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IntroductionEvidence is being consolidated that shows that the utilization of antenatal and immunization services has declined in low-income countries (LICs) during the COVID-19 pandemic. Very little is known about the effects of the pandemic on antenatal and immunization service utilization in The Gambia. We set out to explore the COVID-19-related factors affecting the utilization of antenatal and immunization services in two Local Government Areas (LGAs) in The Gambia.MethodsA qualitative methodology was used to explore patients' and providers' experiences of antenatal and immunization services during the pandemic in two LGAs in The Gambia. Thirty-one study participants were recruited from four health facilities, applying a theory-driven sampling framework, including health workers as well as female patients. Qualitative evidence was collected through theory-driven semi-structured interviews, and was recorded, translated into English, transcribed, and analysed thematically, applying a social-ecological framework.ResultsIn our interviews, we identified themes at five different levels: individual, interpersonal, community, institutional and policy factors. Individual factors revolved around patients' fear of being infected in the facilities, and of being quarantined, and their anxiety about passing on infections to family members. Interpersonal factors involved the reluctance of partners and family members, as well as perceived negligence and disrespect by health workers. Community factors included misinformation within the community and mistrust of vaccines. Institutional factors included the shortage of health workers, closures of health facilities, and the lack of personal protective equipment (PPEs) and essential medicines. Finally, policy factors revolved around the consequences of COVID-19 prevention measures, particularly the shortage of transport options and mandatory wearing of face masks.ConclusionsOur findings suggest that patients' fears of contagion, perceptions of poor treatment in the health system, and a general anxiety around the imposing of prevention measures, undermined the uptake of services. In future emergencies, the government in The Gambia, and governments in other LICs, will need to consider the unintended consequences of epidemic control measures on the uptake of antenatal and immunization services.

BackgroundThe short tenure of primary care physicians undermines the continuity of care, compromising health outcomes in low-, middle and in high-income countries. The purpose of this study was to investigate the contextual and individual factors associated with the tenure of physician in Primary Health Care (PHC) services. We consider individual-level sociodemographic variables such as education and work-related variables, as well as the characteristics of employers and services.MethodsThis study is a retrospective cohort study of 2,335 physicians in 284 Primary Health Care Units across the São Paulo, Brazil, public health care system from 2016 to 2020. A multivariate hierarchical model was selected, and an adjusted Cox regression with multilevel analysis was employed. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist was used to report the findings from the study.ResultsThe average physician tenure was 14.54 ± 12.89 months, and the median was 10.94 months. Differences between Primary Health Care Units accounted for 10.83% of the variance observed in the outcome, while the employing organizations were responsible for only 2.30%. The physician characteristics associated with higher tenure in PHC were age at hire, i.e., being between 30 and 60 years old, [HR: 0.84, 95% CI: (0.75-0.95)] and professional experience over five years [HR: 0.76, 95% CI: (0.59-0.96)]. Specialties not related to PHC practices were associated with a short tenure [HR: 1.25, 95% CI: (1.02-1.54)].ConclusionDifferences between Primary Health Care Units and in the individual characteristics, such as specializations and experience, are related to the low tenure of professionals, but such characteristics can be changed through investments in PHC infrastructure and changes in work conditions, policies, training, and human resource policies. Finding a remedy for the short tenure of physicians is essential for guaranteeing a robust PHC system that can contribute to universal, resilient, and proactive health care.

BackgroundSARS-CoV-2 viremia has been found to be a potential prognostic factor in patients hospitalized for COVID-19.ObjectiveWe aimed to assess the association between SARS-CoV-2 viremia and mortality in COVID-19 hospitalized patients during different epidemic periods.MethodsA prospective COVID-19 registry was queried to extract all COVID-19 patients with an available SARS-CoV-2 viremia performed at hospital admission between March 2020 and January 2022. SARS-CoV-2 viremia was assessed by means of GeneFinderTM COVID-19 Plus RealAmp Kit assay and SARS-CoV-2 ELITe MGB® Kit using ResultsFour hundred and forty-five out of 2,822 COVID-19 patients had an available SARS-CoV-2 viremia, prevalently males (64.9%) with a median age of 65 years (IQR 55-75). Patients with a positive SARS-CoV-2 viremia (86/445; 19.3%) more frequently presented with a severe or critical disease (67.4% vs 57.1%) when compared to those with a negative SARS-CoV-2 viremia. Deceased subjects (88/445; 19.8%) were older [75 (IQR 68-82) vs 63 (IQR 54-72)] and showed more frequently a detectable SARS-CoV-2 viremia at admission (60.2% vs 22.7%) when compared to survivors. In univariable analysis a positive SARS-CoV-2 viremia was associated with a higher odd of death [OR 5.16 (95% CI 3.15-8.45)] which was confirmed in the multivariable analysis adjusted for age, biological sex and, disease severity [AOR 6.48 (95% CI 4.05-10.45)]. The association between positive SARS-CoV-2 viremia and death was consistent in the period 1 February 2021-31 January 2022 [AOR 5.86 (95% CI 3.43-10.16)] and in subgroup analysis according to disease severity: mild/moderate [AOR 6.45 (95% CI 2.84-15.17)] and severe/critical COVID-19 patients [AOR 6.98 (95% CI 3.68-13.66)].ConclusionsSARS-CoV-2 viremia resulted associated to COVID-19 mortality and should be considered in the initial assessment of COVID-19 hospitalized patients.

