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1.
Liver Int ; 44(2): 389-398, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37971775

RESUMO

BACKGROUND & AIMS: Ferritin has been investigated as a biomarker for liver fibrosis and iron in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, whether metabolic hyperferritinaemia predicts progression of liver disease remains unknown. In this study, we sought to understand associations between hyperferritinaemia and (1) adverse clinical outcomes and (2) common genetic variants related to iron metabolism and liver fibrosis. METHODS: This was a retrospective analysis of adults with MASLD seen at the University of Michigan Health System, where MASLD was defined by hepatic steatosis on imaging, biopsy or vibration-controlled transient elastography, plus metabolic risk factors in the absence of chronic liver diseases other than hemochromatosis. The primary predictor was serum ferritin level, which was dichotomized based on a cut-off of 300 or 450 mcg/L for women or men. Primary outcomes included (1) incident cirrhosis, liver-related events, congestive heart failure (CHF), and mortality and (2) distribution of common genetic variants associated with hepatic fibrosis and hereditary hemochromatosis. RESULTS: Of 7333 patients with MASLD, 1468 (20%) had elevated ferritin. In multivariate analysis, ferritinaemia was associated with increased mortality (HR 1.68 [1.35-2.09], p < .001) and incident liver-related events (HR 1.92 [1.11-3.32], p = .019). Furthermore, elevated ferritin was associated with carriage of cirrhosis-promoting alleles including PNPLA3-rs738409-G allele (p = .0068) and TM6SF2-rs58542926-T allele (p = 0.0083) but not with common HFE mutations. CONCLUSIONS: In MASLD patients, metabolic hyperferritinaemia was associated with increased mortality and higher incidence of liver-related events, and cirrhosis-promoting alleles but not with iron overload-promoting HFE mutations.


Assuntos
Fígado Gorduroso , Hemocromatose , Adulto , Masculino , Humanos , Feminino , Hemocromatose/complicações , Hemocromatose/genética , Alelos , Estudos Retrospectivos , Fígado Gorduroso/complicações , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/genética , Cirrose Hepática/patologia , Fibrose , Ferro , Ferritinas
2.
J Pediatr Hematol Oncol ; 44(6): 313-317, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34966100

RESUMO

Many pediatric oncology patients and their families may benefit from genetic counseling and testing; however, identifying the best timing and delivery method for these referrals is sometimes a challenge. The goal of this study was to understand how and when caregivers prefer to receive information about genetic counseling and testing. A total of 56 surveys completed by caregivers at The Johns Hopkins Hospital Pediatric Oncology unit in Baltimore, Maryland were analyzed. A sizeable subset of respondents was interested in receiving information about the availability of genetic counseling from an oncology doctor or nurse, but not a genetic counselor (n=13/55, 24%). Most respondents preferred to be informed about genetic services at diagnosis (n=28/54, 52%) or within 1 to 2 months of diagnosis (n=14/54, 26%). In conclusion, patients and their families may benefit from prompt and early recognition of the risk of cancer predisposition syndromes, preferably within the first 2 months following diagnosis. Oncology professionals are an important source of information, and can introduce the availability of genetic counseling services and motivate families to undergo genetic testing, though alternative communication methods such as brochures may also be useful.


Assuntos
Aconselhamento Genético , Neoplasias , Criança , Aconselhamento Genético/psicologia , Testes Genéticos , Humanos , Oncologia , Neoplasias/diagnóstico , Neoplasias/genética , Inquéritos e Questionários
3.
J Pediatr Hematol Oncol ; 43(6): e891-e896, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33370000

RESUMO

Implementation and adherence to consensus statement criteria for referral of pediatric cancer patients for genetic evaluation are critical to identify the 5% to 10% with a genetic cancer predisposition syndrome. The authors implemented a Plan-Do-Study-Act quality improvement initiative aimed at increasing referrals of at-risk patients. Retrospective chart review was followed by educational intervention-with impact assessed over a 9-month prospective chart review. Referral rate improved >2-fold and there was an improvement in documented oncologic history to at least a third-degree relative. The integration of quality improvement can be an effective tool to improve the referral of patients with an elevated risk for a cancer predisposition syndrome.


