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Stephen J Hannan,1 David Teenan,1 Jan A Venter,1 Keith A Hettinger,1 Colin W Berry,1 Noelle C Hannan,1 Huba J Kiss,1 Dasi Raju,1 Julie M Schallhorn2,3 1Optical Express, Glasgow, United Kingdom; 2University of California, San Francisco, Department of Ophthalmology, San Francisco, CA, USA; 3F.I. Proctor Foundation, University of California, San Francisco, San Francisco, CA, USACorrespondence: Stephen J Hannan, Clinical Services Department, Optical Express, 200 St Vincent St, Glasgow, G2 5SG, United Kingdom, Tel +44 7740592389, Email StephenHannan@opticalexpress.comPurpose: To compare refractive, visual, and patient-reported outcomes associated with a 1st generation wavefront-guided (WFG) treatment with those associated with a 3rd generation WFG treatment.Patients and Methods: This retrospective study included patients who underwent femtosecond laser-assisted in situ keratomileusis (LASIK) for myopia/myopic astigmatism. Two random stratified samples of patients who underwent either 1stgeneration (WaveScan, Johnson & Johnson Vision, Santa Ana, CA) or 3rd generation (iDesign 2.0, Johnson & Johnson Vision, Santa Ana, CA) treatment matched on preoperative refraction were compared (4290 eyes of 2145 patients in each group). One-month postoperative visual, refractive, and patient-reported outcomes were analyzed. Refractive and monocular visual acuity analyses were performed using one random eye of each patient.Results: The percentage of eyes achieving 20/20 or better uncorrected vision was 91.3% (1958/2145) in the 1st generation group and 95.9% (2056/2145) in the 3rd generation group (p< 0.01). Binocularly, the percentage of patients with 20/20 or better UDVA was 97.0% (2080/2145) and 99.2% (2127/2145) in the 1st and 3rd generation groups, respectively (p< 0.01). The mean postoperative MSE was − 0.01 ± 0.33 D in the 1st generation group and +0.19 ± 0.33 D in the 3rd generation group (p< 0.01). Postoperative refractive astigmatism had a mean value of − 0.20 ± 0.26 D and − 0.18 ± 0.24 D in the 1st and 3rd generation groups, respectively (p< 0.01). The mean correction index of refractive astigmatism was 1.09 ± 0.53 in the 1st generation group and 1.02 ± 0.38 in the 3rd generation group, p< 0.01. The overall percentage of patients satisfied with vision was 92.8% (1991/2145 patients) in the 1st generation group and 97.3% (2087/2145 patients) in the 3rd generation group (p< 0.01).Conclusion: For the majority of postoperative variables, there were significant differences between 1st and 3rd generation treatments. The 3rd generation treatments had better visual acuity outcomes and higher patient satisfaction.Keywords: wavefront-guided LASIK, myopia, aberrometer, refractive outcomes, patient-reported outcomes

Activation of c-Jun, a component of the AP-1 family of transcription factors, leads to either promotion or prevention of apoptosis. However, the molecular determinants of c-Jun-mediated cell survival are still unclear. We show here that inducible expression of c-Jun promotes cellular survival by negatively regulating the expression of the tumor-suppressor PTEN, resulting in the concomitant activation of the Akt survival pathway. Consistently, c-jun−/− fibroblasts, which are sensitive to nutrient deprivation, and human cell lines in which c-Jun expression is silenced, express elevated levels of PTEN. siRNA-mediated silencing of PTEN resulted in the reduction of cell-death owing to c-Jun deficiency. c-Jun was found to suppress PTEN expression by binding to a variant AP-1 site found in the 5′ upstream sequences of PTEN promoter. Finally, an inverse correlation between c-Jun and PTEN levels was apparent in a panel of human tumor cell lines, independent of their p53 status. Together, the data demonstrate that c-Jun contributes to the promotion of cellular survival by regulating the expression of PTEN.Cell Death and Differentiation (2007) 14, 218–229. doi:10.1038/sj.cdd.4401946; published online 5 May 2006 [ABSTRACT FROM AUTHOR]

