Objectives
We assessed the prevalence of potentially inappropriate medication (PIM) among older (≥ 65 years) people living with HIV (O‐PLWH) in the region of Madrid.
Methods
We analysed the ...dispensation registry of community and hospital pharmacies from the Madrid Regional Health Service (SERMAS) for the period between 1 January and 30 June 2017, looking specifically at PIMs according to the 2019 Beers criteria. Co‐medications were classified according to the Anatomical Therapeutic Chemical (ATC) classification system.
Results
A total of 6 636 451 individuals received medications. Of these individuals, 22 945 received antiretrovirals (ARVs), and of these 1292 were O‐PLWH. Overall, 1135 (87.8%) O‐PLWH were taking at least one co‐medication, and polypharmacy (at least five co‐medications) was observed in 852 individuals (65.9%). A PIM was identified in 482 (37.3%) O‐PLWH. Factors independently associated with PIM were polypharmacy adjusted odds ratio (aOR) 7.08; 95% confidence interval (CI) 5.16–9.72 and female sex (aOR 1.75; 95% CI 1.30–2.35). The distribution of PIMs according to ATC drug class were nervous system drugs (n = 369; 28.6%), musculoskeletal system drugs (n = 140; 10.8%), gastrointestinal and metabolism drugs (n = 72; 5.6%), cardiovascular drugs (n = 61; 4.7%), respiratory system drugs (n = 13; 1.0%), antineoplastic and immunomodulating drugs (n = 10; 0.8%), and systemic anti‐infectives (n = 2; 0.2%). Five drugs accounted for 84.8% of the 482O PLWH with PIMs: lorazepam (38.2%), ibuprofen (18.0%), diazepam (10.2%), metoclopramide (9.9%), and zolpidem (8.5%).
Conclusions
Prescription of PIMs is highly prevalent in O‐PLWH. Consistent with data in uninfected elderly people, the most frequently observed PIMs were benzodiazepines and nonsteroidal anti‐inflammatory drugs . Targeted interventions are warranted to reduce inappropriate prescribing and polypharmacy in this vulnerable population.
Summary
The aim of the study was to evaluate whether bacterial translocation (BT) predicts the clinical outcome in HIV/HCV‐coinfected patients with compensated cirrhosis. A cohort of 282 ...HIV/HCV‐coinfected patients with cirrhosis and no previous liver decompensation (LD) was recruited. Serum levels of the DNA sequences encoding the well‐conserved 16S rRNA subunit (16S rDNA), the lipopolysaccharide (LPS) and soluble CD14 (sCD14) at diagnosis of cirrhosis were measured. Primary endpoint was the emergence of the first LD and/or death of any cause. Secondary endpoints were LD, liver‐related death (LRD) and death of any cause. After a median (Q1‐Q3) follow‐up of 51 (27‐72) months, 67 patients (24%; 95% CI: 19‐29) developed their first LD or died during follow‐up. Baseline levels of 16S rDNA, LPS and sCD14 were not associated with the probability of developing the primary endpoint of the study. The mean (SD) survival time free of LD and/or death according to levels of 16S rDNA (<83, 83‐196, 197‐355, >355 copies/μL) was 78 (5), 72 (5), 81 (4) and 82 (4) months, respectively (P = .5). The corresponding figures for LPS (<0.1, 0.1‐0.6, 0.6‐1.5, > 1.5 IU/mL) were 76 (5), 71 (5), 77 (5) and 81 (4) months, respectively (P = .4). Baseline levels of BT serum markers were not associated with any of the secondary endpoints analysed in the study. Thus, BT does not seem to be a relevant predictor of clinical outcome in HIV/HCV‐coinfected patients with compensated cirrhosis.
The main targets for neutralizing anti-hepatitis C virus (HCV) antibodies (HCV-nAbs) are the E1 and E2 envelope glycoproteins. We have studied the characteristics of HCV-nAbs through a retrospective ...study involving 29 HIV/HCV-coinfected patients who achieved sustained virological response (SVR) with peg-IFNα + ribavirin anti-HCV therapy. Plasma samples at baseline and week 24 after SVR were used to perform neutralization assays against five JFH1-based HCV recombinant viruses coding for E1 and E2 from genotypes 1a (H77), 1b (J4), 2a (JFH1), 3a (S52) and 4a (ED43). At baseline, the majority of plasma samples neutralized 1a, 1b, 2a, and 4a, but not 3a, genotypes. Twenty-four weeks following SVR, most neutralizing titers declined substantially. Furthermore, titers against 3a and 2a were not detected in many patients. Plasma samples with high HCV-nAb titers neutralized all genotypes, and the highest titers at the starting point correlated with the highest titers at week 24 after SVR. In conclusion, high titers of broad-spectrum HCV-nAbs were detected in HIV/HCV-coinfected individuals, however, those titers declined soon after SVR.
