Live imaging of the Drosophila ovarian niche shows spectrosome and centrosome dynamics during asymmetric germline stem cell division.

Drosophila female germline stem cells (GSCs) are found inside the cellular niche at the tip of the ovary. They undergo asymmetric divisions to renew the stem cell lineage and to produce sibling cystoblasts that will in turn enter differentiation. GSCs and cystoblasts contain spectrosomes, membranous structures essential for orientation of the mitotic spindle and that, particularly in GSCs, change shape depending on the cell cycle phase. Using live imaging and a fusion protein of GFP and the spectrosome component Par-1, we follow the complete spectrosome cycle throughout GSC division and quantify the relative duration of the different spectrosome shapes. We also determine that the Par-1 kinase shuttles between the spectrosome and the cytoplasm during mitosis and observe the continuous addition of new material to the GSC and cystoblast spectrosomes. Next, we use the Fly-FUCCI tool to define, in live and fixed tissues, that GSCs have a shorter G1 compared with the G2 phase. The observation of centrosomes in dividing GSCs allowed us to determine that centrosomes separate very early in G1, before centriole duplication. Furthermore, we show that the anterior centrosome associates with the spectrosome only during mitosis and that, upon mitotic spindle assembly, it translocates to the cell cortex, where it remains anchored until centrosome separation. Finally, we demonstrate that the asymmetric division of GSCs is not an intrinsic property of these cells, as the spectrosome of GSC-like cells located outside of the niche can divide symmetrically. Thus, GSCs display unique properties during division, a behaviour influenced by the surrounding niche.

Improvements in Patient-Reported Outcomes After 12 Months of Maintenance Therapy With Cabotegravir + Rilpivirine Long-Acting Compared With Bictegravir/Emtricitabine/Tenofovir Alafenamide in the Phase 3b SOLAR Study.

SOLAR (NCT04542070; registered 2020-09-09) is a Phase 3b study that demonstrated the noninferior virological efficacy of switching to cabotegravir + rilpivirine long-acting (CAB + RPV LA) dosed every 2 months vs. continuing daily oral bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) over 12 months. Participants were randomised (2:1) to switch to CAB + RPV LA or to continue BIC/FTC/TAF. Patient-reported endpoints included treatment preference, treatment satisfaction (12-item HIV Treatment Satisfaction Questionnaire status version), acceptability of injections (Perception of Injection questionnaire [acceptability domain]) and three single-item questions exploring psychological challenges related to HIV treatment (fear of disclosure, adherence-related anxiety and reminder of HIV status). Of 670 participants, 447 participants switched to CAB + RPV LA and 223 continued BIC/FTC/TAF. Overall, 18% were female, median age was 37 years and 31% were non-White. At Month 12, CAB + RPV LA significantly improved treatment satisfaction vs. BIC/FTC/TAF (mean [95% confidence interval (CI)] change: + 3.36 [2.59, 4.13] vs. -1.59 [-2.71, -0.47]; p < 0.001). At Month 12, a higher proportion of CAB + RPV LA arm participants reported improvements across the psychological challenges related to HIV treatment questions compared with BIC/FTC/TAF participants. Participants indicating ≥ 1 psychological challenge at baseline experienced a statistically significant and clinically meaningful improvement in treatment satisfaction after 12 months of CAB + RPV LA vs. continuing BIC/FTC/TAF (adjusted difference [95% CI]: 7.96 [5.65, 10.26]; p < 0.001). Most (90%, 382/425) questionnaire respondents preferred CAB + RPV LA vs. BIC/FTC/TAF (5%, 21/425). Switching to CAB + RPV LA was associated with significantly improved treatment satisfaction and relief from the fear of disclosure, anxiety surrounding adherence and reminder of HIV status.

