Trachomatous Scar Ranking: A Novel Outcome for Trachoma Studies.
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ABSTRACT:
SUBMITTER: Baldwin A
PROVIDER: S-EPMC5462575 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
Publications
Trachomatous Scar Ranking: A Novel Outcome for Trachoma Studies.
Baldwin Angela A Ryner Alexander M AM Tadesse Zerihun Z Shiferaw Ayalew A Callahan Kelly K Fry Dionna M DM Zhou Zhaoxia Z Lietman Thomas M TM Keenan Jeremy D JD
The American journal of tropical medicine and hygiene 20170601 6
AbstractWe evaluated a new trachoma scarring ranking system with potential use in clinical research. The upper right tarsal conjunctivas of 427 individuals from Ethiopian villages with hyperendemic trachoma were photographed. An expert grader first assigned a scar grade to each photograph using the 1981 World Health Organization (WHO) grading system. Then, all photographs were ranked from least (rank = 1) to most scarring (rank = 427). Photographic grading found 79 (18.5%) conjunctivae without s ...[more]
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Project description:PurposeUnfavorable outcomes after trachomatous trichiasis (TT) surgery are undermining the global trachoma elimination effort. This analysis investigates predictors of postoperative TT (PTT), eyelid contour abnormalities (ECAs), and granuloma in the 2 most common TT surgery procedures: posterior lamellar tarsal rotation (PLTR) and bilamellar tarsal rotation (BLTR).DesignSecondary data analysis from a randomized, controlled, single-masked clinical trial.ParticipantsA total of 1000 patients with TT, with lashes touching the eye or evidence of epilation, in association with tarsal conjunctival scarring.MethodsParticipants were randomly allocated and received BLTR (n = 501) or PLTR (n = 499) surgery. Disease severity at baseline, surgical incisions, sutures, and corrections were graded during and immediately after surgery. Participants were examined at 6 and 12 months by assessors masked to allocation.Main outcome measuresPredictors of PTT, ECA, and granuloma.ResultsData were available for 992 (99.2%) trial participants (496 in each arm). There was strong evidence that performing more peripheral dissection with scissors in PLTR (odd ratio [OR], 0.70; 95% confidence interval [CI], 0.54-0.91; P = 0.008) and BLTR (OR, 0.83; 95% CI, 0.72-0.96; P = 0.01) independently protected against PTT. Baseline major trichiasis and mixed location lashes and immediate postoperative central undercorrection independently predicted PTT in both surgical procedures. Peripheral lashes in PLTR (OR, 5.91; 95% CI, 1.48-23.5; P = 0.01) and external central incision height ?4 mm in BLTR (OR, 2.89; 95% CI, 1.55-5.41; P = 0.001) were independently associated with PTT. Suture interval asymmetry of >2 mm (OR, 3.18; 95% CI, 1.31-7.70; P = 0.01) in PLTR and baseline conjunctival scarring in BLTR (OR, 1.72; 95% CI, 1.06-2.81; P = 0.03) were independently associated with ECA. Older age was independently associated with ECA in both PLTR (P value for trend < 0.0001) and BLTR (P value for trend = 0.03). There was substantial intersurgeon variability in ECA rates for both PLTR (range, 19.0%-36.2%) and BLTR (range, 6.1%-28.7%) procedures. In PLTR surgery, irregular posterior lamellar incision at the center of the eyelid (OR, 6.72; 95% CI, 1.55-29.04; P = 0.01) and ECA (OR, 3.08; 95% CI, 1.37-6.94; P = 0.007) resulted in granuloma formation.ConclusionsPoor postoperative outcomes in TT surgery were associated with inadequate peripheral dissection, irregular incision, asymmetric suture position and tension, inadequate correction, and lash location. Addressing these will improve TT surgical outcomes.
