Search

Policy PointsThe implementation of large‐scale health care interventions relies on a shared vision, commitment to change, coordination across sites, and a spanning of siloed knowledge.Enablers of the system should include building an authorizing environment; providing relevant, meaningful, transparent, and timely data; designating and distributing leadership and decision making; and fostering the emergence of a learning culture.Attention to these four enablers can set up a positive feedback loop to foster positive change that can protect against the loss of key staff, the presence of lone disruptors, and the enervating effects of uncertainty. Context: Large‐scale transformative initiatives have the potential to improve the quality, efficiency, and safety of health care. However, change is expensive, complex, and difficult to implement and sustain. This paper advances system enablers, which will help to guide large‐scale transformation in health care systems. Methods: A realist study of the implementation of a value‐based health care program between 2017 and 2021 was undertaken in every public hospital (n = 221) in New South Wales (NSW), Australia. Four data sources were used to elucidate initial program theories beginning with a set of literature reviews, a program document review, and informal discussions with key stakeholders. Semistructured interviews were then conducted with 56 stakeholders to confirm, refute, or refine the theories. A retroductive analysis produced a series of context‐mechanism‐outcome (CMO) statements. Next, the CMOs were validated with three health care quality expert panels (n = 51). Synthesized data were interrogated to distill the overarching system enablers. Findings: Forty‐two CMO statements from the eight initial program theory areas were developed, refined, and validated. Four system enablers were identified: (1) build an authorizing environment; (2) provide relevant, authentic, timely, and meaningful data; (3) designate and distribute leadership and decision making; and (4) support the emergence of a learning culture. The system enablers provide a nuanced understanding of large‐system transformation that illustrates when, for whom, and in what circumstances large‐system transformation worked well or worked poorly. Conclusions: System enablers offer nuanced guidance for the implementation of large‐scale health care interventions. The four enablers may be portable to similar contexts and provide the empirical basis for an implementation model of large‐system value‐based health care initiatives. With concerted application, these findings can pave the way not just for a better understanding of greater or lesser success in intervening in health care settings but ultimately to contribute higher quality, higher value, and safer care. [ABSTRACT FROM AUTHOR]

Background: As reproductive genetic carrier screening (RGCS) becomes more widely accessible, ensuring uptake by primary healthcare professionals (HCPs) is essential to equitable service provision. This study aimed to identify and prioritise implementation strategies to reduce barriers and support HCPs to routinely offer RGCS in Australia. Methods: HCPs (n = 990) involved in a large national research study, offering couples-based RGCS, were surveyed at three time points: prior to offering RGCS through the study (Survey 1: Barriers); 8+ weeks after offering to their patients (Survey 2: Possible supports); and towards the end of the study (Survey 3: Prioritised supports). HCPs were from primary care (e.g. general practice, midwifery) and tertiary care (e.g. fertility, genetics) settings. Results were analysed via a novel approach of using behaviour change theory (Capability, Opportunity and Motivation – COM.B) to align theory to practice. Results: Survey 1 (n = 599) identified four barrier themes: time constraints, lack of HCP knowledge and skill, patient receptivity, and HCP's perceived value of RGCS. Survey 2 (n = 358) identified 31 supports that could facilitate HCPs offering RGCS. Survey 3 (n = 390) was analysed separately by speciality and clinic location. Prioritised supports for primary care HCPs were 'regular continuing professional development activities' and 'a comprehensive website to direct patients for information'. There was general accordance with the perceived importance of the supports, although some difference in relation to funding between professional groups and clinic locations. Conclusion: This study identified a range of supports acceptable to HCPs across specialties and geographic locations that policymakers may use to direct efforts to ensure the roll out of RGCS is equitable across Australia. As reproductive genetic carrier screening becomes more widely accessible, ensuring uptake by primary health care professionals (HCPs) is essential to equitable service provision. We surveyed HCPs offering reproductive genetic carrier screening and identified a range of priorities to address barriers to and support for routine offering of screening. Top supports included patient resources, funding, and ongoing education. Policymakers may use these findings to direct their future efforts. [ABSTRACT FROM AUTHOR]