This study compared the postoperative analgesic efficacy of intraperitoneal and incisional lidocaine versus ropivacaine in dogs undergoing major abdominal surgeries. Dogs randomly received intraperitoneal lidocaine irrigation (4 mg kg-1, diluted to 5 ml kg-1, L group), ropivacaine (4 mg kg-1, diluted to 5 ml kg-1, R group) or 0.9% saline (5 ml kg-1, C group). Prior to skin closure, dogs received incisional lidocaine 2 mg kg-1 (group L), incisional ropivacaine 2 mg kg-1 (group R) or incisional saline 0.2 ml kg-1 (group C). Pain was assessed at different time points up to 24 hours after extubation, using the Short Form-Glasgow Composite Measure Pain Scale and VAS Scale. In group C, postoperative pain scores were significantly higher than in groups L and R from T0.5 to T6 (p < 0.05). In R group, postoperative pain scores were significantly lower than in groups L and C from T12 to T24 (p < 0.05). Rescue analgesia was administered to 5/11 dogs in L group, 1/10 dogs in R group and 8/10 dogs in C group. Groups L and R experienced a significantly lower postoperative pain during the first 6 hours after extubation, compared with group C. Ropivacaine provided lower postoperative pain scores than lidocaine and saline up to 24 hours after extubation. According to the obtained results, ropivacaine seemed to provide better and longer lasting postoperative analgesia compared with lidocaine. Therefore, intraperitoneal and incisional administration of ropivacaine in dogs undergoing major abdominal surgeries is recommended.

IntroductionThis paper describes how mortality among hospitalised COVID-19 patients changed during the first three waves of the epidemic in Italy.MethodsThis prospective cohort study used the Kaplan-Meier method to analyse the time-dependent probability of death of all of the patients admitted to a COVID-19 referral centre in Milan, Italy, during the three consecutive periods of: 21 February-31 July 2020 (first wave, W1), 1 August 2020-31 January 2021 (second wave, W2), and 1 February-30 April 2021 (third wave, W3). Cox models were used to examine the association between death and the period of admission after adjusting for age, biological sex, the time from symptom onset to admission, disease severity upon admission, obesity, and the comorbidity burden.ResultsOf the 2,023 COVID-19 patients admitted to our hospital during the study period, 553 (27.3%) were admitted during W1, 838 (41.5%) during W2, and 632 (31.2%) during W3. The crude mortality rate during W1, W2 and W3 was respectively 21.3%, 23.7% and 15.8%. After adjusting for potential confounders, hospitalisation during W2 or W3 was independently associated with a significantly lower risk of death than hospitalisation during W1 (adjusted hazard ratios [AHRs]: 0.75, 95% confidence interval [CI] 0.59-0.95, and 0.58, 95% CI 0.44-0.77). Among the patients aged >75 years, there was no significant difference in the probability of death during the three waves (AHRs during W2 and W3 vs W1: 0.93, 95% CI 0.65-1.33, and 0.88, 95% CI 0.59-1.32), whereas those presenting with critical disease during W2 and W3 were at significantly lower risk of dying than those admitted during W1 (AHRs 0.61, 95% CI 0.43-0.88, and 0.44, 95% CI 0.28-0.70).ConclusionsHospitalisation during W2 and W3 was associated with a reduced risk of COVID-19 death in comparison with W1, but there was no difference in survival probability in patients aged >75 years.

