Epidemiological connectivity between humans and animals across an urban landscape.

Urbanization is predicted to be a key driver of disease emergence through human exposure to novel, animal-borne pathogens. However, while we suspect that urban landscapes are primed to expose people to novel animal-borne diseases, evidence for the mechanisms by which this occurs is lacking. To address this, we studied how bacterial genes are shared between wild animals, livestock, and humans (n = 1,428) across Nairobi, Kenya-one of the world's most rapidly developing cities. Applying a multilayer network framework, we show that low biodiversity (of both natural habitat and vertebrate wildlife communities), coupled with livestock management practices and more densely populated urban environments, promotes sharing of Escherichia coli-borne bacterial mobile genetic elements between animals and humans. These results provide empirical support for hypotheses linking resource provision, the biological simplification of urban landscapes, and human and livestock demography to urban dynamics of cross-species pathogen transmission at a landscape scale. Urban areas where high densities of people and livestock live in close association with synanthropes (species such as rodents that are more competent reservoirs for zoonotic pathogens) should be prioritized for disease surveillance and control.

Using Causal Bayesian Networks to Assess the Role of Patient-Centered Care and Psychosocial Factors on Durable HIV Viral Suppression.

We assessed the role of patient-centered care on durable viral suppression (i.e., all viral load test results < 200 copies per ml during 2019) by conducting a retrospective cohort study of clients medically case managed by the Miami-Dade County Ryan White Program (RWP). Summary measures of patient-centered care practices of RWP-affiliated providers were obtained from a survey of 1352 clients. Bayesian network models analyzed the complex relationship between psychosocial and patient-centered care factors. Of 5037 clients, 4135 (82.1%) had durable viral suppression. Household income was the factor most strongly associated with durable viral suppression. Further, mean healthcare relationship score and mean "provider knows patient as a person" score were both associated with durable viral suppression. Healthcare relationship score moderated the association between low household income and lack of durable viral suppression. Although patient-centered care supports patient HIV care success, wrap around support is also needed for people with unmet psychosocial needs.

RESUMEN: Evaluamos el rol de la atención centrada en el paciente en la supresión viral duradera (es decir, todos los resultados de las pruebas de carga viral < 200 copias por ml durante 2019) mediante la realización de un estudio de cohorte retrospectivo de clientes manejados médicamente por el Programa Ryan White del condado de Miami-Dade (RWP). Se obtuvieron medidas resumidas de las prácticas de atención centradas en el paciente de los proveedores afiliados a RWP usando una encuesta de 1352 clientes. Los modelos de redes bayesianos analizaron la relación compleja entre los factores psicosociales y de atención centrada en el paciente. De 5037 clientes, 4135 (82,1%) tenían una supresión viral duradera. Los ingresos del hogar fueron el factor asociado con la supresión viral duradera más fuerte. Además, la puntuación promedia de la relación con proveedores de atención médica y la puntuación promedia de "el proveedor conoce al paciente como persona" fueron asociados con una supresión viral duradera. La puntuación de la relación con proveedores de atención médica moderó la asociación entre los ingresos bajos del hogar y la falta de supresión viral duradera. Aunque la atención centrada en el paciente apoya el éxito de la atención médica del VIH, también se necesita un apoyo integral para las personas con necesidades psicosociales insatisfechas.

Exploring the use of self-management strategies for antiretroviral therapy adherence among women with HIV in the Miami-Dade County Ryan White Program.

