified eligibility criteria, we searched PubMed and EMBASE and identified 105 original research articles (10,813 patients) published or in press (April 6, 2011, to December 31, 2016) focused on safety and/or effectiveness of PED. We constructed meta-regression models to identify predictors of 3 measures of PED treatment success, specifically rates of aneurysm occlusion, modified Rankin Scale score, and death. Rates were loge-transformed, and the adjusted R2 statistic was reported for each model. RESULTS: Aneurysm morphology and type accounted for substantial variation in 1-year aneurysm occlusion rate (14 studies with 689 patients; Radj2 = 88.91%). By contrast, predictors of 6-months aneurysm occlusion rate (aneurysm location, aneurysm type; 24 studies with 1321 patients; Radj2 = 31.67%) and aneurysm occlusion rate at unspecified follow-up time (year of publication, mean duration of angiographic follow-up; 34 studies with 1663 patients, Radj2 = 42.82%) accounted for less variability. Few predictors were identified for death rate (number of patients, aneurysm morphology; 34 studies with 6463 patients, Radj2 = 50.69%) or modified Rankin Scale score ≤2 (year of publication, mean age, aneurysm morphology; 14 studies with 556 patients, Radj2 = 100%). CONCLUSIONS: Few clinically meaningful characteristics appear to be relevant as predictors of the selected measures of PED treatment success. Future studies should attempt to identify additional predictors while focusing on aneurysm morphology as a key predictor of PED outcomes.

Signal detection using change point analysis in postmarket surveillance.

PURPOSE: Signal detection methods have been used extensively in postmarket surveillance to identify elevated risks of adverse events associated with medical products (drugs, vaccines, and devices). However, current popular disproportionality methods ignore useful information such as trends when the data are aggregated over time for signal detection. METHODS: In this paper, we applied change point analysis (CPA) to trend analysis of medical products in a spontaneous adverse event reporting system. CPA was used to detect the time point at which statistical properties of a sequence of observations change over time. Two CPA approaches, change in mean and change in variance, were demonstrated by an example using neurostimulator adverse event dataset. RESULTS: Two significant change points associated with upward trends were detected in June 2008 (n = 20, p < 0.001) and May 2011 (n = 51, p = 0.003). Further investigation confirmed battery issues and expansion of the indication for use could be possible causes for the occurrence of these change points. Two time points showed extremely low number of loss of therapy events, two cases in October 2009 and three in November 2009, which could be the result of reporting issues such as underreporting. CONCLUSION: As a complimentary tool to current signal detection efforts at FDA, CPA can be used to detect changes in the association between medical products and adverse events over time. Detecting these changes could be critical for public health regulation, adverse events surveillance, product recalls, and regulators' understanding of the connection between adverse events and other events regarding regulated products. © 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

Adverse events associated with pelvic organ prolapse surgeries that use implants.

OBJECTIVE: To estimate the rate of vaginal implant exposure associated with biologic grafts and permanent mesh used for pelvic organ prolapse (POP) surgery, to describe treatments used for these complications, and to estimate response rates to these treatments. The secondary aims were to describe the operative and perioperative complications. METHODS: This was a retrospective analysis of female members of Kaiser Permanente Southern and Northern California and Hawaii who underwent POP surgeries with biologic grafts and permanent mesh between September 2008 and May 2010. Inpatient and outpatient electronic medical records were reviewed for postoperative adverse events. RESULTS: During the 21-month period, 1,282 women, mean age of 62 years (±10 standard deviation), median parity of 3 (interquartile range 2-4), and median body mass index of 28 (interquartile range 24-30) underwent prolapse repairs with 1,484 implants with a mean follow-up time of 358 days (±276 standard deviation). Vaginal exposures occurred more often with permanent mesh (53/847 [6%]) than biologic grafts (10/637 [1.6%]) (P<.001). Resolution of vaginal exposure after the first treatment occurred in 24 of 63 (38%), whereas 39 of 63 (62%) required multiple treatments. Surgical excision was performed in 20 of 63 (32%) exposures. Permanent mesh exposures were more likely to require surgical excision (20/53 [38%]) than biologic graft exposures (zero of 10) (P=.02). CONCLUSION: Vaginal exposure occurred more frequently with permanent mesh than biologic graft, may require multiple treatments, and occasionally require surgical excision. LEVEL OF EVIDENCE: : II.

Patterns and predictors of multiple sexual partnerships among newly arrived Latino migrant men.

Multiple sexual partnerships (MSP), both concurrent and serial short gap, are thought to increase the risk of HIV and sexually transmitted infection (STI) acquisition and transmission. In this study we evaluate potential individual and environmental risk factors for engaging in MSP in a cohort of newly arrived Latino migrant men (LMM) in New Orleans, LA, USA. Participants were surveyed at three time points over a nine-month period to examine factors associated with MSP. Of the 113 men, 32.5 % reported ever MSP. In 290 observations, 19.5 % of men had concurrent, and 15.0 % had serial short gap partnerships in at least one interviews. Substance was associated with MSP, OR (95 % CI) 2.00 (1.16, 3.45) whereas belonging to a community organization was found to be protective, OR 0.32 (0.17, 0.59). Interventions to reduce substance use and promote social connection are needed to prevent a potential HIV/STI epidemic in this population.

Patterns and predictors of HIV/STI risk among Latino migrant men in a new receiving community.

The purpose of this study was to examine patterns and predictors of HIV/STI risk over time among Latino migrant men in a new receiving community. Latino men (N = 125) were interviewed quarterly for 18 months and HIV/STI tested annually. Selected individual, environmental and cultural factors by partner type and condom use were explored longitudinally and in a cross-section. Sex with female sex workers (FSWs) and multiple partners decreased, sex with main partners and abstinence increased, while the number of casual partners remained stable. Consistent condom use was highest with FSWs, lowest with main partners and midrange with casual partners with no trends over time. STI morbidity was low; no HIV was detected. Drug use and high mobility were associated with inconsistent condom use with FSW, whereas having family in the household was protective. HIV/STI prevention efforts should focus on drug using Latino migrants who are highly mobile and should foster healthy social connections.

Mycoplasma genitalium: an emerging cause of sexually transmitted disease in women.

Mycoplasma genitalium is an emerging sexually transmitted pathogen implicated in urethritis in men and several inflammatory reproductive tract syndromes in women including cervicitis, pelvic inflammatory disease (PID), and infertility. This comprehensive review critically examines epidemiologic studies of M. genitalium infections in women with the goal of assessing the associations with reproductive tract disease and enhancing awareness of this emerging pathogen. Over 27,000 women from 48 published reports have been screened for M. genitalium urogenital infection in high- or low-risk populations worldwide with an overall prevalence of 7.3% and 2.0%, respectively. M. genitalium was present in the general population at rates between those of Chlamydia trachomatis and Neisseria gonorrhoeae. Considering more than 20 studies of lower tract inflammation, M. genitalium has been positively associated with urethritis, vaginal discharge, and microscopic signs of cervicitis and/or mucopurulent cervical discharge in seven of 14 studies. A consistent case definition of cervicitis is lacking and will be required for comprehensive understanding of these associations. Importantly, evidence for M. genitalium PID and infertility are quite convincing and indicate that a significant proportion of upper tract inflammation may be attributed to this elusive pathogen. Collectively, M. genitalium is highly prevalent in high- and low-risk populations, and should be considered an etiologic agent of select reproductive tract disease syndromes in women.