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Liam D Redden, Kamran M Riaz, David A Murphy, Kai Ding, Mahmoud A Khaimi Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USACorrespondence: Kamran M Riaz, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA, Tel +1-405-271-1095, Fax +1-405-271-3680, Email Kamran-Riaz@dmei.orgPurpose: To evaluate the effectiveness and safety of ab-interno canaloplasty (ABiC) for managing intraocular pressure (IOP) in patients following keratoplasty over a three-year period.Methods: This retrospective analysis focused on post-keratoplasty patients treated with ABiC with the iTrack microcatheter (Nova Eye Medical, Fremont, CA, USA) at a single institution. The study assessed the procedure’s impact on IOP control, graft survival, and reliance on topical hypotensive medications, with additional observation for any postoperative complications. Surgical success criteria included the percentage of eyes with IOP ≤ 15 mmHg, IOP ≤ 18 mmHg, ≥ 20% IOP reduction, medication-free eyes, and eyes with concurrent IOP and medication reductions.Results: ABiC was performed successfully in a cohort of 16 post-keratoplasty (7 penetrating keratoplasty and 9 endothelial keratoplasty (EK)) eyes. Preoperative mean IOP of 25.8± 7.2 mmHg was significantly reduced to 13.4± 2.9 mmHg (p< 0.001) at 1 year postoperatively and maintained at 13.1± 3.9 mmHg (p=0.009) at 3 years postoperatively. The mean number of glaucoma medications was 3.5± 1.7 at baseline, 2.8± 1.3 at 1 year (p=0.107), and 2.5± 1.2 at 3 years postoperatively (p=0.088). Eight eyes (66.7%) maintained IOP ≤ 15 mmHg, and 10 eyes (83.3%) maintained ≥ 20% IOP reduction at 3 years. The mean IOP and medication reductions from baseline at 3 years were − 49.2% and − 28.6%, respectively. Graft clarity was preserved in all patients except for one case of late graft failure that necessitated a repeat EK procedure. Post-ABiC complications included transient hyphema in two patients, neither of which led to long-term adverse outcomes.Conclusion: ABiC appears to be an effective and safe surgical intervention for sustained IOP reduction in post-keratoplasty patients. Graft survival trends are encouraging, and there was a low incidence of complications over a three-year follow-up period.Keywords: ab-interno canaloplasty, keratoplasty, intraocular pressure, glaucoma

Matthew S Ward,1 Andrew C Hou,2 David A Murphy,2 Mason A Schmutz,3 Kamran M Riaz2 1Riverwoods Eye Center, Provo, UT, USA; 2Dean McGee Eye Institute, University of Oklahoma, Oklahoma City, OK, USA; 3Excel Eye Center, Saratoga Springs, UT, USACorrespondence: Kamran M RiazDean McGee Eye Institute, University of Oklahoma, 608 Stanton L Young Blvd, Suite 313, Oklahoma City, OK, 73104, USATel +1 405-271-1095Fax +1 405-271-3680Email Kamran-Riaz@dmei.orgPurpose: To describe surgical technique and report short-term visual outcomes after suture-fixation of a single-piece eyelet-toric (SET) intraocular lens (IOL) for treatment of concurrent aphakia and astigmatism.Design: Retrospective, noncomparative, and non-consecutive case series.Methods: This was a case series of eleven eyes who underwent successful SET. Eligible eyes had loss of capsular support or aphakia with a minimum of symmetric corneal astigmatism 1.75 diopters (D). Outcome measures included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), magnitude of residual refractive cylinder, and complications resulting from the SET procedure.Results: Preoperative UDVA and CDVA in logMAR scale were 1.46 and 0.45, respectively. Mean preoperative keratometric and refractive cylinder were 3.67 D and 2.52D, respectively. Postoperative UDVA and CDVA were 0.51 and 0.27, respectively, three months after surgery (POM3). Residual refractive cylinder at POM3 was 0.93 D.Conclusion: SET technique reduced refractive cylinder and improved UDVA and CDVA. SET may be adapted by surgeons using a readily available IOL and familiar scleral-fixation maneuvers.Keywords: aphakia, toric, suture fixation, secondary lens, astigmatism

Methamphetamine (MA) users are assumed to have a high burden of tooth decay. Less clear is how the distribution and severity of dental caries in MA users differ from the general population. Using a covariate-balancing propensity score strategy, we investigated the differential effects of MA use on dental caries by comparing the patterns of decayed, missing, and filled teeth in a community sample of 571 MA users with a subset of 2,755 demographically similar control individuals selected from a National Health and Nutrition Examination Survey (NHANES) cohort. Recruited over a 2-y period with a stratified sampling protocol, the MA users underwent comprehensive dental examinations by 3 trained and calibrated dentists using NHANES protocols. Propensity scores were estimated with logistic regression based on background characteristics, and a subset of closely matched subjects was stratified into quintiles for comparisons. MA users were twice as likely to have untreated caries (odds ratio [OR] = 2.08; 95% confidence interval [95% CI]: 1.55 to 2.78) and 4 times more likely to have caries experience (OR = 4.06; 95% CI: 2.24 to 7.34) than the control group of NHANES participants. Additionally, MA users were twice as likely to have 2 more decayed, missing, or filled teeth (OR = 2.08; 95% CI: 1.29 to 2.79) than the NHANES participants. The differential involvement of the teeth surfaces in MA users was quite distinctive, with carious surface involvement being highest for the maxillary central incisors, followed by maxillary posterior premolars and molars. Users injecting MA had significantly higher rates of tooth decay compared with noninjectors (P = 0.04). Although MA users experienced decayed and missing dental surfaces more frequently than NHANES participants, NHANES participants had more restored surfaces, especially on molars. The high rates and distinctive patterns of dental caries observed could be used 1) to alert dentists to covert MA use in their patients and 2) as the basis for comprehensive management strategies.