Women with HIV (WWH) face increased difficulties maintaining adherence to antiretroviral therapy (ART) due to a variety of demographic and psychosocial factors. To navigate the complexities of ART regimens, use of strategies to maintain adherence is recommended. Research in this area, however, has largely focused on adherence interventions, and few studies have examined self-reported preferences for adherence strategies. The purpose and objectives of this study were to explore the use of ART self-management strategies among a diverse sample of WWH, examine demographic and psychosocial differences in strategy use, and assess the association between strategies and ART adherence. The current study presents secondary data of 560 WWH enrolled in the Miami-Dade County Ryan White Program. Participants responded to questionnaire items assessing demographic and psychosocial characteristics, use of adherence strategies, and ART adherence during the past month. Principal component analysis identified four categories among the individual strategies and multivariable binomial logistic regression assessed adherence while controlling for individual-level factors. The majority of WWH reported optimal ART adherence, and nearly all used multiple individual strategies. The number of individual strategies used and preferences for strategy types were associated with various demographic and psychosocial characteristics. Adjusting for demographic and psychosocial characteristics, optimal ART adherence during the past month was associated with the use of four or more individual strategies. When conducting regular assessments of adherence, it may be beneficial to also assess use of adherence strategies and to discuss with WWH how using multiple strategies contributes to better adherence.

How patients experience respect in healthcare: findings from a qualitative study among multicultural women living with HIV.

BACKGROUND: Respect is essential to providing high quality healthcare, particularly for groups that are historically marginalized and stigmatized. While ethical principles taught to health professionals focus on patient autonomy as the object of respect for persons, limited studies explore patients' views of respect. The purpose of this study was to explore the perspectives of a multiculturally diverse group of low-income women living with HIV (WLH) regarding their experience of respect from their medical physicians. METHODS: We analyzed 57 semi-structured interviews conducted at HIV case management sites in South Florida as part of a larger qualitative study that explored practices facilitating retention and adherence in care. Women were eligible to participate if they identified as African American (n = 28), Hispanic/Latina (n = 22), or Haitian (n = 7). They were asked to describe instances when they were treated with respect by their medical physicians. Interviews were conducted by a fluent research interviewer in either English, Spanish, or Haitian Creole, depending on participant's language preference. Transcripts were translated, back-translated and reviewed in entirety for any statements or comments about "respect." After independent coding by 3 investigators, we used a consensual thematic analysis approach to determine themes. RESULTS: Results from this study grouped into two overarching classifications: respect manifested in physicians' orientation towards the patient (i.e., interpersonal behaviors in interactions) and respect in medical professionalism (i.e., clinic procedures and practices). Four main themes emerged regarding respect in provider's orientation towards the patient: being treated as a person, treated as an equal, treated without blame or prejudice, and treated with concern/emotional support. Two main themes emerged regarding respect as evidenced in medical professionalism: physician availability and considerations of privacy. CONCLUSIONS: Findings suggest a more robust conception of what 'respect for persons' entails in medical ethics for a diverse group of low-income women living with HIV. Findings have implications for broadening areas of focus of future bioethics education, training, and research to include components of interpersonal relationship development, communication, and clinic procedures. We suggest these areas of training may increase respectful medical care experiences and potentially serve to influence persistent and known social and structural determinants of health through provider interactions and health care delivery.

Sex differences in psychosocial and demographic factors associated with sustained HIV viral suppression in the Miami-Dade County Ryan White Program, 2017.

This exploratory study examined sex differences in psychosocial and demographic factors associated with sustained HIV viral suppression (SVS). The study population included 6,489 Miami-Dade Ryan White Program (RWP) clients receiving services during 2017; administrative data was analyzed. SVS was defined as having all viral load tests during 2017 below 200 copies/ml. Multilevel logistic regression models accounted for clustering by medical case management site. Models were stratified by sex. Overall, a higher proportion of females did not achieve SVS (23.5%) than males (18.1%). For females (n = 1,503), having acquired HIV perinatally and not having a partner oradult household member were associated with not achieving SVS. For males (n = 4,986), lacking access to food, Black or Haitian race/ethnicity, problematic substance use, and unknown physician were associated with not achieving SVS. For both sexes, younger age, lower household income, ever having an AIDS diagnosis, feeling depressed or anxious, and experiencing homelessness were associated with not achieving SVS. Elements of the transition from adolescent to adult HIV care that may differentially impact female clients and factors associated with disclosure should be explored further. Male clients may require additional support for food security. Improving culturally specific care for Haitian and non-Hispanic Black male clients should also be explored.

Barriers and facilitators to retention in care and treatment adherence among racially/ethnically diverse women with HIV in South Florida: a qualitative study.

