Factors associated with keratoconus in Israel-A cross-sectional population-based study.

PURPOSE: To identify potential factors associated with keratoconus. METHODS: This cross-sectional study included data from Israel's largest healthcare provider for the years 2005-2020. Keratoconus patients and age-matched controls were identified. Demographic factors and comorbid conditions, including smoking, diabetes mellitus, asthma, myalgia, mental retardation, Down syndrome, atopic dermatitis and allergy/allergic rhinitis, were compared between the two cohorts. The independent risk factors associated with keratoconus were determined using a multivariable conditional logistic regression model. RESULTS: Overall, 145 508 subjects were reviewed of which 13 228 were keratoconus patients. A ten-fold group (n = 132 280) of age-matched control subjects served as controls for comparisons. In multivariable analysis, several factors were found to be significantly associated with keratoconus. Male gender (OR = 1.27, p < 0.001), Arab ethnicity (OR = 1.50, p < 0.001), diabetes (OR = 1.19, p < 0.001), asthma (OR = 1.50, p < 0.001), myalgia (OR = 1.09, p = 0.02), mental retardation (OR = 2.63, p < 0.001), atopic dermatitis (OR = 1.35, p < 0.001) and allergic rhinitis (OR = 1.21, p < 0.001) were significantly associated with keratoconus. Smoking was significantly protective of keratoconus (OR = 0.66, p < 0.001). CONCLUSIONS: This population-based study reports male gender, Arab ethnicity, diabetes, asthma, myalgia, mental retardation/Down syndrome, atopic dermatitis and allergic rhinitis as factors associated with keratoconus while smoking demonstrates a protective effect. The results of this study could guide enhanced screening strategies and early interventions, particularly for high-risk groups.

Effect of Femtosecond Laser Cataract Surgery on Peripapillary Retinal Nerve Fiber Layer Thickness.

PRCIS: Femtosecond laser-assisted cataract surgery (FLACS) may cause thinning of the peripapillary retinal nerve fiber layer (pRNFL) in healthy eyes. PURPOSE: This prospective cohort study aimed to compare changes of pRNFL after FLACS using a liquid patient interface and conventional phacoemulsification cataract surgery (CPCS). PATIENTS AND METHODS: Included were 261 eyes (261 patients) with age-related cataracts and no ocular diseases scheduled either for FLACS (222 eyes) or CPCS (39 eyes). FLACS was performed using a Ziemer LDV Z8 laser. Average and quadrant pRNFL thickness was measured using optical coherence tomography before surgery and at 1, 3, and 6 months postoperatively. Postoperative changes in pRNFL thickness were compared within and between groups. RESULTS: Mean quadrant and average pRNFL thicknesses significantly increased after both surgeries (P<0.001). However, pRNFL thinning occurred after FLACS and CPCS (17% vs. 5.1%, respectively, P>0.05). FLACS eyes showed a significant and stable decrease of average pRNFL thickness (P=0.057) and a gradual decrease in pRNFL thickness of all quadrants (P≤0.018). CPCS eyes showed an initial increase of pRNFL thickness, followed by a decrease only in the nasal quadrant and average pRNFL. Preoperative pRNFL thickness was associated with thinning of the temporal quadrant (P=0.04). CONCLUSIONS: Both FLACS and CPCS demonstrated pRNFL thinning in some healthy eyes. Although the higher rate of pRNFL thinning after FLACS compared with CPCS lacked statistical significance, a consistent decrease in pRNFL thickness occurred in all quadrants and average pRNFL of FLACS eyes, suggesting that FLACS may lead to pRNFL thinning. Eyes with thinner preoperative pRNFL may be prone to temporal quadrant thinning after FLACS.

Creation and Implementation of a Preoperative Malignant Hyperthermia Screening Tool.

