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Mental health organizations that serve youth are under pressure to adopt measurement-based care (MBC), defined as the continuous collection of client-report data used to support clinical decision-making as part of standard care. However, few frameworks exist to help leadership ascertain how to select an MBC approach for a clinical setting. This paper seeks to define how an MBC approach can display clinical utility to provide such a framework. Broadly, we define clinical utility as evidence that an MBC approach assists stakeholders in fulfilling clinical goals related to care quality (i.e., improve client-clinician alliance and clinical outcomes) at the client (i.e., youth and caregiver), clinician, supervisor, and administrator levels. More specifically, our definition of clinical utility is divided into two categories relevant to the usability and usefulness of an MBC approach for a specific setting: (a) implementability (i.e., evidence indicating ease of use in a clinical setting) and (b) usefulness in aiding clinical activities (i.e., evidence indicating the potential to improve communication and make clinical activities related to care quality easier or more effective). These categories provide valuable information about how easy an MBC approach is to use and the potential benefits that the MBC data will confer. To detail how we arrived at this definition, we review prior definitions of clinical utility, discuss how previous definitions inform our definition of clinical utility for MBC, and provide examples of how the concept of clinical utility can be applied to MBC. We finish with a discussion of future research directions.

Corneal ulcers are a common cause of blindness in low-income and middle-income countries, usually resulting from traumatic corneal abrasions during agricultural work. Antimicrobial prophylaxis of corneal abrasions can help prevent corneal ulcers, but delays in the initiation of therapy are frequent. We aimed to assess whether a community-based programme for corneal ulcer prevention would reduce the incidence of corneal ulceration.A cluster-randomised trial was performed in village development committees (VDCs) in Nepal. VDCs in the catchment area of Bharatpur Eye Hospital, Nepal with less than 15 000 people were eligible for inclusion. We randomly assigned (1:1) VDCs to either an intervention group or a control group. In the intervention VDCs, existing female community health volunteers (FCHVs) were trained to diagnose corneal abrasions and provide a 3-day course of ophthalmic antimicrobials to their patients. In the control VDCs, FCHVs did not provide this intervention. Participants were not masked given the nature of the intervention. Both groups were followed up for 3 years for photographic evidence of corneal ulceration. The primary outcome was the incidence of corneal ulceration, determined by masked assessment of corneal photographs. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01969786.We assessed 112 VDCs, of which 24 were enrolled. The study was performed between Feb 4, 2014, and Oct 20, 2017. 12 VDCs were randomly assigned to the intervention group and 12 to the control group. 252 539 individuals were included in the study (130 579 in the intervention group and 121 960 in the control group). FCHVs diagnosed and provided antimicrobials for 4777 corneal abrasions. The census identified 289 corneal ulcers among 246 893 person-years in the intervention group (incidence 1·21 cases [95% CI 0·85-1·74] per 1000 person-years) and 262 corneal ulcers among 239 170 person-years in the control group (incidence 1·18 cases [0·82-1·70] per 1000 person-years; incidence rate ratio 1·03 [95% CI 0·63-1·67]; p=0·93). Medication allergy was self-reported in 0·2% of participants.We did not detect a reduction in the incidence of corneal ulceration during the first 3 years of a community-based corneal ulcer prevention programme. Further study might be warranted in more rural areas where basic eye care facilities are not available.National Eye Institute.

This study quantifies the performance of an international cohort of cornea specialists in image-based differentiation of bacterial and fungal keratitis, identifying significant regional variation and establishing a reference standard for comparison against machine learning models.

Background: breast cancer has a significant heritable basis, of which ∼60% remains unexplained. Testing for BRCA1/BRCA2 offers useful discrimination of breast cancer risk within families, and identification of additional breast cancer susceptibility genes could offer clinical utility. Patients and methods: we included 2135 invasive breast cancer cases recruited via the Breast and Ovarian Cancer Susceptibility study, a retrospective UK study of familial breast cancer. Eligibility criteria: female, BRCA-negative, white European ethnicity, and one of: (i) breast cancer family history, (ii) bilateral disease, (iii) young age of onset (Results: 159/2135 (7.4%) cases had a qualifying variant in an established breast cancer susceptibility gene, with minimal evidence of signal in other cancer susceptibility genes. Known breast cancer susceptibility genes PALB2, CHEK2, and ATM were the only genes to retain statistical significance after correcting for multiple testing. Due to the enrichment of hereditary cases in the series, we had good power (>80%) to detect a gene of BRCA1-like risk [odds ratio (OR) = 10.6] down to a population minor allele frequency of 4.6 × 10 −5 (1 in 10 799, less than one-tenth that of BRCA1)and of PALB2-like risk (OR = 5.0) down to a population minor allele frequency of 2.8 × 10 −4 (1 in 1779, less than half that of PALB2). Power was lower for identification of novel moderate penetrance genes (OR = 2-3) like CHEK2 and ATM. Conclusions: this is the largest case-control whole-exome analysis of enriched breast cancer published to date. Whilst additional breast cancer susceptibility genes likely exist, those of high penetrance are likely to be of very low mutational frequency. Contention exists regarding the clinical utility of such genes.

Although technical (quality of delivering techniques from a specific treatment) and global (general clinical expertise) competence are believed to be important ingredients of successful psychosocial treatment with youth, there have been few empirical efforts to measure both dimensions. Efforts to understand the role that each competence dimension plays in the process and outcome of youth treatment starts with determining whether the dimensions can be measured separately. This study examined whether scores from measures designed to assess technical and global competence were distinct. Treatment sessions (N = 603) from 38 youths (M age = 9.84 years, SD = 1.65; 60.5% White; 52.6% male) treated for primary anxiety problems within a randomized effectiveness trial were coded. Four coders used observational measures designed to assess technical competence, global competence, protocol adherence, and the alliance. Mean item interrater reliability was .70 (SD = .09) for technical competence and .66 (SD = .05) for global competence. While most components of global competence were distinct from technical competence scores, two components showed redundancy (r > .70). Scores on both competence measures were empirically distinct (r < .70) from scores on measures of protocol adherence and the alliance. Although the measures did not fully distinguish between technical and global competence, our findings do indicate that some components of technical and global competence may provide unique information about competence.

Although the alliance is a consistent predictor of treatment outcomes in psychosocial interventions, few studies have examined this association among youth with autism spectrum disorder (ASD). In particular, youth-therapist alliance has never been examined in social skills interventions (SSIs), a common modality for this population. In this study, thirty-four youth with ASD (Mage = 12.41; 79% male) participated in a community-delivered, group-based SSI in a summer camp format led by eight Head Therapists (Mage = 32.12; 50% male). Early alliance and change in alliance over the course of the treatment were assessed via self- and observer-reported measures. Both self- and observer-rated alliance were associated with positive treatment outcomes as reported by parents (decreased problem behaviors) and other peers in the group (reciprocated friendship and social preference). These results provide the first evidence of the role of the alliance in an SSI for youth with ASD and add to the growing body of literature that demonstrates the importance of assessing and addressing the alliance in treatment for this population.