Summary: Key predictors of three trajectory group membership of potentially preventable hospitalisations were age, the number of comorbidities, the presence of chronic obstructive pulmonary disease and congestive heart failure, and frailty risk at the occurrence of hip fracture. These predictors of their trajectory group could be used in targeting prevention strategies. Purpose: Although older adults with hip fracture have a higher risk of multiple readmissions after index hospitalisation, little is known about potentially preventable hospitalisations (PPH) after discharge. This study examined group-based trajectories of PPH during a five-year period after a hip fracture among older adults and identified factors predictive of their trajectory group membership. Methods: This retrospective cohort study was conducted using linked hospitalisation and mortality data in New South Wales, Australia, between 2013 and 2021. Patients aged ≥ 65 years who were admitted after a hip fracture and discharged between 2014 and 2016 were identified. Group-based trajectory models were derived based on the number of subsequent PPH following the index hospitalisation. Multinominal logistic regression examined factors predictive of trajectory group membership. Results: Three PPH trajectory groups were revealed among 17,591 patients: no PPH (89.5%), low PPH (10.0%), and high PPH (0.4%). Key predictors of PPH trajectory group membership were age, number of comorbidities, dementia, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), frailty risk, place of incident, surgery, rehabilitation, and length of hospital stay. The high PPH had a higher proportion of patients with ≥ 2 comorbidities (OR: 1.86, 95% confidence interval (CI): 1.04–3.32) and COPD (OR: 2.97, 95%CIs: 1.76–5.04) than the low PPH, and the low and high PPHs were more likely to have CHF and high frailty risk as well as ≥ 2 comorbidities and COPD than the no PPH. Conclusions: Identifying trajectories of PPH after a hip fracture and factors predictive of trajectory group membership could be used to target strategies to reduce multiple readmissions. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Objective: This study summarizes findings from a cross-sectional survey conducted among National Collegiate Athletic Association (NCAA) Division 1 football programs, focusing on sport-related concussion (SRC) protocols for the 2018 season. Design: Cross-sectional survey study. Setting: 65 football programs within the Autonomy Five (A5) NCAA conferences. Participants: Athletic trainers and team physicians who attended a football safety meeting at the NCAA offices June 17 to 18, 2019, representing their respective institutions. Intervention: Electronic surveys were distributed on June 14, 2019, before the football safety meeting. Main Outcome Measures: Results for 16 unique questions involving SRC protocols and resources were summarized and evaluated. Results: The survey garnered responses from 46 of 65 programs (response rate = 71%). For baseline testing , 98% measured baseline postural stability and balance, 87% used baseline neurocognitive testing, while only 61% assessed baseline vestibular and/or ocular function. Regarding concussion prevention , 51% did not recommend additional measures, while 4% and 24% recommended cervical compression collars and omega-3 supplementation, respectively. In postconcussion treatment , 26% initiated aerobic exercise 1 day postconcussion if symptoms were stable, 24% waited at least 48 hours, 4% waited for the athlete to return to baseline, 11% waited until the athlete became asymptomatic, and 35% determined procedures on a case-by-case basis. Conclusions: Most institutions assessed postural stability/balance and neurocognitive functioning at baseline and introduced light aerobic exercise within 48 h postconcussion. There was variation in baseline assessment methods and concussion prevention recommendations. These survey findings deepen our understanding of diverse SRC protocols in NCAA football programs. [ABSTRACT FROM AUTHOR]

Context: It is suggested that postinjury pain is difficult to examine; thus, investigators have developed experimental pain models. To minimize pain, cryotherapy (cryo) is applied, but reports on its effectiveness are limited. Objective: To investigate a pain model for the anterior knee and examine cryo in reducing the pain. Design: Controlled laboratory study. Setting: Therapeutic modality laboratory. Participants: 30 physically active healthy male subjects who were free from any lower extremity orthopedic, neurological, cardiovascular, or endocrine pathologies. Main Outcome Measures: Perceived pain was measured every minute. Surface temperature was also assessed in the center of the patella and the popliteal fossa. Results: There was a significant interaction between group and time (F68,864 = 3.0, P = .0001). At the first minute, there was no difference in pain between the 3 groups (saline/cryo = 4.80 ± 4.87 mm, saline/sham = 2.80 ± 3.55 mm, no saline/ cryo = 4.00 ± 3.33 mm). During the first 5 min, pain increased from 4.80 ± 4.87 to 45.90 ± 21.17 mm in the saline/ cryo group and from 2.80 ± 3.55 to 31.10 ± 20.25 mm in the saline/sham group. Pain did not change within the no-saline/cryo group, 4.00 ± 3.33 to 1.70 ± 1.70 mm. Pain for the saline/sham group remained constant for 17 min. Cryo decreased pain for 16 min in the saline/cryo group. There was no difference in preapplication surface temperature between or within each group. No change in temperature occurred within the saline/ sham. Cooling and rewarming were similar in both cryo groups. Ambient temperature fluctuated less than 1°C during data collection. Conclusion: Intermittent infusion of sterile 5% hypertonic saline may be a useful experimental pain model in establishing a constant level of pain in a controlled laboratory setting. Cryotherapy decreased the induced anterior knee pain for 16 min. [ABSTRACT FROM AUTHOR]

