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A systematic review and meta-analysis of the diagnostic accuracy after preimplantation genetic testing for aneuploidy
No full textOBJECTIVE: Aneuploidy accounts for many pregnancy failures and congenital anomalies. Preimplantation genetic testing for aneuploidy (PGT-A) is a screening test applied to embryos created from in vitro fertilization to diminish the chance of an aneuploid conception. The rate of misdiagnosis for both false aneuploidy (false positive) and false euploidy (false negative) test results is unknown. The objective of this study was to determine the rate of misclassification of both aneuploidy and euploidy after PGT-A.
DATA SOURCES: We conducted a systematic review and meta-analysis. We searched Medline, Embase, Cochrane Central, CINAHL and WHO Clinical Trials Registry from inception until April 10, 2024. The protocol was registered in International Prospective Register of Systematic Reviews (PROSPERO CRD 42020219074).
METHODS OF STUDY SELECTION: We included studies that conducted either a pre-clinical validation of the genetic platform for PGT-A using a cell line, studies that compared the embryo biopsy results to those from the whole dissected embryo or its inner cell mass (WE/ICM), and studies that compared the biopsy results to prenatal or postnatal genetic testing.
TABULATION, INTEGRATION, AND RESULTS: Two independent reviewers extracted true and false positives and negatives comparing biopsy results to the reference standard (known karyotype, WE/ICM, pregnancy outcome). For preclinical studies, the main outcome was the positive and negative predictive values. Misdiagnosis rate was the outcome for pregnancy outcome studies. The electronic search yielded 6674 citations, of which 109 were included. For WE/ICM studies (n=40), PPV was 89.2% (95% CI 83.1-94.0) and NPV was 94.2% (95% CI 91.1-96.7, I2=42%) for aneuploid and euploid embryos, respectively. The PPV for mosaic embryos of either a confirmatory mosaic or aneuploid result was 52.8% (95% CI 37.9-67.5). For pregnancy outcome studies (n=43), the misdiagnosis rate after euploid embryo transfer was 0.2% (95% CI 0.0-0.7%, I2=65%). However, the rate for mosaic transfer, with a confirmatory euploid pregnancy outcome, was 21.7% (95% CI: 9.6-36.9, I2=95%).
CONCLUSION: The accuracy of an aneuploid result from PGT-A is excellent and can be relied upon as a screening tool for embryos to avoid aneuploid pregnancies. Similarly, the misdiagnosis rate after euploid embryo transfer is less than 1%. However, there is a significant limitation in the accuracy of mosaic embryos
Unilateral Clear Thin Rhinorrhea: How Often Is It a Cerebrospinal Fluid Leak?
No full textOBJECTIVES: Determine frequencies of conditions causing unilateral clear thin rhinorrhea (UCTR), and assess whether certain clinical features are associated with CSF rhinorrhea.
METHODS: This was a retrospective review identifying all patients presenting with UCTR to one rhinologist over a 6-year period. The conditions causing UCTR were recorded, and the following demographic or clinical variables were collected when available: body-mass index (BMI, kg/m2), gender, age, race, and self-reported drainage volume (whether the UCTR dripped out the nose and could be collected, or it felt like a wet nostril with intermittent running down lip that was unlikely to be collectable).
RESULTS: Of 3,041 patients, 146 were identified with at least UCTR (4.8%). Mean age was 56.2 ± 17.6 years, and 65.8% were female. Amongst UCTR, nonallergic rhinitis (NAR) was the most common cause (45%), followed by CSF rhinorrhea (30%). On multivariate analysis, the following were significantly positively associated with CSF rhinorrhea: BMI≥30 (OR=4.95), ages 45-54 years (OR=3.67) and 55-64 years (OR=4.15), and self-reported UCTR dripping with collectability (OR=5.96)).
