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Introduction: Human metabolomics has made significant strides in understanding metabolic changes and their implications for human health, with promising applications in diagnostics and treatment, particularly regarding the gut microbiome. However, progress is hampered by issues with data comparability and reproducibility across studies, limiting the translation of these discoveries into practical applications., Objectives: This study aims to evaluate the fit-for-purpose of a suite of human stool samples as potential candidate reference materials (RMs) and assess the state of the field regarding harmonizing gut metabolomics measurements., Methods: An interlaboratory study was conducted with 18 participating institutions. The study allowed for the use of preferred analytical techniques, including liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR)., Results: Different laboratories used various methods and analytical platforms to identify the metabolites present in human stool RM samples. The study found a 40% to 70% recurrence in the reported top 20 most abundant metabolites across the four materials. In the full annotation list, the percentage of metabolites reported multiple times after nomenclature standardization was 36% (LC-MS), 58% (GC-MS) and 76% (NMR). Out of 9,300 unique metabolites, only 37 were reported across all three measurement techniques., Conclusion: This collaborative exercise emphasized the broad chemical survey possible with multi-technique approaches. Community engagement is essential for the evaluation and characterization of common materials designed to facilitate comparability and ensure data quality underscoring the value of determining current practices, challenges, and progress of a field through interlaboratory studies., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background/aim: The COVID-19 pandemic brought unprecedented global changes, necessitating adjustments to address public health challenges. The impact on advanced epithelial ovarian cancer (EOC) surgery, marked by increased perioperative risks, and changes in management plans was explored in this study based on promptly published British Gynaecologic Cancer Society (BGCS) and European Society of Gynaecologic Oncology (ESGO) guidelines., Patients and Methods: Retrospective data from 332 patients with advanced EOC who underwent cytoreductive surgery at a UK tertiary center were analyzed, and the outcomes were compared between pre-COVID-19 (2018-2019) (n=189) and COVID-19 era (2020-2021) (n=143) cohorts, covering the same timeframe (March to December). Primary outcomes included residual disease (RD) and progression-free survival (PFS), while secondary outcomes were the ESGO quality indicators (QIs) for advanced EOC surgery. Kaplan-Meier curves were produced to illustrate PFS., Results: Complete cytoreduction rates remained comparable at 74.07% and 72.03% for pre-COVID-19 and COVID-19 groups, respectively. Differences were observed in ECOG performance status (p=0.015), Intensive Care Unit (ICU) admissions (p=0.039) with less interval debulking surgeries (p=0.03), lower surgical complexity scores (p=0.02), and longer operative times in the COVID-19 group (p=0.01) compared to the pre-COVID-19 group. The median PFS rates were 37 months and 34 months in the pre-COVID-19 and COVID-19 groups, respectively (p=0.08). The surgical QIs 1-3 remained uncompromised during the COVID-19 era., Conclusion: Management modifications prompted by the COVID-19 pandemic did not adversely impact cytoreduction rates or PFS., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Cytoreductive surgery is critical for optimal tumor clearance in advanced epithelial ovarian cancer (EOC). Despite best efforts, some patients may experience R2 (>1 cm) resection, while others may not undergo surgery at all. We aimed to compare outcomes between advanced EOC patients undergoing R2 resection and those who had no surgery., Methods: Retrospective data from 51 patients with R2 resection were compared to 122 patients with no surgery between January 2015 and December 2019 at a UK tertiary referral centre. Progression-free survival (PFS) and overall survival (OS) were the study endpoints. Principal Component Analysis and Term Frequency - Inverse Document Frequency scores were utilized for data discrimination and prediction of R>2 cm from computed tomography pre-operative reports, respectively., Results: No statistical significance was observed, except for age (73 vs 67 years in the no- surgery vs R2 group, P : .001). Principal Components explained 34% of data variances. Reasons for no surgery included age, co-morbidities, patient preference, refractory disease, patient deterioration or disease progression, and absence of measurable intra- abdominal disease). The median PFS and OS were 12 and 14 months for no-surgery, vs 14 and 26 months for R2 ( P : .138 and P : .001, respectively). Serous histology and performance status independently predicted PFS in both no-surgery and R2 cohorts. In the no-surgery cohort, serous histology independently predicted OS, while in the R2 cohorts, both serous histology and adjuvant chemotherapy were independent prognostic features for OS. The bi-grams "abdominopelvic ascites" and "solid omental" were amongst those best discriminating between R>2 cm and R1-2 cm., Conclusions: R2 resection and no-surgery cohorts displayed unfavourable prognosis with a notable degree of uniformity. When cytoreduction results in suboptimal results, the survival benefit may still be higher compared to those who underwent no surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study explored possible success factors for passing the Certified Health Data Analyst Administration (CHDA) certification exam. According to the American Health Information Management Association (AHIMA), in 2019, only 10 percent of first-time test-takers passed the CHDA exam. Literature review offered insight into factors related to passing certification exams. Sources included existing, relevant peer-reviewed, and published literature since 1990 within 87 educational and health/medicine databases and 62 other articles and journal databases available at the University of South Dakota library. A correlational design was used in the study. Data was retrieved from AHIMA, cleaned, and data analysis was completed using binary logistic regression analysis. The CHDA study results indicate that candidates between ages 30 and 49 are less likely to pass the exam than those ages 50 and above, and those candidates with a master's degree are more likely to pass the exam than those with an associate or bachelor's degree. This new information will help improve the exam pass rates, provide a foundation for CHDA exam research, and add new knowledge in the HIM professional body of research., (Copyright © 2021 by the American Health Information Management Association.)

