How did the use of ED change during the first wave of the SARS-CoV-2 pandemic in the UK? An observational study.

BACKGROUND: The COVID-19 pandemic has been linked to a sharp drop in ED attendance, but the exact reasons for this are unclear. The aim of this study was to investigate differences between individuals attending the ED before and during the pandemic and the reasons for their choices. METHODS: Two population-based online surveys were conducted before (2019) and during (2020) the pandemic. Participants were recruited by a survey panel to be representative of the UK population aged 18-45 years. Both surveys asked about the circumstances and reasons for the last ED attendance, with specific pandemic-related questions in the second one. Comparisons of characteristics and symptoms of individuals attending during the pandemic were compared with those attending in prior years using χ2 tests. We determined the proportion of patients who had symptoms during the pandemic but did not attend, and the reasons for that choice. RESULTS: Young and high-income people, those with chronic illnesses and those with influenza-like symptoms were more likely to attend the ED during lockdown than before. 18% of respondents had experienced urgent symptoms during the pandemic; 60% of these individuals chose not to go to the ED. While about 30% of this group stated they believed their symptoms were not serious enough, 85% of these individuals mentioned fear of infection or worry about overburdening the system as a reason for not attending. Individuals attending during the pandemic were more likely to consider their visit unnecessary compared with those attending previously. CONCLUSIONS: The study suggests that the decision to use the ED has a discretionary component. This could potentially contribute to unnecessary visits, and raises concerns that some patients who should present at the ED do not go. More effective communication about who should visit EDs during a pandemic, and the safety of doing so, is needed.

Lung function trajectories and bronchial hyperresponsiveness during childhood following severe RSV bronchiolitis in infancy.

BACKGROUND: Children with severe respiratory syncytial virus (RSV) bronchiolitis in infancy have increased risks of asthma and reduced lung function in later life. There are limited studies on the longitudinal changes of lung function and bronchial hyperreactivity from early to late childhood in infants hospitalized for RSV bronchiolitis. METHODS: In a prospective cohort of 206 children with their first episode of RSV-confirmed bronchiolitis in the first year of life, 122 had spirometry performed at least twice between 5-16 years of age. Methacholine bronchoprovocation was available in 127 and 79 children at 7 and 12 years of age, respectively. Longitudinal changes in FEV1 , FVC, and FEV1 /FVC z-scores and methacholine PC20 were analyzed. RESULTS: 55% of the study cohort (N = 122) were male, and 55% were Caucasian. During follow-up, longitudinal changes in z-scores for pre- and post-bronchodilator FEV1 (P < .0001) FVC (P < .0001) and FEV1 /FVC (P < .0001 for pre- and 0.007 for post-bronchodilator) from age 5 to 10-16 years were observed. Declined lung function in late childhood was significantly associated with gender, physician diagnosis of asthma, and allergic sensitization. PC20 geometric mean increased from 0.28 mg/mL at 7 years to 0.53 mg/mL at 12 years of age, and the frequency of abnormal bronchial hyperreactivity decreased from 96% to 78% (P = .0003). CONCLUSIONS: Following severe RSV bronchiolitis, there appear to be significant longitudinal changes in pre- and post-bronchodilator lung function during childhood. The study has several limitations including significant dropouts and the lack of a control group and post-bronchodilator measurements. Bronchial hyperreactivity is common in children following severe RSV bronchiolitis; however, it appears to decrease as they enter late childhood.

Using prediction markets to estimate the reproducibility of scientific research.

Concerns about a lack of reproducibility of statistically significant results have recently been raised in many fields, and it has been argued that this lack comes at substantial economic costs. We here report the results from prediction markets set up to quantify the reproducibility of 44 studies published in prominent psychology journals and replicated in the Reproducibility Project: Psychology. The prediction markets predict the outcomes of the replications well and outperform a survey of market participants' individual forecasts. This shows that prediction markets are a promising tool for assessing the reproducibility of published scientific results. The prediction markets also allow us to estimate probabilities for the hypotheses being true at different testing stages, which provides valuable information regarding the temporal dynamics of scientific discovery. We find that the hypotheses being tested in psychology typically have low prior probabilities of being true (median, 9%) and that a "statistically significant" finding needs to be confirmed in a well-powered replication to have a high probability of being true. We argue that prediction markets could be used to obtain speedy information about reproducibility at low cost and could potentially even be used to determine which studies to replicate to optimally allocate limited resources into replications.