Introduction Studies have found that psychological treatments produce positive clinical outcomes for many problems experienced by youth. However, there is limited research on whether therapist adherence and competence in delivering these treatments are related to differential clinical outcomes. Method We examined the relationship of therapist adherence and competence to clinical outcomes in a sample of 51 youth aged 7-14 years (M age = 10.36, SD = 1.90; 86.3% white; 60.8% male) treated for anxiety disorders with a manualized individual cognitive-behavioral therapy. Adherence and competence were measured via coding of recorded treatment session content and outcomes were measured by caregiver and youth report across multiple timepoints. We used two-level mixed-effects regression models to test the degree to which adherence and competence predicted differential youth clinical outcomes. Results Across multiple caregiver- and child-reported symptom and diagnostic outcomes, we found no statistically significant relationship between adherence or competence and clinical outcomes. Discussion Although there was variability in both treatment integrity and clinical outcome, neither adherence to nor competence in youth anxiety treatment was related to clinical outcomes for youth with anxiety disorders treated with individual cognitive-behavioral treatment (CBT) in a research clinic-based efficacy trial. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

PurposeTo compare the effects of the Ahmed glaucoma valve (AGV; New World Medical, Rancho Cucamonga, CA) with sulcus versus anterior chamber (AC) tube placement on the corneal endothelial density and morphology over time.DesignNonrandomized, interventional study.ParticipantsThis study included 106 eyes from 101 pseudophakic patients who had the AGV tube placed in the AC (acAGV) and 105 eyes from 94 pseudophakic patients who had the AGV tube placed in the ciliary sulcus (sAGV).MethodsAll patients underwent preoperative specular microscopy, which was repeated postoperatively in 2019. The patients' demographic information, glaucoma diagnoses, and basic ocular information were obtained on chart review. Anterior segment OCT was conducted for patients who underwent sAGV to evaluate the sulcus tube position. Gonioscopy was performed to document peripheral anterior synechiae (PAS). Linear mixed-effects models were used to compare the different ocular and endothelial measurements between the 2 groups and to identify risk factors for endothelial cell density (ECD) loss over time.Main outcome measuresMonthly change in corneal endothelial measurements, including ECD and coefficient of variation (CV), calculated as the difference between preoperative and postoperative measurements divided by the number of months from the time of surgery to postoperative specular microscopy.ResultsThe acAGV and sAGV groups were comparable in all baseline characteristics except that the acAGV group had longer follow-up (37.6 vs. 20.1 months, respectively, P < 0.001). Mean monthly loss in central ECD was significantly more in the acAGV group (mean ± standard deviation: 29.3±29.7 cells/mm2) than in the sAGV group (15.3±20.7 cells/mm2, P < 0.0001). Mean monthly change in CV was similar between the 2 groups (P= 0.28). Multivariate analyses revealed that younger age and tube location in the AC were associated with faster central ECD loss (P= 0.02, P < 0.0001, respectively). For patients with sAGV, while PAS was associated with faster central ECD loss (P= 0.002), a more forward tube position tenting the iris was not (P > 0.05).ConclusionsCompared with anterior segment placement, ciliary sulcus tube implantation may be a preferred surgery approach to reduce endothelial cell loss in pseudophakic patients.

Mental health clinicians and administrators are increasingly asked to collect and report treatment outcome data despite numerous challenges to select and use instruments in routine practice. Measurement-based care (MBC) is an evidence-based practice for improving patient care. We propose that data collected from MBC processes with patients can be strategically leveraged by agencies to also support clinicians and respond to accountability requirements. MBC data elements are outlined using the Precision Mental Health Framework (Bickman et al. in Adm Policy Mental Health Mental Health Serv Res 43:271-276, 2016), practical guidance is provided for agency administrators, and conceptual examples illustrate strategic applications of one or more instruments to meet various needs throughout the organization.

Data from an online survey of undergraduate students at 14 colleges and universities were used to estimate the association of autism with six physical and mental health outcomes, accounting for comorbidity with other disabilities (learning disability, attention deficit hyperactivity disorder, sensory impairment, mobility impairment, mental health disorder, or other disabilities). Autism status was determined based on registration for disability accommodations based on autism and/or self-reports of an autism diagnosis. Health outcomes included self-rated physical health, self-rated mental health, depressive symptoms, symptoms of anxiety, sleep deprivation, and binge drinking. Students with autism reported poorer self-rated physical and mental health, more depressive symptoms, and more symptoms of anxiety than other students, even in the presence of controls for other disabilities. Students with autism also reported a lower likelihood of sleep deprivation and binge drinking than other students. Our results extend previous research on the health correlates of autism by considering additional indicators of health and by incorporating a direct comparison to neurotypical students. They encourage consideration of how health services for students with autism can be improved, especially for mental health problems, and argue for integrated support services that address the full constellation of physical and mental health challenges that students on the spectrum experience.Lay abstractStudies have shown that children and older adults on the autism spectrum experience more physical and mental health problems than their neurotypical peers. Less is known about the physical and mental health of college students on the spectrum. Studying college students is important because young adults on the spectrum are enrolling in college at increasing rates and because health problems can be a barrier to succeeding in college. We collected data from 2820 students at 14 colleges and universities using an online survey, some of whom had registered for accommodations based on autism and others of whom had not. We used the data to compare the physical and mental health of students on the spectrum to their neurotypical peers. Because students with autism often report other disabilities that also affect health, we accounted for whether they experienced a learning disability, attention deficit hyperactivity disorder, sensory impairment, mobility impairment, mental health disorder, or any other disabilities. We assessed health using self-reports of how healthy they were physically and mentally, and reports of depressive symptoms, symptoms of anxiety, sleep deprivation, and binge drinking. We found that students with autism reported poorer physical and mental health, more depressive symptoms, and more symptoms of anxiety even after taking into account other disabilities they may have experienced. They were also less likely to report sleep deprivation and binge drinking. Our results argue for developing specialized services to address the physical and mental health challenges of college students on the spectrum.

