Pipette-operable microfluidic devices with hydrophobic valves in sequential dispensing with various liquid samples: multiplex disease assay by RT-LAMP.

Microfluidic dispensing technologies often require additional equipment, posing challenges for their integration into point-of-care testing (POCT) applications. In response to this challenge, we have developed a pipette-operable microfluidic device fabricated using 3D printing technology for precise liquid dispensing. This device features three reaction chambers and three distinct hydrophobic valves to control the flow direction of liquids. Through these valves, the pipette-operable microfluidic device can sequentially dispense and isolate the liquid into the three reaction chambers, allowing for the individual conduction of three distinct reactions. These hydrophobic valves, with optimized flow resistance and burst pressure, can sustain a volumetric flow rate of up to 25 µL s-1, making them compatible with a standard pipette, a syringe, or a dropper operation. Furthermore, the device is successfully used to operate with various liquids, including BSA, DMEM, FBS, plasma, and blood, representing that the device has the potential to be used for various applications. Additionally, distinct RT-LAMP primer sets have been incorporated for diagnosing SARS-CoV-2, influenza A, and influenza B within each chamber through lyophilization. This pipette-operable microfluidic device serves as a versatile tool for diagnosing these three diseases using a single loading process, with results readable by the naked eye or image assay within 30 minutes of incubation. Finally, the design concepts are extended to engineer a microfluidic device with 20 reaction chambers, offering significant potential for multi-disease diagnostics.

Efficacy of Office-Based Salivary Ductal Steroid Irrigation for Managing Post-Irradiation Xerostomia in Head and Neck Cancer Patients: A Retrospective Study.

Post-irradiation xerostomia remains a significant quality of life concern for patients with head and neck cancers. Conventional therapies offer limited effectiveness. This study aims to investigate the therapeutic potential of office-based salivary ductal steroid irrigation in patients with post-irradiation xerostomia. This single-center observational study recruited 147 head and neck cancer patients suffering from post-irradiation xerostomia between November 2020 and October 2022. All included subjects received at least one round of successful salivary ductal cannulation and irrigation. The primary measure of efficacy was improvement in subjective xerostomia and objective salivary amylase levels. A logistic regression was employed to evaluate factors affecting treatment responsiveness. The response rate among nasopharyngeal cancer (NPC) patients was 74.8%, and that among non-NPC cancer was 65.6%, without significant intergroup differences. The statistical analysis revealed no significant influence of age, gender, or disease stage on treatment responsiveness. Post-treatment salivary amylase levels were significantly higher in responsive non-NPC patients. In conclusion, salivary ductal steroid irrigation emerged as a promising therapeutic modality for the management of post-irradiation xerostomia in head and neck cancer patients. While no explicit factors were predictive of responsiveness, the high rate of symptom improvement suggests that this therapy may be a viable alternative for patients that are refractory to standard treatments.

Burning down the house: Pyroptosis in the tumor microenvironment of hepatocellular carcinoma.

A high mortality rate makes hepatocellular carcinoma (HCC) a difficult cancer to treat. When surgery is not possible, liver cancer patients are treated with chemotherapy. However, HCC management and treatment are difficult. Sorafenib, which is a first-line treatment for hepatocellular carcinoma, initially slows disease progression. However, sorafenib resistance limits patient survival. Recent studies have linked HCC to programmed cell death, which has increased researcher interest in therapies targeting cell death. Pyroptosis, which is an inflammatory mode of programmed cell death, may be targeted to treat HCC. Pyroptosis pathways, executors, and effects are examined in this paper. This review summarizes how pyroptosis affects the tumor microenvironment (TME) in HCC, including the role of cytokines such as IL-1ß and IL-18 in regulating immune responses. The use of chemotherapies and their ability to induce cancer cell pyroptosis as alternative treatments and combining them with other drugs to reduce side effects is also discussed. In conclusion, we highlight the potential of inducing pyroptosis to treat HCC and suggest ways to improve patient outcomes. Studies on cancer cell pyroptosis may lead to new HCC treatments.

A Study on the Shrinkage and Compressive Strength of GGBFS and Metakaolin Base Geopolymer under Different NaOH Concentrations.

