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Objective: Our objective was to evaluate the effect of glucocorticoid regimens on renal response, infections, and mortality among patients with lupus nephritis (LN)., Methods: We performed a systematic review and meta-analysis of the control arms of randomized clinical trials (RCTs). We included RCTs of biopsy-proven LN that used a protocolized regimen of glucocorticoids in combination with mycophenolic acid analogs or cyclophosphamide and reported the outcomes of complete response (CR), serious infections, and death. The starting dosage of glucocorticoids, tapering method, and administration of glucocorticoid pulses were abstracted. Meta-analysis of proportions, meta-regression, and subgroup meta-analysis were performed at 6 and 12 months for all outcomes., Results: Fifty RCT arms (3,231 patients with LN) were included. The predicted rates of CR, serious infections, and death when starting on oral prednisone at 25 mg/day without pulses were 19.5% (95% confidence interval [CI] 7.3-31.5), 3.2% (95% CI 2.4-4.0), and 0.2% (95% CI 0.0-0.4), respectively. Starting on prednisone at 60 mg/day (without pulses) increased the rates to 34.6% (95% CI 16.9-52.3), 12.1% (95% CI 9.3-14.9), and 2.7% (95% CI 0.0-5.3), respectively. Adding glucocorticoid pulses increased the rates of CR and death but not serious infections. We observed a dose-response gradient between the initial glucocorticoid dosage and all the outcomes at six months after accounting for the administration of glucocorticoid pulses, underlying immunosuppressant, and baseline proteinuria., Conclusion: A higher exposure to glucocorticoids during the initial therapy of LN was associated with better renal outcomes at the cost of increased infections and death., (© 2024 American College of Rheumatology.)

Objective: To describe the frequency and predictors of nonserious infections (NSI) and compare incidence across biologic agents within the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)., Methods: The BSRBR-RA is a prospective observational cohort study. An NSI was defined as an infection that did not require hospitalization or intravenous therapy. Infections were captured from clinician questionnaires and patient diaries. Individuals were considered "at risk" from the date of initiation of biologic treatment for up to 3 years. Drug exposure was defined by agent: tumor necrosis factor inhibitor (TNFi), interleukin-6 (IL-6) inhibitor, B cell depletion (rituximab), or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) alone. A multiple-failure Cox model was used with multivariable adjustment. Missing data were addressed using multiple imputation., Results: There were 17,304 NSI in 8,145 patients, with an event rate of 27.0 per person per year (95% confidence interval [95% CI] 26.6-27.4). Increasing age, female sex, comorbidity burden, glucocorticoid therapy, higher Disease Activity Score in 28 joints, and higher Health Assessment Questionnaire disability index were associated with an increased risk of NSI. There was a significant reduction in NSI risk with csDMARDs compared to biologic treatments. Compared to TNFi, IL-6 inhibition and rituximab were associated with a higher NSI risk (adjusted hazard ratio 1.45 [95% CI 1.29-1.63] and adjusted hazard ratio 1.28 [95% CI 1.14-1.45], respectively), while the csDMARD cohort had a lower risk (adjusted hazard ratio 0.64 [95% CI 0.59-0.70]). Within the TNFi class, adalimumab was associated with a higher NSI risk than etanercept (adjusted hazard ratio 1.11 [95% CI 1.05-1.17])., Conclusion: NSI occur frequently in RA, and predictors mirror those reported with serious infections. All biologics are associated with a greater risk of NSI, with differences observed between agents. While unmeasured confounding must be considered, the magnitude of effect is large, and a relationship between NSI and targeted immunomodulatory therapy likely exists., (© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Tattooing has been around for many years and is becoming an increasingly common fashion trend. As there are often few regulatory laws regarding the practice, an increase in the incidence of cutaneous reactions to tattoo inks is noted. These include allergic reactions, granulomatous dermatitis, infections, lichenoid dermatoses, and sometimes malignancy. The present study examines the histopathological changes seen in patients with cutaneous reactions to tattoo ink., Method: A prospective observational study was conducted over 18 months in the dermatology clinic of a tertiary care center in western India. The study population included 22 patients with cutaneous reactions over the tattoos. Punch biopsy specimens were sent to study the pattern of histopathological response., Results: All 22 patients studied were between the ages of 17 and 35 years. The mean duration of development of reaction was 8.1 months. Most of the reactions were seen in black ink tattoos performed by amateurs. Perivascular and spongiotic dermatitis suggestive of allergic response was the most common feature on histopathology. Granulomatous response and lichenoid response were seen in five and three biopsies, respectively., Conclusion: Legalization is needed for this practice to prevent tattoo reactions. Histopathological evaluation is important as tattoo reactions may be associated with skin infections and malignancies., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To estimate the incidence of immune checkpoint inhibitor-related myositis (ICI-myositis) in cancer patients receiving ICIs, and to report associated clinical manifestations, patterns of care, and outcomes., Methods: We identified a retrospective cohort of patients receiving ICIs between 2016 and 2019 seen at the University of Texas MD Anderson Cancer Center. Cases of ICI-myositis were identified using International Classification of Disease codes and confirmed by reviewing medical records and pathology, as available., Results: A total of 9,088 patients received an ICI. Thirty-six patients (0.40%) were identified as having ICI-myositis: 17 patients (47%) with ICI-myositis alone and 19 (53%) with overlap manifestations (5 patients with myocarditis, 5 with myasthenia gravis, and 9 with both). The incidence of ICI-myositis was 0.31% in those receiving ICI monotherapy and 0.94% in those receiving combination ICI therapy (relative risk 3.1 [95% confidence interval 1.5-6.1]). Twenty-five patients (69%) received ≥1 treatment in addition to glucocorticoids: plasmapheresis in 17 patients (47%), intravenous immunoglobulin in 12 (33%), and biologics in 11 (31%). Patients with overlap conditions had worse outcomes than those with myositis alone, and 79% of them developed respiratory failure. Eight patients died as a result of ICI-myositis, and all had overlap syndrome with myasthenia gravis or myocarditis (P < 0.05); 75% of these patients had a concomitant infection., Conclusion: ICI-myositis is a rare but severe adverse event. More than half of the patients presented with overlap manifestations and had deleterious outcomes, including respiratory failure and death. None of the patients with ICI-myositis alone died as a result of adverse events. Optimal treatment strategies have yet to be determined., (© 2020, American College of Rheumatology.)

High doses of corticosteroids in combination with rituximab remain an alternative in the treatment in relapsed or refractory chronic lymphocytic leukaemia (CLL) in the current era of targeted therapies. This study retrospectively evaluates the efficacy of an RCD (rituximab, cyclophosphamide and dexamethasone) regimen in the treatment of 51 patients with relapsed CLL (median age, 72 years). Unfavourable prognostic features, such as Rai stage III/IV, unmutated IGHV, del11q, TP53 mutation/deletion, complex karyotype and bulky lymphadenopathy, were frequent. The overall response or complete remission was of 57% and 7%, respectively, and the median progression-free survival (PFS) was of 12.3 months, median time to next treatment 23.1 months and median overall survival 39.2 months. Significant independent predictors of shorter PFS were TP53 deletion/mutation, advanced Rai stage and ≥2 previous lines of treatment. The incidence of neutropenia grade ≥ 3 was of 13%. Serious (CTCAE grade 3-5) infections were found in 20% of patients. Steroid-induced diabetes or diabetes decompensation occurred in 20% patients. Treatment-related adverse events resulted in RCD dose reduction in 35% of patients. In comparison with a historical R-Dex patient group, the treatment response and/or toxicity in our group was largely similar. However, the substantial differences in the baseline clinical characteristics of the groups may affect this comparison. In conclusion, the RCD regimen is an active, time-limited therapeutic strategy for elderly patients with relapsed CLL. Further, the results of our analysis indicate that the addition of cyclophosphamide to the R-Dex regimen maintains a similar efficacy, even after 50% reduction in the dexamethasone dose., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Objective: To report the 2-year efficacy and safety of tocilizumab (TCZ) in patients with polyarticular-course juvenile idiopathic arthritis (JIA)., Methods: Patients ages 2-17 years with active polyarticular-course JIA, in whom treatment with methotrexate was unsuccessful, received 16 weeks of open-label intravenous TCZ in part 1 (once every 4 weeks: 8 mg/kg or 10 mg/kg for body weight [BW] <30 kg; 8 mg/kg for BW ≥30 kg). Assessments were based on the JIA-American College of Rheumatology (ACR) response (defined as percentage of improvement in ≥3 of the 6 JIA core response variables [CRVs]). Patients with at least a JIA-ACR30 response (defined as ≥30% improvement in ≥3 of the 6 JIA CRVs without worsening in >1 of the remaining JIA CRVs by >30%) at week 16 were randomly assigned (1:1) to receive TCZ or placebo in part 2. Patients remained in part 2 until either week 40 or the occurrence of JIA flare. Upon starting part 3, all patients received open-label TCZ. At week 104 of the study, efficacy was assessed using JIA-ACR50/70/90 response rates (defined as 50%, 70%, or 90% improvement, respectively), achievement of inactive disease, and the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71). Safety was assessed in the all-exposure population per 100 patient-years of exposure., Results: Overall, 188 patients entered part 1, 166 patients entered part 2, and 160 patients entered part 3. By week 104, among the 188 patients in the modified intent-to-treat group who received TCZ, JIA-ACR50/70/90 response rates were 80.3%/77.1%/59.6%, respectively, the median JADAS-71 score decreased from 3.6 at week 40 to 0.7 at week 104, 51.1% of patients had achieved inactive disease, and 31 of 66 patients who had been receiving glucocorticoids discontinued them. Adverse event (AE) and serious AE rates were 406.5 per 100 patient-years and 11.1 per 100 patient-years, respectively. The infection rate was 151.4 per 100 patient-years, and the serious infection rate was 5.2 per 100 patient-years., Conclusion: Patients treated with TCZ for polyarticular-course JIA showed high-level disease control for up to 2 years. The TCZ safety profile was consistent with that previously reported., (© 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Infection is a rare occurrence after revision anterior cruciate ligament reconstruction (rACLR). Because of the low rates of infection, it has been difficult to identify risk factors for infection in this patient population. The purpose of this study was to report the rate of infection following rACLR and assess whether infection is associated with patient- and surgeon-dependent risk factors. We reviewed two large prospective cohorts to identify patients with postoperative infections following rACLR. Age, sex, body mass index (BMI), smoking status, history of diabetes, and graft choice were recorded for each patient. The association of these factors with postoperative infection following rACLR was assessed. There were 1423 rACLR cases in the combined cohort, with 9 (0.6%) reporting postoperative infections. Allografts had a higher risk of infection than autografts (odds ratio, 6.8; 95% CI, 0.9-54.5; p = .045). Diabetes (odds ratio, 28.6; 95% CI, 5.5-149.9; p = .004) was a risk factor for infection. Patient age, sex, BMI, and smoking status were not associated with risk of infection after rACLR., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Purpose: There is an increasing number of children with in utero exposure to opioids. Knowledge about opioid safety in pregnancy, particularly for outcomes later in childhood is scarce. It has been suggested that opioids can modulate immune system and increase the risk of infections. Our goal was to study the impact of in utero opioid exposure on the immune system and the risk of infections in childhood., Methods: This population-based cohort study used nationwide registers from Denmark, Norway, and Sweden. Among pregnant women we identified users of opioids for two different indications, opioids used in opioid maintenance therapy (OMT) and opioids used for treatment of pain. We followed the exposed children and studied susceptibility for infections measured as number of antibiotic prescriptions expressed as Incidence rate ratios (IRRs) and diagnoses in specialist health care expressed as hazard ratios (HRs)., Results: After adjustment we did not observe increased risk for filling antibiotic prescriptions in children exposed to OMT opioids compared with OMT discontinuers (IRR, 1.08; 95% CI 0.81-1.44 in Norway and Sweden, and IRR, 0.74; 95% CI 0.63-0.88 in Denmark), or for diagnosis of infection in specialist health care (HR 0.83; 95% CI 0.55-1.26 in Norway and Sweden, and 0.82; 95% CI 0.62-1.10 in Denmark)., Conclusions: In this population-based cohort study, we did not observe increased risk of infections among children prenatally exposed to OMT opioids when compared to OMT discontinuers, nor long-term analgesic opioids exposed when compared to short-term analgesic opioids exposed., (© 2020 John Wiley & Sons Ltd.)