Clinician fidelity to cognitive behavioral therapy (CBT) is an important mechanism by which desired clinical outcomes are achieved and is an indicator of care quality. Despite its importance, there are few fidelity measurement methods that are efficient and have demonstrated reliability and validity. Using a randomized trial design, we compared three methods of assessing CBT adherence-a core component of fidelity-to direct observation, the gold standard. Clinicians recruited from 27 community mental health agencies (n = 126; M age = 37.69 years, SD = 12.84; 75.7% female) were randomized 1:1:1 to one of three fidelity conditions: self-report (n = 41), chart-stimulated recall (semistructured interviews with the chart available; n = 42), or behavioral rehearsal (simulated role-plays; n = 43). All participating clinicians completed fidelity assessments for up to three sessions with three different clients that were recruited from clinicians' caseloads (n = 288; M age = 13.39 years SD = 3.89; 41.7% female); sessions were also audio-recorded and coded for comparison to determine the most accurate method. All fidelity measures had parallel scales that yielded an adherence maximum score (i.e., the highest-rated intervention in a session), a mean of techniques observed, and a count total of observed techniques. Results of three-level mixed effects regression models indicated that behavioral rehearsal produced comparable scores to observation for all adherence scores (all ps gt; .01), indicating no difference between behavioral rehearsal and observation. Self-report and chart-stimulated recall overestimated adherence compared to observation (ps lt; .01). Overall, findings suggested that behavioral rehearsal indexed CBT adherence comparably to direct observation, the gold-standard, in pediatric populations. Behavioral rehearsal may at times be able to replace the need for resource-intensive direct observation in implementation research and practice.

An observational coding system was developed to track clinical change in children with autism spectrum disorder (ASD) during psychotherapy. The Pediatric Autism Spectrum Therapy Observation System (PASTOS) consists of 23 items divided into 5 subscales and is used to rate child behaviors in individual psychotherapy sessions. Manual-based cognitive behavioral therapy session transcripts of 22 children diagnosed with ASD (IQ > 70) and a concurrent anxiety disorder (M = 9.41years, SD = 1.56years) enrolled in a randomized, controlled trial were coded. Results suggested that the PASTOS exhibited promising interrater reliability, internal consistency, convergent validity at post-treatment, and treatment sensitivity. The PASTOS may be a useful tool for studying process and outcome in psychotherapy research on children with ASD.

Though treatment integrity measurement is important for research intended to promote social and behavioral outcomes of children at risk for emotional and behavioral disorders (EBDs) in early childhood settings, measurement gaps exist in the field. This paper reports on the development and preliminary psychometric assessment of the treatment integrity measure for early childhood settings (TIMECS), an observational measure designed to address existing measurement gaps related to treatment integrity with tier 2 interventions in the early childhood field. To assess the preliminary score reliability (interrater) and validity (construct, discriminant) of the TIMECS, live observations (N = 650) in early childhood classrooms from 54 teachers (92.6% female, 7.4% male; 61.1% White) and 91 children (M age = 4.53 years, SD = .44; 45.1% female, 54.9% male; 45.1% Black) at risk for EBDs were scored by 12 coders using the TIMECS and an observational measure designed to assess teacher-child interactions. Teachers also self-reported on the quality of the teacher-child relationship. Interrater reliability (intraclass correlation coefficients, ICC [2,2]) for the quantity (i.e., adherence) item scores had a mean of .81 (SD = .07; range from .68 to .95), and the quality (i.e., competence) item scores had a mean of .69 (SD = .08; range from .52 to .80). Scores on the TIMECS Quantity and Quality items and scales showed evidence of construct validity, with the magnitude of the correlations suggesting that the quantity and quality items assess distinct components of treatment integrity. A TIMECS quantity scale also showed promise for intervention evaluation research by discriminating between teachers who had and had not been trained in a specific evidence-based intervention targeting social and behavioral skills in early childhood. The findings support the potential of the TIMECS to assess treatment integrity of teacher-delivered practices designed to address child social and behavioral outcomes of children at risk for EBDs in early childhood settings.

Doubly or bisconjugated steroid metabolites have long been known as minor components of the steroid profile that have traditionally been studied by laborious and indirect fractionation, hydrolysis and gas chromatography-mass spectrometry (GC-MS) analysis. Recently, the synthesis and characterisation of steroid bis(sulfate) (aka disulfate or bis-sulfate) reference materials enabled the liquid chromatography-tandem mass spectrometry (LC-MS/MS) study of this metabolite class and the development of a constant ion loss (CIL) scan method for the direct and untargeted detection of steroid bis(sulfate) metabolites. Methods for the direct LC-MS/MS detection of other bisconjugated steroids, such as steroid bisglucuronide and mixed steroid sulfate glucuronide metabolites, have great potential to reveal a more complete picture of the steroid profile. However, access to steroid bisglucuronide or sulfate glucuronide reference materials necessary for LC-MS/MS method development, metabolite identification or quantification is severely limited. In this work, ten steroid bisglucuronide and ten steroid sulfate glucuronide reference materials were synthesised through an ordered combination of chemical sulfation and/or enzymatic glucuronylation reactions. All compounds were purified and characterised using NMR and MS methods. Chemistry for the preparation of stable isotope labelled steroid {13C6}-glucuronide internal standards has also been developed and applied to the preparation of two selectively mono-labelled steroid bisglucuronide reference materials used to characterise more completely MS fragmentation pathways. The electrospray ionisation and fragmentation of the bisconjugated steroid reference materials has been studied. Preliminary targeted ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis of the reference materials prepared revealed the presence of three steroid sulfate glucuronides as endogenous human urinary metabolites.

This study describes the academic, social, and health experiences of college students on the autism spectrum as they compare to students with other disabilities and their non-disabled, neurotypical peers. Data were from an online survey of college students at 14 public institutions (N = 3073). There were few significant differences between students on the spectrum and students with other disabilities. Both groups of students reported significantly worse outcomes than neurotypical students on academic performance, social relationships and bullying, and physical and mental health. The findings suggest that some of the challenges students on the spectrum face in college result from the stigma and social rejection associated with disability rather than from the unique characteristics of autism.

We used data from the 2011 Survey of Pathways to Diagnosis and Services (N = 1,420) to evaluate a conceptual model linking social background (race-ethnicity, socioeconomic status [SES]) to parental distress through children’s clinical profiles and parental beliefs about the nature and causes of their child’s autism. Children’s clinical profiles varied by social background; white children and children of more highly educated and affluent parents were less likely to experience comorbid conditions and were more likely to be diagnosed with Asperger’s. Parental beliefs also varied such that parents of racial-ethnic minority children and parents of lower SES perceived their child’s condition as more uncertain and were less likely to attribute it to genetic causes. Parents of Hispanic children and with lower incomes were more likely to be upset by the child’s condition. Although parental beliefs had independent associations with distress, children’s clinical profiles contributed more to explaining variation in distress.