Soundscape studies evaluate the subjective and objective qualities of an environment and attempt to develop a holistic view of the interplay between the acoustic scene and the listener’s experience. Descriptors are used to express the perception of the acoustic environment, while further subjective and quantitative measures are used as indicators that represent features of the acoustic environment. The relationships between descriptors and indicators for a particular soundscape study are often identified by developing linear statistical models. This work describes an experiment to assess heart rate measures, including ultra short term heart rate variability, within the context of the predictor descriptor framework of a soundscape study. The aim of this work is to provide evidence in support of the psychophysiological basis of measures of affect in soundscape evaluation. In this study 15 participants evaluated a randomly ordered set of 8 soundscape recordings in a repeated measures directed listening experiment. Subjective evaluation of the soundscapes was performed using the self-assessment manikin and a sound classification survey. Participants’ heart rate was measured throughout the experiment with a Polar H10 ECG heart rate monitor. Statistically significant relationships were identified between indicators and descriptors that reflect results present in the literature. However, there were no significant interactions between heart rate measures and self-reported affect or classification scores. Future studies should focus on improving the selection of stimuli and the experiment methodology to boost the sensitivity of the experiment in light of small effect sizes.

Objective: This study investigates HIV positive adolescents' health literacy and whether factors associated with health literacy in HIV-positive adults are associated with health literacy among HIV-positive adolescents.Methods: Adolescents in this study were behaviorally and perinatally HIV-infected youth (n=186) from five U.S. cities. Participants had a mean age of 20.5, and 49.5% were male.Results and Conclusions: Contrary to findings for adult HIV-positive patients, among adolescents health literacy was not significantly associated with: medication adherence adjusting for age and education level; viral load; or self-efficacy to adhere to medication regimens. The only significant association was of health literacy with medical care received.Practice Implications: Practice implications are discussed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the degree and impact of HIV-related stigma among HIV positive mothers and their uninfected children. One hundred eighteen HIV-infected mothers and their uninfected early- and middle-adolescent children (mean age=13 years) participated in a study of maternal mental and physical health and child school performance and psychological distress. Mothers and a subset of children (to whom the mother's HIV status had previously been disclosed) were administered a series of questions to measure stigma related to the mother's HIV status. Mothers reporting high levels of HIV-related stigma scored significantly lower on measures of physical, psychological, and social functioning. Mothers' levels of depression were also significantly higher when their levels of stigma were higher. No significant differences were found in children's depression by perceived level of stigma; however, adolescents who perceived high levels of stigma because of their mothers' HIV status were more likely to participate in delinquent behavior, compared with those reporting low HIV-related stigma. The experience of stigma had consequences for many aspects of well-being among the HIV-infected mothers. While their children were aware of and perceived stigma, they appeared to be affected primarily in the realm of delinquent behavior. [ABSTRACT FROM AUTHOR]

HIV symptomatic or AIDS diagnosed women who had a young well child were recruited for a study investigating their adherence to antiretrovirals (N = 46). Very poor rates of adherence were found, ranging from 43% (pill count assessment) to 56% (self-report of 3-day adherence to dose). Several factors were associated with nonadherence, including alcohol use, perceived stress, having a partner and age of youngest child, poor self-efficacy to stay with treatment, and poor outcome expectancies regarding the benefits of following the treatment regimen. Interventions to assist these women in improving adherence are urgently needed. [ABSTRACT FROM AUTHOR]

OBJECTIVES: HIV transmission behaviors and health practices of HIV-infected youths were examined over a period of 15 months after they received a preventive intervention. METHODS: HIV-infected youths aged 13 to 24 years (n = 310; 27% African American, 37% Latino) were assigned by small cohort to (1) a 2-module ('Stay Healthy' and 'Act Safe') intervention totaling 23 sessions or (2) a control condition. Among those in the intervention condition, 73% attended at least 1 session. RESULTS: Subsequent to the 'Stay Healthy' module, number of positive lifestyle changes and active coping styles increased more often among females who attended the intervention condition than among those in the control condition. Social support coping also increased significantly among males and females attending the intervention condition compared with those attending the control condition. Following the 'Act Safe' module, youths who attended the intervention condition reported 82% fewer unprotected sexual acts, 45% fewer sexual partners, 50% fewer HIV-negative sexual partners, and 31% less substance use, on a weighted index, than those in the control condition. CONCLUSIONS: Prevention programs can effectively reduce risk acts among HIV-infected youths. Alternative formats need to be identified for delivering interventions (e.g., telephone groups, individual sessions). [ABSTRACT FROM AUTHOR]

