Quality of Life Outcomes Among Patients Being Screened for Cytomegalovirus Retinitis in Thailand.

PURPOSE: Cytomegalovirus (CMV) retinitis can have debilitating impacts on quality of life (QOL), but few contemporary studies have characterized these ramifications. This study assessed the impact of CMV retinitis on vision-related QOL for those living with HIV/AIDS in Thailand. METHODS: QOL was assessed as part of a prospective interventional cohort study of patients referred to a tertiary hospital in Thailand for CMV retinitis screening. A validated vision-related QOL questionnaire was administered at the baseline screening visit and at the 6-month study visit. Multivariable linear regression models were performed to determine the effect of CMV retinitis diagnosis on QOL score. RESULTS: A total of 152 participants completed the QOL questionnaire at their initial clinic visit. At baseline, a diagnosis of CMV retinitis diagnosis was significantly associated with decreased QOL score: unilateral retinitis was associated with a 0.11 (95% CI: -0.26-0.03) decrement in QOL, and bilateral retinitis was associated with a 0.33 (95% CI: -0.51-0.16) decrement (joint P-value = 0.0009). For the 78 participants with a 6-month visit, changes in QOL from baseline were small and not significant. A diagnosis of CMV retinitis was still associated with decreased QOL score at 6 months (joint P-value = 0.03). CONCLUSIONS: This study found that vision-related QOL was lower in those with CMV retinitis, especially with bilateral involvement, and did not improve after treatment among those with follow-up. These findings reinforce the debilitating clinical manifestations of this disease, and support efforts for earlier screening to detect CMV retinitis before impacts on QOL have occurred.

Sources and Drivers of ARGs in Urban Streams in Atlanta, Georgia, USA.

The spread of antibiotic resistance genes (ARGs) in the aquatic environment is an emerging concern in the interest of protecting public health. Stemming the environmental dissemination of ARGs will require a better understanding of the sources and drivers of ARGs in the water environment. In this study, we used direct measurement of sewage-associated molecular markers, the class 1 integron gene, standard water quality parameters, and watershed characteristics to evaluate the sources and drivers of ARGs in an urban watershed impacted by a gradient of human activities. Quantitative polymerase chain reaction (qPCR) was used to quantify the abundance of the sewage-associated HF183, the E. coli fecal indicator, class 1 integron gene (int1), and the ARGs sulI, sulII, tetW, tetM, ampC, and blaSHV in stream water samples collected from the Proctor Creek watershed in Atlanta, Georgia. Our findings show that ARGs were widely distributed, with detection frequencies of 96% (sulI and sulII), 82% (tetW and tetM), and 49% (ampC and blaSHV). All the ARGs were positively and significantly correlated (r > 0.5) with the HF183 and E. coli markers. Non-linear machine learning models developed using generalized boosting show that more than 70% of the variation in ARG loads in the watershed could be explained by fecal source loading, with other factors such as class 1 integron, which is associated with acquired antibiotic resistance, and environmental factors contributing < 30% to ARG variation. These results suggest that input from fecal sources is a more critical driver of ARG dissemination than environmental stressors or horizontal gene transfer in aquatic environments highly impacted by anthropogenic pollution. Finally, our results provide local watershed managers and stakeholders with information to mitigate the burden of ARGs and fecal bacteria in urban streams.

COVID-19 and Lung Cavitation: A Clue to Pathogenesis?

Description Lung cavitation as a complication of COVID-19 is rare. A 56-year-old male presented with lung cavitation, small volume hemoptysis, and violaceous discoloration of the right great toe, 5 weeks after diagnosis with COVID-19 pneumonia. The digital changes were consistent with previously described microvascular changes called "COVID toe." CT angiography of the chest was negative for pulmonary embolism but showed a 2.5 x 3.1 x 2.2 cm cavitation within the right lung. Extensive evaluation for commonly implicated infectious and autoimmune causes was negative. We concluded that the cavitary lung lesions were likely a complication of COVID-19 pneumonia and may implicate microangiopathy as an important component of pathogenesis. This case highlights a rare complication of COVID-19 of which clinicians should be aware.

Clinic-Based Eye Disease Screening Using Non-Expert Fundus Photo Graders at the Point of Screening: Diagnostic Validity and Yield.