Purpose: The substantial literature showing that offspring of parents with alcohol use disorder (AUD) is at increased risk for externalizing psychopathology rarely examines the differential effects of parental and offspring sex. This literature also has other important limitations, such as modest sample sizes and use of unrepresentative samples. Using a large, nationwide Swedish sample, we aim to investigate the roles of parental and offspring sex in externalizing psychopathology among offspring with parental AUD.Methods: AUD diagnosis and externalizing measures were obtained from national registries. Associations between outcomes and parental AUD were examined using logistic regressions. Parental and offspring sex effects were examined with interaction terms.Results: Risks for externalizing disorders were increased in sons and daughters with parental AUD, with significant differences between sons and daughters for criminal behavior; maternal AUD had a greater impact than paternal AUD (regardless of offspring sex), but having two parents with AUD increased risk for all outcomes substantially more than having one parent; and maternal AUD increased risk of drug abuse for daughters more than sons, while paternal AUD increased risk of AUD and criminal behavior for sons more than daughters.Conclusions: Offspring of parents with AUD are at increased risk for externalizing psychopathology. Maternal and paternal AUD differentially affected sons' vs. daughters' risks for AUD, drug abuse, and criminal behavior. The transmission of psychopathology within the externalizing spectrum appears to have sex-specific elements. [ABSTRACT FROM AUTHOR]

Students who demonstrate the most challenging behaviors are at risk of school failure and are often placed in alternative schools, in which a primary goal is remediating behavioral and academic concerns to facilitate students’ return to their community school. Consistently implemented evidence-based classroom management is necessary toward this goal; yet, many teachers report not having the necessary knowledge or skills to effectively manage behavior in their classroom. Implementation Planning (IP) is a proactive and efficient implementation support that has evidence of being effective when delivered by a consultant during behavioral consultation. The primary aim of this multiple baseline design study was to extend the findings on consultant-mediated IP by evaluating the effect of a self-guided, computer-based version of IP on teacher treatment integrity of classroom management plans. Unlike previous studies of consultant-mediated IP, results from this study indicated a minimal effect across dimensions of teachers’ implementation, and thus also on student disruptions. [ABSTRACT FROM AUTHOR]

Background: Healthcare triage policies are vital for allocating limited resources fairly and equitably. Despite extensive studies of healthcare equity, consensus on the applied definition of equity in triage remains elusive. This study aimed to investigate how the principles of equity are operationalised in Australian hospital physiotherapy triage tools to guide resource distribution. Methods: A retrospective, qualitative content analysis of 13 triage policies from 10 hospitals across Australia was conducted. Triage policies from both inpatient and outpatient settings were sourced. Data were coded deductively using the five discrete domains of the multi-faceted operational definition of health equity posited by Lane et al. (2017): 1) point of equalisation in the health service supply/access/outcome chain, 2) need or potential to benefit, 3) groupings of equalisation, 4) caveats to equalisation, 5) close enough is good enough. Descriptive summative statistics were used to analyse and present the frequency of reported equity domains. Results: Within the included triage tools, four out of five domains of equity were evident in the included documents to guide decision making. Allocation based on perceived patient need and overall health outcomes were the central guiding principles across both inpatient and outpatient settings. Equal provision of service relative to patient need and reducing wait times were also prioritised. However, explicit inclusion of certain equity domains such as discrimination, ensuring equal capability to be healthy and other patient factors was limited. Conclusions: Physiotherapy triage policies consider various domains of equity to guide resource allocation decisions. Policymakers and service providers can use the insights gained from this study to review the application and operationalisation of equity principles within their healthcare systems through mechanisms such as patient triage tools. [ABSTRACT FROM AUTHOR]