Bacteremia is an important cause of morbidity and mortality worldwide and, despite the diagnostic and therapeutic advances of the last decades, the evidence supporting many diagnostic aspects of ...bacteremia is scarce. Information on the epidemiological evolution of this entity is limited and many methodological aspects of blood culture collection and analysis are under discussion. Furthermore, the recommendations of the main scientific societies on many of these aspects are variable and, in many cases, have not been updated recently. In this scenario, we have arranged a series of questions on different aspects of bacteremia and reviewed the literature trying to find proper answers for them. We offer our opinion on the topics where the evidence was weak. The topics covered include epidemiological aspects of bacteremia, indications for blood culture extraction, methods for obtaining and incubating samples, or ways of transmitting results from the microbiology laboratory. We do not intend to summarize the current clinical practice guidelines, nor will we deal with the therapeutic management of this entity. The aim of this paper is to review the current perspective on the diagnosis of bacteremia with a critical approach, to point out the gaps in the literature, to offer the opinion of a team dedicated to infectious diseases and clinical microbiology, and to identify some areas of knowledge on which future studies should focus.
The present outbreak of Human Monkeypox (HMPX) that has begun in May 2022 and has spread across all continents in less than two months has qualitative and quantitative characteristics that make it ...different from the pattern of human disease previously caused by this virus. It has spread with enormous ease, affects almost exclusively adults, behaves as a sexually transmitted disease and focuses on very specific groups and transmission conditions. The high incidence in the city of Madrid in males that have sex with males (MSM) has allowed us to observe and report the experience with the first 30 cases diagnosed in our institution. Patients presented with febrile symptoms, genital and paragenital skin lesions reminiscent of smallpox, but less extensive and severe. The disease may also cause proctitis, pharyngitis and perioral lesions. The PCR test for diagnostic confirmation has been shown to be very sensitive and effective, not only in skin lesions but also in blood and other fluids such as pharyngeal, rectal exudates and blood. A very high proportion of patients with HMPX also have other sexually transmitted diseases that must be actively detected in this context. The spontaneous evolution of our patients has been good and hospitalization has been practically unnecessary. Transmission to non-sexual cohabitants and health personnel has been nonexistent and the lesions have disappeared in less than 30 days without leaving sequelae and no need for specific antiviral treatment.
We analysed hepatitis C virus (HCV) reinfection among participants in a prospective registry of HIV/HCV-coinfected patients treated with all-oral direct-acting antiretroviral (DAA)-based therapy in ...the region of Madrid.
An observational cohort study.
The study period started on the date sustained viral response (SVR) was confirmed. The censoring date was 31 December 2017. SVR was defined as negative HCV-RNA 12 weeks after completion of treatment. Reinfection was defined as a positive HCV-RNA test result after achievement of SVR.
Reinfections were detected in 17 of 2359 HIV/HCV-coinfected patients (0.72%) overall, in 12 out of 177 (6.78%) MSM and in five out of 1459 (0.34%) people who inject drugs (PWID). The incidence of reinfection 95% confidence interval (95% CI) per 100 person-years was 0.48 (0.30-0.77) overall, 5.93 (3.37-10.44) for MSM and 0.21 (0.09-0.52) for PWID. Reinfections were detected a median of 15 weeks (interquartile range 13-26) after SVR. In 10 (58.82%) patients, the reinfection was caused by a different HCV genotype. All 12 MSM with reinfection acknowledged unprotected anal intercourse with several partners, seven used chemsex, six reported fisting and four practiced slamming. A concomitant STI was detected in five patients. Four IDU with reinfection reported injecting drugs following SVR.
HCV reinfection is a matter of concern in HIV-positive MSM treated with all-oral DAA therapy in the region of Madrid. Our data suggest that prevention strategies and frequent testing with HCV-RNA should be applied following SVR in MSM who engage in high-risk practices.