CONCLUSIONS: NAR was the most common cause of UCTR, representing nearly 50% of cases. However, CSF rhinorrhea still represented 30% of cases, reinforcing that UCTR should be worked up for CSF rhinorrhea, ideally with B2-Tf testing. BMI ≥30, ages 45-64 years, and patient-reported higher volume UCTR were positively associated with CSF rhinorrhea. If B2-Tf testing is negative or unobtainable, or clinical suspicion for CSF leak is low, clinicians can consider starting medical therapy for rhinitis or rhinosinusitis before pursuing further invasive CSF confirmatory testing
Diagnosing odontogenic sinusitis and avoiding the trap of maxillary sinus mucosal thickening on computed tomography: A clinical report
No full textOdontogenic sinusitis (ODS) refers to bacterial maxillary sinusitis caused by infectious maxillary dental pathology or dental procedures. ODS is the most common cause of unilateral sinusitis and a common cause of extrasinus infectious complications, including orbital and brain abscesses. While managing ODS has been highly successful, the greatest challenge can be recognizing and confirming the diagnosis. Diagnosing ODS requires confirming infectious maxillary dental pathology with appropriate examination and imaging and, very importantly, infectious sinusitis through nasal endoscopy. Sinus computed tomography is an important complimentary diagnostic method of confirming the location(s) of sinus disease but can be misleading if done without nasal endoscopy. Critical to note, clinicians must distinguish purulent ODS from maxillary sinus mucosal thickening (MSMT) seen on computed tomography, a reactive mucosal inflammation (mucositis) commonly seen with maxillary dental disease or dental treatment. MSMT is usually not infectious and, therefore, not usually ODS. The clinical scenario presented highlights the devastating progression from MSMT to ODS and ultimately a fatal brain abscess, all which had gone undetected for years. Recognizing and managing ODS requires increased ODS awareness and coordinated care between dental providers and otolaryngologists. Such interdisciplinary care will optimize outcomes for patients with ODS and may help prevent catastrophic complications
Practices of North American pediatric gastroenterologists in the management of celiac disease-A survey study
No full textCeliac disease (CD) is a common autoimmune disorder characterized by an immune-mediated reaction to gluten. We conducted a survey study of the pediatric gastroenterology list server to assess the practices of North American pediatric gastroenterologists in the management of CD. Overall, 160 out of 2400 respondents participated in the study, of which 52.5% of the respondents were females and 72.5% were practicing in university hospitals. Overall, respondents were practicing in adherence to the latest guidelines, except only 36% were screening for hepatitis B virus immunization at diagnosis on most of the visits, and 25% were utilizing human leukocyte antigens typing on most visits if serologies were negative. In addition, female respondents screened for vitamin D deficiency more often than males with a p value \u3c 0.05
Connective Tissue Disorder-Induced Diffuse Alveolar Hemorrhage: A Comprehensive Review with an Emphasis on Airway and Respiratory Management
No full textDiffuse alveolar hemorrhage (DAH), a catastrophic complication of connective tissue disorders (CTDs), manifests as rapid-onset hypoxemia, alveolar infiltrates, and progressive bleeding into the airways. While immune-mediated alveolar-endothelial injury primarily drives its pathophysiology, diagnosis is based on bronchoscopy and chest imaging. The clinical urgency lies in securing the compromised airway and stabilizing respiratory failure, a challenge increased by CTD-specific anatomical alterations such as cervical spine instability, cricoarytenoid arthritis, and subglottic stenosis. High-dose corticosteroids and immunosuppression are essential, while severe cases require extracorporeal membrane oxygenation or plasmapheresis. This comprehensive review introduces two novel approaches to address fundamental gaps in the management of CTD-induced DAH: a structured algorithm for a CTD-specific airway risk stratification tool, integrating anatomical screening and the application of lung ultrasounds (LUSs) for post-intubation CTD-induced DAH ventilation management. The need for a multidisciplinary team approach is also discussed. Despite aggressive care, mortality remains high (25-50%), underscoring the necessity for improved early recognition and intervention strategies for these high-risk patients
Direct-acting antivirals lower mortality and recurrence in HCV-related hepatocellular carcinoma post liver resection: A multicenter international study
No full textBACKGROUND: The impact of treatment on hepatitis C virus with direct-acting antivirals on 90-day postoperative outcomes, overall survival, and recurrence-free survival in patients after liver resection for hepatocellular carcinoma is unknown.
METHODS: We conducted a multicenter retrospective study. Adults who underwent liver resection for hepatitis C virus-related hepatocellular carcinoma between January 2000 and December 2018 were included from 7 international institutions. Groups included direct-acting antiviral treated, non-direct-acting antiviral treated, and untreated hepatitis C virus infection. We used a multivariable model to evaluate the association between receipt of preoperative direct-acting antivirals and 90-day postoperative major complications (Clavien-Dindo class ≥ III).