Background: Immune modulating therapies are associated with an increased risk of infections and malignancies. This is of particular concern in elderly inflammatory bowel disease patients. This study aims to compare the safety and efficacy of vedolizumab between young and elderly inflammatory bowel disease patients., Methods: A binational, multicentre, retrospective, cohort study was performed from 2015 to 2019. Patients who underwent treatment with vedolizumab and were followed for at least 14 weeks were studied. They were divided according to age into groups: 40 years or less or 60 years or older. Clinical and endoscopic responses at weeks 14 and 52 and infection development were compared between young and elderly inflammatory bowel disease patient groups., Results: There were 144 patients (82 Crohn's disease and 62 ulcerative colitis) in the elderly cohort and 140 patients (83 Crohn's disease and 57 ulcerative colitis) in the young cohort. The average age was 70.2 ± 7.3 years and 29.6 ± 5.7 years, respectively. Clinical and endoscopic responses were comparable between the groups (week 52 remission of Crohn's disease: 40% vs. 35%, P  = 0.7; week 52 remission of ulcerative colitis: 48% vs. 51%, P  = 0.84). Previous anti-tumour necrosis factor biological therapy was independently associated with poor clinical remission rates at week 52 (Crohn's disease: odds ratio 0.23, 95% confidence interval 0.06-0.79; P  = 0.02 and ulcerative colitis: odds ratio 0.10 95% confidence interval 0.01-0.74; P  = 0.024). There were significantly more infections in the elderly cohort (2% vs. 12%, P  = 0.002), none of which were fatal., Conclusions: Vedolizumab is equally effective in elderly and young inflammatory bowel disease patients. The findings of this study demonstrate an increased risk of infections among the elderly treated with vedolizumab, which may be related to their age and underlying diseases.

Background: Medications used to treat inflammatory bowel disease (IBD) have significantly improved patient outcomes and delayed time to surgery. However, some of these therapies are recognized to increase the general risk of infection and have an unclear impact on postoperative infection risk., Objectives: To assess the impact of perioperative IBD medications on the risk of postoperative infections within 30 days of surgery., Search Methods: We searched the Cochrane IBD Group's Specialized Register (29 October 2019), MEDLINE (January 1966 to October 2019), Embase (January 1985 to October 2019), the Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform from inception up to October 2019, and reference lists of articles., Selection Criteria: Randomized controlled trials, quasi-randomized controlled trials, non-randomized controlled trials, prospective cohort studies, retrospective cohort studies, case-control studies and cross-sectional studies comparing participants treated with an IBD medication preoperatively or within 30 days postoperatively to those who were not taking that medication (either another active medication, placebo, or no treatment). We included published study reports and abstracts., Data Collection and Analysis: Two review authors independently screened titles and abstracts and extracted data. The primary outcome was postoperative infection within 30 days of surgery. Secondary outcomes included incisional infections and wound dehiscence, intra-abdominal infectious complications and extra-abdominal infections. Three review authors assessed risks of bias using the Newcastle-Ottawa Scale. We contacted authors for additional information when data were missing. For the primary and secondary outcomes, we calculated odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) using the generic inverse variance method. When applicable, we analyzed adjusted and unadjusted data separately. We evaluated the certainty of the evidence using GRADE., Main Results: We included 68 observational cohort studies (total number of participants unknown because some studies did not report the number of participants). Of these, 48 studies reported including participants with Crohn's disease, 36 reported including participants with ulcerative colitis and five reported including participants with indeterminate colitis. All 42 studies that reported urgency of surgery included elective surgeries, with 31 (74%) of those also including emergency surgeries. Twenty-four studies had low risk of bias while the rest had very high risk. Based on pooling of adjusted data, we calculated ORs for postoperative total infection rates in participants who received corticosteroids (OR 1.70, 95% CI 1.38 to 2.09; low-certainty evidence), immunomodulators (OR 1.29, 95% CI 0.95 to 1.76; low-certainty evidence), anti-TNF agents (OR 1.60, 95% CI 1.20 to 2.13; very low-certainty evidence) and anti-integrin agents (OR 1.04, 95% CI 0.79 to 1.36; low-certainty evidence). We pooled unadjusted data to assess postoperative total infection rates for the use of aminosalicylates (5-ASA) (OR 0.76, 95% CI 0.51 to 1.14; very low-certainty evidence). One secondary outcome examined was wound-related complications in participants using: corticosteroids (OR 1.41, 95% CI 0.72 to 2.74; very low-certainty evidence), immunomodulators (OR 1.35, 95% CI 0.96 to 1.89; very low-certainty evidence), anti-TNF agents (OR 1.18, 95% CI 0.83 to 1.68; very low-certainty evidence) and anti-integrin agents (OR 1.64, 95% CI 0.77 to 3.50; very low-certainty evidence) compared to controls. Another secondary outcome examined the odds of postoperative intra-abdominal infections in participants using: corticosteroids (OR 1.53, 95% CI 1.28 to 1.84; very low-certainty evidence), 5-ASA (OR 0.77, 95% CI 0.45 to 1.33; very low-certainty evidence), immunomodulators (OR 0.86, 95% CI 0.66 to 1.12; very low-certainty evidence), anti-TNF agents (OR 1.38, 95% CI 1.04 to 1.82; very low-certainty evidence) and anti-integrin agents (OR 0.40, 95% CI 0.14 to 1.20; very low-certainty evidence) compared to controls. Lastly we checked the odds for extra-abdominal infections in participants using: corticosteroids (OR 1.23, 95% CI 0.97 to 1.55; very low-certainty evidence), immunomodulators (OR 1.17, 95% CI 0.80 to 1.71; very low-certainty evidence), anti-TNF agents (OR 1.34, 95% CI 0.96 to 1.87; very low-certainty evidence) and anti-integrin agents (OR 1.15, 95% CI 0.43 to 3.08; very low-certainty evidence) compared to controls., Authors' Conclusions: The evidence for corticosteroids, 5-ASA, immunomodulators, anti-TNF medications and anti-integrin medications was of low or very low certainty. The impact of these medications on postoperative infectious complications is uncertain and we can draw no firm conclusions about their safety in the perioperative period. Decisions on preoperative IBD medications should be tailored to each person's unique circumstances. Future studies should focus on controlling for potential confounding factors to generate higher-quality evidence., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Patients in home health care (HHC), a rapidly growing healthcare sector, are at high risk for infections. This study aimed to identify risk factors for infections among HHC patients using the Outcome and Assessment Information Set (OASIS) data. We used a 5% random sample of the 2013 national OASIS data. Infections were identified if records indicated that patients were hospitalized or received emergency care for one of three types of infections (respiratory, wound site, and urinary tract infection). Multivariate logistic regression models were used to identify risk factors for each individual infection type. The final analysis included 128,163 patients from 8,255 HHC agencies nationwide. Approximately 3.2% of the patients developed infections during their HHC stay that led to hospitalization or emergency care treatment. We found that associations between demographics and infection risk are specific to the type of infection. In general, a history of multiple hospitalizations in past 6 months, comorbidity, having a severe condition at HHC admission, and impaired physical functioning increased HHC patients' risk of infections. We also identified that HHC patients with caregivers who needed training in providing medical procedure or treatment are at higher risk for wound-site infections. Our findings suggest that patients with underlying medical conditions and limited physical function status are more likely to develop infection. The caregiver's lack of training in providing needed care at home also places HHC patients at high risk for infection. Education for patients and caregivers should be tailored based on their health literacy level to ensure complete understanding., (© 2020 Wiley Periodicals LLC.)

Background: Selective immunoglobulin M deficiency (SIgMD) is a rare primary immunodeficiency that is frequently reported in Western countries. However, large epidemiological and clinical studies of SIgMD in China are still lacking. Herein, we describe a cohort of SIgMD subjects in a large tertiary university hospital in China., Methods: A cross-sectional study included 139 668 participants at First Affiliated Hospital of Wenzhou Medical University from January 2014 to October 2018 was conducted. Individuals with a serum IgM level less than 0.3 g/L with normal levels of serum IgA and IgG were defined as having SIgMD., Result: A total of 63 subjects met the criteria for SIgMD(63/139668, 0.045%), with a male-to-female ratio of 0.85, aged from 19 to 99 years. The most common clinical manifestation was autoimmune disorders (38/63, 60.32%), while the second most common manifestation was infections (21/63, 33.33%). Neither allergies nor tumors were found among these 63 SIgMD subjects. Most importantly, there were 30 patients with systemic lupus erythematosus among these 63 SIgMD subjects, accounting for 47.62% of all SIgMD subjects., Conclusion: To our knowledge, we describe here the first large single-center cohort of adult patients affected by SIgMD in China. The most common clinical manifestation was autoimmune disorders, specifically systemic lupus erythematosus., (© 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.)

Background and Purpose: To characterize the frequency and risk of serious infections in patients with myasthenia gravis (MG) relative to age/sex/area-matched comparators., Methods: This was a population-based cohort study in Ontario, Canada of patients with newly-diagnosed MG and 1:4 age/sex/area-matched general population comparators accrued from 1 April 2002 to 31 December 2015. The main outcome was a serious infection, defined by a primary diagnosis code on a hospitalization or emergency department record. We computed crude overall and sex-specific rates of infection among patients with MG and comparators, and the frequency of specific types of infection. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox regression., Results: Among 3823 patients with MG, 1275 (33.4%) experienced a serious infection compared with 2973/15 292 (19.4%) of comparators over a mean follow-up of over 5 years. Crude infection rates among patients with MG were twice those in comparators (72.5 vs. 35.0 per 1000 person-years, respectively). The most common infection types were respiratory infections, particularly bacterial pneumonia. After adjustment for potential confounders, MG was associated with a 39% increased infection risk (adjusted hazard ratio, 1.39; 95% confidence intervals, 1.28-1.51)., Conclusions: Patients with MG are at a significantly higher absolute and relative risk of serious infections compared with age/sex/area-matched comparators. This needs to be considered when selecting MG treatments and when planning vaccination/prophylaxis. Determining whether this risk is due to the use of immunosuppressive medications (vs. MG itself) is an important area for future research., (© 2020 European Academy of Neurology.)