Geopolymers (GPs) are gaining prominence due to their low carbon emissions and sustainable attributes. However, one challenge with GPs, particularly those made with ground granulated blast furnace slag (GGBFS), is their significant shrinkage during the geopolymerization process, limiting its practical applicability. This study focuses on how the substitution ratio of metakaolin (MK) and the concentration of sodium hydroxide (NaOH) in the activator can influence the shrinkage and strength of a GGBFS-based GP. The experimental approach employed a 3 × 3 parameter matrix, which varied MK substitution ratios (0%, 50%, and 100%) and adjusted the NaOH concentration (6 M, 10 M, and 14 M). The results revealed that increasing MK substitution, particularly with 6 M NaOH activation, reduced the GP shrinkage but also diminished compressive strength, requiring higher NaOH concentrations for strength improvement. Statistical tools, including analysis of variance (ANOVA) and second-order response surface methodology (RSM), were employed for analysis. ANOVA results indicated the significant impacts of both the MK content and NaOH concentration on compressive strength, with no observable interaction. However, the shrinkage exhibited a clear interaction between MK content and NaOH concentration. The RSM model accurately predicted compressive strength and shrinkage, demonstrating a high predictive accuracy, for which the coefficients of determination (R2) were 0.99 and 0.98, respectively. The model provides a reliable method for determining the necessary compressive strength and shrinkage for GGBFS-based GP based on MK substitution and NaOH concentration. Within the optimization range, the RSM model compared with experimental results showed a 6.04% error in compressive strength and 0.77% error in shrinkage for one interpolated parameter set. This study establishes an optimized parameter range ensuring a GP performance that is comparable to or surpassing OPC, with a parameter set achieving a compressive strength of 34.9 MPa and shrinkage of 0.287% at 28 days.

Impact of Low Muscle Mass on Hepatocellular Carcinoma Patients Undergoing Transcatheter Liver-Directed Therapies: Systematic Review & Meta-Analysis.

BACKGROUND AND AIM: Transcatheter liver-directed intra-arterial therapies are mainstream treatment options for intermediate-stage hepatocellular carcinoma (HCC). However, the effect of low skeletal muscle mass (LSMM) on overall survival (OS) in these patients remains uncertain. We aimed to ascertain the prevalence and prognostic effect of LSMM in this population. METHOD: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive search was performed in the PubMed and Embase databases until Oct 2023. Random-effects meta-analysis was performed to determine the pooled prevalence of LSMM and calculate the hazard ratio (HR) for OS with a 95% confidence interval (CI) in patients with intermediate-stage HCC undergoing various transarterial therapies, comparing those with and without LSMM. RESULTS: Twelve studies involving 2450 patients were included. The pooled prevalence of LSMM was 46% (95% CI, 38-55%), and the results were consistent across different treatments, regions, and age subgroups. The meta-analysis indicated that LSMM was significantly associated with decreased OS (HR, 1.78; 95% CI, 1.36-2.33; I2, 75%). Subgroup analyses reassured the main findings across various therapies, including transarterial chemoembolization (TACE) (HR, 1.68; 95% CI, 1.23-2.30; I2, 81%), transarterial embolization (TAE) (HR, 2.45; 95% CI, 1.42-4.22; I2, 0%), and transarterial radioembolization (TARE) (HR, 1.94; 95% CI, 1.01-3.73; I2, 0%). CONCLUSIONS: In intermediate-stage HCC, LSMM is common and associated with reduced OS. To achieve an optimal prognosis, clinicians should incorporate routine LSMM measurement into practice, while caring for patients with intermediate-stage HCC, irrespective of TACE, TAE, and TARE.

Acute invasive fungal rhinosinusitis in post-COVID-19 patients in Vietnam.

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFR) is a potentially lethal infection commonly found in immunocompromised patients. It is considered the most aggressive subtype of fungal sinusitis and can lead to severe morbidity and mortality. There was a significant increase in the incidence of AIFR in post-COVID-19 patients compared to AIFR cases before the COVID-19 pandemic. This study aimed to describe the clinical presentation of AIFR associated with COVID-19 illness. METHODS: A retrospective study included 22 patients diagnosed with AIFR with a recent COVID-19 infection. RESULTS: The most frequent disease associated with AIFR was diabetes mellitus (95.5%). The mycological analysis identified infection caused by Aspergillus species in 72.7% of patients. Along with stabilizing hemodynamic parameters and controlling any comorbidities, all patients in the present study underwent combined surgical debridement followed by antifungal medications. The overall survival rate was 72.7%. The chance of developing a fatal outcome was significantly higher if meningitis presented initially (odds ratio 35.63, p < 0.05). CONCLUSION: The presence of meningitis upon initial diagnosis is related to a significantly higher chance of developing a fatal outcome and should be considered, especially in AIFR patients previously treated for COVID-19 infections. Early diagnosis, early use of antifungal agents, aggressive surgical debridement, and control of comorbid conditions remain crucial in managing AIFR.