Steven C Schallhorn,1–3 Julie M Schallhorn,1 Martina Pelouskova,3 Jan A Venter,3 Keith A Hettinger,3 Stephen J Hannan,3 David Teenan3 1Department of Ophthalmology, University of California, San Francisco, CA, USA; 2Roski Eye Institute, University of Southern California, Los Angeles, CA, USA; 3Optical Express, Glasgow UK Purpose: To compare refractive and visual outcomes, patient satisfaction, and complication rates among different age categories of patients who underwent refractive lens exchange (RLE). Methods: A stratified, simple random sample of patients matched on preoperative sphere and cylinder was selected for four age categories: 45–49 years (group A), 50–54 years (group B), 55–59 years (group C), and 60–65 years (group D). Each group contained 320 patients. All patients underwent RLE with a multifocal intraocular lens at least in one eye. Three months postoperative refractive/visual and patient-reported outcomes are presented. Results: The percentage of patients that achieved binocular uncorrected distance visual acuity 20/20 or better was 91.6% (group A), 93.8% (group B), 91.6% (group C), 88.8% (group D), P=0.16. Binocularly, 80.0% of patients in group A, 84.7% in group B, 78.9% in group C, and 77.8% in group D achieved 20/30 or better uncorrected near visual acuity (P=0.13). The proportion of eyes within 0.50 D of emmetropia was 84.4% in group A, 86.8% in group B, 85.7% in group C, and 85.8% in group D (P=0.67). There was no statistically significant difference in postoperative satisfaction, visual phenomena, dry eye symptoms, distance or near vision activities. Apart from higher rate of iritis in the age group 50–55 years, there was no statistically significant difference in postoperative complication rates. Conclusion: RLE can be safely performed in younger as well as older presbyopes. No significant difference was found in clinical or patient-reported outcomes. Keywords: refractive lens exchange, multifocal IOLs, younger/older presbyopes

Steven C Schallhorn,1–3 Jan A Venter,2 David Teenan,2 Julie M Schallhorn,3 Keith A Hettinger,2 Stephen J Hannan,2 Martina Pelouskova2 1Department of Ophthalmology, University of California, San Francisco, CA, USA; 2Optical Express, Glasgow, UK; 3Department of Ophthalmology, University of Southern California, Los Angeles, CA, USA Purpose: The aim of this study was to assess visual and refractive outcomes of laser vision correction (LVC) to correct residual refraction after multifocal intraocular lens (IOL) implantation. Patients and methods: In this retrospective study, 782 eyes that underwent LVC to correct unintended ametropia after multifocal IOL implantation were evaluated. Of all multifocal lenses implanted during primary procedure, 98.7% were refractive and 1.3% had a diffractive design. All eyes were treated with VISX STAR S4 IR excimer laser using a convectional ablation profile. Refractive outcomes, visual acuities, patient satisfaction, and quality of life were evaluated at the last available visit. Results: The mean time between enhancement and last visit was 6.3±4.4 months. Manifest spherical equivalent changed from -0.02±0.83 D (-3.38 D to +2.25 D) pre-enhancement to 0.00±0.34 D (-1.38 D to +1.25 D) post-enhancement. At the last follow-up, the percentage of eyes within 0.50 D and 1.00 D of emmetropia was 90.4% and 99.5%, respectively. Of all eyes, 74.9% achieved monocular uncorrected distance visual acuity 20/20 or better. The mean corrected distance visual acuity remained the same before (-0.04±0.06 logMAR [logarithm of the minimum angle of resolution]) and after LVC procedure (-0.04±0.07 logMAR; P=0.70). There was a slight improvement in visual phenomena (starburst, halo, glare, ghosting/double vision) following the enhancement. No sight-threatening complications related to LVC occurred in this study. Conclusion: LVC in pseudophakic patients with multifocal IOL was safe, effective, and predictable in a large cohort of patients. Keywords: excimer laser enhancements, pseudophakic patients, multifocal IOL

Steven C Schallhorn,1,2 Jan A Venter,2 Stephen J Hannan,2 Keith A Hettinger2 1University of California, San Francisco, CA, USA; 2Optical Express, Glasgow, UK Purpose: The purpose of this study was to evaluate the refractive and visual outcomes of wavefront-guided laser in situ keratomileusis (LASIK) in eyes with myopic astigmatism and cylindrical component ≥2.0 diopter (D).Methods: In this retrospective study, 611 eyes that underwent LASIK for simple or compound myopic astigmatism were analyzed. Preoperative refractive cylinder ranged from -2.00 D to -6.00 D (mean -2.76±0.81 D), and the sphere was between 0.00 D and -9.75 D (mean -2.79±2.32 D). Predictability, visual outcomes, and vector analysis of changes in refractive astigmatism were evaluated.Results: At 3 months after LASIK, 83.8% of eyes had uncorrected distance visual acuity of 20/20 or better, 90.3% had manifest spherical equivalent within ±0.50 D, and 79.1% had residual refractive cylinder within ±0.50 D of intended correction. The mean correction ratio for refractive cylinder was 0.92±0.14, the mean error of angle was -0.45°±2.99°, and the mean error vector was 0.37±0.38 D. A statistically significant correlation was found between the error of magnitude (arithmetic difference in the magnitudes between surgically induced refractive correction and intended refractive correction) and the intended refractive correction (r=0.26, P

