Unmet Needs Among Out of Care and Recently Diagnosed Women of Color With HIV: Opportunities for Focused Interventions.

OBJECTIVE: Women of color (WoC) have lower retention in care and higher HIV/AIDS-related morbidity, compared with other populations. Barriers to care include lack of family support, inadequate HIV/AIDS services, and stigma, and women may face greater unmet needs for services including housing and employment. This descriptive study explores the unmet needs of WoC participating in the Health Resources and Services Administration's Special Projects of National Significance (SPNS) Program, Dissemination of Evidence Informed Interventions (HRSA/SPNS DEII) Initiative. SETTING: Six urban health clinics across the United States. PARTICIPANTS: Eligible participants were cis- or transgender women who were newly diagnosed with HIV/AIDS in the past 12 months, out of care for at least 6 months, or not virally suppressed. Participants enrolled from November 2016 to November 2018. MAIN OUTCOMES: Our primary outcome of interest was unmet needs at enrollment for 6 core services: housing, transportation, benefits, mental health or substance use treatment, medication assistance, and medical care. We examined differences in unmet needs stratified by participant characteristics and used multivariate regression to identify the social and health risk factors associated with higher unmet needs. RESULTS: Among the 529 WoC, the most frequently reported expressed needs were transportation (50.1%), housing (41.2%), benefits (28.2%), medication assistance (24.5%), and substance use or mental health treatment (24.3%). Participants with a significantly higher number of overall unmet needs included those who were older (40 years or older), were unstably housed, had a history of incarceration, identified as a transgender woman, were US born, had no caregiver responsibilities, and did not have a case manager at enrollment. CONCLUSIONS: Our findings indicate the importance of screening for and developing focused strategies to address the unmet needs for WoC if viral suppression is to be achieved.

Practice transformations to optimize the delivery of HIV primary care in community healthcare settings in the United States: A program implementation study.

BACKGROUND: The United States HIV care workforce is shrinking, which could complicate service delivery to people living with HIV (PLWH). In this study, we examined the impact of practice transformations, defined as efficiencies in structures and delivery of care, on demonstration project sites within the Workforce Capacity Building Initiative, a Health Resources and Services Administration (HRSA) Ryan White HIV/AIDS Program Special Projects of National Significance (SPNS). METHODS AND FINDINGS: Data were collected at 14 demonstration project sites in 7 states and the District of Columbia. Organizational assessments were completed at sites once before and 4 times after implementation. They captured 3 transformation approaches: maximizing the HIV care workforce (efforts to increase the number of existing healthcare workforce members involved in the care of PLWH), share-the-care (team-based care giving more responsibility to midlevel providers and staff), and enhancing client engagement in primary HIV care to reduce emergency and inpatient care (e.g., care coordination). We also obtained Ryan White HIV/AIDS Program Services Reports (RSRs) from sites for calendar years (CYs) 2014-2016, corresponding to before, during, and after transformation. The RSR include data on client retention in HIV care, prescription of antiretroviral therapy (ART), and viral suppression. We used generalized estimating equation (GEE) models to analyze changes among sites implementing each practice transformation approach. The demonstration projects had a mean of 18.5 prescribing providers (SD = 23.5). They reported data on more than 13,500 clients per year (mean = 969/site, SD = 1,351). Demographic characteristics remained similar over time. In 2014, a majority of clients were male (71% versus 28% female and 0.2% transgender), with a mean age of 47 (interquartile range [IQR] 37-54). Racial/ethnic characteristics (48% African American, 31% Hispanic/Latino, 14% white) and HIV risk varied (31% men who have sex with men; 31% heterosexual men and women; 7% injection drug use). A substantial minority was on Medicaid (41%). Across sites, there was significant uptake in practices consistent with maximizing the HIV care workforce (18% increase, p < 0.001), share-the-care (25% increase, p < 0.001), and facilitating patient engagement in HIV primary care (13% increase, p < 0.001). There were also significant improvements over time in retention in HIV care (adjusted odds ratio [aOR] = 1.03; 95% confidence interval [CI] 1.02-1.04; p < 0.001), ART prescription levels (aOR = 1.01; 95% CI 1.00-1.01; p < 0.001), and viral suppression (aOR = 1.03; 95% CI 1.02-1.04; p < 0.001). All outcomes improved at sites that implemented transformations to maximize the HIV care workforce or improve client engagement. At sites that implemented share-the-care practices, only retention in care and viral suppression outcomes improved. Study limitations included use of demonstration project sites funded by the Ryan White HIV/AIDS Program (RWHAP), which tend to have better HIV outcomes than other US clinics; varying practice transformation designs; lack of a true control condition; and a potential Hawthorne effect because site teams were aware of the evaluation. CONCLUSIONS: In this study, we found that practice transformations are a potential strategy for addressing anticipated workforce challenges among those providing care to PLWH. They hold the promise of optimizing the use of personnel and ensuring the delivery of care to all in need while potentially enhancing HIV care continuum outcomes.