Assuntos
Neoplasias/genética , Criança , Predisposição Genética para Doença , Testes Genéticos , Humanos , Oncologia , Mutação , Estudos Retrospectivos
4.
Phytopathology ; 105(6): 840-6, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25775105

RESUMO

In spring 2013, 5-year-old nectarine (Prunus persica) trees, grafted on peach rootstock Nemaguard, were found stunted in a propagation block in California. These trees had been propagated from budwood of three nectarine cultivars imported from France and cleared through the post-entry quarantine procedure. Examination of the canopy failed to reveal any obvious symptoms. However, examination of the trunks, after stripping the bark, revealed extensive pitting on the woody cylinder. To investigate the etiological agent, double-stranded RNA was extracted from bark scrapings from the scion and rootstock portions, and a cDNA library was prepared and sequenced using the Illumina platform. BLAST analysis of the contigs generated by the de novo assembly of sequence reads indicated the presence of a novel luteovirus. Complete sequence of the viral genome was determined by sequencing of three overlapping cDNA clones generated by reverse transcription-polymerase chain reaction (RT-PCR) and by rapid amplification of the 5'- and 3'-termini. The virus genome was comprised of 4,991 nucleotides with a gene organization similar to members of the genus Luteovirus (family Luteoviridae). The presence of the virus, tentatively named Nectarine stem pitting-associated virus, was confirmed in symptomatic trees by RT-PCR. Discovery of a new virus in nectarine trees after post-entry quarantine indicates the importance of including (i) metagenomic analysis by next-generation sequencing approach as an essential tool to assess the plant health status, and (ii) examination of the woody cylinders as part of the indexing process.


Assuntos
Genoma Viral/genética , Luteovirus/genética , Metagenômica , Doenças das Plantas/virologia , Prunus/virologia , Sequência de Bases , California , França , Sequenciamento de Nucleotídeos em Larga Escala , Luteovirus/isolamento & purificação , Dados de Sequência Molecular , Filogenia , Caules de Planta/virologia , Quarentena , RNA de Cadeia Dupla/genética , Análise de Sequência de DNA , Árvores
5.
Urol Pract ; 11(6): 940-948, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39196661

RESUMO

INTRODUCTION: Use of placebo in oncology randomized controlled trials (RCT) is ethically controversial. Placebo may introduce bias, as toxicity profiles of treatment arms can inadvertently unblind subjects and investigators. We investigated the use of placebo in urologic oncology RCTs, hypothesizing that most placebo-controlled trials are effectively unblinded, either explicitly with open-label design or implicitly due to large differences in adverse events (AE) or oncologic outcomes. METHODS: Urologic oncology RCTs utilizing placebo were identified via ClinicalTrials.gov. Interventional prostate, bladder/urothelial, and renal cancer trials from 2014 to 2024 were included. Subject incompletion, all-cause mortality, AE rates, and serious AE (SAE) rates were identified and compared between placebo and active arms using χ2 and Fisher's exact tests. RESULTS: Sixty studies met inclusion criteria and included 66 placebo arms with 12,918 subjects and 81 active arms with 16,098 subjects. There was no significant difference in incompletion rates between placebo and active arms. Subjects enrolled in active arms reported statistically significant higher SAE and AE rates compared to those in placebo arms across the majority of physiological domains, including 18/24 domains for SAEs and 13/24 for AEs. This relationship persisted in sensitivity analyses where unblinded trials were excluded. CONCLUSIONS: In urologic oncology placebo-controlled RCTs, active arms are associated with significantly higher rates of AEs and SAEs compared with placebo arms. These findings indicate a strong possibility that true blinding is not possible in oncology RCTs, even with optimal study design, and serve to better inform future clinical trial design and implementation challenges in employing placebo control.


Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Urológicas , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/ética , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Placebos/efeitos adversos , Placebos/administração & dosagem , Placebos/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Oncologia/ética , Oncologia/métodos , Efeito Placebo
6.
Ocul Immunol Inflamm ; : 1-7, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639557

RESUMO

PURPOSE: To report two patients with herpetic zoster panuveitis and chorioretinopathy with choroidal hypopigmentation. METHODS: Retrospective chart review of two patients. RESULTS: We report a series of two patients with a history of HZO with orbital inflammation and panuveitis, who developed patchy choroidal depigmentation consistent with a choroidopathy. The lesions were extensive and involved the posterior pole and mid-periphery in both cases. Both cases demonstrated scattered areas of ellipsoid zone loss, and fluorescein angiography showed corresponding late hyperfluorescence. OCTA in one case demonstrated flow voids at the level of choriocapillaris. CONCLUSIONS: Our series suggests that herpetic chorioretinopathy may be a relatively benign process that presents late and may involve large areas of the posterior choroid.

