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BackgroundTimely linkage to care and ART initiation is critical to decrease the risks of HIV-related morbidity, mortality and HIV transmission, but is often challenging. We report on the implementation and effectiveness of a linkage-to-care intervention in rural KwaZulu-Natal, South Africa.MethodsIn the ANRS 12249 TasP trial on Universal Testing and Treatment (UTT) implemented between 2012-2016, resident individuals ≥16 years were offered home-based HIV testing every six months. Those ascertained to be HIV-positive were referred to trial clinics. Starting May 2013, a linkage-to-care intervention was implemented in both trial arms, consisting of tracking through phone calls and/or home visits to "re-refer" people who had not linked to care to trial clinics within three months of the first home-based referral. Fidelity in implementing the planned intervention was described using Kaplan-Meier estimation to compute conditional probabilities of being tracked and of being re-referred by the linkage-to-care team. Effect of the intervention on time to linkage-to-care was analysed using a Cox regression model censored for death, migration, and end of data follow-up.ResultsAmong the 2,837 individuals (73.7% female) included in the analysis, 904 (32%) were tracked at least once, and 573 of them (63.4%) were re-referred. Probabilities of being re-referred was 17% within six months of first referral and 31% within twelve months. Compared to individuals not re-referred by the intervention, linkage-to-care was significantly higher among those with at least one re-referral through phone call (adjusted hazard ratio [aHR] = 1.82; 95% confidence interval [95% CI] = 1.47-2.25), and among those with re-referral through both phone call and home visit (aHR = 3.94; 95% CI = 2.07-7.48).ConclusionsPhone calls and home visits following HIV testing were challenging to implement, but appeared effective in improving linkage-to-care amongst those receiving the intervention. Such patient-centred strategies should be part of UTT programs to achieve the UNAIDS 95-95-95 targets.

ObjectiveTo evaluate efficacy of a novel adeno-associated virus (AAV) vector, AAV2/4-RS1, for retinal rescue in the retinoschisin knockout (Rs1-KO) mouse model of X-linked retinoschisis (XLRS). Brinzolamide (Azopt®), a carbonic anhydrase inhibitor, was tested for its ability to potentiate the effects of AAV2/4-RS1.MethodsAAV2/4-RS1 with a cytomegalovirus (CMV) promoter (2x1012 viral genomes/mL) was delivered to Rs1-KO mice via intravitreal (N = 5; 1μL) or subretinal (N = 21; 2μL) injections at postnatal day 60-90. Eleven mice treated with subretinal therapy also received topical Azopt® twice a day. Serial full field electroretinography (ERG) was performed starting at day 50-60 post-injection. Mice were evaluated using a visually guided swim assay (VGSA) in light and dark conditions. The experimental groups were compared to untreated Rs1-KO (N = 11), wild-type (N = 12), and Rs1-KO mice receiving only Azopt® (N = 5). Immunofluorescence staining was performed to assess RS1 protein expression following treatment.ResultsThe ERG b/a ratio was significantly higher in the subretinal plus Azopt® (pConclusionsAAV2/4-RS1 shows promise for improving retinal phenotype in the Rs1-KO mouse model. Subretinal delivery was superior to intravitreal. Topical brinzolamide did not improve efficacy. AAV2/4-RS1 may be considered as a potential treatment for XLRS patients.

There continue to be conflicting data regarding the outcomes of people with HIV (PWH) who have COVID-19 infection with most studies describing the early epidemic. We present a single site experience spanning a later timeframe from the first report on January 21, 2020 to January 20, 2021 and describe clinical outcomes and predictors of hospitalization among a cohort of PWH in an urban center in Connecticut, USA. Among 103 PWH with controlled HIV disease, hospitalization occurred in 33% and overall mortality was 1%. HIV associated factors (CD4 count, HIV viral suppression) were not associated with hospitalization. Chronic lung disease (OR: 3.35, 95% CI:1.28-8.72), and cardiovascular disease (OR: 3.4, 95% CI:1.27-9.12) were independently associated with hospitalization. An increasing number of non-communicable comorbidities increased the likelihood of hospitalization (OR: 1.61, 95% CI:1.22-2.13).