On the water transport mechanism through the microporous layers of operando polymer electrolyte fuel cells probed directly by X-ray tomographic microscopy.

Product water transport via the microporous layer (MPL) and gas diffusion layer (GDL) substrate during polymer electrolyte fuel cell (PEFC) operation was directly and quantitatively observed by X-ray tomographic microscopy (XTM). The liquid water distribution in two types of MPLs with different pore size distributions (PSDs) was characterized as a function of the inlet gas relative humidity (RH) and current density under humid operating conditions at 45 °C. During the first minute of PEFC operation, liquid water mainly accumulated at the catalyst layer (CL)/MPL interface and in the GDL substrate close to the flow fields. Furthermore, under all tested conditions, saturation in the MPL was low (<25%), whereas under the rib, the saturation in the GDL was up to ca. 70%. Based on these XTM results, it is confirmed that in the high porosity MPLs, vapor transport was non-negligible even at high humidity conditions. Therefore, on top of the widely discussed MPL pore size and its distribution, it is proposed that the lower thermal conductivity from the high porosity of MPLs can also be a main cause of promoted vapor transport, reducing water saturation near the CL.

Versatile Effects of GABA Oolong Tea on Improvements in Diastolic Blood Pressure, Alpha Brain Waves, and Quality of Life.

Emerging evidence has demonstrated that using a new manufacturing technology to produce γ-aminobutyric acid (GABA)-fortified oolong (GO) tea could relieve human stress and exert versatile physiological benefits. The purpose of this human study was to investigate the therapeutic effects of daily GO tea consumption on improvements in blood pressure, relaxation-related brain waves, and quality of life (QOL) over a period of 28 consecutive days. Total polyphenols, major catechins, and free amino acids were analyzed via an HPLC assay. Changes in heart rate, blood pressure, α brain waves (index of relaxation), and the eight-item QOL score were investigated on days 0, 7, 14, 21, and 28. The chemical analysis results showed that GO tea contained the most abundant amino acids and GABA, contributing to the relaxation activity. Among all study participants, the daily consumption of GO tea could reduce systolic blood pressure on day 21 and diastolic blood pressure on day 28 (p < 0.05 for both). For participants with pre-hypertension, GO tea could effectively reduce heart rate and systolic and diastolic blood pressure on day 28 (p < 0.05). At the end of the study, incremental changes in alpha brain waves and QOL scores were also demonstrated (p < 0.05 for both). This study suggests that GO tea might potentially serve as a natural source for alternative therapy to improve blood pressure, stress relief, and QOL.

Realization of Forest Internet of Things Using Wireless Network Communication Technology of Low-Power Wide-Area Network.

This work implements an intelligent forest monitoring system using the Internet of things (IoT) with the wireless network communication technology of a low-power wide-area network (LPWAN), a long range (LoRa), and a narrow-band Internet of things (NB-IoT). A solar micro-weather station with LoRa-based sensors and communications was built to monitor the forest status and information such as the light intensity, air pressure, ultraviolet intensity, CO2, etc. Moreover, a multi-hop algorithm for the LoRa-based sensors and communications is proposed to solve the problem of long-distance communication without 3G/4G. For the forest without electricity, we installed solar panels to supply electricity for the sensors and other equipment. In order to avoid the problem of insufficient solar panels due to insufficient sunlight in the forest, we also connected each solar panel to a battery to store electricity. The experimental results show the implementation of the proposed method and its performance.

Diphenyl disulfide potentiates the apoptosis of breast cancer cells through Bax proteolytic activation with accompanying autophagy.

