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Objective: We performed a systematic literature review to identify and describe pharmacist-led antimicrobial stewardship programs (ASPs) interventions in low- and middle-income countries (LMICs)., Design: Systematic literature review., Methods: We searched PubMed for studies evaluating pharmacist-led ASP interventions in LMICs from January 1, 2012, to November 4, 2023. We evaluated the article's country of origin, described ASP interventions, and analyzed their reported outcomes., Results: Twenty-four studies were included; ten were conducted in China, two in India, two in Thailand, five in Africa, three in Latin America, and two in the Middle East. The predominant interventions in the studies were education and training followed by audit and feedback. The outcomes reported included reduction in antimicrobial consumption, cost reduction, shortening of the duration of antimicrobial therapy, and de-escalation., Conclusions: Our findings reinforce the importance of clinical pharmacists leading interventions related to antimicrobial stewardship in LMCIs and the global importance of investing in Infectious Disease training., Competing Interests: All authors report no conflict of interest relevant to this article, except MH who is contributor of Up To Date, consultant for the World Health Organization and member of SHEA Antimicrobial Stewardship Committee., (© The Author(s) 2024.)

Purpose: The aim of this work was to investigate whether reirradiation of recurrent glioblastoma with hypofractionated stereotactic radiation therapy (HSRT) consisting of 35 Gy in 5 fractions (35 Gy/5 fx) compared with 25 Gy in 5 fractions (25 Gy/5 fx) improves outcomes while maintaining acceptable toxicity., Methods and Materials: We conducted a prospective randomized phase 2 trial involving patients with recurrent glioblastoma (per the 2007 and 2016 World Health Organization classification). A minimum interval from first radiation therapy of 5 months and gross tumor volume of 150 cc were required. Patients were randomized 1:1 to receive HSRT alone in 25 Gy/5 fx or 35 Gy/5 fx. The primary endpoint was progression-free survival (PFS). We used a randomized phase 2 screening design with a 2-sided α of 0.15 for the primary endpoint., Results: From 2011 to 2019, 40 patients were randomized and received HSRT, with 20 patients in each group. The median age was 50 years (range, 27-71); a new resection before HSRT was performed in 75% of patients. The median PFS was 4.9 months in the 25 Gy/5 fx group and 5.2 months in the 35 Gy/5 fx group (P = .23). Six-month PFS was similar at 40% (85% CI, 24%-55%) for both groups. The median overall survival (OS) was 9.2 months in the 25 Gy/5 fx group and 10 months in the 35 Gy/5 fx group (P = .201). Grade ≥3 necrosis was numerically higher in the 35 Gy/5 fx group (3 [16%] vs 1 [5%]), but the difference was not statistically significant (P = .267). In an exploratory analysis, median OS of patients who developed treatment-related necrosis was 14.1 months, and that of patients who did not was 8.7 months (P = .003)., Conclusions: HSRT alone with 35 Gy/5 fx was not superior to 25 Gy/5 fx in terms of PFS or OS. Due to a potential increase in the rate of clinically meaningful treatment-related necrosis, we suggest 25 Gy/5 fx as the standard dose in HSRT alone. During follow-up, attention should be given to differentiating tumor progression from potentially manageable complications., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate the maternal-fetal hemodynamic effects after osteopathic manipulative treatment by measuring vital signs and Doppler velocimetry in third-trimester pregnant women., Materials and Methods: This is a prospective study with pregnant women undergoing outpatient follow-up and hospitalized in a ward at Instituto Fernandes Figueira/Fiocruz, between August 2021 to August 2022, during the SARS-CoV-2 pandemic. This study was registered in REBEC under Register Number RBR-9q7kvg and approved by the ethics committee under number 32216620.0.0000.5269. The study population was composed of 51 pregnant women between 28 and 40 weeks of gestation, over 18 years of age, allocated in a single group. Pregnancies with multiple fetuses, malformations, premature rupture of the membrane, and active labor were excluded. The procedures evaluated maternal-fetal hemodynamics using three consecutive measures of ultrasound examination with Doppler velocimetry, and three maternal vital signs measured by an electronic blood pressure monitor., Results: Most vital signs changed after osteopathic treatment. However, only the systolic blood pressure (109.92 ±14.42 to 110.71±12.8, p = 0.033), diastolic blood pressure (79.8±11.54 to 77.57±9.44, p = 0.018) and heart rate (87.59±11.93 to 81.12±10.26, p = 0.000) in the sitting position, systolic blood pressure (110.75±13.26 to 108.59±13.07; p = 0.034) in the supine, and heart rate (83.22±11.29 to 80.39±11.0; p = 0.013) in left lateral decubitus reached statistical significance. The oximetry measures (98.55±0.64 to 98.67±0.68; p = 0.098) stayed stable during all three positions. All artery values remained