IntroductionAntiretroviral therapy (ART) has revolutionised the care of HIV-positive individuals resulting in marked decreases in morbidity and mortality, and markedly reduced transmission to sexual partners. However, these benefits can only be realised if individuals are aware of their HIV-positive status, initiated and retained on suppressive lifelong ART. Framed using the socio-ecological model, the present study explores factors contributing to poor ART uptake among community members despite high acceptance of HIV-testing within a Treatment as Prevention (TasP) trial. In this paper we identify barriers and facilitators to treatment across different levels of the socio-ecological framework covering individual, community and health system components.MethodsThis research was embedded within a cluster-randomised trial (ClinicalTrials.gov, number NCT01509508) of HIV treatment as Prevention in rural KwaZulu-Natal, South Africa. Data were collected between January 2013 and July 2014 from resident community members. Ten participants contributed to repeat in-depth interviews whilst 42 participants took part in repeat focus group discussions. Data from individual interviews and focus group discussions were triangulated using community walks to give insights into community members' perception of the barriers and facilitators of ART uptake. We used thematic analysis guided by a socio-ecological framework to analyse participants' narratives from both individual interviews and focus group discussions.ResultsBarriers and facilitators operating at the individual, community and health system levels influence ART uptake. Stigma was an over-arching barrier, across all three levels and expressed variably as fear of HIV disclosure, concerns about segregated HIV clinical services and negative community religious perceptions. Other barriers were individual (substance misuse, fear of ART side effects), community (alternative health beliefs). Facilitators cited by participants included individual (expectations of improved health and longer life expectancy following ART, single tablet regimens), community (availability of ART in the community through mobile trial facilities) and health system factors (fast and efficient service provided by friendly staff).DiscussionWe identified multiple barriers to achieving universal ART uptake. To enhance uptake in HIV care services, and achieve the full benefits of ART requires interventions that tackle persistent HIV stigma, and offer people with HIV respectful, convenient and efficient services. These interventions require evaluation in appropriately designed studies.

OBJECTIVES:Eliminating unnecessary laboratory tests is a good way to reduce costs while maintain patient safety. The aim of this study was to define and process strategies to rationalize laboratory use in Ankara Numune Training and Research Hospital (ANH) and calculate potential savings in costs. METHODS:A collaborative plan was defined by hospital managers; joint meetings with ANHTA and laboratory professors were set; the joint committee invited relevant staff for input, and a laboratory efficiency committee was created. Literature was reviewed systematically to identify strategies used to improve laboratory efficiency. Strategies that would be applicable in local settings were identified for implementation, processed, and the impact on clinical use and costs assessed for 12 months. RESULTS:Laboratory use in ANH differed enormously among clinics. Major use was identified in internal medicine. The mean number of tests per patient was 15.8. Unnecessary testing for chloride, folic acid, free prostate specific antigen, hepatitis and HIV testing were observed. Test panel use was pinpointed as the main cause of overuse of the laboratory and the Hospital Information System test ordering page was reorganized. A significant decrease (between 12.6-85.0%) was observed for the tests that were taken to an alternative page on the computer screen. The one year study saving was equivalent to 371,183 US dollars. CONCLUSION:Hospital-based committees including laboratory professionals and clinicians can define hospital based problems and led to a standardized approach to test use that can help clinicians reduce laboratory costs through appropriate use of laboratory tests.

BACKGROUND:End-tidal CO2 (ETCO2), partial pressure of exhaled CO2 (PECO2), and volume of expired CO2 (VCO2) can be continuously monitored non-invasively to reflect pulmonary ventilation and perfusion status. Although ETCO2 ≥14 mmHg has been shown to be associated with return of an adequate heart rate in neonatal resuscitation and quantifying the PECO2 has the potential to serve as an indicator of resuscitation quality, there is little information regarding capnometric measurement of PECO2 and ETCO2 in detecting return of spontaneous circulation (ROSC) and survivability in asphyxiated neonates receiving cardiopulmonary resuscitation (CPR). METHODS:Seventeen newborn piglets were anesthetized, intubated, instrumented, and exposed to 45-minute normocapnic hypoxia followed by apnea to induce asphyxia. Protocolized resuscitation was initiated when heart rate decreased to 25% of baseline. Respiratory and hemodynamic parameters including ETCO2, PECO2, VCO2, heart rate, cardiac output, and carotid artery flow were continuously measured and analyzed. RESULTS:There were no differences in respiratory and hemodynamic parameters between surviving and non-surviving piglets prior to CPR. Surviving piglets had significantly higher ETCO2, PECO2, VCO2, cardiac index, and carotid artery flow values during CPR compared to non-surviving piglets. CONCLUSION:Surviving piglets had significantly better respiratory and hemodynamic parameters during resuscitation compared to non-surviving piglets. In addition to optimizing resuscitation efforts, capnometry can assist by predicting outcomes of newborns requiring chest compressions.

