Diagnostic accuracy of qPCR and microscopy for cutaneous leishmaniasis in rural Ecuador: A Bayesian latent class analysis.

BACKGROUND: Clinical and laboratory diagnosis of cutaneous leishmaniasis (CL) is hampered by under-ascertainment of direct microscopy. METHODS: This study compared the diagnostic accuracy of qPCR on DNA extracted from filter paper to the accuracy of direct smear slide microscopy in participants presenting with a cutaneous lesion suspected of leishmaniasis to 16 rural healthcare centers in the Ecuadorian Amazon and Pacific regions, from January 2019 to June 2021. We used Bayesian latent class analysis to estimate test sensitivity, specificity, likelihood ratios (LR), and predictive values (PV) with their 95% credible intervals (95%CrI). The impact of sociodemographic and clinical characteristics on predictive values was assessed as a secondary objective. RESULTS: Of 320 initially included participants, paired valid test results were available and included in the diagnostic accuracy analysis for 129 from the Amazon and 185 from the Pacific region. We estimated sensitivity of 68% (95%CrI 49% to 82%) and 73% (95%CrI 73% to 83%) for qPCR, and 51% (95%CrI 36% to 66%) and 76% (95%CrI 65% to 86%) for microscopy in the Amazon and Pacific region, respectively. In the Amazon, with an estimated disease prevalence among participants of 73%, negative PV for qPCR was 54% (95%CrI 5% to 77%) and 44% (95%CrI 4% to 65%) for microscopy. In the Pacific, (prevalence 88%) the negative PV was 34% (95%CrI 3% to 58%) and 37% (95%CrI 3% to 63%). The addition of qPCR parallel to microscopy in the Amazon increases the observed prevalence from 38% to 64% (+26 (95%CrI 19 to 34) percentage points). CONCLUSION: The accuracy of either qPCR on DNA extracted from filter paper or microscopy for CL diagnosis as a stand-alone test seems to be unsatisfactory and region-dependent. We recommend further studies to confirm the clinically relevant increment found in the diagnostic yield due to the addition of qPCR.

Leishmania species and clinical characteristics of Pacific and Amazon cutaneous leishmaniasis in Ecuador and determinants of health-seeking delay: a cross-sectional study.

BACKGROUND: Cutaneous Leishmaniasis (CL) affects up to 5.000 people in Ecuador each year. L. guyanensis and L. braziliensis are the most common of the eight CL-causing Leishmania species. Earlier CL research concentrated on the easily accessible Pacific region. This study aims to describe the Leishmania species in Pacific and Amazon ecoregions, to analyze regional differences in CL patient clinical presentation, and to identify determinants of health-seeking delay. METHODS: All cases in this cross-sectional study were diagnosed using smear slide microscopy, PCR, or both. Cytochrome B gene sequencing was used to identify the causative Leishmania species in qPCR-positive samples. RESULTS: This study included 245 patients, with 154 (63%) infected in the Pacific region and 91 (37%) infected in the Amazon. Causative Leishmania species were identified in 135 patients (73% of qPCR positives). L. guyanensis was identified in 76% (102/135) of the samples and L. braziliensis in 19% (26/135). The Pacific region had a low prevalence of 6% (5/89) of L. braziliensis. For the first time, we report L. guyanensis from the central Amazon, L. braziliensis from the northern Pacific, and L. lainsoni from both the central Amazon and northern Pacific. Amazon cases had a longer median health-seeking delay in months (2.0, IQR 3.0) than Pacific cases (1.0, IQR 1.5). Prolonged health-seeking delay was associated with older age, Amerindian ethnicity, infection at lower altitudes, non-ulcerative lesions, and lesions on the lower limbs. CONCLUSIONS: In the Pacific region, health-seeking delay is relatively short and L. braziliensis prevalence remains low. Limited access to health care and stigma might explain the prolonged health-seeking delay in the Amazon. We recommend larger studies on the distribution of Leishmania species in Amazon CL cases and additional regional research into diagnostic test accuracy. Furthermore, the determinants of health-seeking delay in Ecuador should be investigated further.

Cerebrovascular Events After Transcatheter Edge-to-Edge Repair and Guideline-Directed Medical Therapy in the COAPT Trial.

