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Proteomic profiling for biomarker discovery in heparin-induced thrombocytopenia

Blood Adv. 2024 Apr 8:bloodadvances.2024012782. doi: 10.1182/bloodadvances.2024012782. Online ahead of print.

ABSTRACT

New analytical techniques can assess hundreds of proteins simultaneously with high sensitivity, facilitating the observation of their complex interplay and role in disease mechanisms. We hypothesized that proteomic profiling targeting proteins involved in thrombus formation, inflammation, and the immune response would identify potentially new biomarkers for heparin-induced thrombocytopenia (HIT). Four existing panels of the Olink proximity extension assay covering 356 proteins involved in thrombus formation, inflammation, and immune response were applied to randomly selected patients with suspected HIT (confirmed HIT, n=32; HIT ruled-out, n=38; positive heparin/PF4 [H/PF4] antibodies, n=28). The relative difference in protein concentration was analyzed using a linear regression model adjusted for sex and age. To confirm the test results, soluble P-selectin was determined using ELISA in above mentioned patients and an additional second dataset (n=49). HIT was defined as a positive heparin-induced platelet aggregation test (HIPA; washed platelet assay). Among 98 patients of the primary dataset, the median 4Ts score was 5 in patients with HIT, 4 in patients with positive heparin/PF4 antibodies, and 3 in patients without HIT. The median OD of a polyspecific heparin/PF4 ELISA was 3.0, 0.9, and 0.3, respectively. Soluble P-selectin remained statistically significant after multiple test adjustments. The area under the receiver-operating-characteristics-curve was 0.81 for Olink and 0.8 for ELISA. Future studies shall assess the diagnostic and prognostic value of soluble P-selectin in the management of HIT.

PMID:38588487 | DOI:10.1182/bloodadvances.2024012782

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Knowledge and perceived confidence of Brazilian psychiatrists about eating disorders´ diagnosis and treatment recommendations

Braz J Psychiatry. 2024 Apr 8. doi: 10.47626/1516-4446-2023-3516. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate Brazilian psychiatrists ́ knowledge and perceived confidence, both in diagnosis and in evidence-based treatments for eating disorders (ED).

METHODS: In this cross-sectional study, 259 psychiatrists filled out an online form including: sociodemographic data, questions about ED diagnosis and management based on standard guidelines. Descriptive statistics described sample characteristics and levels of ED knowledge and perceived confidence.

RESULTS: Sample was composed mainly by women (65,64%), with mean age of 42.86, from the Southeast of Brazil (56,37%), working predominantly in private practice (59,85%), with less than ten years of experience in Psychiatry (51,74%). We found that 33.21% of participants correctly chose diagnostic criteria for anorexia nervosa (AN); 29.73% for bulimia nervosa (BN), and 38.22% for binge eating disorder (BED). Correct answers for therapeutic options were similar in BN and BED (20.8%), being considerably lower for AN (2.7%). Additionally, reported ED training were: 15.1% during medical school; 59.8% during medical residency/postgraduate studies; 58.7% as complementary training. Only 8.89% felt satisfied with their ED training; 50.97% felt confident diagnosing ED and 37.07% in managing ED patients.

CONCLUSION: These results demonstrated an important gap in ED knowledge of Brazilian psychiatrists, and its consequences on their confidence and competence in managing ED patients.

PMID:38588459 | DOI:10.47626/1516-4446-2023-3516

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Investigation and Validation of the TEG6s During Rotary Wing Aeromedical Flight

J Trauma Acute Care Surg. 2024 Apr 8. doi: 10.1097/TA.0000000000004335. Online ahead of print.

ABSTRACT

INTRODUCTION: In order to improve rural and austere trauma care, hospital-based testing performed at the point of injury may shorten the time lapsed from injury to intervention. This study aimed to evaluate the use of the TEG6s® device in a rotary wing aircraft. Prior attempts suffered from limitation related to lack of vibration mitigation.

METHODS: This was an investigator initiated, industry supported study. Haemonetics® provided a TEG6s® analyzer. The device underwent a standard validation. It was secured in place on the aircraft utilizing shipping foam for vibration mitigation. Donors provided 2 tubes of sample blood in one sitting. Paired studies were performed on the aircraft during level flight and in the hospital, using the Global Hemostasis with Lysis Cartridge. Both normal and presumed pathologic samples were tested in separate phases. Paired T-tests were performed.