BackgroundThe available data concerning hepatitis B virus (HBV) infection in Uganda are limited, particularly in the case of people living with HIV/AIDS (PLWH). HBV is not routinely tested when starting antiretroviral therapy (ART). We aimed to determine the prevalence, the correlates of the risk of HBV infection, and the association with outcomes of ART among PLWH attending a busy HIV clinic in a referral hospital in Northern Uganda.Patients and methodsFrom April to June 2016, a random sample of 1000 PLWH attending the outpatients' clinic of St. Mary's Hospital, Gulu, Uganda were systematically selected to undergo a rapid hepatitis B surface antigen (HBsAg) test after administering a questionnaire in this cross-sectional study. HIV care parameters were obtained from client files. Multivariate logistic regression and general linear model were used for the analysis.Results950 of the 985 evaluable patients (77% females; mean age 42.8 years) were receiving ART. The overall prevalence of HBsAg was 7.9% (95% confidence interval [CI] 6.2-9.6%), and was significantly lower among the females (6.8% vs 11.7%; p = 0.020). The factors independently associated with higher HBV infection were having lived in an internally displaced persons' camp (adjusted odds ratio [aOR] 1.76, 95% CI 1.03-2.98; p = 0.036) and having shared housing with HBV-infected people during childhood (aOR 3.30, 95% CI 1.49-7.32; p = 0.003). CD4+ T cell counts were significantly lower in HBV patients (p = 0.025), and co-infection was associated with a poorer CD4+ T cell response to ART (AOR 0.88; 95% CI 0.79-0.98; p = 0.030).ConclusionsThe observed prevalence of HBV among the PLWH may be underestimated or a signal of HBV decline in the region. The factors favouring horizontal HBV transmission identified suggest extending HBV screening and vaccine prophylaxis among PLWH.

BackgroundEconomic recessions carry an impact on population health and access to care; less is known on how health systems adapt to the conditions brought by a downturn. This particularly matters now that the COVID-19 epidemic is putting health systems under stress. Brazil is one of the world's most affected countries, and its health system was already experiencing the aftermath of the 2015 recession.MethodsBetween 2018 and 2019 we conducted 46 semi-structured interviews with health practitioners, managers and policy-makers to explore the impact of the 2015 recession on public and private providers in prosperous (São Paulo) and impoverished (Maranhão) states in Brazil. Thematic analysis was employed to identify drivers and consequences of system adaptation and coping strategies. Nvivo software was used to aid data collection and analysis. We followed the Standards for Reporting Qualitative Research to provide an account of the findings.ResultsWe found the concept of 'health sector crisis' to be politically charged among healthcare providers in São Paulo and Maranhão. Contrary to expectations, the public sector was reported to have found ways to compensate for diminishing federal funding, having outsourced services and adopted flexible-if insecure-working arrangements. Following a drop in employment and health plans, private health insurance companies have streamlined their offer, at times at the expenses of coverage. Low-cost walk-in clinics were hit hard by the recession, but were also credited for having moved to cater for higher-income customers in Maranhão.ConclusionsThe 'plates' of a health system may shift and adjust in unexpected ways in response to recessions, and some of these changes might outlast the crisis. As low-income countries enter post-COVID economic recessions, it will be important to monitor the adjustments taking place in health systems, to ensure that past gains in access to care and job security are not eroded.

To improve health outcomes in people living with HIV, adoption of evidence-based interventions (EBIs) using effective and transferable implementation strategies to optimise the delivery of healthcare is needed. ViiV Healthcare's Positive Pathways initiative was established to support the UNAIDS 90-90-90 goals. A compendium of EBIs was developed to address gaps within the HIV care continuum, yet it was unknown whether efforts existed to adapt and implement these EBIs across diverse clinical contexts. Therefore, this review sought to report on the use of implementation science in adapting HIV continuum of care EBIs. A systematic literature review was undertaken to summarise the evaluation of implementation and effectiveness outcomes, and report on the use of implementation science in HIV care. Ten databases were reviewed to identify studies (time-period: 2013-2018; geographic scope: United States, United Kingdom, France, Germany, Italy, Spain, Canada, Australia and Europe; English only publications). Studies were included if they reported on people living with HIV or those at risk of acquiring HIV and used interventions consistent with the EBIs. A broad range of study designs and methods were searched, including hybrid designs. Overall, 118 publications covering 225 interventions consistent with the EBIs were identified. These interventions were evaluated on implementation (N = 183), effectiveness (N = 81), or both outcomes (N = 39). High variability in the methodological approaches was observed. Implementation outcomes were frequently evaluated but use of theoretical frameworks was limited (N = 13). Evaluations undertaken to assess effectiveness were inconsistent, resulting in a range of measures. This review revealed extensive reporting on implementation science as defined using evaluation outcomes. However, high variability was observed in how implementation outcomes and effectiveness were defined, quantified, and reported. A more specific and consistent approach to conducting and reporting on implementation science in HIV could facilitate achievement of UNAIDS 90-90-90 targets.