Background: Hospitalized children present higher rates of undernutrition. Malnutrition can lead to a more complex hospitalization process with an increased length of stay and higher costs. Our aim was to analyze nutrition risk in hospitalized children and its relationship with clinical outcomes in a tertiary level hospital., Methods: This is a single institution prospective observational study. The research involved 282 consecutive children admitted along 3 months. Anthropometric measurements and nutrition risk by means of the Screening Tool for Risk on Nutritional Status and Growth (STRONGkids) tool were performed at admission. The incidence of infectious complications, length of hospital stay, weight loss, hospital expenses, and need of nutrition support were recorded., Results: The percentage of children with high, moderate, and low nutrition risk was 12.8%, 45%, and 42%, respectively. The prevalence of acute and chronic malnutrition was 13.7% and 7.4%. STRONGkids score correlated with clinical outcomes: longer stay, higher hospital expenses, and need of nutrition support were observed in children with high nutrition risk scores compared with the other groups (P < 0.001). The overall incidence of infectious complications was low (3.5%); a higher STRONGkids score did not predict a higher rate., Conclusion: Hospitalized children exposed to high nutrition risk have poorer clinical outcomes: longer stay, higher hospital expenses, and need of nutrition support. More studies are required to assess if applying STRONGkids and starting a nutrition intervention would result in lower costs and a shorter length of stay., (© 2019 American Society for Parenteral and Enteral Nutrition.)

Objective: The objective was to describe the prevalence of baseline comorbidities in patients with advanced NSCLC and the incidence rate of relevant outcomes commonly associated with NSCLC, and its treatments, in the year after diagnosis., Methods: A non-interventional cohort study compared adult patients newly diagnosed with advanced NSCLC during 2006-2013 with the general population. The prevalence of comorbidities one year before and incidence of relevant outcomes one year after NSCLC diagnosis were informed by data on all healthcare visits from two large regional registers. Main summary measures were prevalence, median survival, odds ratios (ORs), incidence rate (IR) and mortality rate (MR) with corresponding 95% confidence intervals (CIs)., Results: A total of 3,834 NSCLC patients were matched to 15,332 comparators. The prevalence of analysed comorbidities was significantly higher for NSCLC patients compared to the general population, with an OR of 2.44 (95% CI 2.27-2.63). Overall, the majority of IRs were higher for NSCLC patients, compared to the general population. The all-cause MR for the NSCLC cohort was significantly higher leading to an IR ratio of 32.5 (95% CI 31.0-34.2)., Conclusions: Advanced NSCLC patients presented with significantly more comorbidities in the year before diagnosis and relevant outcomes of interest in the year after., (© 2019 John Wiley & Sons Ltd.)

Objective: To evaluate predictors of serious infection events (SIEs) during rituximab (RTX) therapy and effects of hypogammaglobulinemia on SIE rates, and humoral response and its persistence after discontinuation of RTX in the treatment of rheumatic and musculoskeletal diseases (RMDs)., Methods: A retrospective longitudinal study of 700 RMD patients treated with RTX in a single center was conducted. Immunoglobulin levels were measured at baseline and at 4-6 months after each treatment cycle. Baseline predictors of SIEs were assessed using multivariable logistic regression; for RTX cycles 2-4, a mixed-effects logistic regression model was used., Results: A total of 507 patients (72%) had rheumatoid arthritis, 94 (13%) had systemic lupus erythematosus, 49 (7%) had antineutrophil cytoplasmic antibody-associated vasculitis, and 50 (7%) had other RMDs. The number of SIEs recorded was 281 in 176 patients (9.8 per 100 person-years). Predictors of SIEs included non-RTX-specific comorbidities (previous history of SIE, cancer, chronic lung disease, diabetes mellitus, and heart failure), higher corticosteroid dose, and RTX-specific factors, including low IgG (<6 gm/liter) both at baseline and during treatment, RTX-associated neutropenia, higher IgM, and longer time to RTX re-treatment, but not B cell count or depletion status. Of 110 patients with low IgG, SIE rates were higher in those with low IgG at baseline (16.4 per 100 person-years) and in those who acquired low IgG during or after RTX treatment (21.3 per 100 person-years) versus those with normal IgG (9.7 per 100 person-years). Five of 8 patients (63%) had impaired humoral response to pneumococcus and hemophilus following vaccination challenge, and only 4 of 11 patients (36%) had IgG normalized after switching biologic disease-modifying antirheumatic drugs., Conclusion: Immunoglobulin levels should be monitored at baseline and before each RTX cycle to identify patients at risk of SIEs. Individualized risk-benefit assessment should be undertaken in those with lower IgG as this is a consistent SIE predictor and may increase infection profiles when RTX is switched to different therapies., (© 2019, American College of Rheumatology.)

Objective: To examine cause-specific mortality beyond cardiovascular diseases (CVDs) in patients with gout compared to the general population., Methods: We included all residents of Skåne (Sweden) age ≥18 years in the year 2002. Using the Skåne Healthcare Register, we identified subjects with a new diagnosis of gout (2003-2013) and matched each person with gout with 10 comparators free of gout, by age and sex. We used information on the underlying cause of death from the Swedish Cause of Death Register (through December 31, 2014) to estimate hazard ratios (HRs, with 95% confidence intervals [95% CIs]) of mortality for specific causes of death in a multi-state Cox model, with adjustment for potential confounders., Results: Among 832,258 persons, 19,497 had a new diagnosis of gout (32% women) and were matched with 194,947 comparators. Subjects with gout had higher prevalence of chronic kidney disease, metabolic disease, and CVD. Gout was associated with 17% increased hazard of all-cause mortality overall (HR 1.17 [95% CI 1.14-1.21]), 23% in women (HR 1.23 [95% CI 1.17-1.30]), and 15% in men (HR 1.15 [95% CI 1.10-1.19]). In terms of cause-specific mortality, the strongest associations were seen in the relationship of gout to the risk of death due to renal disease (HR 1.78 [95% CI 1.34-2.35]), diseases of the digestive system (HR 1.56 [95% 1.34-1.83]), CVD (HR 1.27 [95% CI 1.22-1.33]), infections (HR 1.20 [95% CI 1.06-1.35]), and dementia (HR 0.83 [95% CI 0.72-0.97])., Conclusion: Several non-CV causes of mortality are increased in persons with gout, emphasizing the need for improved management of comorbidities., (© 2019, American College of Rheumatology.)

Objective: To evaluate the efficacy, including capacity for inhibition of radiographic progression, and safety of upadacitinib, a JAK1-selective inhibitor, as compared to placebo or adalimumab in patients with rheumatoid arthritis (RA) who have experienced an inadequate response to methotrexate (MTX)., Methods: In total, 1,629 RA patients with an inadequate response to MTX were randomized (2:2:1) to receive upadacitinib (15 mg once daily), placebo, or adalimumab (40 mg every other week) while continuing to take a stable background dose of MTX. The primary end points were achievement of an American College of Rheumatology 20% (ACR20) improvement response and a Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) of <2.6 in the upadacitinib group compared to the placebo group at week 12; inhibition of radiographic progression was evaluated at week 26. The study was also designed and powered to test for the noninferiority and superiority of upadacitinib compared to adalimumab, as measured both clinically and functionally., Results: At week 12, both primary end points were met in patients receiving upadacitinib compared to those receiving placebo (P ≤ 0.001). An ACR20 improvement response was achieved by 71% of patients in the upadacitinib group compared to 36% in the placebo group, and a DAS28-CRP score of <2.6 was observed in 29% of patients receiving upadacitinib compared to 6% of patients receiving placebo. Upadacitinib was superior to adalimumab based on the ACR50 response rate, achievement of a DAS28-CRP score of ≤3.2, change in pain severity score, and change in the Health Assessment Questionnaire disability index. At week 26, more patients receiving upadacitinib than those receiving placebo or adalimumab achieved low disease activity or remission (P ≤ 0.001). Radiographic progression was significantly inhibited in patients receiving upadacitinib and was observed in fewer upadacitinib-treated patients than placebo-treated patients (P ≤ 0.001). Up to week 26, adverse events (AEs), including serious infections, were comparable between the upadacitinib and adalimumab groups. The proportions of patients with serious AEs and AEs leading to discontinuation were highest in the adalimumab group; the proportions of patients with herpes zoster and those with creatine phosphokinase (CPK) elevations were highest in the upadacitinib group. Three malignancies, 5 major adverse cardiovascular events, and 4 deaths were reported among the groups, but none occurred in patients receiving upadacitinib. Six venous thromboembolic events were reported (1 in the placebo group, 2 in the upadacitinib group, and 3 in the adalimumab group)., Conclusion: Upadacitinib was superior to placebo and adalimumab for improving signs, symptoms, and physical function in RA patients who were receiving background MTX. In addition, radiographic progression was significantly inhibited by upadacitinib as compared to placebo. The overall safety profile of upadacitinib was generally similar to that of adalimumab, except for higher rates of herpes zoster and CPK elevations in patients receiving upadacitinib., (© 2019, American College of Rheumatology.)

Objective: To examine risk of emergency hospital admission and survival following adjuvant chemotherapy for early breast cancer., Methods: Linked data from New South Wales population-based and clinical cancer registries (2008-2012), hospital admissions, official death records and pharmaceutical benefit claims. Women aged ≥18 years receiving adjuvant chemotherapy for early-stage operable breast cancer in NSW public hospitals were included. Odds ratios (OR) for emergency hospitalisation within 6 months following chemotherapy initiation were estimated using logistic regression and survival using Kaplan-Meier and Cox proportional hazards methods., Results: A total of 3,950 women were included and 30.6% were hospitalised. The most common principal diagnosis at admission was neutropenia (30.8%). Women receiving docetaxel/carboplatin/trastuzumab (TCH) and docetaxel/cyclophosphamide (TC) were the most frequently hospitalised. After adjustment for demographic and clinical factors, the increased risk of hospitalisation for TCH and TC remained compared with doxorubicin/cyclophosphamide 3-weekly (OR 1.71, 95% confidence interval [CI] 1.24-2.37 and OR 1.47, 95% CI 1.17-1.85 respectively). Five-year overall survival was similar for women who were (92.2%, 95% CI 90.7-93.8) and were not hospitalised (93.1%, 95% CI 92.1-94.1)., Conclusion: Emergency hospitalisations following chemotherapy for early breast cancer were relatively common, especially following docetaxel-containing protocols. Further examination of reasons for admission is needed to inform actions to improve patient safety., (© 2019 John Wiley & Sons Ltd.)

