National expert consensus on short-acting beta2-agonist overreliance in asthma care in Malaysia.

OBJECTIVE: Inappropriate use of short-acting beta2-agonists (SABA) in asthma has been associated with undesired outcomes. This national expert consensus was developed to spread awareness of SABA overuse and provide recommendations on the ways to eliminate SABA overprescription and overreliance in asthma care in Malaysia. DATA SOURCES: This expert consensus was developed by searching the PubMed database, using index terms to identify SABA overuse-related burden and recommendations made in asthma guidelines. Consensus recommendations were made via the Delphi method, involving a Malaysian expert committee comprising 13 healthcare professionals (five pulmonologists, four family medicine specialists, two emergency medicine physicians and two pharmacists). STUDY SELECTIONS: The articles reviewed include randomized controlled trials, systematic reviews, meta-analyses, observational studies, guidelines, and surveys, with abstracts in English and published up until June 2023. Relevant recommendations were also sourced from the verified websites of medical organizations and societies. RESULTS: Eleven consensus statements were developed, each statement achieving a priori agreement level of at least 70%. The statements reflect SABA overreliance in asthma care, as well as recommendations to eliminate SABA overprescription and overreliance in Malaysia. Supporting evidence in literature as well as expert committee discussions leading to the development of the finalized statements were elaborated. CONCLUSION: This national expert consensus discussed the burden of SABA overreliance and made specific recommendations to eliminate SABA overprescription and overreliance in the Malaysian context. This consensus document is anticipated to impart better awareness among Malaysian healthcare providers and contribute to the continuous improvement of asthma care in the country.

Safety and effectiveness of remdesivir in hospitalized patients with COVID-19 and severe renal impairment: experience at a large medical center.

BACKGROUND: Literature on the safety of remdesivir in hospitalized COVID-19 patients with severe renal impairment is limited. We aimed to investigate the safety and effectiveness of remdesivir in this population. METHODS: We conducted a retrospective cohort study of adult hospitalized COVID-19 patients who received remdesivir between April 2022 and October 2022. Outcomes were compared between estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and ≥30 mL/min/1.73 m2 groups. The primary safety outcomes were acute kidney injury (AKI) and bradycardia, while the primary effectiveness outcomes included mortality in COVID-19-dedicated wards and hospital mortality. Secondary outcomes included laboratory changes, disease progression, and recovery time. RESULTS: A total of 1,343 patients were recruited, with 307 (22.9%) in the eGFR <30 group and 1,036 (77.1%) in the eGFR ≥30 group. Patients with an eGFR <30 had higher risks of AKI (adjusted hazard ratio [aHR] 2.92, 95% CI 1.93-4.44) and hospital mortality (aHR 1.47, 95% CI 1.06-2.05) but had comparable risks of bradycardia (aHR 1.15, 95% CI 0.85-1.56) and mortality in dedicated wards (aHR 1.43, 95% CI 0.90-2.28) than patients with an eGFR ≥30. Risk of disease progression was higher in the eGFR <30 group (adjusted odds ratio 1.62, 95% CI 1.16-2.26). No difference between the two groups in laboratory changes and recovery time. CONCLUSIONS: Hospitalized COVID-19 patients receiving remdesivir with severe renal impairment had an increased risk of AKI, hospital mortality, and COVID-19 disease progression compared to patients without severe renal impairment.

Quantified difference of the collapsed cone convolution (CCC) and Monte Carlo (MC) algorithms based on DVH and gamma analysis for cervical cancer radiation therapy.

