Diffusion MRI-guided theta burst stimulation enhances memory and functional connectivity along the inferior longitudinal fasciculus in mild cognitive impairment.

Mild cognitive impairment (MCI) during aging is often a harbinger of Alzheimer's disease, and, therefore, early intervention to preserve cognitive abilities before the MCI symptoms become medically refractory is particularly critical. Functional MRI­guided transcranial magnetic stimulation is a promising approach for modulating hippocampal functional connectivity and enhancing memory in healthy adults. Here, we extend these previous findings to individuals with MCI and leverage theta burst stimulation (TBS) and white matter tractography derived from diffusion-weighted MRI to target the hippocampus. Our preliminary findings suggested that TBS could be used to improve associative memory performance and increase resting-state functional connectivity of the hippocampus and other brain regions, including the occipital fusiform, frontal orbital cortex, putamen, posterior parahippocampal gyrus, and temporal pole, along the inferior longitudinal fasciculus in MCI. Although the sample size is small, these results shed light on how TBS propagates from the superficial cortex around the parietal lobe to the hippocampus.

Differences in Treatment Patterns and Outcomes of Acute Myocardial Infarction for Low- and High-Income Patients in 6 Countries.

Importance: Differences in the organization and financing of health systems may produce more or less equitable outcomes for advantaged vs disadvantaged populations. We compared treatments and outcomes of older high- and low-income patients across 6 countries. Objective: To determine whether treatment patterns and outcomes for patients presenting with acute myocardial infarction differ for low- vs high-income individuals across 6 countries. Design, Setting, and Participants: Serial cross-sectional cohort study of all adults aged 66 years or older hospitalized with acute myocardial infarction from 2013 through 2018 in the US, Canada, England, the Netherlands, Taiwan, and Israel using population-representative administrative data. Exposures: Being in the top and bottom quintile of income within and across countries. Main Outcomes and Measures: Thirty-day and 1-year mortality; secondary outcomes included rates of cardiac catheterization and revascularization, length of stay, and readmission rates. Results: We studied 289 376 patients hospitalized with ST-segment elevation myocardial infarction (STEMI) and 843 046 hospitalized with non-STEMI (NSTEMI). Adjusted 30-day mortality generally was 1 to 3 percentage points lower for high-income patients. For instance, 30-day mortality among patients admitted with STEMI in the Netherlands was 10.2% for those with high income vs 13.1% for those with low income (difference, -2.8 percentage points [95% CI, -4.1 to -1.5]). One-year mortality differences for STEMI were even larger than 30-day mortality, with the highest difference in Israel (16.2% vs 25.3%; difference, -9.1 percentage points [95% CI, -16.7 to -1.6]). In all countries, rates of cardiac catheterization and percutaneous coronary intervention were higher among high- vs low-income populations, with absolute differences ranging from 1 to 6 percentage points (eg, 73.6% vs 67.4%; difference, 6.1 percentage points [95% CI, 1.2 to 11.0] for percutaneous intervention in England for STEMI). Rates of coronary artery bypass graft surgery for patients with STEMI in low- vs high-income strata were similar but for NSTEMI were generally 1 to 2 percentage points higher among high-income patients (eg, 12.5% vs 11.0% in the US; difference, 1.5 percentage points [95% CI, 1.3 to 1.8 ]). Thirty-day readmission rates generally also were 1 to 3 percentage points lower and hospital length of stay generally was 0.2 to 0.5 days shorter for high-income patients. Conclusions and Relevance: High-income individuals had substantially better survival and were more likely to receive lifesaving revascularization and had shorter hospital lengths of stay and fewer readmissions across almost all countries. Our results suggest that income-based disparities were present even in countries with universal health insurance and robust social safety net systems.

Late hepatitis C virus diagnosis among patients with newly diagnosed hepatocellular carcinoma: a case-control study.