Background: Dental care before pregnancy is critical for preventing poor oral health, which is associated with adverse pregnancy outcomes. People with low incomes, however, may face insurance-related barriers to obtaining dental care. Medicaid expansion under the Affordable Care Act increased access to dental care utilization among adults with low incomes. However, little is known about the impact of Medicaid policies on pre-pregnancy dental care utilization., Objective: To evaluate the impacts on pre-pregnancy dental care utilization of two aspects of Medicaid policy: (1) state level of Medicaid dental coverage and (2) Medicaid expansion overall and by state level of dental coverage., Methods: We used data from Pregnancy Risk Assessment Monitoring System (PRAMS) data phases 7 (2012-15) and 8 (2016-18). To examine the association between state level of dental coverage beyond emergency services (i.e., extensive vs. limited) and pre-pregnancy dental care utilization, we conducted an adjusted logistic regression analysis. To evaluate the impact of Medicaid expansion on pre-pregnancy dental care utilization, we conducted a quasi-experimental event study design, which estimates the percentage point difference in the outcome between expansion and non-expansion states at each time period compared to the period just prior to Medicaid expansion., Results: We found a significant 13% (adjusted odds ratio (OR) = 1.13; 95% CI: 1.05, 1.22) higher odds of pre-pregnancy dental care utilization among the birthing people residing in states that provided extensive dental coverage compared to those in states that provided limited dental coverage. However, Medicaid expansion under the ACA was not associated with pre-pregnancy dental care utilization overall or among either states with extensive or limited Medicaid dental coverage., Competing Interests: Declarations. Ethical Approval: This research received Human Subjects approval from Michigan State University. Consent to Participate: Not applicable. Consent for Publication: None of the content is included in another manuscript, has been published previously, or is currently under consideration for publication elsewhere. Conflict of Interest: The authors have no conflicts of interest/competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the United States, there are profound and persistent racial and ethnic disparities in pregnancy-related health, emphasizing the need to promote racial health equity through public policy. There is evidence that the Affordable Care Act (ACA) increased health insurance coverage, access to health care, and health care utilization, and may have affected some pregnancy-related health outcomes (eg, preterm delivery). It is unclear, however, whether these impacts on pregnancy-related outcomes were equitably distributed across race and ethnicity. Thus, the objective of this study was to fill that gap by summarizing the peer-reviewed evidence regarding the impact of the ACA on racial and ethnic disparities in pregnancy-related health outcomes. The authors conducted a scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR), using broad search terms to identify relevant peer-reviewed literature in PubMed, Web of Science, and EconLit. The authors identified and reviewed n  = 21 studies and found that the current literature suggests that the ACA and its components were differentially associated with contraception-related and fertility-related outcomes by race/ethnicity. Literature regarding pregnancy health, birth outcomes, and postpartum health, however, was sparse and mixed, making it difficult to draw conclusions regarding the impact on racial/ethnic disparities in these outcomes. To inform future health policy that reduces racial disparities, additional work is needed to clarify the impacts of contemporary health policy, like the ACA, on racial disparities in pregnancy health, birth outcomes, and postpartum health.

Importance: Infants and pregnant people in the US fare worse on almost all health measures compared with those in peer nations. Families in the US are more likely to live in poverty and have a less generous social safety net, which has generated debate over the contribution of economic conditions to this disparity., Objective: To assess the association between temporary increases in income during pregnancy through the 2021 expanded Child Tax Credit (CTC) and birth outcomes., Design, Setting, and Participants: This cross-sectional study applied a comparison-population, interrupted time series design to data from US birth certificates (January 1, 2014, through December 31, 2021) to test whether the log odds of low birth weight (LBW) among monthly cohorts of births exposed to the CTC would coincide with a decreased incidence of LBW. All singleton live births to US residents aged 15 to 49 years with available data were included., Exposure: Monthly birth cohorts exposed to the CTC were defined as those born to parous people during the CTC advance payment period from July through December 2021., Main Outcomes and Measures: The main outcome was the natural logarithm of the odds of LBW (<2500 g) among monthly birth cohorts., Results: Among included births (n = 28 866 466), 61.2% were to parous people, the majority were to people aged 20 to 39 years (91.7%), and 6.5% were born LBW. The odds of LBW increased above expected values in 5 of the 6 months of the CTC payments (range of increases, 3.3%-5.4% across the 5 months). The outlier-adjusted odds of LBW increased, on average, by 4.2% (95% CI, 2.7%-5.7%) among the monthly birth cohorts exposed to the CTC., Conclusions and Relevance: This study found that the odds of LBW among birth cohorts exposed to the CTC increased above expected values in 5 of the 6 months of the CTC advance payments. Additional research is needed to evaluate rival explanations for this increase in LBW among births exposed to the CTC payments.