Three modules of zebrafish Mind bomb work cooperatively to promote Delta ubiquitination and endocytosis.

Precise regulation of Notch signaling activity is critical for development of many different tissues. Here, we show that the zebrafish insertional mutation Hi904 attenuates Notch signaling, and is allelic to mind bomb. We show that Mind bomb protein displays E3 ubiquitin ligase activity in vitro and that it is associated with Delta and enhances its ubiquitination and internalization in transfected cells. Furthermore, by functional analysis of three conserved regions of Mind bomb, we show that the N-terminal half is required for Delta association, the ankyrin repeats are important for Delta internalization, and the ring fingers are required for Delta ubiquitination. Thus, the three functionally distinct modules of Mind bomb work cooperatively to regulate Notch signaling by associating with, ubiquitinating, and internalizing Delta.

BVAT distance vs. near stereopsis screening of strabismus, strabismic amblyopia and refractive amblyopia; a prospective study of 68 patients.

PURPOSE: Although there have been studies in the past of the difference between distance and near stereopsis in intermittent exotropia, no such comparisons have been studied and/or reported for other forms of strabismus, nor for strabismic functional amblyopia, or for refractive functional amblyopia. METHODS: The study was prospective: Sixty-eight consecutive patients, ages 6-76 years, with either childhood onset strabismus and no amblyopia, childhood onset strabismus and amblyopia, or refractive amblyopia and no strabismus, had their stereopsis measured. Distance stereopsis was determined on the Mentor BVAT with Random Dot E Test (global stereopsis) and the Circle Test (contour stereopsis). Near stereopsis was determined with the Circle Test of the Randot Stereotest. The data were tabulated and analyzed statistically. RESULTS: Of the 26 strabismus/no amblyopia cases, 14 (54%) appreciated distance stereopsis. Of these, 12/14 were intermittent, and other 2 who were constant had deviations of 8 PD or less. Only 4 of the 14 appreciated global stereopsis at distance (mean = 90 sec. of arc), but all 14 appreciated contour stereopsis at distance (mean = 125 sec. of arc). Of all 26, 21 (81%) had near stereopsis (mean = 137 sec. of arc). For the 21 strabismic amblyopes, only one appreciated global stereopsis at distance (120 sec of arc), and 2 (10%) contour stereopsis at distance (mean = 210 sec. of arc). These two and 4 others (total 29%) had near stereopsis (mean = 162 sec. of arc). For the 21 refractive amblyopes, 3 appreciated global stereopsis at distance (mean = 220 sec. of arc), 11 in all, (52%) contour stereopsis at distance (mean = 121 sec. of arc) and 20 (95%) had near stereopsis (mean = 78 sec. of arc). The percentages of patients in all categories capable of appreciating distance stereopsis were "statistically significantly" (P<.05) or clinically/medically significantly different from (less than) the percentages having near stereopsis. CONCLUSIONS: distance stereopsis is more likely to be reduced or absent than near stereopsis in strabismus, strabismic amblyopia and refractive amblyopia and thus appears to be more sensitive to, and better screening for, binocular vision disorders and a stronger and better outcome standard for treatment of binocular vision disorders than near stereopsis.

Spatiotemporal expression, distribution, and processing of POMC and POMC-derived peptides in murine skin.

