HIV and Hepatitis C-Coinfected Patients Have Lower Low-Density Lipoprotein Cholesterol Despite Higher Proprotein Convertase Subtilisin Kexin 9 (PCSK9): An Apparent "PCSK9-Lipid Paradox".

BackgroundProprotein convertase subtilisin kexin 9 (PCSK9) inhibitors reduce low-density lipoprotein cholesterol (LDL-C) and improve outcomes in the general population. HIV-infected individuals are at increased risk for cardiovascular events and have high rates of dyslipidemia and hepatitis C virus (HCV) coinfection, making PCSK9 inhibition a potentially attractive therapy.Methods and resultsWe studied 567 participants from a clinic-based cohort to compare PCSK9 levels in patients with HIV/HCV coinfection (n=110) with those with HIV infection alone (n=385) and with uninfected controls (n=72). The mean age was 49 years, and the median LDL-C level was 100 mg/dL (IQR 77-124 mg/dL); 21% were taking statins. The 3 groups had similar rates of traditional risk factors. Total cholesterol, LDL-C, and high-density lipoprotein cholesterol levels were lower in coinfected patients compared with controls (P<0.001). PCSK9 was 21% higher in HIV/HCV-coinfected patients versus controls (95% CI 9-34%, P<0.001) and 11% higher in coinfected individuals versus those with HIV infection alone (95% CI 3-20%, P=0.008). After adjustment for cardiovascular risk factors, HIV/HCV coinfection remained significantly associated with 20% higher PCSK9 levels versus controls (95% CI 8-33%, P=0.001). Interleukin-6 levels increased in a stepwise fashion from controls (lowest) to HIV-infected to HIV/HCV-coinfected individuals (highest) and correlated with PCSK9 (r=0.11, P=0.018).ConclusionsDespite having lower LDL-C, circulating PCSK9 levels were increased in patients coinfected with HIV and HCV in parallel with elevations in the inflammatory, proatherogenic cytokine interleukin-6. Clinical trials should be conducted to determine the efficacy of targeted PCSK9 inhibition in the setting of HIV/HCV coinfection

The Strong Maximum Circulation Algorithm: A New Method for Aggregating Preference Rankings

We present a new optimization-based method for aggregating preferences in settings where each decision maker, or voter, expresses preferences over pairs of alternatives. The challenge is to come up with a ranking that agrees as much as possible with the votes cast in cases when some of the votes conflict. Only a collection of votes that contains no cycles is non-conflicting and can induce a partial order over alternatives. Our approach is motivated by the observation that a collection of votes that form a cycle can be treated as ties. The method is then to remove unions of cycles of votes, or circulations, from the vote graph and determine aggregate preferences from the remainder. We introduce the strong maximum circulation which is formed by a union of cycles, the removal of which guarantees a unique outcome in terms of the induced partial order. Furthermore, it contains all the aggregate preferences remaining following the elimination of any maximum circulation. In contrast, the well-known, optimization-based, Kemeny method has non-unique output and can return multiple, conflicting rankings for the same input. In addition, Kemeny's method requires solving an NP-hard problem, whereas our algorithm is efficient, based on network flow techniques, and runs in strongly polynomial time, independent of the number of votes. We address the construction of a ranking from the partial order and show that rankings based on a convex relaxation of Kemeny's model are consistent with our partial order. We then study the properties of removing a maximal circulation versus a maximum circulation and establish that, while maximal circulations will in general identify a larger number of aggregate preferences, the partial orders induced by the removal of different maximal circulations are not unique and may be conflicting. Moreover, finding a minimum maximal circulation is an NP-hard problem.Comment: 22 pages, 4 figure

Artificial Intelligence Application in Assessment of Panoramic Radiographs

The aim of this study was to assess the reliability of the artificial intelligence (AI) automatic evaluation of panoramic radiographs (PRs). Thirty PRs, covering at least six teeth with the possibility of assessing the marginal and apical periodontium, were uploaded to the Diagnocat (LLC Diagnocat, Moscow, Russia) account, and the radiologic report of each was generated as the basis of automatic evaluation. The same PRs were manually evaluated by three independent evaluators with 12, 15, and 28 years of experience in dentistry, respectively. The data were collected in such a way as to allow statistical analysis with SPSS Statistics software (IBM, Armonk, NY, USA). A total of 90 reports were created for 30 PRs. The AI protocol showed very high specificity (above 0.9) in all assessments compared to ground truth except from periodontal bone loss. Statistical analysis showed a high interclass correlation coefficient (ICC > 0.75) for all interevaluator assessments, proving the good credibility of the ground truth and the reproducibility of the reports. Unacceptable reliability was obtained for caries assessment (ICC = 0.681) and periapical lesions assessment (ICC = 0.619). The tested AI system can be helpful as an initial evaluation of screening PRs, giving appropriate credibility reports and suggesting additional diagnostic methods for more accurate evaluation if needed