7.
Biomedicines ; 11(5)2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37238939

RESUMO

Choroidal caverns (CCs) have been described in association with age-related macular degeneration and pachychoroid disease. However, it is unknown if caverns are found in patients with chronic non-infectious uveitis (NIU). Herein, we evaluated patients with NIU who had optical coherence tomography and indocyanine green angiography for CCs. Clinical and demographic characteristics were extracted from the chart review. Univariate and multivariate mixed-effects logistical models were used to assess the association between clinical and demographic factors and the presence of CCs. One hundred thirty-five patients (251 eyes) met the inclusion criteria: 1 eye had anterior uveitis, 5 had intermediate uveitis, 194 had posterior uveitis, and 51 had panuveitis. The prevalence of CCs was 10%. CCs were only observed in patients with posterior and panuveitis, with a prevalence of 10.8% and 7.8%, respectively. Multifocal choroiditis (MFC) was the type of uveitis where CCs were most frequently observed, with 40% of eyes with MFC having CCs. In addition, male sex (p = 0.024) was associated with CCs. There was no significant difference in the degree of intraocular inflammation or mean subfoveal choroidal thickness between CC+ and CC- eyes. This is the first study to describe CCs in uveitis. Overall, these findings suggest that caverns may be a sequela of structural and/or vascular perturbations in the choroid from uveitis.

8.
Am J Ophthalmol ; 250: 82-94, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36709019

RESUMO

PURPOSE: Intraocular infections are sight-threatening conditions that can lead to vision loss. Rapid identification of the etiologies plays a key role in early initiation of effective therapy to save vision. However, current diagnostic modalities are time consuming and lack sensitivity and inclusiveness. We present here a newly developed comprehensive ocular panel designed to improve diagnostic yields and provide a tool for rapid and sensitive pathogen detection. DESIGN: Experimental laboratory investigation. METHODS: A panel containing 46 pathogens and 2 resistance/virulence markers that are commonly detected in intraocular infections was developed. Genomic targets were scrutinized for stretches predicted to be specific for a particular species while being conserved across different strains. A set of primers for sample enrichment, and two 50mer NanoString compatible probes were then designed for each target. Probe-target hybrids were detected and quantified using the NanoString nCounter SPRINT Profiler. Diagnostic feasibility was assessed in a pilot clinical study testing samples from infectious retinitis (n = 15) and endophthalmitis (n = 12) patients, for which the etiologies were confirmed by polymerase chain reaction (PCR) or culture. RESULTS: Analytical studies demonstrated highly sensitive detection of a broad spectrum of pathogens, including bacteria, viruses, and parasites, with limits of detection being as low as 2.5 femtograms per reaction. We also found excellent target specificity, with minimal cross-reactivity detected. The custom-designed NanoString ocular panel correctly identified the causative agent from all clinical specimens positive for a variety of pathogens. CONCLUSION: This highly multiplexed panel for pathogen detection offers a sensitive, comprehensive, and uniform assay run directly on ocular fluids that could significantly improve diagnostics of sight-threatening intraocular infections.


Assuntos
Endoftalmite , Infecções Oculares , Humanos , Sensibilidade e Especificidade , Endoftalmite/diagnóstico , Bactérias/genética , Reação em Cadeia da Polimerase
9.
PLoS One ; 18(6): e0284108, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37285323

RESUMO

Although medical masks have played a key role in decreasing the transmission of communicable disease, they simultaneously reduce the availability of nonverbal cues fundamental to social interaction. In the present study, we determined the collective impact of medical masks on emotional expression recognition and perceived intensity as a function of actor race. Participants completed an emotional expression recognition task involving stimuli with or without medical masks. Across six basic emotional facial expressions, medical masks were associated with significantly more emotional expression recognition errors. Overall, the effects associated with race varied depending on the emotion and appearance of masks. Whereas recognition accuracy was higher for White relative to Black actors for anger and sadness, the opposite pattern was observed for disgust. Medical mask-wearing exacerbated actor-race related recognition differences for anger and surprise, but attenuated these differences for fear. Emotional expression intensity ratings were significantly reduced for all emotions except fear, where masks were associated with increased perceived intensity. Masks further increased already higher intensity ratings for anger in Black versus White actors. In contrast, masks eliminated the tendency to give higher intensity ratings for Black versus White sad and happy facial expressions. Overall, our results suggest that the interaction between actor race and mask wearing status with respect to emotional expression judgements is complex, varying by emotion in both direction and degree. We consider the implications of these results particularly in the context of emotionally charged social contexts, such as in conflict, healthcare, and policing.