BACKGROUND: Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic disorder triggered by certain anesthetic agents. There is currently no standardized preoperative screening tool utilized to identify MH-susceptible individuals. LOCAL PROBLEM: This quality improvement (QI) project aimed to enhance preoperative screening for MH susceptibility (MHS) by implementing an evidence-based screening tool for surgical patients at 2 sites. METHODS: This prospective descriptive QI project evaluated the success of implementing an MHS screening tool preoperatively and its impact on the anesthesia plan. INTERVENTIONS: Anesthesia professionals included the screening tool in their preoperative interview for surgical patients so that positively screened patients could receive MH prevention measures. RESULTS: A total of 95 patients at site A and 234 patients at site B were screened using the MH tool, a cumulative total of 21 patients were positively screened, and 1 anesthetic plan was altered. CONCLUSIONS: This MHS screening tool has the potential to prevent MH episodes when used consistently by staff.

Why do breast cancer survivors decline a couple-based intimacy enhancement intervention trial?

Recruitment challenges hinder behavioral intervention research in cancer survivors. The purpose was to examine the reasons for declining and intervention preferences of study-eligible breast cancer survivors declining a trial of a four-session couple-based Intimacy Enhancement intervention (refusers) and explore whether refusers differed from participants on key characteristics. Partnered, post-treatment breast cancer survivors reporting sexual concerns who were eligible for but declined participation in the intervention trial were approached to complete a standardized 5-min telephone survey assessing reasons for declining and support preferences. Demographic, clinical, and sexual concerns information were collected during screening. Trial participants and refusers were compared on key variables of age, race, hormone therapy use, time since treatment, level of sexual concerns, and recruitment method using t-tests or chi-square tests. Among the 31 women who declined the trial and completed the survey, the most common reasons for declining were time commitment (74%) and partner noninterest (32%). Most (61%) reported that the telephone format played little to no role in their refusal. Eighty-one percent wanted their partners involved in a program addressing sexual concerns. The two most preferred resources were informational websites (45%) and meeting with a professional (26%). Trial participants and refusers did not differ on any key factors examined. Developing intimacy interventions that are very brief, partner-optional, or that use stepped care may bolster uptake. The methods used to examine study-eligible candidates' needs and preferences could be employed in other health populations, thus having broader implications for research design.

Guidelines-Based Cancer Risk Assessment.

OBJECTIVE: To build skills related to cancer risk assessment including: identification of elevated personal or hereditary cancer risks, incorporation of cancer risk models into clinical care, and reviewing elements of cancer risk education and informed consent. DATA SOURCES: Consensus and professional guidelines and published literature. CONCLUSION: Applying consensus guidelines to cancer risk education, along with building partnerships with other providers, is essential for oncology nurses and will ensure proper patient care and follow-up. IMPLICATIONS FOR NURSING PRACTICE: Oncology nursing has embraced advances in genetics and genomics and developed standards of practice that include genetics and genomics competency.

A randomized pilot trial of a couple-based intervention addressing sexual concerns for breast cancer survivors.

The purpose was to test the feasibility, acceptability, and preliminary efficacy of a 4-session couple-based Intimacy Enhancement (IE) intervention addressing breast cancer survivors' sexual concerns delivered via telephone. Twenty-nine post-treatment breast cancer survivors reporting sexual concerns and their intimate partners were randomized (2:1) to the IE intervention or to an educational control condition, both of which were delivered by trained psychosocial providers. Feasibility and acceptability were measured through recruitment, retention, session completion, and post-intervention program evaluations. Couples completed validated sexual, relationship, and psychosocial outcome measures at pre- and post-intervention. Between-group effect sizes and 95% confidence intervals were calculated using the Hedges g. Data supported intervention feasibility and acceptability. For survivors, the IE intervention had medium to large positive effects on all sexual outcomes and most psychosocial outcomes. Effects were less visible for relationship outcomes and were similar but somewhat smaller for partners. The IE intervention demonstrated feasibility, acceptability, and promise in addressing breast cancer survivors' sexual concerns and enhancing their and their partners' intimate relationships and psychosocial well-being. Implications for Psychosocial Oncology Practice The IE intervention demonstrated feasibility and acceptability, suggesting it could be well-received by breast cancer survivors with sexual concerns and their partners. Effects of the IE intervention on breast cancer survivors' sexual concerns and on their and their partners' intimate relationships and psychosocial well-being could not be attributed to therapist time and attention. Interventions that psychosocial providers can use to address breast cancer survivors' sexual concerns are important to the growing number of breast cancer survivors living for many years after their diagnosis.