Health behaviors and mental health symptoms of parents living with AIDS (PLAs) were examined as a function of their sexual and substance-use lifestyles. The lifestyles of PLAs were classified as (1) Safe and Clean: having only protected sex and abstaining from substance use, (2) Safe Users: having protected sex, but engaging in substance use, (3) Unsafe and Clean: having unprotected sex, but abstaining from substance use, and (4) Unsafe Users: having unprotected sex and engaging in substance use. About half of the PLAs were Safe and Clean. Unsafe Users were more likely to miss doctor appointments and to have been diagnosed longer. Safe and Clean PLAs experienced fewer major life events. Changes in specific daily routines were associated with subgroup status; however, there were no consistent patterns across health behaviors linked with lifestyle. These data suggest there are different types of lifestyle changes made by PLAs when they know their serostatus. A disturbing number of PLAs continue to engage in HIV-transmission risk behaviors, demonstrating the need for preventive interventions. [ABSTRACT FROM AUTHOR]

Although AIDS rates have leveled among older gay men in large original epicenters, HIV seroincidence remains high among young men who have sex with men (MSM) in many areas of the country. This research examined patterns of risk behavior among young (age 25 years or less) and older (age 26 years and over) MSM. Nearly 2,000 men entering gay bars in 16 small U.S. cities completed an anonymous survey of their sexual practices in the past 2 months and of psychosocial risk-related characteristics. Young men were more likely than older men to have engaged in unprotected anal intercourse and, specifically, receptive intercourse in the past 2 months. Younger men also reported more frequent occurrences of unprotected anal intercourse. A progressive decline in risk behavior levels was associated with increasing age. Young men less often personally knew someone who had died of AIDS, and deaths were not primarily within their close social networks. Continued HIV prevention efforts directed toward young MSM are needed, including cities traditionally considered as second tier with respect to AIDS. [ABSTRACT FROM AUTHOR]

A simplified version of the prototype HIV vaccine material was developed through (a) reducing reading grade level, (b) restructuring of the organization and categorization of the material, (c) adding pictures designed to emphasize key concepts, and (d) obtaining feedback on the simplified version through focus groups with the target population. Low-income women at risk for HIV (N = 141) recruited from a primary care clinic were randomly assigned to be presented the standard or the simplified version. There were no significant differences between the groups in terms of education or Vocabulary, Block Design, and Passage Comprehension scores. Women who received the simplified version had significantly higher comprehension scores immediately following presentation of the material than did women who received the standard version and were also significantly more likely to recall study benefits and risks. These findings were maintained at 3-month follow-up. Implications for informed consent are discussed. [ABSTRACT FROM AUTHOR]

Background: Community-level interventions may be helpful in population-focused HIV prevention. If members of populations at risk of HIV infection who are popular with other members can be engaged to advocate the benefits of behaviour change to peers, decreases in risk behaviour may be possible. We assessed a community-level intervention to lower the risk of HIV infection, focusing on men patronising gay bars in eight small US cities.Methods: We used a randomised community-level field design. Four cities received the intervention and four control cities did not. Participants were men from each city who went to gay bars. Men completed surveys about their sexual behaviour on entering the bars during 3-night periods at baseline and at 1-year follow-up. In the control cities, HIV educational materials were placed in the bars. In the intervention cities, we recruited popular homosexual men in the community and trained them to spread behaviour-change endorsements and recommendations to their peers through conversation.Findings: Population-level of risk behaviour decreased significantly in the intervention cities compared with the control cities at 1-year follow-up, after exclusion of surveys completed by transients and men with exclusive sexual partners in a city-level analysis, in the intervention cities we found a reduction in the mean frequency of unprotected anal intercourse during the previous 2 months (baseline 1.68 occasions; follow-up 0.59: p = 0.04) and an increase in the mean percentage of occasions of anal intercourse protected by condoms (baseline 44.7%; follow-up 66.8%, p = 0.02). Increased numbers of condoms taken from dispensers in intervention-city bars corroborated risk-behaviour self-reports.Interpretation: Popular and well-liked members of a community who systematically endorse and recommend risk-reduction behaviour can influence the sexual-risk practices of others in their social networks. Natural styles of communication, such as conversations, brought about population-level changes in risk behaviour. [ABSTRACT FROM AUTHOR]

Conceptual formulations of HIV risk reduction and many HIV prevention interventions reported in the literature emphasize the role of sexual assertiveness, negotiation, and communication skills as key elements for enacting behavior change. However, there have been few attempts to determine if objective ratings of individuals' sexual communication skill effectiveness are actually associated with their levels of HIV sexual risk behavior. In the current study, 114 severely mentally ill men and women role-played scenes in which confederates simulated attempts to coerce unprotected sex. Participants' role-played responses were transcribed verbatim and later rated for quality in several areas of assertiveness skill effectiveness. In addition, participants provided detailed information concerning their sexual behavior practices in the past 30 days. Participants were categorized into highly, intermediately, or poorly skilled groups based on effectiveness in role play performance, and the groups were then compared on indices of HIV risk behavior. Individuals with high objectively rated sexual assertiveness skill had the lowest number of unprotected sex acts, the smallest number of different sexual partners, the smallest number of casual sex partners, and the highest levels of condom-protected sex in the past 30 days. Individuals with poor sexual assertiveness roleplay skills had the highest levels of sexual risk behavior. These associations were especially pronounced among women. Findings of this research provide support for teaching individuals to develop and refine their sexual assertiveness and communication skills in HIV prevention programs. Future research issues in this area are highlighted. [ABSTRACT FROM AUTHOR]