RESUMEN: SOLAR (NCT04542070; registrado el 09-09-2020) es un estudio de fase IIIb que ha demostrado la eficacia virológica no inferior de cambiar a cabotegravir+rilpivirina de acción prolongada (CAB+RPV LA) administrado cada 2 meses frente a continuar con la administración oral diaria de bictegravir/emtricitabina/tenofovir alafenamida (BIC/FTC/TAF) durante 12 meses. Los participantes fueron asignados de forma aleatoria (2:1) al grupo de cambio a CAB+RPV LA o de continuación con BIC/FTC/TAF. Los parámetros declarados por los pacientes incluían la preferencia del tratamiento, la satisfacción del tratamiento (versión del estado del cuestionario de satisfacción del tratamiento de VIH de 12 preguntas), la aceptación de las inyecciones (cuestionario de percepción de las inyecciones [dominio de aceptación]) y tres preguntas individuales que analizaban los problemas psicológicos relacionados con el tratamiento del VIH (miedo a la revelación, ansiedad relacionada con el cumplimiento terapéutico y recordatorio del estado del VIH). De los 670 participantes, 447 participantes cambiaron a CAB+RPV LA y 223 continuaron con BIC/FTC/TAF. En general, el 18 % eran mujeres, el promedio de edad era de 37 años y el 31 % no eran blancos. En el mes 12, el tratamiento con CAB+RPV LA aumentó considerablemente la satisfacción del tratamiento frente al BIC/FTC/TAF (cambio [intervalo de confianza (IC) del 95 %] medio: +3.36 [2.59; 4.13] frente a ­1.59 [­2.71; ­0.47]; p<0.001). En el mes 12, una mayor proporción de participantes del grupo de CAB+RPV LA declararon mejoras en todos los problemas psicológicos relacionados con las preguntas sobre el tratamiento del VIH en comparación con los participantes del grupo de BIC/FTC/TAF. Los participantes que indicaron ≥ 1 problema psicológico en el inicio experimentaron una mejora importante estadísticamente y significativa clínicamente con respecto a la satisfacción del tratamiento al cabo de 12 meses del cambio a CAB+RPV LA frente a la continuación con BIC/FTC/TAF (diferencia ajustada [IC del 95 %]: 7.96 [5.65; 10.26]; p<0.001). La mayoría de encuestados (el 90 %, 382/425) preferían CAB+RPV LA frente a BIC/FTC/TAF (el 5 %, 21/425). El cambio a CAB+RPV LA se asoció a un aumento considerable de la satisfacción del tratamiento y al alivio del miedo a la revelación, la ansiedad en torno al cumplimiento terapéutico y el recordatorio del estado del VIH.

Erratum: The Beaker phenomenon and the genomic transformation of northwest Europe.

This corrects the article DOI: 10.1038/nature25738.

The Beaker phenomenon and the genomic transformation of northwest Europe.

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.

Elevated serum hepatic transaminases in apical periodontitis individuals.

AIM: Apical periodontitis (AP) is the chronic inflammation of the periradicular tissues in response to root canal infection. Whilst AP has been linked with systemic inflammation and noncommunicable diseases, its potential association with nonalcoholic fatty liver disease (NAFLD) is unknown. We aimed to evaluate the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels as surrogate markers of hepatic injury, and the systemic inflammatory burden in otherwise healthy individuals with and without AP diagnosis. METHODOLOGY: Cross-sectional study. Individuals with AP (n = 30) and healthy controls (n = 29) were recruited. The number, mean diameter (mm) and periapical index of the apical lesions of endodontic origin (ALEO) were assessed. ALT and AST levels (pg/mL) were measured through enzyme-linked immunosorbent assays. The serum levels of TNF-α, IL-4, IL-9, IL-10, IL-17A and IL-22 were evaluated by Multiplex assay. Inferential analysis was performed using t-test or Mann-Whitney tests according to data distribution and linear regression models. Data were analysed with StataV16 (p < .05). RESULTS: ALT and AST levels were significantly higher in individuals with AP compared to controls (p < .05). Serum inflammatory biomarkers showed no significant differences between the study groups. Bivariate and multivariate analyses confirmed that AP diagnosis was independently associated with ALT and AST elevations (p < .05). Additionally, the number of ALEO positively influenced AST levels (p = .002). IL-22 on the other hand, was associated with reduced ALT levels (p = .043). CONCLUSION: AP is associated with higher serum hepatic transaminases ALT and AST, potentially contributing to NAFLD physiopathology in young adults.