OBJECTIVE: To quantify the difference between the (collapsed cone convolution) CCC algorithm and the (Monte Carlo) MC algorithm and remind that the planners should pay attention to some possible uncertainties of the two algorithms when employing the two algorithms. METHODS: Thirty patients' cervical cancer VMAT plans were designed with a Pinnacle TPS (Philips) and divided equally into two groups: the simple group (SG, target volume was only the PTV) and the complex group (CG, target volume included the PTV and PGTV). The plans from the Pinnacle TPS were transferred to the Monaco TPS (Elekta). The plans' parameters all remained unchanged, and the dose was recalculated. Gamma passing rates (GPRs) obtained from dose distribution from Pinnacle TPS compared with that from Monaco TPS with SNC software based on three triaxial planes (transverse, sagittal and coronal). GPRs and DVH were used to quantify the difference between the CCC algorithm in pinnacle TPS and the MC algorithm in Monaco TPS. RESULTS: Among the statistical dose indexes in DVHs from the Pinnacle and Monaco TPSs, there were 7(7/15) dose indexes difference with statistically significant differences in the SG, and 10(10/18) dose indexes difference with statistically significant differences in the CG. With 3%/3 mm criterion, the most (5/6) GPRs were greater than 95% from the SG and CG. But with 2%/2 mm criterion, the most (5/6) GPRs were less than 90% from the two groups. In addition, we found that GPRs were also related to the selected triaxial planes and the complexity of the plan (GPRs varied with the SG and CG). CONCLUSIONS: Obvious difference between the CCC and MC algorithms from Pinnacle and Monaco TPS. DVH maybe better than 2D gamma analysis on quantifying difference of the CCC and MC algorithms. Some attention should be paid to the uncertainty of the TPS algorithm, especially when the indicator on the DVH is at the critical point of the threshold value, because the algorithm used may overestimate or underestimate the DVH indicator.

Bleeding Risk of Cold Versus Hot Snare Polypectomy for Pedunculated Colorectal Polyps Measuring 10 mm or Less: Subgroup Analysis of a Large Randomized Controlled Trial.

INTRODUCTION: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions. METHODS: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp. RESULTS: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group. DISCUSSION: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm.

College students' perceptions of electronic cigarette risks and benefits: a concept mapping study.

The use of electronic cigarettes (e-cigarettes) is on the rise among young adults, with higher public acceptance than traditional tobacco. A study in Taiwan employed concept mapping to explore risk and benefit perceptions of e-cigarette use among college students. The study involved 100 college students from 11 Taiwanese universities, with 50 being e-cigarette users and 50 non-users. Data collection and analysis were done with the GroupWisdom™ platform. Participants engaged in brainstorming, rating and sorting their perceptions, which were analyzed using multidimensional scaling and hierarchical cluster analyses. The participants' mean age was 19.24 years, and 55% were male. This process resulted in the identification of 10 clusters encompassing 64 statements, with 3 clusters focused on risk perceptions, 6 on benefit perceptions, and 1 dealing with e-cigarette regulations. Notably, risk perceptions were rated higher than benefit perceptions. Non-users held significantly higher risk perceptions and lower benefit perceptions across the nine clusters related to e-cigarette use. Concept mapping proved to be an effective tool for understanding college students' perceptions. These findings can assist health educators in comprehending college students' viewpoints on e-cigarette use and in developing targeted interventions. Additionally, exploring benefit perceptions may enhance students' critical thinking skills regarding e-cigarette advertising.

Injectable hydrogel with doxorubicin-loaded ZIF-8 nanoparticles for tumor postoperative treatments and wound repair.

The need for tumor postoperative treatments aimed at recurrence prevention and tissue regeneration have raised wide considerations in the context of the design and functionalization of implants. Herein, an injectable hydrogel system encapsulated with anti-tumor, anti-oxidant dual functional nanoparticles has been developed in order to prevent tumor relapse after surgery and promote wound repair. The utilization of biocompatible gelatin methacryloyl (GelMA) was geared towards localized therapeutic intervention. Zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, ZC) nanoparticles (NPs) were purposefully devised for their proficiency as reactive oxygen species (ROS) scavengers. Furthermore, injectable GelMA hydrogels loaded with ZC NPs carrying doxorubicin (ZC-DOX@GEL) were tailored as multifunctional postoperative implants, ensuring the efficacious eradication of residual tumor cells and alleviation of oxidative stress. In vitro and in vivo experiments were conducted to substantiate the efficacy in cancer cell elimination and the prevention of tumor recurrence through the synergistic chemotherapy approach employed with ZC-DOX@GEL. The acceleration of tissue regeneration and in vitro ROS scavenging attributes of ZC@GEL were corroborated using rat models of wound healing. The results underscore the potential of the multifaceted hydrogels presented herein for their promising application in tumor postoperative treatments.

The effect of statin treatment on glucose homeostasis in prediabetic individuals: A prospective, randomized, controlled trial.