Background. Hepatic venous pressure gradient (HVPG) is the best indicator of prognosis in patients with compensated cirrhosis. We compared HVPG and transient elastography (TE) for the prediction of ...liver-related events (LREs) in patients with hepatitis C virus (HCV)–related cirrhosis with or without human immunodeficiency virus (HIV) coinfection. Methods. This was a retrospective review of all consecutive patients with compensated HCV-related cirrhosis who were assessed simultaneously using TE and HVPG between January 2005 and December 2011. We used receiver operating characteristic (ROC) curves to determine the ability of TE and HVPG to predict the first LRE (liver decompensation or hepatocellular carcinoma). Results. The study included 60 patients, 36 of whom were coinfected with HIV. After a median follow-up of 42 months, 6 patients died, 8 experienced liver decompensations, and 7 were diagnosed with hepatocellular carcinoma. The area under the ROC curve (AUROC) of TE and HVPG for prediction of LREs in all patients was 0.85 (95% confidence interval CI, .73–.97) and 0.76 (95% CI, .63–.89) (P = .13); for HIV-infected patients, the AUROC was 0.85 (95% CI, .67–1.00) and 0.81 (95% CI, .64–.97) (P = .57); and for non-HIV-infected patients, the AUROC was 0.88 (95% CI, .75–1.00) and 0.77 (95% CI, .57–.97) (P = .19). Based on the AUROC values, 2 TE cutoff points were chosen to predict the absence (<25 kPa) or presence (≥40 kPa) of LREs, thus enabling correct classification of 82% of patients. Conclusions. Our data suggest that TE is at least as valid as HVPG for predicting LREs in patients with compensated HCV-related cirrhosis with or without concomitant HIV coinfection.
Background and importanceTocilizumab is an anti-human IL-6 receptor monoclonal antibody used in the treatment of cytokine release syndrome in patients with pneumonia associated with coronavirus ...disease. Despite the data from the COVACTA study, tocilizumab continues to be the gold standard for patients in our centre.Aim and objectivesTo describe the use of tocilizumab in the first peak versus the second peak of the SARS-CoV-2 pandemic, and to describe the results of the use of tocilizumab in both situations.Material and methodsAll patients treated with tocilizumab were included in the study periods: first peak (March to June 2020) and second peak (August to the present 2020). Demographic and clinical variables were collected. Data were obtained from the electronic medical records and prescription applications.Results65 patients were included, 36 patients (55.38%) in the first peak versus 29 patients (44.62%) in the second peak.Abstract 4CPS-338 Table 1 1st peak 2nd peak Median age (years) 64.8 63 Sex (n (%)) Women 5 (13.9) 4 (13.8) Men 31 (86.1) 25 (86.2) Diagnosis (n (%)) Bilateral pneumonia 31 (86.1) 23 (79.3) Bilobar pneumonia 4 (11.1) 6 (20.7) No pneumonia 1 (2.8) 0 ICU prescription* (n (%)) 28 (77.7) 8 (27.6) No ICU prescription* (n (%)) 8 (22.2) 21 (72.40) Charlson comorbidity index 3.1 3.1 APACHE (ICU patients) 8.0 10.2 FINE score (n (%)) I 1 (2.8) 5 (17.2) II 11 (30.5) 6 (20.7) III 14 (38.9) 11 (37.9) IV 7 (19.4) 6 (20.7) V 3 (8.3) 1 (3.4) Respiratory support at prescription time (n (%)) 36 (100) 29 (100) Mechanic ventilation (MV) (n (%)) 19 (52.7) 2 (6.7) VMASK (30–60%) (n (%)) 8 (22.2) 9 (31) Nasal cannula (n (%)) 3 (8.3) 7 (24.13) VMASK reservoir (n (%)) 8 (22.2) 10 (34.48) High flow oxygen (n (%)) 0 1 (3.44) PaO2/FiO2 125.8 (n=26) 158.3 (n=22) No distress (n (%)) 0 3 (13.63) Mild (n (%)) 6 (23.1) 5 (22.8) Moderate (n (%)) 5 (19.2) 2 (9.1) Severe (n (%)) 15 (57.7) 12 (54.5) Doses administered (mean) 1.5 1.1 Dose administered (mg) 594.4 545 Mean D-dimer prior to administration (ng/mL) 6401 2436 Mean ferritin prior to administration (ng/mL) 1642 1904 Median PCR prior to administration (mg/L) 346 132 Mean LDH prior to administration (U/L) 538 442 Mean PCT prior to administration (ng/mL) 0.38 0.12 Type of corticoid* (n (%)) Dexamethasone 11 (31.4) 25 (86.2) Methylprednisolone 24 (68.5) 4 (13.8) Concomitant antiviral treatment* (n (%)) None 0 24 (82.8) Remdesivir 0 5 (17.2) Other (lopinavir–ritonavir/hydroxychloroquine/azithromycin) 36 (100) 0 Median days hospitalisation 37 12 Median days ICU 14 9 Deceased day 28 (n (%)) 11 (30.5) 9 (31.0) VM day 28 (n (%)) 2 (5.5) 1 (3.4) Oxygen support day 28 (n (%)) 6 (16.6) 1 (3.4) No oxygen day 28 (n (%)) 2 (5.5) 2 (6.7) Not hospitalised day 28 (n (%)) 15 (41.7) 16 (55.2) *p<0.05Conclusion and relevanceIn the first peak, tocilizumab was prescribed to more serious patients: those admitted to the ICU, with a higher FINE score and needing aggressive support therapy. In addition, it was prescribed in patients with a higher D-dimer. Doses and number of administrations were higher in the first peak. New scientific evidence led to the use of different concomitant treatments in the second peak: corticosteroids (second peak dexamethasone versus first peak methylprednisolone) and antiviral therapy (only remdesivir in the second peak). In the second peak, hospital and ICU stays were shorter, probably because tocilizumab was used in less serious patients. Despite this, no differences in mortality were observed. A study limitation was sample size.References and/or acknowledgementsConflict of interestNo conflict of interest
•We evaluated the changes in the medium-term of a large number of biomarkers in HIV/HCV-patients who achieved SVR.•HIV/HCV-patients showed a slight improvement in the overall profile of immune ...biomarkers after achieving SVR with peg-IFN-α/ribavirin.•It would be necessary to evaluate whether these biomarkers approximate levels in those who never had chronic hepatitis C.