This study explored possible success factors for passing the Registered Health Information Administration (RHIA) certification exam. According to the American Health Information Management Association (AHIMA), only 70 percent of first-time test-takers passed the RHIA exam in 2019. A literature review offered insight into factors related to passing certification exams. Sources included existing, relevant peer-reviewed and published literature since 1990 within 87 educational and health/medicine databases and 62 other articles and journal databases available at the University of South Dakota library. A correlational design was used in the study. Data was retrieved from AHIMA, cleaned, and binary logistic regression analysis was completed. A significant relationship was identified between having a prior credential, such as the Registered Health Information Technician (RHIT) credential and passing the RHIA exam. This new information will help improve pass rates, advance the HIM field research base, and help students improve their odds of passing the RHIA exam., (Copyright © 2021 by the American Health Information Management Association.)

This study explored possible success factors for health information management certification exams. Based on the American Health Information Management Association (AHIMA) website, in 2018 and 2019, only 70 percent of first-time test takers passed the Registered Health Information Administrator (RHIA) exam; 26 percent passed the Certified Health Data Analyst (CHDA) exam in 2018; and only 10 percent passed the Certified Health Data Analyst exam in 2019. A quantitative systematic review and meta-analysis offered insight into factors related to passing certification exams. Sources included existing, relevant peer-reviewed and published literature since 1990 within 87 educational and health/medicine databases and 62 other articles and journal databases available at the University of South Dakota library. Outcomes from the systematic review include illumination of factors for passing health information management, healthcare, and education certification exams. Ultimately, this new information will help improve pass rates on certification exams., (Copyright © 2021 by the American Health Information Management Association.)

Background: The foundation of modern ovarian cancer care is cytoreductive surgery to remove all macroscopic disease (R0). Identification of R0 resection patients may help individualise treatment. Machine learning and AI have been shown to be effective systems for classification and prediction. For a disease as heterogenous as ovarian cancer, they could potentially outperform conventional predictive algorithms for routine clinical use. We investigated the performance of an AI system, the k-nearest neighbor (k-NN) classifier, to predict R0, comparing it with logistic regression. Patients diagnosed with advanced stage, high grade serous ovarian, tubal and primary peritoneal cancer, undergoing surgical cytoreduction from 2015 to 2019, was selected from the ovarian database. Performance variables included age, BMI, Charlson Comorbidity Index, timing of surgery, surgical complexity and disease score. The k-NN algorithm classified R0 vs non-R0 patients using 3-20 nearest neighbors. Prediction accuracy was estimated as percentage of observations in the training set correctly classified., Results: 154 patients were identified, with mean age of 64.4 + 10.5 yrs., BMI of 27.2 + 5.8 and mean SCS of 3 + 1 (1-8). Complete and optimal cytoreduction was achieved in 62 and 88% patients. The mean predictive accuracy was 66%. R0 resection prediction of true negatives was as high as 90% using k = 20 neighbors., Conclusions: The k-NN algorithm is a promising and versatile tool for R0 resection prediction. It slightly outperforms logistic regression and is expected to improve accuracy with data expansion.