Objective: To investigate the long-term safety and efficacy of intravenous (IV) belimumab plus standard of care (SOC) therapy for systemic lupus erythematosus (SLE) in patients with active, autoantibody-positive SLE., Methods: The study was designed as a multicenter, open-label, continuation study of IV belimumab given every 4 weeks in conjunction with SOC therapy in patients with SLE who completed a phase II, double-blind study. Adverse events (AEs) and laboratory data were monitored from the first belimumab dose (in either study) until 24 weeks after the final dose. Efficacy assessments included SLE Responder Index (SRI) and flare index scores (each assessed at 16-week intervals) and glucocorticoid use (assessed at 4-week intervals)., Results: Of the 476 patients in the parent study, 298 (62.6%) entered the continuation study, of whom 96 (32.2%) remained in the study. Patients received belimumab for up to 13 years (median duration of exposure 3,334.0 days [range 260-4,332 days], total belimumab exposure 2,294 patient-years, median number of infusions 115.5 [range 7-155]). The percentage of patients with AEs each year remained stable or decreased. Normal serum IgG levels were maintained in the majority of patients over the study, and the rate of infections remained stable. The percentage of patients who achieved an SRI response increased from 32.8% (year 1) to 75.6% of those remaining on treatment at year 12. The glucocorticoid dose was decreased in patients who had been receiving >7.5 mg/day at baseline., Conclusion: This study is the longest to date to assess belimumab treatment in patients with SLE in clinical trials. Belimumab was well tolerated with no new safety concerns, and efficacy was maintained in patients who continued the study. For patients who initially exhibited a satisfactory response to belimumab, the treatment continues to be well tolerated and provides long-term disease control., (© 2019 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Background: Different nutrition assessment tools in surgical cancer patients are used in clinical practice, which results in different prevalence rates of malnutrition. This may impact the interpretation of the association between nutrition status and clinical outcomes. Reduced standardized phase angle (SPA) values are associated with adverse outcomes in patients with cancer. Thus, it is important to assess the association of SPA with nutrition status and relate it to postoperative clinical outcomes., Methods: This prospective observational study included 121 surgical cancer patients. Bioelectrical impedance analysis, subjective global assessment (SGA), anthropometric measurements, and assessment of muscle strength were used to provide nutrition diagnosis 1 day before surgery. The patients were followed for infectious and noninfectious postoperative complications from the first day after the operation until discharge or death., Results: The prevalence of malnutrition was higher according to SGA (63.6%). Patients with an SPA < -1.65 had a greater chance of being diagnosed as malnourished according to the SGA (3.66 [1.35-9.90]), midarm circumference (OR 4.24; CI95%; 1.72-10.43), midarm muscle area (OR 4.38; CI95%; 1.68-11.42), and low handgrip strength (3.84 [1.31-11.25]). Patients with an SPA < -1.65 presented with more infectious complications (OR 4.19; CI95%; 1.52-11.53), but there was no association between SPA and other outcomes or death. SPA was the only significant predictor of infectious complications (AUC, 0.61; 95% CI, 0.51-0.71)., Conclusion: SPA was associated with different nutrition status parameters, and it was able to predict postoperative infectious complications., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Objective: To evaluate the safety and efficacy of belimumab as adjunctive therapy to maintain remission in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)., Methods: In this multicenter, double-blind, placebo-controlled study, patients with AAV (ages ≥18 years) were randomized 1:1 to receive azathioprine (2 mg/kg/day), low-dose oral glucocorticoids (≤10 mg/day), and either intravenous belimumab (10 mg/kg) or placebo, following remission induction with rituximab or cyclophosphamide along with glucocorticoids. The primary end point was time to first protocol-specified event (PSE), with first PSE defined as a Birmingham Vasculitis Activity Score (BVAS) of ≥6, presence of ≥1 major BVAS item, or receipt of prohibited medications for any reason, resulting in treatment failure (adjusted for ANCA type [proteinase 3 (PR3) or myeloperoxidase (MPO)], disease stage at induction, and induction regimen). Vasculitis relapse was defined as the PSE of either a BVAS activity score of ≥6 or receipt of prohibited medications for vasculitis. Changes in treatment practice led to truncation of the study population from ~300 patients to ~100 patients., Results: The intent-to-treat population totaled 105 patients with AAV, of whom 52 (40 with PR3-ANCAs, 12 with MPO-ANCAs) received placebo and 53 (41 with PR3-ANCAs, 12 with MPO-ANCAs) received belimumab; 27 of the patients were in rituximab-induced disease remission, while 78 were in cyclophosphamide-induced disease remission at baseline. Compared with placebo, treatment with belimumab did not reduce the risk of a PSE (adjusted hazard ratio [HR] 1.07, 95% confidence interval [95% CI] 0.44-2.59; P = 0.884) or vasculitis relapse (adjusted HR 0.88, 95% CI 0.29-2.65; P = 0.821). The overall rate of PSEs was low (11 [21.2%] of 52 patients receiving placebo, 10 [18.9%] of 53 patients receiving belimumab). Vasculitis relapse in the placebo group (n = 8) occurred independent of the induction regimen, disease stage, or ANCA type. All vasculitis relapses in the belimumab group (n = 6) occurred in patients who had PR3-ANCA-associated vasculitis with cyclophosphamide-induced disease remission. Adverse events occurred in 49 (92.5%) of 53 patients receiving belimumab and 43 (82.7%) of 52 patients receiving placebo, with no new safety concerns., Conclusion: Belimumab plus azathioprine and glucocorticoids for the maintenance of remission in AAV did not reduce the risk of relapse., (© 2019 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Objective: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Altered lymphocyte cell counts and a potential association with increased infection rates have been reported in RA patients treated with JAK inhibitors. This analysis was undertaken to evaluate the short-, mid-, and long-term effects of tofacitinib on lymphocytes and infection rates in patients with RA., Methods: In this post hoc analysis, absolute lymphocyte counts (ALCs) were obtained from phase III studies (12-24 months; n = 717-958) and phase I/II/III/long-term extension studies of tofacitinib (≤117 months) (All RA population; n = 7,061); lymphocyte subset counts (LSCs) were from phase II studies (1.5-6 months' exposure; n = 236-486), an ORAL Sequel vaccine substudy (~22 months; n = 198), and an ORAL Sequel lymphocyte substudy (~50 months; n = 55-1,035) of tofacitinib. The reversibility of ALC/LSC changes was evaluated. The relationship of ALC and LSC to infections was analyzed in the All RA population. The value of monitoring ALC alone was assessed by examining correlations between ALCs and LSCs., Results: Tofacitinib treatment resulted in an initial increase in ALC versus pretreatment baseline, which gradually declined to steady state by ~48 months. CD4+ and CD8+ T cell counts decreased over long-term treatment, and ALC and LSC changes were reversible upon treatment cessation. Patients with ALCs of <500 cells/mm 3 had an increased risk of serious infections. There was no strong association between CD4+ T cell, CD8+ T cell, B cell, or natural killer cell counts and serious infection incidence rates. ALC and CD4+ or CD8+ T cell counts correlated well (R = 0.65-0.86)., Conclusion: Our findings indicate that monitoring of ALC alone appears to be adequate to assess infection risk in tofacitinib-treated patients with RA., (© 2018 Pfizer Inc. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Background: Enteral nutrition (EN) is a safe and cost-effective intervention with significant morbidity and mortality benefit that can also be associated with complications. Peristomal infections can occur in 5%-30% of cases after percutaneous endoscopic gastrostomy placement. Despite this common occurrence, widespread use of objective diagnostic criteria is not prevalent, possibly leading to overuse of antibiotics., Methods: All patients who were reporting symptoms consistent with peristomal infection were evaluated. Criteria based on erythema, induration, and exudates were applied with cumulative score ≥8 indicating peristomal infection. All patients were followed, with additional factors being collected if available., Results: Forty-three patients noted complaints consistent with peristomal infection. In patients with a score <8 (n = 16), only 2 required antibiotics (12.5%) and 1 patient was hospitalized (6.3%). In patients with a score ≥8 (n = 27), 16 had a score of 8 or 9; all patients responded to antibiotics (100%), and 1 was hospitalized (6.3%). In patients with a score ≥10, all (100%) were treated with antibiotics. Five of 11 (45%) patients were hospitalized, with the most common diagnosis being sepsis. Of the baseline variables analyzed, higher body mass index correlated with score ≥10 (26.36 ± 2.94 vs 22.91 ± 4.35 in score <9, P = .0128)., Conclusions: Objective criteria were effective in risk stratifying patients who presented with reports of peristomal infection. Patients with a score <8 tended to be at low risk, scores of 8-9 were of moderate risk, and patients with a score ≥10 were at high risk and required very close monitoring or hospitalization., (© 2017 American Society for Parenteral and Enteral Nutrition.)

Background: Water immersion during labour and birth is increasingly popular and is becoming widely accepted across many countries, and particularly in midwifery-led care settings. However, there are concerns around neonatal water inhalation, increased requirement for admission to neonatal intensive care unit (NICU), maternal and/or neonatal infection, and obstetric anal sphincter injuries (OASIS). This is an update of a review last published in 2011., Objectives: To assess the effects of water immersion during labour and/or birth (first, second and third stage of labour) on women and their infants., Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (18 July 2017), and reference lists of retrieved trials., Selection Criteria: We included randomised controlled trials (RCTs) comparing water immersion with no immersion, or other non-pharmacological forms of pain management during labour and/or birth in healthy low-risk women at term gestation with a singleton fetus. Quasi-RCTs and cluster-RCTs were eligible for inclusion but none were identified. Cross-over trials were not eligible for inclusion., Data Collection and Analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two review authors assessed the quality of the evidence using the GRADE approach., Main Results: This review includes 15 trials conducted between 1990 and 2015 (3663 women): eight involved water immersion during the first stage of labour; two during the second stage only; four during the first and second stages of labour, and one comparing early versus late immersion during the first stage of labour. No trials evaluated different baths/pools, or third-stage labour management. All trials were undertaken in a hospital labour ward setting, with a varying degree of medical intervention considered as routine practice. No study was carried out in a midwifery-led care setting. Most trial authors did not specify the parity of women. Trials were subject to varying degrees of bias: the intervention could not be blinded and there was a lack of information about randomisation, and whether analyses were undertaken by intention-to-treat.Immersion in water versus no immersion (first stage of labour)There is probably little or no difference in spontaneous vaginal birth between immersion and no immersion (82% versus 83%; risk ratio (RR) 1.01, 95% confidence interval (CI) 0.97 to 1.04; 6 trials; 2559 women; moderate-quality evidence); instrumental vaginal birth (14% versus 12%; RR 0.86, 95% CI 0.70 to 1.05; 6 trials; 2559 women; low-quality evidence); and caesarean section (4% versus 5%; RR 1.27, 95% CI 0.91 to 1.79; 7 trials; 2652 women; low-quality evidence). There is insufficient evidence to determine the effect of immersion on estimated blood loss (mean difference (MD) -14.33 mL, 95% CI -63.03 to 34.37; 2 trials; 153 women; very low-quality evidence) and third- or fourth-degree tears (3% versus 3%; RR 1.36, 95% CI 0.85 to 2.18; 4 trials; 2341 women; moderate-quality evidence). There was a small reduction in the risk of using regional analgesia for women allocated to water immersion from 43% to 39% (RR 0.91, 95% CI 0.83 to 0.99; 5 trials; 2439 women; moderate-quality evidence). Perinatal deaths were not reported, and there is insufficient evidence to determine the impact on neonatal intensive care unit (NICU) admissions (6% versus 8%; average RR 1.30, 95% CI 0.42 to 3.97; 2 trials; 1511 infants; I² = 36%; low-quality evidence), or on neonatal infection rates (1% versus 1%; RR 2.00, 95% CI 0.50 to 7.94; 5 trials; 1295 infants; very low-quality evidence).Immersion in water versus no immersion (second stage of labour)There were no clear differences between groups for spontaneous vaginal birth (97% versus 99%; RR 1.02, 95% CI 0.96 to 1.08; 120 women; 1 trial; low-quality evidence); instrumental vaginal birth (2% versus 2%; RR 1.00, 95% CI 0.06 to 15.62; 1 trial; 120 women; very low-quality evidence); caesarean section (2% versus 1%; RR 0.33, 95% CI 0.01 to 8.02; 1 trial; 120 women; very low-quality evidence), and NICU admissions (11% versus 9%; RR 0.78, 95% CI 0.38 to 1.59; 2 trials; 291 women; very low-quality evidence). Use of regional analgesia was not relevant to the second stage of labour. Third- or fourth-degree tears, and estimated blood loss were not reported in either trial. No trial reported neonatal infection but did report neonatal temperature less than 36.2°C at birth (9% versus 9%; RR 0.98, 95% CI 0.30 to 3.20; 1 trial; 109 infants; very low-quality evidence), greater than 37.5°C at birth (6% versus 15%; RR 2.62, 95% CI 0.73 to 9.35; 1 trial; 109 infants; very low-quality evidence), and fever reported in first week (5% versus 2%; RR 0.53, 95% CI 0.10 to 2.82; 1 trial; 171 infants; very low-quality evidence), with no clear effect between groups being observed. One perinatal death occurred in the immersion group in one trial (RR 3.00, 95% CI 0.12 to 72.20; 1 trial; 120 infants; very low-quality evidence). The infant was born to a mother with HIV and the cause of death was deemed to be intrauterine infection.There is no evidence of increased adverse effects to the baby or woman from either the first or second stage of labour.Only one trial (200 women) compared early and late entry into the water and there were insufficient data to show any clear differences., Authors' Conclusions: In healthy women at low risk of complications there is moderate to low-quality evidence that water immersion during the first stage of labour probably has little effect on mode of birth or perineal trauma, but may reduce the use of regional analgesia. The evidence for immersion during the second stage of labour is limited and does not show clear differences on maternal or neonatal outcomes intensive care. There is no evidence of increased adverse effects to the fetus/neonate or woman from labouring or giving birth in water. Available evidence is limited by clinical variability and heterogeneity across trials, and no trial has been conducted in a midwifery-led setting.