Background Studies suggest diurnal patterns of occurrence of some eye conditions. Leveraging new information sources such as web-based search data to learn more about such patterns could improve the understanding of patients’ eye-related conditions and well-being, better inform timing of clinical and remote eye care, and improve precision when targeting web-based public health campaigns toward underserved populations. Objective To investigate our hypothesis that the public is likely to consistently search about different ophthalmologic conditions at different hours of the day or days of week, we conducted an observational study using search data for terms related to ophthalmologic conditions such as conjunctivitis. We assessed whether search volumes reflected diurnal or day-of-week patterns and if those patterns were distinct from each other. Methods We designed a study to analyze and compare hourly search data for eye-related and control search terms, using time series regression models with trend and periodicity terms to remove outliers and then estimate diurnal effects. We planned a Google Trends setting, extracting data from 10 US states for the entire year of 2018. The exposure was internet search, and the participants were populations who searched through Google’s search engine using our chosen study terms. Our main outcome measures included cyclical hourly and day-of-week web-based search patterns. For statistical analyses, we considered P Results Distinct diurnal (P Conclusions The frequency of web-based searches for various eye conditions can show cyclic patterns according to time of the day or week. Further studies to understand the reasons for these variations may help supplement the current clinical understanding of ophthalmologic symptom presentation and improve the timeliness of patient messaging and care interventions.

Background Recurrent conjunctivitis epidemics are prevalent worldwide. Aetiologies are often undetermined. Methods We surveyed conjunctivitis researchers about perceived trends in prevalence, incidence and aetiologies of conjunctivitis epidemics. Results Of the 155 participants, 7% endorsed globally variable and dynamic microbial aetiologies of conjunctivitis epidemics. Increased incidence of conjunctivitis epidemics over the last decade were reported by 21% of respondents. Peak seasons differed between the northern and southern hemispheres. Conclusions There is regional equipoise regarding the increasing incidence and emerging underlying aetiologies of epidemic conjunctivitis. Further investigation of global surveillance and microbial characterization of conjunctivitis outbreaks could improve prevention and outcomes.

Measurement limitations lessen the conclusions about the role of the alliance in youth psychosocial treatment. This article examined the score reliability, factor structure, and validity of the 9-item Therapy Process Observational Coding System for Child Psychotherapy-Alliance scale (TPOCS-A). The sample, 51 youth aged 7-15 years (Mage = 10.36 years, SD = 1.90; 86.3% White; 60.8% male, 39.2% female), met diagnostic criteria for a principal anxiety disorder and received cognitive-behavioral therapy. Treatment sessions (N = 463) were coded by independent coders using the TPOCS-A along with observational measures of treatment adherence and therapist competence. Youth and therapists also completed self-report alliance measures at the end of each session. Reliability estimates, ICC(2,2), at the item level indicated a mean interrater reliability of .68 (SD = .10) and a mean coder stability of .64 (SD = .11). An exploratory factor analysis identified a one-factor solution with five items. TPOCS-A scores evidenced convergent validity with the therapist and adolescent reports of alliance but did not converge with the child-report alliance measure. TPOCS-A scores evidenced discriminant validity when compared with scores on adherence and competence measures. The reliability and validity profile of the 9- and 5-item versions of the TPOCS-A were similar. Overall, findings support the reliability and validity of the TPOCS-A scores, but questions remain about how best to assess the alliance with children. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Treatment adherence measurement can be time and resource-intensive in clinical trials, so the ability to measure protocol adherence for two distinct treatment programs with a single measure may benefit the field. The present study sought to determine if the Therapy Process Observational Coding System – Revised Strategies Scale (TPOCS-RS) could assess protocol adherence to two youth treatment programs. Treatment sessions (N = 796) from 55 youth (M age = 9.89 years, SD = 1.71; range 7–15 years; 55.0% White; 46.0% female) with primary anxiety problems treatment by 39 clinicians (M age = 40.54 years, SD = 9.56; 50.0% White; 80.0% female) were independently scored by coders using observational treatment adherence and alliance measures. The youth received one of three treatments: (a) Standard (i.e., cognitive-behavioral treatment program), (b) Modular (i.e., a program with cognitive-behavioral and parent training components), or (c) Usual Care. Consultants filled out a self-report measure of protocol adherence within the Standard and Modular conditions. Interrater reliability, ICC(2,2) for the various items for the full sample ranged from .17 to .92 (M ICC = .67; SD = .17). Scores from a TPOCS-RS subscale that mapped onto the specific content of the treatment protocols used in the Standard and Modular conditions evidenced convergent validity with the consultant-report adherence measure and discriminant validity with the alliance measure. The model-specific TPOCS-RS subscales also discriminated between the Standard and Modular treatments and Usual Care. This study provides initial evidence that (a) the TPOCS-RS has utility in estimating protocol adherence in different treatment programs and (b) support the score validity of the self-report consultation records.

A foldable acrylic intraocular lens (IOL) with a 6.0 mm optic was removed through a 2.2 mm corneal incision as a single piece with minimal wound trauma. By viscodissection, the IOL was freed from its position in the capsular bag and moved into the anterior chamber. Vannas scissors were introduced through a 2.2 mm corneal incision. A 4.5 mm straight slit was cut at each optic-haptic junction on opposite sides, perpendicular to each haptic shaft. This pair of parallel cuts generated 3 IOL segments in an S configuration that remained connected. The IOL was grasped by one haptic and removed as a single piece.

Unstructured Abstract Online search data was used to explore a connection between COVID-19 and ocular symptoms. Compared to prior years, searches for sore and burning eyes increased and conjunctivitis search increases were variable based on language.

OBJECTIVE: Delaying cataract surgery is associated with an increased risk of falls, but it is unknown whether routine preoperative testing delays cataract surgery long enough to cause clinical harm. We sought to determine whether the use of routine preoperative testing leads to harm in the form of delayed surgery and falls in Medicare beneficiaries awaiting cataract surgery. DESIGN: Retrospective observational cohort study using 2006-2014 Medicare claims PARTICIPANTS: Medicare beneficiaries age 66+ with a CPT claim for ocular biometry METHODS: We measured the mean and median number of days between ocular biometry and cataract surgery, calculated the proportion of patients waiting >30 days or >90 days for surgery, and determined the odds of having a fall within 90 days of biometry among patients of high-testing physicians (testing performed in ≥75% of their patients) compared to patients of low-testing physicians. We estimated the number of days of delay attributable to high-testing physicians relative to other factors that may determine surgical scheduling. MAIN OUTCOME MEASURES: Incidence of falls occurring between biometry and surgery, odds of falling within 90 days of biometry, and estimated delay in days associated with physician testing behavior . RESULTS: Of 248,345 beneficiaries, 16.4% were patients of high-testing physicians. More patients of high-testing physicians waited >30 days and >90 days to have cataract surgery (31.4% and 8.2% versus 25.0% and 5.5%, respectively, p

