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Functional Gastrointestinal Disorders in Mediterranean Countries According to Rome IV Criteria

J Pediatr Gastroenterol Nutr. 2022 Mar 1;74(3):361-367. doi: 10.1097/MPG.0000000000003358.

ABSTRACT

OBJECTIVES: The aim of this study was to assess the prevalence of functional gastrointestinal disorders (FGIDs) in children of Mediterranean area using Rome IV criteria and to compare the prevalence of FGIDs using Rome IV and Rome III criteria.

METHODS: This was a cross-sectional study enrolling children and adolescents living in Croatia, Greece, Israel, Italy, Macedonia, and Serbia. Subjects were examined in relation to the presence of FGIDs, using the Rome IV criteria. Data were compared with the results of a previous study using Rome III data.

RESULTS: We analyzed 1972 children ages 4 to 9 years (group A), and 2450 adolescents 10 to 18 years old (group B). The overall prevalence of FGIDs was 16% in group A and 26% in group B, with statistical differences among countries in both groups (P < 0.001). In group A, the prevalence of FGIDs and of functional constipation (FC) was significantly lower than in the previous study (P < 0.001), whereas in group B no significant difference was found. In both groups of age, the prevalence of abdominal migraine and irritable bowel syndrome decreased significantly (P < 0.001 and P < 0.001, respectively) using Rome IV versus Rome III criteria, conversely functional dyspepsia increased (P < 0.001).

CONCLUSIONS: FGIDs are common in children and adolescents, their frequency increases with age, and there is a significant variation in the prevalence of some FGIDs among different European countries. The application of the Rome IV criteria resulted in a significantly lower prevalence of FGIDs in children compared with Rome III criteria.

PMID:35226645 | DOI:10.1097/MPG.0000000000003358

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Pediatric Emergency Medicine Fellowship Education on Adolescent Sexual Health Care

Pediatr Emerg Care. 2022 Mar 1;38(3):97-103. doi: 10.1097/PEC.0000000000002612.

ABSTRACT

OBJECTIVES: Many adolescents use the emergency department as their sole resource for primary care and sexual health care. This provides an opportunity to prevent sexually transmitted infections and unintended pregnancy as well as to educate teenagers about their bodies and sexual health. There is no standard curriculum on sexual health as part of pediatric emergency medicine (PEM) fellowship education. Our goal is to evaluate what is taught in PEM fellowship about adolescent sexual health.

METHODS: We administered an anonymous questionnaire to both PEM fellows and program directors (PDs). The questionnaire was distributed through the PEM Program Director Survey Committee. The questionnaire was sent to 88 PDs and 305 fellows total. An introductory email explaining the purpose of the study and a link to the online questionnaire was sent. The questionnaire was created using SurveyMonkey (www.surveymonkey.com). Data were analyzed using descriptive statistics.

RESULTS: We achieved a 43% survey response rate from PDs (38 of 88) and a 24% survey response rate from fellows (73 of 305). The PD respondents included 61% females, and almost all (86%) are between ages 35 and 54 years. Seventy-three percent of the fellows are female, and they are all between 25 to 44 years old. There was a great deal of variability in the amount of adolescent sexual health education PDs provide their fellows in the form of lectures and bedside teaching cases. A majority of survey respondents (86% of fellows and 66% of the PDs) agreed that there should be a standard PEM curriculum to teach about adolescent sexual health. More than half (53% of PDs and 56% of fellows) are not satisfied with the number of training opportunities for adolescent sexual health.

CONCLUSIONS: We found variability in adolescent sexual health training during PEM fellowship, although fellows and PDs agree that there should be a standardized curriculum. We recommend that the American Board of Pediatrics form a committee to decrease variability in the training of PEM fellows on adolescent sexual health.

PMID:35226617 | DOI:10.1097/PEC.0000000000002612

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Pediatric Carbon Monoxide Poisoning: Effects of Hyperbaric Oxygen Therapy on Thiol/Disulfide Balance

Pediatr Emerg Care. 2022 Mar 1;38(3):104-107. doi: 10.1097/PEC.0000000000002619.

ABSTRACT

OBJECTIVES: Carbon monoxide (CO) poisoning remains the foremost cause of poisoning worldwide. This study aimed to investigate the effects of hyperbaric oxygen therapy (HBOT) and normobaric oxygen therapy (NBOT) on thiol/disulfide homeostasis in children with CO intoxication.

METHODS: Eighty-one children aged 0 to 18 years with CO intoxication were included in this cross-sectional study. No changes were made in the routine clinical evaluation and treatment practices of the patients. Thirty-two children who received HBOT and 49 children who received NBOT were compared for serum native thiol, disulfide, and total thiol levels, as well as for the changes in disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios before and after treatment.