Background Resilience has been shown to be protective against alcohol use disorders (AUDs), but the magnitude and nature of the relationship between these 2 phenotypes are not clear. The aim of this study was to examine the strength of this relationship and the degree to which it results from common genetic or common environmental influences. Methods Resilience was assessed on a 9-point scale during a personal interview in 1,653,721 Swedish men aged 17 to 25 years. AUD was identified based on Swedish medical, legal, and pharmacy registries. The magnitude of the relationship between resilience and AUD was examined using logistic regression. The extent to which the relationship arises from common genetic or common environmental factors was examined using a bivariate Cholesky decomposition model. Results The 5 single items that comprised the resilience assessment (social maturity, interest, psychological energy, home environment, and emotional control) all reduced risk for subsequent AUD, with social maturity showing the strongest effect. The linear effect by logistic regression showed that a 1-point increase on the resilience scale was associated with a 29% decrease in odds of AUD. The Cholesky decomposition model demonstrated that the resilience-AUD relationship was largely attributable to overlapping genetic and shared environmental factors (57 and 36%, respectively). Conclusions Resilience is strongly associated with a reduction in risk for AUD. This relationship appears to be the result of overlapping genetic and shared environmental influences that impact resilience and risk of AUD, rather than a directly causal relationship. [ABSTRACT FROM AUTHOR]

Excessive internet use has been linked to psychopathology. Therefore, understanding the genetic and environmental risks underpinning internet use and their relation to psychopathology is important. This study aims to explore the genetic and environmental etiology of internet use measures and their associations with internalizing disorders and substance use disorders. The sample included 2,059 monozygotic (MZ) and dizygotic (DZ) young adult twins from the Brisbane Longitudinal Twin Study (BLTS). Younger participants reported more frequent internet use, while women were more likely to use the internet for interpersonal communication. Familial aggregation in ‘frequency of internet use’ was entirely explained by additive genetic factors accounting for 41% of the variance. Familial aggregation in ‘frequency of use after 11 pm’, ‘using the internet to contact peers’, and ‘using the internet primarily to access social networking sites’ was attributable to varying combinations of additive genetic and shared environmental factors. In terms of psychopathology, there were no significant associations between internet use measures and major depression (MD), but there were positive significant associations between ‘frequency of internet use’ and ‘frequency of use after 11 pm’ with social phobia (SP). ‘Using the internet to contact peers’ was positively associated with alcohol abuse, whereas ‘using the internet to contact peers’ and ‘using the internet primarily to access social networking sites’ were negatively associated with cannabis use disorders and nicotine symptoms. Individual differences in internet use can be attributable to varying degrees of genetic and environmental risks. Despite some significant associations of small effect, variation in internet use appears mostly unrelated to psychopathology. [ABSTRACT FROM PUBLISHER]

Context: Racial and ethnic differences in end-of-life care may be attributable to both patient preferences and health-care disparities. Identifying factors that differentiate preferences from disparities may enhance end-of-life care for critically ill patients and their families.Objectives: To understand the association of minority race/ethnicity and education with family ratings of the quality of dying and death, taking into consideration possible markers of patient and family preferences for end-of-life care as mediators of this association.Methods: Data were obtained from 15 intensive care units participating in a cluster-randomized trial of a palliative care intervention. Family members of decedents completed self-report surveys evaluating quality of dying. We used regression analyses to identify associations between race/ethnicity, education, and quality of dying ratings. We then used path analyses to investigate whether advance directives and life-sustaining treatment acted as mediators between patient characteristics and ratings of quality of dying.Results: Family members returned 1290 surveys for 2850 decedents. Patient and family minority race/ethnicity were both associated with lower ratings of quality of dying. Presence of a living will and dying in the setting of full support mediated the relationship between patient race and family ratings; patient race exerted an indirect, rather than direct, effect on quality of dying. Family minority race had a direct effect on lower ratings of quality of dying. Neither patient nor family education was associated with quality of dying.Conclusion: Minority race/ethnicity was associated with lower family ratings of quality of dying. This association was mediated by factors that may be markers of patient and family preferences (living will, death in the setting of full support); family member minority race/ethnicity was directly associated with lower ratings of quality of dying. Our findings generate hypothesized pathways that require future evaluation. [ABSTRACT FROM AUTHOR]