Women, particularly those from racial/ethnic minority groups, experience disparities in HIV care and treatment, and in achieving viral suppression. This study identified barriers and facilitators influencing retention in HIV care and treatment adherence among women belonging to racial/ethnic minority groups. We conducted semi-structured interviews with 74 African American, Hispanic/Latina and Haitian cisgender women receiving care from the Ryan White HIV/AIDS Program in Miami-Dade County, Florida in 2019. Data were analyzed using a thematic analysis approach. The most salient barriers faced by women were competing life priorities, mental health and substance use issues, medication-related concerns and treatment burden, negative experiences with HIV care services, transportation and parking issues and stigma and discrimination. Important facilitators identified by women included taking personal responsibility for health, social support, and patient-friendly and supportive HIV care services. Our findings suggest that HIV care could be enhanced for this population by understanding the non-HIV needs of the women in care, provide more flexible and relevant services in response to the totality of these needs, and simplify and expand access to care and supportive services.

Increased alcohol use during the COVID-19 pandemic among people with HIV from racial/ethnic minority groups in South Florida.

People with HIV (PWH) from racial/ethnic minority groups may be particularly vulnerable to the effects of the COVID-19 Pandemic. Exacerbated COVID-19-related stressors may lead to maladaptive coping mechanisms such as increased alcohol use. This study examined socioeconomic and psychosocial predictors of increased alcohol use during the first year of the COVID-19 Pandemic among PWH from racial/ethnic minority groups in South Florida. Data were collected from Ryan White Program clients during October 2020-January 2021 using a cross-sectional phone survey, and were analyzed using logistic regression modeling. Among 139 participants, 20% reported increased alcohol use. Findings showed that being unable to buy needed food (adjusted odds ratio [aOR]: 3.37; 95% confidence interval [CI]: 1.01-11.31) and spending more time caring for children (aOR: 5.22, 95% CI: 1.61-16.88) was associated with increased alcohol use during the Pandemic. Providing support to alleviate food insecurity and manage caregiving burden during public health crises like the COVID-19 Pandemic might help prevent increases in alcohol use among PWH.

Genomic epidemiology of Escherichia coli: antimicrobial resistance through a One Health lens in sympatric humans, livestock and peri-domestic wildlife in Nairobi, Kenya.

BACKGROUND: Livestock systems have been proposed as a reservoir for antimicrobial-resistant (AMR) bacteria and AMR genetic determinants that may infect or colonise humans, yet quantitative evidence regarding their epidemiological role remains lacking. Here, we used a combination of genomics, epidemiology and ecology to investigate patterns of AMR gene carriage in Escherichia coli, regarded as a sentinel organism. METHODS: We conducted a structured epidemiological survey of 99 households across Nairobi, Kenya, and whole genome sequenced E. coli isolates from 311 human, 606 livestock and 399 wildlife faecal samples. We used statistical models to investigate the prevalence of AMR carriage and characterise AMR gene diversity and structure of AMR genes in different host populations across the city. We also investigated household-level risk factors for the exchange of AMR genes between sympatric humans and livestock. RESULTS: We detected 56 unique acquired genes along with 13 point mutations present in variable proportions in human and animal isolates, known to confer resistance to nine antibiotic classes. We find that AMR gene community composition is not associated with host species, but AMR genes were frequently co-located, potentially enabling the acquisition and dispersal of multi-drug resistance in a single step. We find that whilst keeping livestock had no influence on human AMR gene carriage, the potential for AMR transmission across human-livestock interfaces is greatest when manure is poorly disposed of and in larger households. CONCLUSIONS: Findings of widespread carriage of AMR bacteria in human and animal populations, including in long-distance wildlife species, in community settings highlight the value of evidence-based surveillance to address antimicrobial resistance on a global scale. Our genomic analysis provided an in-depth understanding of AMR determinants at the interfaces of One Health sectors that will inform AMR prevention and control.