Maternal mortality and morbidity in the United States are high compared with those in similar countries, and racial/ethnic disparities exist, with many of these events occurring in the later postpartum period. Proposed federal and recently enacted state policy interventions extend pregnancy Medicaid from covering 60 days to a full year postpartum. This study estimates the association between maintaining Medicaid eligibility in the later postpartum period (relative to only having pregnancy Medicaid eligibility) with postpartum checkup attendance and depressive symptoms using regression analysis, overall and stratified by race/ethnicity. People with postpartum Medicaid eligibility were 1.0%-1.4% more likely to attend a postpartum checkup relative to those with only pregnancy Medicaid eligibility overall, primarily driven by a 3.8%-4.0% higher likelihood among Hispanic postpartum people. Conversely, postpartum Medicaid is associated with a 2.2%-2.3% lower likelihood of postpartum checkup attendance for Black postpartum people. Postpartum eligibility is also associated with a 9.7%-11.6% lower likelihood of self-reported depressive symptoms compared with only pregnancy Medicaid eligibility for White postpartum people only. Postpartum Medicaid eligibility is associated with some improvements in maternal health care utilization and mental health, but differences by race and ethnicity imply that inequitable systems and structures that cannot be overcome by insurance alone may also play an important role in postpartum health.

Poor perinatal mental health is a common pregnancy-related morbidity with potentially serious impacts that extend beyond the individual to their family. A possible contributing factor to poor perinatal mental health is discontinuity in health insurance coverage, which is particularly important among low-income people. We examined impacts of Medicaid expansion on prepregnancy depression screening and self-reported depression and postpartum depressive symptoms and well-being among low-income people giving birth. Medicaid expansion was associated with a 16 percent decline in self-reported prepregnancy depression but was not associated with postpartum depressive symptoms or well-being. Associations between Medicaid expansion and prepregnancy mental health measures increased with time since expansion. Expanding health insurance coverage to low-income people before pregnancy may improve perinatal mental health.

Purpose: To describe the incidence and risk factors associated with microbial keratitis in a large population of laser vision correction (LVC) patients., Setting: Optical Express centers, Glasgow, United Kingdom., Design: Retrospective case series., Methods: Records were searched to identify all cases of presumed microbial keratitis after LVC between January 1, 2008, and April 1, 2015. Consecutive patients having primary or enhancement LVC during that time served as controls. Data on preoperative age, sex, refraction, procedure, and surgery specifics were collected. A multivariate Cox proportional hazards model was used, and hazard ratios were calculated., Results: Definite or probable microbial keratitis occurred in 26 of 564 165 eyes after laser in situ keratomileusis (LASIK) and in 11 of 81 792 eyes after photorefractive keratectomy (PRK) during the study period, for an overall incidence of 0.0046% (1 case per 21 697 procedures) after LASIK and 0.0013% (1 case per 7434 procedures) after PRK. A multivariate analysis found that those having PRK had a significantly higher incidence of microbial keratitis than those having LASIK (hazard ratio, 2.92; 95% confidence interval, 1.42-6.00; P = .004). No other analyzed factors were significant., Conclusion: Although the incidence of infectious keratitis was higher after PRK, the overall risk after any LVC procedure was very low., (Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