RESULTS: Antioxidant levels, such as native thiol and total thiol, were significantly decreased in patients who received HBOT and increased in those who received NBOT (P = 0.02 and P = 0.01, respectively). There was no statistically significant difference between the 2 groups concerning the change of native thiol/total thiol ratios (P = 0.07). In addition, there was no significant difference regarding changes in disulfide, disulfide/native thiol, and disulfide/total thiol levels before and after treatment (P = 0.39, P = 0.07, and P = 0.07, respectively).

CONCLUSIONS: Although thiol-disulfide balance is maintained in patients treated with HBOT, antioxidant levels decrease significantly compared with NBOT. Despite efficiency of HBOT in CO intoxication, oxidative stress and reperfusion injury due to hyperoxygenation should be considered in the treatment of HBOT.

PMID:35226618 | DOI:10.1097/PEC.0000000000002619

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Neuronal Abnormalities Induced by an Intelligent Virtual Reality System for Methamphetamine Use Disorder

IEEE J Biomed Health Inform. 2022 Feb 28;PP. doi: 10.1109/JBHI.2022.3154759. Online ahead of print.

ABSTRACT

Methamphetamine use disorder (MUD) is a brain disease that leads to altered regional neuronal activity. Virtual reality (VR) is used to induce the drug cue reactivity. Previous studies reported significant frequency-specific abnormalities in patients with MUD during VR induction of drug craving. However, whether those patients exhibit neuronal abnormalities after VR induction that could serve as the treatment target remains unclear. Here, we developed an integrated VR system for inducing drug related changes and investigated the neuronal abnormalities after VR exposure in patients. Fifteen patients with MUD and ten healthy subjects were recruited and exposed to drug-related VR environments. Resting-state EEG were recorded for 5 minutes twice-before and after VR and transformed to obtain the frequency-specific data. Three self-reported scales for measurement of the anxiety levels and impulsivity of participants were obtained after VR task. Statistical tests and machine learning methods were employed to reveal the differences between patients and healthy subjects. The result showed that patients with MUD and healthy subjects significantly differed in, and power changes after VR. These neuronal abnormalities in patients were associated with the self-reported behavioral scales, indicating impaired impulse control. Our findings of resting-state EEG abnormalities in patients with MUD after VR exposure have the translation value and can be used to develop the treatment strategies for methamphetamine use disorder.

PMID:35226611 | DOI:10.1109/JBHI.2022.3154759

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Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort

Ann Intern Med. 2022 Mar 1. doi: 10.7326/M21-3577. Online ahead of print.

ABSTRACT

BACKGROUND: Mammography screening can lead to overdiagnosis-that is, screen-detected breast cancer that would not have caused symptoms or signs in the remaining lifetime. There is no consensus about the frequency of breast cancer overdiagnosis.

OBJECTIVE: To estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer.

DESIGN: Bayesian inference of the natural history of breast cancer using individual screening and diagnosis records, allowing for nonprogressive preclinical cancer. Combination of fitted natural history model with life-table data to predict the rate of overdiagnosis among screen-detected cancer under biennial screening.

SETTING: Breast Cancer Surveillance Consortium (BCSC) facilities.

PARTICIPANTS: Women aged 50 to 74 years at first mammography screen between 2000 and 2018.

MEASUREMENTS: Screening mammograms and screen-detected or interval breast cancer.

RESULTS: The cohort included 35 986 women, 82 677 mammograms, and 718 breast cancer diagnoses. Among all preclinical cancer cases, 4.5% (95% uncertainty interval [UI], 0.1% to 14.8%) were estimated to be nonprogressive. In a program of biennial screening from age 50 to 74 years, 15.4% (UI, 9.4% to 26.5%) of screen-detected cancer cases were estimated to be overdiagnosed, with 6.1% (UI, 0.2% to 20.1%) due to detecting indolent preclinical cancer and 9.3% (UI, 5.5% to 13.5%) due to detecting progressive preclinical cancer in women who would have died of an unrelated cause before clinical diagnosis.

LIMITATIONS: Exclusion of women with first mammography screen outside BCSC.

CONCLUSION: On the basis of an authoritative U.S. population data set, the analysis projected that among biennially screened women aged 50 to 74 years, about 1 in 7 cases of screen-detected cancer is overdiagnosed. This information clarifies the risk for breast cancer overdiagnosis in contemporary screening practice and should facilitate shared and informed decision making about mammography screening.

PRIMARY FUNDING SOURCE: National Cancer Institute.

PMID:35226520 | DOI:10.7326/M21-3577

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Changes in immune profile affect disease progression in hepatocellular carcinoma

Int J Immunopathol Pharmacol. 2022 Jan-Dec;36:3946320221078476. doi: 10.1177/03946320221078476.