BACKGROUND: This study aimed to evaluate the effects of rosuvastatin and pravastatin on glucose homeostasis and other biomarkers in individuals at high risk of developing diabetes. METHODS: This prospective, randomized, open-labeled, and controlled trial included prediabetic individuals with impaired fasting glucose and impaired glucose tolerance. The participants were randomized into three groups: rosuvastatin (10 mg), pravastatin (40 mg), or control. Biomarkers of diabetes and glucose and insulin responses to oral glucose tolerance tests were assessed at baseline and after six months of treatment. The primary outcomes were comparisons of glucose homeostasis and biomarkers of diabetes among groups at baseline and after six months of treatment. RESULTS: A total of 141 subjects with IFG were screened and 41 participants were recruited. Twenty-two subjects were randomized to either the rosuvastatin or pravastatin group and 19 subjects were assigned to the control group. After six months of treatment, all groups had similar cholesterol and triglyceride levels. Likewise, HbA1c levels, glucose, and insulin excursions during oral glucose tolerance test, were similar among the three groups. However, compared to the other groups, the rosuvastatin group had higher HOMA-IR (insulin resistance) and a lower Matsuda index (insulin sensitivity). CONCLUSION: Among prediabetic individuals with IFG, rosuvastatin treatment was associated with increased insulin resistance and decreased insulin sensitivity compared to pravastatin and control groups. Further research is needed to elucidate the underlying mechanisms and clinical implications of these findings.This trial was registered with the statins on glucose homeostasis in subjects with impaired fasting glucose and ClinicalTrials.gov, NCT01816997.

mNGS helped diagnose scrub typhus-associated HLH in children: a report of two cases.

Background: Scrub typhus, caused by the Orientia tsutsugamushi (Ot), is a widespread vector-borne disease transmitted by chigger mites. Hemophagocytic lymphohistiocytosis (HLH) is considered to be one of the potentially severe complications. The diagnosis of scrub typhus-associated HLH may be overlooked due to the non-specific clinical characteristics and the absence of pathognomonic eschar. Case presentation: We obtained clinical data from two patients in the South of Sichuan, China. The first case involved a 6-year-old girl who exhibited an unexplained fever and was initially diagnosed with sepsis, HLH, and pulmonary infection. The other patient presented a more severe condition characterized by multiple organ dysfunction and was initially diagnosed with septic shock, sepsis, HLH, acute kidney injury (AKI), and pulmonary infection. At first, a specific examination for scrub typhus was not performed due to the absence of a characteristic eschar. Conventional peripheral blood cultures yielded negative results in both patients, and neither of them responded to routine antibiotics. Fortunately, the causative pathogen Orientia tsutsugamushi (Ot) was detected in the plasma samples of both patients using metagenomics next-generation sequencing (mNGS) and further confirmed by polymerase chain reaction. Subsequently, they both were treated with doxycycline and recovered quickly. Conclusion: The unbiased mNGS provided a clinically actionable diagnosis for an uncommon pathogen-associated infectious disease that had previously evaded conventional diagnostic approaches.

OTUB1 contributes to the stability and function of Influenza A virus NS2.

The influenza A virus (IAV) consists of 8 single-stranded, negative-sense viral RNA (vRNA) segments. After infection, vRNA is transcribed, replicated, and wrapped by viral nucleoprotein (NP) to form viral ribonucleoprotein (vRNP). The transcription, replication, and nuclear export of the viral genome are regulated by the IAV protein, NS2, which is translated from spliced mRNA transcribed from viral NS vRNA. This splicing is inefficient, explaining why NS2 is present in low abundance after IAV infection. The levels of NS2 and its subsequent accumulation are thought to influence viral RNA replication and vRNP nuclear export. Here we show that NS2 is ubiquitinated at the K64 and K88 residues by K48-linked and K63-linked polyubiquitin (polyUb) chains, leading to the degradation of NS2 by the proteasome. Additionally, we show that a host deubiquitinase, OTUB1, can remove polyUb chains conjugated to NS2, thereby stabilizing NS2. Accordingly, knock down of OTUB1 by siRNA reduces the nuclear export of vRNP, and reduces the overall production of IAV. These results collectively demonstrate that the levels of NS2 in IAV-infected cells are regulated by a ubiquitination-deubiquitination system involving OTUB1 that is necessary for optimal IAV replication.

The resistance patterns and molecular characteristics of ESBL/AmpC-producing Escherichia coli from captive panda ecosystem in China.