RESULTS: We identified 738 patients, including 206 (28%) direct-acting antiviral treated, 241 (33%) non-direct-acting antiviral treated, and 291 (39%) untreated patients. The sustained virologic response rate was 92% in the direct-acting antiviral and 71% in the non-direct-acting antiviral treatment groups. The median follow-up was 7.6 years (95% confidence interval 6.1, 8.6) after surgery for the entire cohort. Patients who received direct-acting antiviral therapy had better 5-year overall and recurrence-free survival than those without antiviral therapy (adjusted hazard ratio [95% confidence interval]: 0.26 [0.19, 0.35] and 0.52 [0.43, 0.64], respectively). Patients who received direct-acting antiviral therapy had better 5-year overall and recurrence-free survival than those who received non-direct-acting antiviral therapy (adjusted hazard ratio [95% confidence interval]: 0.49 [0.36, 0.66] and 0.78 [0.63, 0.96], respectively). There was no significant association between preoperative direct-acting antiviral therapy and 90-day postoperative major complications (adjusted odds ratio 0.34, 95% confidence interval 0.08, 1.01).
CONCLUSION: Direct-acting antiviral therapy is associated with improved 5-year overall and recurrence-free survival, without significantly increased risk of 90-day postoperative complications, in patients undergoing liver resection for hepatitis C virus-related hepatocellular carcinoma
Impact of Post-Implant Mitral Regurgitation on Durable Left Ventricular Assist Device Outcomes
No full textBACKGROUND: The association of significant post-implant mitral regurgitation (PI-MR) with left ventricular assist device (LVAD) outcomes remains controversial. We investigated PI-MR in the setting of contemporary LVAD therapy.
METHODS: The Society of Thoracic Surgeons (STS) Intermacs National Database was queried and identified 2,858 patients with a fully magnetically levitated centrifugal flow LVAD implanted from 2017-2021 who met study inclusion and exclusion criteria. Kaplan-Meir methodology and Cox proportional hazard modeling were used to evaluate the long-term impact of PI-MR on post-LVAD outcomes conditional on surviving 3 months post-LVAD implant. Significant PI-MR was defined as moderate-severe mitral regurgitation (MR) at the 1 or 3-month follow-up echocardiogram.
RESULTS: There were 340 patients with significant PI-MR and 2,518 without PI-MR following LVAD implant. Those with significant PI-MR were younger (53.2 vs 57.7 yrs, P\u3c 0.001), more likely to have a non-ischemic cardiomyopathy etiology of heart failure (66.5% vs. 51.5%, p\u3c .0001), preoperative moderate-severe tricuspid regurgitation (51.5% vs 37.6%, p\u3c .001), and concomitant tricuspid valve replacement/repair (17.1% vs 9.4%, P\u3c .001). Of those with preoperative significant MR, 17% (n=274) had significant PI-MR. Significant PI-MR was associated with worse 2-year survival (88.3% vs 79.5%, p=.008), risk for readmission (HR 1.19, p =.032) and subsequent renal failure (HR 1.84, p=.014).
CONCLUSIONS: Significant PI-MR following contemporary LVAD implant adversely impacts long-term survival and readmission. Strategies to prevent or intervene upon significant PI-MR require further investigation
Causes of death across different locations in the United States, 2015 to 2022
No full textOBJECTIVE: The objective of this study was to investigate the leading underlying causes of death across different locations in the USA from 2015 to 2022.
METHODS: Data on the leading underlying causes of death in each location of death-including medical outpatient facility or emergency room, medical inpatient facility, medical facility/dead on arrival, decedent\u27s home, hospice facility, and nursing home/long-term care-within the USA in individuals ≥18 years were extracted from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database.
RESULTS: There were 22,236,700 deaths in our studied locations during the study period. Most deaths were in the decedents\u27 homes (34.5%), followed by inpatient medical facilities (31.8%). Malignant neoplasms were the leading cause of death in hospice facilities (32.8%-40.0%) and decedents\u27 homes (25.9%-31.5%), followed by heart disease. Heart disease was the most common cause of death in nursing homes/long-term care facilities (20.0%-23.6%), outpatient or emergency medical facilities (36.5%-44.7%), those dead on arrival at medical facilities (35.4%-40.3%), and inpatient medical facilities (14.3%-20.4%), with COVID-19 becoming the top cause of death in 2020 and 2021 in inpatient medical facilities.