Background: Recently, the European Society for Clinical Nutrition and Metabolism (ESPEN) provided novel consensus criteria for malnutrition diagnosis. This study aimed to evaluate the applicability of this instrument in combination with different nutrition screening tools (1) to identify malnutrition and (2) to predict morbidity and mortality in hospitalized patients., Materials and Methods: Observational prospective study in 750 adults admitted to the emergency service of a tertiary public hospital. Subjective Global Assessment (SGA-reference method) and the new ESPEN criteria were used to assess nutrition status of patients, who were initially screened for nutrition risk using 4 different tools. Outcome measures included length of hospital stay, occurrence of infection, and incidence of death during hospitalization, analyzed by logistic regression., Results: There was a lack of agreement between the SGA and ESPEN definition of malnutrition, regardless of the nutrition screening tool applied previously (κ = -0.050 to 0.09). However, when Malnutrition Screening Tool and Nutritional Risk Screening-2002 (NRS-2002) were used as the screening tool, malnourished patients according to ESPEN criteria showed higher probability of infection (relative risk [RR], 1.54; 95% confidence interval [CI], 1.02-2.31 and RR, 2.06; 95% CI, 1.37-3.10, respectively), and when the NRS-2002 was used, the risk for death was 2.7 times higher (hazard ratio, 2.69; 95% CI, 1.07-6.81) in malnourished patients than in well-nourished patients., Conclusion: Although the new ESPEN criteria had a poor diagnostic value, it seems to be a prognostic tool among hospitalized patients, especially when used in combination with the NRS-2002., (© 2017 American Society for Parenteral and Enteral Nutrition.)

Background and Purpose: We set out to revisit and comment on the evidence surrounding a popular figure published in the New England Journal of Medicine (2002), which suggests that the incidence of immune-mediated diseases, including multiple sclerosis (MS), is increased by reduced exposure to infections., Methods: Commentary., Results: We found that, to date (May 2017), this influential article has been cited >2000 times. However, on close investigation of the figure, we noticed some problems. Specifically, we observed several challenges inherent in using ecological data from disparate studies and countries to make conclusions surrounding the temporal patterns and relationships between diseases. For example, the figure depicts incidence data for MS based solely on a limited group of individuals with MS (n = 637; 455 women and 182 men) living within the region of Sassari on the island of Sardinia, known for its unique genealogy and risk of MS. However, the infectious-related data were based primarily on large population studies from the USA, with one derived from army recruits in France., Conclusions: We encourage the scientific community to apply rigorous, consistent methods in order to confirm or refute whether a strong, direct relationship does or does not exist between the incidence of MS and infectious diseases. Further, our article highlights a major knowledge gap that would benefit from a thorough review of the temporal trends related to MS incidence. Collation of this wide body of knowledge may provide a balanced understanding of this important topic and would best serve the progress of MS research., (© 2017 EAN.)

Introduction: Infections represent a major complication of hematological malignancies. C-reactive protein (CRP) and procalcitonin (PCT) have been used as diagnostic biomarkers of infections, but do not produce definitive findings. Recently, a new biomarker, presepsin, has been used as a diagnostic tool for detecting infections in the fields of emergency and neonatal medicine. However, the usefulness of presepsin for identifying infections in patients with hematological malignancies, including those who develop febrile neutropenia, remains unclear., Methods: In this study, we retrospectively analyzed the utility of PCT, presepsin, and CRP as biomarkers of infections during 49 febrile episodes that occurred in 28 patients with hematological malignancies., Results: The levels of PCT, but not those of CRP or presepsin, were significantly higher in the infection group than in the uninfected group (P<.03), indicating that PCT might be a more sensitive biomarker of infections. No differences in presepsin levels were detected between the patients with and without neutropenia, or between the infected and uninfected patients with neutropenia, indicating that presepsin might have less diagnostic value in patients with neutropenia., Conclusions: We conclude that PCT might provide additional information and could be used in combination with other biomarkers to detect infections in patients with hematological malignancies., (© 2017 Wiley Periodicals, Inc.)

The development of biologic drugs revolutionized the management of inflammatory bowel diseases: Crohn's disease and ulcerative colitis. However, while their efficacy has been well established, it remains uncertain to what extent biologic treatments may be associated with important safety risks, such as serious infections, opportunistic infections, or tuberculosis reactivation. Herein, we review and discuss the current evidence on the infection risk associated with biologic therapy in patients with inflammatory bowel disease (IBD)., (© 2017 American Society for Clinical Pharmacology and Therapeutics.)

Background: Early enteral feeding practices are potentially modifiable risk factors for necrotising enterocolitis (NEC) in very preterm or very low birth weight (VLBW) infants. Observational studies suggest that conservative feeding regimens, including slowly advancing enteral feed volumes, reduce the risk of NEC. However, slow feed advancement may delay establishment of full enteral feeding and may be associated with metabolic and infectious morbidities secondary to prolonged exposure to parenteral nutrition., Objectives: To determine effects of slow rates of enteral feed advancement on the incidence of NEC, mortality, and other morbidities in very preterm or VLBW infants., Search Methods: We used the standard Cochrane Neonatal search strategy to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5), MEDLINE via PubMed (1966 to June 2017), Embase (1980 to June 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to June 2017). We searched clinical trials databases, conference proceedings, previous reviews, and reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials., Selection Criteria: Randomised or quasi-randomised controlled trials that assessed effects of slow (up to 24 mL/kg/d) versus faster rates of advancement of enteral feed volumes upon the incidence of NEC in very preterm or VLBW infants., Data Collection and Analysis: Two review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) and risk difference (RD) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model for meta-analyses and explored potential causes of heterogeneity via sensitivity analyses. We assessed the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Main Results: We identified 10 RCTs in which a total of 3753 infants participated (2804 infants participated in one large trial). Most participants were stable very preterm infants of birth weight appropriate for gestation. About one-third of all participants were extremely preterm or extremely low birth weight (ELBW), and about one-fifth were small for gestational age (SGA), growth-restricted, or compromised in utero, as indicated by absent or reversed end-diastolic flow velocity (AREDFV) in the fetal umbilical artery. Trials typically defined slow advancement as daily increments of 15 to 20 mL/kg, and faster advancement as daily increments of 30 to 40 mL/kg. Trials generally were of good methodological quality, although none was blinded.Meta-analyses did not show effects on risk of NEC (typical RR 1.07, 95% CI 0.83 to 1.39; RD 0.0, 95% CI -0.01 to 0.02) or all-cause mortality (typical RR 1.15, 95% CI 0.93 to 1.42; typical RD 0.01, 95% CI -0.01 to 0.03). Subgroup analyses of extremely preterm or ELBW infants, or of SGA or growth-restricted or growth-compromised infants, showed no evidence of an effect on risk of NEC or death. Slow feed advancement delayed establishment of full enteral nutrition by between about one and five days. Meta-analysis showed borderline increased risk of invasive infection (typical RR 1.15, 95% CI 1.00 to 1.32; typical RD 0.03, 95% CI 0.00 to 0.05). The GRADE quality of evidence for primary outcomes was "moderate", downgraded from "high" because of lack of blinding in the included trials., Authors' Conclusions: Available trial data do not provide evidence that advancing enteral feed volumes at daily increments of 15 to 20 mL/kg (compared with 30 to 40 mL/kg) reduces the risk of NEC or death in very preterm or VLBW infants, extremely preterm or ELBW infants, SGA or growth-restricted infants, or infants with antenatal AREDFV. Advancing the volume of enteral feeds at a slow rate results in several days of delay in establishing full enteral feeds and may increase the risk of invasive infection.

Background: Oro/nasopharyngeal suction is a method used to clear secretions from the oropharynx and nasopharynx through the application of negative pressure via a suction catheter or bulb syringe. Traditionally, airway oro/nasopharyngeal suction at birth has been used routinely to remove fluid rapidly from the oropharynx and nasopharynx in vigorous and non-vigorous infants at birth. Concerns relating to the reported adverse effects of oro/nasopharyngeal suctioning led to a practice review and routine oro/nasopharyngeal suctioning is no longer recommended for vigorous infants. However, it is important to know whether there is any clear benefit or harm for infants whose oro/nasopharyngeal airway is suctioned compared to infants who are not suctioned., Objectives: To evaluate the effect of routine oropharyngeal/nasopharyngeal suction compared to no suction on mortality and morbidity in newly born infants., Search Methods: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 3), MEDLINE via PubMed (1966 to April 18, 2016), Embase (1980 to April 18, 2016), and CINAHL (1982 to April 18, 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials., Selection Criteria: Randomised, quasi-randomised controlled trials and cluster randomised trials that evaluated the effect of routine oropharyngeal/nasopharyngeal suction compared to no suction on mortality and morbidity in newly born infants with and without meconium-stained amniotic fluid., Data Collection and Analysis: The review authors extracted from the reports of the clinical trials, data regarding clinical outcomes including mortality, need for resuscitation, admission to neonatal intensive care, five minute Apgar score, episodes of apnoea and length of hospital stay., Main Results: Eight randomised controlled trials met the inclusion criteria and only included term infants (n = 4011). Five studies included infants with no fetal distress and clear amniotic fluid, one large study included vigorous infants with clear or meconium-stained amniotic fluid, and two large studies included infants with thin or thick meconium-stained amniotic fluid. Overall, there was no statistical difference between oro/nasopharyngeal suction and no oro/nasopharyngeal suction for all reported outcomes: mortality (typical RR 2.29, 95% CI 0.94 to 5.53; typical RD 0.01, 95% CI -0.00 to 0.01; I 2 = 0%, studies = 2, participants = 3023), need for resuscitation (typical RR 0.85, 95% CI 0.69 to 1.06; typical RD -0.01, 95% CI -0.03 to 0.00; I 2 = 0%, studies = 5, participants = 3791), admission to NICU (typical RR 0.82, 95% CI 0.62 to 1.08; typical RD -0.03, 95% CI -0.08 to 0.01; I 2 = 27%, studies = 2, participants = 997) and Apgar scores at five minutes (MD -0.03, 95% CI -0.08 to 0.02; I 2 not estimated, studies = 3, participants = 330)., Authors' Conclusions: The currently available evidence does not support or refute the benefits or harms of routine oro/nasopharyngeal suction over no suction. Further high-quality studies are required in preterm infants or term newborn infants with thick meconium amniotic fluid. Studies should investigate long-term effects such as neurodevelopmental outcomes.