PURPOSE: The intent of this study was to determine the diagnostic accuracy of several diagnostic tests for age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, and cataract, as well as the proportions of patients with eye disease from each of 3 enrolling clinics. DESIGN: Diagnostic accuracy study. METHODS: Patients ≥50 years old in a diabetes, thyroid, and general medicine clinic were screened using visual acuity, tonometry, and fundus photography. Photographs were graded at the point-of-screening by non-ophthalmic personnel. Participants with positive screening test results in either eye and a 10% random sample with negative results in both eyes were referred for an in-person, reference-standard ophthalmology examination. RESULTS: Of 889 participants enrolled, 229 participants failed at least 1 test in either eye, of which 189 presented for an ophthalmic examination. An additional 76 participants with completely normal screening test results were referred for examination, of which 50 attended. Fundus photography screening had the highest yield for DR (sensitivity: 67%; 95% confidence interval [CI]: 39%-87%), visual acuity screening for cataract (sensitivity: 89%; 95% CI: 86%-92%), and intraocular pressure screening for glaucoma or suspected glaucoma (sensitivity: 25%; 95% CI: 14%-40%). The burden of disease was relatively high in all 3 clinics, with at least 1 of the diseases of interest (ie, AMD, DR, glaucoma or suspected glaucoma, or cataract) detected in 25% of participants (95% CI: 17-35%) from the diabeteses clinic, 34% (95% CI: 22%-49%) from the thyroid clinic, and 21% (95% CI: 13%-32%) from the general clinic. CONCLUSIONS: Non-expert eye disease screening in health clinics may be a useful model for detection of eye disease in resource-limited settings.

Sediment and fecal indicator bacteria loading in a mixed land use watershed: Contributions from suspended sediment and bedload transport.

Overland transport of fecal bacteria in water and their resuspension from bed sediments are important transport mechanisms that help explain the transport of enteric pathogens in watersheds. In this study, multiyear monitoring along with regression relationships between sediment and fecal indicator bacteria (FIB) were used to investigate annual loading in the South Fork Broad River watershed, located in northeastern Georgia, USA. Suspended transport was the dominant transport mechanism contributing to in-stream total annual loads for sediment (81.4-98.1%) and FIB (>98%). Annual bedload transport of FIB was small and Escherichia coli (up to 1.8%) contributed more to annual bedload FIB than enterococci (≤0.03%). Bedload contributions of FIB increased with the duration of critical discharge exceedance, indicating a prolonged risk of exposure to enteric pathogens during extended periods of high flows, which is important during major storm events. The risk of exposure to enteric pathogens through pathways such as recreational use and drinking water treatment could be much greater because fecal bacteria are released from sediment during higher flows and dominantly transported in suspension when bedload are not actively moving. Therefore, the combined contribution of fecal bacteria from overland and bedload-associated transport should be considered in risk assessments. Discharge, bedload, and FIB data collected over 2 yr in this study can supplement future hydrologic modeling and microbial risk assessment modeling efforts.

Comparison of Smartphone Photography, Single-Lens Reflex Photography, and Field-Grading for Trachoma.

Conjunctival examination for trachomatous inflammation-follicular (TF) guides public health decisions for trachoma. Smartphone cameras may allow remote conjunctival grading, but previous studies have found low sensitivity. A random sample of 412 children aged 1-9 years received an in-person conjunctival examination and then had conjunctival photographs taken with 1) a single-lens reflex (SLR) camera and 2) a smartphone coupled to a 3D-printed magnifying attachment. Three masked graders assessed the conjunctival photographs for TF. Latent class analysis was used to determine the sensitivity and specificity of each grading method for TF. Single-lens reflex photo-grading was 95.0% sensitive and 93.6% specific, and smartphone photo-grading was 84.1% sensitive and 97.6% specific. The sensitivity of the smartphone-CellScope device was considerably higher than that of a previous study using the native smartphone camera, without attachment. Magnification of smartphone images with a simple attachment improved the grading sensitivity while maintaining high specificity in a region with hyperendemic trachoma.

Association of Federal Regulations in the United States and Canada With Potential Corneal Donation by Men Who Have Sex With Men.