Safety of hematopoietic cell infusion in children with malignant and non-malignant diseases.

HPC infusions have been associated with a variety of adverse events related to either patient or HPC product-related factors. Studies documenting infusion-related AEs in children are limited. We reviewed HPC infusion records in 354 children. Infusion-related adverse events were classified as follows: grade 0-absent, grade I-mild, grade II-moderate, grade III-severe, grade IV-life-threatening, and grade V-death. The percentage of patients with grade 0, I, and II-IV AEs was as follows: 0 = 67%, I = 23.4%, and II-V = 9.6% (one patient had fatal anaphylactic reaction to dimethyl sulfoxide). The incidence of grade II-IV hypertension was 7.1%. There was a higher incidence of AEs with infusion of allogeneic bone marrow versus allogeneic PBSCs (47.4% vs 25.3%, P = .001). Cryopreserved products had a lower incidence of infusion-associated AEs compared with fresh HPC products (24% vs 39.4%, P = .003). Allogeneic HPC infusion volume (>100 mL) was a significant risk factor for infusion-associated AEs (P < .001). Patients >10 years who received autologous HPC infusions had higher risk of AEs when compared to patients <10 years (P = .01). Our study demonstrated that despite a high incidence of infusion-associated hypertension, HPC infusion is relatively safe in children. Investigating strategies to optimize management of hypertension in the setting of HPC infusion is warranted.

Outcome Measures for Clinical Trials of Leber Congenital Amaurosis Caused by the Intronic Mutation in the CEP290 Gene.

Purpose: To determine efficacy outcome measures for clinical trials of Leber congenital amaurosis (LCA) associated with a common intronic mutation in the CEP290 gene. Methods: CEP290-LCA patients (ages 5-48) with the intronic mutation (c.2991+1655A>G) were studied as a retrospective observational case series using clinical methods and with full-field sensitivity testing (FST), optical coherence tomography (OCT), autofluorescence imaging (NIR-RAFI), transient pupillary light reflex (TPLR), oculomotor control and instability (OCI), a mobility course, and a questionnaire (NEI-VFQ). Patients were investigated cross-sectionally but a subset was able to be followed longitudinally. Results: With FST, there was no rod function; cone sensitivities had a wide range from not detectable to near normal. OCT analyses indicated retained central photoreceptors with abnormal distal laminae. Based on OCT and FST, most patients had dissociation of structure and function. TPLR was nondetectable in the majority of patients, with responders demonstrating severe losses in light sensitivity. OCI was abnormal in most patients. NEI-VFQ scores had a similar range to those of other severe retinopathies. Mobility scores were consistent with FST sensitivities. In patients examined with FST, OCT, and NIR-RAFI over long-term intervals (7-10 years), there was limited but detectable disease progression. Conclusions: Efficacy would be a quantitative change in foveal cone function and possibly distal laminar structure. FST provides a subjective photoreceptor-based outcome; OCT and NIR-RAFI can assess photoreceptor and RPE structure. TPLR and OCI can provide objective measures of postretinal transmission. Minimal change over a decade indicates that there is no practical value in natural history studies.

Postretinal Structure and Function in Severe Congenital Photoreceptor Blindness Caused by Mutations in the GUCY2D Gene.

