Predicting optical coherence tomography-derived diabetic macular edema grades from fundus photographs using deep learning

Diabetic eye disease is one of the fastest growing causes of preventable blindness. With the advent of anti-VEGF (vascular endothelial growth factor) therapies, it has become increasingly important to detect center-involved diabetic macular edema (ci-DME). However, center-involved diabetic macular edema is diagnosed using optical coherence tomography (OCT), which is not generally available at screening sites because of cost and workflow constraints. Instead, screening programs rely on the detection of hard exudates in color fundus photographs as a proxy for DME, often resulting in high false positive or false negative calls. To improve the accuracy of DME screening, we trained a deep learning model to use color fundus photographs to predict ci-DME. Our model had an ROC-AUC of 0.89 (95% CI: 0.87-0.91), which corresponds to a sensitivity of 85% at a specificity of 80%. In comparison, three retinal specialists had similar sensitivities (82-85%), but only half the specificity (45-50%, p<0.001 for each comparison with model). The positive predictive value (PPV) of the model was 61% (95% CI: 56-66%), approximately double the 36-38% by the retinal specialists. In addition to predicting ci-DME, our model was able to detect the presence of intraretinal fluid with an AUC of 0.81 (95% CI: 0.81-0.86) and subretinal fluid with an AUC of 0.88 (95% CI: 0.85-0.91). The ability of deep learning algorithms to make clinically relevant predictions that generally require sophisticated 3D-imaging equipment from simple 2D images has broad relevance to many other applications in medical imaging

Human intestinal anion exchanger isoforms: expression, distribution, and membrane localization

AbstractA family of anion exchangers (AEs) including AE1, AE2 and AE3 has been described. AE3 gene has been shown to encode two alternatively spliced isoforms termed as bAE3 (brain subtype) and cAE3 (cardiac subtype). The identity of the AE(s) involved in the human intestinal NaCl absorption is not fully understood. Current studies were undertaken to identify the AE isoforms expressed in the human intestine, to define their regional and vertical axis (crypt vs. surface cells) distribution, and to elucidate their membrane localization in the epithelial cells along the entire length of the human intestine. Our studies utilizing reverse transcription (RT)-PCR with total RNA extracted from pinch biopsies from various regions of the human intestine demonstrate that AE2 and bAE3 but not AE1 or cAE3 were expressed in all the regions of the human intestine. Utilizing in situ RT-PCR, we demonstrated that the message of AE2 was expressed throughout the vertical surface–crypt axis of the colon. Our Western blotting studies demonstrated that AE2 and bAE3 are localized to the basolateral but not the apical membranes of the intestinal epithelial cells from the human ileum and colon. In conclusion, our results demonstrated that in the human intestine, AE2 and bAE3, but not AE1 or cAE3, are expressed throughout the tract with the highest expression in the colon compared to the ileum and jejunum. Both the isoforms were found to be localized to the basolateral but not the apical membranes of the epithelial cells. We speculate that, in the human intestine, AE2 and bAE3 may be the ‘housekeeping’ isoforms, and the apical AE, the potential candidate for chloride absorption, remains to be identified

The Impact of Nondisclosure of Geographic Segment Earnings on Earnings Predictability

Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.

Background Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. Purpose We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. Data source We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Study selection Two authors independently reviewed the studies for eligibility. Data extraction Data about studies characteristics, adjusted effect estimates and quality were extracted. Data synthesis Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). Conclusion In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics

Predicting optical coherence tomography-derived diabetic macular edema grades from fundus photographs using deep learning

Center-involved diabetic macular edema (ci-DME) is a major cause of vision loss. Although the gold standard for diagnosis involves 3D imaging, 2D imaging by fundus photography is usually used in screening settings, resulting in high false-positive and false-negative calls. To address this, we train a deep learning model to predict ci-DME from fundus photographs, with an ROC–AUC of 0.89 (95% CI: 0.87–0.91), corresponding to 85% sensitivity at 80% specificity. In comparison, retinal specialists have similar sensitivities (82–85%), but only half the specificity (45–50%, p < 0.001). Our model can also detect the presence of intraretinal fluid (AUC: 0.81; 95% CI: 0.81–0.86) and subretinal fluid (AUC 0.88; 95% CI: 0.85–0.91). Using deep learning to make predictions via simple 2D images without sophisticated 3D-imaging equipment and with better than specialist performance, has broad relevance to many other applications in medical imaging

Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship

Achieved systolic blood pressure in older people: A systematic review and meta-analysis

Background: It remains unclear into which level the systolic blood pressure (SBP) should be lowered in order to provide the best cardiovascular protection among older people. Hypertension guidelines recommendation on attaining SBP levels 33,600 participants) were included. Compared with attaining SBP levels ≥140 mmHg, levels of 130 to <140 mmHg were not associated with lower risk of outcomes in the meta-analysis of RCTs, whereas there was an associated reduction of cardiovascular mortality (RR 0.72, 95% CI 0.59-0.88) and all-cause mortality (RR 0.86, 95% CI 0.75-0.99) in the meta-analysis of post-hoc analyses or subanalyses of RCTs. Limited and conflicting data were available for the SBP levels of <130 mmHg and 140 to <150 mmHg. Conclusions: Among older people, there is suggestive evidence that achieving SBP levels of 130 to <140 mmHg is associated with lower risks of cardiovascular and all-cause mortality. Future trials are required to confirm these findings and to provide additional evidence regarding the <130 and 140 to <150 mmHg SBP levels

Pre-Morbid Body Mass Index and Mortality After Incident Heart Failure

Although obesity is an independent risk factor for heart failure (HF), once HF is established, obesity is associated with lower mortality. It is unclear if the weight loss due to advanced HF leads to this paradoxical finding