SARS-CoV-2 anti-spike antibodies after a fourth dose of COVID-19 vaccine in adult solid-organ transplant recipients.

BACKGROUND: A fourth dose of SARS-CoV-2 vaccine is recommended in solid-organ transplant (SOT) recipients, but the immunogenicity is poorly known. METHODS: We conducted a retrospective, observational, monocentric study between the 1st January 2021 and 31st March 2022 of the anti-Spike antibody titers after one to four doses of vaccine in SOT. RESULTS: 825 SOT were included. Median age at first vaccine injection was 61.2 (IQR 50.9-69.3) years; 66.7 % were male; 63.4 % had received four vaccine doses. The proportion of participants with a strong humoral response (>260 BAU/mL) increased with the number of vaccine doses: 10.6 % after the 1st dose (D1), 35.1 % after the 2nd (D2), 48.5 % after the 3rd (D3), and 65.1 % after the 4th (D4) (p < 0.001). Among the tested patients, the proportion with a detectable humoral response was significantly higher after D4 than after D3 (47 % vs 22 %, p = 0.01). Liver transplant recipients had more frequently a strong humoral response after D2, D3 and D4 (OR = 5.3, 3.7 and 6.6 respectively when compared with other organ transplant recipients, p < 0.001). In kidney transplant recipients, belatacept-containing regimen was associated with a lower rate of detectable humoral (9 % vs 40 %, p = 0.025) after D3, but there was no statistical difference after D4. CONCLUSION: A fourth dose should be proposed to SOT recipients who did not developed an immune response after 3 doses. Kidney transplant recipients receiving belatacept have a poorer, although frequently detectable response.

Dalbavancin in clinical practice: a particular place for the elderly?

We investigate dalbavancin efficiency and tolerance among elderly in Grenoble-Alpes 32 university hospital. Among the 65 patients who received dalbavancin, 51% (33) were considered as old. Patients presented mainly bones and joint infections (52%), surgical site infection 34 (31%), and infective endocarditis (IE) (8%). Clinical cure was confirmed for 79% of old 35 patients at 1, 3, and 6 months. Six adverse events (9%) were reported after 36 dalbavancin's administration, but each time in combination with other antibiotics. 37 Dalbavancin had a significant effectiveness and safety profile and represents a real 38 therapeutic option in the management of deep and complex infections of elderly patients.

Substance use disorders and suicidality in youth: A systematic review and meta-analysis with a focus on the direction of the association.

BACKGROUND: Reviews and meta-analyses suggest that substance use and suicidality (i.e., suicidal ideations and attempts) are associated in youth, but the direction of this association remains unclear. Theoretically, the secondary psychiatric disorder hypothesis (SPDH) posits that substance use leads to suicidality, while the secondary substance use disorder hypothesis (SSUDH) posits that suicidality leads to substance use. To clarify these associations, this meta-analysis systematically reviewed studies that examined the prospective associations between SUDs and suicidality in youth (age 25 and younger) and compared results according to the direction of the association. METHODS: Web of Science, Embase, PsycINFO, PubMed, Medline and ProQuest Dissertations & Theses Global were searched from inception to March 8, 2020, and 55 effect sizes from 23 samples were included and analyzed using a three-level meta-analysis. RESULTS: SUDs significantly predicted subsequent suicidality (OR = 2.16, 95%CI 1.57-2.97), suicidality significantly predicted subsequent SUDs (OR = 2.16, 95%CI 1.53-3.04), and these effect sizes did not differ (p = 0.49). CONCLUSIONS: Considering that 65% of reviewed studies only examined the SPDH, this review highlights that more attention should be given to the SSUDH, and that studies should examine bidirectional associations between SUDs and suicidality across time. Clinically, because SUDs and suicidality were found to influence each other, results suggest that mental health and SUDs should ideally be detected and treated early, and that co-occurring disorders should be assessed and treated concomitantly.

Ultradeep sequencing of B and non-B HIV-1 subtypes: Viral diversity and drug resistance mutations before and after one month of antiretroviral therapy in naive patients.

BACKGROUND: Ultradeep pyrosequencing technologies permit an assessment of the genetic diversity and the presence and frequency of minority variants in a viral population. The effect of these parameters on the outcome of highly active antiretroviral therapy (HAART) in HIV-infected patients is poorly understood. OBJECTIVES: The present study used the pyrosequencing Roche 454 prototype assay to determine whether antiretroviral efficacy is correlated with viral diversity and minority drug resistance mutations in HIV-infected treatment-naive patients and to compare assay performance in B and non-B subtypes. STUDY DESIGN: The study included 30 HIV-1 infected naive patients (20 with subtype non-B and 10 with subtype B). Ultradeep pyrosequencing of protease and reverse transcriptase genes was performed at baseline and 1 month after HAART initiation. Plasma HIV VL was measured at 0 and after 1, 3, and 6 months of HAART. RESULTS: Pre-HAART minority drug resistance mutations were observed to NRTI in 4 patients, to NNRTI in 6 patients, and to PI in 1 patient; there was no difference in HAART-induced VL decay between patients. Pre-HAART diversity was significantly correlated with the time elapsed since HIV-1 infection diagnosis, but not with the subtype, VL, or CD4 count. Patients with an undetectable VL after 3 months of HAART had a higher pre-HAART diversity. Pre- and post-HAART diversities were not statistically different. There was no difference in assay performance between subtype B and non-B. CONCLUSIONS: A high pre-HAART viral diversity might have a positive effect on the outcome of HAART. Pre-therapeutic minority drug resistance mutations are uncommon in naive patients.