stable after treatment, and no statistically significant difference was recorded in the artery results., Conclusion: Responses to osteopathic treatment in women in the third trimester of pregnancy did not affect uteroplacental and fetoplacental circulation. However, some maternal vital signs had statistically significant results, with a decrease in diastolic blood pressure and heart rate, and an increase in systolic blood pressure in the sitting position, a decrease of heart rate in the left lateral decubitus position, and systolic blood pressure in the supine position. All the results observed were maintained in the normal parameters. The study responses attest to the safety of using the osteopathic manipulative treatment for the fetus and for pregnant women with comorbidities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Arruda Correia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This study aimed to elucidate the presence, antigen specificities, and potential clinical associations of anti-neutrophil extracellular trap (anti-NET) antibodies in a multinational cohort of antiphospholipid (aPL) antibody-positive patients who did not have lupus., Methods: Anti-NET IgG/IgM levels were measured in serum samples from 389 aPL-positive patients; 308 patients met the classification criteria for antiphospholipid syndrome. Multivariate logistic regression with best variable model selection was used to determine clinical associations. For a subset of the patients (n = 214), we profiled autoantibodies using an autoantigen microarray platform., Results: We found elevated levels of anti-NET IgG and/or IgM in 45% of the aPL-positive patients. High anti-NET antibody levels are associated with more circulating myeloperoxidase (MPO)-DNA complexes, which are a biomarker of NETs. When considering clinical manifestations, positive anti-NET IgG was associated with lesions affecting the white matter of the brain, even after adjusting for demographic variables and aPL profiles. Anti-NET IgM tracked with complement consumption after controlling for aPL profiles; furthermore, patient serum samples containing high levels of anti-NET IgM efficiently deposited complement C3d on NETs. As determined by autoantigen microarray, positive testing for anti-NET IgG was significantly associated with several autoantibodies, including those recognizing citrullinated histones, heparan sulfate proteoglycan, laminin, MPO-DNA complexes, and nucleosomes. Anti-NET IgM positivity was associated with autoantibodies targeting single-stranded DNA, double-stranded DNA, and proliferating cell nuclear antigen., Conclusion: These data reveal high levels of anti-NET antibodies in 45% of aPL-positive patients, where they potentially activate the complement cascade. While anti-NET IgM may especially recognize DNA in NETs, anti-NET IgG species appear to be more likely to target NET-associated protein antigens., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To describe the baseline characteristics of patients with positivity for antiphospholipid antibodies (aPLs) who were enrolled in an international registry, the Antiphospholipid Syndrome (APS) Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository, overall and by clinical and laboratory subtypes., Methods: The APS ACTION registry includes adults who persistently had positivity for aPLs. We evaluated baseline sociodemographic and aPL-related (APS classification criteria and "non-criteria") characteristics of patients overall and in subgroups (aPL-positive without APS, APS overall, thrombotic APS only, obstetric APS only, and both thrombotic APS/obstetric APS). We assessed baseline characteristics of patients tested for the presence of three aPLs (lupus anticoagulant [LAC] test, anticardiolipin antibody [aCL], and anti-β 2 -glycoprotein I [anti-β 2 GPI]) antibodies by aPL profiles (LAC only, single, double, and triple aPL positivity)., Results: The 804 aPL-positive patients assessed in the present study had a mean age of 45 ± 13 years, were 74% female, and 68% White; additionally, 36% had other systemic autoimmune diseases. Of these 804 aPL-positive patients, 80% were classified as having APS (with 55% having thrombotic APS, 9% obstetric APS, and 15% thrombotic APS/obstetric APS). In the overall cohort, 71% had vascular thrombosis, 50% with a history of pregnancy had obstetric morbidity, and 56% had experienced at least one non-criteria manifestation. Among those with three aPLs tested (n = 660), 42% were triple aPL-positive. While single-, double-, and triple aPL-positive subgroups had similar frequencies of vascular, obstetric, and non-criteria events, these events were lowest in the single aPL subgroup, which consisted of aCLs or anti-β 2 GPI only., Conclusion: Our study demonstrates the heterogeneity of aPL-related clinical manifestations and laboratory profiles in a multicenter international cohort. Within single aPL positivity, LAC may be a major contributor to clinical events. Future prospective analyses, using standardized core laboratory aPL tests, will help clarify aPL risk profiles and improve risk stratification., (© 2020, American College of Rheumatology.)