BACKGROUND: New direct-acting antiviral therapies have revolutionized hepatitis C virus (HCV) infection therapy. Nonetheless, once liver cirrhosis is established, the risk of hepatocellular carcinoma (HCC) still exists despite virus eradication. Late HCV diagnosis hinders timely access to HCV treatment. Thus, we determined trends and risk factors associated with late HCV among patients with a diagnosis of HCC in Taiwan. METHODS: We conducted a population-based unmatched case-control study. 2008-2018 Claims data were derived from the Taiwan National Health Insurance Research Database. Individuals with an initial occurrence of liver cancer between 2012 and 2018 were included. The late HCV group were referred as individuals who were diagnosed with HCC within 3 years after HCV diagnosis. The control group were referred as individuals who were diagnosed more than 3 years after the index date. We used multivariable logistic models to explore individual- and provider-level risk factors associated with a late HCV diagnosis. RESULTS: A decreasing trend was observed in the prevalence of late HCV-related HCC diagnosis between 2012 and 2018 in Taiwan. On an individual level, male, elderly patients, patients with diabetes mellitus (DM), and patients with alcohol-related disease had significantly higher risks of late HCV-related HCC diagnosis. On a provider level, patients who were mainly cared for by male physicians, internists and family medicine physicians had a significantly lower risk of late diagnosis. CONCLUSIONS: Elderly and patients who have DM and alcohol related disease should receive early HCV screening. In addition to comorbidities, physician factors also matter. HCV screening strategies shall take these higher risk patients and physician factors into consideration to avoid missing opportunities for early intervention.

Macrolide-Resistant Mycoplasma pneumoniae Infections in Pediatric Community-Acquired Pneumonia.

A high prevalence rate of macrolide-resistant Mycoplasma pneumoniae (MRMP) has been reported in Asia. We performed a systematic review and meta-analysis to investigate the effect of macrolide resistance on the manifestations and clinical judgment during M. pneumoniae infections. We found no difference in clinical severity between MRMP and macrolide-sensitive Mycoplasma pneumoniae (MSMP) infections. However, in the pooled data, patients infected with MRMP had a longer febrile period (1.71 days), length of hospital stay (1.61 day), antibiotic drug courses (2.93 days), and defervescence time after macrolide treatment (2.04 days) compared with patients infected with MSMP. The risk of fever lasting for >48 hours after macrolide treatment was also significantly increased (OR 21.24), and an increased proportion of patients was changed to second-line treatment (OR 4.42). Our findings indicate diagnostic and therapeutic challenges after the emergence of MRMP. More precise diagnostic tools and clearly defined treatment should be appraised in the future.

Mass Spectrometric Analysis of Glyoxal and Methylglyoxal-Induced Modifications in Human Hemoglobin from Poorly Controlled Type 2 Diabetes Mellitus Patients.

Glyoxal and methylglyoxal are oxoaldehydes derived from the degradation of glucose-protein conjugates and from lipid peroxidation, and they are also present in the environment. This study investigated the site-specific reaction of glyoxal and methylglyoxal with the amino acid residues on human hemoglobin using a shot-gun proteomic approach with nanoflow liquid chromatography/nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS). In human hemoglobin incubated with glyoxal, modification on 8 different sites, including lysine residues at α-Lys-11, α-Lys-16, α-Lys-56, ß-Lys-17, ß-Lys-66, ß-Lys-144, and arginine residues at α-Arg-92 and ß-Arg-30, was observed using a data-dependent scan. In methylglyoxal-treated hemoglobin, there were specific residues, namely, α-Arg-92, ß-Lys-66, ß-Arg-30, and ß-Lys-144, forming carboxyethylation as well as the dehydrated product hydroimidazolone at α-Arg-92 and ß-Arg-30. These lysine and arginine modifications were confirmed by accurate mass measurement and the MS(2) and MS(3) spectra. The most intensive signal of each modified peptide was used as the precursor ion to perform the product ion scan. The relative extent of modifications was semiquantified simultaneously relative to the native reference peptide by nanoLC-NSI/MS/MS under the selected reaction monitoring (SRM) mode. The extent of these modifications increased dose-dependently with increasing concentrations of glyoxal or methylglyoxal. Six out of the eight modifications induced by glyoxal and three out of the six modifications induced by methylglyoxal were detected in hemoglobin freshly isolated from human blood samples. The relative extent of modification of these post-translational modifications was quantified in poorly controlled type 2 diabetes mellitus patients (n = 20) and in nondiabetic control subjects (n = 21). The results show that the carboxymethylated peptides at α-Lys-16, α-Arg-92, ß-Lys-17, ß-Lys-66, and the peptide at α-Arg-92 with methylglyoxal-derived hydroimidazolone are significantly higher in diabetic patients than in normal individuals (p value <0.05). This report identified and quantified glyoxal- and methylglyoxal-modified hemoglobin peptides in humans and revealed the association of the extent of modifications at specific sites with T2DM. Only one drop (10 µL) of fresh blood is needed for this assay, and only an equivalent of 1 µg of hemoglobin was analyzed by the nanoLC-NSI/MS/MS-SRM system. These results suggest the potential use of these specific post-translational modifications in hemoglobin as feasible biomarker candidates to assess protein damage induced by glyoxal and methylglyoxal.