Importance Corneal opacity is a leading cause of visual impairment worldwide; however, the specific features of corneal scars, which decrease visual acuity, have not been well characterized. Objective To investigate which features of a postfungal keratitis corneal scar contribute to decreased visual acuity after an episode of infectious keratitis and evaluate whether any corneal features may be used as outcomes for clinical trials. Design, Setting, and Participants In this ancillary, prospective cross-sectional study, a subset of study participants treated for fungal keratitis (n = 71) as part of the Mycotic Ulcer Treatment Trial I (MUTT I) underwent best spectacle-corrected visual acuity (BSCVA) and best contact lens–corrected visual acuity examination, Scheimpflug imaging, and anterior segment optical coherence tomography at a referral hospital in India approximately 2 years after enrollment. Data were collected from December 3, 2012, to December 19, 2012, and analyses were performed from December 2, 2013, to October 2, 2019. Main Outcomes and Measures Linear regression models were used to evaluate the importance of various corneal features for BSCVA and to assess whether these features could be used to differentiate the 2 treatment arms of the MUTT I trial. Results Seventy-one patients (42 men [59.1%]; median age, 48 [range, 39-60] years) were examined at a median (IQR) time of 1.8 (1.4-2.2) years after enrollment. The mean (SD) logMAR BSCVA was 0.17 (0.19) (Snellen equivalent, 20/32). In multivariable linear regression models, BSCVA was most associated with irregular astigmatism (1.0 line of worse BSCVA per 1-line difference between BSCVA and contact lens visual acuity; 95% CI, 0.6-1.4) and corneal scar density (1.5 lines of worse vision per 10-unit increase in the mean central corneal density; 95% CI, 0.8-2.3). The thinnest point of the cornea was the metric that best discriminated between the natamycin- and voriconazole-treated ulcers in MUTT I, with 29.3 μm (95% CI, 7.1-51.6 μm) less thinning in natamycin-treated eyes. Conclusions and Relevance Both irregular astigmatism and corneal scar density may be important risk factors for BSCVA in a population with relatively mild, healed fungal corneal ulcers. The thinnest point of the corneal scar may be a cornea-specific outcome that could be used to evaluate treatments for corneal ulcers.

Objective To compare oral voriconazole vs placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. Design Non-prespecified, secondary case-control analysis from a multicenter, double-masked, randomized placebo-controlled clinical trial. Methods Study Participants : Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 or worse who eventuated to therapeutic penetrating keratoplasty (TPK). Intervention : Study participants were randomized to oral voriconazole vs oral placebo; all received topical antifungal drops. Main Outcome Measures : TPK button culture positivity. Results A total of 95 of 194 (49.5%) study participants enrolled at Madurai, Coimbatore, or Pondicherry, India eventuated to TPK in an average of 20.9 days (standard deviation 15.2 days, range 2-71 days). TPK button cultures were available for 67 of 95 (71%) of the TPKs performed and were positive for filamentous fungus in 45 of 67 (67%) cases. For each 1-day increase in the time to TPK there was 0.94-fold decreased odds of fungal culture positivity (95% confidence interval [CI] 0.90–0.98, P = .005). Those randomized to oral voriconazole had 1.26-fold increased odds of TPK button culture positivity after controlling for time to TPK and baseline organism, but this was not statistically significant (95% CI 0.32–4.87; P = .74). Those who underwent TPK for lack of response to medical therapy were 10.64-fold more likely to be culture positive than if the indication for surgery was perforation and this was statistically significant (95% CI 2.16–51.70; P = .003). Conclusions There appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. Infection rather than inflammation appears to be the reason for the worsening clinical picture in many of these patients.

The steroid disulfates (akabis-sulfates) are a significant but minor fraction of the urinary steroid metabolome that have not been widely studied because major components are not hydrolyzed by the commercial sulfatases commonly used in steroid metabolomics. In early studies, conjugate fractionation followed by hydrolysis using acidified solvent (solvolysis) was used for the indirect detection of this fraction by GC–MS. This paper describes the application of a specific LC–MS/MS method for the direct identification of disulfates in urine, and their use as markers for the prenatal diagnosis of disorders causing reduced estriol production: STSD (steroid sulfatase deficiency), SLOS (Smith-Lemli-Opitz syndrome) and PORD (P450 oxidoreductase deficiency). Disulfates were detected by monitoring a constant ion loss (CIL) from the molecular di-anion. While focused on disulfates, our methodology included an analysis of intact steroid glucuronides and monosulfates because steroidogenic disorder diagnosis usually requires an examination of the complete steroid profile. In the disorders studied, a few individual steroids (as disulfates) were found particularly informative: pregn-5-ene-3β,20S-diol, pregn-5-ene-3β,21-diol (STSD, neonatal PORD) and 5α-pregnane-3β,20S-diol (pregnancy PORD). Authentic steroid disulfates were synthesized for use in this study as aid to characterization. Tentative identification of 5ξ-pregn-7-ene-3ξ,20S-diol and 5ξ-pregn-7-ene-3ξ,17,20S-triol disulfates was also obtained in samples from SLOS affected pregnancies. Seven ratios between the detected metabolites were applied to distinguish the three selected disorders from control samples. Our results show the potential of the direct detection of steroid conjugates in the diagnosis of pathologies related with steroid biosynthesis.

Observational measurement of treatment adherence has long been considered the gold standard. However, little is known about either the generalizability of the scores from extant observational instruments or the sampling needed. We conducted generalizability (G) and decision (D) studies on two samples of recordings from two randomized controlled trials testing cognitive–behavioral therapy for youth anxiety in two different contexts: research versus community. Two doctoral students independently coded 543 session recordings from 52 patients treated by 13 therapists. The initial G-study demonstrated that context accounted for a disproportionately large share of variance, so we conducted G- and D-studies for the two contexts separately. Results suggested that reliable cognitive–behavioral therapy adherence studies require at least 10 sessions per patient, assuming 12 patients per therapists and two coders—a challenging threshold even in well-funded research. Implications, including the importance of evaluating alternatives to observational measurement, are discussed.

Purpose To identify fungal keratitis patients who are at risk of a poor outcome and may benefit from closer follow-up or more aggressive treatment. Design Secondary analysis of randomized clinical trial data. Methods We compared the clinical outcomes of patients who had positive 6-day fungal cultures with those who did not, using backward stepwise regression with covariates for all baseline clinical characteristics. Subjects : Patients presenting with a smear-positive filamentous fungal ulcer and visual acuity of 20/400 or worse, and who subsequently had a 6-day fungal culture performed at the Aravind Eye Care system (India), Lumbini Eye Hospital (Nepal), or Bharatpur Eye Hospital (Nepal). Main Outcome Measures : The primary outcome is rate of corneal perforation and/or the need for therapeutic penetrating keratoplasty. Secondary outcomes include 3-month best spectacle-corrected visual acuity (BSCVA), 3-month infiltrate and/or scar size, and rate of re-epithelialization. Results Patients who tested positive at their 6-day culture had twice the hazard of experiencing a corneal perforation or the need for therapeutic penetrating keratoplasty (P = .002) than those who tested negative, even after controlling for baseline ulcer characteristics. These patients also had on average 0.26 logMAR lines worse BSCVA at 3 months (P = .001). Culture positivity at day 6 was not a statistically significant predictor of 3-month infiltrate/scar-size (−0.24 mm1; P = .45) or time to re-epithelialization (hazard ratio = .81; P = .31). Conclusions Here we identify a uniquely valuable clinical tool, day 6 culture results, for the treatment of severe fungal keratitis. Risk stratification based on repeat culture positivity is an objective way to assess response to medical therapy and identify patients who are at high risk of a poor clinical outcome. This establishes a new standard of care for severe fungal keratitis management.