Objective:  To evaluate the assistance provided to women victims of sexual violence and their participation in the follow-up treatment after the traumatic event, presenting a sociodemographic profile, gynecological background, and circumstances of the event, and reporting the results, acceptance, and side effects of prophylaxis for sexually transmitted infections (STIs) and pregnancy., Methods:  A retrospective cohort study comprising the period between 2007 and 2016. All women receiving medical care and clinical follow-up after a severe episode of sexual violence were included. Records of domestic violence, male victims, children, and adolescents who reported consensual sexual activity were excluded. The present study included descriptive statistics as frequencies and percentages., Results:  A total of 867 medical records were reviewed and 444 cases of sexual violence were included. The age of the victims ranged from 10 to 77 years old, most of them self-declared white, with between 4 and 8 years of education, and denying having a sexual partner. Sexual violence occurred predominantly at night, on public thoroughfare, being committed by an unknown offender. Most victims were assisted at the referral service center within 72 hours after the violence, enabling the recommended prophylaxis. There was high acceptance of antiretroviral therapy (ART), although half of the users reported side effects. Seroconversion to human immunodeficiency virus (HIV) or to hepatitis B virus (HBV) was not detected in women undergoing prophylaxis., Conclusion:  In the present cohort, the profile of victims of sexual violence was low-educated, young, white women. The traumatic event occurred predominantly at night, on public thoroughfare, being committed by an unknown offender. Assistance within the first 72 hours after sexual violence enables the healthcare center to provide prophylactic interventions against STIs and unwanted pregnancies., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Objective: The APS ACTION Registry studies long-term outcomes in persistently antiphospholipid antibody (aPL)-positive patients. Our primary objective was to determine whether clinically meaningful aPL profiles at baseline remain stable over time. Our secondary objectives were to determine (1) whether baseline characteristics differ between patients with stable and unstable aPL profiles, and (2) predictors of unstable aPL profiles over time., Methods: A clinically meaningful aPL profile was defined as positive lupus anticoagulant (LAC) test and/or anticardiolipin (aCL)/anti-β 2 glycoprotein-I (anti-β 2 -GPI) IgG/M ≥ 40 U. Stable aPL profile was defined as a clinically meaningful aPL profile in at least two-thirds of follow-up measurements. Generalized linear mixed models with logit link were used for primary objective analysis., Results: Of 472 patients with clinically meaningful aPL profile at baseline (median follow-up 5.1 yrs), 366/472 (78%) patients had stable aPL profiles over time, 54 (11%) unstable, and 52 (11%) inconclusive. Time did not significantly affect odds of maintaining a clinically meaningful aPL profile at follow-up in univariate ( P = 0.906) and multivariable analysis ( P = 0.790). Baseline triple aPL positivity decreased (OR 0.25, 95% CI 0.10-0.64, P = 0.004) and isolated LAC test positivity increased (OR 3.3, 95% CI 1.53-7.13, P = 0.002) the odds of an unstable aPL profile over time., Conclusion: Approximately 80% of our international cohort patients with clinically meaningful aPL profiles at baseline remain stable at a median follow-up of 5 years; triple aPL-positivity increase the odds of a stable aPL profile. These results will guide future validation studies of stored blood samples through APS ACTION Core Laboratories., (Copyright © 2021 by the Journal of Rheumatology.)