The impact of three nursing staffing models on nursing outcomes.

AIM: To examine the impact of application of different nursing staffing models on patient safety, quality of care and nursing costs. BACKGROUND: One proposed means of addressing the staff shortage while decreasing nursing costs is the application of nursing staffing models. However, the optimal proportion of registered nurses to nurse aides remains unclear. DESIGN: A retrospective cohort study. METHODS: To examine a total of 667 inpatients of a 20-bed respiratory care centre at a medical centre located in southern Taiwan. Three mixed models of nursing staffing, where the portion of nurses compared with nurse aides was 76% (n = 213), 100% (n = 209) and 92% (n = 245), were applied during three different periods between 2006 - 2010. RESULTS: The 76% RNs group made fewer medication errors than the 100% RNs group; the 76% and 92% RNs groups had a higher rate of urinary tract infections; the 92% RNs group had a lower rate of bloodstream infections; the 76% RNs group had a lower rate of ventilator weaning; and the 76% and 92% RNs groups incurred higher nursing costs. CONCLUSIONS: Use of different nursing staffing models that substitute nurse aides for RNs may negatively affect patient safety and quality of care and increase nursing costs. To avoid this risk, hospitals should employ and train their own nurse aides and develop a training system and education materials for RN and nurse aides.

Exploring the potential of combining transcranial magnetic stimulation and electroencephalography to investigate mild cognitive impairment and Alzheimer's disease: a systematic review.

Transcranial magnetic stimulation (TMS) and electroencephalography (EEG) are non-invasive techniques used for neuromodulation and recording brain electrical activity, respectively. The integration of TMS-EEG has emerged as a valuable tool for investigating the complex mechanisms involved in age-related disorders, such as mild cognitive impairment (MCI) and Alzheimer's disease (AD). By systematically synthesizing TMS-EEG studies, this review aims to shed light on the neurophysiological mechanisms underlying MCI and AD, while also exploring the practical applications of TMS-EEG in clinical settings. PubMed, ScienceDirect, and PsychInfo were selected as the databases for this review. The 22 eligible studies included a total of 592 individuals with MCI or AD as well as 301 cognitively normal adults. TMS-EEG assessments unveiled specific patterns of corticospinal excitability, plasticity, and brain connectivity that distinguished individuals on the AD spectrum from cognitively normal older adults. Moreover, the TMS-induced EEG features were observed to be correlated with cognitive performance and the presence of AD pathological biomarkers. The comprehensive examination of the existing studies demonstrates that the combination of TMS and EEG has yielded valuable insights into the neurophysiology of MCI and AD. This integration shows great potential for early detection, monitoring disease progression, and anticipating response to treatment. Future research is of paramount importance to delve into the potential utilization of TMS-EEG for treatment optimization in individuals with MCI and AD.

Sex-Based Disparities in Acute Myocardial Infarction Treatment Patterns and Outcomes in Older Adults Hospitalized Across 6 High-Income Countries: An Analysis From the International Health Systems Research Collaborative.