Performance-based financing (PBF) schemes have been expanding rapidly across low and middle income countries in the past decade, with considerable external financing from multilateral, bilateral and global health initiatives. Many of these countries have been fragile and conflict-affected (FCAS), but while the influence of context is acknowledged to be important to the operation of PBF, there has been little examination of how it affects adoption and implementation of PBF. This article lays out initial hypotheses about how FCAS contexts may influence the adoption, adaption, implementation and health system effects of PBF. These are then interrogated through a review of available grey and published literature (140 documents in total, covering 23 PBF schemes). We find that PBF has been more common in FCAS contexts, which were also more commonly early adopters. Very little explanation of the rationale for its adoption, in particular in relation with the contextual features, is given in programme documents. However, there are a number of factors which could explain this, including the greater role of external actors and donors, a greater openness to institutional reform, and lower levels of trust within the public system and between government and donors, all of which favour more contractual approaches. These suggest that rather than emerging despite fragility, conditions of fragility may favour the rapid emergence of PBF. We also document few emerging adaptations of PBF to humanitarian settings and limited evidence of health system effects which may be contextually driven, but these require more in-depth analysis. Another area meriting more study is the political economy of PBF and its diffusion across contexts.

Although socioeconomic inequalities in health have long been observed in Europe, few studies have analysed their recent patterning. In this paper, we examined how educational inequalities in self-reported health have evolved in different European countries and welfare state regimes over the last decade, which was troubled by the Great Recession.We used cross-sectional data from the EU-SILC survey for adults from 26 European countries, from 2005 to 2014 (n = 3,030,595). We first calculated education-related absolute (SII) and relative (RII) inequalities in poor self-reported health by country-year, adjusting for age, sex, and EU-SILC survey weights. We then regressed the year- and country-specific RII and SII on a yearly time trend, globally and by welfare regime, adjusting for country fixed effects. We further adjusted the analysis for the economic cycle using GDP growth, unemployment, and income inequality.Overall, absolute inequalities persisted and relative inequalities slightly widened (betaRII = 0.0313, p

Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR.Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization.HCV-RNA kinetics was biphasic, reflecting a mean effectiveness in blocking viral production >99.8%. The first-phase of viral-decline was faster in patients receiving NS5A-inhibitors compared to TVR+PR or sofosbuvir+simeprevir (p

OBJECTIVE:This NMA compared the efficacy and safety between IV antibiotics that are used in the current standard of care for managing adult patients (≥18 years of age) with ABSSSI. METHODS:Comparators were chosen on the basis that both direct and indirect comparisons between the interventions of interest could be performed. Outcomes of the analysis were selected on the basis that they are frequently measured and reported in trials involving ABSSSI patients, and only published randomised control trials of any size and duration and with any blinding status were eligible for inclusion in the analysis. The NMA was performed using both a fixed-effect and random-effect model. Efficacy-related endpoints were (1) clinical treatment success and (2) microbiological success at TOC visit. Safety-related endpoints were (1) number of discontinuations due to AEs/SAEs, (2) patients experiencing AEs, (3) patients experiencing SAEs and (4) all-cause mortality. RESULTS:Study interventions included daptomycin, dalbavancin, linezolid and tigecycline. Vancomycin was the comparator in all studies, except in two where it was linezolid and teicoplanin. The NMA showed that irrespective of patient subgroup, the likelihood of clinical and microbiological success with dalbavancin was statistically similar to the comparators studied. No statistically significant differences were observed between dalbavancin and any of the comparators in the discontinuation rate due to AEs/SAEs. In contrast, dalbavancin was associated with a significantly lower likelihood of experiencing an AE than linezolid, a significantly lower likelihood of experiencing a SAE than vancomycin and daptomycin, and a significantly lower risk of all-cause mortality than vancomycin, linezolid and tigecycline. CONCLUSION:Dalbavancin affords a promising, new alternative IV antimicrobial agent which is as effective as traditional therapies, but with the added benefit of enabling clinicians to treat patients with ABSSSI in different organisational settings. Notwithstanding, any introduction of an effective treatment with a differential mode of administration into healthcare systems must be followed by a change in clinical practice and patient management in order to fully achieve desirable economic outcomes.

