Transcranial alternating current stimulation for treating depression: a randomized controlled trial.

Treatment of depression with antidepressants is partly effective. Transcranial alternating current stimulation can provide a non-pharmacological alternative for adult patients with major depressive disorder. However, no study has used the stimulation to treat first-episode and drug-naïve patients with major depressive disorder. We used a randomized, double-blind, sham-controlled design to examine the clinical efficacy and safety of the stimulation in treating first-episode drug-naïve patients in a Chinese Han population. From 4 June 2018 to 30 December 2019, 100 patients were recruited and randomly assigned to receive 20 daily 40-min, 77.5 Hz, 15 mA, one forehead and two mastoid sessions of active or sham stimulation (n = 50 for each group) in four consecutive weeks (Week 4), and were followed for additional 4-week efficacy/safety assessment without stimulation (Week 8). The primary outcome was a remission rate defined as the 17-item Hamilton Depression Rating Scale (HDRS-17) score ≤ 7 at Week 8. Secondary analyses were response rates (defined as a reduction of ≥ 50% in the HDRS-17), changes in depressive symptoms and severity from baseline to Week 4 and Week 8, and rates of adverse events. Data were analysed in an intention-to-treat sample. Forty-nine in the active and 46 in the sham completed the study. Twenty-seven of 50 (54%) in the active treatment group and 9 of 50 (18%) in the sham group achieved remission at the end of Week 8. The remission rate was significantly higher in the active group compared to that in the sham group with a risk ratio of 1.78 (95% confidence interval, 1.29, 2.47). Compared with the sham, the active group had a significantly higher remission rate at Week 4, response rates at Weeks 4 and 8, and a larger reduction in depressive symptoms from baseline to Weeks 4 and 8. Adverse events were similar between the groups. In conclusion, the stimulation on the frontal cortex and two mastoids significantly improved symptoms in first-episode drug-naïve patients with major depressive disorder and may be considered as a non-pharmacological intervention for them in an outpatient setting.

Vitamin D Supplementation for the Outcomes of Patients with Gestational Diabetes Mellitus and Neonates: A Meta-Analysis and Systematic Review.

Background: Prevention and timely treatment of gestational diabetes mellitus (GDM) are important to the prognosis of pregnant women and neonates. We aimed to conduct a meta-analysis to evaluate the effects and safety of vitamin D supplementation on GDM patients and neonates, to provide insights into clinical GDM treatment. Methods: Two authors searched the Medline, PubMed, Cochrane Library, Web of Science, Embase, CNKI, and Wanfang databases for randomized controlled trials (RCTs) on the effects and safety of vitamin D supplementation in GDM patients. The quality of the included RCTs was evaluated according to Cochrane handbook. RevMan 5.3 software was used for statistical analysis. Results: A total of 20 RCTs involving 1682 GDM patients were finally included, of whom 837 received vitamin D supplementation. Vitamin D supplementation in GDM patients increased the serum 25(OH)D level (SMD = 4.07, 95% CI: (2.73, 5.41)) and HDL level (SMD = 0.41, 95% CI: (0.23, 0.58)) and reduced serum LDL (SMD = -0.49, 95% CI: (-0.68, -0.29)), TG (SMD = -0.59, 95% CI: (-1.01, -0.17)), and TC (SMD = -0.67, 95% CI: (-1.19, -0.14)) levels in GDM patients (all P < 0.05). Besides, vitamin D supplementation reduced the risk of premature birth (OR = 0.37, 95% CI: (0.22, 0.62)), hyperbilirubinemia (OR = 0.38, 95% CI: (0.25, 0.58)), and neonatal hospitalization (OR = 0.38, 95% CI: (0.25, 0.58)) of neonates (all P < 0.05). No significant publication bias in synthesized results was found (all P > 0.05). Conclusions: Vitamin D supplementation improves the blood lipid level in GDM patients and reduces adverse neonatal outcomes. The dose and duration of vitamin D supplementation for safety need to be further investigated in future high-quality studies.

Study on the effect, safety, prognosis quality and application value of extracorporeal shock wave based neural activity in carpal tunnel syndrome patients.