BACKGROUND: Little is known regarding the risk of cerebrovascular events (CVE) in patients with heart failure and severe secondary mitral regurgitation treated with transcatheter edge-to-edge repair (TEER). OBJECTIVES: The study sought to examine the incidence, predictors, timing, and prognostic impact of CVE (stroke or transient ischemic attack) in the COAPT (Cardiovascular Outcomes Assessment of the Mitraclip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial. METHODS: A total of 614 patients with heart failure and severe secondary mitral regurgitation were randomized to TEER plus guideline-directed medical therapy (GDMT) vs GDMT alone. RESULTS: At 4-year follow-up, 50 CVEs occurred in 48 (7.8%) of the 614 total patients enrolled in the COAPT trial; Kaplan-Meier event rates were 12.3% in the TEER group and 10.2 in the GDMT alone group (P = 0.91). Within 30 days of randomization, CVE occurred in 2 (0.7%) patients randomized to TEER and 0% randomized to GDMT (P = 0.15). Baseline renal dysfunction and diabetes were independently associated with increased risk of CVE, while baseline anticoagulation was associated with a reduction of CVE. A significant interaction was present between treatment group and anticoagulation such that TEER compared with GDMT alone was associated with a reduced risk of CVE among patients with anticoagulation (adjusted HR: 0.24; 95% CI: 0.08-0.73) compared with an increased risk of CVE in patients without anticoagulation (adjusted HR: 2.27; 95% CI: 1.08-4.81; Pinteraction = 0.001). CVE was an independent predictor of death within 30 days after the event (HR: 14.37; 95% CI: 7.61, 27.14; P < 0.0001). CONCLUSIONS: In the COAPT trial, the 4-year rate of CVE was similar after TEER or GDMT alone. CVE was strongly associated with mortality. Whether anticoagulation is effective at reducing CVE risk after TEER warrants further study. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT); NCT01626079).

Intravascular Endothelial Hyperplasia of the Foot.

Intravascular endothelial hyperplasia is a benign soft tissue mass rarely reported in the foot. Advanced imaging and confirming a benign diagnosis are critical for any soft tissue mass. This paper identifies 2 patients that developed intravascular endothelial hyperplasia tumors which required surgical excision. A 17-year-old male patient presented to clinic complaining of a painful bump to the arch of his right foot which he related to an injury 9 months prior. Magnetic resonance imaging of the right foot revealed a mass within the plantar subcutaneous fat that was serpiginous in nature similar to adjacent branching vessels favoring a low-flow vascular malformation. A 38-year-old female with Multiple Sclerosis presented with complaints of persistent symptoms of pain to the 1st interspace, difficult ambulation and neuritis. Ultrasound and MRI observed solid, multilobulated mass, with internal vascular malformation, MRI describing intrinsic involvement along the abductor musculature and flexor tendons. Both lesions were surgically excised and sent for pathology. Pathology report indicated a diagnosis of intravascular papillary endothelial hyperplasia or Masson's tumor in both cases. Pathology diagnosis of intravascular papillary endothelial hyperplasia is generally good with wide resection leading to low recurrence rates. Both patients in the current study have progressed postoperatively with resolution of symptoms and without recurrence.

Clinical criteria for Mucosal Leishmaniasis diagnosis in rural South America: A systematic literature review.

BACKGROUND: Mucosal Leishmaniasis (ML), a neglected tropical disease caused by Leishmania parasites, impairs the quality of life of under-resourced populations in South America. If not treated promptly, this disease progresses to facial deformities and death. The low sensitivity of microscopy results and the unavailability of other accurate tests hamper the diagnosis. As clinical criteria are readily available in any setting, these may be combined in a syndromic algorithm, which in turn can be used as a diagnostic tool. We explore potential clinical criteria for a syndromic diagnostic algorithm for ML in rural healthcare settings in South America. METHODOLOGY/PRINCIPAL FINDINGS: The protocol for this systematic review was pre-registered in PROSPERO with the number: CRD42017074148. In patients with ML, described in case series identified through a systematic retrieval process, we explored the cumulative ML detection rates of clinical criteria. Participants: all patients with active mucosal disease from an endemic area in South America. Any original, non-treatment study was eligible, and case reports were excluded. PUBMED, EMBASE, Web of Science, SCIELO, and LILACS databases were searched without restrictions. The risk of bias was assessed with the JBI checklist for case series. We included 10 full texts describing 192 ML patients. Male gender had the highest detection rate (88%), followed by ulcer of the nasal mucosa (77%), age >15 (69%), and symptom duration >4 months (63%). SIGNIFICANCE: Within this selection of patients, we found that the male gender, ulcer of the nasal mucosa, age >15, and symptom duration >4 months lead to the highest detection rates. However, higher detection comes -naturally- with a higher rate of false positives as well. As we only included ML patients, this could not be verified. Therefore, the criteria that we found to be most promising should be validated in a well-designed prospective study.