Virtual town halls addressing vaccine hesitancy among racial/ethnic minorities: Preliminary findings.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic remains a public health priority, and vaccination is important for ending the pandemic. Racial and ethnic minorities are disproportionally affected by COVID-19 yet report high levels of vaccination hesitancy. OBJECTIVE: We conducted virtual town halls to address vaccine hesitancy among racial and ethnic minorities in South Florida. METHODS: Our approach used social influence and persuasion models. In a formative phase, we gathered meeting preferences from our communities and developed and tested our approach. In an implementation phase, we conducted 6 virtual town halls in partnership with minority community-based organizations. RESULTS: The town halls reached 383 participants (mean age 37.5 years; 63.4% female, 33.9% male, 2.7% nonbinary; 59% racial/ethnic minority) who completed pre- and postmeeting assessments. Among nonvaccinated participants, at the prepoll, 58% reported a high likelihood of seeking vaccination, rising to 63% at the postassessment. Unvaccinated non-hesitant and hesitant groups were compared on trusted information sources and reasons and barriers for vaccination. Nonhesitant participants reported significantly greater trust in the COVID-19 Task Force (97.3% vs. 83.3%) as a source of vaccine information than did hesitant participants. Nonhesitant participants were significantly more likely to endorse family safety (82.5% vs. 63.2%), community safety (72.5% vs. 26.3%), personal safety (85% vs. 36.8%), and wanting to return to a normal life (70% vs. 31.6%) as reasons for vaccination than were hesitant participants. Hesitant participants were significantly more likely to endorse concerns about vaccine safety doubts (63.2% vs. 17.5%) and not believing the pandemic is as bad as people say it is (21.1% vs. 5%) as barriers to vaccination than were nonhesitant participants. Qualitative data revealed high consumer satisfaction with the town halls. CONCLUSION: This study supports the feasibility, acceptability, and potential impact of virtual town halls for addressing vaccine hesitancy among racial/ethnic minorities; however, our approach was resource intensive, required an extensive community-university collaborative infrastructure, and yielded a small effect.

Coast-wide evidence of low pH amelioration by seagrass ecosystems.

Global-scale ocean acidification has spurred interest in the capacity of seagrass ecosystems to increase seawater pH within crucial shoreline habitats through photosynthetic activity. However, the dynamic variability of the coastal carbonate system has impeded generalization into whether seagrass aerobic metabolism ameliorates low pH on physiologically and ecologically relevant timescales. Here we present results of the most extensive study to date of pH modulation by seagrasses, spanning seven meadows (Zostera marina) and 1000 km of U.S. west coast over 6 years. Amelioration by seagrass ecosystems compared to non-vegetated areas occurred 65% of the time (mean increase 0.07 ± 0.008 SE). Events of continuous elevation in pH within seagrass ecosystems, indicating amelioration of low pH, were longer and of greater magnitude than opposing cases of reduced pH or exacerbation. Sustained elevations in pH of >0.1, comparable to a 30% decrease in [H+ ], were not restricted only to daylight hours but instead persisted for up to 21 days. Maximal pH elevations occurred in spring and summer during the seagrass growth season, with a tendency for stronger effects in higher latitude meadows. These results indicate that seagrass meadows can locally alleviate low pH conditions for extended periods of time with important implications for the conservation and management of coastal ecosystems.

Socio-ecological drivers of vertebrate biodiversity and human-animal interfaces across an urban landscape.

Urbanization can have profound impacts on the distributional ecology of wildlife and livestock, with implications for biodiversity conservation, ecosystem services and human health. A wealth of studies have assessed biotic responses to urbanization in North America and Europe, but there is little empirical evidence that directly links human activities to urban biodiversity in the tropics. Results from a large-scale field study conducted in Nairobi, Kenya, are used to explore the impact of human activities on the biodiversity of wildlife and livestock with which humans co-exist across the city. The structure of sympatric wildlife, livestock and human populations are characterized using unsupervised machine learning, and statistical modelling is used to relate compositional variation in these communities to socio-ecological drivers occurring across the city. By characterizing landscape-scale drivers acting on these interfaces, we demonstrate that socioeconomics, elevation and subsequent changes in habitat have measurable impacts upon the diversity, density and species assemblage of wildlife, livestock and humans. Restructuring of wildlife and livestock assemblages (both in terms of species diversity and composition) has important implications for the emergence of novel diseases at urban interfaces, and we therefore use our results to generate a set of testable hypotheses that explore the influence of urban change on microbial communities. These results provide novel insight into the impact of urbanization on biodiversity in the tropics. An understanding of associations between urban processes and the structure of human and animal populations is required to link urban development to conservation efforts and risks posed by disease emergence to human health, ultimately informing sustainable urban development policy.