Objective: Although systemic lupus erythematosus (SLE) is the most common autoimmune disease associated with antiphospholipid antibodies (aPL), limited data exist regarding the impact of SLE on the clinical phenotype of aPL-positive patients. The primary objective of this study was to compare the clinical, laboratory, and treatment characteristics of aPL-positive patients with SLE with those of aPL-positive patients without SLE., Methods: A secure web-based data capture system was used to store patient demographic characteristics and aPL-related clinical and laboratory characteristics. Inclusion criteria included positive aPL according to the updated Sapporo classification criteria. Antiphospholipid antibody-positive patients fulfilling the American College of Rheumatology criteria for the classification of SLE ("aPL with SLE") and those with no other autoimmune diseases ("aPL only") were included in the analysis., Results: Six hundred seventy-two aPL-positive patients were recruited from 24 international centers; 426 of these patients did not have other autoimmune disease, and 197 had SLE. The frequency of thrombocytopenia, hemolytic anemia, low complement levels, and IgA anti-β 2 -glycoprotein I (anti-β 2 GPI) antibodies was higher in the aPL-positive patients with SLE, whereas the frequency of cognitive dysfunction and IgG anti-β 2 GPI antibodies was higher in the aPL-only group. The frequency of arterial and venous thromboses (including recurrent) as well as pregnancy morbidity was similar in the 2 groups. The prevalence of cardiovascular disease risk factors at the time of entry into the registry entry did not differ between the 2 groups, with the exception of current smoking, which was more frequent in aPL-positive patients with SLE., Conclusion: Although the frequencies of thrombosis and pregnancy morbidity are similar in aPL-positive patients with and those without SLE, the diagnosis of SLE in patients with persistently positive aPL is associated with an increased frequency of thrombocytopenia, hemolytic anemia, low complement levels, and positive IgA anti-β 2 GPI antibodies., (© 2018, American College of Rheumatology.)

This study analyzed maternal and fetal outcomes of pregnancies of neuropsychiatric systemic lupus erythematosus patients followed in a reference unit. This retrospective cohort study included 26 pregnancies of patients seen between 2011 and 2015 included with history and/or active neuropsychiatric systemic lupus erythematosus among 135 pregnancies. Three patients had active neuropsychiatric systemic lupus erythematosus at conception, but only one remained with neurological activity during gestation, characteristically related to the inadvertent suspension of medications. Twenty six percent of the newborns were small for gestational age and 40% of live births were premature, with no neonatal death or early complications of prematurity. Preeclampsia was diagnosed in nine pregnancies, with two cases of early severe form that resulted in intrauterine fetal death. Patients with neuropsychiatric systemic lupus erythematosus had more prematurity and preeclampsia compared to patients without neuropsychiatric disease. However, when concomitant lupus nephritis was excluded, the gestational results of neuropsychiatric systemic lupus erythematosus patients were more favorable.

Even though the association of anti-phospholipid antibodies (aPL) with infertility is debated, infertile women are commonly screened for aPL. To review evidence, a systematic PubMed search was conducted to retrieve papers addressing (i) the association between aPL and infertility, (ii) the positivity rate of criteria and non-criteria aPL in women with infertility, (iii) the association between aPL and assisted reproduction technologies (ART) outcome, (iv) the efficacy of medical treatments on ART outcome, and (v) the effects of ART on thrombotic risk. A total of 46 papers were considered; several limitations emerged: (i) wide heterogeneity in study populations, (ii) non-prospective design in 90% of studies, and (iii) aPL cutoffs not conforming to international guidelines in more than 75% of studies; aPL positivity not confirmed in 89% of studies. Most studies evinced an association between infertility and anti-β2GPI antibodies and almost all non-criteria aPL. The association rate with infertility was below 50% for lupus anti-coagulant, anti-cardiolipin antibodies (aCL), and anti-phosphatidic acid antibodies. According to our estimates, overall positivity rates of criteria and non-criteria aPL tests are 6% and 3% among infertile women, 1% and 2% among controls, respectively. A significant difference in the positivity rate of patients versus controls emerged for aCL only. Five of 18 studies reported a detrimental effect of aPL on ART outcome. Only one of the six studies assessing the effects of treatment on ART outcome among aPL-positive infertile women reported a benefit. All relevant studies reported no increase in the rate of thrombosis among aPL-positive women undergoing ART., (Copyright © 2016. Published by Elsevier B.V.)