BACKGROUND: Sex differences in acute myocardial infarction treatment and outcomes are well documented, but it is unclear whether differences are consistent across countries. The objective of this study was to investigate the epidemiology, use of interventional procedures, and outcomes for older females and males hospitalized with ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction (NSTEMI) in 6 diverse countries. METHODS: We conducted a serial cross-sectional cohort study of 1 508 205 adults aged ≥66 years hospitalized with STEMI and NSTEMI between 2011 and 2018 in the United States, Canada, England, the Netherlands, Taiwan, and Israel using administrative data. We compared females and males within each country with respect to age-standardized hospitalization rates, rates of cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft surgery within 90 days of hospitalization, and 30-day age- and comorbidity-adjusted mortality. RESULTS: Hospitalization rates for STEMI and NSTEMI decreased between 2011 and 2018 in all countries, although the hospitalization rate ratio (rate in males/rate in females) increased in virtually all countries (eg, US STEMI ratio, 1.58:1 in 2011 and 1.73:1 in 2018; Israel NSTEMI ratio, 1.71:1 in 2011 and 2.11:1 in 2018). Rates of cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft surgery were lower for females than males for STEMI in all countries and years (eg, US cardiac catheterization in 2018, 88.6% for females versus 91.5% for males; Israel percutaneous coronary intervention in 2018, 76.7% for females versus 84.8% for males) with similar findings for NSTEMI. Adjusted mortality for STEMI in 2018 was higher for females than males in 5 countries (the United States, Canada, the Netherlands, Israel, and Taiwan) but lower for females than males in 5 countries for NSTEMI. CONCLUSIONS: We observed a larger decline in acute myocardial infarction hospitalizations for females than males between 2011 and 2018. Females were less likely to receive cardiac interventions and had higher mortality after STEMI. Sex disparities seem to transcend borders, raising questions about the underlying causes and remedies.

Hospital partnership and patient outcomes among postacute patients with stroke.

OBJECTIVES: Postacute care (PAC) heavily relies on effective connection between acute and postacute providers. However, little is known about whether and to what extent providers' patient-sharing relationships influence patient outcomes. This study aimed to examine whether patients with stroke who were discharged to PAC hospitals with which the originating hospital had a strong patient-sharing relationship have a lower rate of rehospitalization and lower mortality risk. STUDY DESIGN: This population-based retrospective cohort study used the Taiwan National Health Insurance Research Database. A total of 1988 patients initially hospitalized for stroke between July 1, 2017, and June 30, 2018, who were newly discharged to 193 PAC hospitals from 175 originating hospitals were included. METHODS: We described the partnership between originating acute hospitals and PAC hospitals using tie strength and referral concentration. The main outcome included unplanned readmission and mortality. Hierarchical logistic regression analysis and Cox proportional hazards models were applied. RESULTS: A dose-response relationship was clearly observed between tie strength and patient outcomes. Patients with stroke who were discharged to a PAC hospital that had the strongest tie strength with the originating hospital were least likely to be readmitted and had the lowest mortality risk. Moreover, patients who received care from hospital pairs with highly or moderately concentrated referrals also had lower readmission and mortality risk. CONCLUSIONS: A greater number of shared patients and a more concentrated referral linkage between acute and PAC providers may reduce potential adverse outcomes in PAC patients. Instead of attaining more partners, PAC policies should encourage providers to strengthen their patient-sharing relationship with their existing PAC partners.

Antimicrobial Susceptibility of E. coli Isolates from Intra-Abdominal Infections in the Asia-Pacific Region: Trends in Ciprofloxacin, Ceftriaxone, Cefepime, and Piperacillin/Tazobactam Susceptibility.

Purpose: To investigate the antibiotic susceptibility of Escherichia coli isolates in patients diagnosed with intra-abdominal infections (IAIs) in the Asia-Pacific region. Patients and Methods: This study was conducted at 50 medical hospitals across 9 countries/regions as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program from 2014 to 2018. Nonduplicate isolates of aerobic and facultative gram-negative bacilli were collected and processed for further antimicrobial susceptibility testing. Results: A total of 10,709 isolates were collected, with E. coli (n=4737, 44.2%) being the leading pathogen causing IAIs, followed by Klebsiella pneumoniae (n=2429, 22.7%) and Pseudomonas aeruginosa (n=931, 8.7%). Community-associated (CA) E. coli isolates generally exhibited higher susceptibility rates for most antibiotics than hospital-associated (HA) isolates. In countries/regions other than Hong Kong, South Korea, and Singapore, HA isolates displayed lower susceptibility rates for multiple classes (≥4) of antibiotics. Among the commonly used antibiotics in IAIs, the overall susceptibility rate for ciprofloxacin was low, with an average of 41.3%. Ceftriaxone susceptibility rates in all selected countries were below 80% starting in 2018, ranging from 23.3% to 75.8%. The cefepime susceptibility rates varied across regions, with consistently reduced susceptibility ranging from 45.5% to 57.8% in India, Thailand, and Vietnam. Piperacillin/tazobactam demonstrated effectiveness against E. coli isolates in almost all countries except India, with a downward trend observed in the Philippines and Taiwan. Carbapenems remained effective against more than 90% of E. coli isolates, except in India. Conclusion: Prudent use of fluoroquinolones and ceftriaxone is advised when treating both CA and HA IAIs in the Asia-Pacific region. The low susceptibility rate of cefepime in India, Thailand, and Vietnam needs careful consideration in its administration. Moreover, the increase in nonsusceptibility to piperacillin/tazobactam in the Philippines and Taiwan poses a potential risk that should be closely monitored.