Radiographic Analysis of the Lateral Column Lengthening Procedure in Stage II Adult Acquired Flatfoot Deformity.

Adult acquired flat foot deformity (AAFD) is a progressive, tri-planar deformity involving collapse of the medial longitudinal arch, valgus deformity of the rear foot, and abduction of the mid-foot on the rear foot. There are a wide variety of surgical treatment options for this deformity, including lateral column lengthening (LCL) which results in tri-planar correction of AAFD. We retrospectively reviewed weightbearing preoperative radiographs and weight-bearing 6-week postoperative radiographs of 34 patients with stage II AAFD who underwent LCL (with and without concurrent procedures) with a minimum of 1-year of follow up. Outcomes, including complications and postoperative differences in 6 types of angle measurements were evaluated. Radiographic evaluation showed statistically significant differences in preoperative and postoperative measures in the following angles: calcaneal inclination, Meary's, Simmons, talocalcaneal, and metatarsus adductus (each p ≤ .05). Postoperative Engel's angle difference did not reach statistical significance (p = .07). Paired t tests showed TN coverage angles increased greater with LCL plus a Cotton osteotomy as compared to isolated LCL. Additionally, there was no significant difference in TN coverage angle based on LCL graft size (p = .20). Furthermore, the distance of the osteotomy from the calcaneocuboid joint on anteroposterior and lateral radiographs did not significantly predict TN coverage angle change. Our study suggests that LCL corrects AAFD in three planes while decreasing the metatarsus adductus angle. LCL appears to be more effective when performed with a Cotton osteotomy. Wedge size (6 mm, 8 mm, 10 mm) and osteotomy location did not demonstrate a relationship with postoperative TN coverage angle or incidence of lateral column overload.

First Tarsometatarsal Joint Arthrodesis for Hallux Valgus With and Without Intermetatarsal Screw Fixation: A Comparison of Correction and Maintenance of Correction.

Tarsometatarsal joint arthrodesis is a commonly accepted procedure for hallux valgus associated with severe deformity and first ray hypermobility or medial column instability. This study evaluates the correction of hallux valgus deformity and the maintenance of correction with and without the use of a stabilization screw between the first and second metatarsal bases. Through retrospective review of first tarsometatarsal joint arthrodesis within our institution we evaluated 63 patients. Twenty-seven patients did not have a first to second metatarsal base screw and were placed into the no screw cohort. Thirty-six patients did have a first to second metatarsal base screw and were placed into the screw cohort. This study population had an osseous union rate of 95%. Clinical and radiographic recurrence occurred in 5 of 63 patients (8%). At 1-y postop the measurements demonstrated that the screw cohort had an average intermetatarsal angle correction of 11.6 degrees while the no screw cohort had an average correction of 7.8 degrees. Additionally, at 1-y postop the screw cohort had greater maintenance of the intermetatarsal angle correction with an average change of 0.5 degrees compared to 2.3 degrees in the no screw cohort. We conclude that the addition of the stabilization screw improves the first tarsometatarsal joint arthrodesis construct resulting in a greater degree of realignment and maintenance of correction.

Radiographic Outcomes of Talonavicular Joint Arthrodesis With Varying Fixation Techniques in Stage III Adult Acquired Flatfoot Reconstruction.