| S-EPMC5540045 | biostudies-literature
Project description:BackgroundAlthough trachoma causes more cases of preventable blindness than any other infectious disease, a combination of strategies is reducing its global prevalence. As a district moves toward eliminating trachoma as a public health problem, national programs conduct trachoma impact surveys (TIS) to assess whether to stop preventative interventions and trachoma surveillance surveys (TSS) to determine whether the prevalence of active trachoma has rebounded after interventions have halted. In some contexts, programs also conduct trachomatous trichiasis (TT)-only surveys. A few costing studies of trachoma prevalence surveys exist, but none examine TIS, TSS, or TT-only surveys.Methodology/principal findingsWe assessed the incremental financial cost to the national program of TIS, TSS, and TT-only surveys, which are standardized cluster-sampled prevalence surveys. We conducted a retrospective review of expenditures and grant disbursements for TIS and TSS in 322 evaluation units in 11 countries between 2011 and 2018. We also assessed the costs of three pilot and five standard TT-only surveys in four countries between 2017 and 2018. The median cost of TIS and TSS was $8,298 per evaluation unit [interquartile range (IQR): $6,532-$10,111, 2017 USD]. Based on a linear regression with bootstrapped confidence intervals, after controlling for country, costs per survey did not change significantly over time but did decline by $83 per survey implemented in a single round (95% CI: -$108 --$63). Of total costs, 80% went to survey fieldwork; of that, 58% went towards per diems and 38% towards travel. TT-only surveys cost a median of $9,707 (IQR: $8,537-$11,635); within a given country, they cost slightly more (106% [IQR: 94%-136%]) than TIS and TSS.Conclusions/significanceThe World Health Organization requires trachoma prevalence estimates for validating the elimination of trachoma as a public health problem. This study will help programs improve their planning as they assemble resources for that effort.
| S-EPMC6728015 | biostudies-literature
Project description:BackgroundOver 1.2 million people are blind from trachomatous trichiasis (TT). Lid rotation surgery is the mainstay of treatment, but recurrence rates can be high. We investigated the outcomes (recurrence rates and other complications) of posterior lamellar tarsal rotation (PLTR) surgery, one of the two most widely practised TT procedures in endemic settings.Methodology/principal findingsWe conducted a two-year follow-up study of 1300 participants who had PLTR surgery, conducted by one of five TT nurse surgeons. None had previously undergone TT surgery. All participants received a detailed trachoma eye examination at baseline and 6, 12, 18 and 24 months post-operatively. The study investigated the recurrence rates, other complications and factors associated with recurrence. Recurrence occurred in 207/635 (32.6%) and 108/641 (16.9%) of participants with pre-operative major (>5 trichiatic lashes) and minor (<5 lashes) TT respectively. Of the 315 recurrences, 42/315 (3.3% overall) had >5 lashes (major recurrence). Recurrence was greatest in the first six months after surgery: 172 cases (55%) occurring in this period. Recurrence was associated with major TT pre-operatively (OR 2.39, 95% CI 1.83-3.11), pre-operative entropic lashes compared to misdirected/metaplastic lashes (OR 1.99, 95% CI 1.23-3.20), age over 40 years (OR 1.59, 95% CI 1.14-2.20) and specific surgeons (surgeon recurrence risk range: 18%-53%). Granuloma occurred in 69 (5.7%) and notching in 156 (13.0%).Conclusions/significanceRisk of recurrence is high despite high volume, highly trained surgeons. However, the vast majority are minor recurrences, which may not have significant corneal or visual consequences. Inter-surgeon variation in recurrence is concerning; surgical technique, training and immediate post-operative lid position require further investigation.
| S-EPMC3749971 | biostudies-literature
Project description:BackgroundTrachoma, a chronic conjunctivitis caused by Chlamydia trachomatis, is the leading infectious cause of blindness worldwide. Trachoma has been targeted for elimination as a public health problem which includes reducing trachomatous inflammation-follicular prevalence in children and reducing trachomatous trichiasis prevalence in adults. The rate of development of trachomatous trichiasis, the potentially blinding late-stage trachoma sequelae, depends on the rate of trachomatous scarring development and progression. Few studies to date have evaluated the progression of trachomatous scarring in communities that have recently transitioned to a low trachomatous inflammation-follicular prevalence.Methodology/principal findingsWomen aged 15 and older were randomly selected from households in 48 communities within Kongwa district, Tanzania and followed over 3.5 years for this longitudinal study. Trachomatous inflammation-follicular prevalence was 5% at baseline and at follow-up in children aged 1-9 in Kongwa, Tanzania. 1018 women aged 15 and older had trachomatous scarring at baseline and were at risk for trachomatous scarring progression; 691 (68%) completed follow-up assessments. Photographs of the upper tarsal conjunctiva were obtained at baseline and follow-up and graded for trachomatous scarring using a previously published four-step severity scale. The overall cumulative 3.5-year progression rate of scarring was 35.3% (95% CI 31.6-39.1). The odds of TS progression increased with an increase in age in women younger than 50, (OR 1.03, 95% CI 1.01-1.05, p = 0.005) as well as an increase in the household poverty index (OR 1.29, 95% CI 1.13-1.48, p = 0.0002).Conclusions/significanceThe 3.5-year progression of scarring among women in Kongwa, a formerly hyperendemic now turned hypoendemic district in central Tanzania, was high despite a low active trachoma prevalence. This suggests that the drivers of scarring progression are likely not related to on-going trachoma transmission in this district.