RESULTS: For normal donors, mean R (minutes) for laboratory compared to the aircraft was 6.2 vs. 7.2 (p = 0.025). Mean CRT MA (mm) was 59.3 and 55.9 ± 7.3 (p < 0.001) for lab and aircraft (p < 0.001). Among normal donors, R was within normal range for 17/18 laboratory and 18/18 aircraft tests (p > 0.99).During the testing of pathologic samples mean R time was 14.8 for lab samples and 12.6 minutes for aircraft (p = 0.02). Aircraft samples were classified as abnormal in 78% of samples, this was not significantly different than lab samples (p = 0.5).

CONCLUSIONS: The use of the TEG6s® for inflight viscoelastic testing appears promising. While statistically significant differences are seen in some results, these values are not considered clinically significant. Classifying samples as normal or abnormal demonstrated a higher correlation. Future studies should focus on longer flight times to evaluate for LY30, takeoff and landing effects. Overall, this study suggests that TEG6s® can be utilized in a prehospital environment, and further study is warranted.

LEVEL OF EVIDENCE: Level II, Diagnostic Tests or Criteria.

PMID:38587897 | DOI:10.1097/TA.0000000000004335

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Understanding Adolescents’ Experiences With Menstrual Pain to Inform the User-Centered Design of a Mindfulness-Based App: Mixed Methods Investigation Study

JMIR Pediatr Parent. 2024 Apr 8;7:e54658. doi: 10.2196/54658.

ABSTRACT

BACKGROUND: Digital interventions are increasingly popular for the provision of nonpharmacological pain interventions, but few exist for adolescents with menstrual pain. User-centered design involves incorporating users across phases of digital health intervention design, development, and implementation and leads to improved user engagement and outcomes. A needs assessment is the first step of this approach.

OBJECTIVE: The goal of this study was to conduct a needs assessment to understand menstrual pain management needs and preferences and mindfulness experiences, preferences, and knowledge of adolescents with menstrual pain to inform the future development of an app for managing menstrual pain.

METHODS: We used an explanatory sequential mixed method design that included a survey followed by focus groups. Adolescents aged 13-17 years completed a survey (n=111) and participated in focus groups (n=16). Data were analyzed using descriptive statistics and thematic content analysis and synthesized to provide specific recommendations based on adolescent responses.

RESULTS: Adolescents (n=111) who completed the survey reported a moderate understanding of mindfulness and menstrual pain. Over three-quarters (n=87, 78%) of participants practiced some form of mindfulness and 87% (n=97) of survey participants used nonpharmacological pain management strategies. Teens had a moderate perception that mindfulness could help their menstrual pain (mean 4.51/10, SD 2.45, with higher scores suggesting more interest). Themes were generated related to mindfulness experiences, menstrual pain knowledge and experiences, and app functionality. These themes underscored adolescents’ need for continued support and flexible access to mindfulness activities; their awareness of multiple influences to pain, with potential for further education in this area; and the need for menstrual pain-specific content, along with content relevant to typical day-to-day experiences of adolescents.

CONCLUSIONS: Adolescents with menstrual pain have an interest in using a mindfulness app for pain but have unique needs that need to be addressed to ensure app engagement and relevance for this population. Concrete recommendations for future app development are provided.

PMID:38587886 | DOI:10.2196/54658

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Early Seizure Prophylaxis in Mild and Moderate Traumatic Brain Injury: A Systematic Review and Meta-Analysis

JAMA Neurol. 2024 Apr 8. doi: 10.1001/jamaneurol.2024.0689. Online ahead of print.

ABSTRACT

IMPORTANCE: Guidelines recommend seizure prophylaxis for early posttraumatic seizures (PTS) after severe traumatic brain injury (TBI). Use of antiseizure medications for early seizure prophylaxis after mild or moderate TBI remains controversial.

OBJECTIVE: To determine the association between seizure prophylaxis and risk reduction for early PTS in mild and moderate TBI.

DATA SOURCES: PubMed, Google Scholar, and Web of Science (January 1, 1991, to April 18, 2023) were systematically searched.