BACKGROUND: Mild to moderate CTS is the most common median nerve compression disease in middle-aged and elderly women, mainly manifested by hand numbness and pain. This paper analyzes the extracorporeal shock wave of patients with mild to moderate CTS after nerve mobilization. METHODS: The clinical data of 92 patients with CTS from June 2020 to June 2022 are analyzed and randomly divided into extracorporeal shock wave group (n = 47) and routine group (n = 45). The routine group undergoes nerve mobilization, and the extracorporeal shock wave group receives extracorporeal shock wave therapy on the basis of the routine group. The clinical efficacy, symptom improvement, pain score, median nerve electrophysiological examination results, upper limb symptom and function scores, and ADL scores before and after treatment are observed. The Spearman correlation coefficient is used to analyze the correlation between upper limb function and ADL score, and the incidence of complications after treatment is analyzed. RESULTS: The clinical efficacy, symptom improvement, pain score, median nerve electrophysiological examination results, upper limb symptom and function score, ADL score and the incidence of complications in the extracorporeal shock wave group are significantly better than those in the conventional group (P < 0.05). ADL scores are negatively correlated. CONCLUSION: Extracorporeal shock wave combined with nerve mobilization has a significant effect in the treatment of CTS patients, which can significantly improve the symptoms and pain scores of patients, and enhance the function of patients' upper limbs. At the same time, the incidence of complications in patients is less, and it has high safety.

Utilization of and Outcomes Associated with Intravascular Ultrasound during Deep Venous Stent Placement among Medicare Beneficiaries.

PURPOSE: To evaluate temporal trends, practice variation, and associated outcomes with the use of intravascular ultrasound (US) during deep venous stent placement among Medicare beneficiaries. MATERIALS AND METHODS: All lower extremity deep venous stent placement procedures performed between January 1, 2017, and December 31, 2019 among Medicare beneficiaries were included. Temporal trends in intravascular US use were stratified by procedural setting and physician specialty. The primary outcome was a composite of 12-month all-cause mortality, all-cause hospitalization, or repeat target vessel intervention. The secondary outcome was a composite of 12-month stent thrombosis, embolization, or restenosis. RESULTS: Among the 20,984 deep venous interventions performed during the study period, 15,184 (72.4%) utilized intravascular US. Moderate growth in intravascular US use was observed during the study period in all clinical settings. There was a variation in the use of intravascular US among all operators (median, 77.3% of cases; interquartile range, 20.0%-99.2%). In weighted analyses, intravascular US use during deep venous stent placement was associated with a lower risk of both the primary (adjusted hazard ratio, 0.72; 95% confidence interval [CI], 0.69-0.76; P < .001) and secondary (adjusted hazard ratio, 0.32; 95% CI, 0.27-0.39; P < .001) composite end points. CONCLUSIONS: Intravascular US is frequently used during deep venous stent placement among Medicare beneficiaries, with further increase in use from 2017 to 2019. The utilization of intravascular US as part of a procedural strategy was associated with a lower cumulative incidence of adverse outcomes after the procedure, including venous stent thrombosis and embolization.

Transition to adult care in cystic fibrosis: The challenges and the structure.

In developed countries, it is projected that there will be a 70% increase in the number of adults living with Cystic Fibrosis (CF) between 2010 and 2025. This shift in demographics highlights the importance of high-quality transition programmes with developmentally appropriate integrated health care services as the individual moves through adolescence to adulthood. Adolescents living with CF face additional and unique challenges that may have long-term impacts on their health, quality of life and life-expectancy. CF specific issues around socially challenging symptoms, body image, reproductive health and treatment burden differentiate people with CF from their peers and require clinicians to identify and address these issues during the transition process. This review provides an overview of the health, developmental and psychosocial challenges faced by individuals with CF, their guardians and health care teams considering the fundamental components and tools that are required to build a transition programme that can be tailored to suit individual CF clinics.

Guidelines for the prevention and management of children and adolescents with COVID-19.

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. CONCLUSION: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged. WHAT IS KNOWN: • Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence. WHAT IS NEW: • The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.

Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma.

Five biologicals have been approved for severe eosinophilic asthma, a well-recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (three RCTs for benralizumab, three RCTs for dupilumab, three RCTs for mepolizumab, five RCTs for omalizumab and five RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72), dupilumab (IRR) 0.43 (95% CI 0.32 to 0.59), mepolizumab IRR 0.49 (95% CI 0.38 to 0.66), omalizumab (IRR) 0.56 (95% CI 0.40 to 0.77) and reslizumab (IRR) 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV1 , without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality-adjusted life year value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalizations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV1 . More data on long-term safety are needed together with more efficacy data in the paediatric population.

The multifaceted role of CD146/MCAM in the promotion of melanoma progression.