Importance: Federal policy in the United States prohibits corneal donation by men who have had sex with another man (MSM) in the preceding 5 years, whereas Canada enforces a 12-month ban. The potential consequences of these policies on corneal donations should be evaluated. Objective: To estimate the number of potential corneal donations associated with MSM deferral policies in the United States and Canada. Design, Setting, and Participants: A nonvalidated telephone survey study was conducted of all 65 eye banks in the United States and Canada to investigate how many potential corneal donors were disqualified in 2018 because of federal MSM restrictions. Published demographic data were also used to arrive at a separate estimate. Survey data were gathered from May 2019 to February 2020. Main Outcomes and Measures: Eye banks were asked if they keep records of referrals disqualified specifically because of the federal MSM restrictions and, if so, how many referrals they disqualified in 2018 owing to MSM status. Results: Fifty-four of 65 eye banks (83%) responded to the survey, with 30 eye banks reporting they do not keep specific records of MSM deferrals. The remaining 24 eye banks reported disqualifying 360 referrals in 2018 because of MSM status, equating to 720 corneas. The 24 eye banks accounted for 46.2% of corneal donations in the United States and Canada in 2018, yielding an estimate of approximately 1558 corneas rejected that year because of MSM status. A separate estimate using published MSM demographic data indicates that up to 3217 potential corneal donations may have been disqualified in 2018 because of these federal policies. Conclusions and Relevance: Findings suggest that between 1558 and 3217 corneal donations were disqualified in 2018 because of federal regulations prohibiting corneal donation by men who have had sex with another man in the preceding 5 years in the United States or 1 year in Canada. With modern virologic testing that is reliable within days of HIV exposure and given the global shortage of corneal tissue, these policies should be reevaluated using current scientific evidence to increase the availability of vision-restoring surgery worldwide.

Evaluation of the soil and water assessment tool (SWAT) for simulating E. coli concentrations at the watershed-scale.

Water quality management at the watershed level requires a framework to identify sources, apportion water quality risks and develop mitigation strategies to reduce health risks. Watershed-scale models have been used as a support tool to understand the sources, fate and transport of fecal bacteria and pathogens in the environment. The Soil and Water Assessment Tool (SWAT) model was applied in this study to understand the sources and drivers of microbial water quality in the Clouds Creek watershed in Georgia, USA. A criterion to evaluate the performance of the SWAT bacterial model was also developed in this study using the Nash-Sutcliffe Efficiency (NSE) performance measure. The SWAT model was successfully calibrated and validated for flow with Nash-Sutcliffe Efficiency (NSE) of 0.81 and 0.55, respectively. Escherichia coli (E. coli) predictions were good with NSE of 0.32 and 0.34 for the calibration and validation timeframes, respectively. Based on the criteria developed in this study, SWAT bacterial model for E. coli and fecal coliform can be judged as "satisfactory" when NSE > 0.20. The contribution of sources followed this order: in-stream cattle manure deposition > cattle manure application > poultry manure application > septic systems > wildlife manure, suggesting that a reduction in livestock access to streams would be the most effective approach to reduce fecal bacterial loads in this watershed and others impacted by fecal contamination. Finally, our results suggest that the SWAT model is capable of simulating E. coli dynamics in the Clouds Creek watershed and can provide insights into source impacts for risk management.

Accuracy of computer-assisted vertical cup-to-disk ratio grading for glaucoma screening.

PURPOSE: Glaucoma screening can be performed by assessing the vertical-cup-to-disk ratio (VCDR) of the optic nerve head from fundus photography, but VCDR grading is inherently subjective. This study investigated whether computer software could improve the accuracy and repeatability of VCDR assessment. METHODS: In this cross-sectional diagnostic accuracy study, 5 ophthalmologists independently assessed the VCDR from a set of 200 optic disk images, with the median grade used as the reference standard for subsequent analyses. Eight non-ophthalmologists graded each image by two different methods: by visual inspection and with assistance from a custom-made publicly available software program. Agreement with the reference standard grade was assessed for each method by calculating the intraclass correlation coefficient (ICC), and the sensitivity and specificity determined relative to a median ophthalmologist grade of ≥0.7. RESULTS: VCDR grades ranged from 0.1 to 0.9 for visual assessment and from 0.1 to 1.0 for software-assisted grading, with a median grade of 0.4 for each. Agreement between each of the 8 graders and the reference standard was higher for visual inspection (median ICC 0.65, interquartile range 0.57 to 0.82) than for software-assisted grading (median ICC 0.59, IQR 0.44 to 0.71); P = 0.02, Wilcoxon signed-rank test). Visual inspection and software assistance had similar sensitivity and specificity for detecting glaucomatous cupping. CONCLUSION: The computer software used in this study did not improve the reproducibility or validity of VCDR grading from fundus photographs compared with simple visual inspection. More clinical experience was correlated with higher agreement with the ophthalmologist VCDR reference standard.

