Efficacy and acceptability of noninvasive brain stimulation for treating posttraumatic stress disorder symptoms: A network meta-analysis of randomized controlled trials.

INTRODUCTION: Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta-analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management. METHODS: We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason). RESULTS: We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high-frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms, including depression and anxiety symptoms, and overall PTSD severity. CONCLUSIONS: This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms. TRIAL REGISTRATION: PROSPERO CRD42023391562.

Efficacy and acceptability of different probiotic products plus laxatives for pediatric functional constipation: a network meta-analysis of randomized controlled trials.

The prevalence of pediatric constipation ranges from 0.7 to 29.6% across different countries. Functional constipation accounts for 95% of pediatric constipation, and the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. We aimed to compare the efficacy and acceptability of different probiotic supplements for pediatric functional constipation. The current frequentist model-based network meta-analysis (NMA) included RCTs of probiotic supplements for functional constipation in children. The primary outcome was changes in bowel movement or stool frequency; acceptability outcome was all-cause discontinuation. Nine RCTs were included (N = 710; mean age = 5.5 years; 49.4% girls). Most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives (standardized mean difference (SMD) = 1.87, 95% confidence interval (95% CI) = 0.85 to 2.90) were associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments (SMD = 1.37, 95% CI: 0.32 to 2.43). All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.  Conclusion: The results of our NMA support the application of an advanced combination of probiotics and laxatives for pediatric functional constipation if there is no concurrent contraindication.  Registration: PROSPERO (CRD42022298724). What is Known: • Despite of the high prevalence of pediatric constipation, which ranges from 0.7% to 29.6%, the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. The widely heterogeneous strains of probiotics let the traditional meta-analysis, which pooled all different strains into one group, be nonsense and insignificant. What is New: • By conducting a comprehensive network meta-analysis, we aimed to compare the efficacy and acceptability of different strains of probiotic supplements for pediatric functional constipation. Network meta-analysis of nine randomized controlled trials revealed that the most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives was associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments. All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.

Prophylaxis for paediatric emergence delirium in desflurane-based anaesthesia: a network meta-analysis.

PURPOSE: The prevalence of postoperative emergence delirium in paediatric patients (pedED) following desflurane anaesthesia is considerably high at 50-80%. Although several pharmacological prophylactic strategies have been introduced to reduce the risk of pedED, conclusive evidence about the superiority of these individual regimens is lacking. The aim of the current study was to assess the potential prophylactic effect and safety of individual pharmacotherapies in the prevention of pedED following desflurane anaesthesia. METHODS: This frequentist model network meta-analysis (NMA) of randomized controlled trials (RCTs) included peer-reviewed RCTs of either placebo-controlled or active-controlled design in paediatric patients under desflurane anaesthesia. RESULTS: Seven studies comprising 573 participants were included. Overall, the ketamine + propofol administration [odds ratio (OR) = 0.05, 95% confidence intervals (95%CIs) 0.01-0.33], dexmedetomidine alone (OR = 0.13, 95%CIs 0.05-0.31), and propofol administration (OR = 0.30, 95%CIs 0.10-0.91) were associated with a significantly lower incidence of pedED than the placebo/control groups. In addition, only gabapentin and dexmedetomidine were associated with a significantly higher improvement in the severity of emergence delirium than the placebo/control groups. Finally, the ketamine + propofol administration was associated with the lowest incidence of pedED, whereas gabapentin was associated with the lowest severity of pedED among all of the pharmacologic interventions studied. CONCLUSIONS: The current NMA showed that ketamine + propofol administration was associated with the lowest incidence of pedED among all of the pharmacologic interventions studied. Future large-scale trials to more fully elucidate the comparative benefits of different combination regimens are warranted. TRIAL REGISTRATION: PROSPERO CRD42021285200.

Efficacy and acceptability of anti-inflammatory eicosapentaenoic acid for cognitive function in Alzheimer's dementia: A network meta-analysis of randomized, placebo-controlled trials with omega-3 fatty acids and FDA-approved pharmacotherapy.