ABSTRACT

Objective: Hepatocellular carcinoma (HCC) as a chronic liver condition is largely associated with immune responses. Previous studies have revealed that different subsets of lymphocytes play fundamental roles in controlling or improving the development and outcome of solid tumors like HCC. Hence, this study aimed to investigate whether immune system changes were related to disease development in HCC patients. Methods: Peripheral blood mononuclear cells were isolated from 30 HCC patients and 30 healthy volunteers using Ficoll density centrifugation. The isolated cells were stained with different primary antibodies and percentages of different immune cells were determined by flow cytometry. Results: HCC patients indicated significant reductions in the numbers of CD4+ cells, Tbet+IFNγ+cells, and GATA+IL-4+cells in peripheral blood in comparison with healthy individuals (p < 0.05). There was no significant change in IL-17+RORγt+cells between patient and healthy groups. In contrast, Foxp3+CD127lowcell frequency was significantly higher in patients than healthy subjects (p < 0.0001). The numbers of Th1, Th2, and Th17 cells were significantly lower in HCC patients than healthy control (p < 0.0001), although the reduction in Th2 cell numbers was not statistically significant. On the contrary, Treg percentage showed a significant increase in patients compared to healthy subjects (p < 0.0001). Other data revealed that Th1, Th2, and Th17 cell frequencies were significantly higher in healthy individuals than patients with different TNM stages of HCC, with the exception of Th2 in patients with stage II HCC (p < 0.01-0.05). Treg percentage was significantly increased in patients with different TNM stages (p < 0.0001). Among all CD4+ T cells, the frequency of Th2 cell was significantly associated with TNM stages of HCC (p < 0.05). Conclusion: Our data provide further evidence to show that immune changes may participate in determining HCC progression and disease outcome. However, it should be mentioned that more investigations are needed to clarify our results and explain possible impacts of other immune cells on the pathogenesis of HCC.

PMID:35226515 | DOI:10.1177/03946320221078476

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Soluble ACE2 and TMPRSS2 Levels in the Serum of Asthmatic Patients

J Korean Med Sci. 2022 Feb 28;37(8):e65. doi: 10.3346/jkms.2022.37.e65.

ABSTRACT

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2) are key proteins mediating viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although gene expressions of ACE2 and TMPRSS2 have been analyzed in various organs and diseases, their soluble forms have been less studied, particularly in asthma. Therefore, we aimed to measure circulating ACE2 and TMPRSS2 in the serum of asthmatics and examine their relationship with clinical characteristics.

METHODS: Clinical data and serum samples of 400 participants were obtained from an asthma cohort. The soluble ACE2 (sACE2) and soluble TMPRSS2 (sTMPRSS2) level was measured by enzyme-linked immunosorbent assay, and the values underwent a natural log transformation. Associations between sACE2 and TMPRSS2 levels and various clinical variables were analyzed.

RESULTS: The patients younger than 70 years old, those with eosinophilic asthma (eosinophils ≥ 200 cells/µL), and inhaled corticosteroids (ICS) non-users were associated with higher levels of sACE2. Blood eosinophils and fractionated exhaled nitric oxide levels were positively correlated with serum ACE2. In contrast, lower levels of sTMPRSS2 were noted in patients below 70 years and those with eosinophilic asthma, while no association was noted between ICS use and sTMPRSS2. The level of sTMPRSS2 also differed according to sex, smoking history, coexisting hypertension, and forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio. The proportion of sputum neutrophils was positively correlated with sTMPRSS2, while the FEV1/FVC ratio reported a negative correlation with sTMPRSS2.

CONCLUSION: The levels of ACE2 and TMPRSS2 were differently expressed according to age, ICS use, and several inflammatory markers. These findings suggest variable susceptibility and prognosis of SARS-CoV-2 infection among asthmatic patients.

PMID:35226423 | DOI:10.3346/jkms.2022.37.e65

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Determinants of Exercise Capacity in Patients With Hypertrophic Cardiomyopathy

J Korean Med Sci. 2022 Feb 28;37(8):e62. doi: 10.3346/jkms.2022.37.e62.

ABSTRACT

BACKGROUND: Reduced exercise capacity reflects symptom severity and clinical outcomes in patients with hypertrophic cardiomyopathy (HCM). The present study aimed to identify factors that may affect exercise capacity in patients with HCM.

METHODS: In 294 patients with HCM and preserved left ventricular (LV) ejection fraction, we compared peak oxygen consumption (peak VO2) evaluated by cardiopulmonary exercise testing as a representative parameter of exercise tolerance with clinical and laboratory data, including N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP), diastolic parameters on echocardiography, and the grade of myocardial fibrosis on cardiac magnetic resonance imaging (CMR).

