Transgender women sex workers (TGW-SW) are disproportionally affected by HIV and have reduced access to testing. Moreover, information regarding their behaviours and health needs is scarce.
A ...behavioural survey and a targeted testing programme in prostitution sites were conducted in Milan and Monza areas. The non-profit organisation 'ALA Milano Onlus' and 'San Gerardo' Hospital (Monza) implemented a mobile HIV testing unit involving a TGW peer educator, four physicians, a counsellor, a psychologist and a cultural mediator. All TGW-SW were offered anonymous HIV and hepatitis C virus (HCV) oral testing and asked to fill a questionnaire on sexual habits, drug abuse, and knowledge and attitudes towards HIV and STDs.
Between May and July 2017, 130 TGW-SW, predominantly migrants, were contacted during 15 street visits; among them, 78 (60%) were interviewed. HIV and HCV testing were accepted by 53 (42%) and 67 (52%) TGW-SW, respectively. Twenty-five (19.8%) subjects who reported already established HIV infection were not retested. Seven patients received a new diagnosis of HIV, while nobody tested positive for HCV. Overall, HIV prevalence was 13.2% (25% including those with already known HIV infection). Recent arrival in Italy and young age were associated with risk of undiagnosed HIV infection. Inconsistent condom use was commonly reported during commercial sex (27%) and with non-commercial partners (64%). Alcohol and cocaine abuse were common problems which facilitated risky behaviours.
Oral rapid HIV and HCV testing for TGW-SW in outreach settings were feasible and acceptable and led to a considerable number of new diagnoses. Interventions tailored to TGW-SW, focused on HIV prevention, testing and engagement in care, are fundamental.
Data regarding CD4+ recovery after switching from protease inhibitor (PI)-based regimens to regimens not containing PI are scarce.
Subjects with virological success on first-PI-regimens who switched ...to NNRTI therapy (NNRTI group) or to nucleoside reverse transcriptase (NRTI)-only (NRTI group) were studied. The effect of the switch on the ongoing CD4+ trend was assessed by two-phase linear regression (TPLR), allowing us to evaluate whether a change in the CD4+ trend (hinge) occurred and the time of its occurrence. Furthermore, we described the evolution of the frequencies in CD4-count classes across four relevant time-points (baseline, before and immediately after the switch, and last visit). Finally, we explored whether the CD4+ counts evolved differently in patients who switched to NNRTI or NRTI-only regimens by considering: the overall CD4+ trends, the time to CD4+≥ 500/mm3 after the switch, and the area-under-the-curve (AUC) of the CD4+ after the switch.
Eight hundred and ninety-six patients, followed for a median of 2,121 days, were included. At TPLR, hinges occurred in 581/844 (68.9%), but in only 40/581 (6.9%) within a time interval (180 days) compatible with a possible relationship to the switch; furthermore, in 19/40 cases, CD4+ counts appeared to decrease after the hinges. In comparison with the NNRTI group, the NRTI group showed CD4+ count greater at baseline (P = 0.0234) and before the switch (P ≤ 0.0001), superior CD4+ T-cell increases after HAART was started, lower probability of not achieving CD4+ ≥ 500/mm3 (P = 0.0024), and, finally, no significant differences in the CD4+ T-cell AUC after the switch after adjusting for possible confounders (propensity score and pre-switch AUC). Persistence at CD4+ < 200/mm3 was observed in 34/435 (7.5%) patients, and a decrease below this level was found in only 10/259 (3.9%) with baseline CD4+ ≥ 350/mm3.