An international expert group which includes 30 organisations (pharmaceutical companies, contract research organisations, academic institutions and regulatory bodies) has shared data on the use of recovery animals in the assessment of pharmaceutical safety for early development. These data have been used as an evidence-base to make recommendations on the inclusion of recovery animals in toxicology studies to achieve scientific objectives, while reducing animal use. Recovery animals are used in pharmaceutical development to provide information on the potential for a toxic effect to translate into long-term human risk. They are included on toxicology studies to assess whether effects observed during dosing persist or reverse once treatment ends. The group devised a questionnaire to collect information on the use of recovery animals in general regulatory toxicology studies to support first-in-human studies. Questions focused on study design, the rationale behind inclusion or exclusion and the impact this had on internal and regulatory decisions. Data on 137 compounds (including 53 biologicals and 78 small molecules) from 259 studies showed wide variation in where, when and why recovery animals were included. An analysis of individual study and programme design shows that there are opportunities to reduce the use of recovery animals without impacting drug development., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the relationship between low-light pupil size and patient-reported outcomes 1 month after wavefront-guided LASIK in young patients with myopia., Methods: Retrospective case series of 10,944 eyes of 5,563 young patients with myopia who underwent wavefront-guided LASIK (6.0-mm optical zone). Preoperative pupil size was measured under low-light conditions with an infrared pupillometer. Visual and refractive outcomes were evaluated at 1 month postoperatively. A questionnaire was administered to assess patient-reported outcomes including satisfaction with the procedure, night driving, and glare and halo visual symptoms., Results: The average patient age was 29.8 years (range: 18 to 40 years). The mean preoperative manifest spherical equivalent of -3.49 diopters (D) (range: -0.50 to -11.75 D) was reduced to -0.04 ± 0.29 D at 1 month, with 94% of eyes achieving an uncorrected distance visual acuity of 20/20 or better. The mean low-light pupil diameter was 6.6 mm (range: 4 to 9 mm) and 1,514 patients (27.2%) had a diameter of 8 mm or larger. No correlation between pupil diameter and patient-reported outcomes was found (r range: -0.02 to 0.07). Logistic regression analysis identified postoperative uncorrected distance visual acuity and postoperative manifest refraction as significant predictors of night halo complaints after wavefront-guided LASIK (P < .01)., Conclusions: In this large series of young patients with myopia treated with wavefront-guided LASIK, low-light pupil diameter was not predictive of surgery satisfaction, ability to perform activities, or visual symptoms at 1 month postoperatively., (Copyright 2014, SLACK Incorporated.)

Purpose: To provide an initial retrospective evaluation of early postoperative outcomes after wavefront-guided myopic LASIK using a new-generation Hartmann-Shack wavefront sensor., Methods: A noncomparative, retrospective study of 243 eyes of 126 patients that underwent primary wavefront-guided LASIK, using wavefront data obtained with a new Hartmann-Shack aberrometer (iDesign Advanced WaveScan aberrometer; Abbott Medical Optics, Inc., Santa Ana, CA). Visual acuity, refraction, and patient satisfaction were evaluated 1 month after surgery., Results: The manifest spherical equivalent was reduced from -3.28 ± 1.79 diopters (D) (range: -9.88 to -0.38 D) before surgery to -0.03 ± 0.29 D (range: -1.00 to +1.25 D) 1 month after surgery. The manifest spherical equivalent was within 0.50 and 1.00 D of target in 93.0% and 99.6% of eyes, respectively. Manifest astigmatism preoperatively (-0.72 ± 0.67 [range: 0.0 to -5.00 D]) was reduced to -0.14 ± 0.20 (range: 0.0 to -1.00 D) at 1 month and the vector-derived correction ratio (surgically induced refractive change/intended refractive correction) was 1.02 ± 0.30. Uncorrected distance visual acuity of 20/16, 20/20, and 20/25 or better was achieved in 79.0%, 93.4%, and 96.7% of eyes, respectively. No eyes lost two or more lines of corrected distance visual acuity, whereas a gain of one or more lines was observed in 14.0%. Most patients (98.5%) reported that they were satisfied with the outcome of their procedure., Conclusions: Wavefront-guided LASIK using the new aberrometer in this retrospective evaluation was effective, safe, and predictable in the early postoperative time period for the correction of myopia with high patient satisfaction., (Copyright 2014, SLACK Incorporated.)

Purpose: In this preclinical study, we examined the biodistribution of hypericin formulated as its water-soluble PVP-hypericin complex in the different layers (urothelium, submucosa, muscle) of a normal rat bladder and a rat bladder bearing a malignant urothelium composed of syngeneic AY-27 tumor cells. The results were compared with the biodistribution of hexaminolevulinate (HAL)-induced protoporphyrin IX (PpIX)., Methods: Freshly prepared PVP-hypericin and HAL solutions were instilled in both normal as well as tumor-bearing rat bladders. Following instillation, bladders were removed and snap frozen in liquid nitrogen. Fluorescence of PVP-hypericin or PpIX-induced HAL was measured in the bladder layers and quantified using image analysis software., Results: The results of these experiments show that PVP-hypericin (30 μM) accumulated about 3.5-fold more in malignant urothelial tissue when compared to normal urothelium, whereas PpIX accumulated to the same extent in malignant and normal urothelium, both after intrabladder instillation of 8 or 16 mM HAL. Besides, PVP-hypericin and PpIX accumulated selectively in the urothelium with a tumor-to-muscle ratio of 30.6 for PVP-hypericin and 3.7-8.3 for 16 and 8 mM HAL, respectively., Conclusions: This study shows that PVP-hypericin appears to have great potential as a photodynamic agent against non-muscle-invasive bladder cancers after intravesical administration, with a limited risk of affecting the deeper layers of the bladder.