There are a lack of consistency among articles in regards to the evolution of peripheral immune biomarkers after HCV therapy. We aimed to detect the most relevant changes in peripheral immune biomarkers among HIV/HCV-coinfected patients who achieved sustained virologic response (SVR) following peg-IFN-α/ribavirin therapy and to evaluate its normalization with respect to an HIV-monoinfected control group.
We performed a prospective cohort study in 99 HIV/HCV-coinfected patients with samples at baseline (HIV/HCV-b-group) and at week 24 after SVR (HIV/HCV-f-group). We also used a control group of 39 HIV-monoinfected patients (HIV-group) negative for HCV and HBV infections, and who had undetectable HIV viral load and CD4+ >500 cells/mm3. Peripheral T cell subsets were assessed by flow cytometry and plasma biomarkers by immunoassays.
HIV/HCV-coinfected patients had higher values of in IL-10, IL-4, IP-10, IL-8, IL-1β, IL-18, IL-6, IFN-γ, IL-12p70, TNF-α, sVCAM-1, sICAM-1, and sTNFR-1 than HIV control subjects, both at the beginning and at the end of follow-up. Moreover, three biomarkers (CD4+CD38+, telomere length, and IL-1RA) were normalized in relation to the control group at the end of follow-up (the HIV/HCV-b group had higher values and the HIV/HCV-f group had similar values as the HIV-group). Additionally, LPS, IL-2, and IL-17A levels were higher in the HIV/HCV-f group than the HIV-group (24 weeks after SVR). During the follow-up, HIV/HCV-coinfected patients had a significant decrease by the end of follow-up in CD8+CD45RA−CD28+, CD4+CD38+, CD4+CD25+CD127−/low, CD4+CD25+CD127−/low CD45RA−, FABP2, LBP, IP-10, sVCAM1. Only CD4+CD38+ was normalized.
HIV/HCV-patients showed a slight improvement in the overall profile of immune biomarkers after achieving SVR.
Advanced cirrhosis is related to alterations in immunity. We aimed to evaluate the levels of peripheral CD4⁺ T cells (Tregs) and plasma cytokine in patients coinfected with human immunodeficiency ...virus and hepatitis C virus (HIV/HCV) according to liver fibrosis stages evaluated as liver stiffness measure (LSM) and their linear relationship.
We performed a cross-sectional study on 238 HIV/HCV-coinfected patients (119 had <12.5 kPa, 73 had 12.5⁻25 kPa, and 46 had >25 kPa). Peripheral T-cell subsets were phenotyped by flow cytometry, plasma biomarkers were assessed by multiplex immunoassays, and LSM was assessed by transient elastography. Results
We found HIV/HCV-coinfected patients had higher values of CD4⁺ Tregs (
< 0.001), memory Tregs (
≤ 0.001), and plasma cytokine levels IFN-γ (
≤ 0.05) and IL-10 (
≤ 0.01) compared with healthy donors and HIV-monoinfected patients. In the multivariate analysis, higher LSM values were associated with reduced levels of IL-10 (adjusted arithmetic mean ratio (aAMR) = 0.83;
= 0.019), IL-2 (aAMR = 0.78;
= 0.017), TNF-α (aAMR = 0.67;
< 0.001), and IL-17A (aAMR = 0.75;
= 0.006). When we focus on HIV/HCV-coinfected patients analyzed by LSM strata, patients with ≥25 kPa had lower values of IL-2 (aAMR = 0.66;
= 0.021), TNF-α (aAMR = 0.565;
= 0.003), and IL-17A (aAMR = 0.58;
= 0.003) than patients with <12.5 kPa.
HIV/HCV-coinfected patients showed an immunosuppressive profile compared to healthy controls and HIV-monoinfected patients. Additionally, HIV/HCV-coinfected patients with advanced cirrhosis (LSM ≥ 25 kPa) had the lowest plasma values of cytokines related to Th1 (IL-2 and TNF-α) and Th17 (IL-17A) response.
PDF