Alzheimer's dementia (AD) is a major contributor to global disability, and effective therapies to modify disease progression are currently lacking. The neuro-inflammatory theory is a potential etiology underlying this neurodegenerative disease. Previous randomized, controlled trials (RCTs) have provided inconclusive results regarding efficacy of omega-3 polyunsaturated fatty acids (PUFAs) regimens, which might provide anti-inflammatory benefits in the management of AD, in improving cognitive function among participants with AD. The objective of this frequentist-model based network meta-analysis (NMA) was to evaluate the potential advantages of omega-3 PUFAs and currently FDA-approved medications for AD on overall cognitive function in AD individuals. The primary outcomes were: (1) changes in cognitive function, and (2) acceptability, which refers to all-cause discontinuation. Additionally, secondary outcomes included quality of life, behavioral disturbances and safety/tolerability, which was assessed through the frequency of any reported adverse event. This NMA included 52 RCTs (6 with omega-3 PUFAs and 46 with FDA-approved medications) involving 21,111 participants. The results showed that long-term high-dose (1500-2000 mg/day) of eicosapentaenoic acid (EPA)-dominant omega-3 PUFAs augmented with anti-oxidants had the highest potential for cognitive improvement among all investigated treatments [standardized mean difference = 3.00, 95% confidence intervals (95 %CIs) = 1.84-4.16]. Compared to placebo, omega-3 PUFAs had similar acceptability [odds ratio (OR) = 0.46, 95 %CIs = 0.04 to 5.87] and safety profiles (OR = 1.24, 95 %CIs = 0.66 to 2.33)o. These findings support the potential neurotherapeutic effects of high dosage EPA-dominant omega-3 PUFAs for the amelioration of cognitive decline in patients with AD. Future large-scale, long-term RCTs should focus on different dosages of EPA-dominant omega-3 PUFAs regimens on improving cognitive dysfunction in patients with AD at different levels of inflammatory status and psychopathology.

Treatment Efficacy of Pharmacotherapies for Frontotemporal Dementia: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The neuropsychiatric symptoms of frontotemporal dementia (FTD) have a profound negative impact on disease outcomes and care burden. Available pharmacotherapies might be supported by small-scale randomized controlled trials (RCTs); however, clinical recommendations might not be conclusive. METHODS: We systematically searched several databases from inception to April 30, 2022, for RCTs of drug therapy in patients with FTD and neuropsychiatric symptoms (primary outcome). Secondary outcomes included changes in caregiver stress, daily interactive activities, cognitive function, and acceptability (adverse event or dropout rates). The network meta-analysis (NMA) procedure was performed under the frequency model, showing effect sizes as standardized mean differences (SMD) or odds ratios (OR) with 95% confidence intervals (95% CIs). RESULTS: Seven RCTs with 243 participants were included. Compared with placebo, high-dose oxytocin (72 international units) was associated with the greatest improvement in patients' neuropsychiatric symptoms (SMD = -1.17, 95% CIs = -2.25 to -0.08, z = -2.10, p = 0.035). Piracetam significantly worsened neuropsychiatric symptoms (SMD = 3.48, 95% CIs = 1.58 to 5.37, z = 3.60, p < 0.001) and caregiver stress (SMD = 2.40, 95% CIs = 0.80-4.01, z = 2.94, p = 0.003). Trazodone had significantly higher rates of adverse events (OR = 9.53, 95% CIs = 1.85-49.20, z = 2.69, p = 0.007). No pharmacological intervention significantly benefited cognitive function. CONCLUSIONS: This study provides the first NMA for clinical recommendation to support the use of high-dose oxytocin and caution regarding the use of piracetam for neuropsychiatric symptoms in patients with FTD.

Sacubitril/valsartan improves all-cause mortality in heart failure patients with reduced ejection fraction and chronic kidney disease.

