Juthaporn Cowan

A Retrospective Longitudinal Within-Subject Risk Interval Analysis of Immunoglobulin Treatment for Recurrent Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Background Recurrent acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common, debilitating, costly and often difficult to prevent. Methods We reviewed records of patients who had COPD and immunoglobulin (Ig) treatment as adjunctive preventative treatment for AECOPD, and documented all AECOPD episodes for one year before and after initiation of Ig treatment. We graded AECOPD episodes as moderate for prescription of antibiotics and/or corticosteroids or for visit to the Emergency Department, and as severe for hospital admission. We conducted a retrospective within-subject self-controlled risk interval analysis to compare the outcome of annual AECOPD rate before and after treatment. Results We identified 22 cases of certain COPD, of which three had early discontinuation of Ig treatment due to rash and local swelling to subcutaneous Ig, and five had incomplete records leaving 14 cases for analyses. The median baseline IgG level was 5.9 g/L (interquartile range 4.1–7.4). Eight had CT radiographic bronchiectasis. Overall, the incidence of AECOPD was consistently and significantly reduced in frequency from mean 4.7 (± 3.1) per patient-year before, to 0.6 (± 1.0) after the Ig treatment (p = 0.0001). There were twelve episodes of severe AECOPD (in seven cases) in the year prior, and one in the year after Ig treatment initiation (p = 0.016). Conclusions Ig treatment appears to decrease the frequency of moderate and severe recurrent AECOPD. A prospective, controlled evaluation of adjunctive Ig treatment to standard therapy of recurrent AECOPD is warranted.

The effects of lysine analogs during pelvic surgery: a systematic review and meta-analysis.

Pelvic vasculature is complex and inconsistent while pelvic bones impede access to pelvic organs. These anatomical characteristics render pelvic surgery inherently difficult, and some of these procedures are frequently associated with blood loss that necessitates blood transfusion. The aim of this study was to review the literature on the use of lysine analogs to prevent bleeding and blood transfusion during pelvic surgery. The objective of this study was to assess the safety and efficacy of lysine analogs during pelvic surgery. A systematic literature search was performed using Medline, Cochrane Register of Clinical Trials, Embase, and the reference lists of relevant articles. Randomized controlled trials or observational cohort studies comparing a lysine analog to placebo or standard care were included. Outcomes collected were blood transfusion, blood loss, thromboembolic adverse events (myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism), nonthromboembolic adverse events, and death. There were no language limitations. Fifty-six articles reported on 68 comparisons between a lysine analog and an inactive comparator, involving a total of 7244 patients published between 1961 and 2013. Thirty-nine studies evaluated urologic procedures, and 21 evaluated gynecologic procedures. Thirty-six studies (60%) were published before 1980. Of the 43 randomized comparisons, only 30 (44%) had a score of 3 or higher on Jadads 5-point scale of methodological quality. Among randomized trials, lysine analogs reduced the risk of blood transfusion (pooled odds ratio [OR], 0.47; 95% confidence interval [CI], 0.35-0.64) and blood loss (pooled OR, 0.22; 95% CI, 0.18-0.27). There was a small statistically insignificant increased risk of thromboembolic events (pooled OR, 1.07; 95% CI, 0.72-1.59) and no-thrombotic serious adverse events (pooled OR, 1.11; 95% CI, 0.67-1.83). In the 17 randomized trials published since the year 2000, only 6 thrombotic events were reported, 4 of which occurred in the placebo arm. Lysine analogs did not increase risk of death (pooled OR, 0.91; 95% CI, 0.34-2.48). These results are significant as they indicate that lysine analogs significantly reduce blood loss and blood transfusion during pelvic surgery. Although there does not appear to be a large increase in the risk of thromboembolic and nonthrombotic adverse events, more data are required to definitively assess these outcomes. Based on this review, lysine analogs during pelvic surgery seem to reduce bleeding and blood transfusion requirements. Although there does not seem to be a significant risk of adverse effects, larger studies would help clarify risks, if any, associated with lysine analog use.