Switching from first-line PI to NNRTI- or NRTI-based regimens did not seem to impair CD4+ trend over long-term follow-up. Although the greater CD4+ increases in patients who switched to the NRTI-only regimen was due to higher CD4+ counts before the switch, several statistical analyses consistently showed that switching to this regimen did not damage the ongoing immune-reconstitution. Lastly, the observation that CD4+ T-cell counts remained low or decreased in the long term despite virological success merits further investigation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Grafting molecular precursors on partially dehydroxylated silica followed by a thermal treatment yields silica-supported M(III) sites for a broad range of metals. They display unique properties such ...as high activity in olefin polymerization and alkane dehydrogenation (M = Cr) or efficient luminescence properties (M = Yb and Eu) essential for bioimaging. Here, we interrogate the local structure of the M(III) surface sites obtained from two molecular precursors, amides M(N(SiMe3)2)3 vs siloxides (M(OSi(OtBu)3)3·L with L = (THF)2 or HOSi(OtBu)3 for M = Cr, Yb, Eu, and Y, by a combination of advanced spectroscopic techniques (EPR, IR, XAS, UV–vis, NMR, luminescence spectroscopies). For paramagnetic Cr(III), EPR (HYSCORE) spectroscopy shows hyperfine coupling to nitrogen only when the amide precursor is used, consistent with the presence of nitrogen neighbors. This changes their specific reactivity compared to Cr(III) sites in oxygen environments obtained from siloxide precursors: no coordination of CO and oligomer formation during the polymerization of ethylene due to the presence of a N-donor ligand. The presence of the N-ligand also affects the photophysical properties of Yb and Eu by decreasing their lifetime, probably due to nonradiative deactivation of excited states by N–H bonds. Both types of precursors lead to a distribution of surface sites according to reactivity for Cr, luminescence spectroscopy for Yb and Eu, and dynamic nuclear polarization surface-enhanced 89Y NMR spectroscopy (DNP SENS). In particular, DNP SENS provides molecular-level information about the structure of surface sites by evidencing the presence of tri-, tetra-, and pentacoordinated Y-surface sites. This study provides unprecedented evidence and tools to assess the local structure of metal surface sites in relation to their chemical and physical properties.
Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid ...equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking.
We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering
dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (
/
) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14.
677 randomised patients were included. Findings are reported as methylprednisolone (n=337)
dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%)
41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14)
24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%)
45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%)
9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11)
14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in
/
ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points.
Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia.
Italian guidelines recommend HIV pre-exposure prophylaxis (PrEP) only upon satisfying strict eligibility criteria. The objective of this study is to evaluate if PrEP candidates attending a ...community-based service comply with these criteria and whether these prescribing conditions affect retention in care and sexually transmitted infections (STIs) acquisition. A retrospective analysis was performed on PrEP candidates evaluated from January 2019 to June 2022. Data were collected from self-administered questionnaires and clinical files. The population was divided in subjects with 0/1 (0/1 C) and ≥ 2 (≥ 2 C) criteria. Descriptive statistics and non-parametric tests were employed to describe study population. Incidence of PrEP discontinuation and of STIs was estimated per 100 persons-year of follow up (PYFU), and incidence rate ratio (IRR) was calculated. Univariate and multivariable Cox regression analyses were used to evaluate the association strength between PrEP drop out and other variables. The analyses enrolled 659 individuals: 422 individuals were included in 0/1 C, 237 in ≥ 2 C group, respectively. Inconsistent condom use was the most reported prescribing criteria (399 individuals, 60.6%), followed by a previous STI (186 individuals, 28.2%). 0/1 C exhibited lower STIs incidence. PrEP discontinuation was 29% in 0/1 C and 38% in ≥ 2 C (
p
= 0.031). Cox model revealed that inconsistent condom use was the only prescribing criteria associated to PrEP persistence. The majority of PrEP candidate did not comply with prescribing conditions. Eligibility criteria failed to identify individuals with better retention in care. Our results suggest that Italian guidelines should be updated removing barriers to prescription.
Strategic extension! A modular strategy, involving the recognition and assembly of three molecular components, was used to decorate complexes of NiII and CoII with halogen bonds of I⋅⋅⋅S and I⋅⋅⋅O ...type. In addition to this rational implementation of halogen bonding to extend coordination structures, the resulting materials also demonstrate the self‐assembly through I⋅⋅⋅π interactions as a means to form polymers based on coordination and halogen bonds (see graphic).