BACKGROUND: Impaired renal function is frequently observed in patients with heart failure and reduced ejection fraction (HFrEF). The differential effect of sacubitril/valsartan and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEIs/ARBs) on the clinical and renal outcomes in patients with HFrEF and chronic kidney disease (CKD) remains unknown. AIMS: This study aimed to explore the differential effect of sacubitril/valsartan and ACEI/ARB on the clinical and renal outcomes as well as renal function over a 12-month follow-up period in HFrEF patients with and without CKD. METHODS: Patients with HfrEF (LVEF ≤35%) and NYHA class ≥II were enrolled from the Chang Gung Research Database between 2017 and 2020. Baseline characteristics were compared between patients prescribed sacubitril/valsartan and ACEI/ARB. After propensity score matching, the following clinical and renal outcomes were compared between the two groups in patients with and without CKD over a 12-month follow-up period: acute kidney injury (AKI), emergent dialysis/renal death, HF hospitalization, cardiovascular mortality, and all-cause mortality. RESULTS: This study enrolled 3735 HFrEF patients with a mean left ventricular EF of 27.56 ± 5.86%, who had been prescribed sacubitril/valsartan (N = 1708) or ACEI/ARB (N = 2027). After propensity score matching, the clinical and renal outcomes did not differ between the sacubitril/valsartan and ACEI/ARB groups in patients without CKD. In patients with CKD, the ACEI/ARB group had a significantly higher incidence of all-cause mortality than the sacubitril/valsartan group (14.89% vs. 10.50%; hazard ratio 1.46; 95% confidence interval 1.06-2.00; p = 0.02), and the incidence of AKI, HF hospitalization, and CV mortality did not differ between the two groups. CONCLUSIONS: Sacubitril/valsartan had a lower all-cause mortality compared to ACEI/ARB in symptomatic HFrEF patients with CKD. Further prospective randomized studies are warranted to confirm our findings.

Impact of Coexisting Risk Factors on Outcomes in Patients with Acute Coronary Syndrome: A Real-World Analysis Using the Taiwan Chang Gung Research Database.

BACKGROUND Diabetes mellitus (DM), chronic kidney disease (CKD), and advanced age are associated with poor outcomes in patients with acute coronary syndrome (ACS). This real-world study utilized data from the Taiwan Chang Gung Research Database (CGRD) to compare outcomes in ACS patients with DM, CKD, and the elderly. MATERIAL AND METHODS The study enrolled 28,613 ACS patients diagnosed based on CGRD medical records between January 2005 and December 2019. Baseline characteristics and clinical outcomes were compared among groups based on patient characteristics. RESULTS Within the ACS cohort, 42.1% had DM, 48.2% had CKD, and 33.6% were elderly. Among them, 10.7% (3,070) were elderly patients with both DM and CKD. Elderly patients with DM and CKD had significantly higher risks of gastrointestinal bleeding (hazard ratio=11.32), cardiovascular events (HR=7.29), and all-cause mortality (HR=8.59). Patients with three or at least two of these risk factors had a 2.20-2.99-fold increased risk of recurrent ACS during the three-year follow-up period. CONCLUSIONS Patients with the combination of DM, CKD, and advanced age (elderly) experienced an 11.32-fold increased risk of gastrointestinal bleeding, 7.29-fold increased risk of cardiovascular events, and 8.59-fold increased risk of all-cause mortality compared to those without these risk factors. Furthermore, patients with two or more of these risk factors had a 2- to 3-fold increased risk of recurrent ACS. These findings emphasize the importance of managing multiple risk factors in ACS patients to improve outcomes.

Mouth puffing phenomena of patients with obstructive sleep apnea when mouth-taped: device's efficacy confirmed with physical video observation.

PURPOSE: This study aimed to design a device to monitor mouth puffing phenomena of patients with obstructive sleep apnea when mouth-taped and to employ video recording and computing algorithms to double-check and verify the efficacy of the device. METHODS: A mouth puffing detector (MPD) was developed, and a video camera was set to record the patients' mouth puffing phenomena in order to make ensure the data obtained from the device was appropriate and valid. Ten patients were recruited and had polysomnography. A program written in Python was used to investigate the efficacy of the program's algorithms and the relationship between variables in polysomnography (sleep stage, apnea-hypopnea index or AHI, oxygen-related variables) and mouth puffing signals (MPSs). The video recording was used to validate the program. Bland-Altman plot, correlations, independent sample t-test, and ANOVA were analyzed by SPSS 24.0. RESULTS: Patients were found to mouth puff when they sleep with their mouths taped. An MPD was able to detect the signals of mouth puffing. Mouth puffing signals were noted and categorized into four types of MPSs by our algorithms. MPSs were found to be significantly related to relative OSA indices. When all participants' data were divided into minutes, intermittent mouth puffing (IMP) was found to be significantly different from non-mouth puffing in AHI, oxygen desaturation index (ODI), and time of oxygen saturation under 90% (T90) (AHI: 0.75 vs. 0.31; ODI: 0.75 vs. 0.30; T90: 5.52 vs. 1.25; p < 0.001). Participants with severe OSA showed a higher IMP percentage compared to participants with mild to moderate OSA and the control group (severe: 38%, mild-to-moderate: 65%, control: 95%; p < 0.001). CONCLUSIONS: This study established a simple way to detect mouth puffing phenomena when patients were mouth-taped during sleep, and the signals were classified into four types of MPSs. We propose that MPSs obtained from patients wearing the MPD can be used as a complement for clinicians to evaluate OSA.