Effect of Reducing Field of View on Multidetector Quantitative Computed Tomography Parameters of Airway Wall Thickness in Asthma.

OBJECTIVE: We reduced the computed tomography (CT)-reconstructed field of view (FOV), increasing pixel density across airway structures and reducing partial volume effects, to determine whether this would improve accuracy of airway wall thickness quantification. METHODS: We performed CT imaging on a lung phantom and 29 participants. Images were reconstructed at 30-, 15-, and 10-cm FOV using a medium-smooth kernel. Cross-sectional airway dimensions were compared at each FOV with repeated-measures analysis of variance. RESULTS: Phantom measurements were more accurate when FOV decreased from 30 to 15 cm (P < 0.05). Decreasing FOV further to 10 cm did not significantly improve accuracy. Human airway measurements similarly decreased by decreasing FOV (P < 0.001). Percent changes in all measurements when reducing FOV from 30 to 15 cm were less than 3%. CONCLUSIONS: Airway measurements at 30-cm FOV are near the limits of CT resolution using a medium-smooth kernel. Reducing reconstructed FOV would minimally increase sensitivity to detect differences in airway dimensions.

A randomized controlled trial to evaluate inhibition of T-cell costimulation in allergen-induced airway inflammation.

RATIONALE: T lymphocytes are important in the pathogenesis of allergic asthma. Costimulation through CD28 is critical for optimal activation of T cells, and inhibition of this pathway with CTLA4Ig has been shown to be effective in preventing airway inflammation and hyperresponsiveness in animal models of asthma. Abatacept, a humanized version of CTLA4Ig, has been approved for treatment of rheumatoid arthritis, providing the opportunity to test whether inhibition of costimulation is an effective strategy to treat people with asthma. OBJECTIVES: To determine if 3 months of treatment with abatacept reduced allergen-induced airway inflammation in people with mild atopic asthma. METHODS: Randomized, placebo-controlled, double-blinded study. Bronchoscopically directed segmental allergen challenge was performed on 24 subjects followed by bronchoalveolar lavage 48 hours later. Subjects were randomized 1:1 to receive abatacept or placebo, followed by a second allergen challenge protocol after 3 months of study drug. MEASUREMENTS AND MAIN RESULTS: There was no significant reduction in allergen-induced eosinophilic inflammation in the abatacept-treated group compared with placebo (17.71% ± 17.25% vs. 46.39% ± 29.21%; P = 0.26). In addition, we did not detect an effect of abatacept on FEV1, provocative concentration of methacholine sufficient to induce a 20% decline in FEV1, or asthma symptoms. Subjects treated with abatacept had an increased percentage of naive and a corresponding decrease in memory CD4(+) T cells in the blood compared with placebo. CONCLUSIONS: Inhibition of CD28-mediated costimulation with abatacept does not seem to alter the inflammatory response to segmental allergen challenge or clinical measures of asthma symptoms in people with mild atopic asthma. Clinical trial registered with ClinicalTrials.gov (NCT 00784459).

Causes of mortality in anuran amphibians from an ex situ survival assurance colony in Panama.

The success of ex situ survival assurance populations as tools for amphibian conservation depends on the health and reproductive success of founder populations. Necropsy examination and histopathology of animals that die in assurance populations are useful for the identification of population-limiting disease problems and can help to direct applied research efforts in areas such as amphibian husbandry and nutrition. This study reviewed postmortem findings in 167 frogs from 13 species that died in a large Panamanian rescue and survival assurance population between 2006 and 2011. Common problems identified in long-term captive animals, especially in Atelopus species, were epithelial squamous metaplasia suggestive of vitamin A deficiency and a polycystic nephropathy resembling lesions seen in laboratory animals with electrolyte imbalances. Metabolic bone disease was a significant contributor to morbidity in captive-bred juvenile frogs of Gastrotheca cornuta, Hemiphractus fasciatus, and Hylomantis lemur. Findings common to multiple species included poor overall nutritional condition that was sometimes attributable to maladaptation to captive husbandry and epidermal hyperplasia and hyperkeratosis possibly reflecting environmental skin irritation. Infectious diseases and endoparasitism were most common in recently captured animals and included chytridiomycosis and Rhabdias sp. lungworms. Applied research efforts to improve sustainability of survival assurance populations should focus on elucidating optimal husbandry practices for diverse species, improving methods for nutritional supplementation of cultured insects and examination of the role of water composition in disease development.