Utilization of the talonavicular joint (TN) arthrodesis as an isolated procedure or in combination with hindfoot arthrodesis has been described in the literature for treatment of numerous hindfoot conditions. When used in isolation or with concomitant hindfoot arthrodesis, the TN joint has demonstrated nonunion rates reported as high as 37% in the literature. Despite previous research, there remains a lack of agreement upon the ideal fixation technique for TN joint arthrodesis with and without concomitant subtalar joint arthrodesis. The purpose of this study was to retrospectively compare the radiographic and clinical results of TN joint arthrodesis as part of double arthrodesis procedure utilizing 4 separate fixation constructs in the treatment of advanced hindfoot malalignment in stage III adult-acquired flatfoot deformity. We retrospectively reviewed 105 patients who underwent TN joint arthrodesis as part of double arthrodesis procedure utilizing 4 separate fixation constructs. Our results demonstrated a nonunion rate of 16.2%, with 17 nonunions identified within our patient population. One (2.4%) nonunion was observed in the 3-screw cohort, 7 (33.3%) nonunions were observed in the 2-screw cohort, 4 (16.0%) nonunions were observed in the 2-screw plus plate cohort, and 5 (29.4%) nonunions were observed in the 1-screw plus plate cohort. The difference in nonunion rate between the 4 cohorts was statistically significant. Based on these results, we conclude that the use of a 3-screw construct for TN joint arthrodesis as part of double arthrodesis procedure demonstrates a statistically significant reduction in nonunion rate and should be considered a superior fixation construct for this procedure.

Radiographic Outcomes of Isolated Subtalar Joint Arthrodesis With Varying Fixation Technique.

Subtalar joint (STJ) arthrodesis is a well-established and accepted surgical procedure utilized for the treatment of various hindfoot conditions including primary or posttraumatic subtalar osteoarthritis, hindfoot valgus deformity, hindfoot varus deformity, complex acute calcaneal fracture, symptomatic residual congenital deformity, tarsal coalition, and other conditions causing pain and deformity about the hindfoot. Union rates associated with isolated subtalar joint arthrodesis are generally thought to be favorable, though reports have varied significantly, with non-union rates ranging from 0 to 46%. Various fixation constructs have been recommended for STJ arthrodesis. The purpose of this study was to compare radiographic union in a 2-screw fixation technique to a 3-screw fixation technique for patients undergoing primary isolated STJ arthrodesis. To this end, we retrospectively reviewed 54 patients; 26 in the 2-screw group and 28 in the 3-screw group. We found the median time to radiographic union to be 9 weeks for the 2-screw cohort and 7 weeks for the 3-screw cohort. Additionally, we found that the 2-screw fixation cohort had a radiographic non-union rate of 26.9% while the 3-screw cohort had no non-unions. We conclude that the use of a 3-screw construct for isolated STJ arthrodesis has a lower non-union rate and time to union when compared to the traditional 2-screw construct and should be considered as a fixation option for STJ arthrodesis.

Radiographic Analysis and Clinical Efficacy of Hindfoot Arthrodesis With Versus Without Cotton Osteotomy in Stage III Adult Acquired Flatfoot Deformity.

Forefoot varus develops as a result of longstanding adult-acquired flatfoot deformity (AAFD). This occurs with varying degrees of deformity and flexibility. Residual forefoot varus following hindfoot realignment in AAFD can lead to lateral column loading and a persistent pronatory moment in efforts to reestablish contact between the forefoot and the ground. The Cotton osteotomy may serve as a reasonable adjunct procedure to help avoid complications and poor outcomes associated with residual forefoot varus in patients undergoing hindfoot arthrodesis for stage III AAFD. The aim of this study was to compare the radiographic outcomes in patients undergoing isolated hindfoot arthrodesis to patients undergoing hindfoot arthrodesis with adjunctive cotton osteotomy. We retrospectively reviewed 47 patients matched based upon age, sex, and comorbidities who underwent hindfoot reconstruction for the treatment of stage III AAFD between 2015 and 2019. A retrospective radiographic review was performed on standard weightbearing radiographs including anterior-posterior and lateral views preoperatively, postoperatively at the initiation of full weightbearing, and at final follow-up. Statistical analysis utilizing paired t test to calculate p values where <.05 was statistically significant. At final follow-up, radiographic measurements showed statistically significant differences in CAA, calcaneal inclination, talo-calcaneal, and talar tilt (p value <.05). The Cotton osteotomy group showed a quicker return to presurgical activity level and a decreased incident of tibiotalar valgus. Our study suggests that the Cotton osteotomy can address residual forefoot varus and potentially prevent further progression of ankle valgus in AAFD when used in combination with hindfoot arthrodesis.