Purpose: To examine how severe congenital blindness resulting from mutations of the GUCY2D gene alters brain structure and function, and to relate these findings to the notable preservation of retinal architecture in this form of Leber congenital amaurosis (LCA). Methods: Six GUCY2D-LCA patients (ages 20-46) were studied with optical coherence tomography of the retina and multimodal magnetic resonance imaging (MRI) of the brain. Measurements from this group were compared to those obtained from populations of normally sighted controls and people with congenital blindness of a variety of causes. Results: Patients with GUCY2D-LCA had preservation of the photoreceptors, ganglion cells, and nerve fiber layer. Despite this, visual function in these patients ranged from 20/160 acuity to no light perception, and functional MRI responses to light stimulation were attenuated and restricted. This severe visual impairment was reflected in substantial thickening of the gray matter layer of area V1, accompanied by an alteration of resting-state correlations within the occipital lobe, similar to a comparison group of congenitally blind people with structural damage to the retina. In contrast to the comparison blind population, however, the GUCY2D-LCA group had preservation of the size of the optic chiasm, and the fractional anisotropy of the optic radiations as measured with diffusion tensor imaging was also normal. Conclusions: These results identify dissociable effects of blindness upon the visual pathway. Further, the relatively intact postgeniculate white matter pathway in GUCY2D-LCA is encouraging for the prospect of recovery of visual function with gene augmentation therapy.

Defining Outcomes for Clinical Trials of Leber Congenital Amaurosis Caused by GUCY2D Mutations.

PURPOSE: To determine outcome measures for a clinical trial of Leber congenital amaurosis (LCA) associated with mutations in the GUCY2D gene. DESIGN: Retrospective observational case series. METHODS: Twenty-eight patients with GUCY2D-LCA (aged 2-59 years) were studied clinically and with chromatic full-field sensitivity testing (FST), optical coherence tomography (OCT), pupillometry, and the NEI Visual Function Questionnaire (VFQ). RESULTS: FST permitted quantitation of cone and rod sensitivity in these patients with severe visual impairment. For most patients, the degree of rod and cone sensitivity losses showed a relationship, thereby providing an opportunity to divide patients into cohorts by severity of rod and cone dysfunction. OCT analyses indicated that retinal structure could be used not only as an objective safety measure but also as an exploratory efficacy outcome. A foveal bulge was not present in 67% of patients. The intensity of inner segment/outer segment (ellipsoid zone line) reflectivity was reduced significantly at the fovea and in the rod-dense superior retina. Based on OCT and FST parameters, most patients had dissociation of structure and function. Abnormal pupillometry sensitivity in the majority of GUCY2D-LCA patients provided another objective efficacy outcome. NEI VFQ scores showed a similar range of findings to those of other severe retinal diseases. CONCLUSION: Conventional outcome measures, such as visual acuity and the NEI VFQ, will need to be complemented by methods more specific to this GUCY2D-LCA population. Any therapeutic strategy should determine if there is an effect on rod as well as cone function and structure. FST provides a photoreceptor-based subjective outcome; and OCT in 2 retinal regions, fovea and superior retina, can assess photoreceptor structure. A change in the relationship of structure and function away from baseline becomes evidence of efficacy.

Variegated yet non-random rod and cone photoreceptor disease patterns in RPGR-ORF15-associated retinal degeneration.

Mutations in the ORF15 exon of the RPGR gene cause a common form of X-linked retinitis pigmentosa, which often results in severe loss of vision. In dogs and mice, gene augmentation therapy has been shown to arrest the progressive degeneration of rod and cone photoreceptors. However, the distribution of potentially treatable photoreceptors across the human retinas and the rate of degeneration are not known. Here, we have defined structural and functional features of the disease in 70 individuals with ORF15 mutations. We also correlated the features observed in patients with those of three Rpgr-mutant (Rpgr-ko, Rd9, and Rpgr-cko) mice. In patients, there was pronounced macular disease. Across the retina, rod and cone dysfunction showed a range of patterns and a spectrum of severity between individuals, but a high symmetry was observed between eyes of each individual. Genotype was not related to disease expression. In the Rpgr-ko mice, there were intra-retinal differences in rhodopsin and cone opsin trafficking. In Rd9 and Rpgr-cko mice, retinal degeneration showed inter-ocular symmetry. Longitudinal results in patients revealed localized rod and cone dysfunction with progression rates of 0.8 to 1.3 log per decade in sensitivity loss. Relatively retained rod and cone photoreceptors in mid- and far-peripheral temporal-inferior and nasal-inferior visual field regions should be good targets for future localized gene therapies in patients.