STUDY SELECTION: Observational studies of adult patients presenting to trauma centers in high-income countries with mild (Glasgow Coma Scale [GCS], 13-15) and moderate (GCS, 9-12) TBI comparing rates of early PTS among patients with seizure prophylaxis with those without seizure prophylaxis.

DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) reporting guidelines were used. Two authors independently reviewed all titles and abstracts, and 3 authors reviewed final studies for inclusion. A meta-analysis was performed using a random-effects model with absolute risk reduction.

MAIN OUTCOME MEASURES: The main outcome was absolute risk reduction of early PTS, defined as seizures within 7 days of initial injury, in patients with mild or moderate TBI receiving seizure prophylaxis in the first week after injury. A secondary analysis was performed in patients with only mild TBI.

RESULTS: A total of 64 full articles were reviewed after screening; 8 studies (including 5637 patients) were included for the mild and moderate TBI analysis, and 5 studies (including 3803 patients) were included for the mild TBI analysis. The absolute risk reduction of seizure prophylaxis for early PTS in mild to moderate TBI (GCS, 9-15) was 0.6% (95% CI, 0.1%-1.2%; P = .02). The absolute risk reduction for mild TBI alone was similar 0.6% (95% CI, 0.01%-1.2%; P = .04). The number needed to treat to prevent 1 seizure was 167 patients.

CONCLUSION AND RELEVANCE: Seizure prophylaxis after mild and moderate TBI was associated with a small but statistically significant reduced risk of early posttraumatic seizures after mild and moderate TBI. The small absolute risk reduction and low prevalence of early seizures should be weighed against potential acute risks of antiseizure medications as well as the risk of inappropriate continuation beyond 7 days.

PMID:38587858 | DOI:10.1001/jamaneurol.2024.0689

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Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy: A Nonrandomized Controlled Trial

JAMA Pediatr. 2024 Apr 8. doi: 10.1001/jamapediatrics.2024.0492. Online ahead of print.

ABSTRACT

IMPORTANCE: There is increasing evidence that early diagnosis and treatment are key for outcomes in infants with spinal muscular atrophy (SMA), and newborn screening programs have been implemented to detect the disease before onset of symptoms. However, data from controlled studies that reliably confirm the benefits of newborn screening are lacking.

OBJECTIVE: To compare data obtained on patients with SMA diagnosed through newborn screening and those diagnosed after clinical symptom onset.

DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized controlled trial used data from the SMARTCARE registry to evaluate all children born between January 2018 and September 2021 with genetically confirmed SMA and up to 3 SMN2 copies. The registry includes data from 70 participating centers in Germany, Austria, and Switzerland. Data analysis was performed in February 2023 so that all patients had a minimal follow-up of 18 months.

EXPOSURE: Patients born in 2 federal states in Germany underwent screening in a newborn screening pilot project. All other patients were diagnosed after clinical symptom onset. All patients received standard care within the same health care system.

MAIN OUTCOMES: The primary end point was the achievement of motor milestones.

RESULTS: A total of 234 children (123 [52.6%] female) were identified who met inclusion criteria and were included in the analysis: 44 (18.8%) in the newborn screening cohort and 190 children (81.2%) in the clinical symptom onset cohort. The mean (SD) age at start of treatment with 1 of the approved disease-modifying drugs was 1.3 (2.2) months in the newborn screening cohort and 10.7 (9.1) months in the clinical symptom onset cohort. In the newborn screening cohort, 40 of 44 children (90.9%) gained the ability to sit independently vs 141 of 190 (74.2%) in the clinical symptom onset cohort. For independent ambulation, the ratio was 28 of 40 (63.6%) vs 28 of 190 (14.7%).

CONCLUSIONS AND RELEVANCE: This nonrandomized controlled trial demonstrated effectiveness of newborn screening for infants with SMA in the real-world setting. Functional outcomes and thus the response to treatment were significantly better in the newborn screening cohort compared to the unscreened clinical symptom onset group.

TRIAL REGISTRATION: German Clinical Trials Register: DRKS00012699.

PMID:38587854 | DOI:10.1001/jamapediatrics.2024.0492

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Driver’s Licensure and Driving Outcomes Among Youths With Mood Disorders

JAMA Netw Open. 2024 Apr 1;7(4):e245543. doi: 10.1001/jamanetworkopen.2024.5543.