Nutrition and health in amphibian husbandry.

Amphibian biology is intricate, and there are many inter-related factors that need to be understood before establishing successful Conservation Breeding Programs (CBPs). Nutritional needs of amphibians are highly integrated with disease and their husbandry needs, and the diversity of developmental stages, natural habitats, and feeding strategies result in many different recommendations for proper care and feeding. This review identifies several areas where there is substantial room for improvement in maintaining healthy ex situ amphibian populations specifically in the areas of obtaining and utilizing natural history data for both amphibians and their dietary items, achieving more appropriate environmental parameters, understanding stress and hormone production, and promoting better physical and population health. Using a scientific or research framework to answer questions about disease, nutrition, husbandry, genetics, and endocrinology of ex situ amphibians will improve specialists' understanding of the needs of these species. In general, there is a lack of baseline data and comparative information for most basic aspects of amphibian biology as well as standardized laboratory approaches. Instituting a formalized research approach in multiple scientific disciplines will be beneficial not only to the management of current ex situ populations, but also in moving forward with future conservation and reintroduction projects. This overview of gaps in knowledge concerning ex situ amphibian care should serve as a foundation for much needed future research in these areas.

A Light Touch: Solar Photocatalysis Detoxifies Oil Sands Process-Affected Waters Prior to Significant Treatment of Naphthenic Acids.

Environmental reclamation of Canada's oil sands tailings ponds is among the single largest water treatment challenges globally. The toxicity of oil sands process-affected water (OSPW) has been associated with its dissolved organics, a complex mixture of naphthenic acid fraction components (NAFCs). Here, we evaluated solar treatment with buoyant photocatalysts (BPCs) as a passive advanced oxidation process (P-AOP) for OSPW remediation. Photocatalysis fully degraded naphthenic acids (NAs) and acid extractable organics (AEO) in 3 different OSPW samples. However, classical NAs and AEO, traditionally considered among the principal toxicants in OSPW, were not correlated with OSPW toxicity herein. Instead, nontarget petroleomic analysis revealed that low-polarity organosulfur compounds, composing <10% of the total AEO, apparently accounted for the majority of waters' toxicity to fish, as described by a model of tissue partitioning. These findings have implications for OSPW release, for which a less extensive but more selective treatment may be required than previously expected.

Utilizing Artificial Intelligence and Chat Generative Pretrained Transformer to Answer Questions About Clinical Scenarios in Neuroanesthesiology.

OBJECTIVE: We tested the ability of chat generative pretrained transformer (ChatGPT), an artificial intelligence chatbot, to answer questions relevant to scenarios covered in 3 clinical guidelines, published by the Society for Neuroscience in Anesthesiology and Critical Care (SNACC), which has published management guidelines: endovascular treatment of stroke, perioperative stroke (Stroke), and care of patients undergoing complex spine surgery (Spine). METHODS: Four neuroanesthesiologists independently assessed whether ChatGPT could apply 52 high-quality recommendations (HQRs) included in the 3 SNACC guidelines. HQRs were deemed present in the ChatGPT responses if noted by at least 3 of the 4 reviewers. Reviewers also identified incorrect references, potentially harmful recommendations, and whether ChatGPT cited the SNACC guidelines. RESULTS: The overall reviewer agreement for the presence of HQRs in the ChatGPT answers ranged from 0% to 100%. Only 4 of 52 (8%) HQRs were deemed present by at least 3 of the 4 reviewers after 5 generic questions, and 23 (44%) HQRs were deemed present after at least 1 additional targeted question. Potentially harmful recommendations were identified for each of the 3 clinical scenarios and ChatGPT failed to cite the SNACC guidelines. CONCLUSIONS: The ChatGPT answers were open to human interpretation regarding whether the responses included the HQRs. Though targeted questions resulted in the inclusion of more HQRs than generic questions, fewer than 50% of HQRs were noted even after targeted questions. This suggests that ChatGPT should not currently be considered a reliable source of information for clinical decision-making. Future iterations of ChatGPT may refine algorithms to improve its reliability as a source of clinical information.

Reduction in intraocular pressure after cataract extraction: the Ocular Hypertension Treatment Study.