Smartphone photography as a possible method of post-validation trachoma surveillance in resource-limited settings.

BACKGROUND: Validation of trachoma elimination requires monitoring after discontinuation of trachoma program activities, though such evaluations are not commonly done. METHODS: Conjunctival examinations and smartphone photography were performed on a random sample of pre-school children from 15 villages in a region of Burkina Faso thought to have eliminated trachoma. RESULTS: No clinically active trachoma was detected by in-field or photographic evaluation. Smartphone images demonstrated high agreement with field grading (>99% concordance). CONCLUSIONS: Trachoma appears to have been eliminated from this area of Burkina Faso. Smartphone cameras may be a useful aid for monitoring in resource-limited settings.

Visual acuity outcomes in cytomegalovirus retinitis: early versus late diagnosis.

AIMS: To determine if early dilated fundus examination for cytomegalovirus (CMV) retinitis leads to better visual outcomes in areas with limited HIV care, where patients may have long-standing retinitis before they are diagnosed with HIV. METHODS: Twenty-four eyes of 17 patients with CMV retinitis who were seen at an urban HIV clinic in Chiang Mai, Thailand, were included in this retrospective cohort study. Participants were divided into two groups based on the amount of time from the first documented CD4 count below 100 cells/mm3 to the first eye examination for CMV retinitis. Average visual acuity in each group was calculated at the time CMV retinitis was first detected, and then at 3, 6 and 12 months after diagnosis. RESULTS: The group of patients who received an eye examination within approximately 4 months of the initial low CD4 count measurement had better baseline visual acuity (median 20/30,IQR 20/20 to 20/60) compared with patients who presented later (median 20/80, 20/60 to hand motion); p=0.03). Visual acuity did not change significantly during the 12-month study period in either the early group (p=0.69) or late group (p=0.17). CONCLUSION: In this study, patients who were examined sooner after a low CD4 count had better vision than patients who were examined later. Routine early screening of patients with CD4 counts under below 100 cells/mm3 may detect earlier disease and prevent vision loss.

Effect of Antibiotics on Short-Term Growth among Children in Burkina Faso: A Randomized Trial.

Antibiotics improve both weight and height gain in randomized trials of preschool children with preexisting morbidity. Here, we assess the effect of a short course of three different antibiotics (amoxicillin, azithromycin, and cotrimoxazole) on short-term linear and ponderal growth in a population-based sample of preschool children in rural Burkina Faso. We randomized households with at least two children in the Nouna district, Burkina Faso, to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic-randomized household, one child was randomly assigned to receive the antibiotic and the other to receive the placebo. Weight and height measurements were taken at baseline and 30 days following the last study medication dose. Weight-for-height Z (WHZ), height-for-age Z (HAZ), and weight-for-age Z (WAZ) scoreswere calculated based on the 2006 World Health Organization standards. Of the 124 households and 248 children enrolled, 229 had anthropometry measurements at 1 month and were analyzed. Children randomized to amoxicillin gained significantly more weight compared with both the placebo household (mean difference 317 g, 95% confidence interval [CI]: 115-519 g) and placebo sibling (mean difference 315 g, 95% CI: 147-482 g) controls. Growth velocity in g/kg/day, and WHZ and WAZ scores were higher in amoxicillin-treated children compared with placebo households and siblings. There were no differences in weight gain in children randomized to azithromycin or cotrimoxazole compared with placebo households or placebo siblings. There were no differences in height gain or HAZ across any of the study arms. Amoxicillin may have short-term growth-promoting effects in healthy children.

