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Integrated Transcriptome Analysis Reveals Novel Molecular Signatures for Schizophrenia Characterization
No full textSchizophrenia (SCZ) is a complex psychiatric disorder presenting challenges for characterization. The current study aimed to identify and evaluate disease-responsive essential genes (DREGs) to enhance the molecular characterization of SCZ. RNA-sequencing data from PsychENCODE (536 SCZ patients, 832 controls) and peripheral blood transcriptome data from 144 recruited subjects (59 SCZ patients, 6 non-SCZ psychiatric patients, 79 controls) are analyzed. Shared differential expression genes are obtained using three algorithms. Support vector machine (SVM)-based recursive feature elimination is employed to identify DREGs. The biological relevance of these DREGs is examined through protein-protein interaction network, pathway enrichment, polygenic scoring, and brain tissue expression. Key DREGs are validated in SCZ animal models. A DREGs-based machine-learning model for SCZ characterization is developed and its performance is assessed using multiple datasets. The analysis identified 184 DREGs forming an interconnected network involved in synaptic plasticity, inflammation, neuronal development, and neurotransmission. DREGs exhibited distinct expression in SCZ-related brain regions and animal models. Their genetic contributions are comparable to genome-wide polygenic risk scores. The DREG-based SVM model demonstrated high performance (AUC 85% for SCZ characterization, 79% for specificity). These findings provide new insights into the molecular mechanisms underlying SCZ and emphasize the potential of DREGs in improving SCZ characterization
Contextual factors influencing bubble continuous positive airway pressure implementation for paediatric respiratory distress in low-income and middle-income countries: a realist review
No full textBACKGROUND: Bubble continuous positive airway pressure (bCPAP) is a low-cost, non-invasive respiratory support therapy for children with respiratory distress, but its effectiveness is dependent on the context. We aimed to understand contextual factors influencing bCPAP implementation for children aged 1-59 months in low-income and middle-income countries (LMICs) and to develop a theory explaining how these factors influence implementation outcomes.
METHODS: In this realist review, we generated an initial programme theory comprising candidate context-mechanism-outcome configurations (CMOCs) via review of key references and team discussion. On July 25, 2023, we conducted a search for peer-reviewed and grey literature, without date restrictions, describing bCPAP use for paediatric respiratory distress in LMICs. We included references describing related contexts, mechanisms, or outcomes. We coded statements from the literature supporting each CMOC, iteratively revising and adding CMOCs using inductive and deductive logic. We assembled an international, interdisciplinary panel of 22 bCPAP stakeholders to refine CMOCs using iterative surveys, focus groups, and interviews until we reached thematic saturation. This realist review is registered with PROSPERO (CRD42023403584).
FINDINGS: Of 1640 peer-reviewed references and eight grey literature references retrieved, 38 peer-reviewed articles and two grey literature documents were deemed eligible for inclusion after removal of duplicates and screening. After four rounds of expert surveys and three focus groups, we identified 18 CMOCs. CMOCs were synthesised into a final programme theory operating at five levels to influence implementation feasibility, fidelity, and sustainability: (1) the bCPAP device, (2) local partnerships and infrastructure, (3) clinical and technical teams, (4) caregivers and the community, and (5) institutional practices.
INTERPRETATION: Using realist methods with a diverse, international stakeholder panel, we generated a theory that could explain how bCPAP therapy works in different contexts. This theory could be leveraged to enhance the rigour of future bCPAP implementation trials.
FUNDING: Yale National Clinician Scholars Program, US National Center for Advancing Translational Science (TL1TR001864), and National Heart, Lung, and Blood Institute (T32HL155000)
Disparities in Buprenorphine Administration for Opioid Use Disorder in the Emergency Department
No full textSTUDY OBJECTIVE: Although buprenorphine is an effective treatment for opioid use disorder (OUD), this treatment is often not universally provided in the emergency department (ED). We aimed to determine whether patient characteristics, particularly race and ethnicity, were associated with buprenorphine administration.
METHODS: This was a retrospective cross-sectional study of adult patients who had a positive screening result for opioid misuse in the ED at a single urban hospital. Univariate and multivariable logistic regressions were used to assess the association of patient characteristics (race, ethnicity, age, sex, insurance type, and Area Deprivation Index) with buprenorphine administration.
RESULTS: Of 1082 patients who screened positive for opioid misuse, 133 (12%) were treated with buprenorphine and 949 (88%) were not. Despite representing over half the patient sample, Black patients (n = 682) were less likely than White patients (n = 310) to be treated with buprenorphine (multivariable: OR, 0.56; 95% CI, 0.35-0.88; P = 0.023). Age, sex, insurance type, ethnicity, and Area Deprivation Index were not associated with buprenorphine administration.