Assuntos
Reconhecimento Facial , Máscaras , Humanos , Emoções , Medo , Felicidade , Ira , Expressão Facial
10.
Urol Pract ; 10(6): 666-670, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37498667

RESUMO

INTRODUCTION: This study investigated the effectiveness of buprenorphine as an alternative to the use of conventional opioids perioperatively in an effort to help mitigate the impact of the use of perioperative conventional opioids for patients undergoing robotic-assisted laparoscopic prostatectomy. METHODS: Outcomes of patients with localized prostate cancer undergoing robotic-assisted laparoscopic prostatectomy were examined before and after implementation of novel quality improvement study that included receiving buprenorphine compared to conventional opioids for pain control intraoperatively and postoperatively. The primary end point was adequate pain control with secondary end points being analgesic consumption at home, opioid-related side effects, and patient satisfaction. RESULTS: When analyzing the secondary end point of oral morphine milligram equivalents, the buprenorphine group received significantly less morphine milligram equivalent compared to the conventional opioid group (15.19 vs 47.91, P = .006). The buprenorphine group also had lower reported pain scores at discharge (4.3; scale 1-10) compared to the conventional opioid group (5.4), though this did not reach significance (P = .069). In the buprenorphine group, 76.9% strongly agreed that their pain was adequately controlled in the hospital compared to 57.5% of the conventional opioid group (P = .223). There was no difference in overall satisfaction at postoperative day 5 (P = .358). CONCLUSIONS: Our study demonstrates buprenorphine's analgesic capabilities to maintain adequate pain control and patient satisfaction compared to conventional opioids during robotic-assisted laparoscopic prostatectomy, while decreasing perioperative opioid use.

11.
Ocul Immunol Inflamm ; : 1-6, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36521074

RESUMO

PURPOSE: To determine the sensitivity and positive predictive value (PPV) of a contiguous, perineural retinal vascular leakage fluorescein angiography (FA) pattern in birdshot chorioretinopathy (BSCR) patients. METHODS: Patients with BSCR and other posterior uveitis/retinal vasculitis and a FA were identified. Two graders reviewed the first FA for leakage primarily around the optic nerve and along the larger arcade vessels. We compared the rates of this pattern in BSCR and non-BSCR patients and calculated sensitivity and PPV. We compared clinical characteristics of BSCR patients with and without this pattern. RESULTS: 64 BSCR and 98 non-BSCR patients were identified. The FA pattern's sensitivity, specificity, and PPV were 57.8%, 91.8%, and 82.2%. This pattern was significantly more common in BSCR patients earlier in their disease (p = .004). CONCLUSIONS: A contiguous, perineural retinal vascular leakage FA pattern can help identify potential BSCR patients for further testing. This pattern is more common closer to symptom onset.

12.
Clin Psychol Rev ; 98: 102186, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36240695

RESUMO

Historically, empathy has been thought to motivate prosocial behaviour and inhibit aggressive behaviour. Contrary to current assumptions and theoretical support, a meta-analysis revealed a small effect of empathy on aggression among adults (Vachon, Lynam, & Johnson, 2014). The current study sought to determine whether broadening the focus from empathy to include other socially relevant affective characteristics (i.e., callous-unemotional traits) was advantageous in predicting aggressive behaviour. As little is known about the strength of this association among youth, the current study meta-analytically examined 192 unique effect sizes drawn from published and unpublished studies reporting on samples of children and adolescents. Analyses were conducted across general, cognitive, and emotional empathy, as well as callous-unemotional traits, and general, direct, indirect, proactive, and reactive aggression. Significant variability was noted across effect sizes. Consistent with a prior meta-analysis involving adults (Vachon et al., 2014), small to moderate associations were identified between aggression and traditional measures of empathy (i.e., general, emotional, cognitive); these effects ranged from r = -0.06 to -0.26. Among broader measures of emotional style (i.e., callous-unemotional traits), moderate to large effects were found; ranging from r = 0.30 to 0.37. Results suggested that broader affective measures may be more strongly associated with aggression than empathy alone. The results raise questions about the nature of empathy assessment and indicate the utility of targeting multiple emotion-related factors during treatment to effectively reduce aggressive behaviour. In particular, the results underscore of the importance of considering the limited prosocial emotions specifier (perhaps trans-diagnostically given the varied nature of the sample) when considering implications for prognosis and treatment targets.