Objective To evaluate the importance of therapeutic processes in two brief school-based psychosocial treatments targeting homework problems in adolescents with attention-deficit/hyperactivity disorder (ADHD) as delivered by school mental health professionals. Method A sample of 222 middle school students (72% male; Mage = 12.00 years, SD = 1.02) diagnosed with ADHD was randomized to receive either a contingency-management or a skills-based treatment for homework problems. Both treatments included 16 individual sessions (20-min each) and 2 parent/family meetings. Adolescents and school mental health professionals reported on the working alliance in the middle of the treatment; professionals rated adolescent involvement at each of the 16 sessions, parent involvement during both parent meetings, and parent commitment to carry out the established homework plan. Attendance at parent meetings was also recorded. Results Therapeutic processes predicted objective, parent-reported, and teacher-reported academic outcomes. Parent engagement was particularly important for the contingency-based treatment, whereas working alliance and adolescent involvement were most important for the skills-based treatment. Conclusions Therapeutic processes such as developing a strong working alliance and engaging parents and students are key elements of treatment delivery and receipt in school-based mental health programming and should be explicitly trained and monitored. (PsycINFO Database Record

Author(s): Ung, Lawson; Acharya, Nisha R; Agarwal, Tushar; Alfonso, Eduardo C; Bagga, Bhupesh; Bispo, Paulo Jm; Burton, Matthew J; Dart, John Kg; Doan, Thuy; Fleiszig, Suzanne Mj; Garg, Prashant; Gilmore, Michael S; Gritz, David C; Hazlett, Linda D; Iovieno, Alfonso; Jhanji, Vishal; Kempen, John H; Lee, Cecilia S; Lietman, Thomas M; Margolis, Todd P; McLeod, Stephen D; Mehta, Jod S; Miller, Darlene; Pearlman, Eric; Prajna, Lalitha; Prajna, N Venkatesh; Seitzman, Gerami D; Shanbhag, Swapna S; Sharma, Namrata; Sharma, Savitri; Srinivasan, Muthiah; Stapleton, Fiona; Tan, Donald Th; Tandon, Radhika; Taylor, Hugh R; Tu, Elmer Y; Tuli, Sonal S; Vajpayee, Rasik B; Van Gelder, Russell N; Watson, Stephanie L; Zegans, Michael E; Chodosh, James

Objective We examined whether motivation and treatment credibility predicted alliance in a 10-session cognitive behavioral treatment delivered in community clinics for youth anxiety disorders. Method Ninety-one clinic-referred youths (meanage = 11.4 years, standard deviation = 2.1, range 8–15 years, 49.5% boys) with anxiety disorders-rated treatment motivation at pretreatment and perceived treatment credibility after session 1. Youths and therapists (YT) rated alliance after session 3 (early) and session 7 (late). Hierarchical linear models were applied to examine whether motivation and treatment credibility predicted YT early alliance, YT alliance change, and YT alliance agreement. Results Motivation predicted high early YT alliance, but not YT alliance change or alliance agreement. Youth-rated treatment credibility predicted high early youth alliance and high YT positive alliance change, but not early therapist alliance or alliance agreement. Conclusion Conclusion Efforts to enhance youth motivation and treatment credibility early in treatment could facilitate the formation of a strong YT alliance.

OBJECTIVE: Evidence-based treatments (EBTs) for youthare typically developed and established through studies in research settingsdesigned to ensure treatment integrity—i.e., protocol adherence and competence by therapists. An important question for implementation science is how well integrity is maintained when these EBTs are delivered in community settings.The present study investigated whetherthe integrity achieved by therapists in community settings achieved a benchmark set by therapists in a research setting when they delivered the same EBT—an individual cognitive-behavioral treatment (ICBT)for youth anxiety. METHOD: Therapists (N = 29; 68.97% White; 13.79% male) provided ICBT to 68 youths (M age = 10.60 years, SD = 2.03; 82.35% White; 52.94% male) diagnosed with a principal anxiety disorder in research or community settings. Training and supervision protocols were the same across settings. Two independent teams of trained coders rated 744 sessionsusing observational instruments designed to assess ICBT adherence and competence. RESULTS: Both adherence and competence were higher in the research setting. Group differences in competence were consistent across treatment, but differences in adherence were most pronounced when treatment shifted to exposure, widely-viewed as the most critical component of ICBT. CONCLUSIONS: When using the benchmarks from the research setting, therapists from the community settings fell short for indices of adherence and competence. However, given differences between therapists and clients as well as the fact that treatment outcomes were similar across settings, our findings raise questions about whether it is appropriate to use treatment integrity benchmarks from research settings for community.

Teachers sometimes struggle to deliver evidence-based programs designed to prevent and ameliorate chronic problem behaviors of young children with integrity. Identifying factors associated with variations in the quantity and quality of delivery is thus an important goal for the field. This study investigated factors associated with teacher treatment integrity of BEST in CLASS, a tier-2 prevention program designed for young children at risk for developing emotional/behavioral disorders. Ninety-two early childhood teachers and 231 young children at-risk for emotional/behavioral disorders participated in the study. Latent growth curve analyses indicated that both adherence and competence of delivery increased across six observed time points. Results suggest that teacher education and initial levels of classroom quality may be important factors to consider when teachers deliver tier-2 (i.e., targeted to children who are not responsive to universal or tier-1 programming) prevention programs in early childhood settings. Teachers with higher levels of education delivered the program with more adherence and competence initially. Teachers with higher initial scores on the Emotional Support subscale of the Classroom Assessment Scoring System (CLASS) delivered the program with more competence initially and exhibited higher growth in both adherence and competence of delivery across time. Teachers with higher initial scores on the Classroom Organization subscale of the CLASS exhibited lower growth in adherence across time. Contrary to hypotheses, teacher self-efficacy did not predict adherence, and teachers who reported higher initial levels of student engagement self-efficacy exhibited lower growth in competence of delivery. Results are discussed in relation to teacher delivery of evidence-based programs in early childhood classrooms.