CONCLUSIONS: Patient race was associated with buprenorphine administration, even after controlling for multiple other social determinants of health. These data suggest racial disparities in care that should be investigated through further research to optimize equitable administration of buprenorphine
The Role of Sunscreen in Protection from Melanoma
No full textMelanoma is one of the leading causes of skin cancer deaths and is driven by ultraviolet (UV) radiation and subsequent DNA damage. Although studies on sunscreen\u27s effectiveness in preventing melanoma are inconsistent and limited, the available high-quality data suggest that sunscreen use can reduce melanoma incidence. Challenges include increased sun exposure with sunscreen use, poor sunscreen application, and limited UVA protection of sunscreens. Current guidelines recommend broad-spectrum sunscreens with sun protection factor greater than 30, regular reapplication, and additional sun-protective measures. Ongoing research is essential to better understand melanoma and refine prevention strategies
Pearls for dermatology resident education in cosmetic and laser procedures
No full textComprehensive education in cosmetic and laser procedures is fundamental during dermatology residency to meet the demand for cosmetic medical procedures and effectively treat a myriad of complex dermatological conditions. This article highlights the importance of structured learning to provide step-wise opportunities for proficiency throughout residency. Although reading assignments and didactic sessions create a solid foundation, focused workshops, resident cosmetic clinics, and offsite electives serve as important experiences for residents to practice hands-on skills. This article provides guidance for curriculum development and establishing hands-on procedural learning. Additionally, the importance of joining professional societies to receive unique training as well as mentorship is highlighted. Having a structured and comprehensive cosmetic curriculum will equip dermatology residents with the toolkit to successfully care for diverse patient needs effectively and safely
An Expert Consensus Delphi Panel in Metabolic Dysfunction- and Alcohol-associated Liver Disease: Opportunities and Challenges in Clinical Practice
No full textBACKGROUND & AIMS: Metabolic dysfunction- and alcohol-associated liver disease (MetALD) is a recently defined entity for individuals with liver steatosis, metabolic dysfunction, and increased alcohol intake. However, the current definition of MetALD poses multiple challenges in clinical practice and research. In this Delphi consensus, we provide practical recommendations for the clinical assessment and management of MetALD to address current clinical challenges in MetALD.
METHODS: We used a modified Delphi process, including 2 surveys involving a panel of 28 experts from 10 countries spanning 4 continents. We predefined consensus as requiring an ≥80% agreement.
RESULTS: The panel reached consensus on 28 statements. Recommendations emphasize the importance of a comprehensive assessment of patients with presumed MetALD, including the quantification of alcohol intake using validated questionnaires and the use of objective biomarkers of alcohol use, such as phosphatidylethanol. The need to reassess metabolic risk factors and liver disease after a period of alcohol abstinence was highlighted to distinguish the primary driver of liver injury. Noninvasive tests were recommended to assess liver disease severity, whereas routine liver biopsy was deemed unnecessary unless other diagnoses were suspected. Comprehensive management strategies should involve multidisciplinary care focusing on lifestyle modifications, alcohol reduction or cessation, weight loss, and exercise. Finally, the panel identified significant gaps in knowledge, advocating for standardized research protocols, longitudinal studies, exploration of pathophysiological mechanisms to inform precision medicine approaches, and the validation of quantitative alcohol biomarkers for identifying MetALD.
CONCLUSIONS: This Delphi consensus provides clear recommendations for the clinical assessment and management of MetALD, addressing the unique challenges posed by this condition
Endocuff-Assisted Colonoscopy for Identifying Sessile Serrated Polyps and Adenomas During Routine Colorectal Cancer Screening: A Retrospective Cohort Study
No full textBACKGROUND AND AIMS: Polyps located in less accessible areas of the colon, such as inner curves of flexures, are often difficult to visualize. Colonoscope attachments such as the Endocuff have been developed to improve the visualization of these polyps. We aimed to assess the utility of Endocuff-assisted colonoscopy (EAC) in the detection of tubular adenomas and sessile serrated polyps (SSP) compared to conventional colonoscopy during routine colorectal cancer screening.
PATIENTS AND METHODS: This retrospective cohort study included patients who underwent colorectal cancer screening with either conventional colonoscopy or EAC between November 2022 and March 2023. The primary outcomes were SSP and tubular adenoma detection rates. Secondary outcomes included total procedure time, cecal intubation time, and ileal intubation rates.
RESULTS: Of the 435 patients included, 189 (43%) underwent EAC, and 246 (57%) underwent conventional colonoscopy. The mean ± standard deviation number of polyps detected was 1.7 ± 2.2, the mean procedure time was 18.7 ± 7.5 min, and the mean cecal intubation time was 4.4 ± 3.3 min, with no significant differences between groups. A smaller proportion of patients in the EAC group had successful ileal intubation (14% vs. 55%; p \u3c 0.01). The tubular adenoma detection rate was similar between EAC and conventional colonoscopy (41% vs. 39%; p = 0.70), but the SSP detection rate was significantly higher with EAC (16% vs. 8.5%; p \u3c 0.01).
CONCLUSION: EAC may enhance the detection of difficult-to-visualize SSPs during screening colonoscopies without affecting overall procedure time. However, physicians should consider the examination indication when selecting EAC, as ileal intubation may be more challenging
MMF Is an Effective and Safer Treatment Options for Treatment-Naïve Patients With Autoimmune Hepatitis Compared to Azathioprine: A Systematic Review and Meta-Analysis
No full textOBJECTIVES: Autoimmune Hepatitis (AIH) is a chronic inflammatory liver disease with significant morbidity and mortality if untreated. Current first-line treatment involves corticosteroids and azathioprine (AZA), which are effective but are associated with significant adverse effects and treatment intolerance. Mycophenolate mofetil (MMF), an immunosuppressive agent with a potentially better safety profile, has emerged as an alternative. This meta-analysis evaluated the efficacy and safety of MMF compared to AZA in treatment-naïve AIH patients.