Brief screening procedures are needed that identify persons at risk for HIV among high-risk groups, in order to begin preparing for future HIV/AIDS vaccine trials. The sensitivity and specificity of brief screening procedures were evaluated among 481 African-American and Latina women (both English- and Spanish-speaking) and 143 gay men to identify people at risk for HIV who may benefit from participation in an HIV/AIDS vaccine trial. There were significant ethnic and population differences in sensitivity and specificity. Overall, the brief screening instrument has a sensitivity rate of 94.8% and specificity rate of 88.6%; these rates are significantly better than earlier screening procedures employed to assess risk acts. [ABSTRACT FROM AUTHOR]

The level and consistency of HIV-related sexual and substance-use risk acts, health status, and medical adherence were examined among 102 HIV+ youths aged 14 to 23 years (27% African American, 33% Latino). Over their lifetime, youths engaged in unprotected sexual acts with multiple partners (M = 284; Median = 44; consistent condom protection, 5%) and substance use (21% injecting drug use; 68% hard drugs). When current risk behaviors were assessed twice over two consecutive 3-month periods, almost one third had been sexually abstinent. Among youths who were currently sexually active, most had multiple sexual partners (M = 5.7, Time 1; 4.9, Time 2) and used condoms (72-77% sexual acts protected); most of the youths (63-64%) always used condoms. Use of alcohol (63%), marijuana (41%), hard drugs (36%), and injecting drugs (12%) was substantial. Youths were relatively healthy (M T cells = 521.4; 14% T cells < 200; 1.9 diseases and 3.7 physical symptoms in the previous 3 months); they attended about one third of their medical appointments. While all youths were linked to adolescent HIV programs, unhealthy behavior and risk acts remained common. More effective and intensive intervention appears required. [ABSTRACT FROM AUTHOR]

Abstract Background This paper presents the model and results to evaluate the use of teriparatide as a first-line treatment of severe postmenopausal osteoporosis (PMO) and Glucocorticoid-induced osteoporosis (GIOP). The study’s objective was to determine if teriparatide is cost effective against oral bisphosphonates for two large and high risk cohorts. Methods A computer simulation model was created to model treatment, osteoporosis related fractures, and the remaining life of PMO and GIOP patients. Natural mortality and additional mortality from osteoporosis related fractures were included in the model. Costs for treatment with both teriparatide and oral bisphosphonates were included. Drug efficacy was modeled as a reduction to the relative fracture risk for subsequent osteoporosis related fractures. Patient health utilities associated with age, gender, and osteoporosis related fractures were included in the model. Patient costs and utilities were summarized and incremental cost-effectiveness ratios (ICERs) for teriparatide versus oral bisphosphonates and teriparatide versus no treatment were estimated. For each of the PMO and GIOP populations, two cohorts differentiated by fracture history were simulated. The first contained patients with both a historical vertebral fracture and an incident vertebral fracture. The second contained patients with only an incident vertebral fracture. The PMO cohorts simulated had an initial Bone Mineral Density (BMD) T-Score of −3.0. The GIOP cohorts simulated had an initial BMD T-Score of −2.5. Results The ICERs for teriparatide versus bisphosphonate use for the one and two fracture PMO cohorts were €36,995 per QALY and €19,371 per QALY. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture GIOP cohorts were €20,826 per QALY and €15,155 per QALY, respectively. Conclusions The selection of teriparatide versus oral bisphosphonates as a first-line treatment for the high risk PMO and GIOP cohorts evaluated is justified at a cost per QALY threshold of €50,000.

Abstract Electronic health records are increasingly being used to facilitate referral communication in the outpatient setting. However, despite support by technology, referral communication between primary care providers and specialists is often unsatisfactory and is unable to eliminate care delays. This may be in part due to lack of attention to how information and communication technology fits within the social environment of health care. Making electronic referral communication effective requires a multifaceted “socio-technical” approach. Using an 8-dimensional socio-technical model for health information technology as a framework, we describe ten recommendations that represent good clinical practices to design, develop, implement, improve, and monitor electronic referral communication in the outpatient setting. These recommendations were developed on the basis of our previous work, current literature, sound clinical practice, and a systems-based approach to understanding and implementing health information technology solutions. Recommendations are relevant to system designers, practicing clinicians, and other stakeholders considering use of electronic health records to support referral communication.

Abstract Background Abnormal health anxiety, also called hypochondriasis, has been successfully treated by cognitive behaviour therapy (CBT) in patients recruited from primary care, but only one pilot trial has been carried out among those attending secondary medical clinics where health anxiety is likely to be more common and have a greater impact on services. The CHAMP study extends this work to examine both the clinical and cost effectiveness of CBT in this population. Method/Design The study is a randomized controlled trial with two parallel arms and equal randomization of 466 eligible patients (assuming a 20% drop-out) to an active treatment group of 5-10 sessions of cognitive behaviour therapy and to a control group. The aim at baseline, after completion of all assessments but before randomization, was to give a standard simple explanation of the nature of health anxiety for all participants. Subsequently the control group was to receive whatever care might usually be available in the clinics, which is normally a combination of clinical assessment, appropriate tests and reassurance. Those allocated to the active treatment group were planned to receive between 5 and 10 sessions of an adapted form of cognitive behaviour therapy based on the Salkovskis/Warwick model, in which a set of treatment strategies are chosen aimed at helping patients understand the factors that drive and maintain health anxiety. The therapy was planned to be given by graduate research workers, nurses or other health professionals trained for this intervention whom would also have their competence assessed independently during the course of treatment. The primary outcome is reduction in health anxiety symptoms after one year and the main secondary outcome is the cost of care after two years. Discussion This represents the first trial of adapted cognitive behaviour therapy in health anxiety that is large enough to test not only the clinical benefits of treatment but also whether the cost of treatment is offset by savings from reduced use of other health services in comparison to the control group. Cognitive behaviour therapy for Health Anxiety in Medical Patients (CHAMP) Trial registration Current Controlled Trials ISRCTN14565822