ABSTRACT

IMPORTANCE: Mood disorders are prevalent among adolescents and young adults, and their onset often coincides with driving eligibility. The understanding of how mood disorders are associated with youth driving outcomes is limited.

OBJECTIVE: To examine the association between the presence of a mood disorder and rates of licensing, crashes, violations, and suspensions among adolescents and young adults.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted among New Jersey residents who were born 1987 to 2000, age eligible to acquire a driver’s license from 2004 to 2017, and patients of the Children’s Hospital of Philadelphia network within 2 years of licensure eligibility at age 17 years. The presence of a current (ie, ≤2 years of driving eligibility) mood disorder was identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Rates of licensure and driving outcomes among youths who were licensed were compared among 1879 youths with and 84 294 youths without a current mood disorder from 2004 to 2017. Data were analyzed from June 2022 to July 2023.

MAIN OUTCOMES AND MEASURES: Acquisition of a driver’s license and first involvement as a driver in a police-reported crash and rates of other adverse driving outcomes were assessed. Survival analysis was used to estimate adjusted hazard ratios (aHRs) for licensing and driving outcomes. Adjusted rate ratios (aRRs) were estimated for driving outcomes 12 and 48 months after licensure.

RESULTS: Among 86 173 youths (median [IQR] age at the end of the study, 22.8 [19.7-26.5] years; 42 894 female [49.8%]), there were 1879 youths with and 84 294 youths without a mood disorder. A greater proportion of youths with mood disorders were female (1226 female [65.2%]) compared with those without mood disorders (41 668 female [49.4%]). At 48 months after licensure eligibility, 75.5% (95% CI, 73.3%-77.7%) and 83.8% (95% CI, 83.5%-84.1%) of youths with and without mood disorders, respectively, had acquired a license. Youths with mood disorders were 30% less likely to acquire a license than those without a mood disorder (aHR, 0.70 [95% CI, 0.66-0.74]). Licensed youths with mood disorders had higher overall crash rates than those without mood disorders over the first 48 months of driving (137.8 vs 104.8 crashes per 10 000 driver-months; aRR, 1.19 [95% CI, 1.08-1.31]); licensed youths with mood disorders also had higher rates of moving violations (aRR, 1.25 [95% CI, 1.13-1.38]) and license suspensions (aRR, 1.95 [95% CI, 1.53-2.49]).

CONCLUSIONS AND RELEVANCE: This study found that youths with mood disorders were less likely to be licensed and had higher rates of adverse driving outcomes than youths without mood disorders. These findings suggest that opportunities may exist to enhance driving mobility in this population and elucidate the mechanisms by which mood disorders are associated with crash risk.

PMID:38587843 | DOI:10.1001/jamanetworkopen.2024.5543

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d-Mannose for Prevention of Recurrent Urinary Tract Infection Among Women: A Randomized Clinical Trial

JAMA Intern Med. 2024 Apr 8. doi: 10.1001/jamainternmed.2024.0264. Online ahead of print.

ABSTRACT

IMPORTANCE: Recurrent urinary tract infection (UTI) is a common debilitating condition in women, with limited prophylactic options. d-Mannose has shown promise in trials based in secondary care, but effectiveness in placebo-controlled studies and community settings has not been established.

OBJECTIVE: To determine whether d-mannose taken for 6 months reduces the proportion of women with recurrent UTI experiencing a medically attended UTI.

DESIGN, SETTING, AND PARTICIPANTS: This 2-group, double-blind randomized placebo-controlled trial took place across 99 primary care centers in the UK. Participants were recruited between March 28, 2019, and January 31, 2020, with 6 months of follow-up. Participants were female, 18 years or older, living in the community, and had evidence in their primary care record of consultations for at least 2 UTIs in the preceding 6 months or 3 UTIs in 12 months. Invitation to participate was made by their primary care center. A total of 7591 participants were approached, 830 responded, and 232 were ineligible or did not proceed to randomization. Statistical analysis was reported in December 2022.

INTERVENTION: Two grams daily of d-mannose powder or matched volume of placebo powder.