Human malignant melanoma is a common primary malignant cutaneous tumour derived from transformed epidermal melanocytes. Patients with melanoma have a high rate of mortality due to resistance to chemotherapeutic drugs, a major obstacle to a successful treatment. Several reports have suggested that CD146 plays an important role as a signalling molecule in human melanoma. This role includes CD146 as a participant in inflammation, differentiation, adhesion, tumourigenicity, metastasis, invasion and angiogenesis among other processes, which suggests that this molecule promotes the progression of human melanoma as a multifaceted regulator. In this article, we explore the effects and corresponding mechanisms with respect to the role of CD146/MUC18 in the promotion of human melanoma progression. Collectively, the studies indicated that targeting CD146, because it is a suitable marker of poor patient outcome, might be useful in the design of future strategies for the prevention and treatment of human melanoma.

Dexmedetomidine Combined with Low-Dose Norepinephrine Continuous Pumping to Prevent Hypotension after Cesaresan Section: A Randomized Controlled Trial.

Objective: The aim of the study is to explore the clinical effect of dexmedetomidine combined with low-dose norepinephrine (NE) continuous pumping in preventing supine hypotension. Methods: A total of 160 puerperaes who underwent elective cesarean section were selected. The puerperaes were equally divided into S group (saline), D group (dexmedetomidine), N group (norepinephrine), and DN group (dexmedetomidine combined with norepinephrine) by a random number table method. Apgar scores and umbilical cord venous blood gas values were recorded at 1 and 5 minutes. Results: There were no statistically significant differences in the age, gestational age, body mass index, bleeding volume, fluid supplement volume, Apgar scores of new borns at the 1st and 5th minute, the blood gas values of umbilical cord arterial and venous in the four groups (P > 0.05). Compared with the S group, the incidence of supine hypotension, the number of NE supplements, the supplementary doses of NE, and the incidence of adverse reactions were significantly reduced in the D, N, and DN groups after spinal anesthesia (P < 0.05). Compared with group D, the incidence of supine hypotension, the number of additional NE, additional dose of NE, and the incidence of adverse reactions in the DN group after spinal anesthesia were significantly reduced (P < 0.05). Compared with the N group, the incidence of supine hypotension, the number of additional NE, the additional dose of NE, and the incidence of adverse reactions in the DN group after spinal anesthesia were significantly reduced (P < 0.05). Conclusion: Dexmedetomidine combined with continuous pumping of low-dose norepinephrine can effectively prevent the occurrence of supine hypotension, reduce the occurrence of other adverse reactions, and have no obvious adverse effects on neonates. Registration. Chinese Clinical Trial Registry (https://www.chictr.org.cn/enIndex.aspx; ChiCTR2000040979).

Environmental and Mobility Strategies During Early COVID-19: Insights From an Empirical Study Focusing on Park Visitations in El Paso, TX.

OBJECTIVES: We explored the importance of environmental and mobility strategies during early COVID-19 by age and ethnicity and investigated predictors of park visitations considering the COVID-19 impacts. BACKGROUND: Parks are safe and accessible venues to stay active and reduce social isolation, which is especially important considering COVID-19 and the associated lockdowns. METHODS: We analyzed online survey data from 683 residents (collected July 2020) of El Paso, TX, and objective measures of neighborhood park characteristics. Chi-square tests and mixed-effects logistic regression analyses were performed to examine the environmental/mobility strategies, personal and environmental factors, and park visitations, considering the COVID-19 impacts. RESULTS: The percentage of those who visited (1+ times/week) parks or trails/paths in the neighborhood dropped from 41.7% to 19.5% since the start of COVID-19 (OR = 0.015, p < .001). Before COVID-19, middle-aged and older adults were less likely to visit parks than younger adults, while this difference became insignificant during early COVID-19. Hispanic adults were more likely to visit parks than non-Hispanics both before and during early COVID-19. Positive environmental predictors of park visitations included park availability in the neighborhood, proximity to the closest park, seeing people being physically active in the neighborhood, and neighborhood aesthetics. CONCLUSIONS: Proximately located parks, trails, and paths well integrated into residential communities, and high aesthetic quality of the neighborhood are the potential features of pandemic-resilient communities and should be considered an important national priority to maintain and promote the health and well-being of the population, especially during pandemics like COVID-19.

The preventive effects of inulin, cellulose, and their mixture on colorectal cancer liver metastasis in mice by regulating gut microbiota.