Placebo effects on all-cause mortality of patients with COVID-19 in randomized controlled trials of interleukin 6 antagonists: A systematic review and network meta-analysis.

AIM: Many randomized controlled trials (RCTs) have investigated the use of interleukin 6 antagonists for the treatment of coronavirus disease 2019 (COVID-19), yielding inconsistent results. This network meta-analysis (NMA) aimed to identify the source of these inconsistent results by reassessing whether participants treated with standard of care (SoC) plus placebo have different all-cause mortality from those treated with SoC alone and to reevaluate the efficacy of interleukin 6 antagonists in the treatment of COVID-19. METHODS: We conducted a systematic search for relevant RCTs from the inception of electronic databases through 1 September 2022. The primary outcome was all-cause mortality. The secondary outcomes were the incidences of major medical events, secondary infections, all-cause discontinuation, and serious adverse events. RESULTS: The results of NMA of 33 RCTs showed that patients with COVID-19 treated with SoC plus placebo had lower odds of all-cause mortality than those who received SoC alone (OR, 0.75 [95% confidence interval, 0.58-0.97]). This finding remained consistent after excluding studies with no incident deaths. In addition, when we consider the impact of the widely promoted COVID-19 vaccination and newly developed antiviral treatment strategy, the results from the analysis of the RCT published in 2021 and 2022 remained similar. CONCLUSION: These findings suggest the potential influence of placebo effects on the treatment outcomes of COVID-19 in RCTs. When evaluating the efficacy of treatment strategies for COVID-19, it is crucial to consider the use of placebo in the design of clinical trials.

The efficacy of exogenous melatonin supplement in ameliorating irritable bowel syndrome severity: A meta-analysis of randomized controlled trials.

BACKGROUND: Irritable bowel syndrome (IBS) was found in 11% of the general population worldwide. The current pharmacologic management of IBS was unsatisfactory, and it was accompanied by a number of adverse events. Melatonin was found to play an important role in gastrointestinal smooth muscle motility. Dysregulation of endogenous melatonin secretion has been found in IBS patients. Exogenous melatonin supplement has become one alternative treatment for IBS, but the evidence is inconclusive. The current meta-analysis sought to determine the efficacy of exogenous melatonin supplement in improving IBS severity in IBS patients. METHODS: We included randomized controlled trials (RCTs) that investigated the efficacy of exogenous melatonin supplement in ameliorating IBS severity in IBS patients. This meta-analysis was conducted using a random effects model. The primary target outcomes were changes in IBS severity associated with melatonin or placebo. RESULTS: This meta-analysis of 4 RCTs and 115 participants revealed that exogenous melatonin supplement was associated with significantly better improvement in overall IBS severity than placebo (k = 4, Hedges' g = 0.746, 95% confidence intervals = 0.401-1.091, p < 0.001). The subgroup without concurrent medication had the same result (p < 0.001). In addition, exogenous melatonin supplement was also associated with significantly better improvement in IBS pain severity (p < 0.001) and quality of life (p = 0.007) than placebo, but not in abdominal distension (p = 0.111) or sleep quality (p = 0.142). Finally, melatonin was associated with similar safety profiles with placebo. CONCLUSION: This meta-analysis provides evidence for the use of exogenous melatonin in IBS patients to ameliorate overall IBS severity, IBS pain severity, and quality of life. TRIAL REGISTRATION: PROSPERO CRD42021269451.

The Impact of FEV1/FVC Ratio on the Clinical Outcomes in Acute Coronary Syndrome Patients Treated with Dual Anti-Platelet Agents.