Reduced C-reactive protein levels after root canal treatment in clinically healthy young apical periodontitis individuals at cardiovascular risk. A prospective study.

AIM: To determine the systemic inflammatory burden, including hsCRP and its monomeric forms, in patients with apical lesions of endodontic origin treated with root canal treatment (RCT). METHODOLOGY: Prospective pre-/post-study. Apical periodontitis (AP) individuals aged 16-40 were included (N = 29). Individuals received RCT and were followed at 1 and 6 months. Fasting blood samples were obtained. Apical lesions of endodontic origin (ALEO) diameter (mm), and periapical index (PAI), were recorded. The serum concentrations of total hsCRP were determined by turbidimetry. Tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, IL-1ß, and soluble (s) E-selectin were assessed by Multiplex assay. Additionally, mCRP forms were determined in the serum of AP patients with a baseline moderate to high cardiovascular risk based on hsCRP stratification (hsCRP ≥1 mg/L) by immunowestern blot (n = 15). Also, CRP isoforms were explored in ALEOs from AP individuals (n = 4). Data were analysed with StataV16. RESULTS: Periapical index and ALEO sizes were reduced at both follow-up visits after RCT (p < .05). Serum levels of TNF-α, IL-6, IL-10, IL-1ß, and sE-selectin did not show significant differences. CRP was borderline reduced at 1 month (p = .04); however, in AP individuals at cardiovascular risk (hsCRP ≥ 1 mg/L), hsCRP and its monomeric isoform significantly decreased at 1 and 6 months (p < .05). CONCLUSIONS: High-sensitivity CRP and mCRP are reduced after RCT in AP individuals at cardiovascular risk.

Efficacy of sustained knowledge translation (KT) interventions in chronic disease management in older adults: systematic review and meta-analysis of complex interventions.

BACKGROUND: Chronic disease management (CDM) through sustained knowledge translation (KT) interventions ensures long-term, high-quality care. We assessed implementation of KT interventions for supporting CDM and their efficacy when sustained in older adults. METHODS: Design: Systematic review with meta-analysis engaging 17 knowledge users using integrated KT. ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) including adults (> 65 years old) with chronic disease(s), their caregivers, health and/or policy-decision makers receiving a KT intervention to carry out a CDM intervention for at least 12 months (versus other KT interventions or usual care). INFORMATION SOURCES: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from each database's inception to March 2020. OUTCOME MEASURES: Sustainability, fidelity, adherence of KT interventions for CDM practice, quality of life (QOL) and quality of care (QOC). Data extraction, risk of bias (ROB) assessment: We screened, abstracted and appraised articles (Effective Practice and Organisation of Care ROB tool) independently and in duplicate. DATA SYNTHESIS: We performed both random-effects and fixed-effect meta-analyses and estimated mean differences (MDs) for continuous and odds ratios (ORs) for dichotomous data. RESULTS: We included 158 RCTs (973,074 participants [961,745 patients, 5540 caregivers, 5789 providers]) and 39 companion reports comprising 329 KT interventions, involving patients (43.2%), healthcare providers (20.7%) or both (10.9%). We identified 16 studies described as assessing sustainability in 8.1% interventions, 67 studies as assessing adherence in 35.6% interventions and 20 studies as assessing fidelity in 8.7% of the interventions. Most meta-analyses suggested that KT interventions improved QOL, but imprecisely (36 item Short-Form mental [SF-36 mental]: MD 1.11, 95% confidence interval [CI] [- 1.25, 3.47], 14 RCTs, 5876 participants, I2 = 96%; European QOL-5 dimensions: MD 0.01, 95% CI [- 0.01, 0.02], 15 RCTs, 6628 participants, I2 = 25%; St George's Respiratory Questionnaire: MD - 2.12, 95% CI [- 3.72, - 0.51] 44 12 RCTs, 2893 participants, I2 = 44%). KT interventions improved QOC (OR 1.55, 95% CI [1.29, 1.85], 12 RCTS, 5271 participants, I2 = 21%). CONCLUSIONS: KT intervention sustainability was infrequently defined and assessed. Sustained KT interventions have the potential to improve QOL and QOC in older adults with CDM. However, their overall efficacy remains uncertain and it varies by effect modifiers, including intervention type, chronic disease number, comorbidities, and participant age. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018084810.