Does delivery of the same manual-based individual cognitive-behavioral treatment (ICBT) program for youth anxiety differ across research and practice settings? We examined this question in a sample of eighty-nine youths (M age = 10.56, SD = 1.99; 63.70% Caucasian; 52.80% male) diagnosed with a primary anxiety disorder. The youths received (a) ICBT in a research setting, (b) ICBT in practice settings, or (c) non-manual-based usual care (UC) in practice settings. Treatment delivery was assessed using four theory-based subscales (Cognitive-behavioral, Psychodynamic, Client-Centered, Family) from the Therapy Process Observational Coding System for Child Psychotherapy–Revised Strategies scale (TPOCS-RS). Reliable independent coders, using the TPOCS-RS, rated 954 treatment sessions from two randomized controlled trials (1 efficacy and 1 effectiveness trial). In both settings, therapists trained and supervised in ICBT delivered comparable levels of cognitive-behavioral interventions at the beginning of treatment. However, therapists trained in ICBT in the research setting increased their use of cognitive-behavioral interventions as treatment progressed whereas their practice setting counterparts waned over time. Relative to the two ICBT groups, the UC therapists delivered a significantly higher dose of psychodynamic and family interventions and a significantly lower dose of cognitive-behavioral interventions. Overall, results indicate that there were more similarities than differences in manual-based ICBT delivery across research and practice settings. Future research should explore why the delivery of cognitive-behavioral interventions in the ICBT program changed over time and across settings, and whether the answers to these questions could inform implementation of ICBT programs.

To determine whether patients who had a positive repeated culture was predictive of worse clinical outcome than those who achieved microbiological cure at 6 days in the Mycotic Ulcer Treatment Trial I (MUTT-I).Secondary analysis from a multicenter, double-masked, randomized clinical trial.setting: Multiple hospital sites of the Aravind Eye Care System, India.Patients with culture-positive filamentous fungal ulcers and visual acuity of 20/40 to 20/400 reexamined 6 days after initiation of treatment.Corneal scraping and cultures were obtained from study participants at day 6 after enrollment.We assessed 3-month best spectacle-corrected visual acuity (BSCVA), 3-month infiltrate/scar size, corneal perforation, and re-epithelialization rates stratified by culture positivity at day 6.Of the 323 patients with smear-positive ulcers enrolled in MUTT-I, 299 (92.6%) were scraped and cultured 6 days after enrollment. Repeat culture positivity was 31% (92/299). Among patients who tested positive at enrollment, those with positive 6-day cultures had significantly worse 3-month BSCVA (0.39 logMAR; 95% confidence interval [CI]: 0.24-0.44; P.001), had larger 3-month scar size (0.39 mm; 95% CI: 0.06-0.73; P = .02), were more likely to perforate or require therapeutic penetrating keratoplasty (odds ratio: 6.27; 95% CI: 2.73-14.40; P.001), and were slower to re-epithelialize (hazard ratio: 0.33; 95% CI: 0.21-0.50; P.001) than those with a negative 6-day culture result.Early microbiological cure on culture is a predictor of clinical response to treatment.

Therapist competence is an important component of treatment integrity. This article reports on the development and initial psychometric assessment of the Cognitive-Behavioral Treatment for Anxiety in Youth Competence Scale (CBAY-C), an observational instrument designed to capture therapist limited-domain competence (i.e., competence in the delivery of core interventions and delivery methods found in a specific psychosocial treatment program) in the delivery of the core practice elements in individual cognitive-behavioral treatment (ICBT) for youth anxiety. Treatment sessions (N = 744) from 68 youth participants (M age = 10.60 years, SD = 2.03; 82.3% Caucasian; 52.9% male) of the same ICBT program for youth anxiety from (a) an efficacy study and (b) an effectiveness study were independently scored by 4 coders using observational instruments designed to assess therapist competence, treatment adherence, treatment differentiation, alliance, and client involvement. Interrater reliability-intraclass correlation coefficients (2,2)-for the item scores averaged 0.69 (SD = 0.11). The CBAY-C item, scale, and subscale (Skills, Exposure) scores showed evidence of validity via associations with observational instruments of treatment adherence to ICBT for youth anxiety, theory-based domains (cognitive-behavioral treatment, psychodynamic, family, client centered), alliance, and client involvement. Important to note, although the CBAY-C scale, subscale, and item scores did overlap with a corresponding observational treatment adherence instrument independently rated by coders, the degree of overlap was moderate, indicating that the CBAY-C assesses a distinct component of treatment integrity. Applications of the instrument and future research directions discussed include the measurement of treatment integrity and testing integrity-outcome relations.

Most efforts to assess treatment integrity-the degree to which a treatment is delivered as intended-have conflated content (i.e., therapeutic interventions) and delivery (i.e., strategies for conveying the content, such as modeling). However, there may be value in measuring content and delivery separately. This study examined whether the quantity (how much) and quality (how well) of delivery strategies for individual cognitive behavioral therapy (ICBT) for youth anxiety varied when the same evidence-based treatment was implemented in research and community settings. Therapists (N = 29; 69.0% White; 13.8% male) provided ICBT to 68 youths (M age = 10.60 years, SD = 2.03; 82.4% white; 52.9% male) diagnosed with a principal anxiety disorder in research or community settings. Training and supervision protocols for therapists were comparable across settings. Two independent teams of trained coders rated 744 sessions using observational instruments designed to assess the quantity and quality of delivery of interventions found in ICBT approaches. Overall, both the quantity and quality of delivery of interventions found in ICBT approaches were significantly lower in the community settings. The extent to which didactic teaching, collaborative teaching, and rehearsal were used systematically varied over the course of treatment. In general, differences in the quantity and quality of delivery observed between settings held when differences in youth characteristics between settings were included in the model. Our findings suggest the potential relevance of measuring how therapists deliver treatment separate from the content.

Purpose: To determine the repeatability and reproducibility of anterior segment optical coherence tomography (AS-OCT) and Scheimpflug photography for several measurements of corneal scars, including scar size, scar depth, and corneal thickness. Methods: A series of patients treated for fungal keratitis at a tertiary eye care center in South India were recalled two years after successful treatment. Eyes with corneal scars had a slit lamp examination performed by two ophthalmologists masked to the other's examination. For AS-OCT and Scheimpflug photography, each eye had two scans taken by one technician and a third scan taken by a separate technician. Scar measurements were subsequently assessed from AS-OCT images by three graders masked to each other's results. Repeatability and reproducibility were assessed by calculating the intra-class correlation coefficient (ICC) from mixed effects linear regression models. Results: Fifty eyes had all measurements taken. The corneal scar size, measured as the geometric mean of the two longest perpendicular meridians, ranged from 0.8 to 5.4 (mean 2.8 mm, 95%CI 2.6 to 3.1). Scar size measurements taken by two separate individuals were most reproducible when the border of the scar was traced from the OCT (ICC 0.90, 95%CI 0.86 to 0.94), and least repeatable when assessed from slit lamp examination (ICC 0.80, 95%CI 0.70 to 0.90). Conclusions: AS-OCT and Scheimpflug imaging of corneal scars produced measurements with acceptable reproducibility that could be useful as cornea-specific outcomes for clinical trials.