Subcutaneous Immunoglobulin Therapy in the Chronic Management of Myasthenia Gravis: A Retrospective Cohort Study

Background Immunoglobulin therapy has become a major treatment option in several autoimmune neuromuscular disorders. For patients with Myasthenia Gravis (MG), intravenous immunoglobulin (IVIg) has been used for both crisis and chronic management. Subcutaneous Immunoglobulins (SCIg), which offer the advantage of home administration, may be a practical and effective option in chronic management of MG. We analyzed clinical outcomes and patient satisfaction in nine cases of chronic disabling MG who were either transitioned to, or started de novo on SCIg. Methods and Findings This was a retrospective cohort study for the period of 2015–2016, with a mean follow-up period of 6.8 months after initiation of SCIg. All patients with MG treated with SCIg at the Ottawa Hospital, a large Canadian tertiary hospital with subspecialty expertise in neuromuscular disorders were included, regardless of MG severity, clinical subtype and antibody status. The primary outcome was MG disease activity after SCIg initiation. This outcome was measured by 1) the Myasthenia Gravis Foundation of America (MGFA) clinical classification, and 2) subjective scales of disease activity including the Myasthenia Gravis activities of daily living profile (MG-ADL), Myasthenia Gravis Quality-of-life (MG-QOL 15), Visual Analog (VA) satisfaction scale. We also assessed any requirement for emergency department visits or hospitalizations. Safety outcomes included any SCIg related complication. All patients were stable or improved for MGFA class after SCIg initiation. Statistically significant improvements were documented in the MG-ADL, MG-QOL and VAS scales. There were no exacerbations after switching therapy and no severe SCIg related complications. Conclusions SCIg may be a beneficial therapy in the chronic management of MG, with favorable clinical outcome and patient satisfaction results.

Protocol for updating a systematic review of randomised controlled trials on the prophylactic use of intravenous immunoglobulin for patients undergoing haematopoietic stem cell transplantation

Introduction Haematopoietic stem cell transplantation (HSCT) is commonly employed in the management of haematological malignancies. This intervention results in an increased risk of infectious and immune-related complications. Prophylactic immunoglobulin therapy has been used to prevent post-HSCT complications, including infections, with varying efficacy. We sought to update the current evidence supporting the use of immunoglobulins in the modern HSCT era. Methods/analysis Using a structured search strategy, we will perform a systematic review of the literature from MEDLINE, EMBASE and all EBM Reviews databases. We will include randomised clinical trials investigating clinical outcomes of prophylactic polyvalent immunoglobulin or cytomegalovirus (CMV)-specific immunoglobulin or plasma in patients undergoing HSCT. Clinical outcomes will include overall survival, transplant-related mortality, CMV infection, CMV disease, graft-versus-host disease, interstitial pneumonitis/fibrosis and hepatic veno-occlusive disease. Studies that only reported the results of biochemical tests will be excluded. Data will be extracted by two investigators independently. Study quality assessment will be evaluated using a validated five-point system as proposed by Jadad. Trial quality will be further assessed by identifying whether there was adequate allocation concealment. Where appropriate, a meta-analysis will be performed where relative risk will be used as the primary summary measure with 95% CIs. Pooled measures will be calculated for randomised clinical trials using a random-effects model. The Cochrane Q/χ2 test and I2 statistic will also be calculated to evaluate heterogeneity. We will also use a visual inspection of a funnel plot to assess potential publication bias. Discussion This systematic review aims to provide current evidence to justify the use of immunoglobulin prophylaxis in HSCT recipients. We will discuss whether current HSCT guidelines are supported by the current evidence, and whether further trials are needed, given the changing landscape of patients undergoing HSCT and the immunoglobulin manufacturing process. Systematic review registration PROSPERO CRD42015016684.

A national survey of screening and management of hypogammaglobulinemia in Canadian transplantation centers

Infection remains one of the most common transplant‐related causes of death in patients undergoing transplantation. Secondary hypogammaglobulinemia (HGG) as a component of immune suppression and deficiency is associated with both solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT). Available data and clinical experience for the supplementation of immunoglobulin (Ig) in these patients is conflicting, and differing clinical opinion accounts for non‐uniform practice in the use of Ig treatment. We aimed to survey lead transplant practitioners for current practice around polyvalent Ig use in post‐transplant recipients across Canada.

Long‐term low‐dose macrolides for chronic rhinosinusitis in adults – a systematic review of the literature

Chronic rhinosinusitis is a very common inflammatory disease that impairs quality of life and is associated with high healthcare spending. Chronic rhinosinusitis treatment commonly involves the use of intranasal corticosteroids, oral antibiotics, and surgery. Macrolides have been identified as a potential treatment option for chronic rhinosinusitis due to their immunomodulatory effects; however, the evidence supporting their use is still conflicting.