Emergence and dissemination of multidrug-resistant Escherichia coli ST8346 coharboring blaNDM-5 and blaOXA-181 in Southern Taiwan, 2017-2021.

BACKGROUND: Enterobacterales carrying blaNDM represent an emerging challenge in treating infectious diseases. In this study, we aimed to investigate the characteristics of blaNDM-producing Enterobacterales from three hospitals in southern Taiwan. METHODS: Enterobacterales strains that were nonsusceptible to more than one carbapenem (ertapenem, meropenem, imipenem, or doripenem) were collected from hospitalized patients. Molecular typing for New Delhi metallo-ß-lactamase (NDM) and antibiotic susceptibility tests were performed, followed by multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and plasmid analysis by PCR-based replicon typing. RESULTS: A total of 1311 carbapenem-nonsusceptible Enterobacterales were isolated from 2017 to 2021. blaNDM-encoding genes were detected in 108 isolates, with 53 (49.1%) harboring blaNDM-1 and 55 (50.9%) harboring blaNDM-5. The rate of blaNDM-1 detection among isolates decreased to 2% in 2021. However, the rate of E. coli harboring blaNDM-5 increased from 1% to 12% of total isolates during the study period. Of 47 NDM-5-positive E. coli isolates, 44 (93.6%) were ST8346 with high genetic relatedness. E. coli ST8346 isolates showed high-level resistance to both carbapenems and aminoglycosides. Most (38 out of 47, 80.9%) blaNDM-5-harboring E. coli isolates co-harbored blaOXA-181. We analyzed the regions harboring blaNDM-5 in E. coli ST8346 via PCR amplification. blaNDM-5 and blaOXA-181 were located on two separate plasmids, IncF and IncX3, respectively. CONCLUSION: The dissemination of E. coli ST8346 caused an increase in blaNDM-5 and blaOXA-181 co-harboring Enterobacterales in southern Taiwan, which show high-level resistance to both carbapenems and aminoglycosides. We identified a distinct IncF plasmid encoding blaNDM-5 that has the potential for rapid spread and needs further surveillance.

Variation in care for patients presenting with hip fracture in six high-income countries: A cross-sectional cohort study.

BACKGROUND: Hip fractures are costly and common in older adults, but there is limited understanding of how treatment patterns and outcomes might differ between countries. METHODS: We performed a retrospective serial cross-sectional cohort study of adults aged ≥66 years hospitalized with hip fracture between 2011 and 2018 in the US, Canada, England, the Netherlands, Taiwan, and Israel using population-representative administrative data. We examined mortality, hip fracture treatment approaches (total hip arthroplasty [THA], hemiarthroplasty [HA], internal fixation [IF], and nonoperative), and health system performance measures, including hospital length of stay (LOS), 30-day readmission rates, and time-to-surgery. RESULTS: The total number of hip fracture admissions between 2011 and 2018 ranged from 23,941 in Israel to 1,219,696 in the US. In 2018, 30-day mortality varied from 3% (16% at 1 year) in Taiwan to 10% (27%) in the Netherlands. With regards to processes of care, the proportion of hip fractures treated with HA (range 23%-45%) and THA (0.2%-10%) differed widely across countries. For example, in 2018, THA was used to treat approximately 9% of patients in England and Israel but less than 1% in Taiwan. Overall, IF was the most common surgery performed in all countries (40%-60% of patients). IF was used in approximately 60% of patients in the US and Israel, but only 40% in England. In 2018, rates of nonoperative management ranged from 5% of patients in Taiwan to nearly 10% in England. Mean hospital LOS in 2018 ranged from 6.4 days (US) to 18.7 days (England). The 30-day readmission rate in 2018 ranged from 8% (in Canada and the Netherlands) to nearly 18% in England. The mean days to surgery in 2018 ranged from 0.5 days (Israel) to 1.6 days (Canada). CONCLUSIONS: We observed substantial between-country variation in mortality, surgical approaches, and health system performance measures. These findings underscore the need for further research to inform evidence-based surgical approaches.