Characterization of paramagnetic compounds, in particular regarding the detailed conformation and electronic structure, remains a challenge, and - still today it often relies solely on the use of ...X-ray crystallography, thus limiting the access to electronic structure information. This is particularly true for lanthanide elements that are often associated with peculiar structural and electronic features in relation to their partially filled f-shell. Here, we develop a methodology based on the combined use of state-of-the-art magnetic resonance spectroscopies (EPR and solid-state NMR) and computational approaches as well as magnetic susceptibility measurements to determine the electronic structure and geometry of a paramagnetic Yb(III) alkyl complex, Yb(III)CH(SiMe
)
, a prototypical example, which contains notable structural features according to X-ray crystallography. Each of these techniques revealed specific information about the geometry and electronic structure of the complex. Taken together, both EPR and NMR, augmented by quantum chemical calculations, provide a detailed and complementary understanding of such paramagnetic compounds. In particular, the EPR and NMR signatures point to the presence of three-centre-two-electron Yb-γ-Me-β-Si secondary metal-ligand interactions in this otherwise tri-coordinate metal complex, similarly to its diamagnetic Lu analogues. The electronic structure of Yb(III) can be described as a single 4f
configuration, while an unusually large crystal-field splitting results in a thermally isolated ground Kramers doublet. Furthermore, the computational data indicate that the Yb-carbon bond contains some π-character, reminiscent of the so-called α-H agostic interaction.
BACKGROUND:Efavirenz (EFV) association with neurocognitive impairment is debated. Whether switching away from EFV improves neurocognitive performances is still controversial.
METHODS:In a randomized ...open-label controlled trial, patients under effective treatment with tenofovir disoproxil-fumarate (TDF), emtricitabine (FTC) and EFV, who had altered neurocognitive assessment (z-transformed score below −1 in at least one cognitive domain), depression, anxiety or low sleep-quality, were randomized 1 : 1 to immediate or delayed (24-weeks) switch to TDF/FTC/rilpivirine (RPV). Treatment efficacy, neurocognitive function, symptoms and quality of life were evaluated 12, 24 and 48 weeks after randomization.
FINDINGS:Seventy-four patients were randomized to immediate (36 patients) or delayed switch (38 patients). At baseline, 63 and 25% of patients had z-scores below −1 in at least one or two neurocognitive domains, 31.1, 17.6 and 44.6% had significant depression or anxiety symptoms or low sleep quality. At week 24 (primary end-point), overall neurocognitive improvement was observed, with no statistically significant differences between arms, neither considering the global z score (between arms difference +0.1; P = 0.458), nor domain-specific z scores. Patients switching away from EFV had significant greater improvement of sleep quality index (between-arm difference −1.5; P = 0.011), self-reported cognitive failures (−6.2; P = 0.001) and CNS symptoms score (−5; P = 0.002), but not of anxiety or depression. No protocol defined virological failure, grade at least 3 lab abnormalities or drug-related serious adverse events were reported.
CONCLUSION:Our results do not support the hypothesis that switching to RPV improves cognitive function in patient under stable treatment with EFV. Nonetheless, improvements in neuropsychiatric symptoms, sleep quality and self-perceived cognition were observed.
Objectives
To investigate whether efavirenz (EFV) or 8‐hydroxy‐EFV (8‐OH‐EFV) plasma levels are associated with neurocognitive impairment and central nervous system (CNS) side effects.
Methods
We ...conducted a cross‐sectional analysis to explore the potential links between EFV/8‐OH‐EFV levels and cognitive performance or CNS‐related side effects in patients screened within a randomized trial involving a switch from EFV to rilpivirine. The Mann–Whitney test was employed to compare drug levels in patients with or without cognitive impairment, depression, anxiety, sleep disorder or CNS symptoms. Additionally, Spearman's test was used to assess correlations between drug levels and test scores.
Results
Among 104 patients, neither EFV nor 8‐OH‐EFV levels were linked to cognitive impairment, although trends towards higher EFV levels were observed in those with impaired executive function (p = 0.055) and language performances (p = 0.021). On the other hand, elevated 8‐OH‐EFV levels, but not EFV levels, were associated with more CNS side effects (222 vs. 151 ng/mL, p = 0.027), depressive symptoms (247 vs. 164 ng/mL, p = 0.067) and sleep impairment (247 vs. 164 ng/mL, p = 0.078). Consistently, a trend towards a correlation between EFV levels and lower z‐scores in executive function and motor function was observed, while 8‐OH‐EFV levels, but not EFV levels, were directly correlated with symptom scores.
Conclusions
Higher levels of 8‐OH‐EFV were associated with CNS side effects, while EFV levels were only marginally associated with cognitive performance, thus suggesting that EFV and its metabolite may act differently in determining detrimental neurological effects.
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