Factors Associated with Treatment Satisfaction Among People Living with HIV in Japan and Other Selected Countries: Examination of the Intertwined Roles of Medication, Patient, and Provider Characteristics.

We examined satisfaction and perceived challenges with antiretroviral therapy (ART) among people living with HIV (PLHIV) in Japan vs three other Asian countries (China, Taiwan, South Korea), and 21 non-Asian countries, using data from the 2019 Positive Perspectives Study (pooled sample size from all 25 countries = 2389). Participants in other Asian countries were more likely than those in Japan to report they missed ART ≥ 1 time in the past month because they were depressed/overwhelmed (57.4%[89/155] vs 32.0%[24/75]), had privacy concerns (56.8%[88/155] vs 30.7%[23/75]), were concerned about the potential long-term negative impacts of ART (46.5%[72/155] vs 26.7%[20/75]), or just wanted to forget about HIV (45.8%[71/155] vs 22.7%[17/75]). ART satisfaction however did not differ significantly between surveyed PLHIV in Japan (54.7%[41/75]) vs those in other Asian countries (47.7%[74/155]). The percentage who felt that daily ART dosing limited their lives was 36.0%[27/75] among participants from Japan, 48.4%[75/155] among participants from other Asian countries, and 27.3%[589/2159] among those from non-Asian countries. Within a structural equation model using pooled data from all 25 countries, positive correlations were seen between ART satisfaction and "provider engagement" (ß = 0.35), high perceived control over ART dosing schedule (ß = 0.28), and the belief that ART prevents HIV transmission (ß = 0.16). Conversely, negative correlations were seen between ART satisfaction and experience of ART side-effects (ß = - 0.24), high "ART anxiety" (ß = - 0.20); and being on multi-tablet regimens (ß = - 0.13). Those ART-satisfied reported higher self-rated health and greater ART adherence. These findings underscore the need for patient-centered care to enhance treatment satisfaction and improve ART adherence.

Treatment challenges and health conditions among people living with HIV with or without substance use disorder in the Russian Federation.

We quantified treatment challenges faced by people living with HIV (PLHIV) in Russia. Cross-sectional data of 150 PLHIV in Russia were from the 2019 Positive Perspectives Survey. Mean age was 38.3 y. Two-thirds (68.0%[102/150]) had ever disguised their HIV pills, and 43.3%[65/150] said they would be stressed if someone saw their HIV pills. Overall, 14.7%[22/150] reported being ever diagnosed with substance use disorder (SUD). Self-rated optimal health was significantly lower among those with vs without a report of SUD on multiple health domains: sexual (40.9%[9/22] vs. 70.3%[90/128], p = 0.007), physical (22.7%[5/22] vs. 68.0%[87/128], p < 0.001), and overall health (27.3%[6/22] vs. 68.8%[88/128], p < 0.001). Those reporting SUD were more likely to miss HIV medication ≥ 1 time in the past month because they used recreational drugs (age and gender-adjusted prevalence ratio [APR] = 8.23, 95%CI = 6.99-9.68), could not afford their medication (APR = 3.28, 95%CI = 2.90-3.72), had to work (APR = 3.27, 95%CI = 2.97-3.60), or to avoid side effects (APR = 2.62, 95%CI = 2.37-2.89). Furthermore, self-reported SUD was strongly associated with numerous poor health conditions, including self-reported diagnosis of cancer (APR = 6.67, 95%CI = 5.24-8.48), mental illness (APR = 5.01, 95%CI = 4.53-5.55), and liver disease (APR = 4.29, 95%CI = 3.98-4.61). The distinct patterns of poorer health-related outcomes among PLHIV with SUD underscore the need to address behavioral and psychosocial challenges as part of holistic HIV care.