IntroductionLittle information is available on the efficacy and safety of the dual combination of ripivirine plus dolutegravir. This work aims at beginning to fill this gap.MethodsAll HIV-1 infected subjects treated with ripivirine plus dolutegravir between October 2014 and September 2015 in eight Italian centres were included in an observational cohort. Data were collected at baseline and at weeks 4, 12, 24 and 48.ResultsOne hundred and thirty-two subjects were followed for a median of 24 months, mean 33 months. One subject discontinued the study drug at week 24 for headache, one for drug interaction and one died after week 24 of illicit drug abuse. The mean age was 51.8, females 31.7% and non-caucasians 10%. Fifty-seven (43.2%) had at least one failure in their treatment history. Reasons for switching were simplification (53.0%), toxicity (34.8%), drug interactions (n = 7), persistent low-level viremia (n = 4), non-adherence (n = 3) and viral failure (n = 2). Sixty patients (45.5%) had reverse transcriptase (RT) mutations and 69 (44,7%) had protease (PR) mutations. Sixteen had baseline viral replication, 27 had < 50 HIV-1 RNA copies/mL and in 89 (67.4%) no virus was detected (NVD, 0 copies/mL). At w4, 114 (86.4%) had NVD, 15 had 1 to 49 HIV-1 RNA copies/mL and 3 had 50 to 57 copies/mL. At week 24 one subject had viral rebound without mutations due to missed drug refill, 19 had 1 to 49 copies/mL, and 112 had NVD. All 132 subjects were tested at weeks 4 and 24. Of the 50 subjects who had a 48-week follow-up, one had a treatment interruption, four had 1 to 49 copies/mL and 45 had NVD. Among the entire population, one subject had low-level, one intermediate and 4 high-level resistance to rilpivirine: none failed by week 48. Mean serum creatinine increased by +0.1 mg/dL. During the follow-up one patient reported headache and insomnia.ConclusionsRipivirine plus dolutegravir proved safe and effective in this cohort of non-naïve HIV-1 infected subjects.

The present article describes the case study of a "real world" HIV practice within the debate concerning the strategic role of Clinical Governance (CG) tools in the management of a National Healthcare System's sustainability. The study aimed at assessing the impact of a Clinical Pathway (CP) implementation, required by the Regional Healthcare Service, in terms of effectiveness (virological and immunological conditions) and efficiency (economic resources absorption), from the budget holder perspective. Data derived from a multi-centre cohort of patients treated in 6 Hospitals that provided care to approximately 42% of the total HIV+ patients, in Lombardy Region, Italy. Two phases were compared: Pre-CP (2009-2010) vs. Post-CP implementation (2011-2012). All HIV infected adults, observed in the participating hospitals during the study periods, were enrolled and stratified into the 3 categories defined by the Regional CP: first-line, switch for toxicity/other, and switch for failure. The study population was composed of 1,284 patients (Pre-CP phase) and 1,135 patients (Post-CP phase). The results showed that the same level of virological and immunological effectiveness was guaranteed to HIV+ patients: 81.2% of Pre-CP phase population and 83.2% of Post-CP phase population had undetectable HIV-RNA (defined as

There are no data comparing the response to PI/r-based regimens in people presenting for care with low CD4 counts or AIDS (LC).To compare the response to LPV/r-, DRV/r- or ATV/r-based cART regimens in LC initiating cART from ART-naive.We included people enrolled in Icona with either CD4 counts ≤350 cells/mm3 (low CD4-LC) or CD4 counts ≤200 cells/mm3 (very low CD4-VLC) and/or AIDS, starting their first PI/r-based regimen after 2008. Initial regimens were compared by intention-to-treat: i) time to viral failure (VF) (first of 2 consecutive VL>200 copies/mL after≥6 months); II) time to PI/r discontinuation/switching for any cause (TD) and for toxicity (TDT); III) treatment failure (TF) (VF or TD). Kaplan-Meier and Cox analyses were used.1,362 LC patients were included (DRV/r 607; ATV/r 552; LPV/r 203); 813 VLC. In a median of 18 months (IQR:7-35), the 1-year probability of VF and TF were 2.8% (1.9-3.8) and 21.1% (18.7-23.4). In the adjusted analysis, patients initiating ATV/r had a 53% lower chance, and those initiating DRV/r a 61% lower chance of TD, as compared to LPV/r; the risk of TF was more likely in people starting LPV/r. Results were similar among VLC; in this subgroup LPV/r including regimens demonstrated a lower chance of VF.We confirmed in LC a low chance of virological failure by 1 year, with small differences according to PI/r. However, larger differences were observed when comparing longer-term endpoints such as treatment failure. These results are important for people presenting late for care.