Background: Few studies have investigated the clinical efficacy and pulmonary side effects of different P2Y12 inhibitors in acute coronary syndrome (ACS) patients. The aim of this study was to explore the impact of forced expiratory volume in 1 second over forced vital capacity (FEV1/FVC) ratio on the clinical outcomes in ACS patients treated with dual antiplatelet therapy after percutaneous coronary intervention (PCI). Methods: ACS patients who underwent PCI, had documented pre-existing spirometry tests, and received aspirin with either ticagrelor or clopidogrel were enrolled for retrospective analysis. Results: Of the enrolled ACS patients, 275 and 247 received ticagrelor and clopidogrel, respectively. The incidence of wheeze was significantly higher in the ticagrelor group compared to the clopidogrel group within 360 days (14.91% vs. 8.09%, p = 0.016). Multivariable analysis revealed that ticagrelor treatment, as compared to clopidogrel treatment, independently predicted 1-year hospitalization for acute exacerbation (AE) of obstructive airway disease (hazard ratio: 3.44; 95% confidence interval: 1.92 to 6.15; p < 0.01). The receiver operating characteristic curve indicated that an FEV1/FVC ratio of 63.85% had the highest sensitivity and specificity for predicting the incidence of AE of obstructive airway disease within 1 year (p < 0.001). The 1-year hospitalization rate for AE of obstructive airway disease was significantly higher in the ticagrelor group when the FEV1/FVC ratio was < 63%. Conclusions: This study demonstrated higher incidence of wheeze and hospitalization for AE of obstructive airway disease in ACS patients treated with ticagrelor compared to clopidogrel. Furthermore, the FEV1/FVC ratio ≤ 63% in the ACS patients predicted hospitalization for AE of obstructive airway disease in 1 year.

The Relationship of Conduction Disorder and Prognosis in Patients with Acute Coronary Syndrome.

Objective: Conduction disorders with a widened QRS are associated with poor prognosis in patients with acute coronary syndrome (ACS). Conduction disorders include left bundle branch block (LBBB), right bundle branch block (RBBB), and nonspecific intraventricular conduction delay (NICD). Previous studies did not have conflicting results regarding the type of bundle branch block (BBB) with the worst prognosis, and few studies have focused on the prognosis of patients with NICD. Methods: Patients with ACS were enrolled between January 2005 and December 2019, and their medical history (International Classification of Diseases codes) was obtained from the Chang Gung Research Database. Age, sex, comorbidities, left ventricular ejection fraction (LVEF), and drug use were compared between the patients with and without conduction disorders. The following clinical outcomes were compared between patients with and without conduction disorders: heart failure (HF) hospitalization, cardiovascular (CV) mortality, and all-cause mortality. After propensity score matching, the Kaplan-Meier curve analysis for HF hospitalization, CV mortality, and all-cause mortality were compared among patients with LBBB, RBBB, and NICD. Results: This study enrolled a total of 33970 participants and involved 3392 and 30578 patients with and without conduction disorders, respectively. Older age and a higher prevalence of comorbidities were noted in patients with conduction disorders. Lower mean LVEF was exhibited in the patients with conduction disorders (with vs. without; 44.64 ± 20.73% vs. 49.85 ± 20.63%; p < 0.001). During the 3-year follow-up period, higher incidences of HF hospitalization (21.55% vs. 17.51%; p < 0.001), CV mortality (17.98% vs. 12.14%; p < 0.001), and all-cause mortality (38.86% vs. 31.15%; p < 0.001) were noted in the patients with conduction disorder. After ACS events, 10.0% of patients presented with conduction disorders, with LBBB in 3.3%, RBBB in 6.0%, and NICD in 0.7%. The lowest mean of LVEF was presented in the patients with NICD (LBBB vs. RBBB vs. NICD; 41.00 ± 19.47% vs. 47.73 ± 20.82% vs. 34.57 ± 20.02%; p < 0.001). Among the three groups, the highest incidence of HF hospitalization was noted in patients with LBBB after propensity score matching. The lowest incidence of CV and all-cause mortality was observed in patients with RBBB. After adjustment of age, gender, comorbidities, medication, and mean LVEF, those with LBBB had the highest hazard ratio for major adverse cardiovascular events (MACEs) of 1.113 (p=0.029; 95% CI = 1.013-1.266). Conclusions: In the ACS population, patients with conduction delay had a poor prognosis due to a higher prevalence of comorbidities and lower mean LVEF. Among the patients with LBBB, RBBB, and NICD, those with LBBB and NICD had a higher incidence of HF hospitalization, CV mortality, and all-cause mortality. Patients with NICD had the lowest mean LVEF compared to those with LBBB and RBBB. Patients with LBBB had a significantly highest HR of MACE.

Using Deep Transfer Learning to Detect Hyperkalemia From Ambulatory Electrocardiogram Monitors in Intensive Care Units: Personalized Medicine Approach.