Objective: While infection burden is high among patients with systemic lupus erythematosus (SLE), there is uncertainty about whether infection rates differ by immunosuppressive drug regimens. We undertook this study to compare infection rates among SLE patients newly initiating immunosuppressive therapy with mycophenolate mofetil (MMF), azathioprine (AZA), or cyclophosphamide (CYC)., Methods: Within the Medicaid Analytic eXtract database (2000-2010; 29 most populated US states), we identified adults with SLE starting MMF, AZA, or CYC treatment. We estimated propensity scores for receipt of MMF versus AZA and MMF versus CYC based on sociodemographic, comorbidity, and medication use information. After 1:1 propensity score matching, we estimated incidence rates of serious infections up to 6 and 12 months after drug initiation and used Cox regression to estimate hazard ratios (HRs) of first infection and death, with 95% confidence intervals (95% CIs). We performed primary intent-to-treat (ITT) and secondary as-treated analyses., Results: We studied 1,350 propensity score-matched pairs of MMF and AZA initiators and 674 propensity score-matched pairs of MMF and CYC initiators. In 6-month ITT analyses, the incidence rate per 100 person-years for first serious hospitalized infection was 14.6 in MMF users and 15.2 in AZA users (HR of MMF versus AZA 0.99 [95% CI 0.74-1.32]). Comparing MMF to CYC, the incidence rate per 100 person-years for first serious infection was 24.1 in MMF users and 24.6 in CYC users (HR 0.95 [95% CI 0.69-1.32]). There were no differences in mortality in either comparison. As-treated analyses yielded similar results., Conclusion: In a nationwide longitudinal study of Medicaid SLE patients at high risk of infection, rates of serious infection and mortality did not differ among new users of MMF, AZA, or CYC., (© 2016, American College of Rheumatology.)

Background: Bowel resection is required in the majority of patients with Crohn's disease (CD) during their lifetime. The Prognostic Nutritional Index (PNI) is a useful tool for predicting postoperative outcomes in patients undergoing cancer surgery. We examined the ability of the PNI to predict short-term outcomes in patients with CD-related bowel resection., Materials and Methods: Seventy-three patients who underwent bowel resection for CD were retrospectively enrolled in the study. The PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mL). Patients were divided into 2 groups: PNI <40 (n = 30) and PNI ≥40 (n = 43)., Results: A significant difference was found in body mass index (17.9 ± 2.4 vs 19.2 ± 2.2, P = .018) between the 2 groups. Postoperative overall and infectious complications occurred more frequently in patients with PNI <40 than in those with PNI ≥40 (50.0% and 46.7% vs 23.3% and 16.3%, P = .018 and P = .005, respectively). In the univariate analysis, body mass index <18.5, penetrating behavior, open surgery, and PNI <40 were associated with an increased risk of overall complications and infectious complications. In the multivariate analysis, only PNI <40 was an independent prognostic factor for infectious complications (odds ratio: 3.846, 95% confidence interval: 1.145-12.821)., Conclusions: Preoperative PNI is a useful predictor of postoperative infectious complications in patients with CD-related bowel resection.

Aims: Several clinical conditions may precipitate acute heart failure (AHF) and influence clinical outcome. In this study we hypothesized that precipitating factors are independently associated with 90-day risk of death in AHF., Methods and Results: The study population consisted of 15 828 AHF patients from Europe and Asia. The primary outcome was 90-day all-cause mortality according to identified precipitating factors of AHF [acute coronary syndrome (ACS), infection, atrial fibrillation (AF), hypertension, and non-compliance]. Mortality at 90 days was 15.8%. AHF precipitated by ACS or by infection showed increased 90-day risk of death compared with AHF without identified precipitants [hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.44-1.97, P < 0.001; and HR 1.51, 95% CI 1.18-1.92, P = 0.001), while AHF precipitated by AF showed lower 90-day risk of death (HR 0.56, 95% CI 0.42-0.75, P < 0.001), after multivariable adjustment. The risk of death in AHF precipitated by ACS was the highest during the first week after admission, while in AHF precipitated by infection the risk of death had a delayed peak at week 3. In AHF precipitated by AF, a trend toward reduced risk of death during the first weeks was shown. At weeks 5-6, AHF precipitated by ACS, infection, or AF showed similar risk of death to that of AHF without identified precipitants., Conclusions: Precipitating factors are independently associated with 90-day mortality in AHF. AHF precipitated by ACS or infection is independently associated with higher, while AHF precipitated by AF is associated with lower 90-day risk of death., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)

Objective: Tumor necrosis factor inhibitors are effective in reducing inflammation in rheumatic diseases but increase the risk of infections. This study was undertaken to investigate the relationship between the trough serum concentration of infliximab (IFX) and the risk of a first infection episode., Methods: We retrospectively included all patients who started IFX treatment for an approved indication in our department. Patients were followed up based on recommended IFX infusion schedules. We studied the relationship between the occurrence of a first infection episode requiring hospitalization, anti-infection treatment, or IFX infusion deferral, and the last trough IFX concentration and mean of the last 3 trough IFX concentrations measured before the infection episode., Results: Of the 201 patients included in the analysis, 173 had spondyloarthritis (SpA). The SpA patients had a mean ± SD age of 46 ± 12 years and a disease duration of 6.2 ± 6.1 years. During a median follow-up of 1.1 year, 87 SpA patients had at least 1 infection episode. Using Cox models, we found that the probability of survival without infection was significantly higher in patients with a mean of the last 3 trough IFX concentrations lower than the median (<11.3 mg/liter) than in patients with a mean concentration greater than the median (P = 0.048 by log-rank test). Glucocorticoid use and IFX concentration were significantly associated with the risk of a first infection episode in the multivariable analysis (P = 0.004 for both). The risk of infection episode was significantly increased in the highest quartile of the mean of the last 3 trough IFX concentrations (>20.3 mg/liter) (hazard ratio 2.65 [95% confidence interval 1.14-6.14], P = 0.023)., Conclusion: Our findings indicate that a high IFX concentration is correlated with a higher risk of a first infection episode, but these findings need to be replicated in further prospective studies., (© 2016, American College of Rheumatology.)

Background: Chorioamnionitis is a leading cause of perinatal morbidity and mortality. Amnioinfusion aims at reducing the adverse effects of chorioamnionitis by dilution of the infective organisms or by an anti-microbial effect of the fluid infused., Objectives: The objective of this review was to determine the effect of amnioinfusion on clinical and sub-clinical chorioamnionitis, fetal well-being, fetal heart rate characteristics and perinatal and maternal morbidity and mortality., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 July 2016), PubMed, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (6 July 2016) and reference lists of retrieved studies., Selection Criteria: Randomised clinical trials (RCTs) of amnioinfusion (treatment group) versus no amnioinfusion in women with chorioamnionitis.We would have also considered trials comparing amnioinfusion with sham amnioinfusion; different types or volumes of amnioinfusion fluid but none were identified.Cluster-RCTs and quasi-RCTs were eligible for inclusion but none were identified. We identified one study published in abstract form but it did not contain any numerical data and has therefore been excluded. Studies using a cross-over design are not an appropriate study design and thus were not eligible for inclusion in this review., Data Collection and Analysis: Two review authors independently assessed potential studies for inclusion and assessed trial quality. Both review authors independently extracted data and data were checked for accuracy., Main Results: We included one small trial (with data from 34 participants) comparing transcervical amnioinfusion with no amnioinfusion. The trial was considered to be at a high risk of bias overall, due to small numbers, inconsistency in the reporting and lack of information on blinding. Meta-analysis was not possible. Transcervical amnioinfusion was with room temperature saline at 10 mL per minute for 60 minutes, then 3 mL per minute until delivery versus no amnioinfusion. All women received intrauterine pressure catheter, acetaminophen and antibiotics (ampicillin or, if receiving Group B beta streptococcal prophylaxis, penicillin and gentamycin). We did not identify any trials that used transabdominal amnioinfusion.Compared to no amnioinfusion, transcervical amnioinfusion had no clear effect on the incidence of postpartum endometritis (risk ratio (RR) 1.50, 95% confidence interval (CI) 0.29 to 7.87; absolute risk 176/1000 (95% CI 34 to 96) versus 118/1000;low-quality evidence). Nor was there a clear effect in the incidence of neonatal infection (RR 3.00, 95% CI 0.13 to 68.84; absolute risk 0/1000 (95% CI 0 to 0) versus 0/1000; low-quality evidence). The outcome of perinatal death or severe morbidity (such as neonatal encephalopathy, intraventricular haemorrhage, admission to intensive/high care) was not reported in the included trial.In terms of this review's secondary outcomes, the rate of caesarean section was the same in both groups (RR 1.00, 95% CI 0.35 to 2.83; absolute risk 294/1000 (95% CI 103 to 832) versus 294/1000; low-quality evidence). There was no clear difference in the duration of maternal antibiotic treatment between the amnioinfusion and no amnioinfusion control group (mean difference (MD) 16 hours, 95% CI -1.75 to 33.75); nor in the duration of hospitalisation (MD 3.00 hours, 95% CI -15.49 to 21.49). The study did not report any information about how many babies had a low Apgar score at five minutes after birth.Women in the amnioinfusion group had a lower temperature at delivery compared to women in the control group (MD -0.38°C, 95% CI -0.74 to -0.02) but this outcome was not pre-specified in the protocol for this review.The majority of this review's secondary outcomes were not reported in the included study., Authors' Conclusions: There is insufficient evidence to fully evaluate the effectiveness of using transcervical amnioinfusion for chorioamnionitis and to assess the safety of this intervention or women's satisfaction. We did not identify any trials that used transabdominal amnioinfusion. The evidence in this review can neither support nor refute the use of transcervical amnioinfusion outside of clinical trials. We included one small study that reported on a limited number of outcomes of interest in this review. The numbers included in this review are too small for meaningful assessment of substantive outcomes, where reported. For those outcomes we assessed using GRADE (postpartum endometritis, neonatal infection, and caesarean section), we downgraded the quality of the evidence to low - with downgrading decisions based on small numbers and a lack of information on blinding. The included study did not report on this review's other primary outcome (perinatal death or severe morbidity).The reduction in pyrexia, though not a pre-specified outcome of this review, may be of relevance in terms of benefits to the fetus of reduced exposure to heat. We postulate that the temperature reduction found may be a direct cooling effect of amnioinfusion with room temperature fluid, rather than reduction of infection. Larger trials are needed to confirm and extend the findings of the trial reviewed here. These should be randomised controlled trials; participants, women with chorioamnionitis; interventions, amnioinfusion; comparisons, no amnioinfusion; outcomes, maternal and perinatal outcomes including neurodevelopmental measures.Further research is justified to determine possible benefits or risks of amnioinfusion for chorioamnionitis, and to investigate possible benefits of reducing temperature in fetuses considered at risk of neurological damage. Research should include randomised trials to examine transcervical or transabdominal amnioinfusion compared with no infusion for chorioamnionitis and examine outcomes listed in the methods of this review.