To establish a process for the development of a prioritization tool for a clinical decision support build within a computerized provider order entry system and concurrently to prioritize alerts for Saint Luke's Health System. The process of prioritizing clinical decision support alerts included (a) consensus sessions to establish a prioritization process and identify clinical decision support alerts through a modified Delphi process and (b) a clinical decision support survey to validate the results. All members of our health system's physician quality organization, Saint Luke's Care as well as clinicians, administrators, and pharmacy staff throughout Saint Luke's Health System, were invited to participate in this confidential survey. The consensus sessions yielded a prioritization process through alert contextualization and associated Likert-type scales. Utilizing this process, the clinical decision support survey polled the opinions of 850 clinicians with a 64.7 percent response rate. Three of the top rated alerts were approved for the pre-implementation build at Saint Luke's Health System: Acute Myocardial Infarction Core Measure Sets, Deep Vein Thrombosis Prophylaxis within 4 h, and Criteria for Sepsis. This study establishes a process for developing a prioritization tool for a clinical decision support build within a computerized provider order entry system that may be applicable to similar institutions., (© The Author(s) 2015.)

The mechanisms responsible for the onset and progressive worsening of episodic muscle stiffness and weakness in hyperkalemic periodic paralysis (HyperKPP) are not fully understood. Using a knock-in HyperKPP mouse model harboring the M1592V NaV1.4 channel mutant, we interrogated changes in physiological defects during the first year, including tetrodotoxin-sensitive Na(+) influx, hindlimb electromyographic (EMG) activity and immobility, muscle weakness induced by elevated [K(+)]e, myofiber-type composition, and myofiber damage. In situ EMG activity was greater in HyperKPP than wild-type gastrocnemius, whereas spontaneous muscle contractions were observed in vitro. We suggest that both the greater EMG activity and spontaneous contractions are related to periods of hyperexcitability during which fibers generate action potentials by themselves in the absence of any stimulation and that these periods are the cause of the muscle stiffness reported by patients. HyperKPP muscles had a greater sensitivity to the K(+)-induced force depression than wild-type muscles. So, an increased interstitial K(+) concentration locally near subsets of myofibers as a result of the hyperexcitability likely produced partial loss of force rather than complete paralysis. NaV1.4 channel protein content reached adult level by 3 weeks postnatal in both wild type and HyperKPP and apparent symptoms did not worsen after the first month of age suggesting (i) that the phenotypic behavior of M1592V HyperKPP muscles results from defective function of mutant NaV1.4 channels rather than other changes in protein expression after the first month and (ii) that the lag in onset during the first decade and the progression of human HyperKPP symptoms during adolescence are a function of NaV1.4 channel content., (© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Hyperkalemic periodic paralysis (HyperKPP) is characterized by myotonic discharges that occur between episodic attacks of paralysis. Individuals with HyperKPP rarely suffer respiratory distress even though diaphragm muscle expresses the same defective Na(+) channel isoform (NaV1.4) that causes symptoms in limb muscles. We tested the hypothesis that the extent of the HyperKPP phenotype (low force generation and shift toward oxidative type I and IIA fibers) in muscle is a function of 1) the NaV1.4 channel content and 2) the Na(+) influx through the defective channels [i.e., the tetrodotoxin (TTX)-sensitive Na(+) influx]. We measured NaV1.4 channel protein content, TTX-sensitive Na(+) influx, force generation, and myosin isoform expression in four muscles from knock-in mice expressing a NaV1.4 isoform corresponding to the human M1592V mutant. The HyperKPP flexor digitorum brevis muscle showed no contractile abnormalities, which correlated well with its low NaV1.4 protein content and by far the lowest TTX-sensitive Na(+) influx. In contrast, diaphragm muscle expressing the HyperKPP mutant contained high levels of NaV1.4 protein and exhibited a TTX-sensitive Na(+) influx that was 22% higher compared with affected extensor digitorum longus (EDL) and soleus muscles. Surprisingly, despite this high burden of Na(+) influx, the contractility phenotype was very mild in mutant diaphragm compared with the robust abnormalities observed in EDL and soleus. This study provides evidence that HyperKPP phenotype does not depend solely on the NaV1.4 content or Na(+) influx and that the diaphragm does not depend solely on Na(+)-K(+) pumps to ameliorate the phenotype., (Copyright © 2014 the American Physiological Society.)