BACKGROUND: Hyperkalemia is a critical condition, especially in intensive care units. So far, there have been no accurate and noninvasive methods for recognizing hyperkalemia events on ambulatory electrocardiogram monitors. OBJECTIVE: This study aimed to improve the accuracy of hyperkalemia predictions from ambulatory electrocardiogram (ECG) monitors using a personalized transfer learning method; this would be done by training a generic model and refining it with personal data. METHODS: This retrospective cohort study used open source data from the Waveform Database Matched Subset of the Medical Information Mart From Intensive Care III (MIMIC-III). We included patients with multiple serum potassium test results and matched ECG data from the MIMIC-III database. A 1D convolutional neural network-based deep learning model was first developed to predict hyperkalemia in a generic population. Once the model achieved a state-of-the-art performance, it was used in an active transfer learning process to perform patient-adaptive heartbeat classification tasks. RESULTS: The results show that by acquiring data from each new patient, the personalized model can improve the accuracy of hyperkalemia detection significantly, from an average of 0.604 (SD 0.211) to 0.980 (SD 0.078), when compared with the generic model. Moreover, the area under the receiver operating characteristic curve level improved from 0.729 (SD 0.240) to 0.945 (SD 0.094). CONCLUSIONS: By using the deep transfer learning method, we were able to build a clinical standard model for hyperkalemia detection using ambulatory ECG monitors. These findings could potentially be extended to applications that continuously monitor one's ECGs for early alerts of hyperkalemia and help avoid unnecessary blood tests.

Age and sex differences on the association between anxiety disorders and obstructive sleep apnea: A nationwide case-control study in Taiwan.

AIM: The aim of this study was to examine the association between anxiety disorders and obstructive sleep apnea (OSA). METHODS: This is a population-based, retrospective case-control study using Taiwan's nationwide database. We included patients with OSA aged ≥12 years, diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes: 327 and 780. Each enrolled patient with OSA needed to undergo a polysomnography examination within 1 year pre- or post-OSA occurrence. Patients with OSA and controls were selected in a 1:4 ratio. Patients with anxiety disorders (ICD-9-CM code 300) were diagnosed by board-certified psychiatrists and required to visit the outpatient clinic at least three times per year. Multivariate logistic regression and interaction analyses were used to evaluate the objective association. RESULTS: This study enrolled 7987 and 31 948 participants with and without OSA, respectively. A significant difference in anxiety exposure was observed only pre-OSA diagnosis but not post-OSA diagnosis. Compared with patients without anxiety disorders: (i) those with anxiety disorders had an adjusted odds ratio (aOR) of ≈1.864 in OSA comorbidity (aOR = 1.864; 95% confidence interval [CI] = 1.337-2.405); and (ii) subgroup analysis showed a significant interaction that anxiety patients of male sex, aged 18 to 44 years, aged 45 to 64 years, and hypertension had a higher aOR in OSA comorbidity (aOR = 2.104 [95% CI = 1.436-2.589], aOR = 1.942 [95% CI = 1.390-2.503], aOR = 2.179 [95% CI = 1.564-2.811], and aOR = 2.092 [95% CI = 1.497-2.706], respectively). CONCLUSION: The study revealed a higher ratio of previous anxiety exposure in patients with OSA. Compared with those without anxiety, anxiety patients of male sex, aged 18 to 64 years, and with hypertension had a higher risk of OSA comorbidity.

Multiple comparison of different noninvasive brain stimulation and pharmacologic interventions in patients with methamphetamine use disorders: A network meta-analysis of randomized controlled trials.