The colonization and development of gut microbiota immediately after birth is highly variable and depends on several factors, such as delivery mode and modality of feeding during the first months of life. A cohort of 31 mother and neonate pairs, including 25 at-term caesarean (CS) and 6 vaginally (V) delivered neonates (DNs), were included in this study and 121 meconium/faecal samples were collected at days 1 through 30 following birth. Operational taxonomic units (OTUs) were assessed in 69 stool samples by phylogenetic microarray HITChip and inter- and intra-individual distributions were established by inter-OTUs correlation matrices and OTUs co-occurrence or co-exclusion networks. 1H-NMR metabolites were determined in 70 stool samples, PCA analysis was performed on 55 CS DNs samples, and metabolome/OTUs co-correlations were assessed in 45 CS samples, providing an integrated map of the early microbiota OTUs-metabolome. A microbiota "core" of OTUs was identified that was independent of delivery mode and lactation stage, suggesting highly specialized communities that act as seminal colonizers of microbial networks. Correlations among OTUs, metabolites, and OTUs-metabolites revealed metabolic profiles associated with early microbial ecological dynamics, maturation of milk components, and host physiology.

INTRODUCTION:Ritonavir-boosted atazanavir (ATV/r) is a relatively well tolerated antiretroviral drug. However, side effects including hyperbilirubinemia, dyslipidemia, nephrolithiasis and cholelithiasis have been reported in the medium and long term. Unboosted ATV may be selected for some patients because it has fewer gastrointestinal adverse effects, less hyperbilirubinemia and less impact on lipid profiles. METHODS:We investigated the distribution of ATV plasma trough concentrations according to drug dosage and the potential relationship between ATV plasma trough concentrations and drug-related adverse events in a consecutive series of 240 HIV-infected patients treated with ATV/r 300/100 mg (68%) or ATV 400 mg (32%). RESULTS:43.9% of patients treated with ATV/r 300/100 mg had ATV concentrations exceeding the upper therapeutic threshold. A significant and direct association has been observed between the severity of hyperbilirubinemia and ATV plasma trough concentrations (ATV concentrations: 271 [77-555], 548 [206-902], 793 [440-1164], 768 [494-1527] and 1491 [1122-1798] ng/mL in patients with grade 0, 1, 2, 3 and 4 hyperbilirubinemia, respectively). In an exploratory analysis we found that patients with dyslipidemia or nephrolitiasis had ATV concentrations significantly higher (582 [266-1148], and 1098 [631-1238] ng/mL, respectively) (p

Although both alcohol and fructose are particularly steatogenic, their long-term effect in the development of a metabolic syndrome has not been studied in vivo. Consumption of fructose generally leads to obesity, whereas ethanol can induce liver damage in the absence of overweight. Here, Sprague-Dawley rats were fed ad libitum for 28 days on five diets: chow (control), liquid Lieber-DeCarli (LDC) diet, LDC +30%J of ethanol (L-Et) or fructose (L-Fr), and LDC combined with 30%J ethanol and 30%J fructose (L-EF). Body weight (BW) and liver weight (LW) were measured. Blood and liver samples were harvested and subjected to biochemical tests, histopathological examinations, and RT-PCR. Alcohol-containing diets substantially reduced the food intake and BW (≤3rd week), whereas fructose-fed animals had higher LW than controls (P

ObjectiveTo estimate the lifetime cost utility of two antiretroviral regimens (once-daily atazanavir plus ritonavir [ATV+r] versus twice-daily lopinavir/ritonavir [LPV/r]) in Italian human immunodeficiency virus (HIV)-infected patients naïve to treatment.DesignWith this observational retrospective study we collected the clinical data of a cohort of HIV-infected patients receiving first-line treatment with LPV/r or ATV+r.MethodologyA Markov microsimulation model including direct costs and health outcomes of first- and second-line highly active retroviral therapy was developed from a third-party (Italian National Healthcare Service) payer's perspective. Health and monetary outcomes associated with the long-term use of ATV+r and LPV/r regimens were evaluated on the basis of eight health states, incidence of diarrhoea and hyperbilirubinemia, AIDS events, opportunistic infections, coronary heart disease events and, for the first time in an economic evaluation, chronic kidney disease (CKD) events. In order to account for possible deviations between real-life data and randomised controlled trial results, a second control arm (ATV+r 2) was created with differential transition probabilities taken from the literature.ResultsThe average survival was 24.061 years for patients receiving LPV/r, 24.081 and 24.084 for those receiving ATV+r 1 and 2 respectively. The mean quality-adjusted life-years (QALYs) were higher for the patients receiving LPV/r than those receiving ATV+r (13.322 vs. 13.060 and 13.261 for ATV+r 1 and 2). The cost-utility values were 15,310.56 for LPV/r, 15,902.99 and 15,524.85 for ATV+r 1 and 2.ConclusionsUsing real-life data, the model produced significantly different results compared with other studies. With the innovative addition of an evaluation of CKD events, the model showed a cost-utility value advantage for twice-daily LPV/r over once-daily ATV+r, thus providing evidence for its continued use in the treatment of HIV.