Dietary diversity and nutritional status among children in rural Burkina Faso.

Background: Burkina Faso has a seasonal malnutrition pattern, with higher malnutrition prevalence during the rainy season when crop yields are low. We investigated the association between dietary diversity and nutritional status among children aged 6-59 mo during the low crop yield season in rural Burkina Faso to assess the role of dietary diversity during the lean season on childhood nutritional status. Methods: Caregivers reported the dietary diversity of the past 7 d, consisting of 11 food groups, summed into a scale. Anthropometric measurements were taken from all children. Height-for-age (HAZ), weight-for-height (WHZ) and weight-for-age (WAZ) z-scores were calculated based on 2006 WHO standards. Stunting, wasting and underweight were defined as HAZ, WHZ and WAZ <-2 SD, respectively. Multivariable regression models adjusting for potential confounders including household food insecurity and animal ownership were used to assess the relationship between anthropometric indices and dietary diversity. Results: Of 251 children enrolled in the study, 20.6% were stunted, 10.0% wasted and 13.9% underweight. Greater dietary diversity was associated with greater HAZ (SD 0.14, 95% CI 0.04 to 0.25) among all children. There was no association between dietary diversity and wasting or mid-upper arm circumference in this study. Conclusions: Increasing dietary diversity may be an approach to reduce the burden of stunting and chronic malnutrition among young children in regions with seasonal food insecurity.

Greater distance to an academic medical center is associated with poorer melanoma prognostic factors: The University of Colorado Experience.

INTRODUCTION: Numerous studies report a correlation between distance to diagnostic provider in an academic medical center and poorer prognosis ofdisease. Limited research on this topic exists with respect to melanoma. METHODS: This was a retrospective chart review of 1,463 adults (≥18 years) initially diagnosed with melanoma between 2006-2016. Associations between distance traveled and Breslow depth and presence of metastatic disease were assessed via cumulative and binary logistic regression models, adjusting for patient and tumor characteristics. RESULTS: Subjects traveling ≥50 miles had 58% greater odds of having an increased Breslow depth than those traveling less than that distance (OR: 1.58; 95% CI: 1.24-2.01; p<0.0001), and had four times the odds of presenting with metastatic disease (OR: 4.04; 95% CI: 3.00-5.46; p<0.0001). DISCUSSION: We highlight the correlation between increased distance to our academic medical center with greater Breslow depths and the presence ofmetastatic disease at presentation. CONCLUSION: Future studies assessing other factors and regional differences that limit access to diagnosis might help improve screening efforts to prevent poorer prognosis for patients in these areas.

Development of a Sensitive Outcome for Economical Drug Screening for Progressive Multiple Sclerosis Treatment.

Therapeutic advance in progressive multiple sclerosis (MS) has been very slow. Based on the transformative role magnetic resonance imaging (MRI) contrast-enhancing lesions had on drug development for relapsing-remitting MS, we consider the lack of sensitive outcomes to be the greatest barrier for developing new treatments for progressive MS. The purpose of this study was to compare 58 prospectively acquired candidate outcomes in the real-world situation of progressive MS trials to select and validate the best-performing outcome. The 1-year pre-treatment period of adaptively designed IPPoMS (ClinicalTrials.gov #NCT00950248) and RIVITaLISe (ClinicalTrials.gov #NCT01212094) Phase II trials served to determine the primary outcome for the subsequent blinded treatment phase by comparing 8 clinical, 1 electrophysiological, 1 optical coherence tomography, 7 MRI volumetric, 9 quantitative T1 MRI, and 32 diffusion tensor imaging MRI outcomes. Fifteen outcomes demonstrated significant progression over 1 year (Δ) in the predetermined analysis and seven out of these were validated in two independent cohorts. Validated MRI outcomes had limited correlations with clinical scales, relatively poor signal-to-noise ratios (SNR) and recorded overlapping values between healthy subjects and MS patients with moderate-severe disability. Clinical measures correlated better, even though each reflects a somewhat different disability domain. Therefore, using machine-learning techniques, we developed a combinatorial weight-adjusted disability score (CombiWISE) that integrates four clinical scales: expanded disability status scale (EDSS), Scripps neurological rating scale, 25 foot walk and 9 hole peg test. CombiWISE outperformed all clinical scales (Δ = 9.10%; p = 0.0003) and all MRI outcomes. CombiWISE recorded no overlapping values between healthy subjects and disabled MS patients, had high SNR, and predicted changes in EDSS in a longitudinal assessment of 98 progressive MS patients and in a cross-sectional cohort of 303 untreated subjects. One point change in EDSS corresponds on average to 7.50 point change in CombiWISE with a standard error of 0.10. The novel validated clinical outcome, CombiWISE, outperforms the current broadly utilized MRI brain atrophy outcome and more than doubles sensitivity in detecting clinical deterioration in progressive MS in comparison to the scale traditionally used for regulatory approval, EDSS.