Cardiac abnormalities determined by tissue Doppler imaging and arrhythmias in adolescents with anorexia nervosa.

BACKGROUND: Anorexia nervosa has a prevalence of 0.5-3% in adolescents, placing this population at increased risk of cardiac anomalies including arrhythmias, pericardial effusion, and myocardial dysfunction. Our objective is to describe cardiovascular anomalies observed by tissue Doppler imaging in patients with anorexia nervosa. METHODS: We retrospectively reviewed electrocardiogram, Holter, and echocardiography findings in 28 patients diagnosed with anorexia nervosa. RESULTS: Electrocardiogram was abnormal in 71% of patients with sinus bradycardia observed in 57%. Holter confirmed sinus bradycardia without significant pauses. Prolonged QTc, low voltage, and ectopic beats were each seen in 14% of patients. Wenckebach atrioventricular block was observed in one patient. Supraventricular or ventricular tachycardia was not observed. Echocardiography showed structurally normal heart in all patients. Pericardial effusion was seen in 7.1% of patients and left ventricular mass was decreased in 10.7%. Mean ejection fraction was 0.73 and mean fractional shortening was 38.4%. Tissue Doppler imaging revealed systolic or diastolic dysfunction in four patients with e', a', and s' velocities in the lateral and septal basal segments more than two standard deviations below the mean. Two patients had decreased left ventricular mass but no significant difference in disease duration from the group. Basal segment velocities below one standard deviation were also observed in an additional seven patients. CONCLUSION: A trend for decreased tissue Doppler imaging velocities was seen in 25.0% of patients, while significant systolic and diastolic dysfunction was seen in 14.3% of patients, associated with a significant reduction in left ventricular mass and independent of disease duration.

Aubergine and piRNAs promote germline stem cell self-renewal by repressing the proto-oncogene Cbl.

PIWI proteins play essential roles in germ cells and stem cell lineages. In Drosophila, Piwi is required in somatic niche cells and germline stem cells (GSCs) to support GSC self-renewal and differentiation. Whether and how other PIWI proteins are involved in GSC biology remains unknown. Here, we show that Aubergine (Aub), another PIWI protein, is intrinsically required in GSCs for their self-renewal and differentiation. Aub needs to be loaded with piRNAs to control GSC self-renewal and acts through direct mRNA regulation. We identify the Cbl proto-oncogene, a regulator of mammalian hematopoietic stem cells, as a novel GSC differentiation factor. Aub stimulates GSC self-renewal by repressing Cbl mRNA translation and does so in part through recruitment of the CCR4-NOT complex. This study reveals the role of piRNAs and PIWI proteins in controlling stem cell homeostasis via translational repression and highlights piRNAs as major post-transcriptional regulators in key developmental decisions.

piRNAs and PIWI proteins: regulators of gene expression in development and stem cells.

PIWI proteins and Piwi-interacting RNAs (piRNAs) have established and conserved roles in repressing transposable elements (TEs) in the germline of animals. However, in several biological contexts, a large proportion of piRNAs are not related to TE sequences and, accordingly, functions for piRNAs and PIWI proteins that are independent of TE regulation have been identified. This aspect of piRNA biology is expanding rapidly. Indeed, recent reports have revealed the role of piRNAs in the regulation of endogenous gene expression programs in germ cells, as well as in somatic tissues, challenging dogma in the piRNA field. In this Review, we focus on recent data addressing the biological and developmental functions of piRNAs, highlighting their roles in embryonic patterning, germ cell specification, stem cell biology, neuronal activity and metabolism.

Undetectable equals untransmittable (U = U): awareness and associations with health outcomes among people living with HIV in 25 countries.