Escherichia coli (E. coli) plays an important ecological role, and is a useful bioindicator to recognize the evolution of resistance in human, animal and environment. Recently, extended-spectrum ß-lactamases (ESBL) producing E.coli has posed a threat to public health. Generally, captive healthy giant pandas are not exposed to antibiotics; however, they still acquire antimicrobial resistant bacteria. In order to understand whether there is an exchange of resistance genes within the ecosystems of captive giant pandas, this study explored resistance characteristics of 330 commensal E. coli isolates from feces of giant pandas, the surroundings, and breeders. Isolates from different sources showed similar resistance phenotype, and ESBL/AmpC-producing isolates showed more profound resistance to antibiotics than non-ESBL/AmpC-producing isolates (P<0.05). Furthermore, the occurrence of broad-spectrum ß-lactamase related resistance genes and colistin resistance genes was detected, and isolates phylogenetic typing and multilocus sequence typing (MLST) were applied in this study. Seven different ß-lactamase resistance genes (blaCTX-M-55, blaCTX-M-15, blaCTX-M-27, blaCTX-M-65, blaTEM-1, blaOXA-1 and blaCMY) and mcr-1 were found in 68 ESBL/AmpC-producing isolates. blaCTX-M-55 (48.53 %) was found the most predominant resistance genes, followed by blaTEM-1 (19.12 %) and blaCTX-M-27 (16.18 %). Nonetheless, blaCTX-M-55 was commonly detected in the isolates from giant pandas (63.16 %), the surroundings (43.48 %), and breeders (33.33 %). However, there were no carbapenemase genes detected in this study. mcr-1 was harbored in only one isolate from giant panda. Forty-five tansconjugants were successfully obtained in the conjugation experiments. The presence of antimicrobial resistance and related resistance genes tested were observed in the transconjugants. The results indicated that 52.63 % of the isolates from giant panda 73.91 % of the isolates from surroundings, and 100 % of the isolates from breeders were phylogroup A. Total of 27 sequence types (ST) were recognized from the isolate by MLST and found that ST48 (19/68; 27.94 %) was the predominant ST type, especially in the isolates from giant pandas and the surroundings. In conclusion, commensal ESBL/AmpC-producing E. coli becomes a reservoir of ESBL resistance genes, which is a potential threaten to health of giant pandas. The interaction between giant pandas, surroundings and breeders contribute to development of resistant phenotypes and genotypes which might transfer across species or the surroundings easily; hence, strict monitoring based on a "One Health" approach is recommended.

Polygenic risk score predicting susceptibility and outcome of benign prostatic hyperplasia in the Han Chinese.

BACKGROUND: Given the high prevalence of BPH among elderly men, pinpointing those at elevated risk can aid in early intervention and effective management. This study aimed to explore that polygenic risk score (PRS) is effective in predicting benign prostatic hyperplasia (BPH) incidence, prognosis and risk of operation in Han Chinese. METHODS: A retrospective cohort study included 12,474 male participants (6,237 with BPH and 6,237 non-BPH controls) from the Taiwan Precision Medicine Initiative (TPMI). Genotyping was performed using the Affymetrix Genome-Wide TWB 2.0 SNP Array. PRS was calculated using PGS001865, comprising 1,712 single nucleotide polymorphisms. Logistic regression models assessed the association between PRS and BPH incidence, adjusting for age and prostate-specific antigen (PSA) levels. The study also examined the relationship between PSA, prostate volume, and response to 5-α-reductase inhibitor (5ARI) treatment, as well as the association between PRS and the risk of TURP. RESULTS: Individuals in the highest PRS quartile (Q4) had a significantly higher risk of BPH compared to the lowest quartile (Q1) (OR = 1.51, 95% CI = 1.274-1.783, p < 0.0001), after adjusting for PSA level. The Q4 group exhibited larger prostate volumes and a smaller volume reduction after 5ARI treatment. The Q1 group had a lower cumulative TURP probability at 3, 5, and 10 years compared to the Q4 group. PRS Q4 was an independent risk factor for TURP. CONCLUSIONS: In this Han Chinese cohort, higher PRS was associated with an increased susceptibility to BPH, larger prostate volumes, poorer response to 5ARI treatment, and a higher risk of TURP. Larger prospective studies with longer follow-up are warranted to further validate these findings.

Retrospective Comparison of the Anesthetic Effects of Tiletamine-Zolazepam with Dexmedetomidine and Ketamine with Dexmedetomidine in Captive Formosan Serow (Capricornis swinhoei).