Seagrass-driven changes in carbonate chemistry enhance oyster shell growth.

Quantifying the strength of non-trophic interactions exerted by foundation species is critical to understanding how natural communities respond to environmental stress. In the case of ocean acidification (OA), submerged marine macrophytes, such as seagrasses, may create local areas of elevated pH due to their capacity to sequester dissolved inorganic carbon through photosynthesis. However, although seagrasses may increase seawater pH during the day, they can also decrease pH at night due to respiration. Therefore, it remains unclear how consequences of such diel fluctuations may unfold for organisms vulnerable to OA. We established mesocosms containing different levels of seagrass biomass (Zostera marina) to create a gradient of carbonate chemistry conditions and explored consequences for growth of juvenile and adult oysters (Crassostrea gigas), a non-native species widely used in aquaculture that can co-occur, and is often grown, in proximity to seagrass beds. In particular, we investigated whether increased diel fluctuations in pH due to seagrass metabolism affected oyster growth. Seagrasses increased daytime pH up to 0.4 units but had little effect on nighttime pH (reductions less than 0.02 units). Thus, both the average pH and the amplitude of diel pH fluctuations increased with greater seagrass biomass. The highest seagrass biomass increased oyster shell growth rate (mm day-1) up to 40%. Oyster somatic tissue weight and oyster condition index exhibited a different pattern, peaking at intermediate levels of seagrass biomass. This work demonstrates the ability of seagrasses to facilitate oyster calcification and illustrates how non-trophic metabolic interactions can modulate effects of environmental change.

Healthcare Workers' Strategies for Doffing Personal Protective Equipment.

BACKGROUND: Personal protective equipment (PPE) helps protect healthcare workers (HCWs) from pathogens and prevents cross-contamination. PPE effectiveness is often undermined by inappropriate doffing methods. Our knowledge of how HCWs approach doffing PPE in practice is limited. In this qualitative study, we examine HCWs' perspectives about doffing PPE. METHODS: Thirty participants at a Midwestern academic hospital were recruited and assigned to 1 of 3 doffing simulation scenarios: 3 mask designs (n = 10), 2 gown designs (n = 10), or 2 glove designs (n = 10). Participants were instructed to doff PPE as they would in routine practice. Their performances were video-recorded and reviewed with participants. Semistructured interviews about their doffing approaches were conducted and audio-recorded, then transcribed and thematically analyzed. RESULTS: Three overarching themes were identified in interviews: doffing strategies, cognitive processes, and barriers and facilitators. Doffing strategies included doffing safely (minimizing self-contamination) and doffing expediently (eg, ripping PPE off). Cognitive processes during doffing largely pertained to tracking contaminated PPE surfaces, examining PPE design cues (eg, straps), or improvising based on prior experience from training or similar PPE designs. Doffing barriers and facilitators typically related to PPE design, such as PPE fit (or lack of it) and fastener type. Some participants also described personal barriers (eg, glasses, long hair); however, some PPE designs helped mitigate these barriers. CONCLUSIONS: Efforts to improve HCWs' doffing performance need to address HCWs' preferences for both safety and expediency when using PPE, which has implications for PPE design, training approaches, and hospital policies and procedures.

Are Food Animals Responsible for Transfer of Antimicrobial-Resistant Escherichia coli or Their Resistance Determinants to Human Populations? A Systematic Review.