PURPOSE: To determine the change in intraocular pressure (IOP) after cataract extraction in the observation group of the Ocular Hypertension Treatment Study. DESIGN: Comparative case series. PARTICIPANTS: Forty-two participants (63 eyes) who underwent cataract surgery in at least 1 eye during the study and a control group of 743 participants (743 eyes) who did not undergo cataract surgery. METHODS: We defined the "split date" as the study visit date at which cataract surgery was reported in the cataract surgery group and a corresponding date in the control group. Preoperative IOP was defined as the mean IOP of up to 3 visits before the split date. Postoperative IOP was the mean IOP of up to 3 visits including the split date (0, 6, and 12 months' with "0 months" equaling the split date). In both groups, we censored data after initiation of ocular hypotensive medication or glaucoma surgery of any kind. MAIN OUTCOME MEASURES: Difference in preoperative and postoperative IOP. RESULTS: In the cataract group, postoperative IOP was significantly lower than the preoperative IOP (19.8 ± 3.2 mmHg vs. 23.9 ± 3.2 mmHg; P<0.001). The postoperative IOP remained lower than the preoperative IOP for at least 36 months. The average decrease in postoperative IOP from preoperative IOP was 16.5%, and 39.7% of eyes had postoperative IOP ≥ 20% below preoperative IOP. A greater reduction in postoperative IOP occurred in the eyes with the highest preoperative IOP. In the control group, the corresponding mean IOPs were 23.8 ± 3.6 before the split date and 23.4 ± 3.9 after the split date. CONCLUSIONS: Cataract surgery decreases IOP in patients with ocular hypertension over a long period of time.

Hamstring graft preparation using a needleless suture loop.

Placement of running, locking stitches during the harvest and preparation of hamstring tendons can be time consuming and requires placement of suture in the most distal and proximal 2 to 3 cm of the tendons. The authors have regularly used a needleless suture loop technique to both harvest and prepare autograft gracilis and semitendinosis tendons and to tension quadrupled hamstring tendon grafts during anterior cruciate ligament reconstruction. This cost-effective technique reduces exposure to needles, the time required to harvest and prepare the grafts, and the amount of suture in the tibial tunnel, while providing adequate fixation to tension the tendons as needed.

Extending the notion of customer value to surfing camps.

This study applies the germane principles of service-dominant logic by investigating how different dimensions of service value impact customers' satisfaction and related behavioral intentions in the surf camps context. An empirical model was developed and tested via survey responses from 300 Portuguese surf camps tourists who profiled their experience. Data were analyzed using Structural Equation Modeling, specifically Partial Least Squares (PLS-PM). Results highlight the respective impact the numerous value dimensions (functional, emotional, social, epistemic, experiential, and contextual) have on the overall level of perceived value as well as its resultant impact on satisfaction and repurchase intentions.

Impaired tumor necrosis factor-α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze.

BACKGROUND: Infants with severe respiratory syncytial virus (RSV) bronchiolitis have an increased risk of recurrent wheezing and asthma. We aimed to evaluate the relationships between regulatory T cell (Treg) percentage and cytokine production of in vitro-stimulated CD4+ T cells during acute bronchiolitis and the development of recurrent wheezing in the first 3 years of life. METHODS: We obtained peripheral blood from 166 infants hospitalized with their first episode of RSV-confirmed bronchiolitis. Granzyme B (GZB) expression, and interleukin-10, interferon-γ, tumor necrosis factor-α (TNF-α), IL-4, and IL-5 production by in vitro anti-CD3/CD28- and anti-CD3/CD46-activated CD4+ T cells, and percentage of peripheral Treg (CD4+CD25hi Foxp3hi ) cells were measured by flow cytometry. Wheezing was assessed every 6 months. Recurrent wheezing was defined as three or more episodes following the initial RSV bronchiolitis. RESULTS: Sixty-seven percent (n = 111) of children had wheezing after their initial RSV infection, with 30% having recurrent wheezing. The percentage of peripheral Treg (CD4+CD25hi Foxp3hi ) cells was not significantly different between the wheezing groups. Decreased TNF-α production from anti-CD3/CD28- and anti-CD3/CD46- activated CD4+ T cells was observed in the recurrent wheezers, compared with nonwheezers (p = .048 and .03, respectively). There were no significant differences in the GZB+ CD4+ T cells and production of other inflammatory cytokines between these groups. CONCLUSIONS: We demonstrated lower TNF-α production by in vitro stimulated CD4+ T cells during severe RSV bronchiolitis in children that subsequently developed recurrent wheezing, compared with children with no subsequent wheeze. These findings support the role of CD4+ T cell immunity in the development of subsequent wheezing in these children.