Complexity of the Class B Phenotype in Autosomal Dominant Retinitis Pigmentosa Due to Rhodopsin Mutations.

PURPOSE: Previously, patients with RHO mutations and a class A phenotype were found to have severe early-onset loss of rod function, whereas patients with a class B phenotype retained rod function at least in certain retinal regions. Here class B patients were studied at different disease stages to understand the topographic details of the phenotype in preparation for therapies of this regionalized retinopathy. METHODS: A cohort of patients with RHO mutations and class B phenotype (n = 28; ages 10-80 years) were studied with rod and cone perimetry and optical coherence tomography (OCT). RESULTS: At least three components of the phenotype were identified in these cross-sectional studies. Patients could have hemifield dysfunction, pericentral loss of function, or a diffuse rod sensitivity loss across the visual field. Combinations of these different patterns were also found. Colocalized photoreceptor layer thicknesses were in agreement with the psychophysical results. CONCLUSIONS: These disorders with regional retinal variation of severity require pre-evaluations before enrollment into clinical trials to seek answers to questions about where in the retina would be appropriate to deliver focal treatments, and, for retina-wide treatment strategies, where in the retina should be monitored for therapeutic efficacy (or safety).

Adapting a couple-based intimacy enhancement intervention to breast cancer: A developmental study.

OBJECTIVE: Sexual concerns continue to be poorly addressed for women treated for breast cancer and evidence-based interventions that adequately address these concerns are scarce. The objective of this study was to adapt a telephone-based intimacy enhancement intervention, previously tested in couples facing colorectal cancer, to the needs of women with breast cancer through qualitative focus groups, cognitive interviews, and expert review. METHOD: Three semistructured qualitative focus groups in partnered posttreatment breast cancer survivors (n = 15) reporting sexual concerns were conducted to investigate experiences of breast cancer-related sexual concerns and intervention preferences. Focus group data were coded using the framework approach to qualitative analysis; 8 key themes were identified and used to develop the content and format of the intervention. Feedback from cognitive interviews with study-naïve breast cancer survivors (n = 4) and expert review of materials were also incorporated in finalizing the intervention materials. RESULTS: Qualitative findings centered on the impact of breast cancer and its treatment on women's sexuality and on the intimate relationship, experiences of helpful and unhelpful coping methods, and explicit intervention preferences. Focus group data were particularly helpful in identifying the scope of educational topics and in determining how to structure intervention skills practice (e.g., intimacy-related communication) to be optimally relevant and helpful for both women and their partners. Cognitive interview feedback helped refine intervention materials. CONCLUSION: An intimacy enhancement intervention was adapted for women with breast cancer and their partners. This intervention offers a promising, potentially disseminable approach to addressing breast cancer-related sexual concerns. (PsycINFO Database Record

Outer Retinal Changes Including the Ellipsoid Zone Band in Usher Syndrome 1B due to MYO7A Mutations.

PURPOSE: To study transition zones from normal to abnormal retina in Usher syndrome IB (USH1B) caused by myosin 7A (MYO7A) mutations. METHODS: Optical coherence tomography (OCT) scattering layers in outer retina were segmented in patients (n = 16, ages 2-42; eight patients had serial data, average interval 4.5 years) to quantify outer nuclear layer (ONL) and outer segments (OS) as well as the locus of EZ (ellipsoid zone) edge and its extent from the fovea. Static perimetry was measured under dark-adapted (DA) and light-adapted (LA) conditions. RESULTS: Ellipsoid zone edge in USH1B-MYO7A could be located up to 23° from the fovea. Ellipsoid zone extent constricted at a rate of 0.51°/year with slower rates at smaller eccentricities. A well-defined EZ line could be associated with normal or abnormal ONL and/or OS thickness; detectable ONL extended well beyond EZ edge. At the EZ edge, the local slope of LA sensitivity loss was 2.6 (±1.7) dB/deg for central transition zones. At greater eccentricities, the local slope of cone sensitivity loss was shallower (1.1 ± 0.4 dB/deg for LA) than that of rod sensitivity loss (2.8 ± 1.2 dB/deg for DA). CONCLUSIONS: In USH1B-MYO7A, constriction rate of EZ extent depends on the initial eccentricity of the transition. Ellipsoid zone edges in the macula correspond to large local changes in cone vision, but extramacular EZ edges show more pronounced losses on rod-based vision tests. It is advisable to use not only the EZ line but also other structural and functional parameters for estimating natural history of disease and possible therapeutic effects in future clinical trials of USH1B-MYO7A.

