scholarly journals CCR5 Blockade in Inflammatory PML and PML-IRIS Associated With Chronic Inflammatory Diseases' Treatments

2021 ◽  
Vol 9 (1) ◽  
pp. e1097
Author(s):  
Raphael Bernard-Valnet ◽  
Xavier Moisset ◽  
Nicolas Maubeuge ◽  
Mathilde Lefebvre ◽  
Jean-Christophe Ouallet ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Immune Reconstitution ◽  
Adjusted Odds Ratio ◽  
Inflammatory Diseases ◽  
Case Reports ◽  
Treatment Withdrawal ◽  
University Hospitals ◽  
Chronic Inflammatory Diseases ◽  
Ccr5 Blockade ◽  
Clinical Worsening

Background and ObjectivesProgressive multifocal leukoencephalopathy (PML) is a disabling neurologic disorder resulting from the infection of the CNS by JC polyomavirus in immunocompromised individuals. For the last 2 decades, increasing use of immunotherapies leads to iatrogenic PML. Iatrogenic PML is often associated with signs of inflammation at onset (inflammatory PML) and/or after treatment withdrawal immune reconstitution inflammatory syndrome (PML-IRIS). Although immune reconstitution is a key element for viral clearance, it may also be harmful and induce clinical worsening. A C-C chemokine receptor type 5 (CCR5) antagonist (maraviroc) has been proposed to prevent and/or limit the deleterious immune responses underlying PML-IRIS. However, the data to support its use remain scarce and disputed.MethodsWe conducted a multicenter retrospective cohort study at 8 university hospitals in France and Switzerland by collecting clinical, biological, and radiologic data of patients who developed inflammatory PML (iPML) or PML-IRIS related to immunosuppressive therapies used for chronic inflammatory diseases between 2010 and 2020. We added to this cohort, a meta-analysis of individual case reports of patients with iPML/PML-IRIS treated with maraviroc published up to 2021.ResultsOverall, 27 cases were identified in the cohort and 9 from the literature. Among them, 27 met the inclusion criteria: 16 treated with maraviroc and 11 with standard of care (including corticosteroids use). Most cases were related to MS (92.6%) and natalizumab (88%). Inflammatory features (iPML) were present at onset in 12 patients (44.4%), and most patients (92.6%) received corticosteroids within the course of PML. Aggravation due to PML-IRIS was not prevented by maraviroc compared with patients who received only corticosteroids (adjusted odds ratio: 0.408, 95% CI: 0.06–2.63). Similarly, maraviroc did not influence time to clinical worsening due to PML-IRIS (adjusted hazard ratio = 0.529, 95% CI: 0.14–2.0) or disability at the last follow-up (adjusted odds ratio: 2, 95% CI: 0.23–17.3).DiscussionThe use of CCR5 blockade did not help to keep deleterious immune reconstitution in check even when associated with corticosteroids. Despite maraviroc's reassuring safety profile, this study does not support its use in iPML/PML-IRIS.Classification of EvidenceThis study provides Class IV evidence showing that adding maraviroc to the management of iatrogenic iPML/PML-IRIS does not improve the outcome.

A Multicenter Case-Control Prospective Study to Assess the Risk of Immune Thrombocytopenia (ITP) Associated with Vaccines in Adults Using the PGRx-ITP Registry

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1169-1169 ◽  
Author(s):  
Lamiae Grimaldi-Bensouda ◽  
Marc Michel ◽  
Jean-François Viallard ◽  
Daniel Adoue ◽  
Nadine Magy-Bertrand ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Odds Ratio ◽  
Immune Thrombocytopenia ◽  
Index Date ◽  
Adjusted Odds Ratio ◽  
Time Window ◽  
Case Reports ◽  
Secondary Analysis ◽  
Case Control ◽  
Research Fellowship