In murine skin, after depilation-induced anagen, there was a differential spatial and temporal expression of pro-opiomelanocortin (POMC) mRNA, of the POMC-derived peptides beta-endorphin, ACTH, beta-MSH, and alpha-MSH, and of the prohormone convertases PC1 and PC2 in epidermal and hair follicle keratinocytes and in the cells of sebaceous units. Using a combination of in situ hybridization histochemistry and immunohistochemistry, we found cell-specific variations in the expression of POMC mRNA that were consistent with immunoreactivities for POMC-derived peptides. Cells that contained POMC peptide immunoreactivity (IR) also expressed POMC mRNA, and where the IR increased there was a parallel increase in mRNA. The levels of PC1-IR and PC2-IR also showed cell-specific variations and were present in the same cells that contained the POMC peptides. Based on the cleavage specificities of these convertases and on the spatial and temporal expression of the convertases and of ACTH, beta-endorphin, beta-MSH, and alpha-MSH, we can infer that the activities of PC1 and PC2 are responsible for the cell-specific differential processing of POMC in murine skin.

Distance stereopsis as a screening device.

PURPOSE: To determine the efficacy of distance stereotesting as a screening device. METHODS: Distance stereoacuity using the global Random Dot and contour Circle test of the Mentor BVAT II-SG computerized testing system was measured for 216 patients, ages 6 to 18 years, before the clinical examination. Patients were classified into pass/fail groups in the areas of refractive error change (REC), ocular deviation (DEV), visual acuity (VA), and all three together (EXAM). Legitimate cutoff scores were obtained when patients were classified as 'pass' as follows: REC if the change was 0.50 D or less in sphere or cylinder relative to the habitual correction or to emmetropia if no habitual correction; DEV if there was no heterophoria or strabismus at distance (criteria of heterophoria of < 6 prism diopters and heterophorias of any magnitude were also tested); VA if the acuity at distance was better than or equal to 20/25 in the poorer eye and better than or equal to 20/20 in the better eye; EXAM if they were pass in REC, DEV, and VA. Optimal pass/fail cutoff values for the stereopsis measurements were determined by finding the maximum chi2 value from contingency tables constructed using pass/fail levels for the screening test at each of the observed levels. RESULTS: The pass rates for REC, DEV, VA, and EXAM were 45%, 72%, 42%, and 24%, respectively. Patients passed the BVAT at the analytically determined optimal cutoff values of less than or equal to 120 sec arc for global and less than or equal to 30 sec arc for contour stereopsis. The sensitivity and specificity for global stereopsis were 0.90 and 0.40 for REC, 0.89 and 0.30 for DEV, 0.93 and 0.51 for VA, and 0.87 and 0.63 for EXAM. For contour stereopsis, the corresponding values were 0.85 and 0.42, 0.89 and 0.34, 0.91 and 0.53, and 0.84 and 0.62. CONCLUSION: Distance stereotesting is highly sensitive to small refractive error changes, heterophorias and strabismus, visual acuities < 20/25, or any of the three. Global stereopsis is only slightly better than contour stereopsis at classifying patients. Distance stereotesting has potential as an effective screening test.

Streptococcus gordonii biofilm formation: identification of genes that code for biofilm phenotypes.

Viridans streptococci, which include Streptococcus gordonii, are pioneer oral bacteria that initiate dental plaque formation. Sessile bacteria in a biofilm exhibit a mode of growth that is distinct from that of planktonic bacteria. Biofilm formation of S. gordonii Challis was characterized using an in vitro biofilm formation assay on polystyrene surfaces. The same assay was used as a nonbiased method to screen isogenic mutants generated by Tn916 transposon mutagenesis for defective biofilm formation. Biofilms formed optimally when bacteria were grown in a minimal medium under anaerobic conditions. Biofilm formation was affected by changes in pH, osmolarity, and carbohydrate content of the growth media. Eighteen biofilm-defective mutants of S. gordonii Challis were identified based on Southern hybridization with a Tn916-based probe and DNA sequences of the Tn916-flanking regions. Molecular analyses of these mutants showed that some of the genes required for biofilm formation are involved in signal transduction, peptidoglycan biosynthesis, and adhesion. These characteristics are associated with quorum sensing, osmoadaptation, and adhesion functions in oral streptococci. Only nine of the biofilm-defective mutants had defects in genes of known function, suggesting that novel aspects of bacterial physiology may play a part in biofilm formation. Further identification and characterization of biofilm-associated genes will provide insight into the molecular mechanisms of biofilm formation of oral streptococci.