AIM: In recent decades, the prevalence of amphetamine and methamphetamine use disorders has at least doubled in some regions/countries, with accompanying high risks of drug overdose-associated mortality. Noninvasive brain stimulation (NIBS) methods may be effective treatments. However, the comparative efficacy of the NIBS protocol for amphetamine/methamphetamine use disorder (AUD/MUD) remains unknown to date. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various NIBS methods/protocols for AUD/MUD management. METHODS: A frequentist model-based NMA was conducted. We included randomized controlled trials (RCTs) that investigated the efficacy of NIBS and guideline-recommended pharmacologic treatments to reduce craving severity in patients with either AUD or MUD. RESULTS: Twenty-two RCTs including 1888 participants met the eligibility criteria. Compared with the sham/placebo group (study = 19, subjects = 891), a combination of intermittent theta burst stimulation over the left dorsolateral prefrontal cortex (DLPFC) and continuous TBS over the left ventromedial prefrontal cortex (study = 1, subjects = 19) was associated with the largest decreases in craving severity [standardized mean difference (SMD) = -1.50; 95% confidence intervals (95%CIs) = -2.70 to -0.31]. High-frequency repetitive transcranial magnetic stimulation over the left DLPFC was associated with the largest improvements in depression and quality of sleep (study = 3, subjects = 86) (SMD = -2.48; 95%CIs = -3.25 to -1.71 and SMD = -2.43; 95%CIs = -3.38 to -1.48, respectively). The drop-out rate of most investigated treatments did not significantly differ between groups. CONCLUSION: The combined TBS protocol over the prefrontal cortex was associated with the greatest improvement in craving severity. Since few studies were available for inclusion, additional large-scale randomized controlled trials are warranted.

The association of changes of sleep architecture related to donepezil: A systematic review and meta-analysis.

BACKGROUND: Donepezil had been recognized to have impact on sleep quality in demented patients. However, there was insufficient evidences about the actual effect of donepezil in the sleep architectures. Our meta-analysis aimed to evaluate the changes of sleep architectures related to donepezil use. METHODS: Followed the PRISMA2020 and AMSTAR2 guidelines, electronic search had been performed on the databases of PubMed, Embase, ScienceDirect, ClinicalKey, Cochrane CENTRAL, ProQuest, Web of Science, and ClinicalTrials.gov. The outcome measurement was changes of sleep parameters detected by polysomnography. A random-effects meta-analysis was conducted. RESULTS: Total twelve studies had been involved. The percentage of REM sleep would significantly increase after donepezil treatment (Hedges' g = 0.694, p < 0.001). Compared to placebo/controls, subjects with donepezil would had significantly increased percentage of REM sleep stage (Hedges' g = 0.556, p = 0.018). Furthermore, donepezil was also associated with the decreased stage 2 sleep percentage, sleep efficiency, or total sleep time in different analysis conditions. CONCLUSION: Our meta-analysis provided detailed changes of sleep architectures related to donepezil treatment. Further larger sample size studies with stricter control of potential moderators are needed to clarify these issues.

Effectiveness and acceptability of noninvasive brain and nerve stimulation techniques for migraine prophylaxis: a network meta-analysis of randomized controlled trials.

BACKGROUND: Current pharmacologic prophylactic strategies for migraine have exhibited limited efficacy, with response rates as low as 40%-50%. In addition to the limited efficacy, the acceptability of those pharmacologic prophylactic strategies were unacceptable. Although noninvasive brain/nerve stimulation strategies may be effective, the evidence has been inconsistent. The aim of this network meta-analysis (NMA) was to compare strategies of noninvasive brain/nerve stimulation for migraine prophylaxis with respect to their effectiveness and acceptability. METHODS: The PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov , ClinicalKey, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov databases were systematically searched to date of June 4th, 2021 for randomized controlled trials (RCTs). Patients with diagnosis of migraine, either episodic migraine or chronic migraine, were included. All NMA procedures were conducted under the frequentist model. RESULTS: Nineteen RCTs were included (N = 1493; mean age = 38.2 years; 82.0% women). We determined that the high frequency repetitive transcranial magnetic stimulation (rTMS) over C3 yielded the most decreased monthly migraine days among all the interventions [mean difference = - 8.70 days, 95% confidence intervals (95%CIs): - 14.45 to - 2.95 compared to sham/control groups]. Only alternating frequency (2/100 Hz) transcutaneous occipital nerve stimulation (tONS) over the Oz (RR = 0.36, 95%CIs: 0.16 to 0.82) yielded a significantly lower drop-out rate than the sham/control groups did. CONCLUSIONS: The current study provided a new direction for the design of more methodologically robust and larger RCTs based on the findings of the potentially beneficial effect on migraine prophylaxis in participants with migraine by different noninvasive brain/nerve stimulation, especially the application of rTMS and tONS. TRIAL REGISTRATION: CRD42021252638. The current study had been approval by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center (TSGHIRB No. B-109-29).

Tinnitus Associated with Mild Osteomyelitis of the Temporal Bone Reversed after Conservative Antibiotic Treatment: A Case Series.