Family therapy has the strongest evidence base for treating adolescent conduct and substance use problems, yet there remain substantial barriers to widespread delivery of this approach in community settings. This study aimed to promote the feasibility of implementing family-based interventions in usual care by empirically distilling the core practice elements of three manualized treatments. The study sampled 302 high-fidelity treatment sessions from 196 cases enrolled in 1 of 3 manualized family therapy models: multidimensional family therapy (102 sessions/56 cases), brief strategic family therapy (100 sessions/94 cases), or functional family therapy (100 sessions/46 cases). Adolescents were 57% male; 41% were African American, 31% White non-Hispanic, 9% Hispanic American, 6% another race/ethnicity, and 13% unknown. The observational fidelity measures of all three models were used to code all 302 sessions. Fidelity ratings were analyzed to derive model-shared treatment techniques via exploratory factor analyses on half the sample; the derived factors were then validated via confirmatory factor analyses supplemented by Bayesian structural equation modeling on the remaining half. Factor analyses distilled 4 clinically coherent practice elements with strong internal consistency: Interactional Change (6 treatment techniques; Cronbach's α = .93), Relational Reframe (7 techniques; α = .79), Adolescent Engagement (4 techniques; α = .68), and Relational Emphasis (4 techniques; α = .67). The 4 empirically derived factors represent the core elements of 3 manualized family therapy models for adolescent behavior problems, setting the foundation of a more sustainable option for delivering evidence-based family interventions in routine practice settings. Public Health Significance: Increasing implementation of high-fidelity family-based interventions would improve the quality of treatment services for adolescent conduct and substance use problems.

Intracerebral hemorrhage (ICH) is an important stroke subtype, but preclinical research is limited by a lack of translational animal models. Large animal models are useful to comparatively investigate key pathophysiological parameters in human ICH. To (i) establish an acute model of moderate ICH in adult sheep and (ii) an advanced neuroimage processing pipeline for automatic brain tissue and hemorrhagic lesion determination; 14 adult sheep were assigned for stereotactically induced ICH into cerebral white matter under physiological monitoring. Six hours after ICH neuroimaging using 1.5T MRI including structural as well as perfusion and diffusion, weighted imaging was performed before scarification and subsequent neuropathological investigation including immunohistological staining. Controlled, stereotactic application of autologous blood caused a space-occupying intracerebral hematoma of moderate severity, predominantly affecting white matter at 5 h post-injection. Neuroimage post-processing including lesion probability maps enabled automatic quantification of structural alterations including perilesional diffusion and perfusion restrictions. Neuropathological and immunohistological investigation confirmed perilesional vacuolation, axonal damage, and perivascular blood as seen after human ICH. The model and imaging platform reflects key aspects of human ICH and enables future translational research on hematoma expansion/evacuation, white matter changes, hematoma evacuation, and other aspects.

Almost every experimental treatment strategy using non-autologous cell, tissue or organ transplantation is tested in small and large animal models before clinical translation. Because these strategies require immunosuppression in most cases, immunosuppressive protocols are a key element in transplantation experiments. However, standard immunosuppressive protocols are often applied without detailed knowledge regarding their efficacy within the particular experimental setting and in the chosen model species. Optimization of such protocols is pertinent to the translation of experimental results to human patients and thus warrants further investigation. This review summarizes current knowledge regarding immunosuppressive drug classes as well as their dosages and application regimens with consideration of species-specific drug metabolization and side effects. It also summarizes contemporary knowledge of novel immunomodulatory strategies, such as the use of mesenchymal stem cells or antibodies. Thus, this review is intended to serve as a state-of-the-art compendium for researchers to refine applied experimental immunosuppression and immunomodulation strategies to enhance the predictive value of preclinical transplantation studies.

Educators are increasingly being encouraged to implement evidence-based interventions and practices to address the social, emotional, and behavioral needs of young children who exhibit problem behavior in early childhood settings. Given the nature of social-emotional learning during the early childhood years and the lack of a common set of core evidence-based practices within the early childhood literature, selection of instructional practices that foster positive social, emotional, and behavioral outcomes for children in early childhood settings can be difficult. The purpose of this paper is to report findings from a study designed to identify common practice elements found in comprehensive intervention models (i.e., manualized interventions that include a number of components) or discrete practices (i.e., a specific behavior or action) designed to target social, emotional, and behavioral learning of young children who exhibit problem behavior. We conducted a systematic review of early childhood classroom interventions that had been evaluated in randomized group designs, quasi-experimental designs, and single-case experimental designs. A total of 49 published articles were identified, and an iterative process was used to identify common practice elements. The practice elements were subsequently reviewed by experts in social-emotional and behavioral interventions for young children. Twenty-four practice elements were identified and classified into content (the goal or general principle that guides a practice element) and delivery (the way in which a teacher provides instruction to the child) categories. We discuss implications that the identification of these practice elements found in the early childhood literature has for efforts to implement models and practices.

Leptomeningeal collateral vessels, linking the 3 major arterial territories over the surface of the brain, have been recognized for >140 years.1 More widespread use of advanced clinical imaging in the past decade has led to increasing recognition of the key importance of collaterals in ischemic stroke outcome.2 However, recent studies from several groups indicate that failure of initially good collateral supply is a key feature of patients with delayed infarct expansion.3,4 This clinically challenging problem typically occurs in the first 1 to 2 days after hospital admission in patients with initially mild stroke symptoms. Rethrombosis of reperfused vessels was previously thought to be the likely cause of delayed infarct expansion in most patients. However, this theory is not supported by more recent evidence from imaging studies. Despite the important recent observations, there is limited understanding of the dynamic control of the collateral circulation, in particular, the cause of collateral blood flow failure. In this article, we will discuss recent observations from our experimental stroke model, indicating a dramatic increase in intracranial pressure (ICP) occurring around 24 hours after onset of even small stroke.5,6 We have also shown a significant linear reduction of collateral blood flow in response to progressive ICP elevation.7 We believe that a similar transient ICP elevation occurring during the first 1 to 2 days post stroke is a likely mechanism to explain delayed infarct expansion in patients with minor stroke. Perhaps surprisingly, we can find no published data on ICP at 24 hours in patients with minor stroke. The preclinical findings suggest that gathering such data should be a priority. ### Human Stroke There is a strong association between the extent of leptomeningeal collaterals and clinical stroke outcome. Initial studies using digital subtraction angiography permitted direct visualization of collateral vessels and …