OBJECTIVES: 'Undetectable equals Untransmittable' (U=U) is an empowering message that may enable people living with HIV (PLHIV) to reach and maintain undetectability. We estimated the percentage of PLHIV who ever discussed U=U with their main HIV care provider, and measured associations with health-related outcomes. Secondarily, we evaluated whether the impact of the U=U message varied between those who heard it from their healthcare provider (HCP) vs from elsewhere. METHODS: Data were from the 25-country 2019 Positive Perspectives Survey of PLHIV on treatment (n=2389). PLHIV were classified as having discussed U=U with their HCP if they indicated that their HCP had ever told them about U=U. Those who had not discussed U=U with their HCP but were nonetheless aware that 'My HIV medication prevents me from passing on HIV to others' were classified as being made aware of U=U from non-HCP sources. Multivariable logistic regression was used to measure associations between exposure to U=U messages and health outcomes. RESULTS: Overall, 66.5% reported ever discussing U=U with their HCP, from 38.0% (South Korea) to 87.3% (Switzerland). Prevalence was lowest among heterosexual men (57.6%) and PLHIV in Asia (51.3%). Compared with those unaware of U=U, those reporting U=U discussions with their HCP had lower odds of suboptimal adherence (AOR=0.59, 95% CI 0.44 to 0.78) and higher odds of self-reported viral suppression (AOR=2.34, 95% CI 1.72 to 3.20), optimal sexual health (AOR=1.48, 95% CI 1.14 to 1.92) and reporting they 'always shared' their HIV status (AOR=2.99, 95% CI 1.42 to 6.28). While exposure to U=U information from non-HCP sources was beneficial too, the observed associations were attenuated relative to those seen with reported discussions with HCPs. CONCLUSION: HCP discussion of U=U with PLHIV was associated with favourable health outcomes. However, missed opportunities exist since a third of PLHIV reported not having any U=U discussion with their HCP. U=U discussions with PLHIV should be considered as a standard of care in clinical guidelines.

Regional differences in perceived treatments needs and priorities in relation to antiretroviral therapy among people living with HIV in 25 countries.

While geographic differences in HIV burden are well documented, less is known about regional differences in perceived treatment needs. To fill this gap, the 2019 Positive Perspectives study of people living with HIV (PLHIV) was conducted in 25 countries across Northern America, Latin America, the Asian region, Europe (EU/Schengen countries), Russia, Australia, and South Africa (n = 2389). Overall mean duration of HIV was 10.1 (SD = 9.6) years. The perception that HIV had a negative impact on day-to-day life was lowest among participants from South Africa (14.0%[25/179]) and highest among participants from the Asian region (55.2%[127/230]). Most of the regional gap in the perception that HIV had a negative impact on daily life was explained by regional differences in medication-related unmet needs, stigma, demographic factors, and comorbidities. The percentage who felt they understood their treatment was highest among participants from Australia (87.5%[105/120]) and lowest among those from Russia (62.0%[93/150]), the Asian region (62.2%[143/230]), and South Africa (62.6%[112/179]). Among participants from Northern America, Europe, and Latin America, the treatment goals with the largest absolute increase in perceived importance, from time of starting treatment to time of survey among those diagnosed for ≥1 year, were minimizing the long term impact of antiretroviral treatment and keeping the number of medicines in their antiretroviral regimen at a minimum. Tailored approaches to care of PLHIV are needed as different regions have different disease burden and treatment needs. Equitable approaches to HIV care are needed across and within regions to ensure that patients' unmet needs and preferences are addressed to improve their overall wellbeing and health-related quality of life.

Physical, Emotional, and Psychosocial Challenges Associated with Daily Dosing of HIV Medications and Their Impact on Indicators of Quality of Life: Findings from the Positive Perspectives Study.

To assess challenges with daily oral antiretroviral therapy (ART), we analyzed data for 2389 participants in the 2019 Positive Perspectives survey of people living with HIV in 25 countries. ART-related challenges reported included difficulty swallowing pills (33.1% [790/2389]); stress from daily dosing routine (33.3% [795/2389]); bad memories from daily intake of HIV medication (35.1%[839/2389]), and concern "that having to take pills every day means a greater chance of revealing my HIV status to others" (37.9% [906/2389]). Individuals who felt empowered by daily oral dosing ["taking my pill(s) every day reassures me that my HIV is being kept under control"] had 69% higher odds of optimal overall health (AOR 1.69, 95% CI 1.40-2.04). Conversely, odds of optimal overall health were lower among those who felt daily pill intake "limits my day-to-day life" (AOR 0.53, 95% CI 0.44-0.64). These findings show that there is need for increased flexibility of ART delivery to meet diverse patient needs.