The role of farm animals in the emergence and dissemination of both AMR bacteria and their resistance determinants to humans is poorly understood and controversial. Here, we systematically reviewed the current evidence that food animals are responsible for transfer of AMR to humans. We searched PubMed, Web of Science, and EMBASE for literature published between 1940 and 2016. Our results show that eight studies (18%) suggested evidence of transmission of AMR from food animals to humans, 25 studies (56%) suggested transmission between animals and humans with no direction specified and 12 studies (26%) did not support transmission. Quality of evidence was variable among the included studies; one study (2%) used high resolution typing tools, 36 (80%) used intermediate resolution typing tools, six (13%) relied on low resolution typing tools, and two (5%) based conclusions on co-occurrence of resistance. While some studies suggested to provide evidence that transmission of AMR from food animals to humans may occur, robust conclusions on the directionality of transmission cannot be drawn due to limitations in study methodologies. Our findings highlight the need to combine high resolution genomic data analysis with systematically collected epidemiological evidence to reconstruct patterns of AMR transmission between food animals and humans.

Utility of Whole-Genome Sequencing of Escherichia coli O157 for Outbreak Detection and Epidemiological Surveillance.

Detailed laboratory characterization of Escherichia coli O157 is essential to inform epidemiological investigations. This study assessed the utility of whole-genome sequencing (WGS) for outbreak detection and epidemiological surveillance of E. coli O157, and the data were used to identify discernible associations between genotypes and clinical outcomes. One hundred five E. coli O157 strains isolated over a 5-year period from human fecal samples in Lothian, Scotland, were sequenced with the Ion Torrent Personal Genome Machine. A total of 8,721 variable sites in the core genome were identified among the 105 isolates; 47% of the single nucleotide polymorphisms (SNPs) were attributable to six "atypical" E. coli O157 strains and included recombinant regions. Phylogenetic analyses showed that WGS correlated well with the epidemiological data. Epidemiological links existed between cases whose isolates differed by three or fewer SNPs. WGS also correlated well with multilocus variable-number tandem repeat analysis (MLVA) typing data, with only three discordant results observed, all among isolates from cases not known to be epidemiologically related. WGS produced a better-supported, higher-resolution phylogeny than MLVA, confirming that the method is more suitable for epidemiological surveillance of E. coli O157. A combination of in silico analyses (VirulenceFinder, ResFinder, and local BLAST searches) were used to determine stx subtypes, multilocus sequence types (15 loci), and the presence of virulence and acquired antimicrobial resistance genes. There was a high level of correlation between the WGS data and our routine typing methods, although some discordant results were observed, mostly related to the limitation of short sequence read assembly. The data were used to identify sublineages and clades of E. coli O157, and when they were correlated with the clinical outcome data, they showed that one clade, Ic3, was significantly associated with severe disease. Together, the results show that WGS data can provide higher resolution of the relationships between E. coli O157 isolates than that provided by MLVA. The method has the potential to streamline the laboratory workflow and provide detailed information for the clinical management of patients and public health interventions.

Dynamics of the emergence and establishment of a newly dominant genotype of Japanese encephalitis virus throughout Asia.