Abstract Background Platelet-activating factor and nitric oxide may be involved in the initiation of human labour as inflammatory mediators. The aim of this study was to test whether platelet-activating factor and lipopolysaccharide were able to induce nitric oxide synthase expression and stimulate the production of nitric oxide in human fetal membrane explants in culture. Methods Fetal membranes were collected from Caesarean sections at term. RNA was extracted from membranes and subjected to a qualitative RT-PCR to assess the baseline expression of iNOS. Discs of fetal membranes were cultured for 24 hours in the presence of platelet-activating factor at a dose range of 0.1 nanomolar – 1 micomolar or 1 microgram/ml lipopolysaccharide. Nitric oxide production was measured via nitrite ions in the culture medium and mRNA for iNOS was detected by RT-PCR. Results Culturing the membrane discs in medium containing serum induced nitric oxide synthase expression and platelet-activating factor significantly stimulated the production of nitric oxide under these conditions. When cultured without serum inducible nitric oxide synthase expression was induced by lipopolysaccharide, but not by platelet-activating factor. Conclusion Platelet-activating factor may have a role in the initiation of labour, at term or preterm, via the increased local production of nitric oxide as an inflammatory mediator. In this model of intrauterine infection, lipopolysaccharide was found to induce iNOS expression by fetal membranes, and this mechanism could be involved in preterm labour.

An assessment of the effects of HIV/AIDS patients' empowered behaviours on the patient-provider relationship was undertaken. Participants were 50 HIV-positive women ranging in age from 23 to 48 years, with 60% of the sample African American, 24% Latina, 6% White and 10% mixed/other race. Descriptive and canonical correlation analyses were used to investigate the interrelationships between patients' empowered behaviours and self-reported interactions with their providers. Positive associations were noted between patients' medical decision-making involvement and patient-provider interactions. Patients reporting greater decision-making involvement, had higher levels of communication with their providers, and received more information and positive affect from their providers. Health care providers of HIV-positive women are encouraged to cultivate empowered behaviours in their patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe human immunodeficiency virus (HIV) testing patterns among high-risk, uninfected adolescents and HIV-infected adolescents, and factors associated with testing. METHODS: HIV-infected adolescents (N = 246) and high-risk, uninfected adolescents (N = 141) at 15 sites nationwide were asked about the number of times they were tested for HIV, the type of agency at which testing occurred, and reasons for testing. RESULTS: The majority of participants reported being influenced to obtain testing by health care providers (53.1% of the HIV-infected group and 66.1% of the HIV-uninfected group, respectively). Female participants were somewhat more likely to have used a confidential or anonymous site for the most recent test, compared with male participants (73.5% and 67.5%, respectively). Among the HIV-infected group, feeling sick was the only factor associated with number of tests. Among the HIV-uninfected group, having more male partners, marijuana use in the past 3 months, white race, and having had same-gender partners in their lifetime (males only) were associated with number of tests. Multivariate analyses identified 2 significant models. Modeling the probability of having been tested 3 or more times, black participants were less likely to be tested than white participants (odds ratio [OR] = 0.4), and participants who felt sick were more likely to be tested than those who did not (OR = 1.7). Modeling the probability that the last test would be positive, black participants were more likely than white participants to test positive (OR = 2.3); those who were tested because they thought they might have gotten HIV from sex (OR = 3.0) or they felt sick (OR = 3.9) were more likely to test positive; participants who were tested because a health care professional recommended it were actually less likely (OR = 0.5) to test positive. CONCLUSIONS: Overall, these findings highlight the importance of making HIV testing more routinely available to sexually active adolescents. More work needs to be done to normalize HIV testing among adolescents, and more innovative approaches need to be implemented on a wide scale. [Abstract for this article also available on page 613 of printed version. Full article available at http://www.pediatrics.org/cgi/content/full/110/3/e36] [ABSTRACT FROM AUTHOR]