Polyvinylpyrrolidone (PVP)-hypericin is a potent photosensitizer that is used in the urological clinic to photodiagnose with high-sensitivity nonmuscle invasive bladder cancer (NMIBC). We examined the differential accumulation and therapeutic effects of PVP-hypericin using spheroids composed of a human urothelial cell carcinoma cell line (T24) and normal human urothelial (NHU) cells. The in vitro biodistribution was assessed using fluorescence image analysis of 5-μm cryostat sections of spheroids that were incubated with PVP-hypericin. The results show that PVP-hypericin accumulated to a much higher extent in T24 spheroids as compared to NHU spheroids, thereby reproducing the clinical situation. Subsequently, spheroids were exposed to different PDT regimes with a light dose ranging from 0.3 to 18 J∕cm2. When using low fluence rates, only minor differences in cell survival were seen between normal and malignant spheroids. High light fluence rates induced a substantial difference in cell survival between the two spheroid types, killing ∼80% of the cells present in the T24 spheroids. It was concluded that further in vivo experiments are required to fully evaluate the potential of PVP-hypericin as a phototherapeutic for NMIBC, focusing on the combination of the compound with methods that enhance the oxygenation of the urothelium.

Diabetic peripheral neuropathic pain affects the functionality, mood, and sleep patterns of approximately 10 to 20 percent of patients with diabetes mellitus. Treatment goals include restoring function and improving pain control. Patients can realistically expect a 30 to 50 percent reduction in discomfort with improved functionality. The main classes of agents used to treat diabetic peripheral neuropathic pain include tricyclic antidepressants, anticonvulsants, serotonin-norepinephrine reuptake inhibitors, opiates and opiate-like substances, and topical medications. Physicians should ask patients whether they have tried complementary and alternative medicine therapies for their pain. Only two medications are approved specifically for the treatment of diabetic peripheral neuropathic pain: pregabalin and duloxetine. However, evidence supports the use of other therapies, and unless there are contraindications, tricyclic antidepressants are the first-line treatment. Because patients often have multiple comorbidities, physicians must consider potential adverse effects and possible drug interactions before prescribing a medication.

Purpose: To assess the role of depressive symptoms in patient satisfaction with visual quality after laser in situ keratomileusis (LASIK)., Setting: Navy Refractive Surgery Center, Ophthalmology Department, Naval Medical Center, San Diego, California, USA., Methods: This was a prospective study of active-duty military patients having bilateral conventional LASIK to treat low to moderate myopia with or without astigmatism. Patients completed the Armstrong Laboratory Personality Survey Depression scale preoperatively. Patients were also given a 10-point Navy questionnaire that included an assessment of patient satisfaction with visual quality at the 1- and 6-month follow-up examinations. Patients were stratified by their visual quality rating after LASIK as highly satisfied, satisfied, and less satisfied and by their depression scale score into low, medium, and high groups. A proportional odds model was developed to compare the visual quality rating between the 3 depression groups 1 and 6 months post LASIK., Results: The study comprised 370 patients. An uncorrected visual acuity of at least 20/20 was achieved in 88.6% of eyes. Patients with higher levels of depressive symptoms had 3.0 times higher odds (95% confidence interval [CI], 1.2 to 7.4) of being less satisfied than those with low levels of depressive symptoms 1 month after LASIK (P