Assuntos
Transtorno da Conduta , Criança , Adulto , Adolescente , Humanos , Transtorno da Conduta/psicologia , Empatia , Agressão/psicologia , Emoções
13.
Ophthalmic Epidemiol ; 29(1): 25-30, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33622166

RESUMO

PURPOSE: To determine if angiotensin converting enzyme-inhibitors (ACE-I) alter the incidence of non-infectious uveitis (NIU). METHODS: Patients in a large healthcare claims database who initiated ACE-I (n = 695,557) were compared to patients who initiated angiotensin receptor blockers (ARB, n = 354,295). A second comparison was also made between patients who initiated ACE-I (n = 505,958) and those who initiated beta-blockers (BB, n = 538,109). The primary outcome was incident NIU defined as a first diagnosis code for NIU followed by a second instance of a NIU code within 120 days. For the secondary outcome, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the NIU diagnosis code was used instead of the second NIU diagnosis code. Data were analyzed using Cox regression modeling with inverse probability of treatment weighting (IPTW). Sub-analyses were performed by anatomic subtype. RESULTS: When comparing ACE-I to ARB initiators, the hazard ratio (HR) for incident NIU was not significantly different for the primary outcome [HR = 0.95, 95% Confidence Interval (CI): 0.85-1.07, P = .41] or secondary outcome [HR = 0.96, 95% CI: 0.86-1.07, P = .44]. Similarly, in the ACE-I and BB initiators comparison, the HR for incident NIU was not significantly different comparing ACE-I and BB initiators for either outcome definition or any of the NIU anatomical subtypes. CONCLUSION: Our results suggest there is no evidence that ACE-I have a protective effect on NIU.


Assuntos
Infecções Oculares Bacterianas , Uveíte , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Atenção à Saúde , Humanos , Incidência , Peptidil Dipeptidase A , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Uveíte/epidemiologia
14.
Am J Ophthalmol ; 244: 11-18, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35948088

RESUMO

PURPOSE: To investigate a causal relationship between Vitamin D levels and non-infectious uveitis and scleritis using Mendelian randomization (MR) techniques. DESIGN: Two-sample Mendelian randomization case-control study. METHODS: The study setting was a biobank of an academic, integrated health care system. The patient population comprised 375 case patients with a non-infectious uveitis and/or scleritis diagnosis and no diagnosis of infectious, trauma-related, or drug-induced uveitis/scleritis. In addition, there were 4167 controls with no uveitis or scleritis diagnosis. Causal effect estimates of low 25-hydroxy Vitamin D (25OHD) on uveitis/scleritis risk were calculated. RESULTS: We found an association of genetically decreased 25OHD with uveitis/scleritis risk (odds ratio [OR] = 2.16, 95% CI = 1.01-4.64, P = .049, per SD decrease in log25OHD). In a first sensitivity MR analysis excluding the genetic variants that are unlikely to have a role in biologically active 25OHD, effect estimates were consistent with those from the primary analysis (OR = 2.38, 95% CI =1.06-5.36, P = 0.035, per SD of log25OHD). Furthermore, in a second sensitivity analysis using only the 6 variants within the CYP2R1 locus (which encodes 25OHD hydroxylase, the liver enzyme responsible for converting Vitamin D to 25OHD), genetically decreased 25OHD was strongly associated with increased uveitis/scleritis risk (OR = 6.42, 95% CI = 3.19-12.89, P = 1.7 × 10-7, per SD of log25OHD). CONCLUSIONS: Our findings suggest a causal relationship between low Vitamin D levels and higher risk of non-infectious uveitis and scleritis. Vitamin D supplementation may be a low-cost, low-risk intervention to mitigate non-infectious uveitis and scleritis risk, and should be explored in a prospective trial.