Breast cancer is a leading cause of cancer-related death worldwide, and chemoresistance often leads to poor patient outcomes. In this study, we investigated the anticancer activity of synthetic diphenyl disulfide (DPDS) in breast cancer cell lines. DPDS inhibited cellular proliferation and viability in a dose-dependent manner and reduced colony formation, an index of clonogenicity. Annexin-V and 7-AAD double staining showed that DPDS could induce the apoptosis of breast cancer cells. Western blotting of the expression of Bax p21 and its cleaved form p18 suggested the activation of p18 Bax-induced apoptosis. Furthermore, the increased expression of the autophagy marker LC3B-II indicated autophagic lysosome accumulation induced by DPDS. Our findings suggest that DPDS has potential as a candidate for treating breast cancer, and further modifications and optimizations are warranted.

Prevalence and Effect of Low Skeletal Muscle Mass among Hepatocellular Carcinoma Patients Undergoing Systemic Therapy: A Systematic Review and Meta-Analysis.

Low skeletal muscle mass (LSMM) is associated with poor outcomes in hepatocellular carcinoma (HCC) patients. With the emergence of new systemic therapeutics, understanding the effect of LSMM on HCC treatment outcomes is critically important. This systematic review and meta-analysis investigates the prevalence and effect of LSMM among HCC patients undergoing systemic therapy as reported in studies identified in searches of the PubMed and Embase databases published through 5 April 2023. The included studies (n = 20; 2377 HCC patients undergoing systemic therapy) reported the prevalence of LSMM assessed by computer tomography (CT) and compared the survival outcomes [overall survival (OS) or progression-free survival (PFS)] between HCC patients with and without LSMM. The pooled prevalence of LSMM was 43.4% (95% CI, 37.0-50.0%). A random-effects meta-analysis showed that HCC patients receiving systemic therapy with comorbid LSMM had a lower OS (HR, 1.70; 95% CI, 1.46-1.97) and PFS (HR, 1.32; 95% CI, 1.16-1.51) than did those without. Subgroup analysis according to systemic therapy type (sorafenib, lenvatinib, or immunotherapy) yielded similar results. In conclusion, LSMM is prevalent among HCC patients undergoing systemic therapy and is associated with poorer survival. Early intervention or prevention strategies to improve muscle mass may be necessary for this patient population.

Factors Associated with the Underestimation of Manual CPAP Titration Pressure.

During the SARS-CoV-2 pandemic, the use of in-laboratory positive airway pressure (PAP) titration studies was not routinely suggested. PAP pressure prediction calculations are emerging as alternative methods for the treatment of these patients. The underestimation of PAP titration pressure usually leads to unsatisfactory results for PAP therapy. This study aimed to evaluate the factors associated with the underestimation of PAP titration pressure when using PAP pressure prediction equations. Estimated PAP pressure formulas based on body mass index (BMI) and apnea-hypopnea index (AHI) were chosen to validate the accuracy of equations in the successful prediction of titration pressure. Among 341 adult patients diagnosed with obstructive sleep apnea (OSA) by overnight polysomnography (PSG) and who received overnight PAP titration in order to select a successful pressure, the mean age of the total subjects was 55.4 years old and 78.9% of patients were male. The average BMI and AHI scores were 27.1 ± 4.8 and 37 ± 21.7, respectively. After multivariate stepwise regression analysis, the odds ratio of participants with a pretitration AHI was 1.017 (95% CI: 1.005-1.030). Only the severity of OSA was significantly different between the underestimated group and the adequately assessed group. In conclusion, a high AHI, but not BMI, is associated with an underestimated CPAP titration pressure in adult patients with OSA.

Degassing a Decellularized Scaffold Enhances Wound Healing and Reduces Fibrosis during Tracheal Defect Reconstruction: A Preliminary Animal Study.

Few efforts have been made regarding the optimization of porcine small intestinal submucosa (SIS) to improve its biocompatibility. This study aims to evaluate the effect of SIS degassing on the promotion of cell attachment and wound healing. The degassed SIS was evaluated in vitro and in vivo, compared with the nondegassed SIS control. In the cell sheet reattachment model, the reattached cell sheet coverage was significantly higher in the degassed SIS group than in the nondegassed group. Cell sheet viability was also significantly higher in the SIS group than in the control group. In vivo studies showed that the tracheal defect repaired by the degassed SIS patch showed enhanced healing and reductions in fibrosis and luminal stenosis compared to the nondegassed SIS control group, with the thickness of the transplanted grafts in the degassed SIS group significantly lower than those in the control group (346.82 ± 28.02 µm vs. 771.29 ± 20.41 µm, p < 0.05). Degassing the SIS mesh significantly promoted cell sheet attachment and wound healing by reducing luminal fibrosis and stenosis compared to the nondegassed control SIS. The results suggest that the degassing processing might be a simple and effective way to improve the biocompatibility of SIS.