Many studies have found that dietary fiber can protect against colorectal cancer (CRC). Survival in CRC patients is significantly reduced due to metastasis. However, little is known regarding the impact of dietary fiber on the CRC metastasis. In this study, we analyzed the effects of inulin, cellulose, and their mixture on CRC metastasis in a murine orthotopic transplantation model. BALB/C male mice were divided into the normal control (NC) (AIN-93 M diet), MOD (AIN-93 M diet), INU (10% w/w inulin), CEL (10% w/w cellulose), and MIX (5% w/w inulin + 5% w/w cellulose) groups. Dietary fiber intake inhibited the weights of the orthotopic tumors, liver weights, and liver metastasis area (p < 0.05) and improved the survival rate of tumor-bearing mice. Compared to the NC, the expression of ß-catenin and the epithelial marker E-cadherin were lower, and that of mesenchymal markers, such as N-cadherin, MMP-9, and VEGF, were higher in the MOD group. All inulin, cellulose, and their mixture restored the gut microbiota diversity, and they, respectively, increased the relative abundance of Bifidobacteriales, Lactobacillus, and Lachnospiraceae. Inulin restored the levels of acetic acid, propionic acid, isobutyric acid, and butyric acid. Spearman correlation analysis results showed that there was a positive correlation between five genera and six short-chain fatty acids (SCFAs) (adjusted p < 0.05). In conclusion, all inulin, cellulose, and their mixture have inhibitory effects on CRC metastasis, which may be achieved by the regulation of gut microbiota, the production of SCFAs, and the inhibition of the epithelial-to-mesenchymal transition process. Among the three dietary fiber intervention groups, the inhibitory effect of inulin is more significant.

Association Between Claims-Defined Frailty and Outcomes Following 30 Versus 12 Months of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: Findings From the EXTEND-DAPT Study.

Background Frailty is rarely assessed in clinical trials of patients who receive dual antiplatelet therapy (DAPT) after percutaneous coronary intervention. This study investigated whether frailty defined using claims data is associated with outcomes following percutaneous coronary intervention, and if there is a differential association in patients receiving standard versus extended duration DAPT. Methods and Results Patients ≥65 years of age in the DAPT (Dual Antiplatelet Therapy) Study, a randomized trial comparing 30 versus 12 months of DAPT following percutaneous coronary intervention, had data linked to Medicare claims (n=1326), and a previously validated claims-based index was used to define frailty. Net adverse clinical events, a composite of all-cause mortality, myocardial infarction, stroke, and major bleeding, were compared between frail and nonfrail patients. Patients defined as frail using claims data (12.0% of the cohort) had higher incidence of net adverse clinical events (23.1%) compared with nonfrail patients (10.7%; P<0.001) at 18-month follow-up and increased risk after multivariable adjustment (adjusted hazard ratio [HR], 2.24 [95% CI, 1.38-3.63]). There were no differences in effects of extended duration DAPT on net adverse clinical events for frail (HR, 1.42 [95% CI, 0.73-2.75]) and nonfrail patients (HR, 1.18 [95% CI, 0.83-1.68]; interaction P=0.61), although analyses were underpowered. Bleeding was highest among frail patients who received extended duration DAPT. Conclusions Among older patients in the DAPT Study, claims-defined frailty was associated with higher net adverse clinical events. Effects of extended duration DAPT were not different for frail patients, although comparisons were underpowered. Further investigation of how frailty influences ischemic and bleeding risks with DAPT are warranted. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00977938.

Latin America and the Caribbean Code Against Cancer 1st Edition: Medical interventions including hormone replacement therapy and cancer screening.

Prostate, breast, colorectal, cervical, and lung cancers are the leading cause of cancer in Latin America and the Caribbean (LAC) accounting for nearly 50% of cancer cases and cancer deaths in the region. Following the IARC Code Against Cancer methodology, a group of Latin American experts evaluated the evidence on several medical interventions to reduce cancer incidence and mortality considering the cancer burden in the region. A recommendation to limit the use of HRT was issued based on the risk associated to develop breast, endometrial, and ovarian cancer and on growing concerns related to the over-the-counter and without prescription sales, which in turn bias estimations on current use in LAC. In alignment with WHO breast and cervical cancer initiatives, biennial screening by clinical breast examination (performed by trained health professionals) from the age of 40 years and biennial screening by mammography from the age of 50 years to 74, as well as cervical screening by HPV testing (either self-sampling or provider-sampling) every 5-10 years for women aged 30-64 years, were recommended. The steadily increasing rates of colorectal cancer in LAC also led to recommend colorectal screening by occult blood testing every two years or by endoscopic examination of the colorectum every 10 years for both men and women aged 50-74 years. After evaluating the evidence, the experts decided not to issue recommendations for prostate and lung cancer screening; while there was insufficient evidence on prostate cancer mortality reduction by prostate-specific antigen (PSA) testing, there was evidence of mortality reduction by low-dose computed tomography (LDCT) targeting high-risk individuals (mainly heavy and/or long-term smokers) but not individuals with average risk to whom recommendations of this Code are directed. Finally, the group of experts adapted the gathered evidence to develop a competency-based online microlearning program for building cancer prevention capacity of primary care health professionals.