IntroductionMozambique continues to face a severe HIV epidemic and high cost for its control, largely born by international donors. We assessed feasible targets, likely impact and costs for the 2015-2019 national strategic HIV/AIDS plan (NSP).MethodsThe HIV epidemic and response was modelled in the Spectrum/Goals/Resource Needs dynamical simulation model, separately for North/Center/South regions, fitted to antenatal clinic surveillance data, household and key risk group surveys, program statistics, and financial records. Intervention targets were defined in collaboration with the National AIDS Council, Ministry of Health, technical partners and implementing NGOs, considering existing commitments.ResultsImplementing the NSP to meet existing coverage targets would reduce annual new infections among all ages from 105,000 in 2014 to 78,000 in 2019, and reduce annual HIV/AIDS-related deaths from 80,000 to 56,000. Additional scale-up of prevention interventions targeting high-risk groups, with improved patient retention on ART, could further reduce burden to 65,000 new infections and 51,000 HIV-related deaths in 2019. Program cost would increase from US$ 273 million in 2014, to US$ 433 million in 2019 for 'Current targets', or US$ 495 million in 2019 for 'Accelerated scale-up'. The 'Accelerated scale-up' would lower cost per infection averted, due to an enhanced focus on behavioural prevention for high-risk groups. Cost and mortality impact are driven by ART, which accounts for 53% of resource needs in 2019. Infections averted are driven by scale-up of interventions targeting sex work (North, rising epidemic) and voluntary male circumcision (Center & South, generalized epidemics).ConclusionThe NSP could aim to reduce annual new HIV infections and deaths by 2019 by 30% and 40%, respectively, from 2014 levels. Achieving incidence and mortality reductions corresponding to UNAIDS' 'Fast track' targets will require increased ART coverage and additional behavioural prevention targeting key risk groups.

Unprotected anal intercourse (UAI) is a major pathway towards secondary HIV transmission among men who have sex with men (MSM). We explored the socio-cultural environment and individual beliefs and experiences conducive to UAI in the context of Southern China.We employed an ethnographic approach utilizing a socio-ecological framework to conduct repeated in-depth interviews with thirty one newly diagnosed HIV positive MSM as well as participant observations in Shenzhen based healthcare settings, MSM venues and NGO offices.Some men (6/31) reported continuing to practice UAI after an initial diagnosis of being HIV positive. For MSM who had existing lovers or stable partners, the fear of losing partners in a context of non-serostatus disclosure was testified to be a major concern. MSM with casual partners reported that anonymous sexual encounters and moral judgments played a significant role in their sexual risk behaviors. Simultaneously, self-reported negative emotional and psychological status, perception and idiosyncratic risk interpretation, as well as substance abuse informed the intrapersonal context for UAI.UAI among these HIV positive MSM was embedded in an intrapersonal context, related to partner type, shaped by anonymous sexual encounters, psychological status, and moral judgments. It is important that prevention and intervention for secondary HIV transmission among newly diagnosed HIV positive MSM in China take into account these contextual factors.

Population-based HIV surveillance is crucial to inform understanding of the HIV pandemic and evaluate HIV interventions, but little is known about longitudinal participation patterns in such settings. We investigated the dynamics of longitudinal participation patterns in a high HIV prevalence surveillance setting in rural South Africa between 2003 and 2012, taking into account demographic dynamics. At any given survey round, 22,708 to 30,495 persons were eligible. Although the yearly participation rates were relatively modest (26% to 46%), cumulative rates increased substantially with multiple recruitment opportunities: 68% of eligible persons participated at least once, 48% at least twice and 31% at least three times after five survey rounds. We identified two types of study fatigue: at the individual level, contact and consent rates decreased with multiple recruitment opportunities and, at the population level, these rates also decreased over calendar time, independently of multiple recruitment opportunities. Using sequence analysis and hierarchical clustering, we identified three broad individual participation profiles: consenters (20%), switchers (43%) and refusers (37%). Men were over represented among refusers, women among consenters, and temporary non-residents among switchers. The specific subgroup of persons who were systemically not contacted or refusers constitutes a challenge for population-based surveillance and interventions.

ObjectivesMillions of children and adolescents in rural China are left behind as their parents move away for work. Little is known about the impact of parental migration on their smoking and self-efficacy. This study explores the associations among parental migration, self-efficacy and smoking.MethodsA cross-sectional study was conducted among middle school students in Liangying Township, Guangdong, China. Socio-demographic and parental migration characteristics, as well as adolescent past 30-day smoking and self-efficacy level were collected using a self-administered questionnaire. Univariate and multivariate analyses were performed to estimate the risk of parental migration features for smoking and self-efficacy. Hierarchical regression was fitted to examine the relationship among parental migration, self-efficacy and smoking.Results2609 students (93.4%) participated into the study, 44% of who were with parents who had ever been or were currently migrating. Smoking prevalence was 9.7% in boys and 0.9% in girls. Paternal migration was protective for adolescent smoking, whilst maternal migration increased the risk. Both paternal and maternal migration had adverse effects on self-efficacy, a strong influencing factor for smoking. No significant relationship was found between other migration features and smoking and self-efficacy. The smoking risk of maternal migration was partly mediated by self-efficacy. There were no differences between boys and girls.ConclusionsOur findings suggest that adolescents whose mothers migrate from home to work elsewhere are at elevated risk for smoking. Improving self-efficacy may be an effective means to keep adolescents away from smoking, especially for those with maternal migration.