Prevalence of ocular findings regardless of visual acuity status in older adults from the Brazilian Amazon Region.

Recently, it has been recommended that population-based studies report not only frequencies of vision impairment and blindness but also any ocular abnormalities that might lead an individual to seek for eyecare services. The current study aimed to determine prevalence of ocular findings regardless of visual acuity (VA) status in older adults from the Brazilian Amazon Region. Disturbances were grouped into: Eyelids; Anterior Segment; Posterior Segment; Increased intraocular pressure; and Overall Globe. The presence of an ocular finding was considered positive when any abnormality was noted, regardless of VA. Refractive errors were not considered. A total 2384 eligible persons were enumerated and 2041 (85.6%) examined. The prevalence of ocular disturbances in either eye was 87.0% and was associated with male gender, older age, lower education, and rural residence. Overall, main findings were pterygium, cataract, and pinguecula, occurring in 58.8%, 45.4% and 17.4%, respectively. Among individuals with 20/20 VA in both eyes, the most frequent findings were pterygium, pinguecula, and glaucoma cupping, occurring in 47.4%, 31.2% and 6.5%, respectively. The high prevalence of ocular findings observed in this population reinforces that different conditions might not immediately decrease VA but can indicate risk and/or discomfort symptoms and should be considered when planning public health ophthalmic services.

A One Health Approach to Compare Self-Prescribed Antibiotic Use across Rural and Semi-urban Populations in San Lucas Tolimán, Guatemala.

Antimicrobial resistance resulting from antibiotic overuse represents an increasing public health challenge. The purpose of this study was to investigate antibiotic self-medication practices in a rural, indigenous Guatemalan population, and to compare self-prescribing patterns in rural and semi-urban populations using a One Health integrated approach, a framework acknowledging that health arises at the interface of humans, animals, and the environment. We conducted a mixed methods study using semi-structured interviews in and around San Lucas Tolimán, Guatemala. Antibiotic self-medication was common in both rural and semi-urban populations, regardless of demographic characteristics. Antibiotic usage in animals, while less common, almost always occurred without a veterinary consult. Although subjects recognized that self-medication could be harmful to health, they face significant barriers to accessing appropriate care. These patterns of use have impacts on the rise of antimicrobial resistance locally, and have the potential to contribute to the spread of such resistance globally.

Reconstruction of ancient microbial genomes from the human gut.

Loss of gut microbial diversity1-6 in industrial populations is associated with chronic diseases7, underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. Here we performed a large-scale de novo assembly of microbial genomes from palaeofaeces. From eight authenticated human palaeofaeces samples (1,000-2,000 years old) with well-preserved DNA from southwestern USA and Mexico, we reconstructed 498 medium- and high-quality microbial genomes. Among the 181 genomes with the strongest evidence of being ancient and of human gut origin, 39% represent previously undescribed species-level genome bins. Tip dating suggests an approximate diversification timeline for the key human symbiont Methanobrevibacter smithii. In comparison to 789 present-day human gut microbiome samples from eight countries, the palaeofaeces samples are more similar to non-industrialized than industrialized human gut microbiomes. Functional profiling of the palaeofaeces samples reveals a markedly lower abundance of antibiotic-resistance and mucin-degrading genes, as well as enrichment of mobile genetic elements relative to industrial gut microbiomes. This study facilitates the discovery and characterization of previously undescribed gut microorganisms from ancient microbiomes and the investigation of the evolutionary history of the human gut microbiota through genome reconstruction from palaeofaeces.

The Fate of Morbidly Obese Patients With Joint Pain: A Retrospective Study of Patient Outcomes.