ObjectiveThe false-positive rate (FPR) is a percentage-score provided by Geno2Pheno-algorithm indicating the likelihood that a V3-sequence is falsely predicted as CXCR4-using. We evaluated the correlation between FPR obtained by V3 population-sequencing and the burden of CXCR4-using variants detected by V3 ultra-deep sequencing (UDPS) and Enhanced-Sensitivity Trofile assay (ESTA).Methods54 HIV-1 B-subtype infected-patients (all maraviroc-naïve), with viremia >10,000copies/ml, were analyzed. HIV-tropism was assessed by V3 population-sequencing, UDPS (considering variants with >0.5% prevalence), and ESTA.ResultsBy UDPS, CCR5-using variants were detected in 53/54 patients, irrespective of FPR values, and their intra-patient prevalence progressively increased by increasing the FPR obtained by V3 population-sequencing (rho = 0.75, p = 5.0e-8). Conversely, the intra-patient prevalence of CXCR4-using variants in the 54 patients analyzed progressively decreased by increasing the FPR (rho = -0.61; p = 9.3e-6). Indeed, no CXCR4-using variants were detected in 13/13 patients with FPR>60. They were present in 7/18 (38.8%) patients with FPR 20-60 (intra-patient prevalence range: 2.1%-18.4%), in 5/7 (71.4%) with FPR 10-20, in 4/6 (66.7%) with FPR 5-10, and in 10/10(100%) with FPRConclusionsFPR by V3 population-sequencing can predict the burden of CXCR4-using variants. This information can be used to optimize the management of tropism determination in clinical practice. Due to its low cost and short turnaround time, V3 population-sequencing may represent the most feasible test for HIV-1 tropism determination. More sensitive methodologies (as UDPS) might be useful when V3 population-sequencing provides a FPR >20 (particularly in the range 20-60), allowing a more careful identification of patients harboring CXCR4-using variants.

Eradication of hepatitis C virus (HCV) infection, both spontaneous and treatment-induced, is marked by the wildtype allele C of a single nucleotide polymorphism upstream of the IL28B gene, rs12979860. This favorable allele was recently described to be in linkage disequilibrium with the wildtype allele TT of a dinucleotide polymorphism, ss469415590, located within a new protein-coding gene. While the TT allele introduces a frame-shift and disrupts the open reading frame, only the variant allele, ΔG, creates a novel type III interferon (IFN) protein, IFN-λ4/IFNL4. Absence of IFNL4 is thus supposed to favor resolution of HCV infection. As to date IFNL4 mRNA transcription has only been investigated in polyI:C-stimulated primary human hepatocytes and not yet in HCV infection in vivo, this study analyzed IFNL4 mRNA expression in human liver biopsy specimens. Samples were obtained from patients with a broad panel of disorders including no liver disease, liver diseases of non-viral etiology, chronic hepatitis B and chronic hepatitis C. Hepatic IFNL4 transcripts were detectable exclusively in a subgroup of chronic hepatitis C patients (24/45). Their amounts were positively related to liver HCV RNA copy numbers (p = 0.0023, r = 0.56) suggesting that the hepatic viral load influences IFNL4 transcription irrespective of IFNL4 governing genotype. Both, the IFNL4 creating allele ΔG (p

Treatment with tenofovir sometimes leads to non-reversible kidney and/or bone diseases. Factors associated with these drug-related adverse events are poorly characterized. Our objective was to investigate such factors in patients treated long term with daily tenofovir. One-hundred Caucasian HIV-positive patients with basal creatinine clearance >80 mL/min treated with tenofovir for at least 6 months and with at least one assessment of tenofovir plasma trough concentrations were considered. Tenofovir-associated adverse events were defined as the appearance of pathological proteinuria, worsening of renal function or bone demineralization. By multivariate regression analysis, we found that serum creatinine (p = 0.003) and body weight (p = 0.002) were the factors independently associated with plasma tenofovir concentrations. In particular, women with body weight50 Kg (160±93 vs.71±52 ng/mL, p