Reactive nitrogen oxide species-induced post-translational modifications in human hemoglobin and the association with cigarette smoking.

Nitric oxide (NO) is essential for normal physiology, but excessive production of NO during inflammatory processes can damage the neighboring tissues. Reactive nitrogen oxide species (RNOx), including peroxynitrite (ONOO(-)), are powerful nitrating agents. Biological protein nitration is involved in several disease states, including inflammatory diseases, and it is evident by detection of 3-nitrotyrosine (3NT) in inflamed tissues. In this study, we identified peroxynitrite-induced post-translational modifications (PTMs) in human hemoglobin by accurate mass measurement as well as by the MS(2) and MS(3) spectra. Nitration on Tyr-24, Tyr-42 (α-globin), and Tyr-130 (ß-globin) as well as nitrosation on Tyr-24 (α-globin) were identified. Also characterized were oxidation of all three methionine residues, α-Met-32, α-Met-76, and ß-Met-55 to the sulfoxide, as well as cysteine oxidation determined as sulfinic acid on α-Cys-104 and sulfonic acid on α-Cys-104, ß-Cys-93, and ß-Cys-112. These modifications are detected in hemoglobin freshly isolated from human blood and the extents of modifications were semiquantified relative to the reference peptides by nanoflow liquid chromatography-nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS) under the selected reaction monitoring (SRM) mode. The results showed a statistically significant positive correlation between cigarette smoking and the extents of tyrosine nitration at α-Tyr-24 and at α-Tyr-42. To our knowledge, this is the first report on identification and quantification of multiple PTMs in hemoglobin from human blood and association of a specific 3NT-containing peptide with cigarette smoking. This highly sensitive and specific assay only requires hemoglobin isolated from one drop (∼10 µL) of blood. Thus, measurement of these PTMs in hemoglobin might be feasible for assessing nitrative stress in vivo.

Deep-Learning-Based Automated Classification of Chinese Speech Sound Disorders.

This article describes a system for analyzing acoustic data to assist in the diagnosis and classification of children's speech sound disorders (SSDs) using a computer. The analysis concentrated on identifying and categorizing four distinct types of Chinese SSDs. The study collected and generated a speech corpus containing 2540 stopping, backing, final consonant deletion process (FCDP), and affrication samples from 90 children aged 3-6 years with normal or pathological articulatory features. Each recording was accompanied by a detailed diagnostic annotation by two speech-language pathologists (SLPs). Classification of the speech samples was accomplished using three well-established neural network models for image classification. The feature maps were created using three sets of MFCC (Mel-frequency cepstral coefficients) parameters extracted from speech sounds and aggregated into a three-dimensional data structure as model input. We employed six techniques for data augmentation to augment the available dataset while avoiding overfitting. The experiments examine the usability of four different categories of Chinese phrases and characters. Experiments with different data subsets demonstrate the system's ability to accurately detect the analyzed pronunciation disorders. The best multi-class classification using a single Chinese phrase achieves an accuracy of 74.4 percent.

Factors associated with nonadherence to surveillance for hepatocellular carcinoma among patients with hepatic C virus cirrhosis, 2000-2015.

Hepatocellular carcinoma (HCC) surveillance can detect the early stage of tumors and lead to improved survival. Adherence to guideline-concordant HCC surveillance is crucial in at-risk populations, including patients with hepatic C virus (HCV) cirrhosis. This study was conducted to identify patient and provider factors associated with nonadherence to HCC surveillance in patients with HCV cirrhosis. Data were primarily obtained from the Taiwan National Health Insurance Research Database for the 2000 to 2015 period. Adult patients newly diagnosed as having HCV cirrhosis between 2003 and 2012 were enrolled. Each patient was followed up for 3 years and until the end of 2015. Annual HCC surveillance was defined as the uptake of an abdominal ultrasound and alpha-fetoprotein (AFP) test annually during the 3-years follow-up. Nonannual surveillance was defined as the lack of an annual abdominal ultrasound and AFP test during the same 3-years period. Multinomial logistic regression models were applied to determine factors influencing adherence or nonadherence to annual HCC surveillance. We included a total of 4641 patients with HCV cirrhosis for analysis. Of these patients, only 14% adhered to annual HCC surveillance. HCC surveillance improved in later years, compared with the earlier phases of the study period. Patients with HCV cirrhosis comorbid with coronary artery disease (CAD) or chronic obstructive pulmonary disease (COPD) or those with a relatively high number of comorbidities had a significantly higher likelihood of nonadherence. Patients who primarily received care from internists were significantly less likely to exhibit nonadherence to annual HCC surveillance compared with patients receiving care from physicians of other specialties. Patients who primarily received care from physicians practicing in larger hospitals were significantly less likely to exhibit nonadherence. HCC surveillance rates remain unacceptably low among high-risk patients, and our findings may be helpful in the development of effective interventions to increase HCC surveillance. The effective incorporation of HCC surveillance into routine visits for other chronic comorbidities, particularly for CAD or COPD, may be crucial for increasing HCC surveillance.