BACKGROUND: The number of obese patients seeking a total joint arthroplasty (TJA) continues to increase. Weight loss is often recommended to treat joint pain and reduce risks associated with TJA. We sought to determine the effectiveness of an orthopedic surgeon's recommendation to lose weight. METHODS: We identified morbidly obese (body mass index (BMI) 40-49.9 kg/m2) and super obese (BMI ≥50 kg/m2) patients with hip or knee osteoarthritis. Patients with less than 3-month follow-up were excluded. Patient characteristics (age, gender, BMI, comorbidities), disease characteristics (joint affected, radiographic osteoarthritis grading), and treatments were recorded. Clinically meaningful weight loss was defined as weight loss greater than 5%. RESULTS: Two hundred thirty morbid and 50 super obese patients were identified. Super obese patients were more likely to be referred to weight management (52.0% vs 21.7%, P < .001) and were less likely to receive TJA (20.0% vs 41.7%, P = .004). Each 1 kg/m2 increase in BMI decreased the odds of TJA by 10.9% (odds ratio = 0.891, 95% confidence interval: 0.833-0.953, P = .001). Forty (23.0%) of the nonoperatively treated patients achieved clinically meaningful weight loss, and 19 (17.9%) patients who underwent TJA lost weight before surgery. After surgery, the number of patients who achieved a clinically meaningful weight loss grew to 32 (30.2%). CONCLUSION: In morbid and super obese patients, increasing BMI reduces the likelihood that a patient will receive TJA, and when counseled by their orthopedic surgeon, few patients participate in weight-loss programs or are otherwise able to lose weight. Weight loss is an inconsistently modifiable risk factor for joint replacement surgery.

Considerations to Support Use of Patient-Reported Outcomes Measurement Information System Pediatric Measures in Ambulatory Clinics.

OBJECTIVE: To identify challenges to the use of Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric measures in the ambulatory pediatric setting and possible solutions to these challenges. STUDY DESIGN: Eighteen semistructured telephone interviews of health system leaders, measurement implementers, and ambulatory pediatric clinicians were conducted. Five coders used applied thematic analysis to iteratively identify and refine themes in interview data. RESULTS: Most interviewees had roles in leadership or the implementation of patient-centered outcomes; 39% were clinicians. Some had experience using PROMIS clinically (44%) and 6% were considering this use. Analyses yielded 6 themes: (1) selection of PROMIS measures, (2) method of administration, (3) use of PROMIS Parent Proxy measures, (4) privacy and confidentiality of PROMIS responses, (5) interpretation of PROMIS scores, and (6) using PROMIS scores clinically. Within the themes, interviewees illuminated specific unique considerations for using PROMIS with children, including care transitions and privacy. CONCLUSIONS: Real-world challenges continue to hamper PROMIS use. Ongoing efforts to disseminate information about the integration of PROMIS measures in clinical care is critical to impacting the health of children.

Reliability of Spinopelvic Measurements That May Influence the Cup Position in Total Hip Arthroplasty.

BACKGROUND: Spinopelvic pathology has been identified as a potential risk factor for instability after total hip arthroplasty. Spinopelvic radiographic parameters used to diagnose spinopelvic disease may also impact optimal cup placement. The purpose of this study was to assess the arthroplasty surgeon accuracy in making spinopelvic measurements. METHODS: Five fellowship-trained or in-training arthroplasty surgeons reviewed 44 lateral lumbar radiographs in two sessions. All evaluators were instructed how to perform measurements but had little experience in doing so. Traditional measurements included the pelvic tilt (PT), pelvic incidence (PI), and sacral slope (SS), and novel measurements included the acetabular ante-inclination (AI) and pelvic femoral angle. Surgeon measurements were compared with those made by experienced engineers. intraclass coefficients (ICCs) were calculated and interpreted. RESULTS: The interobserver reliability for 4 of 5 of the spinopelvic parameters was good to excellent (ICC >0.75) with the highest reliability seen for PI measurement (ICC = 0.939). Only moderate interobserver reliability was observed for AI measurement (ICC = 0.559). Intraobserver reliability was the highest for the PI and SS, ranging from moderate to good (ICC, 0.718 to 0.896). The lowest intraobserver reliability was seen for the AI (ICC range, 0.026 to 0.545) and pelvic femoral angle (ICC range, 0.035 to 0.828). Surgeon measurements of PT and SS were compared with engineer measurements with extremely poor correlation observed (ICC <0 for all). CONCLUSION: Surgeon intraobserver and interobserver reliability in making novel radiographic measurements was low compared with traditional radiographic measurements. Surgeon reliability in making traditional measurements of the PT and SS was very poor compared with experienced assessors using software-based measurements.