Abstract Abstract 1169 Background and objectives Immune thrombocytopenia (ITP) is thought to result from an autoimmune mechanism, and some case-reports have suggested that immunizations could be involved and trigger the autoimmune process. This prospective multicenter case-control study investigated for the first time associations between ITP and vaccination in adults, particularly between ITP and influenza vaccinations. Methods Over a three year period, a network of 15 physicians from hematology and internal medicine referral centers across France recruited newly diagnosed cases of primary ITP in patients aged over 15 years fulfilling the ITP standardized criteria of the American Society of Hematology. Recruiting physicians completed standardized forms for each patient and every patient underwent a standardized 1 hour-interview focused on previous medications and vaccinations in the last 12 months. Incident ITP cases were compared to sex and age-matched controls selected and recruited from general practice settings, also from the same geographically areas of France. The method of referent recruitment has been described elsewhere (Grimaldi-Bensouda et al. 2010 Pharmacoepidemiol Drug Saf 2010;19(6):591–5). Controls were also interviewed in the same standardized way as cases. Cases and control were compared in respect of various descriptive factors and potential risk factors for ITP. Written or other confirmation of vaccinations was sought from both the patient and his/her physician. The time window defining exposure to vaccines was 12 months before the index date. In secondary analysis, the most prevalent vaccines in adults were analyzed. Results Two hundred and twenty four cases fulfilling the inclusion criteria and 4412 were included in the study. Seventy eight of the 224 cases (34.8%) and 1566 of 4412 controls (35.5%) received a vaccination within this time window [adjusted odds ratio 0.97, 95% confidence interval 0.70–1.33]. Twenty percent of the cases and 26% of controls received an influenza vaccine [adjusted odds ratio 0.66, 95% confidence interval 0.45–0.98]. Other prevalent vaccines in adult are currently under study. Conclusions This systematic case-control design is well-suited to study rare disorders such as ITP and few such studies have been conducted. Another advantage was the minimization of recall bias because questions about vaccinations were included in a standardized interview focusing on exposure to all medications. When all vaccines were considered, we found no association between vaccination and the incidence of ITP in either crude or adjusted analyses. Moreover, cases were less likely than controls to have been vaccinated against influenza in the 12 months before the index date. Disclosures: Grimaldi-Bensouda: LA-SER: Employment; INSERM: I was the recipient of a research fellowship from the INSERM (French National Institute for Health and Medical Research) at the time of the study. Leighton:LA-SER Europe Ltd: Employment. Aubrun:LA-SER Europe Ltd: Employment. Abenhaim:LA-SER Europe Ltd: I'm a stock owner and chairman of LA-SER, the company conducting the study.

scholarly journals Ocular and Mucocutaneous Sequelae among Survivors of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Togo

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Bayaki Saka ◽  
Abla Séfako Akakpo ◽  
Julienne Noude Teclessou ◽  
Garba Mahamadou ◽  
Abas Mouhari-Toure ◽  
...  
Keyword(s):  
Risk Factors ◽  
Medical Records ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Late Complications ◽  
Acute Stage ◽  
Stevens Johnson Syndrome ◽  
Ocular Involvement ◽  
University Hospitals ◽  
Retrospective Assessment

Aim. The aim of this study was to assess ocular and mucocutaneous sequelae among SJS/TEN survivors and identify risk factors of ocular sequelae. Patients and Method. Late complications among SJS/TEN survivors were assessed using 2 methods: a retrospective assessment of medical records only or a retrospective assessment of medical records and physical examination of survivors who were contacted by phone. Results. Between January 1995 and December 2017, 177 cases of SJS/TEN (138 cases of SJS, 29 cases of TEN, and 10 cases SJS/TEN overlap) were admitted into two university hospitals of Lomé (Togo). There were 113 women and 64 men, with an average age of 31.7±13.0 years (range: 5 to 80 years). The most used drugs were antibacterial sulfonamides (35.6%) and nevirapine (24.3%). HIV serology was positive in 68 (59.1%) of the 115 patients tested. Sixty-four (52,5%) of the 122 patients, who had been examined by an ophthalmologist during the acute stage, had acute ocular involvement, which was mild in 27.9% of patients, moderate in 13.1%, and severe in 11.5%. We recorded 17 deaths (i.e., three cases of SJS, 12 of TEN, and two of SJS/TEN overlap), including 11 cases of HIV infected patients. Of the 160 SJS/TEN survivors, only 71 patients were assessed 6 months after hospital discharge. Among them, forty-three (60.6%) patients had sequelae. Concerning mucocutaneous sequelae, the main lesions were diffuse dyschromic macules (38.0% of patients) and ocular sequelae were dominated by decreased visual acuity (14.1% of patients). In multivariate analysis, exposure to sulfadoxine (odds adjusted ratio = 5.95; 95%CI= [1.36-31.35]) and moderate (adjusted odds ratio = 5.85; 95%CI = [1.23-31.81]) or severe (adjusted odds ratio = 48.30; 95%CI = [6.25-1063.66]) ocular involvement at acute stage were associated with ocular sequelae. Conclusion. Ocular and mucocutaneous sequelae are common in SJS/TEN survivors. Exposure to sulfadoxine and severity of acute ocular involvement are risk factors of ocular sequelae.