| S-EPMC8604323 | biostudies-literature
Project description:BackgroundEfforts are underway to eliminate trachoma as a public health problem by 2020. Programmatic guidelines are based on clinical signs that correlate poorly with Chlamydia trachomatis (Ct) infection in post-treatment and low-endemicity settings. Age-specific seroprevalence of anti Ct Pgp3 antibodies has been proposed as an alternative indicator of the need for intervention. To standardise the use of these tools, it is necessary to develop an analytical approach that performs reproducibly both within and between studies.MethodologyDried blood spots were collected in 2014 from children aged 1-9 years in Laos (n = 952) and Uganda (n = 2700) and from people aged 1-90 years in The Gambia (n = 1868). Anti-Pgp3 antibodies were detected by ELISA. A number of visual and statistical analytical approaches for defining serological status were compared.Principal findingsSeroprevalence was estimated at 11.3% (Laos), 13.4% (Uganda) and 29.3% (The Gambia) by visual inspection of the inflection point. The expectation-maximisation algorithm estimated seroprevalence at 10.4% (Laos), 24.3% (Uganda) and 29.3% (The Gambia). Finite mixture model estimates were 15.6% (Laos), 17.1% (Uganda) and 26.2% (The Gambia). Receiver operating characteristic (ROC) curve analysis using a threshold calibrated against external reference specimens estimated the seroprevalence at 6.7% (Laos), 6.8% (Uganda) and 20.9% (The Gambia) when the threshold was set to optimise Youden's J index. The ROC curve analysis was found to estimate seroprevalence at lower levels than estimates based on thresholds established using internal reference data. Thresholds defined using internal reference threshold methods did not vary substantially between population samples.ConclusionsInternally calibrated approaches to threshold specification are reproducible and consistent and thus have advantages over methods that require external calibrators. We propose that future serological analyses in trachoma use a finite mixture model or expectation-maximisation algorithm as a means of setting the threshold for ELISA data. This will facilitate standardisation and harmonisation between studies and eliminate the need to establish and maintain a global calibration standard.
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Project description:In cancer research, high-throughput genomic studies have been extensively conducted, searching for markers associated with cancer diagnosis, prognosis and variation in response to treatment. In this article, we analyze cancer prognosis studies and investigate ranking markers based on their marginal prognosis power. To avoid ambiguity, we focus on microarray gene expression studies where genes are the markers, but note that the methodology and results are applicable to other high-throughput studies. The objectives of this study are 2-fold. First, we investigate ranking markers under three commonly adopted semiparametric models, namely the Cox, accelerated failure time and additive risk models. Data analysis shows that the ranking may vary significantly under different models. Second, we describe a nonparametric concordance measure, which has roots in the time-dependent ROC (receiver operating characteristic) framework and relies on much weaker assumptions than the semiparametric models. In simulation, it is shown that ranking using the concordance measure is not sensitive to model specification whereas ranking under the semiparametric models is. In data analysis, the concordance measure generates rankings significantly different from those under the semiparametric models.