A genome-wide association study of polycystic ovary syndrome identified from electronic health records.

BACKGROUND: Polycystic ovary syndrome is the most common endocrine disorder affecting women of reproductive age. A number of criteria have been developed for clinical diagnosis of polycystic ovary syndrome, with the Rotterdam criteria being the most inclusive. Evidence suggests that polycystic ovary syndrome is significantly heritable, and previous studies have identified genetic variants associated with polycystic ovary syndrome diagnosed using different criteria. The widely adopted electronic health record system provides an opportunity to identify patients with polycystic ovary syndrome using the Rotterdam criteria for genetic studies. OBJECTIVE: To identify novel associated genetic variants under the same phenotype definition, we extracted polycystic ovary syndrome cases and unaffected controls based on the Rotterdam criteria from the electronic health records and performed a discovery-validation genome-wide association study. STUDY DESIGN: We developed a polycystic ovary syndrome phenotyping algorithm on the basis of the Rotterdam criteria and applied it to 3 electronic health record-linked biobanks to identify cases and controls for genetic study. In the discovery phase, we performed an individual genome-wide association study using the Geisinger MyCode and the Electronic Medical Records and Genomics cohorts, which were then meta-analyzed. We attempted validation of the significant association loci (P<1×10-6) in the BioVU cohort. All association analyses used logistic regression, assuming an additive genetic model, and adjusted for principal components to control for population stratification. An inverse-variance fixed-effect model was adopted for meta-analysis. In addition, we examined the top variants to evaluate their associations with each criterion in the phenotyping algorithm. We used the STRING database to characterize protein-protein interaction network. RESULTS: Using the same algorithm based on the Rotterdam criteria, we identified 2995 patients with polycystic ovary syndrome and 53,599 population controls in total (2742 cases and 51,438 controls from the discovery phase; 253 cases and 2161 controls in the validation phase). We identified 1 novel genome-wide significant variant rs17186366 (odds ratio [OR]=1.37 [1.23, 1.54], P=2.8×10-8) located near SOD2. In addition, 2 loci with suggestive association were also identified: rs113168128 (OR=1.72 [1.42, 2.10], P=5.2×10-8), an intronic variant of ERBB4 that is independent from the previously published variants, and rs144248326 (OR=2.13 [1.52, 2.86], P=8.45×10-7), a novel intronic variant in WWTR1. In the further association tests of the top 3 single-nucleotide polymorphisms with each criterion in the polycystic ovary syndrome algorithm, we found that rs17186366 (SOD2) was associated with polycystic ovaries and hyperandrogenism, whereas rs11316812 (ERBB4) and rs144248326 (WWTR1) were mainly associated with oligomenorrhea or infertility. We also validated the previously reported association with DENND1A1. Using the STRING database to characterize protein-protein interactions, we found both ERBB4 and WWTR1 can interact with YAP1, which has been previously associated with polycystic ovary syndrome. CONCLUSION: Through a discovery-validation genome-wide association study on polycystic ovary syndrome identified from electronic health records using an algorithm based on Rotterdam criteria, we identified and validated a novel genome-wide significant association with a variant near SOD2. We also identified a novel independent variant within ERBB4 and a suggestive association with WWTR1. With previously identified polycystic ovary syndrome gene YAP1, the ERBB4-YAP1-WWTR1 network suggests involvement of the epidermal growth factor receptor and the Hippo pathway in the multifactorial etiology of polycystic ovary syndrome.

Pterygium in adults from the Brazilian Amazon Region: prevalence, visual status and refractive errors.