Human peripheral blood mononuclear cells (PBMCs) are used to examine biological processes and disease, when basal variability in cellular activation and splicing is described and unexplained. Using isolation systems that maintained buffy coat cells (PBMCs, platelets) in their own plasma, poly-A enriched RNA-sequencing (RNASeq) detected 42,720 Ensembl gene IDs, including >95% of the top 100 Genotype Tissue Expression Project (GTEx)-expressed genes in lung, colon, heart, skeletal muscle and liver, and 10/17 clinically-actionable genes listed by the Pharmacogenomics Knowledgebase. Transcriptome changes were defined after 1h treatment with 32°C hypothermia (hsp70 family member change), 10 μmol/L ferric citrate that had no discernible effect, and 100 μg/mL cycloheximide leading to induction of primary response (immediate early) genes including IL1B and TNF. Same-donor PBMCs prepared conventionally using washes then resuspension in serum-supplemented media demonstrated basal upregulation of stress signalling pathway genes that masked and overlapped differential gene expression profiles after 100 µg/L cycloheximide. Plasma-resuspended PBMCs demonstrated minor transcriptome changes after 40 μmol/L ferric citrate, whereas consistent and greater magnitude changes were observed for washed/media-resuspended PBMCs. We conclude that endogenous plasma-maintained PBMCs provide a more robust platform to interrogate acute cellular perturbations triggering innate immunity, and that varying susceptibility of PBMCs to preparative stresses is an important component of experimental variability., Competing Interests: The authors have no direct conflict of interest to declare. The use of MEK inhibitors for treatment of bleeding in hereditary haemorrhagic telangiectasia (HHT) is the subject of a patent application by Imperial College London.

Sexual and gender minority youth (SGMY) are vulnerable to acquiring HIV and need HIV prevention and health services, but may have competing needs. A prior analysis found that PrEP use reports increased in a combination intervention study arm with coaching, peer support, and automated text-messages. This paper examines ancillary support and healthcare services utilization as secondary intervention objectives. SGMY (N = 895, 40% Black, 29% Latino) in Los Angeles and New Orleans were recruited from May, 2017 to August, 2019 and randomized to four intervention conditions: (a) automated text-messaging and monitoring intervention (AMMI), (b) AMMI plus peer support online (AMMI+PS), (c) AMMI plus strengths-based coaching by near-peer paraprofessionals (AMMI+C), or (d) all three (AMMI+PS+C). Intent-to-treat multivariate regression analyses evaluated the interventions' efficacy on past 4-month reports of ancillary support services use, having a regular healthcare provider, receiving care from doctor's office or clinic and mental health specialists, and participation in mental health support groups and HIV prevention programs. Ancillary services utilization reports declined from 40% of youth reporting an average of 4.4 services at baseline to 22.6% reporting 2.5 services by 24 months. Food, housing, transportation, and other basic services were utilized most frequently. Youth in the two coaching interventions maintained higher reports of services use over time compared to AMMI-only (both OR 1.23, 95%CI 1.12-1.35) and to AMMI+PS (both OR 1.20 95%CI 1.08-1.33). Our coaching intervention may support SGMY to stay engaged in support services. Results may be limited by self-report biases. It is unclear if these services are related to better long-term outcomes., Competing Interests: Declarations. Conflict of interest: Dr. Arnold was a consultant on project funded by Merck, Sharpe, and Dohme and has current funding from this entity. However, these projects are not related to the current study/manuscript. The other authors declare no competing interests, financial or non-financial. Ethical Approval: All study methods were approved by the IRB. The Institutional Review Board (IRB) of the University of California, Los Angeles served as the single IRB of Record for each collaborating university/agency partner (#16-001674-CR-00003), and the trial was registered at clinicaltrials.gov (#03134833). Consent to Participants: All participants provided informed consent per the IRB-approved process., (© 2024. The Author(s).)