Variability of intraocular pressure measurements in observation participants in the ocular hypertension treatment study.

PURPOSE: To describe variability of intraocular pressure (IOP) measurements within the same eye and between right and left eyes over a 60-month period in participants in the Ocular Hypertension Treatment Study. DESIGN: Analysis of data from a prospective, randomized clinical trial. PARTICIPANTS: Eight hundred ten participants randomized to the observation group. METHODS: Intraocular pressure measurements were obtained at the baseline visit and every 6 months thereafter. Pearson correlation coefficients were calculated for IOP measurements in the same eye between visits and for IOP measurements between right and left eyes of participants at each visit. Differences in IOP measurements between visits are reported in percent change (>15%, >20%, and >30%) and in millimeters of mercury (<3 mmHg, 3-5 mmHg, and >5 mmHg). The effects of regression to the mean, consistency in time of day, and sequence of IOP measurement of right and left eyes were examined. MAIN OUTCOME MEASURES: Correlation of IOP measurements between consecutive 6-month visits. RESULTS: The correlation of IOP measurements within the same eye between consecutive visits was r = 0.62, whereas the correlation of IOP measurements between right and left eyes at the same visit was r = 0.72. Thirteen percent of eyes had >20% change in IOP between consecutive visits. Sixty-six percent of eyes had a change in IOP within 3 mmHg, and 10% of eyes had a change in IOP >5 mmHg between visits. Eyes with a higher baseline IOP had a lower IOP at 6 months. There was a stronger correlation of IOP measured within 2 hours of the time of day between visits (r = 0.56) than >2 hours apart (r = 0.39). IOP of the right eye, which was measured first, was 0.3+/-2.8 mmHg higher than the left eye. CONCLUSIONS: The variability of IOP measurements in the same eye between consecutive visits is moderate and is greater than the variability of IOP measurements between right and left eyes at the same visit. Factors affecting the variability of IOP measurement include regression to the mean, time of day, and measurement order. Knowledge of variability in IOP and its measurements may help clinicians establish a more accurate baseline IOP, target IOP, and assessment of medication effect.

Are more experienced clinicians better able to tolerate uncertainty and manage risks? A vignette study of doctors in three NHS emergency departments in England.

BACKGROUND: Risk aversion among junior doctors that manifests as greater intervention (ordering of tests, diagnostic procedures and so on) has been proposed as one of the possible causes for increased pressure in emergency departments (EDs). Here we tested the prediction that doctors with more experience would be more tolerant of uncertainty and therefore less risk-averse in decision making. METHODS: In this cross-sectional, vignette-based study, doctors working in three EDs were asked to complete a questionnaire measuring experience (length of service in EDs), reactions to uncertainty (Gerrity et al, 1995) and risk aversion (responses about the appropriateness of patient management decisions). RESULTS: Data from 90 doctors were analysed. Doctors had worked in the ED for between 5 weeks and 21 years. We found a large association between experience and risk aversion so that more experienced clinicians made less risk-averse decisions (r=0.47, p<0.001). We also found a large association between experience and reactions to uncertainty (r=-0.50, p<0.001), with more experienced doctors being much more at ease with uncertainty. Mediation analyses indicated that tolerance of uncertainty partially mediated the relationship between experience and lower risk aversion, explaining about a quarter of the effect. CONCLUSION: While we might be tempted to conclude from this research that experience and the ability to tolerate uncertainty lead to positive outcomes for patients (less risk-averse management strategies and higher levels of safety netting), what we are unable to conclude from this design is that these less risk-averse strategies improve patient safety.

The relationship between spindly leg syndrome incidence and water composition, overfeeding, and diet in newly metamorphosed harlequin frogs (Atelopus spp.).

Spindly Leg Syndrome (SLS) is a persistent animal welfare issue associated with the rearing of amphibians in captivity. We conducted two experiments to investigate the effects of diet, water composition and overfeeding on prevalence of SLS in newly metamorphosed harlequin frogs (Atelopus spp.). In our first experiment, we offered 400 full-sibling tadpoles of Atelopus certus isocaloric diets in treatments of 31%, 37%, 42% and 48% crude protein respectively. Tadpoles fed higher protein diets metamorphosed faster, but the incidence of SLS exceeded 80% in all treatments leading to the conclusion that variation in dietary protein was not responsible for causing SLS. We used 720 full-sibling Atelopus glyphus tadpoles in a second experiment to examine the effects of diet type, water composition and diet ration on SLS. We found that an overall incidence of 58% spindly leg in tadpoles reared in tap water, but reduced to about 10% in water treated by reverse osmosis and then reconstituted. It is possible that the reverse osmosis treatment removed some factor that caused the SLS, or that the reconstitution may have added a mineral lacking in the original tap water. Within tap water treatments, overfeeding tadpoles in tanks increased the incidence of SLS. We recommend further experimental research into this condition to identify the causative factors in the water. Additional research into the nutritional composition of food available to wild tadpoles would be useful in formulating captive diets, that have to date been solely based on surrogate species.