A Two-Flap Combination for Auricular Elevation in Microtia Reconstruction.

BACKGROUND: The aims of this study were to describe and evaluate the effectiveness of combined flaps, a modification of the Nagata technique, for providing a reasonable projection for reconstructed auricles. METHODS: The authors modified the Nagata method for covering the cartilage block by introducing a new combined flap technique, including the temporoparietal skin flap and retroauricular flap. The authors compared the shape, size, and position of the reconstructed ear to the opposite ear, and we evaluated postoperative complications and patient satisfaction levels. They verified the effectiveness of the combined flap by assessing flap necrosis, skin color, thickness, hair in the auricular area, and scars. RESULTS: A total of 38 consecutive patients (39 ears) with microtia, aged 6 to 34 years, underwent reconstruction using the modified method and were followed up for 33.6 months on average. The reconstructed auricle's shape was well defined, with 41.0% having good and 15.4% having excellent results. Most cases achieved good and acceptable levels in size, position, medial longitudinal axis angle, and auriculocephalic angles, and 79.9% of patients/their families were satisfied. The authors observed no cases of flap necrosis or hypertrophic scarring, and there were low rates of flap complications, such as unmatched skin color (7.7%), unacceptable thickness (5.1%), or hair and stretch marks (10.3%). CONCLUSIONS: The modified method's reconstructed ear achieved stable projection, symmetric appearance, and obvious anatomical landmarks with high patient satisfaction. The combined flap method showed certain advantages: high survival rate, less skin contrast, no hypertrophic scars, and fewer complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Castability of a Ti-7.5Mo alloy for fabricating frameworks for removable partial dentures.

STATEMENT OF PROBLEM: The properties of commercially pure titanium are better than those of cobalt chromium alloys in various ways. However, casting pure titanium is challenging because of its high melting point and chemical reactivity. Because of excellent mechanical strength, a titanium alloy, Ti-6Al-4V, has been commonly adopted, but the aluminum and vanadium ions released may be cytotoxic. PURPOSE: The purpose of the present study was to evaluate a new titanium alloy, Ti-7.5Mo, developed by the National Cheng Kung University for casting removable denture frameworks. The casting success rate, porosity, and guide plane or rest fit were compared among frameworks cast with Ti-7.5Mo alloy and pure titanium for 3 types of edentulism. MATERIAL AND METHODS: Ti-7.5Mo alloy and pure titanium were used to cast frameworks for Kennedy Class I and II and completely edentulous conditions, with 5 frameworks for each condition. Wax patterns of the frameworks were designed and fabricated by using computer-aided design and computer-aided manufacture (CAD-CAM) technology to ensure their geometrical consistency. They were then invested with aluminum oxide-based material and cast. The castings were examined with microcomputed tomography (µCT) for porosity, and fit was evaluated from the thickness of a vinyl polyether silicone material at the guide plane or the rest by using an optical microscope. The casting was determined to be successful if the frameworks were complete. The porosity and fit were statistically evaluated by using 2-way ANOVA (α=.05). RESULTS: Using pure titanium, the casting success rate was 80%, with only 64% of the major connectors in the deficient castings being complete. The µCT images showed that the percentage of casting defects in Ti-7.5Mo castings was one-third of the pure titanium castings. Furthermore, internal voids were detected in the clasps of the pure titanium castings, while the Ti-7.5Mo castings had few defects in the minor connectors and no radiographically detectable defects in the clasps. The fit analysis demonstrated smaller gaps over both guide planes and rests in the Ti-7.5Mo castings. CONCLUSIONS: Ti-7.5Mo alloy had better castability than pure titanium. Based on the results, Ti-7.5Mo alloy is suitable for dental casting and may provide better performance.