The BEACON CRC study demonstrated that encorafenib (Enco)+cetuximab (Cetux)±binimetinib (Bini) significantly improved overall survival (OS) versus Cetux + chemotherapy in previously treated patients with BRAF-V600E-mutant mCRC, providing the basis for the approval of the Enco+Cetux regimen in the United States and the European Union. A greater understanding of biomarkers predictive of response to Enco+Cetux±Bini treatment is of clinical relevance. In this prespecified, exploratory biomarker analysis of the BEACON CRC study, we characterize genomic and transcriptomic correlates of clinical outcomes and acquired resistance mechanisms through integrated clinical and molecular analysis, including whole-exome and -transcriptome tissue sequencing and circulating tumor DNA genomic profiling. Tumors with higher immune signatures showed a trend towards increased OS benefit with Enco+Bini+Cetux. RAS, MAP2K1 and MET alterations were most commonly acquired with Enco+Cetux±Bini, and more frequent in patients with a high baseline cell-cycle gene signature; baseline TP53 mutation was associated with acquired MET amplification. Acquired mutations were subclonal and polyclonal, with evidence of increased tumor mutation rate with Enco+Cetux±Bini and mutational signatures (SBS17a/b). These findings support treatment with Enco+Cetux±Bini for patients with BRAF-V600E-mutant mCRC and provide insights into the biology of response and resistance to MAPK-pathway-targeted therapy. ClinicalTrials.gov registration: NCT02928224., Competing Interests: Competing interests S.K.: Stock and Other Ownership Interests: Iylon, Lutris, MolecularMatch, Navire. Consulting or Advisory Role: AbbVie, Amal Therapeutics, AstraZeneca/MedImmune, Bayer Health, Bicara Therapeutics, Boehringer Ingelheim, Boston Biomedical, Carina Biotech, Daiichi Sankyo, EMD Serono, Endeavor BioMedicines, Flame Biosciences, Genentech, Gilead Sciences, GSK, HalioDx, Holy Stone Healthcare, Inivata, Ipsen, Iylon, Jacobio, Jazz Pharmaceuticals, Lilly, Lutris, Merck, Mirati Therapeutics, Natera, Novartis, Numab, Pfizer, Pierre Fabre, Redx Pharma, Repare Therapeutics, Servier, Xilis. Research Funding: Amgen (Inst), Array BioPharma (Inst), Biocartis (Inst), Daiichi Sankyo (Inst), EMD Serono (Inst), Genentech/Roche (Inst), Guardant Health (Inst), Lilly (Inst), MedImmune (Inst), Novartis (Inst), Sanofi (Inst). D.A.M.: Employment: Formerly Pfizer. Stock and Other Ownership Interests: Pfizer. J.P.: Employment: Formerly Pfizer. Stock and Other Ownership Interests: Pfizer. F.C.: Consulting or Advisory Role: Amgen, Bayer, Merck KGaA, Pfizer, Roche/Genentech. Research Funding: Amgen (Inst), Bayer (Inst), Bristol Myers Squibb (Inst), Ipsen (Inst), Merck KGaA (Inst), MSD (Inst), Roche/Genentech (Inst), Servier (Inst), Symphogen (Inst). J.D.: Consulting or Advisory Role: Amgen (Inst), Bayer, BeiGene, Daiichi Sankyo, Eisai, GSK, Merck KGaA, Pierre Fabre. Research Funding: AstraZeneca/MedImmune (Inst), BeiGene (Inst), Bionomics (Inst), Bristol Myers Squibb (Inst), GSK (Inst), Lilly (Inst), Novartis (Inst), Roche (Inst). E.V.C.: Consulting or Advisory Role: AbbVie, Agenus, ALX, Amgen, Arcus Biosciences, Astellas Pharma, AstraZeneca, Bayer, BeiGene, BioNTech, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Debiopharm, ElmediX, Eisai, GSK, Hookipa Biotech, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Pfizer, Roche, Seagen, Servier, Simcere, Takeda, Taiho Pharmaceutical, Terumo. H.S.W.: Consulting or Advisory Role: Amgen, Bayer, Bristol Myers Squibb (Celgene), Boehringer Ingelheim (DMC), BTG, EXACT Therapeutics, Erytech Pharma, Incyte, Merck KGaA, Oaktree Life Sciences, OncoSil, Pfizer, Pierre Fabre, Roche/Genentech, Seagen, Servier, Shire, Sirtex Medical, Takeda (Hutchinson Med), Zymeworks. Research Funding: Merck KGaA (Inst), MSD (Inst), Pfizer (Inst), Sirtex Medical (Inst). T.Y.: Honoraria: Bayer Yakuhin, Chugai Pharma, Merck KGaA, MSD, Ono Pharmaceutical, Sumitomo Corp., Takeda. Research Funding: Amgen (Inst), Boehringer Ingelheim (Inst), Chugai Pharma (Inst), Daiichi Sankyo Co., Ltd. (Inst), Eisai, FALCO Biosystems, Genomedia (Inst), Molecular Health, MSD (Inst), Nippon Boehringer Ingelheim, Ono Pharmaceutical (Inst), Pfizer (Inst), Roche Diagnostics, Sanofi (Inst), Sumitomo Dainippon (Inst), Sysmex (Inst), Taiho Pharmaceutical (Inst). H.S.: Employment: Pfizer. Stock and Other Ownership Interests: Pfizer. X.Z.: Employment: Pfizer. Stock and Other Ownership Interests: Pfizer. Patents, Royalties, Other Intellectual Property: Johns Hopkins University. P.H.: Employment: Pfizer. Stock and Other Ownership Interests: Pfizer. T.X.: Employment: Pfizer. Stock and Other Ownership Interests: Pfizer. R.Y.: Consulting or Advisory Role: Array BioPharma/Pfizer, Mirati Therapeutics, Zai Lab, Amgen. Research Funding: Array BioPharma (Inst), Boehringer Ingelheim (Inst), Mirati Therapeutics (Inst), Pfizer (Inst), Daiichi Sankyo (Inst). J.T.: Consulting or Advisory Role: Array BioPharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai Pharma, Daiichi Sankyo, F. Hoffmann-La Roche, Genentech, HalioDx, Hutchison MediPharma, Ikena Oncology, Inspirna Inc., IQVIA, Lilly, Menarini, Merck Serono, Merus, Mirati Therapeutics, MSD, NeoPhore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seagen Inc., Servier, Taiho Pharmaceutical, Tessa Therapeutics, TheraMyc. Other Relationship: Amgen, Array Biopharma, BeiGene, Boehringer Ingelheim, BMS, Cancer Research UK, Celgene, Debiopharm, F. Hoffman-La Roche, Fundación Científica de la Asociación Española Contra el Cáncer, Genentech, HalioDX, Hutchinson Medipharma, Imedex, Janssen-Cilag, MedImmune, Medscape, Menarini, Merck Health KGaA, MJH Life Sciences, MSD, Merus, Mirati, Novartis, Oniria Therapeutics, PeerView Institute for Medical Education, Pfizer, PharmaMar, Physicans’ Education Resource, Sanofi-Aventis, Servier, Taiho Pharmaceutical., (© 2024. The Author(s).)