Relationship between anisometropia, amblyopia, and binocularity.

PURPOSE: To determine if higher degrees of anisometropia cause deeper amblyopia and poorer binocularity than lower degrees of anisometropia in children and adults. METHODS: The clinical records for 60 patients with untreated anisometropic amblyopia without strabismus, ranging in age from 3 to 39 years, were reviewed. The refractive error, the initial best corrected visual acuities in the amblyopic and nonamblyopic eyes, and the level of binocularity were recorded from each chart. The degree of anisometropia was determined by: (1) calculating the difference between spherical equivalents for each eye; (2) calculating the difference in the vertical meridians for each eye; (3) calculating the difference in the horizontal meridians for each eye; and (4) calculating the root mean square difference which also takes into account differences in astigmatic axis. The depth of amblyopia was determined by converting the visual acuity score to its logarithmic value, logarithm of the minimum angle of resolution (logMAR), and calculating the difference between the amblyopic and nonamblyopic eye. The level of binocularity was determined from stereopsis testing. RESULTS: For all patients, there was a significant relationship between the four measures of anisometropia, the depth of amblyopia, and the level of binocularity (median correlations 0.61 and 0.61, respectively). For the myopes (N = 10), there was no significant relationship between the 4 measures of anisometropia, the depth of amblyopia, and the level of binocularity (median correlations 0.34 and 0.61, respectively). For the hyperopes (N = 50), the relationship was significant for all 4 measures of anisometropia (median correlations 0.72 and 0.62, respectively). CONCLUSION: As the degree of anisometropia increases, the depth of amblyopia becomes greater and the level of binocularity becomes poorer, at least for hyperopic patients.

Efficacy of silicone punctal plugs as adjuncts to topical pharmacotherapy of glaucoma--a pilot study. Punctal Plugs in Glaucoma Study Group.

BACKGROUND: The concept of enhancing the ocular hypotensive effects of topical antiglaucoma medications by impeding lacrimal drainage of medication has been insufficiently studied. This investigation sought to evaluate the effect of bilateral inferior punctal occlusion using silicone punctal plugs on the ocular hypotensive effect of topically applied timolol. METHODS: A randomized, double-masked, cross-over clinical trial was conducted, comparing the ocular hypotensive effect of timolol maleate 0.25 percent, both with and without occlusion of the inferior punctum with the Freeman silicone punctal plug. Following a 2-week washout of topical medication, 17 subjects with early primary open-angle glaucoma or ocular hypertension received one drop of timolol 0.25 percent in each eye with or without punctal plugs in place. Blood pressure, resting pulse rate, and intraocular pressure were measured both before timolol instillation and at intervals of 1, 2, 4, 8, and 12 hours following drop instillation. Following a 2-week washout period, the subjects were evaluated with the alternative treatment. RESULTS: There was no statistically significant difference (p = 0.648) in IOP levels between treatment groups. CONCLUSIONS: This pilot suggests that need for a longer-term study with larger numbers of subjects to evaluate the potential role of silicone punctal plugs to enhance the ocular bioavailability of topically applied antiglaucoma medications.

Ocular tolerability of timolol in Gelrite in young glaucoma patients.