UNLABELLED: In recent years, genotype I (GI) of Japanese encephalitis virus (JEV) has displaced genotype III (GIII) as the dominant virus genotype throughout Asia. In this study, the largest collection of GIII and GI envelope gene-derived viral sequences assembled to date was used to reconstruct the spatiotemporal chronology of genotype displacement throughout Asia and to determine the evolutionary and epidemiological dynamics underlying this significant event. GI consists of two clades, GI-a and GI-b, with the latter being associated with displacement of GIII as the dominant JEV genotype throughout Asia in the 1990s. Phylogeographic analysis indicated that GI-a diverged in Thailand or Cambodia and has remained confined to tropical Asia, whereas GI-b diverged in Vietnam and then dispersed northwards to China, where it was subsequently dispersed to Japan, Korea, and Taiwan. Molecular adaptation was detected by more than one method at one site (residue 15), and coevolution was detected at two pairs of sites (residues 89 to 360 and 129 to 141) within the GI E gene protein alignment. Viral multiplication and temperature sensitivity analyses in avian and mosquito cells revealed that the GI-b isolate JE-91 had significantly higher infectivity titers in mosquito cells from 24 to 48 h postinfection than did the GI-a and GIII isolates. If the JE-91 isolate is indeed representative of GI-b, an increased multiplicative ability of GI-b viruses compared to that of GIII viruses early in mosquito infection may have resulted in a shortened extrinsic incubation period that led to an increased number of GI enzootic transmission cycles and the subsequent displacement of GIII. IMPORTANCE: Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, represents the most significant etiology of childhood viral neurological infection in Asia. Despite the existence of effective vaccines, JEV is responsible for an estimated 68,000 human cases and a reported 10,000 to 15,000 deaths annually. Phylogenetic studies divided JEV into five geographically and epidemiologically distinct genotypes (GI to GV). GIII has been the source of numerous JEV epidemics throughout history and was the most frequently isolated genotype throughout most of Asia from 1935 until the 1990s. In recent years, GI has displaced GIII as the most frequently isolated virus genotype. To date, the mechanism of this genotype replacement has remained unknown. In this study, we have identified genetic determinants underlying the genotype displacement as it unfolded across Asia. JEV provides a paradigm for other flaviviruses, including West Nile, yellow fever, and dengue viruses, and the critical role of the selective advantages in the mosquito vector.

Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation.

Growing evidence suggests that pretransplant alpha-fetoprotein (AFP) predicts outcomes of hepatocellular carcinoma (HCC) patients treated with liver transplantation. We aimed to determine whether pretransplant AFP, Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3), and des-gamma-carboxyprothrombin (DCP) predicted HCC recurrence after transplantation. A retrospective cohort study of 313 HCC patients undergoing transplantation between 2000 and 2008 was conducted, and 48 (15.3%) developed recurrence during a median follow-up of 90.8 months. The 127 patients with available serum drawn before transplantation were included; they included 86 without recurrence and 41 with recurrence. Serum was tested for AFP, AFP-L3%, and DCP in a blinded fashion with the µTASWako i30 immunoanalyzer. All biomarkers were significantly associated with HCC recurrence. The hazard ratios (HRs) were 3.5 [95% confidence interval (CI), 1.9-6.7; P < 0.0001] for DCP ≥ 7.5 ng/mL and 2.8 (95% CI, 1.4-5.4; P = 0.002) for AFP ≥ 250 ng/mL. The HR increased to 5.2 (95% CI, 2.3-12.0; P < 0.0001) when AFP ≥ 250 ng/mL and DCP ≥7.5 ng/mL were considered together. When they were combined with the Milan criteria, the HR increased from 2.6 (95% CI, 1.4-4.7; P = 0.003) for outside the Milan criteria to 8.6 (95% CI, 3.0-24.6; P < 0.0001) for outside the Milan criteria and AFP ≥ 250 ng/mL and to 7.2 (95% CI, 2.8-18.1; P < 0.0001) for outside the Milan criteria and DCP ≥7.5 ng/mL. Our findings suggest that biomarkers are useful for predicting the risk of HCC recurrence after transplantation. Using both biomarkers and the Milan criteria may be better than using the Milan criteria alone in optimizing the decision of liver transplantation eligibility.

Association of a bundled intervention with surgical site infections among patients undergoing cardiac, hip, or knee surgery.