Non-specific binding to biosensor surfaces is a major obstacle to quantitative analysis of selective retention of analytes at immobilized target molecules. Although a range of chemical antifouling monolayers has been developed to address this problem, many macromolecular interactions still remain refractive to analysis due to the prevalent high degree of non-specific binding. In this manuscript we explore the dynamic process of the formation of self-assembled monolayers and optimize physical and chemical properties thus reducing considerably non-specific binding while maintaining the integrity of the immobilized biomolecules. As a result, analysis of specific binding of analytes to immobilized target molecules is significantly facilitated.

BACKGROUND: The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development. METHODOLOGY/PRINCIPAL: Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat). In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNgamma were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin. CONCLUSIONS: It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in BioBreeding diabetes prone rats. Taken collectively, these data suggest that the gut and the gut microbiota are potential agents of influence in type 1 diabetes development. These data also support therapeutic efforts that seek to modify gut microbiota as a means to modulate development of this disorder.

BACKGROUND: Men who have sex with other men (MSM) are a vulnerable population in Africa that has been insufficiently explored. Given the high rate of bisexuality among MSM (73% in the past year), it is important to understand their risk-taking behaviors regarding both men and women. METHODOLOGY/PRINCIPAL FINDINGS: A socio-behavioral survey was carried out in 2007 among 501 MSM recruited using the snowball sampling method. We explore in this article why a condom was not used during last sexual intercourse with a man and with a woman, taking into account the respondent's characteristics, type of relationship and the context of the sexual act. In the survey, 489 men reported that they had had sexual intercourse at least once with another man during the previous year, and 358 with a man and with a woman. The main risk factors for not using a condom at last sexual intercourse with another man were having sex in a public place (aOR = 6.26 [95%CI: 2.71-14.46]), non-participation in an MSM prevention program (aOR = 3.47 [95%CI: 2.12-5.69]), a 19 years old or younger partner (aOR = 2.6 [95%CI: 1.23-4.53]), being 24 years or younger (aOR = 2.07 [95%CI: 1.20-3.58]) or being 35 years or over (aOR = 3.08 [95%CI:1.11-8.53]) and being unemployed (aOR = 0.36 [95%CI: 0.10-1.25]). The last sexual intercourse with the respondent's wife was hardly ever protected (2%). With women, the other factors were a 15 years or younger partner (aOR = 6.45 [95%CI: 2.56-16.28]), being educated (primary: aOR = 0.45 [95%CI: 0.21-0.95], secondary or higher: aOR = 0.26 [95%CI: 0.11-0.62]), being a student (aOR = 2.20 [95%CI: 1.07-4.54]) or unemployed (aOR = 3.72 [95%CI: 1.31-10.61]) and having participated in a MSM prevention program (aOR = 0.57 [95%CI: 0.34-0.93]). CONCLUSION: Having participated in a prevention program specifically targeting MSM constitutes a major prevention factor. However, these programs targeting MSM must address their heterosexual practices and the specific risks involved.

A multistate listeriosis outbreak associated with cantaloupe consumption was reported in the United States in September, 2011. The outbreak investigation recorded a total of 146 invasive illnesses, 30 deaths and one miscarriage. Subtyping of the outbreak associated clinical, food and environmental isolates revealed two serotypes (1/2a and 1/2b) and four pulsed-field gel electrophoresis two-enzyme pattern combinations I, II, III, and IV, including one rarely seen before this outbreak. A DNA-microarray, Listeria GeneChip®, developed by FDA from 24 Listeria monocytogenes genome sequences, was used to further characterize a representative sample of the outbreak isolates. The microarray data (in the form of present or absent calls of specific DNA sequences) separated the isolates into two distinct groups as per their serotypes. The gene content of the outbreak-associated isolates was distinct from that of the previously-reported outbreak strains belonging to the same serotypes. Although the 1/2b outbreak associated isolates are closely related to each other, the 1/2a isolates could be further divided into two distinct genomic groups, one represented by pattern combination I strains and the other represented by highly similar pattern combinations III and IV strains. Gene content analysis of these groups revealed unique genomic sequences associated with these two 1/2a genovars. This work underscores the utility of multiple approaches, such as serotyping, PFGE and DNA microarray analysis to characterize the composition of complex polyclonal listeriosis outbreaks.