Bacterial bloodstream infections in pediatric allogeneic hematopoietic stem cell recipients before and after implementation of a central line-associated bloodstream infection protocol: A single-center experience.

INTRODUCTION: There are only few reports describing the influence of central line-associated bloodstream infection (CLABSI) prevention strategies on the incidence of bacterial bloodstream infections (BBSIs). METHODS: We performed a retrospective cohort study among pediatric recipients of allogeneic hematopoietic stem cell transplantation (allo-HCT) to assess potential changes in BBSI rates during 3 time periods: pre-CLABSI prevention era (era 1, 2004-2005), CLABSI prevention implementation era (era 2, 2006-2009), and maintenance of CLABSI prevention era (era 3, 2010-2012). BBSI from day 0-365 following allo-HCT were studied. The comparison of person-years incidence rates among different periods was carried out by Poisson regression analysis. RESULTS: The mean age of patients was 10.0 years. During the study period, 126 (65%) of 190 patients had at least a single BBSI. From day 0-30, day 31-100, day 101-180, and day 181-365, 20%, 28%, 30%, and 17% of patients, respectively, experienced BBSIs. The rate of Staphylococcus epidermidis and gram-negative pathogens significantly declined from 3.16-0.93 and 6.32-2.21 per 100 person-months during era 1 and era 3, respectively (P = .001). CONCLUSIONS: Patients undergoing allo-HCT during era 3 were associated with decreased risk of BBSI (P = .012). Maintenance of CLABSI protocols by nursing staff and appropriate education of other care providers is essential to lower incidence of BBSI in this high-risk population, and further strategies to decrease infection burden should be studied.

Causal identification: a charge of epidemiology in danger of marginalization.

The requirement for framing all causal questions as well-defined interventions is being promoted in the causal inference literature within epidemiology. One can consider this perspective as an intervention on the field which requires a refocusing of epidemiologic questions and retooling of epidemiologic methods. Although this intervention has produced many positive results, we think that its underlying assumptions and the possibilities of unintended consequences warrant examination. In so doing, we argue that this approach can lead to the neglect of causal identification as a useful link between associations and the estimation of intervention effects.

SPATA7: Evolving phenotype from cone-rod dystrophy to retinitis pigmentosa.

BACKGROUND: SPATA7 mutations have been associated with different autosomal recessive retinal degeneration phenotypes. Long-term follow-up has not been described in detail. MATERIALS AND METHODS: A Hispanic patient with SPATA7 mutations was evaluated serially over a 12-year period with kinetic and static chromatic perimetry, optical coherence tomography (OCT), and fundus autofluorescence (AF) imaging. Electroretinography (ERG) was performed at the initial visit. RESULTS: The patient was homozygous for a mutation in SPATA7 (p.V458fs). At age 9, the ERG showed an abnormally reduced but preserved rod b-wave and no detectable cone signals. There were two islands of vision: a midperipheral island with greater cone than rod dysfunction and a central island with normal cone but no rod function. Serial measures of rod and cone vision and co-localized retinal structure showed that the midperipheral island slowly became undetectable. By age 21, only the central island and its cone function remained, but it had become more abnormal in structure and function. CONCLUSION: The disease resulting from SPATA7 mutations in this patient initially presented as a cone-rod dystrophy (CRD), but changed over time into a phenotype more reminiscent of late-stage retinitis pigmentosa (RP). The differential diagnosis for both CRD and RP should include this rare molecular cause of autosomal retinal degeneration. An evolving phenotype complicates not only clinical diagnosis and patient counselling but also future strategies aimed at treating specific retinal regions.