Background & Aims: Accurate disease staging in chronic hepatitis C (CHC) infection helps guide treatment and may provide prognostic information. Liver biopsies are invasive, costly, and associated with morbidity. We hypothesized that a noninvasive test of liver fibrosis can accurately stage liver fibrosis. We prospectively evaluated the FIBROSpect II (FSII) biomarker panel versus pathology assessment and a quantitative measure of fibrosis., Methods: Liver biopsy specimens and serum were obtained from 252 CHC patients, including 50 posttransplant, from 3 tertiary centers. Biopsy specimens were scored centrally and independently at each site, along with central quantification of fibrosis by digitized morphometry. Serum tests were performed blinded to clinical or histologic evaluation., Results: The mean biopsy specimen length was 1.95 +/- 0.87 cm; prevalence of stage F2 through F4 fibrosis was 77%. Agreement between central and site readings for individual stages was modest (k = 0.674), with concordant readings in 106 of 248 (43%) biopsy specimens. The area under the receiver operating characteristic curve for FSII and morphometry for stages F2 through F4 for concordant biopsy specimens were 0.823 and 0.728, respectively. Sensitivity and specificity for FSII were 83.5% and 66.7%, respectively, with an accuracy of 80.2%. The aspartate aminotransferase to platelet ratio index sensitivity and specificity for predicting F2 through F4 were 30.4% and 100%, respectively, the indeterminate rate was 40.4%, and the accuracy rate was 48.4%. The accuracy of FSII in concordant biopsy specimens in the posttransplant cohort was 73%., Conclusions: Serum biomarkers can differentiate mild from moderate-to-severe fibrosis. This prospective study validates the performance characteristics of FSII in CHC patients and a posttransplant cohort. Assessing the diagnostic utility of biomarkers is limited by variability in methods to quantify fibrosis and poor interobserver agreement for histologic staging.

Serum markers of liver fibrosis are difficult to validate, due to the sampling error and observer variability associated with percutaneous liver biopsies. Laparoscopic biopsy decreases sampling error and increases the reliability of histopathologic assessment. We prospectively evaluated the FIBROSpect(SM) II serum marker test for viral liver fibrosis against laparoscopic biopsies by studying 145 patients with chronic hepatitis B or C who underwent laparoscopy in a tertiary care setting. Serum samples obtained at biopsy were tested with FIBROSpect II to assess the degree of fibrosis. Multiple biopsies were obtained from each patient and scored blindly using the Batts-Ludwig system. An average biopsy stage was calculated and the performance of the test panel assessed. FIBROSpect II was able to rule in significant fibrosis (stages 2-4), with a likelihood ratio of 2.6. It correctly indicated absence of disease in 74% of stages 0-1 patients and correctly predicted significant disease in 67% of stages 2-4 patients. Test correlation was highest with Batts-Ludwig stages 3 (77%) and 4 (96%) and lowest with stage 2 (43%). Multiple biopsies from 52% of patients differed by at least 1 stage. In 13 patients (9%), cirrhosis was detected by laparoscopy but not histologically; in 4 (3%), a stage of 4 was obtained, but cirrhosis was not evident by laparoscopy. FIBROSpect II provided valuable additional information for assessing fibrosis. The discordance in fibrosis stage seen in multiple biopsies from the same patient underscores the need to consider all available information when assessing fibrosis. This study confirms and extends results of previous studies evaluating FIBROSpect II using percutaneous liver biopsy.

A hyperdiploid karyotype is found in 30% of B-cell precursor acute lymphoblastic leukemias in childhood. The time of nondisjunction of chromosomes leading to hyperdiploidy during leukemogenesis is unknown. We used the 3 clonotypic immunoglobulin heavy chain (IgH) gene rearrangements as molecular markers for each of the 3 chromosomes 14 in a case with hyperdiploid acute lymphoblastic leukemia to define the order of events-namely, somatic recombination and nondisjunction of chromosomes-during leukemia development. A partial sequence homology of the incomplete DJ(H) rearrangement with 1 of the 2 nonfunctional VDJ(H) rearrangements suggests that the doubling of chromosomes had occurred after this DJ(H) rearrangement and thus during early B-cell differentiation. The occurrence of the nondisjunction of chromosomes as well as ongoing rearrangement processes in utero were confirmed by the presence of all 3 IgH rearrangements in neonatal blood spots, providing the first evidence that hyperdiploidy formation is an early event in leukemogenesis in these leukemias.