IMPORTANCE: Previous studies suggested that a bundled intervention was associated with lower rates of Staphylococcus aureus surgical site infections (SSIs) among patients having cardiac or orthopedic operations. OBJECTIVE: To evaluate whether the implementation of an evidence-based bundle is associated with a lower risk of S. aureus SSIs in patients undergoing cardiac operations or hip or knee arthroplasties. DESIGN, SETTING, AND PARTICIPANTS: Twenty hospitals in 9 US states participated in this pragmatic study; rates of SSIs were collected for a median of 39 months (range, 39-43) during the preintervention period (March 1, 2009, to intervention) and a median of 21 months (range, 14-22) during the intervention period (from intervention start through March 31, 2014). INTERVENTIONS: Patients whose preoperative nares screens were positive for methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA) were asked to apply mupirocin intranasally twice daily for up to 5 days and to bathe daily with chlorhexidine-gluconate (CHG) for up to 5 days before their operations. MRSA carriers received vancomycin and cefazolin or cefuroxime for perioperative prophylaxis; all others received cefazolin or cefuroxime. Patients who were MRSA-negative and MSSA-negative bathed with CHG the night before and morning of their operations. Patients were treated as MRSA-positive if screening results were unknown. MAIN OUTCOMES AND MEASURES: The primary outcome was complex (deep incisional or organ space) S. aureus SSIs. Monthly SSI counts were analyzed using Poisson regression analysis. RESULTS: After a 3-month phase-in period, bundle adherence was 83% (39% full adherence; 44% partial adherence). Overall, 101 complex S. aureus SSIs occurred after 28,218 operations during the preintervention period and 29 occurred after 14,316 operations during the intervention period (mean rate per 10,000 operations, 36 for preintervention period vs 21 for intervention period, difference, -15 [95% CI, -35 to -2]; rate ratio [RR], 0.58 [95% CI, 0.37 to 0.92]). The rates of complex S. aureus SSIs decreased for hip or knee arthroplasties (difference per 10,000 operations, -17 [95% CI, -39 to 0]; RR, 0.48 [95% CI, 0.29 to 0.80]) and for cardiac operations (difference per 10,000 operations, -6 [95% CI, -48 to 8]; RR, 0.86 [95% CI, 0.47 to 1.57]). CONCLUSIONS AND RELEVANCE: In this multicenter study, a bundle comprising S. aureus screening, decolonization, and targeted prophylaxis was associated with a modest, statistically significant decrease in complex S. aureus SSIs.

Searching for an optimal hand hygiene bundle: a meta-analysis.

Many studies have evaluated bundled interventions to improve hand hygiene compliance. However, there are few evidence-based recommendations on optimal interventions for implementation. We aimed to systematically review all studies on interventions to improve hand hygiene compliance to evaluate existing bundles and identify areas of promise to target high-quality studies. Adjusted risk ratios were pooled to assess common bundles. Of the 8148 studies evaluated, 6 randomized controlled trials and 39 quasi-experimental studies met inclusion criteria. Three studies evaluated the interventions education, reminders, feedback, administrative support, and access to alcohol-based hand rub as a bundle, which was associated with improved hand hygiene compliance (pooled odds ratio [OR], 1.82; 95% confidence interval [CI], 1.69-1.97). Another bundle of education, reminders, and feedback evaluated in 3 studies was associated with improved compliance (pooled OR, 1.47; 95% CI, 1.12-1.94). These bundles should be further studied using high-quality study designs and compared with other interventions.

Estimating the rate of intersubtype recombination in early HIV-1 group M strains.

West Central Africa has been implicated as the epicenter of the HIV-1 epidemic, and almost all group M subtypes can be found there. Previous analysis of early HIV-1 group M sequences from Kinshasa in the Democratic Republic of Congo, formerly Zaire, revealed that isolates from a number of individuals fall in different positions in phylogenetic trees constructed from sequences from opposite ends of the genome as a result of recombination between viruses of different subtypes. Here, we use discrete ancestral trait mapping to develop a procedure for quantifying HIV-1 group M intersubtype recombination across phylogenies, using individuals' gag (p17) and env (gp41) subtypes. The method was applied to previously described HIV-1 group M sequences from samples obtained in Kinshasa early in the global radiation of HIV. Nine different p17 and gp41 intersubtype recombinant combinations were present in the data set. The mean number of excess ancestral subtype transitions (NEST) required to map individuals' p17 subtypes onto the gp14 phylogeny samples, compared to the number required to map them onto the p17 phylogenies, and vice versa, indicated that excess subtype transitions occurred at a rate of approximately 7 × 10(-3) to 8 × 10(-3) per lineage per year as a result of intersubtype recombination. Our results imply that intersubtype recombination may have occurred in approximately 20% of lineages evolving over a period of 30 years and confirm intersubtype recombination as a substantial force in generating HIV-1 group M diversity.