Chronic Inflammatory Diseases: Progress and Prospect with Herbal Medicine

2015 ◽  
Vol 22 (2) ◽  
pp. 247-264 ◽  
Author(s):  
Nilanjan Ghosh ◽  
Asif Ali ◽  
Rituparna Ghosh ◽  
Shaileyee Das ◽  
Subhash C. Mandal ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Diseases

Exploiting Anti-Inflammation Effects of Flavonoids in Chronic Inflammatory Diseases

2020 ◽  
Vol 26 (22) ◽  
pp. 2610-2619 ◽  
Author(s):  
Tarique Hussain ◽  
Ghulam Murtaza ◽  
Huansheng Yang ◽  
Muhammad S. Kalhoro ◽  
Dildar H. Kalhoro
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Cellular Level ◽  
Antiinflammatory Drugs ◽  
Suitable Alternative ◽  
Chronic Inflammatory Diseases

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

Comparison of Clinical Outcomes of Persons Living With HIV by Enrollment Status in Washington, DC: Evaluation of a Large Longitudinal HIV Cohort Study (Preprint)

2019 ◽  
Author(s):  
Jenevieve Opoku ◽  
Rupali K Doshi ◽  
Amanda D Castel ◽  
Ian Sorensen ◽  
Michael Horberg ◽  
...  
Keyword(s):  
Cohort Study ◽  
Health Outcomes ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Hiv Care ◽  
Disease Stage ◽  
People Living With Hiv ◽  
Hiv Disease ◽  
Persons Living With Hiv ◽  
Living With Hiv

BACKGROUND HIV cohort studies have been used to assess health outcomes and inform the care and treatment of people living with HIV disease. However, there may be similarities and differences between cohort participants and the general population from which they are drawn. OBJECTIVE The objective of this analysis was to compare people living with HIV who have and have not been enrolled in the DC Cohort study and assess whether participants are a representative citywide sample of people living with HIV in the District of Columbia (DC). METHODS Data from the DC Health (DCDOH) HIV surveillance system and the DC Cohort study were matched to identify people living with HIV who were DC residents and had consented for the study by the end of 2016. Analysis was performed to identify differences between DC Cohort and noncohort participants by demographics and comorbid conditions. HIV disease stage, receipt of care, and viral suppression were evaluated. Adjusted logistic regression assessed correlates of health outcomes between the two groups. RESULTS There were 12,964 known people living with HIV in DC at the end of 2016, of which 40.1% were DC Cohort participants. Compared with nonparticipants, participants were less likely to be male (68.0% vs 74.9%, <i>P</i>&lt;.001) but more likely to be black (82.3% vs 69.5%, <i>P</i>&lt;.001) and have a heterosexual contact HIV transmission risk (30.3% vs 25.9%, <i>P</i>&lt;.001). DC Cohort participants were also more likely to have ever been diagnosed with stage 3 HIV disease (59.6% vs 47.0%, <i>P</i>&lt;.001), have a CD4 &lt;200 cells/µL in 2017 (6.2% vs 4.6%, <i>P</i>&lt;.001), be retained in any HIV care in 2017 (72.9% vs 59.4%, <i>P</i>&lt;.001), and be virally suppressed in 2017. After adjusting for demographics, DC Cohort participants were significantly more likely to have received care in 2017 (adjusted odds ratio 1.8, 95% CI 1.70-2.00) and to have ever been virally suppressed (adjusted odds ratio 1.3, 95% CI 1.20-1.40). CONCLUSIONS These data have important implications when assessing the representativeness of patients enrolled in clinic-based cohorts compared with the DC-area general HIV population. As participants continue to enroll in the DC Cohort study, ongoing assessment of representativeness will be required.