Shared Decision Making Between Patients and Healthcare Providers and its Association with Favorable Health Outcomes Among People Living with HIV.

We assessed patient-provider communication in HIV care; data were from the 2019 Positive Perspectives Survey of people living with HIV (PLHIV) from 25 countries (n = 2389). A significantly greater proportion of recently diagnosed individuals were interested in being involved when it comes to decisions about their HIV treatment compared with any other group (72.8% [399/548], 63.1% [576/913], and 62.6% [581/928], diagnosis year: 2017-2019, 2010-2016, and pre-2010 respectively) but reported less understanding of their treatment compared with those reporting the longest duration (66.8% [366/548], 68.6% [626/913], and 77.3% [717/928], respectively). One-third of PLHIV with salient treatment-related concerns were uncomfortable discussing with providers. Of participants who felt that their HIV medication limited their life but did not discuss their concerns with their provider (n = 203), top reasons for not discussing were: perception nothing could be done (49.3% [100/203]), provider never brought up the issue (37.9% [77/203]), and not wanting to appear difficult (30.5% [62/203]). To continue to identify and address unmet treatment needs among PLHIV, providers need to ensure that there is ongoing open dialogue.

Guidance for identification and treatment of individuals with attention deficit/hyperactivity disorder and autism spectrum disorder based upon expert consensus.

BACKGROUND: Individuals with co-occurring hyperactivity disorder/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) can have complex presentations that may complicate diagnosis and treatment. There are established guidelines with regard to the identification and treatment of ADHD and ASD as independent conditions. However, ADHD and ASD were not formally recognised diagnostically as co-occurring conditions until the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) was published in 2013. Hence, awareness and understanding of both conditions when they co-occur is less established and there is little guidance in the clinical literature. This has led to uncertainty among healthcare practitioners when working with children, young people and adults who present with co-existing ADHD and ASD. The United Kingdom ADHD Partnership (UKAP) therefore convened a meeting of professional experts that aimed to address this gap and reach expert consensus on the topic that will aid healthcare practitioners and allied professionals when working with this complex and vulnerable population. METHOD: UK experts from multiple disciplines in the fields of ADHD and ASD convened in London in December 2017. The meeting provided the opportunity to address the complexities of ADHD and ASD as a co-occurring presentation from different perspectives and included presentations, discussion and group work. The authors considered the clinical challenges of working with this complex group of individuals, producing a consensus for a unified approach when working with male and female, children, adolescents and adults with co-occurring ADHD and ASD. This was written up, circulated and endorsed by all authors. RESULTS: The authors reached a consensus of practical recommendations for working across the lifespan with males and females with ADHD and ASD. Consensus was reached on topics of (1) identification and assessment using rating scales, clinical diagnostic interviews and objective supporting assessments; outcomes of assessment, including standards of clinical reporting; (2) non-pharmacological interventions and care management, including psychoeducation, carer interventions/carer training, behavioural/environmental and Cognitive Behavioural Therapy (CBT) approaches; and multi-agency liaison, including educational interventions, career advice, occupational skills and training, and (3) pharmacological treatments. CONCLUSIONS: The guidance and practice recommendations (Tables 1, 4, 5, 7, 8 and 10) will support healthcare practitioners and allied professionals to meet the needs of this complex group from a multidisciplinary perspective. Further research is needed to enhance our understanding of the diagnosis, treatment and management of individuals presenting with comorbid ADHD and ASD.

Prevalence, determinants, and impact of suboptimal adherence to HIV medication in 25 countries.