Longitudinal changes in visual acuity in keratoconus.

PURPOSE: The present investigation aimed to identify factors that predict reduced visual acuity in keratoconus from a prospective, longitudinal study. METHODS: This report from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study used 7 years of follow-up data from 953 CLEK subjects who did not have penetrating keratoplasty in either eye at baseline and who provided enough data to compute the slope of the change over time in high- or low-contrast best-corrected visual acuity (BCVA). Outcome measures included these slopes and whether the number of letters correctly read decreased by 10 letters or more in at least one eye in 7 years. RESULTS: Mean age of the subjects at the first follow-up visit was 40.2 +/- 11.0 years (mean +/- SD). Overall, 44.4% were female, and 71.9% were white. The slope of the change in high- and low-contrast BCVA (-0.29 +/- 1.5 and -0.58 +/- 1.7 letters correct/year, respectively) translated into expected 7-year decreases of 2.03 high- and 4.06 low-contrast letters correct. High- and low-contrast visual acuity decreases of 10 or more letters correct occurred in 19.0% and 30.8% of subjects, respectively. Independent predictors of reduced high- and low-contrast BCVA included better baseline acuity, steeper first definite apical clearance lens (FDACL), and fundus abnormalities. Each diopter of steeper baseline FDACL predicted an increased deterioration of 0.49 high- and 0.63 low-contrast letters correct. CONCLUSIONS: CLEK Study subjects with keratoconus exhibited a slow but clear decrease in BCVA during follow-up, with low-contrast acuity deteriorating more rapidly than high-contrast. Better baseline BCVA, steeper FDACL, and fundus abnormalities were predictive of greater acuity loss with time.

Estimation of the incidence and factors predictive of corneal scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study.

PURPOSE: The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1209 keratoconus patients. We report methods to define incident corneal scarring and baseline factors predictive of incident corneal scarring in nonsurgical eyes of CLEK Study keratoconus patients through their fifth year of follow-up. METHODS: Of the 1,209 patients, 878 patients with at least one unscarred cornea at baseline were included in this study. The cumulative 5-year incidence of scarring is defined as the proportion of patients who developed central corneal opacification as detected by a clinician examining the patient with a slit-lamp biomicroscope and by masked readings of corneal photographs at the CLEK Photography Reading Center. Logistic regression analysis was used to test for relationships between baseline factors and incident corneal scarring. Baseline factors analyzed included age, sex, race, atopic disease, contact lens wear, family history of keratoconus, corneal curvature, and central corneal fluorescein staining, among others. RESULTS: The 5-year incidence of corneal scarring was 13.7% (120 of 878) overall, 16.7% (102 of 609) for contact lens-wearing eyes, and 38.0% (46 of 121) for contact lens-wearing eyes with corneal curvature greater than 52 D. Baseline factors predictive of incident scarring included corneal curvature greater than 52 D (odds ratio [OR] = 4.79; 95% confidence interval [CI], 3.08, 7.45; P < 0.001), contact lens wear (OR = 2.50; 95% CI, 1.40, 4.76; P = 0.003), marked corneal staining (OR = 2.38; 95% CI, 1.49, 3.76; P = 0.0002), and age less than 20 years (OR = 6.34; 95% CI, 2.57, 15.00; P < 0.0001). CONCLUSIONS: Multivariate analyses of 5-year prospective data from the CLEK Study cohort showed that baseline corneal curvature, contact lens wear, corneal staining, and younger age were predictive of the development of corneal scarring. The 5-year incidence of scarring is 13.7% for the overall sample and 38.0% for those eyes with corneal curvature greater than 52 D that wore contact lenses. Contact lens wear increased the risk of incident scarring more than 2-fold. These findings suggest a causal contribution of contact lens wear to corneal scarring in keratoconus and imply that corneal scarring might be reduced by modifying the contact lens fit.