Physician Accuracy in Interpreting Potential ST‐Segment Elevation Myocardial Infarction Electrocardiograms

Background: With adoption of telemedicine, physicians are increasingly asked to diagnose ST‐segment elevation myocardial infarctions (STEMIs) based on electrocardiograms (ECGs) with minimal associated clinical information. We sought to determine physicians' diagnostic agreement and accuracy when interpreting potential STEMI ECGs. Methods and Results: A cross‐sectional survey was performed consisting of 36 deidentified ECGs that had previously resulted in putative STEMI diagnoses. Emergency physicians, cardiologists, and interventional cardiologists participated in the survey. For each ECG, physicians were asked, “based on the ECG above, is there a blocked coronary artery present causing a STEMI?” The reference standard for ascertaining the STEMI diagnosis was subsequent emergent coronary arteriography. Responses were analyzed with generalized estimating equations to account for nested and repeated measures. One hundred twenty‐four physicians interpreted a total of 4392 ECGs. Among all physicians, interreader agreement (kappa) for ECG interpretation was 0.33, reflecting poor agreement. The sensitivity to identify “true” STEMIs was 65% (95% CI: 63 to 67) and the specificity was 79% (95% CI: 77 to 81). There was a 6% increase in the odds of accurate ECG interpretation for every 5 years of experience since medical school graduation (OR 1.06, 95% CI: 1.02 to 1.10, P=0.01). After adjusting for experience, there was no significant difference in the odds of accurate interpretation by specialty—Emergency Medicine (reference), General Cardiology (AOR 0.97, 95% CI: 0.79 to 1.2, P=0.80), or Interventional Cardiology physicians (AOR 1.24, 95% CI: 0.93 to 1.7, P=0.15). Conclusions: There is significant physician disagreement in interpreting ECGs with features concerning for STEMI. Such ECGs lack the necessary sensitivity and specificity to act as a suitable “stand‐alone” diagnostic test

Esophageal sphincter device for gastroesophageal reflux disease

BACKGROUND Patients with gastroesophageal reflux disease who have a partial response to proton-pump inhibitors often seek alternative therapy. We evaluated the safety and effectiveness of a new magnetic device to augment the lower esophageal sphincter. METHODS We prospectively assessed 100 patients with gastroesophageal reflux disease before and after sphincter augmentation. The study did not include a concurrent control group. The primary outcome measure was normalization of esophageal acid exposure or a 50% or greater reduction in exposure at 1 year. Secondary outcomes were 50% or greater improvement in quality of life related to gastroesophageal reflux disease and a 50% or greater reduction in the use of proton-pump inhibitors at 1 year. For each outcome, the prespecified definition of successful treatment was achievement of the outcome in at least 60% of the patients. The 3-year results of a 5-year study are reported. RESULTS The primary outcome was achieved in 64% of patients (95% confidence interval [CI], 54 to 73). For the secondary outcomes, a reduction of 50% or more in the use of proton-pump inhibitors occurred in 93% of patients, and there was improvement of 50% or more in quality-of-life scores in 92%, as compared with scores for patients assessed at baseline while they were not taking proton-pump inhibitors. The most frequent adverse event was dysphagia (in 68% of patients postoperatively, in 11% at 1 year, and in 4% at 3 years). Serious adverse events occurred in six patients, and in six patients the device was removed. CONCLUSIONS In this single-group evaluation of 100 patients before and after sphincter augmentation with a magnetic device, exposure to esophageal acid decreased, reflux symptoms improved, and use of proton-pump inhibitors decreased. Follow-up studies are needed to assess long-term safety. (Funded by Torax Medical; ClinicalTrials.gov number, NCT00776997.

Process of diffusing cancer survivorship care into oncology practice

The LIVESTRONG Centers of Excellence were funded to increase the effectiveness of survivorship care in oncology practice. This study describes the ongoing process of adopting and implementing survivorship care using the framework of the diffusion of innovation theory of change. Primary data collection included telephone interviews with 39 members from the eight centers and site visits. Organizational characteristics, overall progress, and challenges for implementation were collected from proposals and annual reports. Creating an awareness of cancer survivorship care was a major accomplishment (relative advantage). Adoption depended on the fit within the cancer center (compatibility), and changed over time based on trial and error (trialability). Implementing survivorship care within the existing culture of oncology and breaking down resistance to change was a lengthy process (complexity). Survivorship care became sustainable as it became reimbursed, and more new patients were seen (observability). Innovators and early adopters were crucial to success. Diffusion of innovation theory can provide a strategy to evaluate adoption and implementation of cancer survivorship programs into clinical practice