Background: Minority race and lower socioeconomic status are associated with poorer patient ratings of health care quality and provider communication. Objective: To examine the association of race/ethnicity or socioeconomic status with patients' and families' ratings of end-of-life care and communication about end-of-life care provided by physicians-in-training. Methods: As a component of a randomized trial evaluating a program designed to improve clinician communication about end-of-life care, patients and patients' families completed preintervention survey data regarding care and communication provided by internal medicine residents and medical subspecialty fellows. We examined associations between patient and family race or socioeconomic status and ratings they gave trainees on two questionnaires: the Quality of End-of-Life Care (QEOLC) and Quality of Communication (QOC). Results: Patients from racial/ethnic minority groups, patients with lower income, and patients with lower educational attainment gave trainees higher ratings on the end-of-life care subscale of the QOC (QOCeol). In path models, patient educational attainment and income had a direct effect on outcomes, while race/ethnicity did not. Lower family educational attainment was also associated with higher trainee ratings on the QOCeol, while family non-white race was associated with lower trainee ratings on the QEOLC and general subscale of the QOC. Conclusions: Patient race is associated with perceptions of the quality of communication about end-of-life care provided by physicians-in-training, but the association was opposite to our hypothesis and appears to be mediated by socioeconomic status. Family member predictors of these perceptions differ from those observed for patients. Further investigation of these associations may guide interventions to improve care delivered to patients and families. [ABSTRACT FROM AUTHOR]

Given the individual and systemic stress endured by children and families during the COVID-19 pandemic, research examining culturally responsive school experiences and supports to enhance resilience is critical. This study examined the relationship between caregivers' perceptions of COVID-19 impact, mental health distress among children and caregivers, and school-based sociocultural protective factors, including culturally responsive practices in schools and the relationships between teachers and caregivers, concurrently and longitudinally. Data were collected from caregivers of elementary-aged children at two-time points from March to April 2020 (N = 174) and one year later in 2021 (N = 114). Regression analyses revealed that COVID-19 impact positively predicted and parent-teacher joining negatively predicted mental health concerns among children and families, concurrently and longitudinally. Furthermore, there was a positive relationship between caregivers' perceptions of teachers' social awareness and justice practices and mental health symptoms for children in 2020. Parent-teacher joining longitudinally moderated the relationship between COVID-19 impact and caregivers' mental health concerns. This study provides implications regarding sociocultural resilience factors that should be considered in schools amidst the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Patient‐reported outcome measures (PROMs) are questionnaires that collect health outcomes directly from the people who experience them. This review critically synthesizes information on generic and selected condition‐specific PROMs to describe trends and contemporary issues regarding their development, validation and application. Methods: We reviewed academic and grey literature on validated PROMs by searching databases, prominent websites, Google Scholar and Google Search. The identification of condition‐specific PROMs was limited to common conditions and those with a high burden of disease (eg cancers, cardiovascular disorders). Trends and contemporary issues in the development, validation and application of PROMs were critically evaluated. Results: The search yielded 315 generic and condition‐specific PROMs. The largest numbers of measures were identified for generic PROMs, musculoskeletal conditions and cancers. The earliest published PROMs were in mental health‐related conditions. The number of PROMs grew substantially between 1980s and 2000s but slowed more recently. The number of publications discussing PROMs continues to increase. Issues identified include the use of computer‐adaptive testing and increasing concerns about the appropriateness of using PROMs developed and validated for specific purposes (eg research) for other reasons (eg clinical decision making). Conclusions: The term PROM is a relatively new designation for a range of measures that have existed since at least the 1960s. Although literature on PROMs continues to expand, challenges remain in selecting reliable and valid tools that are fit‐for‐purpose from the many existing instruments. Patient or public contribution: Consumers were not directly involved in this review; however, its outcome will be used in programmes that engage and partner with consumers. [ABSTRACT FROM AUTHOR]