AIMS: To determine prevalence of pterygium, its role as main cause of unilateral and bilateral visual impairment and blindness and its impact on refractive errors from adults living in a high ultraviolet exposure area in the Brazilian Amazon Region. METHODS: Cluster sampling was used in randomly selecting subjects ≥45 years of age from urban and rural areas of Parintins city. Eligible subjects were enumerated through a door-to-door household survey and invited for an eye exam including refraction. Pterygium was assessed considering location (nasal, temporal or both) and size (<3 mm or ≥3 mm reaching or not pupillary margin). RESULTS: A total of 2384 persons were enumerated and 2041 (85.6%) were examined. Prevalence of pterygium was 58.8% (95% CI 53.8% to 63.7%) and associated with male gender (OR=1.63; 95% CI 1.37 to 1.94; p=0.001), while higher education was a protective factor (OR=0.63; 95% CI 0.44 to 0.92; p=0.018). Older age and rural residence were associated with pterygium ≥3 mm reaching or not pupillary margin, while higher education was a protective factor for pterygium ≥3 mm reaching pupillary margin. Prevalence of pterygium as cause of visual impairment and blindness was 14.3% and 3.9%, respectively. Significantly higher hyperopic refractive errors were found in eyes with pterygium ≥3 mm reaching or not pupillary margin. CONCLUSIONS: Pterygium was highly prevalent and the second cause of visual impairment and blindness after provision of refractive correction. Risk factors for pterygium were male gender, advanced age, lower education and rural residency. Strategies to provide pterygium early detection and proper management should be considered by healthcare authorities in this population.

Prevalence and Causes of Visual Impairment and Blindness in Adults Aged 45 Years and Older from Parintins: The Brazilian Amazon Region Eye Survey.

Purpose: To determine the prevalence and causes of visual impairment and blindness in adults aged 45 years and older from Parintins, Brazilian Amazon Region. Methods: A random cluster sampling method was used to identify subjects 45 years of age and older from urban and rural census sectors of Parintins city, Amazonas State, from March 2014 to May 2015. Participants underwent a detailed ocular examination, including presenting (PVA) and best corrected visual acuity (BCVA). The main cause of PVA<20/32 per eye was determined. Results: A total of 2384 subjects were enumerated and 2041 (85.6%) examined. The prevalence of presenting mild visual impairment - MiVI (<20/32 - ≥20/63) in the better-seeing eye was 17.0% [95% CI: 15.3-18.7%], and 8.5% [95% CI: 7.3-9.7%] with best correction. The prevalence of presenting moderate visual impairment - MVI (<20/63 - ≥20/200) was 18.4% [95% CI: 16.2-20.6%], and 6.9% [95% CI: 5.8-8.0%] with best correction. The prevalence of presenting bilateral VA <20/200 was 4.3% [95% CI: 3.6-5.0%], and 3.3% [95% CI: 2.5-4.0%] with best correction and increased with older age. Cataract (47.8%) and glaucoma (7.5%) were its main causes. In less severely affected eyes, uncorrected refractive errors (MVI: 42.6%; MiVI: 79.0%), cataract (MVI: 40.6%; MiVI: 13.7%) and pterygium (MVI: 7.6%; MiVI: 2.7%) were the main causes. Conclusions: Most cases of visual impairment in Parintins are either preventable or treatable, and public health initiatives should target cataract surgical services and refraction with spectacle provision.

Vision Status in Older Adults: The Brazilian Amazon Region Eye Survey.

Older adults living in remote areas with limited access to health services are at higher risk to develop visual impairment and blindness. We conducted a population-based survey to determine the vision status in subjects 45 years of age and older from urban and rural areas of Parintins city, Brazilian Amazon Region. Participants underwent ophthalmic examination, including uncorrected (UCVA), presenting (PVA) and best-corrected visual acuity (BCVA). Vision status was described as lines of visual acuity (VA) impairment and lines of VA improvement from UCVA to BCVA and from PVA to BCVA in the better-seeing eye. A total of 2384 subjects were enumerated, 2041 (85.6%) were examined, with reliable VA measurements obtained from 2025 participants. Vision status in lines of VA impairment was (mean ± standard deviation): 3.44 ± 3.53 for UCVA, 2.85 ± 3.52 for PVA and 1.50 ± 3.51 for BCVA. Female gender, older age and lower education were associated with ≥6 lines of UCVA impairment. Lines of improvement ≥3 was found in 626 (30.9%) participants and associated with female gender and rural residency. In conclusion, a third of participants could have at least three lines of VA improvement with proper refraction. Strategies to improve access to eye care and affordable glasses are needed.