Effectiveness of immunoglobulin prophylaxis in reducing clinical complications of hematopoietic stem cell transplantation: a systematic review and meta-analysis: IMMUNOGLOBULIN PROPHYLAXIS IN HSCT

Prophylactic immunoglobulin has been used with varying efficacy to reduce complications in hematopoietic stem cell transplant recipients.

Prevalence of Hypogammaglobulinemia in Adult Invasive Pneumococcal Disease

Background Patients with humoral immune deficiency are susceptible to invasive pneumococcal disease (IPD). This study estimates the prevalence of underlying hypogammaglobulinemia in admitted IPD cases and examines whether IPD cases had received preventative treatment. Methods All adult IPD cases (Streptococcus pneumoniae in blood or cerebrospinal fluid) admitted to The Ottawa Hospital (TOH) from January 2013 to December 2015 were identified through the Eastern Ontario Regional Laboratory. Documented clinical demographics, S. pneumoniae serotype, serum immunoglobulins measured previously or in convalescence, and vaccination status of the cases were collected retrospectively for descriptive analyses. Results There were 134 IPD in 133 patients (47.4% male; mean age 63, standard deviation [SD] = 15.6 years) during a 3-year observation period. All-cause mortality rate was 22.6% over a mean follow-up time of 362, SD = 345 days. Fifty-seven patients (42.9%) had serum immunoglobulin levels measured. Eighteen were either found to have hypogammaglobulinemia in convalescence (8/18) or previously known to have hypogammaglobulinemia (10/18). None of the known hypogammaglobulinemic patients had received antibiotic prophylaxis and/or immunoglobulin replacement therapy within 4 months prior to IPD. The high and low estimates of prevalence of hypogammaglobulinemia were 31.6% (of all measured) and 13.5% (of all cases). Among 18 patients with hematological malignancies in our cohort, 13 had hypogammaglobulinemia. Many isolates were vaccine serotypes; however, only 8 had documented previous pneumococcal vaccination. Conclusions IPD has high mortality, and hypogammaglobulinemia was present in at least 13.5% of IPD cases. Secondary hypogammaglobulinemia is especially common in cases with hematological malignancy and IPD.

Incidence Rate of Post-Kidney Transplant Infection: A Retrospective Cohort Study Examining Infection Rates at a Large Canadian Multicenter Tertiary-Care Facility

Background: Reducing post-operative infections among kidney transplant patients is critical to improve long-term outcomes. With shifting disease demographics and implementation of new transplantation protocols, frequent evaluation of infection rate and type is necessary. Objective: Our objectives were to assess the incidence and types of post-operative infections in kidney transplant recipients at a large tertiary-care facility and determine sample sizes needed for future intervention trials. Design: Retrospective cohort study. Setting: The Ottawa Hospital, Ottawa, Ontario. Patients: Adult kidney transplant patients, N = 142. Measurements: Demographic data, transplant protocol, infections up to 2 years following transplantation. Methods: Infections within 2 years following transplantation in all kidney transplant recipients between January 2011 and December 2012 were reviewed. Sample sizes were determined using all-cause infection rates and infection-free survival data. Results: Of 142 patients, 44 (31.0%) had at least one infection. The incidence of infection was 36.2 per 100 patient-years by 2 years post-transplant. A total of 32 (22.5%) patients had 56 infection-related hospitalizations with 73.2% occurring in the first year. In the first 2 years, urinary tract infections had the highest incidence (18.1 per 100 patient-years) followed by skin (3.9 per 100 patient-years), cytomegalovirus (3.9 per 100 patient-years), and bacteremia (3.9 per 100 patient-years). Results indicate that 206 patients per study arm would be needed to show a 30% reduction in the 2-year incidence of infection post-transplantation. Limitations: Infection rates may be slightly underestimated due to the relatively short 2-year follow-up; however, the highest infection-risk period was captured within this time frame. Conclusions: Infections post-kidney transplant are still common, particularly urinary tract infections. They are associated with significant morbidity and hospitalization. Given the feasible sample sizes calculated in this study, intervention trials are indicated to further reduce infection rates within the first 2 years post-kidney transplantation.