Modern antiretroviral therapy (ART) has improved the lives of people living with HIV (PLHIV) but currently requires daily adherence. We assessed prevalence and correlates of suboptimal adherence, and measured associations with self-reported health outcomes. Data were from web-based surveys of confirmed HIV+ adults on antiretroviral treatment within 25 countries during 2019 (n = 2389). Suboptimal adherence was a report of ≥1 reason for missing ART ≥5 times within the past month. Multivariable logistic regression examined associations between suboptimal adherence and self-reported overall health and virologic suppression. Overall, 24.1% (575/2389) reported suboptimal adherence, from 10.0% (5/50) in Austria, to 62.0% (31/50) in China. The most common reasons for missing ART ≥5 times in the overall population were feeling depressed/overwhelmed (7.4%, 176/2389), trying to forget about HIV (7.0%, 168/2389), and work (6.1%, 145/2389). Correlates of suboptimal adherence included being heterosexual, <50 years old, ≤high school, having gastrointestinal treatment side effects, and privacy concerns. Odds of suboptimal overall health were 1.41 (95%CI, 1.11-1.80), 2.10 (95%CI, 1.65-2.68), and 2.55 (95%CI, 2.00-3.25) among those who reported the maximum number of times missed ART for any reason within the past month as 1, 2-4, or ≥5 times respectively, vs not missing at all. Odds of virologic nonsuppression were 1.80 (95%CI, 1.33-2.45), and 2.24 (95%CI, 1.66-3.02) for 2-4, or ≥5 times of missed ART respectively, vs not missing at all; missing for only 1 time was not significantly associated with virologic nonsuppression. Novel ART strategies designed to improve adherence along with interventions to empower PLHIV and support self-medication may improve health outcomes and quality of life.

Relationship Between Polypharmacy and Quality of Life Among People in 24 Countries Living With HIV.

INTRODUCTION: People living with HIV (PLHIV) have greater risk of having multiple health conditions. We measured the relationship between increased medication and overall quality of life among PLHIV from 24 countries. METHODS: We analyzed data for 2,112 adult PLHIV on antiretroviral therapy (ART) in 24 countries who completed the 2019 Positive Perspectives survey. Polypharmacy was defined as taking 5 or more pills a day or currently taking medications for 5 or more conditions. Outcomes were self-rated overall health, treatment satisfaction, and self-reported virologic control. New treatment concerns were issues not prioritized at ART initiation but now deemed paramount. Data were analyzed with descriptive and multivariable statistics. RESULTS: Overall prevalence of polypharmacy was 42.1%. People reporting polypharmacy had significantly poorer health outcomes independent of existing comorbidities; their odds of treatment satisfaction, optimal overall health, and virologic control were lower by 27.0% (adjusted odds ratio [AOR] = 0.73; 95% CI, 0.59-0.91), 36.0% (AOR = 0.64; 95% CI, 0.53-0.78), and 46.0% (AOR = 0.54, 95% CI, 0.42-0.70), respectively, compared with those without polypharmacy (all P < .05). Most PLHIV (56.6%) were concerned about taking more medicines as they age, and 73.1% were interested in ARTs with fewer medicines. Top reasons for switching ART among those who had ever switched (n = 1,550) were to reduce severity and frequency of side effects (45.3%), number of pills (35.0%), or number of medicines (26.8%). People reporting polypharmacy had significantly higher odds of having new concerns relative to when they initiated ART, regarding risks of drug-drug interactions (AOR = 1.32; 95% CI, 1.02-1.71) and side effects (AOR = 1.31; 95% CI, 1.02-1.68). CONCLUSION: Polypharmacy was associated with poorer health-related outcomes among PLHIV. Many PLHIV expressed concerns about side effects of ART. Clinicians should carefully consider patient preferences, comorbidities, and drug profiles when prescribing ART.

[Imaging approach to acute aortic syndrome]. / Estudio imagenológico del síndrome aórtico agudo.

Acute aortic syndromes include a spectrum of life-threatening aortic conditions. A review of the diagnostic aspects of the acute aortic syndrome was made, from the perspective of the imaging techniques available for this purpose. The advantages and disadvantages of each technique and its diagnostic performance were evaluated. Emphasis was placed on the relevance of clinical information as a fundamental tool for suspecting this syndrome and appropriately choosing the imaging technique. Our main objective is to provide information about the diagnosis of this condition, especially in the context of emergency services.