Purpose: The identification of infections in electronic health databases is a key issue for pharmacoepidemiology research. The aim of this study was to assess the positive predictive values (PPVs) of hospitalizations for infection in the Système National d'Information Inter-régimes de l'Assurance Maladie, that is the electronic database recording in-and-out hospital data for the entire French population (66 million inhabitants)., Methods: The source of data was the database of hospitalizations (Programme de Médicalisation des Systèmes d'Informations) of Toulouse University hospital, South of France (2880 beds). Among all hospital stays between September and December 2014, we randomly selected 100 stays with an International Classification of Diseases, 10th revision code of infection as primary diagnosis and 100 as related diagnosis. Medical charts were reviewed to assess the PPV of infection codes, as well as the PPV of correct coding of infection type among the true positive cases., Results: The PPVs of codes of infection as reason for hospitalization were 0.97, 95% confidence interval (CI) [0.93-1.00] for primary diagnosis codes and 0.70, 95% CI [0.61-0.71] for related diagnosis codes. Among the true positive cases, the PPVs of correct coding of the type of infection were, respectively, 0.98, 95% CI [0.95-1.00] and 0.93, 95% CI [0.88-0.98]., Conclusions: Hospitalizations for infection codes have very good PPVs in the Programme de Médicalisation des Systèmes d'Informations. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Objective: To assess the incidence of infections leading to hospitalization, the mortality rate related to infections, and the determinants of these factors in patients with giant cell arteritis (GCA)., Methods: In total, 486 patients with GCA (75% women) were enrolled at the time of diagnosis. All patients fulfilled the American College of Rheumatology criteria for GCA. As controls, age- and sex-matched subjects were randomly selected from the general population and matched to patients at the time of diagnosis of GCA. Both groups were prospectively followed up over a 5-year period., Results: Severe infections were more frequent among patients with GCA during the first year after diagnosis, compared to general population controls (incidence rate ratio 2.1, 95% confidence interval [95% CI] 1.2-3.4; incidence rate 11.1/100 patient-years [95% CI 8.3-14.6] in patients with GCA versus 5.9/100 patient-years [95% CI 4-8.4] in controls). Specifically, septic shock and infectious colitis were more frequent among the patients with GCA. Mortality caused by infections was higher in patients with GCA compared to controls (P < 0.0001 by log rank test). In analyses adjusted for age, among patients with GCA, a diagnosis of diabetes (hazard ratio [HR] 3.3, 95% CI 1.4-7.7) and a corticosteroid dosage that was >10 mg/day after 12 months of treatment (HR 4.61, 95% CI 1.38-15.36) were associated with death attributed to severe infection. The observed overall incidence of mortality was increased in patients with GCA during the early period of enrollment in the study (before 1997) (P = 0.0001 by log rank test), but thereafter was the same as that in the general population controls., Conclusion: Frequencies of severe infections and rates of infection-related mortality are increased during the first year after the diagnosis of GCA. The risk of infection increases in GCA patients with older age or in the presence of diabetes, or is greater when the dosage of corticosteroids has been increased to >10 mg/day after 12 months of treatment., (© 2016, American College of Rheumatology.)

Objective: We examined the use of antimicrobial medication as a proxy for infections in large patient cohort treated for binge-eating disorder (BED), bulimia nervosa (BN), and anorexia nervosa (AN) over the five-year period preceding eating disorder treatment., Method: Patients (N = 1592) at the Eating Disorder Unit of Helsinki University Central Hospital between 2000 and 2010 were compared with matched general population controls (N = 6368). The study population was linked to the prescription data of antibacterial, antifungal and antiviral medication from the Register on Reimbursed Prescription Medicine. Data were analyzed using regression models., Results: Individuals with BN and BED had received more often antimicrobial medication prescriptions compared to their controls (OR: 1.7, 95% CI: 1.3-2.1; OR: 2.6, 95% CI: 1.4-4.6, respectively), while no significant difference emerged in AN (OR: 0.9, 95% CI: 0.7-1.0, p = 0.10). Of the main drug categories, the respective pattern was seen in antibacterial and antifungal medication, while increased use for antivirals appeared only in BN (OR: 1.6, 95% CI: 1.1-2.3). Measured with the mean number of prescriptions or mean Defined Daily Doses per individual, patients with BN, BED and males with AN had also higher total antimicrobial medication use., Discussion: Indicating increased infections, we found elevated use of antimicrobial medication in BN, BED and in males with AN. Infections may be consequence of hyperglycemia, weight gain, or dysregulation of intestinal microbiota associated with core eating disorder behaviors. Or the other way round; changes in intestinal microbiota due to infections, inflammation, or antibacterial medications might contribute to eating disorders in multiple ways. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:542-552)., (© 2016 Wiley Periodicals, Inc.)

Objective: Animal studies and in vitro human studies suggest that certain opioid analgesics impair crucial immune functions. This study was undertaken to determine whether opioid use is associated with increased risk of serious infection in patients with rheumatoid arthritis (RA)., Methods: We conducted a self-controlled case series analysis on a retrospective cohort of 13,796 patients with RA enrolled in Tennessee Medicaid in 1995-2009. Within-person comparisons of the risk of hospitalization for serious infection during periods of opioid use versus non-use were performed using conditional Poisson regression. Fixed confounders were accounted for by design; time-varying confounders included age and use of disease-modifying antirheumatic drugs, glucocorticoids, and proton-pump inhibitors. In additional analyses, risks associated with new opioid use, use of opioids known to have immunosuppressive properties, use of long-acting opioids, and different opioid dosages were assessed. Sensitivity analyses were performed to account for potential protopathic bias and confounding by indication., Results: Among 1,790 patients with RA who had at least 1 hospitalization for serious infection, the adjusted incidence rate of serious infection was higher during periods of current opioid use compared to non-use, with an incidence rate ratio (IRR) of 1.39 (95% confidence interval [95% CI] 1.19-1.62). The incidence rate was also higher during periods of long-acting opioid use, immunosuppressive opioid use, and new opioid use compared to non-use (IRR 2.01 [95% CI 1.52-2.66], IRR 1.72 [95% CI 1.33-2.23], and IRR 2.38 [95% CI 1.65-3.42], respectively). Results of sensitivity analyses were consistent with the main findings., Conclusion: In within-person comparisons of patients with RA, opioid use was associated with an increased risk of hospitalization for serious infection., (© 2016, American College of Rheumatology.)

Objective: In pivotal trials, canakinumab has been shown to be effective in the treatment of systemic juvenile idiopathic arthritis (JIA), but reported adverse events have included macrophage activation syndrome (MAS). This study was undertaken to assess the impact of canakinumab on MAS incidence., Methods: An independent MAS Adjudication Committee (MASAC), consisting of 3 of the authors, was convened, and a search of databases from clinical studies of canakinumab treatment in systemic JIA was performed using MASAC-specified adverse event terms to identify potential MAS events. These were then adjudicated as "probable MAS," "possible MAS," or "MAS unlikely," using criteria developed by the MASAC. MAS rates were expressed as numbers of cases per 100 patient-years., Results: Of 72 potential MAS cases identified, 21 events (19 with canakinumab treatment; 2 with placebo treatment) in 19 patients were adjudicated as being probable MAS and 10 events in 9 patients as being possible MAS. Systemic JIA was well controlled in the majority of canakinumab-treated patients at the time of MAS. The time period between initiation of canakinumab treatment and onset of MAS ranged from 3 to 1,358 days (median 292 days). When the rates of probable MAS events were compared between canakinumab-treated patients (2.8 per 100 patient-years) and placebo-treated patients (7.7 per 100 patient-years), the difference was not significant (-4.9 [95% confidence interval -15.6, 5.9]). There were 3 deaths due to MAS-related complications (2 in patients receiving canakinumab; 1 in a patient receiving placebo); full recovery was reported in all other patients. Infections were the most common trigger of MAS, and the clinical features of MAS were not modified by canakinumab., Conclusion: Canakinumab does not have a significant effect on MAS risk or its clinical features in patients with systemic JIA. Infections are the most common trigger, and MAS occurs even in patients whose systemic JIA is well controlled with this treatment., (© 2016, American College of Rheumatology.)

Objective: The risks of hospitalized infection associated with biologic agents used to treat rheumatoid arthritis (RA) are unclear. The aim of this study was to determine whether the associated risk of hospitalized infections differed between specific biologic agents used to treat RA., Methods: In a retrospective cohort study using Medicare data from 2006-2011 for all enrolled patients with RA, new episodes of treatment with etanercept, adalimumab, certolizumab, golimumab, infliximab, abatacept, rituximab, and tocilizumab were identified. Patients were required to have received another biologic agent previously and to have been continuously enrolled in Medicare medical and pharmacy plans during the baseline period and throughout followup. Followup started on the date of initiation of treatment with the new biologic agent (after previous treatment with a different biologic agent) and ended on the date of the earliest hospitalized infection, at 12 months, after an exposure gap of >30 days, or at the time of death or loss of Medicare coverage. Cox regression analysis was used to calculate the adjusted hazard ratio (HR) for hospitalized infection, adjusting for an infection risk score and other confounders., Results: Of 31,801 new biologic treatment episodes in patients who had previously received another biologic agent, 12.0% were with etanercept, 15.2% with adalimumab, 5.9% with certolizumab, 4.4% with golimumab, 12.4% with infliximab, 28.9% with abatacept, 14.8% with rituximab, and 6.3% with tocilizumab. During followup, we identified 2,530 hospitalized infections; incidence rates ranged from 13.1 per 100 person-years (abatacept) to 18.7 per 100 person-years (rituximab). After adjustment, etanercept (HR 1.24, 95% confidence interval [95% CI] 1.07-1.45), infliximab (HR 1.39, 95% CI 1.21-1.60), and rituximab (HR 1.36, 95% CI 1.21-1.53) had significantly higher HRs for hospitalized infection compared with abatacept., Conclusion: In RA patients with prior exposure to a biologic agent, exposure to etanercept, infliximab, or rituximab was associated with a greater 1-year risk of hospitalized infection compared with the risk associated with exposure to abatacept., (© 2016, American College of Rheumatology.)