scholarly journals Gamma models for estimating the odds ratio for a skewed biomarker measured in pools and subject to errors

Biostatistics ◽  
2019 ◽  
Author(s):  
Dane R Van Domelen ◽  
Emily M Mitchell ◽  
Neil J Perkins ◽  
Enrique F Schisterman ◽  
Amita K Manatunga ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Lower Cost ◽  
Cost Effective ◽  
Ratio Estimation ◽  
Statistical Efficiency ◽  
Function Model ◽  
Processing Error ◽  
Wide Range ◽  
Pooled Samples

SUMMARYMeasuring a biomarker in pooled samples from multiple cases or controls can lead to cost-effective estimation of a covariate-adjusted odds ratio, particularly for expensive assays. But pooled measurements may be affected by assay-related measurement error (ME) and/or pooling-related processing error (PE), which can induce bias if ignored. Building on recently developed methods for a normal biomarker subject to additive errors, we present two related estimators for a right-skewed biomarker subject to multiplicative errors: one based on logistic regression and the other based on a Gamma discriminant function model. Applied to a reproductive health dataset with a right-skewed cytokine measured in pools of size 1 and 2, both methods suggest no association with spontaneous abortion. The fitted models indicate little ME but fairly severe PE, the latter of which is much too large to ignore. Simulations mimicking these data with a non-unity odds ratio confirm validity of the estimators and illustrate how PE can detract from pooling-related gains in statistical efficiency. These methods address a key issue associated with the homogeneous pools study design and should facilitate valid odds ratio estimation at a lower cost in a wide range of scenarios.

scholarly journals Sex modulates the association of radial artery augmentation index with renal function decline in individuals without chronic kidney disease

2021 ◽  
Author(s):  
Qiao Qin ◽  
Fangfang Fan ◽  
Jia Jia ◽  
Yan Zhang ◽  
Bo Zheng
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Arterial Stiffness ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Augmentation Index ◽  
Renal Function Decline

Abstract Purpose An increase in arterial stiffness is associated with rapid renal function decline (RFD) in patients with chronic kidney disease (CKD). The aim of this study was to investigate whether the radial augmentation index (rAI), a surrogate marker of arterial stiffness, affects RFD in individuals without CKD. Methods A total of 3165 Chinese participants from an atherosclerosis cohort with estimated glomerular filtration rates (eGFR) of ≥ 60 mL/min/1.73 m2 were included in this study. The baseline rAI normalized to a heart rate of 75 beats/min (rAIp75) was obtained using an arterial applanation tonometry probe. The eGFRs at both baseline and follow-up were calculated using the equation derived from the Chronic Kidney Disease Epidemiology Collaboration. The association of the rAIp75 with RFD (defined as a drop in the eGFR category accompanied by a ≥ 25% drop in eGFR from baseline or a sustained decline in eGFR of > 5 mL/min/1.73 m2/year) was evaluated using the multivariate regression model. Results During the 2.35-year follow-up, the incidence of RFD was 7.30%. The rAIp75 had no statistically independent association with RFD after adjustment for possible confounders (adjusted odds ratio = 1.12, 95% confidence interval: 0.99–1.27, p = 0.074). When stratified according to sex, the rAIp75 was significantly associated with RFD in women, but not in men (adjusted odds ratio and 95% confidence interval: 1.23[1.06–1.43], p = 0.007 for women, 0.94[0.76–1.16], p = 0.542 for men; p for interaction = 0.038). Conclusion The rAI might help screen for those at high risk of early rapid RFD in women without CKD.

scholarly journals Epidemiology of hypertension in selected towns of Wollega zones, Western Ethiopia, 2019: A community-based cross-sectional study

2021 ◽  
Vol 9 ◽  
pp. 205031212110245
Author(s):  
Getu Mosisa ◽  
Bikila Regassa ◽  
Bayise Biru
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Alcohol Consumption ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Cross Sectional Study ◽  
Care Providers ◽  
Sectional Study ◽  
Community Based ◽  
Cross Sectional