Purpose: High-dose chemotherapy (HDCT) followed by autologous stem-cell transplantation (PBSCT) has become the standard treatment for patients with relapsed Hodgkin's lymphoma (HL). The intensity of treatment needed is unclear. This European intergroup study evaluated the impact of sequential high-dose chemotherapy (SHDCT) before myeloablative therapy., Patients and Methods: Patients with histologically confirmed, relapsed HL were treated with two cycles of dexamethasone, cytarabine, and cisplatin, and those without disease progression were randomly assigned. In the standard arm (A), patients received myeloablative therapy with carmustine, BEAM (carmustine, etoposide, cytarabine, and melphalan) followed by PBSCT. Patients in the experimental arm (B) also received sequential cyclophosphamide, methotrexate, and etoposide in high-doses before BEAM. Freedom from treatment failure (FFTF) was the primary end point. Remission rates, overall survival (OS), and toxicity of treatment were secondary end points., Results: From a total of 284 patients included, 241 responding patients were randomly assigned after two cycles of dexamethasone, cytarabine, and cisplatinum. Patients treated in arm B had longer treatment duration and experienced more toxicity and protocol violations (P < .05). Mortality was similar in both arms (20% and 18%). With a median observation time of 42 months, there was no significant difference in terms of FFTF (P = .56) and OS (P = .82) between arms. FFTF at 3 years was 62% (95% CI, 56% to 68%) and OS was 80% (95% CI, 75% to 85%). Patients with stage IV, early relapse, multiple relapse, anemia, or B symptoms had a higher risk of recurrence (P < .001)., Conclusion: Compared with conventional high-dose chemotherapy, additional SHDCT is associated with more adverse effects and does not improve the prognosis of patients with relapsed HL.

Acute spinal cord injury is a serious medical condition that results in 10,000 new cases of paralysis each year. Initial physical damage to the spinal cord is followed by chemical damage, resulting in cell death and scar tissue formation. Methylprednisolone therapy has proven effective in suppressing the chemical damage, particularly when started within 8 hours of injury. A protocol developed by the Pharmacy Department at Methodist Medical Center in Dallas, Texas, is described. This protocol facilitates accurate, efficient preparation and administration of this emergency therapy. The protocol takes advantage of the pharmacist's unique expertise to lessen the risk of calculation errors and mistakes in preparation, by providing a tailored drug admixture for administration at a fixed flow rate. The protocol and a sample of the pharmacy work sheet are presented.

The use of methotrexate in rheumatoid arthritis is reviewed. Methotrexate, a folic acid antagonist, is sometimes employed in an attempt to symptomatically control patients whose disease does not respond adequately to conventional therapies. Systemic administration of 7.5-15 mg/wk in a "pulse" fashion appears to be effective without precipitating severe adverse effects. However, concern over potentially serious side effects and a lack of well-controlled clinical trials have limited its use to severe, refractory disease. Further studies are needed before its role in rheumatoid arthritis can justifiably be expanded.

Effect of thyrotropic releasing hormone (TRH) on plasma arginine vasopressin (AVP) was studied in human subjects. All 7 normal controls and 2 hypothyrotropic hypothyroid subjects failed to show any rise of AVP on TRH administration. The 4 primary hypothyroid subjects had elevated basal AVP level and showed further elevation on TRH administration. Our data suggests that elevated TRH in primary hypothyroid subjects may act directly as a nonosmotic stimulus or modulate the osmoreceptor and hypothalamic neurohypophyseal system for AVP release.

Methotrexate, a folic acid antagonist, is being employed more frequently in an attempt to control rheumatoid arthritis that has not responded adequately to conventional therapies. Systemic administration of 7.5-15 mg weekly in a pulse fashion appears to be effective without precipitating serious adverse effects. Concern over potentially serious adverse effects and lack of well-controlled clinical trials have limited its use to severe, refractory disease. Its use in the future is likely to increase in these patients because of its ease of administration and the high response rate noted in clinical studies.