BACKGROUND: Although initial patient response to timolol maleate in Gelrite (Timoptic XE) has been generally favorable in clinical settings, anecdotal reports of blurred vision warrant further investigation comparing the tolerability of this new formulation with that of timolol maleate in conventional solution. METHODS: A prospective, double-masked, randomized, cross-over study was performed using 28 normal volunteers who had no evidence of ocular disease, including glaucoma. Mean subject age was 32.5 years. Subjects were randomized to receive one drop in each eye of either timolol maleate in solution (TS) 0.5 percent or timolol maleate in Gelrite (TXE) 0.5 percent. Subjects rated each medication, using a visual analog scale, at the following time intervals: prior to drug instillation, immediately following instillation, 1 min, and at 15 min, 30 min, 1 hour, 2 hours, and 4 hours. RESULTS: Wilcoxon Matched Paris Test showed statistically significant differences at 1 minute for tearing (p = 0.003), blurred vision (p = 0.001) and drug acceptance (p = 0.028) in favor of TS. At 15 minutes and thereafter, however, none of the differences between groups was significant. Visual acuities were unaffected by either TS or TXE. CONCLUSIONS: These data suggest that TXE may impair visual function more than TS, but these effects are briefly and transitory. TXE appears to be a clinically acceptable drug delivery vehicle for use during the young glaucoma patient's waking hours.

Comparison of efficacy and tolerance between 1% hydroxyamphetamine plus 0.25% tropicamide (Paremyd) and 0.5% tropicamide combined with 2.5% phenylephrine.

BACKGROUND: Paremyd, consisting of a combination of 1.0 percent hydroxyamphetamine and 0.25 percent tropicamide, is a commercially available eyedrop used clinically for diagnostic mydriasis. This study sought to determine if one drop of Paremyd is equally effective and tolerable as the traditional combination of one drop each of 2.5 percent phenylephrine and 0.5 percent tropicamide. METHODS: A prospective, double-masked, randomized, cross-over study was conducted in 60 normal volunteers ranging from age 20 to 35 years (mean 24.3 years). Twenty-two subjects (36.7 percent) were male, and 32 subjects (53.3 percent) had brown irides. Pupil diameter, amplitude of accommodation, distance and near visual acuity, and subjective comfort of eyedrop instillation were assessed for 8 hours following drug instillation. RESULTS: Significantly more subjects (p < 0.05) experienced adverse ocular symptoms with the tropicamide plus phenylephrine (TP) combination than with Paremyd (P). There was no statistically significant (p > 0.05) difference in mydriatic response between TP and P. During the first hour, however, TP and P demonstrated significant (p = 0.001) differences in cycloplegic effect. CONCLUSIONS: Paremyd appears to be as effective a mydriatic as TP, but with greater comfort on instillation. Paremyd has less effect on accommodation.

The expression of proopiomelanocortin (POMC) and of corticotropin releasing hormone receptor (CRH-R) genes in mouse skin.

The proopiomelanocortin (POMC) and the corticotropin releasing hormone receptor (CRH-R) genes are expressed in the skin of the C57BL/6 mouse throughout the entire hair cycle, and CRH immunoreactivity is present in the pilosebaceous unit of the hair follicle and the epidermis. These findings suggest that some components of hypothalamo-pituitary axis are operating in mouse skin.

Clinical implications of intra- and inter-reader agreement in four different automated visual fields.

BACKGROUND: This study was designed and conducted to examine the degree of inter- and intra-reader agreement when four readers evaluate visual fields in patients known to have glaucoma and patients known to not have glaucoma. METHODS: Fifty-three patients known to have glaucoma and 60 patients known not to have glaucoma were selected randomly from a population at the University of Alabama at Birmingham School of Optometry. Four visual fields were performed on each patient, non-dilated, with the proper correction in place. The fields were performed on three different instruments by technicians who were unaware of the diagnostic status of the patient. Four independent (blinded) clinicians read the visual fields and judged them as: "glaucoma field defect," "no glaucoma field defect," and "poor reliability-cannot judge." RESULTS: Statistical analysis revealed that a single reader's interpretation of four different types of visual fields are very different from, are poorer than, and are more consistent than are the four readers' interpretations of a single type of visual field. The analysis also shows that the readers consistently underestimated the number of glaucoma patients with one instrument and overestimated the number with another. CONCLUSIONS: This results suggest that a single visual field will discriminate patients with glaucoma with an accuracy in the 70 to 75 percent range. For one of the instruments, the shorter protocol was almost as effective in discriminating glaucomatous fields as the longer protocol. This study also suggests that repeating the visual fields or analysis of a single field by two readers improves reliability.

The relationship between duration of superior oblique palsy and vertical fusional vergence, cyclodeviation, and diplopia.