Objective: To describe the incidence of subsequent serious infections in patients who received systemic drug therapy after an initial serious infection., Methods: Patients with rheumatic conditions (rheumatoid arthritis [RA], psoriatic arthritis, ankylosing spondylitis) or psoriasis who experienced a serious infection between January 1, 2006 and December 31, 2011 were identified in a claims database. Patients were required to be continuously enrolled in the Truven Health Analytics MarketScan Research Database for 12 months prior to and at least 60 days after the date of discharge or the end of intravenous antibiotic therapy for the index serious infection. Subsequent serious infection incidence rates per 100 patient-years with 95% confidence intervals (95% CIs) were calculated for up to 18 months post-index, starting 60 days post-index. Cox proportional hazards models were used to adjust for baseline demographic and clinical characteristics, treatment duration, and changes during followup., Results: Among the 21,699 patients who met the inclusion criteria, the majority (84.3%) had RA. Patients who received tumor necrosis factor (TNF) inhibitor therapy after their index infection had a lower rate of subsequent serious infections (18.1 per 100 patient-years for those treated with a TNF inhibitor alone and 17.3 per 100 patient-years for those treated with a TNF inhibitor plus a nonbiologic disease-modifying antirheumatic drug [DMARD]) compared with those treated with a nonbiologic DMARD alone (21.4 per 100 patient-years). Etanercept, either alone (adjusted hazard ratio [HR] 0.87, 95% CI 0.77-0.99) or in combination with a nonbiologic DMARD (adjusted HR 0.76, 95% CI 0.66-0.88), and infliximab (only in combination with a nonbiologic DMARD) (adjusted HR 0.80, 95% CI 0.67-0.95) were associated with a significantly lower risk of subsequent serious infections compared with a nonbiologic DMARD alone., Conclusion: We did not observe an increased risk of subsequent infection in patients who received TNF inhibitor treatment following a serious infection. The risk of a subsequent serious infection was lower in patients treated with both a TNF inhibitor and a nonbiologic DMARD compared with that in patients treated with a nonbiologic DMARD alone., (© 2016, American College of Rheumatology.)

Introduction: The aim of this study was to study the impact of body mass index (BMI) and smoking on the outcome of hysterectomy and whether effects of these factors vary between abdominal, laparoscopic and vaginal hysterectomy., Material and Methods: Pre-, per- and postoperative (8 weeks) data were retrieved from the Swedish National Register for Gynecological Surgery on 28 537 hysterectomies performed because of a benign indication between 2004 and 2013. Multivariable logistic regression analyses were used to identify independent factors affecting the rate of complications, presented as adjusted odds ratios (adjOR) with 95% confidence intervals (CI)., Results: Overweight and obesity had the strongest impact on complications in the abdominal hysterectomy group. In women with a BMI ≥ 30 an increased adjOR could be seen for bleeding >1000 mL (2.90; 95% CI 2.23-3.77), peroperative complications (1.54; 95% CI 1.26-1.88), operation time >120 min (2.67; 95% CI 2.33-3.03), postoperative complications (1.21; 95% CI 1.08-1.34) and postoperative infections (1.73; 95% CI 1.50-1.99). With vaginal hysterectomy, the effect of BMI ≥ 30 could be seen in relation to excessive bleeding >500 mL (1.63; 95% CI 1.22-2.17) and operative time >120 min (2.00; 95% CI 1.60-2.50). With laparoscopic hysterectomy (LH), a BMI ≥ 30 had a higher adjOR for prolonged surgery (1.71; 95% CI 1.30-2.26). Smokers had an increased risk of postoperative infection in the abdominal hysterectomy (1.23; 95% CI 1.07-1.40) and vaginal hysterectomy groups (1.21; 95% CI 1.02-1.43) but not in the LH group., Conclusions: Body mass index and smoking had a negative effect with all hysterectomy approaches but to a lesser extent in vaginal and laparoscopic hysterectomies. This should be taken into consideration in advance of surgery to improve outcome., (© 2015 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: There is little consensus about the best management of pediatric deep neck space infections (DNSIs) and limited information about the national disease burden. The purpose of this study is to examine the health care burden, management, and complications of DNSIs from a national perspective., Study Design: Retrospective administrative data set review., Setting: National pediatric admission database., Subjects and Methods: Pediatric patients diagnosed with a parapharyngeal space and/or retropharyngeal abscess were identified from the 2009 KIDS' Inpatient Database. Patient demographic, hospital, and clinical characteristics were compared between patients who received surgical and nonsurgical management. All results for the analyses were weighted, clustered, and stratified appropriately according to the sampling design of the KIDS' Inpatient Database., Results: The prevalence of DNSIs was 3444 in 2009, and the estimated incidence was 4.6 per 100,000 children. The total hospital charges were >$75 million. The patients who were drained surgically had a 22% longer length of stay (mean = 4.19 days) than that of those who were managed without surgery (mean = 3.44 days). Mean hospital charges for patients who were drained surgically were almost twice those of patients who were managed medically ($28,969 vs $17,022); 165 patients (4.8%) had a complication., Results: There are >3400 admissions for pediatric DNSIs annually, and they account for a significant number of inpatient days and hospital charges. A randomized controlled trial of management may be indicated from a public health perspective., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

Objective: To examine the epidemiology of serious infections, a significant cause of morbidity and mortality in systemic lupus erythematosus (SLE), in a nationwide cohort of SLE and lupus nephritis (LN) patients., Methods: Using the Medicaid Analytic eXtract database for the years 2000-2006, we identified patients ages 18-64 years who had SLE and the subset who had LN. We ascertained cases of serious hospitalized infections using validated algorithms, and we determined 30-day mortality rates. Poisson regression was used to calculate infection incidence rates and multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) for the first infection, adjusted for sociodemographic variables, medication use, and an SLE-specific risk adjustment index., Results: We identified 33,565 patients with SLE, 7,113 of whom had LN. There were 9,078 serious infections in 5,078 SLE patients and 3,494 infections in 1,825 LN patients. The infection incidence rate per 100 person-years was 10.8 in the SLE cohort and 23.9 in the LN subcohort. In adjusted models for the SLE cohort, we observed increased risks of infection in men as compared to women (HR 1.33 [95% confidence interval (95% CI) 1.20-1.47]), in blacks as compared to whites (HR 1.14 [95% CI 1.06-1.21]), and in users of glucocorticoids (HR 1.51 [95% CI 1.43-1.61]) and immunosuppressive drugs (HR 1.11 [95% CI 1.03-1.20]) as compared to never users. Hydroxychloroquine users had a reduced risk of infection as compared to never users (HR 0.73 [95% CI 0.68-0.77]). The 30-day mortality rate per 1,000 person-years among those hospitalized with infections was 21.4 in the SLE cohort and 38.6 in the LN subcohort., Conclusion: In this diverse, nationwide cohort of SLE patients, we observed a substantial burden of serious infections with many subsequent deaths, particularly among those with LN., (© 2015, American College of Rheumatology.)

Objective: Denosumab is a biologic agent used to treat osteoporosis. Its safety profile given concurrently with biologic drugs for rheumatoid arthritis (RA) has not been well studied. We evaluated hospitalized infections among patients treated with biologic agents for RA who initiated denosumab or zoledronic acid (ZA), a parenteral bisphosphonate without known associations with infection. We hypothesized that the rate of hospitalized infection with denosumab would be noninferior to ZA., Methods: We identified RA patients enrolled in Medicare in 2006-2012 treated with biologic agents who initiated denosumab or ZA. Cox proportional hazards models compared the risk for hospitalized infection, comparing denosumab users to ZA users and adjusting for potentially confounding factors. A noninferiority margin was specified a priori to demonstrate that denosumab had no greater infection risk than ZA if the upper bound of the 95% confidence interval (95% CI) of the hazard ratio (HR) was <1.5., Results: Eligible RA patients receiving biologic agents initiated denosumab (n = 1,354) or ZA (n = 4,460). Characteristics of the denosumab users were as follows: mean ± SD age 73.0 ± 8.9, 98.2% women, with a majority receiving infliximab (35.7%) or abatacept (18.6%). Denosumab users had a higher prevalence of prior infections (11.5% hospitalized and 48.3% outpatient) and infection-related risk factors. The crude rate of hospitalized infections for denosumab (14.9/100 person-years [95% CI 12.2-18.1]) was comparable to that for ZA (13.9/100 person-years [95% CI 12.5-15.4]). After adjustment, the HR of hospitalized infection for denosumab users was noninferior to that for ZA users (HR 0.89 [95% CI 0.69-1.15])., Conclusion: The rate of hospitalized infection among RA patients receiving denosumab concurrently with biologic agents for RA was not increased compared to those receiving zoledronate., (© 2015, American College of Rheumatology.)

Background: A substantial body of experimental and epidemiological evidence has been accumulated suggesting that stressful events in early life including acute perinatal stress, maternal deprivation or separation, and variation in maternal care may lead to neuroendocrine perturbations thereby affecting reproductive performance, cognitive functions, and stress responses as well as the risk for infectious, cardio-metabolic and psychiatric diseases in later life., Results: Findings from recent studies based on both genome-wide and candidate gene approaches highlighted the importance of mechanisms that are involved in epigenetic regulation of gene expression, such as DNA methylation, histone modifications, and non-coding RNAs, in the long-term effects of exposure to stress in early life., Conclusions: This review is focused on the findings from human studies indicating the role of epigenetic mechanisms in the causal link between early-life stress and later-life health outcomes., (© 2014 Wiley Periodicals, Inc.)

Background and Purpose: There is an increasing interest in new risk factors for ischaemic stroke. Acute and chronic infections could contribute to different aetiological mechanisms of atherosclerosis that lead to cerebrovascular disease. The aim of this study was to investigate the hypothesis that previous infections and Chlamydia pneumoniae in particular increase the risk of ischaemic stroke in the population., Methods: This was a prospective case-control study involving 11 Italian stroke units. Controls were age- and sex-matched with cases, represented by patients admitted to hospital for acute ischaemic stroke. For each participant classical vascular risk factors and previous inflammatory and infectious events up to 1 month before were registered. Blood samples were collected to analyse inflammatory markers and titres of antibodies against C. pneumoniae., Results: A total of 1002 participants were included (mean age 69 years) with 749 ischaemic stroke patients. Infections occurred within 1 month previously in 12% of the entire sample with a higher prevalence in the case group (14.4% vs. 3.9%). At multivariate analysis of the seropositivity of IgA antibodies against C. pneumoniae increased the risk of stroke significantly (relative risk 2.121; 95% confidence interval 1.255-3.584) and an early previous infection (up to 7 days before the event) contributed to a rise in probability of acute cerebral ischaemia (relative risk 3.692; 95% confidence interval 1.134-6.875)., Conclusions: Early previous infections and persistent chronic infection of C. pneumoniae could contribute to increase the risk of ischaemic stroke significantly, in the elderly especially., (© 2014 EAN.)

Objective: To determine the rate of infection and all-cause mortality across tofacitinib phase II, phase III, and long-term extension (LTE) studies in patients with moderately to severely active rheumatoid arthritis (RA)., Methods: Pooled data from studies of tofacitinib in patients with RA were analyzed. In these studies, tofacitinib was administered as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs. The cutoff date for inclusion of data was April 19, 2012., Results: Across phase II, phase III, and LTE studies, 4,789 patients received tofacitinib (8,460 patient-years of exposure). The overall rate of serious infection was 3.09 events per 100 patient-years (95% confidence interval [95% CI] 2.73-3.49), and rates were stable over time. A Cox proportional hazards model showed that age, corticosteroid dose, diabetes, and tofacitinib dose were independently linked to the risk of serious infection. Lymphocyte counts of <0.5 × 10(3) /mm(3) were rare but were associated with an increased risk of treated and/or serious infection. Overall, all-cause mortality rates were 0.30 events per 100 patient-years (95% CI 0.20-0.44)., Conclusion: The overall risk of infection (including serious infection) and mortality rates in RA patients treated with tofacitinib appear to be similar to those observed in RA patients treated with biologic agents. The rates of serious infection were stable over time., (© 2014 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.)