Assuntos
Esclerite , Uveíte , Humanos , Análise da Randomização Mendeliana/métodos , Esclerite/diagnóstico , Esclerite/tratamento farmacológico , Esclerite/genética , Estudos de Casos e Controles , Estudos Prospectivos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Vitamina D , Vitaminas , Uveíte/diagnóstico , Uveíte/genética , Estudo de Associação Genômica Ampla
15.
Curr Eye Res ; 47(10): 1389-1396, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35815717

RESUMO

Purpose: The purpose of the South Indian GeNetics of DiAbeTic Retinopathy (SIGNATR) Study is to identify non-genetic and genetic risk factors associated with diabetic retinopathy (DR). This report examines the non-genetic risk factors for DR in South Indian patients.Methods: Participants with South Indian ancestry and type 2 diabetes (T2D) were included from two sources: the Sankara Nethralaya Diabetic Retinopathy and Molecular Genetics Study (SN-DREAMS) and prospective recruitment at Sankara Nethralaya affiliates. Fundus photography and optical coherence tomography (OCT) were obtained on participants. Fundus images were graded for DR severity and OCTs were graded for center-involved diabetic macular edema (ciDME). Multivariate analyses were performed using stepwise logistic regression to assess effects of the demographic and clinical factors on proliferative DR (PDR) and DME.Results: Among the 2941 participants with DR grading, participants with PDR were more likely to be younger [odds ratio (OR)=0.95], men (OR = 1.83), have a longer duration of diabetes (OR = 1.10), have a higher hemoglobin A1c (OR = 1.12), have albuminuria (OR = 5.83), have hypertension (OR = 1.69), have a higher HDL (OR = 1.02) and a lower total cholesterol (OR = 0.99) (all p < 0.05). Among the 483 participants with gradable OCT scans, participants who had ciDME were more likely to be younger (OR = 0.97), men (OR = 2.80), have a longer duration of diabetes (OR = 1.06), have lower triglycerides (OR = 0.99), and have albuminuria (OR = 3.12) (all p < 0.05).Conclusions: Younger age, male sex, longer duration of diabetes, higher HbA1c, and presence of albuminuria were identified as risk factors for PDR and DME in a South Indian population with T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Edema Macular , Albuminúria/complicações , Albuminúria/diagnóstico , Albuminúria/genética , Colesterol , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/genética , Hemoglobinas Glicadas , Humanos , Edema Macular/etiologia , Edema Macular/genética , Masculino , Estudos Prospectivos , Fatores de Risco , Triglicerídeos
16.
Am J Ophthalmol ; 233: 111-123, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34166655

RESUMO

To identify functionally related genes associated with diabetic retinopathy (DR) risk using gene set enrichment analyses applied to genome-wide association study meta-analyses. METHODS: We analyzed DR GWAS meta-analyses performed on 3246 Europeans and 2611 African Americans with type 2 diabetes. Gene sets relevant to 5 key DR pathophysiology processes were investigated: tissue injury, vascular events, metabolic events and glial dysregulation, neuronal dysfunction, and inflammation. Keywords relevant to these processes were queried in 4 pathway and ontology databases. Two GSEA methods, Meta-Analysis Gene set Enrichment of variaNT Associations (MAGENTA) and Multi-marker Analysis of GenoMic Annotation (MAGMA), were used. Gene sets were defined to be enriched for gene associations with DR if the P value corrected for multiple testing (Pcorr) was <.05. RESULTS: Five gene sets were significantly enriched for numerous modest genetic associations with DR in one method (MAGENTA or MAGMA) and also at least nominally significant (uncorrected P < .05) in the other method. These pathways were regulation of the lipid catabolic process (2-fold enrichment, Pcorr = .014); nitric oxide biosynthesis (1.92-fold enrichment, Pcorr = .022); lipid digestion, mobilization, and transport (1.6-fold enrichment, P = .032); apoptosis (1.53-fold enrichment, P = .041); and retinal ganglion cell degeneration (2-fold enrichment, Pcorr = .049). The interferon gamma (IFNG) gene, previously implicated in DR by protein-protein interactions in our GWAS, was among the top ranked genes in the nitric oxide pathway (best variant P = .0001). CONCLUSIONS: These GSEA indicate that variants in genes involved in oxidative stress, lipid transport and catabolism, and cell degeneration are enriched for genes associated with DR risk. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Diabetes Mellitus Tipo 2/genética , Retinopatia Diabética/genética , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco
17.
Front Public Health ; 9: 697501, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513783