BACKGROUND: The purpose of this study was to explore the relationship between the duration of superior oblique palsy (SOP) and relevant clinical findings. METHODS: We studied 39 patients with SOP and 14 patients with normal binocular vision (NBV). Vertical fusional vergences and cyclodeviations were measured through the habitual prescription. Each patient was asked if he or she currently experienced diplopia. To establish duration of SOP, those patients were asked and grouped according to whether they were diagnosed within the past 5 years, within the past 6 to 15 years, or more than 15 years ago. RESULTS: The SOP patients were significantly different from the NBV patients on every measure except the infra recovery value. Among the SOP patients, the infra break value and the total break amplitude (infra plus supra) were the measures that were significantly different for the three SOP groups, increasing with the duration of the deviation. Since the infra break value was measured relative to any corrective prism in place, the total break amplitude proved to be the best distinguishing feature of duration of the SOP. There was no monotonic relation between the duration and the magnitude of the cyclodeviation. Likewise, there was no significant difference among the SOP groups in the frequency of reported diplopia even though there was a monotonic decrease in the percentage of diplopic patients with increasing duration of SOP. CONCLUSIONS: While an increased vergence amplitude and the presence of both diplopia and excyclodeviation distinguish patients with SOP from those with NBV, the total break amplitude is the only significant distinguishing feature of the duration of SOP.

A comprehensive model of clinical decision making.

BACKGROUND: Accountability in health care delivery requires that the ratio of patient benefits to patient costs be maximized. This goal is achieved by optimizing patient outcomes, expressed in terms of the degree to which discomfort and dysfunction are alleviated. To achieve this goal it is necessary to understand how diagnostic problem solving and clinical decision making under conditions of uncertainty are best carried out. METHODS: This paper synthesizes several studies of clinical problem solving and decision making into a coherent and comprehensive descriptive model. RESULTS/CONCLUSIONS: This model should serve as a framework within which the more specific quantitative techniques necessary for optimizing patient outcomes can be developed. The ongoing development of such a model has profound implications not only for clinical practice but also for the education of clinicians and for clinical research.

A statistical analysis of Modified Clinical Technique vision screening of preschoolers by optometry students.

Fourth year optometry students screened 745 preschoolers using a slightly altered Modified Clinical Technique (MCT) under the supervision of a faculty doctor. Children who failed the MCT were randomly selected and then matched by age, sex, and ethnic origin to children who had passed the screening battery. The 61 screening failures and 45 matched controls were later given full eye examinations with cycloplegia by University of Alabama at Birmingham faculty doctors who were unaware of the screening results. The positive predictive value (PPV) (0.52) and negative predictive value (NPV) (0.78) of the MCT were calculated directly from the 2 x 2 contingency table crossing screening results and a standard diagnosis. Sensitivity [0.50, k(1,0) = 0.29], specificity [0.79, k(0,0) = 0.30], efficiency [0.70, k(0.5,0) = 0.29] of the MCT, and the prevalence (0.30) of children failing the standard diagnosis were estimated using statistics appropriate to the prospective sampling design. The reproducibility of the diagnosis, estimated by analyzing multiple, independent diagnosis of each study child by seven doctors was moderate (kappa D 0.58). Statistics summarizing the agreement between the MCT and the diagnosis by the individual study doctor are similar to those obtained with comparison to the standard diagnosis. The characteristics of the MCT may be generalized only to similar populations that are screened by clinicians with similar experience, using the same tests.

The Alabama preterm birth prevention project.

A preterm birth prevention program consisting of risk scoring, intensive weekly observation including cervical examinations, and detailed education about preterm labor signs and symptoms was tested in a predominantly black, indigent population. One thousand high-risk women were randomized to treatment or control groups. Although more preterm labor was diagnosed and treated in the treatment group, there were no significant differences between the groups with respect to mean birth weight or gestational age, spontaneous preterm delivery rates, or low or very low birth weight rates. The rates of respiratory distress syndrome and fetal and neonatal mortality, although greater in the treatment group, were not statistically different. However, the treatment-group infants had significantly more intracranial hemorrhages and spent more days on ventilators. At this institution, the preterm birth prevention program was not effective.