We performed sensitive polymerase chain reaction-based minimal residual disease (MRD) analyses on bone marrow samples at 9 follow-up time points in 71 children with T-lineage acute lymphoblastic leukemia (T-ALL) and compared the results with the precursor B-lineage ALL (B-ALL) results (n = 210) of our previous study. At the first 5 follow-up time points, the frequency of MRD-positive patients and the MRD levels were higher in T-ALL than in precursor-B-ALL, reflecting the more frequent occurrence of resistant disease in T-ALL. Subsequently, patients were classified according to their MRD level at time point 1 (TP1), taken at the end of induction treatment (5 weeks), and at TP2 just before the start of consolidation treatment (3 months). Patients were considered at low risk if TP1 and TP2 were MRD negative and at high risk if MRD levels at TP1 and TP2 were 10(-3) or higher; remaining patients were considered at intermediate risk. The relative distribution of patients with T-ALL (n = 43) over the MRD-based risk groups differed significantly from that of precursor B-ALL (n = 109). Twenty-three percent of patients with T-ALL and 46% of patients with precursor B-ALL were classified in the low-risk group (P =.01) and had a 5-year relapse-free survival (RFS) rate of 98% or greater. In contrast, 28% of patients with T-ALL were classified in the MRD-based high-risk group compared to only 11% of patients with precursor B-ALL (P =.02), and the RFS rates were 0% and 25%, respectively (P =.03). Not only was the distribution of patients with T-ALL different over the MRD-based risk groups, the prognostic value of MRD levels at TP1 and TP2 was higher in T-ALL (larger RFS gradient), and consistently higher RFS rates were found for MRD-negative T-ALL patients at the first 5 follow-up time points.

Background: Sensitive techniques for detection of minimal residual disease (MRD) at degrees of one leukaemic cell per 10(3)-10(6) cells (10(-3)-10(-6)) during follow-up of children with acute lymphoblastic leukaemia (ALL) can provide insight into the effectiveness of cytotoxic treatment. However, it is not yet clear how information on MRD can be applied to treatment protocols., Methods: We monitored 240 patients with childhood ALL who were treated according to national protocols of the International BFM Study Group. 60 patients relapsed and the patients in continuous complete remission (CCR) had a median event-free follow-up of 48 months. Bone-marrow samples were collected at up to nine time points during and after treatment. Standardised PCR analysis of patient-specific immunoglobulin and T-cell receptor gene rearrangements and TAL1 deletions were used as targets for semiquantitative estimation of MRD. Amount of MRD was classed as 10(-2) or more, 10(-3), and 10(-4) or less., Findings: MRD negativity at the various follow-up times was associated with low relapse rates (3-15% at 3 years), but five-fold to ten-fold higher relapse rates (39-86% at 3 years) were found in MRD-positive patients. The distinct degrees of MRD appeared to have independent prognostic value (p [trend]<0.001) at all separate time points, especially at the first two time points (at the end of induction treatment and before consolidation treatment). At these two time points a high degree of MRD (> or = 10(-2)) was associated with a three-fold higher relapse rate when compared with patients with a low degree of MRD (< or = 10(-4)). At later time points (including the end of treatment) even a low degree of MRD was associated with a poor outcome. Positivity in patients in CCR after treatment was rare (< 1%). With the combined MRD information from the first two follow-up time points, it was possible to recognise three different risk groups--55 (43%) were in a low-risk group and had a 3-year relapse rate of only 2% (95% CI 0.05-12%); 19 (15%) were in a high-risk group and had a relapse rate of 75% (55-95%); and 55 (43%) were in an intermediate-risk group and had a 3-year relapse rate of 23% (13-36%)., Interpretation: Our collaborative MRD study shows that monitoring patients with childhood ALL at consecutive time points gives clinically relevant insight into the effectiveness of treatment. Combined information on MRD from the first 3 months of treatment distinguishes patients with good prognoses from those with poor prognoses, and this helps in decisions whether and how to modify treatment.

The preferential occurrence of immature T-cell receptor (TCR) delta rearrangements (i.e. incomplete Ddelta2-Ddelta3 and Vdelta2-Ddelta3) in B-cell precursor acute lymphoblastic leukaemia (BCP ALL) and of predominantly mature rearrangements (incomplete Ddelta2-Jdelta1, complete Vdelta1, Vdelta2, Vdelta3 to Jdelta1) in T-lineage ALL prompted us to establish two separate multiplex PCR systems for the identification of clonal TCRdelta rearrangements. PCR products of the expected size for the specific rearrangements were detectable from a dilution of 100-1000 clonal cells in 150000 polyclonal cells. Both multiplex PCR systems were used to analyse samples from 86 childhood BCPALLs and 30 T-lineage ALLs. The results of the multiplex PCRs were controlled by standard PCR analyses for the individual rearrangements and Southern blots, which were identical. Only immature TCRdelta rearrangements were detected in BCP ALL (59%), whereas no rearrangement was found in the remaining BCP leukaemias, thus confirming the exclusive presence of immature TCRdelta rearrangements in B-lineage cells. 50% of the T-lineage ALLs contained mature rearrangements, but no immature rearrangements were found. These two multiplex PCR techniques appear to be reliable and fast aids in the analysis of clonal TCRdelta rearrangements in ALL.