RESUMO

Introduction: Despite the growing efforts to standardize coding for social determinants of health (SDOH), they are infrequently captured in electronic health records (EHRs). Most SDOH variables are still captured in the unstructured fields (i.e., free-text) of EHRs. In this study we attempt to evaluate a practical text mining approach (i.e., advanced pattern matching techniques) in identifying phrases referring to housing issues, an important SDOH domain affecting value-based healthcare providers, using EHR of a large multispecialty medical group in the New England region, United States. To present how this approach would help the health systems to address the SDOH challenges of their patients we assess the demographic and clinical characteristics of patients with and without housing issues and briefly look into the patterns of healthcare utilization among the study population and for those with and without housing challenges. Methods: We identified five categories of housing issues [i.e., homelessness current (HC), homelessness history (HH), homelessness addressed (HA), housing instability (HI), and building quality (BQ)] and developed several phrases addressing each one through collaboration with SDOH experts, consulting the literature, and reviewing existing coding standards. We developed pattern-matching algorithms (i.e., advanced regular expressions), and then applied them in the selected EHR. We assessed the text mining approach for recall (sensitivity) and precision (positive predictive value) after comparing the identified phrases with manually annotated free-text for different housing issues. Results: The study dataset included EHR structured data for a total of 20,342 patients and 2,564,344 free-text clinical notes. The mean (SD) age in the study population was 75.96 (7.51). Additionally, 58.78% of the cohort were female. BQ and HI were the most frequent housing issues documented in EHR free-text notes and HH was the least frequent one. The regular expression methodology, when compared to manual annotation, had a high level of precision (positive predictive value) at phrase, note, and patient levels (96.36, 95.00, and 94.44%, respectively) across different categories of housing issues, but the recall (sensitivity) rate was relatively low (30.11, 32.20, and 41.46%, respectively). Conclusion: Results of this study can be used to advance the research in this domain, to assess the potential value of EHR's free-text in identifying patients with a high risk of housing issues, to improve patient care and outcomes, and to eventually mitigate socioeconomic disparities across individuals and communities.


Assuntos
Registros Eletrônicos de Saúde , Habitação , Mineração de Dados , Feminino , Humanos , Estudos Retrospectivos , Determinantes Sociais da Saúde , Estados Unidos
18.
J Endourol ; 34(7): 746-751, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31964178

RESUMO

Introduction: The purpose of this study was to evaluate factors during ureteroscopy that can potentially impact procedure cost. Materials and Methods: A retrospective review of 129 consecutive elective ureteroscopy cases was performed to determine direct procedure cost. Direct cost was defined as cost incurred because of operating room expenses, including operating room time, staffing expenses, equipment, and supply costs. Data regarding patient, procedural, and operating room staffing characteristics were compared between the most and least expensive cases. Univariate and logistic regression analysis were performed to identify factors predictive of higher costs. Results: The average direct ureteroscopy cost was $3298/case. On univariate analysis, ureteroscopies in the highest 50th cost percentile had larger stone burden (170.1 vs 146 mm2; p = 0.03) and longer operative times (95.3 vs 49.9 minutes; p < 0.01), were more likely performed for non-stone indications (21.4% vs 7.2%; p = 0.03), more likely to include a resident (65.5% vs 43.6%; p = 0.02), and less likely to have a dedicated urology scrub technician (38.2% vs 61.8%; p = 0.01) compared to cases in the lowest 50th percentile. The presence of a resident, larger stone burden, absence of a dedicated scrub technician, and longer operative time were associated with an average cost increase of $516, $700, $1122, and $1401, respectively. Logistic regression analysis showed that operating room time was the only factor predicting higher cost (OR [odds ratio] 12.8, 95% confidence interval [CI] 2.0-84.0). A post-hoc logistic regression analysis demonstrated that the presence of a resident during ureteroscopy (OR 2.9, 95% CI 1.1-8.0) and larger stone burden (OR 1.01, 95% CI 1.0-1.013) were significantly associated with longer operative times. Conclusion: Operating room time is the primary determinant of ureteroscopy case cost. All efforts should be made to decrease operative time, although balancing patient safety and maintaining a quality training environment.


Assuntos
Cálculos Ureterais , Urologia , Humanos , Duração da Cirurgia , Estudos Retrospectivos , Ureteroscopia , Recursos Humanos
19.
Urol Pract ; 11(6): 948, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39196662
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