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Project description:BackgroundDesirability of outcome ranking (DOOR) is an innovative approach in clinical trials to evaluate the global benefits and risks of an intervention. We developed and validated a DOOR endpoint for Staphylococcus aureus bloodstream infection (BSI) through a survey to infectious diseases clinicians and secondary analysis of trial data.MethodsWe administered a survey of 20 cases of S. aureus BSI, asking respondents to rank outcomes by global desirability. Correlations and percentage of pairwise agreement among rankings were estimated to inform development of a DOOR endpoint, which was applied to 2 prior S. aureus BSI trials. The probability that a patient randomly assigned to experimental treatment would have a better DOOR ranking than if assigned to control was estimated. Results were also analyzed using partial credit, which is analogous to scoring an academic test, assigning 100% to the most desirable outcome, 0% to the least, and "partial credit" to intermediate ranks.ResultsForty-two recipients (97%) completed the survey. The DOOR endpoint fitting these rankings (r = 0.89; 95% confidence interval, 0.67 to 0.94) incorporated survival plus cumulative occurrence of adverse events, cure, infectious complications, and ongoing symptoms. Tailored versions of this endpoint were applied to 2 S. aureus BSI trials, and both demonstrated no benefit of the experimental treatment using DOOR and partial credit analysis.ConclusionsUsing S. aureus BSI as an exemplar, we developed a DOOR endpoint that can be used as a template for development of DOOR endpoints for other diseases. Future trials can incorporate DOOR to allow for global assessment of patient experience.
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Project description:Genome-wide association studies (GWAS) analyze genetic variation (SNPs) across the entire human genome, searching for SNPs that are associated with certain phenotypes, most often diseases, such as breast cancer. In GWAS, we seek a ranking of SNPs in terms of their relevance to the given phenotype. However, because certain SNPs are known to be highly correlated with one another across individuals, it can be beneficial to take into account these correlations when ranking. If a SNP appears associated with the phenotype, and we question whether this association is real, the extent to which its neighbors (correlated SNPs) also appear associated can be informative. Therefore, we propose CollectRank, a ranking approach which allows SNPs to reinforce one another via the correlation structure. CollectRank is loosely analogous to the well-known PageRank algorithm. We first evaluate CollectRank on synthetic data generated from a variety of genetic models under different settings. The numerical results suggest CollectRank can significantly outperform common GWAS methods at the cost of a small amount of extra computation. We further evaluate CollectRank on two real-world GWAS on breast cancer and atrial fibrillation/flutter, and CollectRank performs well in both studies. We finally provide a theoretical analysis that also suggests CollectRank's advantages.
| S-EPMC7191672 | biostudies-literature
Project description:Consensus-scoring methods are commonly used with molecular docking in virtual screening campaigns to filter potential ligands for a protein target. Traditional consensus methods combine results from different docking programs by averaging the score or rank of each molecule obtained from individual programs. Unfortunately, these methods fail if one of the docking programs has poor performance, which is likely to occur due to training-set dependencies and scoring-function parameterization. In this work, we introduce a novel consensus method that overcomes these limitations. We combine the results from individual docking programs using a sum of exponential distributions as a function of the molecule rank for each program. We test the method over several benchmark systems using individual and ensembles of target structures from diverse protein families with challenging decoy/ligand datasets. The results demonstrate that the novel method outperforms the best traditional consensus strategies over a wide range of systems. Moreover, because the novel method is based on the rank rather than the score, it is independent of the score units, scales and offsets, which can hinder the combination of results from different structures or programs. Our method is simple and robust, providing a theoretical basis not only for molecular docking but also for any consensus strategy in general.
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Project description:When identifying differentially expressed (DE) genes from high-throughput gene expression measurements, we would like to take both statistical significance (such as P-value) and biological relevance (such as fold change) into consideration. In gene set enrichment analysis (GSEA), a score that can combine fold change and P-value together is needed for better gene ranking.We defined a gene significance score ?-value by combining expression fold change and statistical significance (P-value), and explored its statistical properties. When compared to various existing methods, ?-value based approach is more robust in selecting DE genes, with the largest area under curve in its receiver operating characteristic curve. We applied ?-value to GSEA and found it comparable to P-value and t-statistic based methods, with added protection against false discovery in certain situations. Finally, in a gene functional study of breast cancer profiles, we showed that using ?-value helps elucidating otherwise overlooked important biological functions.http://gccri.uthscsa.edu/Pi_Value_Supplementary.aspxy@ieee.org, cheny8@uthscsa.eduSupplementary data are available at Bioinformatics online.
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