[Role and mission of health service access points]. / Rôle et mission des permanences d'accès aux soins de santé.

Part of the health and social care landscape since 1998, health service access points (in French, permanences d'accès aux soins de santé) were set up in response to a health and social care problem. The objective is to help disadvantaged people integrate the healthcare pathway. The ultimate aim is to ensure everyone has access to the appropriate care at a fair price.

Performance of an antigen-antibody combined assay for hepatitis C virus testing without venipuncture.

BACKGROUND: Hepatitis C virus (HCV) is underdiagnosed and therefore increasing the opportunities for HCV testing without venipuncture may be useful. OBJECTIVES: We evaluated the analytical performance of a modified, commercially available, combined HCV antigen-antibody assay (cEIA) (Monolisa(®) HCV-Ag-Ab-ULTRA) and a commercially available point-of-care (POC) device (OraQuick(®) HCV) on fingerstick blood (FSB) and oral mucosal transudate (OMT). STUDY DESIGN: FSB, OMT and serum samples were collected from 113 cases of HCV-antibody-positive patients and 88 HCV-antibody-negative controls. The HCV-antibody-positive group included 63 patients with quantifiable HCV-RNA (56%) and 17 HIV/HCV co-infected patients (15%). FSB and OMT specimens were collected as dried blood spots (DBSs) or with the OraSure collection system, before testing with cEIA. RESULTS: With FSB specimens, the cEIA and the POC device exhibited 100% specificity and 98.2% and 97.4% sensitivity, respectively. The specificity of the cEIA in FSB sharply decreased if stored 3days at room temperature. With OMT specimens, the cEIA sensitivity (71.7%) and specificity (94.3%) were significantly lower than the performance of OraQuick(®) HCV (sensitivity, 94.6%; specificity, 100%). The optical densities obtained with the cEIA in FSB and OMT were lower in HIV/HCV co-infected patients compared with HCV monoinfected patients. CONCLUSION: The cEIA using FSB specimens collected on DBSs preserved in appropriate storage conditions was a reliable alternative, equivalent to the POC assay, for HCV testing without venipuncture. The cEIA was not adapted for HCV testing on OMT.

[HIV infection and diabetes: experience and quality of life in patients with two chronic diseases]. / Infection par le virus de l'immunodéficience humaine et diabète: vécu et qualité de vie des patients confrontés à deux maladies chroniques.

OBJECTIVES: Diabetes mellitus is frequently associated with HIV infection but there's only limited evidence regarding the control and impact of this co-morbidity. This study aimed to estimate the prevalence of diabetes, compliance with treatment, perception and quality of life of HIV patients with diabetes. METHODS: We conducted a cross-sectional study among patients treated for diabetes and registered in the DMI2 databasis in a French university hospital in January 2010. Clinical assessment and follow-up data were collected using chart review and self-administered questionnaires. Quality of life (MOS SF-12) and compliance with treatment (simplified medication adherence questionnaire) were assessed using validated scales. RESULTS: The prevalence of treated diabetes mellitus was 3.9% (29/748, 95% confidence interval, 2.6% to 5.5%). Among these 29 HIV diabetic patients, 93% had a virologic control of HIV infection while only 22% had well-controlled diabetes. Ninety-six percent of patients were scared to die from HIV-which was rated as the main pathology-compared with 71% of patients for diabetes. The mean score for physical quality of life was 43.1 (13.2), which was lower than estimates for overall population. Non-compliance with treatment was reported for 35% of patients. DISCUSSION: Although anti-retroviral treatments turned HIV infection into a chronic disease, patient perception was not altered. This study shows a better control of HIV infection than diabetes. We have to find out ways (e.g. patient education programs, annual multidisciplinary consultation...) to give the patient a global feel for his health thereby improving prognosis and quality of life.

[Metabolic abnormalities, lipodystrophy and cardiovascular risk in HIV-infected patients]. / Troubles métaboliques, risque vasculaire, lipodystrophie chez le patient infecté par le VIH.

Life expectancy of HIV-infected patients has improved considerably with HAART. However long term use of HAART is linked with lipodystrophy syndrom (subcutaneous lipoatrophy and central fat accumulation) associated with dyslipemia (hypoHDL, hyperLDL and hypertriglyceridemia) and insulin resistance. It is also linked with mitochondrial toxicity clinically expressed by chronic fatigue syndrom and premature aging. The induced metabolic syndrom has cardiovascular consequences and myocardial infarction is the cause of 7% of the HIV-infected deaths in 2000. Assessment of these complications should be done at least every year. Treatment options concern antiretroviral therapy with the search for the least toxic drug (but with equal antiviral efficacy), symptomatic treatment (statin, fibrates, thiazolidinediones, metformin) and lifestyle modifications (first of all, stopping cigarette smoking!)