Factors Related to Ventilation Tube Extrusion Time in Children and Adults.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the factors affecting extrusion time in both children and adults with ventilation tube (VT) insertion, providing useful information for clinicians for better decision-making, follow strategy, and potentially improve clinical outcomes for these patients. METHODS: Data from patients receiving myringotomy with VT insertion from January 1, 2007, to June 30, 2012, were retrospectively collected and analyzed by the end of 2018. Various factors, including age, gender, history of VT insertion, tympanogram, size of VT used, local finding of tympanic membrane, hypertension, diabetes mellitus, hyperlipidemia, and postoperative ear infection, were included and analyzed to examine the effects of these factors on extrusion time. RESULTS: A total of 447 patients were included in this study (Child group-Adult group = 237:210). The overall average extrusion time was 225.85 days. In the subgroup analysis, the average time was 221.3 days and 231.0 days for children and adults, respectively. The results showed that the VT extrusion time was significantly longer in participants without a history of VT insertion and in those where larger sized VTs were inserted in both age-groups. Male gender had an influence on extrusion time in children. In addition, a history of VT insertion and VT size were determined to be factors related to extrusion before 12 months in children. CONCLUSION: History of VT insertion and VT size were significantly related to VT extrusion time in both children and adults and defined as factors associated with extrusion before 12 months in children. The findings suggest avoiding VT with a diameter < 1 mm and considering an appropriately larger size in patients with a history of VT insertion to optimize VT retention.

Prognostic Factors for the Outcome of Salivary Gland Holmium: YAG Laser Intraductal Lithotripsy.

OBJECTIVES: Holmium: YAG laser has gained its popularity throughout the years and is used to treat sialolithiasis, which helps to overcome the limitations of traditional sialendoscopic lithotripsy for larger-sized salivary stones. However, little information is available regarding factors predicting the success rate of Holmium: YAG laser intraductal lithotripsy. The purpose of this study is to investigate the factors affecting the success rates of Holmium: YAG laser lithotripsy for salivary stones treatment in a tertiary care hospital. METHODS: A retrospective study conducted in patients receiving sialolithiasis surgery under sialendoscopy from May 2013 to March 2015 at Mackay Memorial Hospital, Taiwan. Data on various factors, including patients' age, gender, glands, size of largest stone, multiple stones (≥2 stones), location of the stone (distal duct, middle duct, proximal duct, and hilum), and operative time. The success of the surgery defined as patients without any complaints such as swelling or tenderness. Logistic regression and Fisher exact tests were employed to examine these factors on the success rate. RESULTS: Fifty-four patients who received sialendoscopy surgery with a mean age of 35.74 years old recruited. Logistic regression identified the operation time exceeding 210 minutes showed 23.497 folds higher odd ratio of having a result of operation failure (P < .05). CONCLUSION: The prolonged operation time is the sole independent factor affecting the successful outcome for salivary gland intraductal laser lithotripsy. We recommend operative time be no more than 210 minutes to increase the success rate in salivary gland Holmium: YAG laser intraductal lithotripsy.

Trends in the incidence of peripheral vestibular disorders: a Nationwide population-based study.

Purpose: This study aimed to examines the long-term trend of incidence of peripheral vestibular disorders between 2010 and 2018 in Taiwan. Methods: Study-eligible patients were identified from Taiwan's Longitudinal Health Insurance Database 2005 maintained by the Ministry of Health and Welfare in Taiwan. We retrieved 230,566 patients with a first-time diagnosis of peripheral vestibular disorders between 2010 and 2018. We calculated annual incidence rates of peripheral vestibular disorders per 100,000 population. We used the annual percent change (APC) to test the trend of peripheral vestibular disorders over time. Results: The mean annual incidence rate of peripheral vestibular disorders during the study period was 1489.6 per 100,000 population. Incidence showed a statistically significant steady decrease from 2010 to 2018 with a mean APC of -6.15% (95% CI = -6.97% ~ -5.32%). The decline was led by Meniere's disease (APC = -9.83, 95% CI = -10.66% ~ -8.99%), followed by benign paroxysmal positional vertigo (APC = -3.69, 95% CI = -4.53% ~ -3.03%), vestibular neuritis (APC = -7.85, 95% CI = -8.96 ~ -6.73), and other peripheral vestibular dizziness (APC = -5.56, 95% CI = -6.69% ~ -4.43%). Conclusion: The incidence of peripheral vestibular disorders, overall, and the four major subgroups, benign paroxysmal positional vertigo, Meniere's disease, vestibular neuritis, and other peripheral vestibular dizziness, all decreased substantially, year by year within the 2010-2018 period.