RESULTS: Median peak VO2, was 29.0 mL/kg/min (interquartile range [IQR], 25.0-34.0). Age (estimated β = -0.140, P < 0.001), female sex (β = -5.362, P < 0.001), NT-proBNP (β = -1.256, P < 0.001), and E/e’ ratio on echocardiography (β = -0.209, P = 0.019) were significantly associated with exercise capacity. Peak VO2 was not associated with the amount of myocardial fibrosis on CMR (mean of late gadolinium enhancement 12.25 ± 9.67%LV).

CONCLUSION: Decreased exercise capacity was associated with age, female sex, increased NT-proBNP level, and E/e’ ratio on echocardiography. Hemodynamic changes and increased filling pressure on echocardiography should be monitored in this population for improved outcomes.

PMID:35226420 | DOI:10.3346/jkms.2022.37.e62

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Changes in the Incidence of Intussusception and Infectious Diseases After the COVID-19 Pandemic in Korea

J Korean Med Sci. 2022 Feb 28;37(8):e60. doi: 10.3346/jkms.2022.37.e60.

ABSTRACT

BACKGROUND: Intussusception refers to the invagination of a part of the intestine into itself. The exact cause for this condition is unknown in most cases. The active implementation of coronavirus disease 2019 (COVID-19) infection control guidelines has reduced the spread of COVID-19 and the incidence of other infectious diseases in children. The current study aimed to identify changes in pediatric intussusception and infectious diseases after the implementation of infection control guidelines and confirm the association between intussusception and contagious diseases.

METHODS: We analyzed the electronic medical records of pediatric patients diagnosed with intussusception from seven hospitals in Korea between January 2017 and December 2020. We used open data from the Korea Disease Control and Prevention Agency to investigate changes in infectious diseases over the same period.

RESULTS: Altogether, we evaluated 390 children with intussusception. There was a statistically significant decrease in the incidence of monthly visits with intussusception in the COVID-19 period group (9.0 vs. 3.5, P < 0.001). When the monthly incidence of infectious diseases was compared between the pre-COVID-19 and the COVID-19 periods, a statistically significant decrease in respiratory viruses (7979.0 vs. 815.2, P < 0.001), enterovirus infection (262.2 vs. 6.6, P < 0.001), and viral enteritis (916.2 vs. 197.8, P < 0.001) were confirmed in the COVID-19 period. Through interrupted time series analysis, it was confirmed that the incidence of intussusception and viral infectious diseases have drastically decreased since March 2020, when COVID-19 infection control guidelines were actively implemented.

CONCLUSION: We confirmed that implementing infection control guidelines during the COVID-19 pandemic resulted in a decrease in intussusception and viral infectious diseases. Through this result, it was possible to indirectly confirm the existing hypothesis that viral infections play a significant role in the pathophysiologic mechanism of intussusception.

PMID:35226418 | DOI:10.3346/jkms.2022.37.e60

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Outcomes associated with once-daily versus multiple-daily dosing of buprenorphine/naloxone for opioid use disorder

Am J Addict. 2022 Feb 28. doi: 10.1111/ajad.13267. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Clinical studies examining once-daily versus multiple-daily dosing of buprenorphine/naloxone in patients with opioid use disorder (OUD) in the absence of comorbid pain are lacking.

METHODS: This retrospective chart review aimed to compare 100 patients prescribed single-daily buprenorphine/naloxone (n = 50) to those prescribed multiple-daily buprenorphine/naloxone (n = 50) to elucidate the impact that dosing frequency has on negative urine drug screens (UDS) and the number of relapses in OUD.

RESULTS: The once-daily cohort produced 84% negative UDSs compared with 74% in the multiple-daily cohort which was statistically significant (p = .034). There were a total of 43 relapses reported in the once-daily cohort, compared with 141 relapses in the multiple-daily cohort (p < .001). The average number of relapses per patient in the single-daily cohort was 0.68 compared with the multiple-daily cohort average of 2.16 (p < .001). In the once-daily cohort, 14% of patients experienced at least one relapse throughout the study, compared with 31% in the multiple-daily cohort (p < .002). There were no significant differences between time to relapse, adherence to treatment, or treatment retention. Statistically significantly more patients in the multiple-daily cohort were using methamphetamines (p = .005); there were no significant differences between groups with the use of any other illicit or non-prescribed substances.

DISCUSSION AND CONCLUSIONS: Once-daily dosing was associated with more negative UDSs and fewer opioid relapses compared with multiple-daily dosing.

SCIENTIFIC SIGNIFICANCE: This was the first study to evaluate buprenorphine/naloxone dosing frequency for opioid use disorder, in the absence of chronic pain. Additional studies evaluating optimal dosing schedules for relapse prevention are warranted.

PMID:35226393 | DOI:10.1111/ajad.13267