METHODS: We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Databases were searched for articles published up to May 2024. Statistical analysis was performed using RevMan, employing a random-effects model.
RESULTS: Five studies involving 621 patients were included. MMF showed significantly higher rates of complete biochemical response compared to AZA (odds ratio [OR] 3.64, 95% confidence interval [CI] 2.07-6.40, p \u3c 0.00001) and lower non-response rates (OR 0.45, 95% CI 0.24-0.85, p = 0.01). Corticosteroid withdrawal rates were also higher in the MMF group (OR 2.89, 95% CI 1.69-4.94, p = 0.0001). Relapse rate and cumulative prednisolone dose were comparable between the two groups. MMF demonstrated a better safety profile, with significantly lower rates of gastrointestinal symptoms (OR 0.46, 95% CI 0.27-0.79, p = 0.005).
CONCLUSIONS: MMF shows superior efficacy and tolerability compared to AZA in treatment-naïve AIH patients and may serve as a preferred first-line therapy, offering improved patient adherence and clinical outcomes. Further randomized controlled trials are warranted to confirm these findings
White Blood Counts of Hospitalized Patients Without Infection, Malignancy, or Immune Dysfunction
No full textOBJECTIVES: An elevated white blood cell (WBC) count may indicate malignancy, infection, and immune dysfunction. In diagnosing these conditions, physicians generally evaluate laboratory results compared with reference ranges based on healthy populations. Reference ranges for hospitalized patients are lacking. This study aims to define a normal reference range for WBC count in hospitalized patients without malignancy, infection, or immune dysfunction.
METHODS: This was a retrospective cross-sectional study of nonsurgical patients hospitalized from 2017 to 2018 in the Cleveland Clinic Health System without malignancy, infection, or immunological dysfunction. WBC count, absolute neutrophil count, and absolute lymphocyte count were collected. We calculated means, standard deviations, and the reference range for each variable.
RESULTS: A total of 46,419 patients had WBC counts. Mean WBC count was 8.0 (standard deviation 3.31, reference range 1.6-14.5). In a multivariable linear regression, mean WBC count decreased with age, Black race relative to White race, and congestive heart failure. Body mass index, diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease, and steroid use were associated with higher WBC count. In total, 13.5% of patients in this cohort had WBC counts above the normal threshold of 11.
CONCLUSIONS: Among hospitalized patients without infection, malignancy, or immune dysfunction, the normal range for WBC count was 1.6 to 14.5 × 10(9) WBCs/L. Age, race, body mass index, steroid use, and several comorbidities were associated with WBC count variation from the reference levels established based on healthy populations. Physicians should be cautious when interpreting WBC counts between 11 and 14.5 × 10(9) WBCs/L, which appear to represent normal values in the hospital
Clindamycin Phosphate 1.2%/Adapalene 0.15%/ Benzoyl Peroxide 3.1% for Acne: Results From A 6-Month Open-Label Study
No full textBACKGROUND: Treatment of acne may require many months of treatment before maximal benefits are observed, and acne sequelae (eg, scarring, dyspigmentation) can persist long after lesion resolution. In 12-week clinical trials, triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel (CAB) demonstrated efficacy and tolerability in the treatment of moderate to severe acne. This study assessed CAB long-term efficacy/tolerability and reductions in acne scarring/dyspigmentation.
METHODS: This 24-week, single-center, open-label study assessed once-daily CAB in participants (N=25) aged ≥12 years with moderate acne (Investigator’s Global Assessment [IGA] score=3). Endpoints included change from baseline in IGA score, inflammatory/noninflammatory lesions, skin appearance (dryness, postinflammatory hyperpigmentation [PIH], and postinflammatory erythema [PIE]), and scarring. Tolerability parameters (itching, burning, redness, swelling) and adverse events were assessed. At baseline and week 24, participants’ foreheads were swabbed to assess Cutibacterium acnes.
Results: At week 24, 68% of participants achieved treatment success ( ≥ 2-grade IGA score reduction from baseline and clear/almost clear skin), and significant inflammatory/noninflammatory lesion reductions from baseline were observed (89%; 70%; P\u3c 0.001, both). Decreases from baseline in investigator- and participant-assessed PIH (77%; 82%) and PIE (84%; 88%) and investigator-assessed scarring severity (33%) were statistically significant (P ≤ 0.001, all). There were no significant increases in skin dryness or any tolerability parameter, and no adverse events occurred. C. acnes assessment indicated no development of antibiotic resistance with long-term CAB treatment.
Conclusions: With 24 weeks of once-daily use, CAB was efficacious, well-tolerated, and significantly improved acne-related scarring and dyspigmentation. These results support the long-term use of CAB in the topical treatment of acne