BackgroundLong term efficacy of raltegravir (RAL)-including regimens in highly pre-treated HIV-1-infected patients has been demonstrated in registration trials. However, few studies have assessed durability in routine clinical settings.MethodsAntiretroviral treatment-experienced patients initiating a RAL-containing salvage regimen were enrolled. Routine clinical and laboratory follow-up was performed at baseline, week 4, 12, and every 12 weeks thereafter. Data were censored at week 96.ResultsOut of 320 patients enrolled, 292 (91.25%) subjects maintained their initial regimen for 96 weeks; 28 discontinued prematurely for various reasons: death (11), viral failure (8), adverse events (5), loss to follow-up (3), consent withdrawal (1). Eight among these 28 subjects maintained RAL but changed the accompanying drugs. The mean CD4+ T-cell increase at week 96 was 227/mm(3); 273 out of 300 patients (91%), who were still receiving RAL at week 96, achieved viral suppression (HIV-1 RNA 4 (n = 40), CD4+ T-cell gain was similar across strata: +270, +214, +216, and +240 cells/mm(3), respectively, as was the proportion of subjects with undetectable viral load. Laboratory abnormalities (elevation of liver enzymes, total cholesterol and triglycerides) were rare, ranging from 0.9 to 3.1%. The mean 96-week total cholesterol increase was 23.6 mg/dL.ConclusionsIn a routine clinical setting, a RAL-based regimen allowed most patients in salvage therapy to achieve optimal viral suppression for at least 96 weeks, with relevant immunologic gain and very few adverse events.

BACKGROUND: In HIV-infected individuals, mechanisms underlying unsatisfactory immune recovery during effective combination antiretroviral therapy (cART) have yet to be fully understood. We investigated whether polymorphism of genes encoding immune-regulating molecules, such as killer immunoglobulin-like receptors (KIR) and their ligands class I human leukocyte antigen (HLA), could influence immunological response to cART. METHODS: KIR and HLA frequencies were analyzed in 154 HIV-infected and cART-treated patients with undetectable viral load divided into two groups: 'immunological non responders' (INR, N = 50, CD4(+) T-cell count 350/mm(3)). Molecular KIR were typed using polymerase chain reaction-based genotyping. Comparisons were adjusted for baseline patient characteristics. RESULTS: The frequency of KIR2DL3 allele was significantly higher in FR than in INR (83.7% vs. 62%, P = 0.005). The functional compound genotype HLA-C1(+)/KIR2DL3(+), even at multivariable analysis, when adjusted for nadir CD4(+) T-cell count, was associated with reduced risk of INR status: odds ratio (95% Confidence Intervals) 0.34 (0.13-0.88), P = 0.03. CONCLUSIONS: Reduced presence of the inhibitory KIR2DL3 genotype detected in INR might provoke an imbalance in NK function, possibly leading to increased immune activation, impaired killing of latently infected cells, and higher proviral burden. These factors would hinder full immune recovery during therapy.

Background: Supportive parenting is critical for promoting healthy child development in the face of stressors, such as those occurring during COVID-19. Here, we address a knowledge gap regarding specific household risk factors associated with parenting quality during the pandemic and incorporate first-person accounts of family challenges and needs., Methods: Mixed methods were applied to data collected between April 14th - 28th, 2020 from the "Parenting During the Pandemic" survey. Participants included 656 primary caregivers (e.g., mothers, fathers, foster parents) of least one child age 1.5-8 years of which 555 (84.6%) responded to at least one parenting questionnaire. Parenting quality was assessed across stressful, negative, and positive parenting dimensions. Household risk was examined across pandemic- linked (e.g., caregiver depression, unmet childcare needs) and stable factors (i.e., annual income, mental illness history). Significant correlates were examined with regressions in Mplus. Thematic analysis identified caregiver challenges and unmet needs from open-ended questions., Findings: Caregiver depression, higher child parity, unmet childcare needs, and relationship distress predicted lower-quality parenting. Caregiver depression was the most significant predictor across every parenting dimension, with analyses indicating medium effect sizes, ds = .39 - .73. Qualitative findings highlighted severe strains on parent capacities including managing psychological distress, limited social supports, and too much unstructured time., Interpretations: Lower quality parenting during COVID-19 is associated with multiple household and pandemic risk factors, with caregiver depression consistently linked to parent- child relationship disruptions. Focused efforts are needed to address caregiver mental health to protect child health as part of the pandemic response., Competing Interests: The authors have declared that no competing interests exist.