The symptomatology and diagnostic tools for osteomyelitis of the temporal bone have not been well documented. Diagnosis of early stage (i.e., mild form) osteomyelitis of the temporal bone may be delayed due to the limitations of traditional computed tomography's (CT) imaging resolution. With the advancement of high-resolution CT (HRCT) images, clinicians can now observe images that could not be observed with traditional CT imaging. In this neuro-image report, we present three patients with refractory/untreatable tinnitus. In their HRCT images, mild osteomyelitis of the temporal bone was revealed by mucosa thickening with bony sequestration of air cells, mild opacification of the air cells, and soft tissue density in the middle ear cavity, mild opacification, and bony sequestration attributed to mucosa thickening of the mastoid air cells (along with the cortical bone). All of the clinical presentations and findings in the pure tone audiometry of the reported patients improved after adequate antibiotic treatment. The current report highlights the potential benefit of HRCT to diagnose this in such patients. In addition, immediate and conservative antibiotic treatment is recommended for managing these patients shortly after the detection of mild osteomyelitis of the temporal bone. This treatment could reduce the risk of progression to the severe form.

The Performance of Risk Scores for Bleeding and Ischemia as Outcome Predictors in Acute Myocardial Infarction Patients with End-Stage Renal Disease.

Background: In patients with end-stage renal disease (ESRD), acute myocardial infarction (AMI) increases the risks of cardiovascular events, death, and bleeding. Several scores have been developed for predicting ischemic and bleeding outcomes in AMI patients, but none have been validated specifically for ESRD patients. Objectives: To compare and validate different risk scores as predictors of ischemic and bleeding outcomes in AMI patients with ESRD. Methods: This retrospective study enrolled 340 patients who had received percutaneous coronary intervention for AMI while undergoing maintenance hemodialysis for ESRD. Ischemic risk scores (TIMI-STEMI, TIMI-NSTEMI, GRACE, DAPT) and bleeding risk scores (PRECISE-DAPT, CRUSADE, ACUITY, ACTION, SWEDEHEART) were calculated. The ischemic outcome mainly focused on major adverse cardiovascular events (MACEs) within 14 days after hospitalization, and the bleeding outcome was 14-day major bleeding according to the CRUSADE criteria. Results: The GRACE score was superior in discriminating ischemic outcomes, especially in 14-day MACEs [area under curve (AUC) 0.791, p < 0.001]. None of the scores could ideally discriminate 14-day CRUSADE major bleeding, while the PRECISE- DAPT score had the best discriminative power (AUC 0.636, p < 0.001). Either GRACE score > 222 or PRECISE-DAPT score > 48 was associated with higher net adverse cardiovascular events (a composite of 14-day MACEs and 14-day CRUSADE major bleeding). Conclusions: In AMI patients with ESRD, the GRACE score can effectively discriminate the risk of short-term ischemic events. None of the scores could ideally discriminate the bleeding risk, but a high PRECISE-DAPT score still represented a higher rate of bleeding events.

Efficacy and acceptability of noninvasive brain stimulation interventions for weight reduction in obesity: a pilot network meta-analysis.

BACKGROUND/OBJECTIVES: Obesity has recently been recognized as a neurocognitive disorder involving circuits associated with the reward system and the dorsolateral prefrontal cortex (DLPFC). Noninvasive brain stimulation (NIBS) has been proposed as a strategy for the management of obesity. However, the results have been inconclusive. The aim of the current network meta-analysis (NMA) was to evaluate the efficacy and acceptability of different NIBS modalities for weight reduction in participants with obesity. METHODS: Randomized controlled trials (RCTs) examining NIBS interventions in patients with obesity were analyzed using the frequentist model of NMA. The coprimary outcome was change in body mass index (BMI) and acceptability, which was calculated using the dropout rate. RESULTS: Overall, the current NMA, consisting of eight RCTs, revealed that the high-frequency repetitive transcranial magnetic stimulation (TMS) over the left DLPFC was ranked to be associated with the second-largest decrease in BMI and the largest decrease in total energy intake and craving severity, whereas the high-frequency deep TMS over bilateral DLPFC and the insula was ranked to be associated with the largest decrease in BMI. CONCLUSION: This pilot study provided a "signal" for the design of more methodologically robust and larger RCTs based on the findings of the potentially beneficial effect on weight reduction in participants with obesity by different NIBS interventions.