In a previous systematic literature search, we demonstrated that the frequencies of antiphospholipid antibodies (aPL) in general-population patients with pregnancy morbidity (PM), deep vein thrombosis (DVT), myocardial infarction (MI), and stroke (ST) are 6%, 10%, 11%, and 14%. To determine the association between aPL and clinical outcomes, we conducted a follow-up analysis of the 120 studies included in the original paper. Based on the analysis of 81 studies, a significant difference in the frequency of aPL criteria tests between patients and controls emerged considering all the outcomes together (10% versus 3%). In particular, a significant difference was reported for overall PM, pregnancy loss (PrL), late PrL, severe preeclampsia (PEC), ST, MI, and DVT. No difference emerged for early PrL, intrauterine growth restriction (IUGR), PEC, eclampsia (EC), and HELLP. A positive association was found in more than half of the studies for overall PrL, severe PEC, HELLP, ST, MI, and DVT and in less than half for early and late PrL, PEC, EC, and IUGR. The positive association between aPL and clinical outcomes included in the antiphospholipid syndrome classification criteria is not supported by every study, being particularly inconsistent for early PL, IUGR, PEC, EC, and HELLP., (© The Author(s) 2015.)

Systemic lupus erythematosus (SLE) is a chronic, multisystemic autoimmune disease that occurs predominantly in women of fertile age. The association of SLE and pregnancy, mainly with active disease and especially with nephritis, has poorer pregnancy outcomes, with increased frequency of preeclampsia, fetal loss, prematurity, growth restriction, and newborns small for gestational age. Therefore, SLE pregnancies are considered high risk condition, should be monitored frequently during pregnancy and delivery should occur in a controlled setting. Pregnancy induces dramatic immune and neuroendocrine changes in the maternal body in order to protect the fetus from immunologic attack and these modifications can be affected by SLE. The risk of flares depends on the level of maternal disease activity in the 6-12 months before conception and is higher in women with repeated flares before conception, in those who discontinue useful medications and in women with active glomerulonephritis at conception. It is a challenge to differentiate lupus nephritis from preeclampsia and, in this context, the angiogenic and antiangiogenic cytokines are promising. Prenatal care of pregnant patients with SLE requires close collaboration between rheumatologist and obstetrician. Planning pregnancy is essential to increase the probability of successful pregnancies.

Pregnancy morbidity is one of the clinical manifestations used for classification criteria of antiphospholipid syndrome (APS). During the 14th International Congress on Antiphospholipid Antibodies (aPL), a Task Force with internationally-known experts was created to carry out a critical appraisal of the literature available regarding the association of aPL with obstetric manifestations present in actual classification criteria (recurrent early miscarriage, fetal death, preeclampsia and placental insufficiency) and the quality of the evidence that treatment(s) provide benefit in terms of avoiding recurrent adverse obstetric outcomes. The association of infertility with aPL and the effectiveness of the treatment of patients with infertility and positive aPL was also investigated. This report presents current knowledge and limitations of published studies regarding pregnancy morbidity, infertility and aPL, identifying areas that need better investigative efforts and proposing how critical flaws could be avoided in future studies, as suggested by participants of the Task Force. Except for fetal death, there are limitations in the quality of the data supporting the association of aPL with obstetric complications included in the current APS classification criteria. Recommended treatments for all pregnancy morbidity associated to APS also lack well-designed studies to confirm its efficacy. APL does not seem to be associated with infertility and treatment does not improve the outcomes in infertile patients with aPL. In another section of the Task Force, Dr. Jane Salmon reviewed complement-mediated inflammation in reproductive failure in APS, considering new therapeutic targets to obstetric APS (Ob APS)., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Recurrent early miscarriages (excluding chromosomal anomalies), late fetal loss, and maternal thrombosis are characteristic of obstetric antiphospholipid syndrome (APS). Obstetric complications such as preeclampsia, fetal growth restriction, premature delivery, and fetal death also occur in higher frequency in APS patients than in the general population. A high-risk obstetric center is needed for proper evaluation of and intervention with pregnant women with APS. Association with lupus carries additional risk of thrombosis when antiphospholipid antibodies (aPLs) are present. Gestational results with live births are improved to about 80% when antithrombotic therapy is used, but failure in 20% to 30% of the cases despite correct treatment with low-dose aspirin with or without heparin reveals new pathways for pregnancy loss in APS and unmet needs. At the moment, there is no recommendation to investigate patients with infertility for the presence of aPLs.