Context: An enhanced understanding of trainee attitudes about end-of-life care is needed to inform interventions to improve clinician communication about dying and death.Objectives: To examine changes in trainee pessimism about end-of-life care over the course of one academic year and to explore predictors of pessimism among residents, fellows, and nurse practitioners.Methods: We used baseline and follow-up surveys completed by trainees during a randomized controlled trial of an intervention to improve clinician communication skills. Surveys addressed trainee feelings about end-of-life care. Latent variable modeling was used to identify indicators of trainee pessimism, and this pessimism construct was used to assess temporal changes in trainee attitudes about end-of-life care. We also examined predictors of trainee pessimism at baseline and follow-up. Data were available for 383 trainees from two training programs.Results: There was a significant decrease in pessimism between baseline and follow-up assessments. Age had a significant inverse effect on baseline pessimism, with older trainees being less pessimistic. There was a direct association of race/ethnicity on pessimism at follow-up, with greater pessimism among minority trainees (P = 0.028). The model suggests that between baseline and follow-up, pessimism among younger white non-Hispanic trainees decreased, whereas pessimism among younger trainees in racial/ethnic minorities increased over the same period.Conclusion: Overall, trainee pessimism about end-of-life care decreases over time. Pessimism about end-of-life care among minority trainees may reflect the influence of culture on clinician attitudes about communication with seriously ill patients. Further research is needed to understand the evolution of trainee attitudes about end-of-life care during clinical training. [ABSTRACT FROM AUTHOR]

Background Dementia is a syndrome associated with stigma and social isolation. Forty-two percent of people with dementia in the United States and almost 40% in the United Kingdom live in assisted living and residential care facilities. Up to 90% of residents with dementia experience behavioral and psychological symptoms of dementia (BPSD). Currently psychotropic drugs are often used to manage BPSD, despite the drugs' limited efficacy and adverse effects. Even though psychosocial approaches are as effective as medical ones without side effects, their uptake has been slow. Social networks that investigate the structure of relationships among residents and staff may represent an important resource to increase the uptake of psychosocial approaches and facilitate improvements in care. Objectives To conduct a systematic review of social network studies set in long-term care (LTC), including residents with dementia, and identify network factors influencing the care available to residents. Method Peer-reviewed articles across CINAHL, EMBASE, IBSS, Medline, PsychInfo, Scopus, and Web of Science were searched from January 1994 to December 2014 inclusive, using PRISMA guidelines. Studies included those examining social networks of residents or staff in LTC. Results Nine articles from studies in the United States, Europe, Asia, and Australia met search criteria. Resident networks had few social connections. One study proposed that residents with high centrality be encouraged to welcome new residents and disseminate information. The high density in 2 staff network studies was associated with the cooperation needed to provide care to residents with dementia. Staff's boundary-spanning led to higher-status nurses becoming more involved in decision-making and problem-solving in one study. In another, the outcome was staff treating residents with more respect and actively caring for them. Conclusion These studies suggest interventions using a network approach may improve care services in LTC. [ABSTRACT FROM AUTHOR]

Purpose: Consistent and non-specific associations have been found between parenting style and major depression, anxiety disorders, and externalizing behavior. Although often considered part of twins' shared environment, parenting can also be conceptualized as non-shared environment. Non-shared environmental influences have important effects on development but are difficult to test and sort out because of the possible confounding effects of gene-environment interactions and evocative gene-environment correlations. The monozygotic (MZ) differences approach is one way to analytically investigate non-shared environment.Methods: The aim of the present study is to use the MZ differences approach to investigate the relationship between differential parenting among 1303 twin pairs (mean age 36.69 ± 8.56) and differences in total symptom counts of major depression (MD), generalized anxiety disorder (GAD), conduct disorder (CD), and anti-social behavior (ASB) during adulthood.Results: Although effect sizes tended to be small, a number of results were significantly different from zero. Perceived differences in parental coldness was positively associated with internalizing disorders. Differences in protectiveness were negatively associated with MD, GAD, and ASB. Differences in authoritarianism were positively associated with MD and CD, but negatively associated with ASB.Conclusions: Perceived differences in parenting style are associated with differences in MD, GAD, CD, and ASB outcomes in a sample of MZ twins. Despite the lack of a basis for making causal inferences about parenting style and psychopathology, these results are suggestive of such a relationship and show that non-shared environmental influence of parenting does in some cases significantly predict adult psychopathology. [ABSTRACT FROM AUTHOR]