Circulating pediatric respiratory pathogens in Taiwan during 2020: Dynamic change under low COVID-19 incidence.

BACKGROUND: In Taiwan, there were only 799 confirmed COVID-19 cases in 2020. The unique backdrop amidst a pandemic and promotion of nonpharmaceutical interventions generated some distinct changes in the epidemiology of common respiratory pathogens. In this study, we aimed to investigate the dynamic changes in respiratory pathogens in children during 2020. METHODS: We performed a retrospective cohort study at a tertiary hospital in southern Taiwan during 2020. Patients aged 0-18 years who visited the pediatric emergency department were enrolled. Children who presented with clinical symptoms (fever or respiratory illness) and received nasopharyngeal swabs for multiplex polymerase chain reaction (PCR) were included in our analysis. We also compared respiratory syncytial virus (RSV) trends from previous years by PCR and lateral flow immunochromatographic assays from 2017 to 2020. RESULTS: A total of 120 children were tested. The overall detection rate was 55%. With strengthened restrictions, the detection rate dropped from 70% to 30%. However, non-enveloped viruses (rhinovirus/enterovirus and adenovirus) were in constant circulation. Upon easing prevention measures, the detection rate remained above 60%, and an outbreak of an enveloped virus (RSV and parainfluenza virus) was noted. Compared with 2017-2019, the cyclical RSV epidemic was delayed, with a large surge in late 2020. CONCLUSIONS: We observed a constant circulation of non-enveloped viruses when strict nonpharmaceutical interventions were employed and a delayed surge of enveloped viruses during the easing of restrictions. Continuous surveillance and monitoring of the evolutionary dynamics of respiratory viruses is important, while easing restrictions requires balanced judgment.

Distribution of ß-lactamases and emergence of carbapenemases co-occurring Enterobacterales isolates with high-level antibiotic resistance identified from patients with intra-abdominal infection in the Asia-Pacific region, 2015-2018.

PURPOSE: In this study, we aimed to assess the geographic distribution and molecular characteristics of ß-lactamases among Enterobacterales isolates causing intra-abdominal infections (IAIs) from 2015 to 2018 in the Asia-Pacific region. METHOD: Isolates were investigated for extended-spectrum ß-lactamases (ESBLs), AmpC ß-lactamases, and carbapenemases using multiplex PCR assays and full-gene DNA sequencing. RESULT: A total of 832 Enterobacterales isolates from 8 different countries with ß-lactamase genes were analysed. Plasmid-mediated ESBLs and AmpC ß-lactamases were encoded in 598 (71.9 %) and 314 (37.7 %) isolates, respectively. In 710 (85.3 %) carbapenemase-negative isolates, positivity for both AmpC ß-lactamases and ESBLs was identified in 51 (8.5 %) Escherichia coli and 24 (3.4 %) Klebsiella pneumoniae isolates. The most prevalent countries were Taiwan and Vietnam, and the co-occurrence of CMY/CTX-M in E. coli and DHA-1/ESBLs in K. pneumoniae was predominant. All isolates showed high susceptibility to colistin, but susceptibility to carbapenems varied among different resistance mechanism combinations. Among 122 (14.7 %) isolates encoding carbapenemase, NDM (n = 67, including 64.2 % NDM-1) was the most common, followed by the OXA-48-type (n = 49), KPC (n = 24) and IMP (n = 4). The most prevalent country was Thailand (n = 44), followed by Vietnam (n = 35) and the Philippines (n = 21). Twenty-two isolates were found to encode multiple carbapenemases, 16 of which were collected from Thailand and harbored NDM-1, OXA-232 and CTX-M-15. Despite high susceptibility to amikacin, susceptibility to colistin was only 56 %. CONCLUSION: The emergence of carbapenem-non-susceptible AmpC/ESBL co-occurring Enterobacterales and colistin non-susceptible carbapenemases co-occurring K. pneumoniae highlights potential therapeutic challenges in the Asia-Pacific region.