Introduction: Hypertension remains an emerging public health problem globally, particularly in developing countries. Age, income level, obesity, alcohol consumption, smoking, vegetables and fruit consumption, physical activity and chat chewing were some risk factors of hypertension. However, there are limited data on the epidemiology of hypertension in Ethiopia. This study aimed to assess Epidemiology of Hypertension among the community of selected towns of Wollega zones. Methods: A community-based cross-sectional study was conducted from 1 to 30 June 2019 in selected towns of Wollega zones. A multistage sampling technique was used to select 840 study participants. Data were collected using the WHO STEP wise approach. The data were coded and entered into EpiData 3, and exported to SPSS version 20.0 for analysis. Bivariate and multivariable logistic regression analyses were conducted. Statistical significance was declared at p-value < 0.05. Results: The study included a total of 838 respondents with a response rate of 99.7%. The prevalence of hypertension was found to be 189 (22.6%) (95% confidence interval = 19.9%–25.2%). Of this, 108 (12.9%) and 81 (9.7%) of female and male were hypertensive, respectively. Age groups of 30–44 years (adjusted odds ratio = 2.65 (1.43, 4.89)), 45–59 years (adjusted odds ratio = 3.55 (1.79, 7.04)), above 60 years (adjusted odds ratio = 2.97 (1.43, 6.18)), having history of alcohol consumption (adjusted odds ratio = 4.29 (2.4, 7.66)), involving in vigorous physical activity (adjusted odds ratio = 0.096 (0.028, 0.33)), not walking to and from the work (adjusted odds ratio = 13.12 (8.34, 20.67)), being overweight (adjusted odds ratio = 1.98 (1.21, 3.25)), inadequate fruits serving per day (adjusted odds ratio = 2.93 (1.75, 4.88)) were significantly associated with hypertension. Conclusion: The prevalence of hypertension was found to be high in the study area. Older age, alcohol consumption, not engaging in vigorous activity, physical inactivity, being overweight and inadequate intake of fruits were found to be risk factors for hypertension. Therefore, health care providers should provide extensive health education and promotion on recommended lifestyle modification to tackle the burden of hypertension.

scholarly journals Pulmonary restriction predicts long-term pulmonary impairment in people with HIV and tuberculosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sara C. Auld ◽  
Hardy Kornfeld ◽  
Pholo Maenetje ◽  
Mandla Mlotshwa ◽  
William Chase ◽  
...  
Keyword(s):  
Lung Function ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Logistic Regression Models ◽  
Pulmonary Impairment ◽  
Mixed Pattern

Abstract Background While tuberculosis is considered a risk factor for chronic obstructive pulmonary disease, a restrictive pattern of pulmonary impairment may actually be more common among tuberculosis survivors. We aimed to determine the nature of pulmonary impairment before and after treatment among people with HIV and tuberculosis and identify risk factors for long-term impairment. Methods In this prospective cohort study conducted in South Africa, we enrolled adults newly diagnosed with HIV and tuberculosis who were initiating antiretroviral therapy and tuberculosis treatment. We measured lung function and symptoms at baseline, 6, and 12 months. We compared participants with and without pulmonary impairment and constructed logistic regression models to identify characteristics associated with pulmonary impairment. Results Among 134 participants with a median CD4 count of 110 cells/μl, 112 (83%) completed baseline spirometry at which time 32 (29%) had restriction, 13 (12%) had obstruction, and 9 (7%) had a mixed pattern. Lung function was dynamic over time and 30 (33%) participants had impaired lung function at 12 months. Baseline restriction was associated with greater symptoms and with long-term pulmonary impairment (adjusted odds ratio 5.44, 95% confidence interval 1.16–25.45), while baseline obstruction was not (adjusted odds ratio 1.95, 95% confidence interval 0.28–13.78). Conclusions In this cohort of people with HIV and tuberculosis, restriction was the most common, symptomatic, and persistent pattern of pulmonary impairment. These data can help to raise awareness among clinicians about the heterogeneity of post-tuberculosis pulmonary impairment, and highlight the need for further research into mediators of lung injury in this vulnerable population.

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