MAIN OUTCOMES AND MEASURES: The primary outcome measure was the proportion of women experiencing at least 1 further episode of clinically suspected UTI for which they contacted ambulatory care within 6 months of study entry. Secondary outcomes included symptom duration, antibiotic use, time to next medically attended UTI, number of suspected UTIs, and UTI-related hospital admissions.

RESULTS: Of 598 women eligible (mean [range] age, 58 [18-93] years), 303 were randomized to d-mannose (50.7%) and 295 to placebo (49.3%). Primary outcome data were available for 583 participants (97.5%). The proportion contacting ambulatory care with a clinically suspected UTI was 150 of 294 (51.0%) in the d-mannose group and 161 of 289 (55.7%) in the placebo group (risk difference, -5%; 95% CI, -13% to 3%; P = .26). Estimates were similar in per protocol analyses, imputation analyses, and preplanned subgroups. There were no statistically significant differences in any secondary outcome measures.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, daily d-mannose did not reduce the proportion of women with recurrent UTI in primary care who experienced a subsequent clinically suspected UTI. d-Mannose should not be recommended for prophylaxis in this patient group.

TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN13283516.

PMID:38587819 | DOI:10.1001/jamainternmed.2024.0264

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A Classification-Based Adaptive Segmentation Pipeline: Feasibility Study Using Polycystic Liver Disease and Metastases from Colorectal Cancer CT Images

J Imaging Inform Med. 2024 Apr 8. doi: 10.1007/s10278-024-01072-3. Online ahead of print.

ABSTRACT

Automated segmentation tools often encounter accuracy and adaptability issues when applied to images of different pathology. The purpose of this study is to explore the feasibility of building a workflow to efficiently route images to specifically trained segmentation models. By implementing a deep learning classifier to automatically classify the images and route them to appropriate segmentation models, we hope that our workflow can segment the images with different pathology accurately. The data we used in this study are 350 CT images from patients affected by polycystic liver disease and 350 CT images from patients presenting with liver metastases from colorectal cancer. All images had the liver manually segmented by trained imaging analysts. Our proposed adaptive segmentation workflow achieved a statistically significant improvement for the task of total liver segmentation compared to the generic single-segmentation model (non-parametric Wilcoxon signed rank test, n = 100, p-value << 0.001). This approach is applicable in a wide range of scenarios and should prove useful in clinical implementations of segmentation pipelines.

PMID:38587766 | DOI:10.1007/s10278-024-01072-3

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The effect of significant weight loss after bariatric surgery on echocardiographic indices: an observational study focusing on left ventricular deformation by 2D speckle echocardiography and right ventricular size

Egypt Heart J. 2024 Apr 8;76(1):44. doi: 10.1186/s43044-024-00474-6.

ABSTRACT

BACKGROUND: Obesity is a known risk factor for atherosclerosis and cardiac disease.

HYPOTHESIS: This study evaluated the effect of significant weight loss following bariatric surgery on myocardial deformation indices and right ventricular size (RV). This was a prospective cohort study. Morbid obese patients scheduled for bariatric surgery from July 2017 to February 2018 at Firoozgar Hospital were included in our study and referred for transthoracic echocardiography at Rajaie Cardiovascular Medical and Research Center.

RESULTS: Thirty-four patients entered the study. The absolute value of global longitudinal strain (GLS) at baseline, 3, and 6 months after surgery was 17.42 ± 2.94%, 18.24 ± 3.09%, and 19.52 ± 2.78%, respectively, with a statistically significant difference from baseline to after six months (P value < 0.001). The absolute value of global circumferential strain (GCS) at baseline, 3, and 6 months after surgery was 20.14 ± 4.22%, 23.32 ± 4.66%, and 24.53 ± 4.52%, respectively, with statistically significant changes (P value < 0.001) from baseline to three months and from baseline to six months and no significant difference from three months to six months. A significant decrease was reported in mechanical dispersion of circumferential strain (38.05 ± 23.81-23.37 ± 20.86 ms, P value = 0.006) 6 months after surgery. Right ventricular size three- and six-month post-surgery showed a significant decrease relative to baseline echocardiography.

CONCLUSIONS: Bariatric surgery could enhance cardiac function, as proven by 2D speckle echocardiography. Changes in RV size may be related to weight loss and should be considered when assessing patients who have undergone bariatric surgery.

PMID:38587759 | DOI:10.1186/s43044-024-00474-6