Severe Mycoplasma pneumoniae infections with prolonged fever in a child: Delayed treatment is as important as macrolide resistance.

We report a 7-year-old girl who got Mycoplasma pneumoniae infection with prolonged fever. Macrolide was used on day 14 of illness but fever persisted with progressive lung consolidation. Oral prednisolone was administered on day 33 then fever subsided with dramatically clinical improvement (decreased CRP and resolution of lung consolidation). In this case, delayed effective antibiotic treatment with inflammation may be the major factor contributing to the fever rather than ongoing infection.

Weight Gain Associated with COVID-19 Lockdown in Children and Adolescents: A Systematic Review and Meta-Analysis.

BACKGROUND: Lockdown is an effective nonpharmaceutical intervention to reduce coronavirus disease 2019 (COVID-19) transmission, but it restricts daily activity. We aimed to investigate the impact of lockdown on pediatric body weight and body mass index (BMI). METHODS: The systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Four online databases (EMBASE, Medline, the Cochrane Library and CINAHL) were searched. RESULTS: The pooled results showed that lockdown was associated with significant body weight gain (MD 2.67, 95% CI 2.12-3.23; p < 0.00001). The BMI of children with comorbidities or obesity did not change significantly. The BMI of general population was significantly higher during lockdown than before the pandemic (MD 0.94, 95% CI 0.32-1.56; p = 0.003). However, heterogeneity was high (I2 = 84%). Among changes in weight classification, increases in the rates of obesity (OR 1.23, 95% CI 1.10-1.37; p = 0.0002) and overweight (OR 1.17, 95% CI 1.06-1.29; p = 0.001) were reported. CONCLUSIONS: Our meta-analysis showed significant increases in body weight and BMI during lockdown among school-age children and adolescents. The prevalence of obesity and overweight also increased. The COVID-19 pandemic worsened the burden of childhood obesity.

Prevalence and Initial Diagnosis of Cerebral Palsy in Preterm and Term-Born Children in Taiwan: A Nationwide, Population-Based Cohort Study.

The aim of this long-term longitudinal study in Taiwan was to estimate and compare the prevalence of cerebral palsy (CP) and to identify the age of CP diagnosis of term-born and preterm children with different birthweights. Records of 1494 extremely low birth weight (ELBW, <1000 g), 3961 very low birth weight (VLBW, 1000-1499 g), 19,612 low birth weight (LBW, 1500-2499 g) preterm, and 100,268 matched term-born children were retrieved from Taiwan's National Health Insurance Research Database. According to a 12-year retrospective data review, the results showed the highest prevalence of CP in preterm ELBW children (147.3 cases per 1000 neonatal survivors), followed by preterm VLBW (97.2 cases), preterm LBW (27.7 cases), with the lowest prevalence in term-born children (2.5 cases). Regardless of the birthweight group, 90% of preterm children with CP were diagnosed by 4 years of age, but it was 7 years before 90% of term-born children with CP were diagnosed. After removing the children whose CP was caused by brain infections, injuries, or cerebrovascular accidents after 4 months of age, there were similar mean ages at the initial CP diagnosis (1.58-1.64 years of age) across birthweight groups born prematurely, but initial diagnosis occurred at an older age (2.41 years of age) in term-born children. The results indicate that birthweight is reversely correlated with the prevalence of CP in preterm children. Although the three preterm birthweight groups received different types of developmental follow-up programs after birth, it did not influence their age at the initial diagnosis of CP. Furthermore, we suggest that follow-up for at least 4 years after birth for preterm children, and 7 years for term-born children, is optimal for estimating CP prevalence. In order to identify and provide early intervention for term-born children with CP earlier, it is suggested that parents routinely fill out a self-reported motor developmental screening questionnaire and pediatricians conduct a motor developmental examination on term-born children at each time of scheduled vaccination injections.