In 2010, an outbreak of febrile illness with arthralgic manifestations was detected at La Estación village, Portuguesa State, Venezuela. The etiologic agent was determined to be Mayaro virus (MAYV), a reemerging South American alphavirus. A total of 77 cases was reported and 19 were confirmed as seropositive. MAYV was isolated from acute-phase serum samples from 6 symptomatic patients. We sequenced 27 complete genomes representing the full spectrum of MAYV genetic diversity, which facilitated detection of a new genotype, designated N. Phylogenetic analysis of genomic sequences indicated that etiologic strains from Venezuela belong to genotype D. Results indicate that MAYV is highly conserved genetically, showing ≈17% nucleotide divergence across all 3 genotypes and 4% among genotype D strains in the most variable genes. Coalescent analyses suggested genotypes D and L diverged ≈150 years ago and genotype diverged N ≈250 years ago. This virus commonly infects persons residing near enzootic transmission foci because of anthropogenic incursions. [ABSTRACT FROM AUTHOR]

Studies are needed that examine neurobiological characteristics in high-risk individuals prior to substance use disorder (SUD) development. In this pilot study, 4 adolescent subjects at high risk for SUD (having at least 1 parent with an SUD) were compared with 4 adolescent reference subjects on a cortico-limbic reactivity paradigm, where they were presented with affect-laden faces or geometric shapes. Functional magnetic resonance imaging was used to measure cortical activation in response to these stimuli. High-risk subjects, compared to low-risk, exhibited greater left amygdala activation (t = 2.76,df = 6,p = 0.03), suggesting they may exhibit hyperresponsivity of the amygdala in response to emotional stimuli. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims Adolescents with substance use disorders (SUD) have difficulties with cognitive, behavioral and affective regulation. White matter (WM) disorganization has been observed in adolescents with SUD and may be related to psychological dysregulation. This study compared adolescents with SUD and control adolescents to investigate relationships among psychological dysregulation, WM disorganization and SUD symptoms. Design Cross-sectional observation. Setting Adolescents with SUD were recruited from SUD treatment programs. Controls were recruited from the community. Participants The 55 participants were aged 14-19; 35 with SUD and 20 controls without SUD. Measurements Psychological dysregulation was characterized by the Behavior Rating Inventory of Executive Function. WM disorganization was measured by diffusion tensor imaging, and fractional anisotropy, radial diffusivity and axial diffusivity were examined within cortical regions of interest. Findings Compared to controls, SUD adolescents showed significantly greater psychological dysregulation and prefrontal and parietal WM disorganization. WM disorganization was correlated positively with psychological dysregulation and cannabis-related symptoms. In multivariate mediation models, the results were consistent with both the neurodevelopmental immaturity model, in which WM disorganization leads to psychological dysregulation and cannabis-related symptoms, and with the substance effects model, in which cannabis-related symptoms lead to WM disorganization and psychological dysregulation. Conclusions In adolescents, substance use disorder and psychological dysregulation appear to be associated with reduced frontoparietal network white matter maturation. [ABSTRACT FROM AUTHOR]

Background: Immune mediated changes in circulating α-1-acid glycoprotein (AAG), a type 1 acute phase protein, which binds protease inhibitors (PI), may alter protein binding and contribute to PI’s pharmacokinetic (PK) variability. Methods: In a prospective, 2-phase intensive PK study on antiretroviral naive human immunodeficiency virus (HIV)-infected subjects treated with a lopinavir-/ritonavir-based regimen, steady state PK sampling and AAG assays were performed at weeks 2 and 16 of treatment. Results: Median entry age was 43 years (n = 16). Median plasma log10 HIV-1 RNA, CD4 T-cell counts, and AAG were 5.16 copies/mL, 28 cells/µL, and 143 mg/dL, respectively.The total lopinavir area under the concentration time curve (AUC12_total) and maximum concentration (Cmax_total) changed linearly with AAG at mean rates of 16±7 mg*hr/L (slope ± SE); P = .04, and 1.6 ± 0.6 mg/L, P = .02, per 100 mg/dL increase in AAG levels, respectively (n = 15).A 29% drop in AAG levels between week 2 and week 16 was associated with 14% (geometric mean ratio [GMR] = 0.86; 90% confidence interval [CI] = 0.74-0.98) and 13% (GMR = 0.87; 90% CI = 0.79-0.95) reduction in AUC12_total and Cmax_total, respectively. Neither free lopinavir PK parameters nor antiviral activity (HIV-1 RNA average AUC minus baseline) was affected by change in plasma AAG. Conclusions: Changes in plasma AAG levels alter total lopinavir concentrations, but not the free lopinavir exposure or antiviral activity. This observation may have implications in therapeutic drug monitoring. [ABSTRACT FROM PUBLISHER]