No dose-response relationship of clarithromycin utilization on cardiovascular outcomes in patients with stable coronary heart disease: Analysis of Taiwan's national health insurance claims data.

Background: Clarithromycin is widely used to treat various bacterial infections and has been reported to have potential cardiovascular risk. However, it is uncertain whether this association was dose dependent and confounded by indication bias in patients with stable coronary heart disease (CHD). Methods: This cohort study retrospectively analyzed a national health insurance claims data from Taiwan's 2005 Longitudinal Generation Tracking Database. We used a new-user design and 1:1 propensity score matching. A total of 9,631 eligible clarithromycin users and 9,631 non-users in 2004-2015 were subject to final analysis. All patients were followed-up after receiving clarithromycin or on the matched corresponding date until occurrence of cardiovascular morbidity in the presence of competing mortality, all-cause and cause-specific mortality, or through the end of 2015. The effect of cumulative dose, exposure duration, and indications of clarithromycin on cardiovascular outcomes were also addressed. Results: Clarithromycin use, compared with non-use, was associated with higher risk for all-cause [adjusted hazard ratios (aHR), 1.43; 95% confidence interval, 1.29-1.58], cardiovascular (1.35; 1.09-1.67), and non-cardiovascular (1.45; 1.29-1.63) mortality, but not for overall cardiovascular morbidity. Further analysis of individual cardiovascular morbidity demonstrated major risk for heart events (1.25; 1.04-1.51) in clarithromycin users than non-users. However, there was no relationship of cumulative dose, exposure duration, and indications of clarithromycin on cardiovascular outcomes. Analyses of the effects over time showed that clarithromycin increased cardiovascular morbidity (1.21; 1.01-1.45), especially heart events (1.39; 1.10-1.45), all-cause (1.57; 1.38-1.80), cardiovascular (1.58; 1.20-2.08), and non-cardiovascular (1.57; 1.35-1.83) mortality during the first 3 years. Thereafter, clarithromycin effect on all outcomes almost dissipated. Conclusion: Clarithromycin use was associated with increased risk for short-term cardiovascular morbidity (especially, heart events) and mortality without a dose-response relationship in patients with stable CHD, which was not dose dependent and confounded by indications. Hence, patients with stable CHD while receiving clarithromycin should watch for these short-term potential risks.

Impact of Acid Suppression Therapy on Renal and Survival Outcomes in Patients with Chronic Kidney Disease: A Taiwanese Nationwide Cohort Study.

Histamine-2-receptor antagonist (H2RA) has shown beneficial effects on the kidney, heart, and sepsis in animal models and on the heart and COVID-19 infection in clinical studies. However, H2RAshave been used as a reference in most epidemiological studies examining the association of proton pump inhibitors (PPI) with outcomes. Therefore, we aimed to evaluate the effect of H2RA on renal and survival outcomes in chronic kidney disease (CKD) patients. We used a Taiwanese nationalhealth insurance database from 2001 to 2016 to screen 45,767 CKD patients for eligibility. We identified new users of PPI (n = 7121), H2RA (n = 48,609), and users of neither PPI nor H2RA (as controls) (n = 47,072) during follow-up, and finally created 1:1:1 propensityscore-matchedcohorts; each cohort contained 4361 patients. Participants were followed up after receivingacid-suppression agents or on the corresponding date until the occurrence of end-stage renal disease (ESRD) in the presence of competing mortality, death, or through the end of 2016. Compared toneither users, H2RAand PPI users demonstrated adjusted hazard ratios of 0.40 (95% confidence interval, 0.30-0.53) for ESRDand 0.64 (0.57-0.72) for death and 1.15 (0.91-1.45) for ESRD and 1.83 (1.65-2.03) for death, respectively. A dose-response relationship betweenH2RA use with ESRD and overall, cardiovascular, and non-cardiovascular mortality was detected. H2RA consistently provided renal and survival benefits on multivariable stratified analyses and multiple sensitivity analyses. In conclusion, dose-dependent H2RA use was associated with a reduced risk of ESRD and overall mortality in CKD patients, whereas PPI use was associated with an increased risk of overall mortality, not in a dose-dependent manner.