CONCLUSION: Overall, heart disease and malignant neoplasm were among the top three causes of death in all studied locations in our study period
HEART Camp Connect-Promoting adherence to exercise in adults with heart failure with preserved ejection fraction
No full textAIMS: Most adults with stable heart failure are safe to exercise at a moderate intensity for 150 min/week. Regular participation in exercise may improve outcomes in adults with heart failure with preserved ejection fraction (HFpEF). Few adults with HFpEF initiate and sustain long-term exercise. To promote exercise adherence in adults with HFpEF, we developed the Heart Failure Exercise and Resistance Training (HEART) Camp Connect intervention that is tested in this clinical trial. This trial tests our central hypothesis that theory-informed coaching strategies delivered virtually will promote long-term adherence to exercise in adults with HFpEF and drive clinically meaningful, and cost-effective improvements in physiological and patient-reported outcomes. Our aims are to (a) evaluate the effects of virtual and in-person exercise and coaching on long-term adherence, (b) determine a benchmark of minutes of moderate intensity exercise associated with health status as related to key biobehavioural outcomes, (c) examine behaviour change theory-defined constructs as mediators of exercise adherence and (d) evaluate intervention costs.
METHODS: This 18 month, three-group, repeated measures randomized controlled trial is enrolling 300 adults with HFpEF. Participants are randomized to enhanced usual care (EUC), virtual coaching, or in-person coaching. Our intervention applies coaching strategies, informed by behaviour change theories, in one-on-one and group settings weekly for 12 months. Our objective is to compare the effects of each delivery method to the other and EUC on exercise adherence (defined as ≥ 120 min of moderate intensity exercise/week) at 12 months (primary endpoint) and 18 months (sustainability endpoint). Secondary outcomes include minutes of moderate intensity exercise needed to drive minimal clinically important differences in health status, biomarkers, patient-reported symptoms and cost. Behaviour change theory-defined constructs (e.g., self-efficacy and outcome expectations) will be tested as mediators of exercise adherence.
RESULTS: We expect that virtual coaching is equally as efficacious and more cost effective at promoting exercise adherence as in-person coaching. Effects on exercise adherence may be mediated by theory-defined constructs. We also expect to identify a threshold for minutes of moderate intensity exercise to potentially serve as an adherence benchmark in adults with HFpEF, one that may differ from the 120 min of exercise in our current definition.
CONCLUSIONS: These findings could shift the paradigm of exercise coaching in HF towards virtual delivery and increase the generalizability and reach of exercise training. This is especially important for adults with HFpEF as they are excluded from Medicare reimbursement for traditional cardiopulmonary rehabilitation
Suicide Risk Screening in Jails: Protocol for a Pilot Study Leveraging the Mental Health Research Network Algorithm and Health Care Data
No full textBACKGROUND: Suicide in local jails occurs at a higher rate than in the general population, requiring improvements to risk screening methods. Current suicide risk screening practices in jails are insufficient: They are commonly not conducted using validated screening instruments, not collected by clinically trained professionals, and unlikely to capture honest responses due to the chaotic nature of booking areas. Therefore, new technologies could improve such practices. Several studies have indicated that machine learning (ML) models considerably improve accuracy and have positive predictive value in detecting suicide risk compared with practice as usual (PAU). This study will use administrative data and ML modeling to improve suicide risk detection at jail booking.
OBJECTIVE: This study is primarily focused on gathering preliminary information about the feasibility and practicality of using administrative data and ML modeling for suicide risk detection but also incorporates elements of hypothesis testing pertaining to clinical outcomes.
METHODS: The study uniquely contributes to our understanding of suicide risk by further validating an existing ML model developed and previously validated by the Mental Health Research Network using Medicaid outpatient health care claims data. This validation uses complete claims data on a sample of approximately 6000 individuals booked into 2 diverse jails in a midwestern state. This model validation uses 313 unique demographic and clinical characteristics from 5 years of historical health care data. It detects suicide risk in jails and postrelease by using merged jail, Medicaid, and vital records data. The study will use jail administrative data for September 1, 2021, through February 28, 2022; Medicaid records data for September 1, 2016, through March 31, 2023; and vital records data for March 1, 2022, through March 31, 2023.
RESULTS: First, the algorithm will be validated on the data gathered for the jail sample using the C-statistic and area under the receiver operating characteristic curve. Second, the resulting model will be compared with the jails\u27 suicide identification PAU to assess risk and detection of identified suicide attempts and deaths from intake through 120 days and 13 months after jail release. The funding timeline for this project is August 1, 2022, through July 31, 2025. The algorithm\u27s predictions and actual event incidence will be linked and validated in the spring of 2025, with results ready for publication in the fall of 2025.
CONCLUSIONS: The study will also investigate implementation factors, such as feasibility, acceptability, and appropriateness, to optimize jail uptake. Interview data on the implementation factors will be gathered in the summer of 2025, with expected dissemination in 2026. We hypothesize that a combination of intake screening PAU and the ML model will be the optimal approach, in that the combination will be more accurate and can have practical application in this context.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/68517