Purpose of Review: This review explores recent advancements in robotic cardiac surgery, specifically focusing on its application in diverse mitral valve surgeries. The aim is to provide an overview of current clinical practices and supporting evidence in this evolving field., Recent Findings: A literature review indicates a 30% surge in robotic mitral valve repair from 2015 to 2021, paralleled by a decline in sternotomy-based repair per the STS database. Robotic mitral valve repair consistently shows effective and safe outcomes, with comparable mortality but lower morbidity risks than sternotomy and thoracotomy. The robotic approach exhibits lower conversion to valve replacement, shorter ICU stays, and reduced 30-day readmissions. For experienced programs, robotic techniques prove versatile in various pathologies, including rheumatic heart valve disease, infective endocarditis, ischemic cardiomyopathy, and mitral annular calcification necessitating valve replacement. Literature supports their selective use in high-risk scenarios, including redo surgeries and elderly patients., Summary: Recent evidence supports the growing use of robotic approaches in mitral valve surgery, highlighting their efficacy with comparable mortality rates but lower morbidity risks. Robotic techniques consistently yield positive outcomes across various pathologies and patient profiles, signaling a potential paradigm shift in mitral valve interventions., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Keratoconus (KC) is a corneal thinning dystrophy that leads to visual impairment. While the cause of KC remains poorly understood, changes in sex hormone levels have been correlated with KC development. This study investigated circulating gonadotropin-releasing hormone (GnRH) in control and KC subjects to determine if this master hormone regulator is linked to the KC pathology. Plasma and saliva were collected from KC subjects (n = 227 and n = 274, respectively) and non-KC controls (n = 58 and n = 101, respectively), in concert with patient demographics and clinical features. GnRH levels in both plasma and saliva were significantly lower in KC subjects compared to controls. This finding was retained in plasma when subjects were stratified based on age, sex, and KC severity. Control and KC corneal fibroblasts (HKCs) stimulated with recombinant GnRH protein in vitro revealed significantly increased luteinizing hormone receptor by HKCs and reduced expression of α-smooth muscle actin with treatment suggesting that GnRH may modulate hormonal and fibrotic responses in the KC corneal stroma. Further studies are needed to reveal the role of the hypothalamic-pituitary-gonadal axis in the onset and progression of KC and to explore this pathway as a novel therapeutic target.

Objective: Safety and sustainability are key elements of a robotic mitral valve (MV) program at any stage of development. Challenges include the positioning of the surgeon at the robotic console, increasing patient complexity, and upstream administrative staffing difficulties. We instituted a systems approach to maximize patient safety and maintain robotic service viability., Methods: A single dedicated robotic operating room (OR) was equipped as a microsystem with team training in the operative steps, ergonomics, digital tools, and an explicit culture of safety. Outcomes of all robotic mitral procedures including concomitant procedures in the microsystem OR by a single surgeon were retrospectively reviewed., Results: From January 2014 through December 2023, 1,529 consecutive MV patients were operated with an endoscopic robotic approach. Ten patients (0.65%) were converted to conventional approaches. Overall, 1,300 MV repairs (85%) were performed with residual MV regurgitation of none to trace in 1,205 patients (92.7%), mild in 92 patients (7.1%), and moderate in 3 patients (0.23%). MV replacements were performed in 229 patients (15%) with no paravalvular leaks. Mortality was 0.08% in the repair group and 0.87% in the replacement group. No deaths have occurred in the last 38 months. Stroke occurred in 0.31% of repair patients and 1.3% of replacement patients. One patient developed transient renal failure., Conclusions: Organization of the robotic OR as a microsystem is associated with surgical efficacy and very low morbidity and mortality. A comparable microsystem approach using all or select components may promote safety and sustainability for robotic MV programs at all levels., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Douglas A. Murphy is a consultant to Intuitive Surgical, Inc. and Edwards Lifesciences.

Purpose: To evaluate the effectiveness and stability of refractive astigmatism reduction after penetrating femtosecond laser-assisted arcuate keratotomy performed at the time of femtosecond laser-assisted cataract surgery., Methods: Non-randomized retrospective data analysis of all patients that underwent femtosecond laser-assisted cataract surgery with femtosecond laser-assisted arcuate keratotomy over a 4-year period with a non-toric monofocal intraocular lens (2017-2021) at a tertiary care academic center. Postoperative visual acuity, manifest refraction, and predicted residual refractive error were also recorded at 1 month, 3-6 months, 12-18 months, and 2 years postoperatively. Preoperative keratometric astigmatism was compared to postoperative refractive astigmatism using vector calculations and the ASCRS double-angle plot tool., Results: This study comprised 266 eyes (179 patients) that met inclusion criteria. The mean preoperative keratometric astigmatism magnitude was 0.99 ± 0.53 D. At 1 month, 3-6 months, 12-18 months, and 2 years postoperatively, the mean refractive cylinder was 0.49 ± 0.45 D, 0.49 ± 0.45 D, 0.55 ± 0.54 D, and 0.52 ± 0.46 D, respectively. Horizontal against-the-rule astigmatism showed a higher tendency toward undercorrection than vertical with-the-rule astigmatism, which had a slightly higher tendency toward overcorrection. With-the-rule astigmatism had smaller difference vectors between target-induced astigmatism and surgically induced astigmatism., Conclusions: Femtosecond laser-assisted arcuate keratotomy performed at the time of femtosecond laser-assisted cataract surgery was an effective option for correcting low-to-moderate corneal astigmatism for up to 2 years.