Formosan serows are endemic to the mountainous regions of Taiwan. This crossover study aimed to assess and compare the anesthetic induction and recovery using either dexmedetomidine-tiletamine-zolazepam (DZ) or dexmedetomidine-ketamine (DK) by intramuscular injection from a blow-dart in a zoo environment. Ten anesthetic procedures were performed with five adult Formosan serows. Each participant was anesthetized with both combinations at least once with a minimal 12-month washout. The average dosages were 22.6 ± 8.3 µg/kg and 35.8 ± 2.5 µg/kg for dexmedetomidine and 185.6 ± 123.6 and 357.8 ± 25.2 µg/kg for atipamezole for the DZ and DK groups, respectively. The doses of tiletamine-zolazepam and ketamine were 2.1 ± 0.25 mg/kg and 3.6 ± 0.3 mg/kg, respectively, in the DZ and DK groups. All participants were induced within 10 min (median: 8 min for both groups), except one serow in the DK group with an induction time of 22 min. Serows in the DZ group had a lower respiratory rate (p = 0.016) and lower rectal temperature (p = 0.008) than those in the DK group. The quality of recovery was poor for DZ because of paddling, prolonged recovery, and ataxia after antagonism of dexmedetomidine with atipamezole. The induction of anesthesia with dexmedetomidine-tiletamine-zolazepam was uneventful and rapid. However, recovery from this combination was not smooth.

Efficacy of resilience-related psychological interventions in patients with long-term diseases: A meta-analysis of randomised controlled trials.

Patients with long-term disease experience low resilience, emphasising the importance of psychological interventions to improve resilience. However, there is no comprehensive evidence on the efficacy of resilience-related psychological interventions (RRPIs) in this population. Therefore, we performed a meta-analysis to evaluate and extend knowledge from previous meta-analyses on the efficacy of RRPIs on resilience, stress, anxiety, depression and quality of life among patients with long-term disease. Cochrane Library, Embase, Ovid-MEDLINE, PubMed, Scopus, Web of Science and CINAHL electronic databases were searched until 3 February 2023. The pooled effect size of the efficacy of RRPIs was calculated using the Hedges' g (g) with random-effects model, while Cochrane Q-statistics and I2 tests assessed heterogeneity in Comprehensive Meta-Analysis 3.0 software. The Cochrane Risk of Bias 2.0 tool evaluated the quality of studies. Moderator analysis was used to explore sources of heterogeneity. Twenty randomised controlled trial studies were identified, representing a total of 1388 individuals with long-term disease. RRPIs significantly enhance resilience (g = 0.79), alleviate stress (g = -0.78), decrease anxiety (g = -1.14), mitigate depression (g = -0.96) and improve quality of life (g = 0.48). Positive psychology, mindfulness, cognitive behavioural therapy, acceptance and commitment-based intervention exhibited medium effects in strengthening resilience. Short-term effects of RRPIs on enhancing resilience were observed at 3-month follow-up period (g = 0.50). The incorporation of RRPIs into the management of patients with long-term disease shows a positive impact on their resilience, stress, anxiety, depression and quality of life. The results offer an evidence-based foundation for nurses in promoting resilience among patients with long-term disease.

Advancing climate-resilient flood mitigation: Utilizing transformer-LSTM for water level forecasting at pumping stations.

Proactive management of pumping stations using artificial intelligence (AI) technology is vital for effectively mitigating the impacts of flood events caused by climate change. Accurate water level forecasts are pivotal in advancing the intelligent operation of pumping stations. This study proposed a novel Transformer-LSTM model to offer accurate multi-step-ahead forecasts of the flood storage pond (FSP) and river water levels for the Zhongshan pumping station in Taipei, Taiwan. A total of 19,647 ten-minute-based datasets of pumping operation and storm sewer, FSP, and river water levels were collected between 2014 and 2020 and further divided into training (70 %), validation (10 %), and test (20 %) datasets for model construction. The results demonstrate that the proposed model dramatically outperforms benchmark models by producing more accurate and reliable water level forecasts at 10-minute (T + 1) to 60-minute (T + 6) horizons. The proposed model effectively enhances the connections between input factors through the Transformer module and increases the connectivity across consecutive time series using the LSTM module. This study reveals interconnected dynamics among pumping operation and storm sewer, FSP, and river water levels, enhancing flood management. Understanding these dynamics is crucial for effective execution of management strategies and infrastructure revitalization against climate impacts. The Transformer-LSTM model's forecasts encourage water practices, resilience, and disaster risk reduction for extreme weather events.