Characterizing relationships among fecal indicator bacteria, microbial source tracking markers, and associated waterborne pathogen occurrence in stream water and sediments in a mixed land use watershed.

Bed sediments of streams and rivers may store high concentrations of fecal indicator bacteria (FIB) and pathogens. Due to resuspension events, these contaminants can be mobilized into the water column and affect overall water quality. Other bacterial indicators such as microbial source tracking (MST) markers, developed to determine potential sources of fecal contamination, can also be resuspended from bed sediments. The primary objective of this study was to predict occurrence of waterborne pathogens in water and streambed sediments using a simple statistical model that includes traditionally measured FIB, environmental parameters and source allocation, using MST markers as predictor variables. Synoptic sampling events were conducted during baseflow conditions downstream from agricultural (AG), forested (FORS), and wastewater pollution control plant (WPCP) land uses. Concentrations of FIB and MST markers were measured in water and sediments, along with occurrences of the enteric pathogens Campylobacter, Listeria and Salmonella, and the virulence gene that carries Shiga toxin, stx2. Pathogens were detected in water more often than in underlying sediments. Shiga toxin was significantly related to land use, with concentrations of the ruminant marker selected as an independent variable that could correctly classify 76% and 64% of observed Shiga toxin occurrences in water and sediment, respectively. FIB concentrations and water quality parameters were also selected as independent variables that correctly classified Shiga toxin occurrences in water and sediment (54%-87%), and Salmonella occurrences in water (96%). Relationships between pathogens and indicator variables were generally inconsistent and no single indicator adequately described occurrence of all pathogens. Because of inconsistent relationships between individual pathogens and FIB/MST markers, incorporating a combination of FIB, water quality measurements, and MST markers may be the best way to assess microbial water quality in mixed land use systems.

Decay of fecal indicator bacterial populations and bovine-associated source-tracking markers in freshly deposited cow pats.

Understanding the survival of fecal indicator bacteria (FIB) and microbial source-tracking (MST) markers is critical to developing pathogen fate and transport models. Although pathogen survival in water microcosms and manure-amended soils is well documented, little is known about their survival in intact cow pats deposited on pastures. We conducted a study to determine decay rates of fecal indicator bacteria (Escherichia coli and enterococci) and bovine-associated MST markers (CowM3, Rum-2-bac, and GenBac) in 18 freshly deposited cattle feces from three farms in northern Georgia. Samples were randomly assigned to shaded or unshaded treatment in order to determine the effects of sunlight, moisture, and temperature on decay rates. A general linear model (GLM) framework was used to determine decay rates. Shading significantly decreased the decay rate of the E. coli population (P < 0.0001), with a rate of -0.176 day(-1) for the shaded treatment and -0.297 day(-1) for the unshaded treatment. Shading had no significant effect on decay rates of enterococci, CowM3, Rum-2-bac, and GenBac (P > 0.05). In addition, E. coli populations showed a significant growth rate (0.881 day(-1)) in the unshaded samples during the first 5 days after deposition. UV-B was the most important parameter explaining the decay rate of E. coli populations. A comparison of the decay behaviors among all markers indicated that enterococcus concentrations exhibit a better correlation with the MST markers than E. coli concentrations. Our results indicate that bovine-associated MST markers can survive in cow pats for at least 1 month after excretion, and although their decay dynamic differs from the decay dynamic of E. coli populations, they seem to be reliable markers to use in combination with enterococci to monitor fecal pollution from pasture lands.