[Effect of Xingnao Kaiqiao acupuncture on safety of rt-PA intravenous thrombolysis in patients with cerebral infarction: a randomized controlled trial].

OBJECTIVE: To assess the effect of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on the efficacy and safety of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with cerebral infarction. METHODS: A total number of 142 patients of cerebral infarction undergoing rt-PA intravenous thrombolysis were randomized into an acupuncture-medication group (71 cases) and a western medication group (71 cases, 1 case dropped off). In the western medication group, rt-PA intravenous thrombolysis was given. In the acupuncture-medication group, besides the intervention as the control group, Xingnao Kaiqiao acupuncture was provided at Shuigou (GV 26), Neiguan (PC 6), Sanyinjiao (SP 6), Jiquan (HT 1), etc. once daily. One treatment session contained 6 treatments and 1 session was required. Before and after treatment, the score of the National Institute of Health stroke scale (NIHSS), the levels of the relevant indexes of symptomatic intracerebral hemorrhage (sICH) (platelet [PLT], D-dimer and fibrinogen), the incidences of sICH and adverse effect were compared between groups. The efficacy was assessed in two groups. RESULTS: After treatment, NIHSS scores and the levels of D-dimer were reduced compared with those before treatment in both groups (P<0.05), and those in the acupuncture-medication group were lower than the western medication group (P<0.05). The level of fibrinogen in the acupuncture-medication group was increased in comparison with that before treatment (P<0.05), and also higher than the western medication group (P<0.05). The incidence of sICH was 0% (0/71) in the acupuncture-medication group, lower than 8.6% (6/70) in the western medication group (P<0.05). The effective rate was 97.2% (69/71) in the acupuncture-medication group, higher than 87.1% (61/70) in the western medication group (P<0.05). The incidence of adverse effect was 2.8% (2/71) in the acupuncture-medication group, lower than 12.9% (9/70) in the western medication group (P<0.05). CONCLUSION: Xingnao Kaiqiao acupuncture may improve the efficacy of rt-PA intravenous thrombolysis in the patients with cerebral infraction and decrease the incidences of sICH and adverse effect. The mechanism may be related to the regulation of fibrinogen and D-dimer levels.

Plasma renin and aldosterone concentrations related to endovascular ultrasound renal denervation in the RADIANCE-HTN SOLO trial.

OBJECTIVE: The RADIANCE-HTN SOLO trial demonstrated a greater reduction in daytime ambulatory SBP at 2 months by endovascular ultrasound renal denervation than sham procedure. We hypothesized that plasma renin and aldosterone concentrations would be associated with the SBP response to renal denervation. METHODS: Hypertensive patients were randomized to renal denervation (n = 74) or sham (n = 72) after a 4-week washout of antihypertensive medications. In a 53-patient subset, 2-month and 6-month plasma renin and aldosterone concentration were measured. Dietary sodium was not controlled. RESULTS: Mean age of the 29 treatment and 24 sham patients was 54 years; 62% were men; 17% black. Daytime ambulatory SBP fell in the denervation but not the sham group at 2 months (-7.8 ±â€Š10.7 vs. -0.1 ±â€Š10.1 mmHg; P = 0.048). Baseline plasma renin and aldosterone concentrations were in the low-normal range, did not change significantly at 2 months in either group and did not predict response to renal denervation. At 6 months, after the addition of antihypertensive medications, there was a significant rise in renin in the sham but not the denervation group. CONCLUSION: Although renal denervation but not sham resulted in a decrease in daytime ambulatory SBP at 2 months, renin and aldosterone concentrations did neither predict the BP response to renal denervation; nor did they fall after denervation. A rise in renin at 6 months in the sham group likely represents confounding from antihypertensive medications. Whether the BP-lowering effect of renal denervation depends on reducing local intrarenal renin release requires further study.

Age, gender, geographic and clinical differences for gallstones in China: a nationwide study.

Background: The etiology of gallstones at different anatomical locations may be varied. However, it has not been well studied about the prevalence of gallstones by anatomical locations and their associated factors in China. Methods: We used the data set from preventive health screening centers covering all provinces in mainland China except for Tibet, and a total of 10,937,993 adults were included, who received abdominal ultrasonography in 2017. We analyzed the prevalence of gallstones classified by anatomical locations, including gallbladder (GB) stones, intrahepatic bile duct (IHD) stones, and extrahepatic bile duct (EHD) stones. Further, their associated factors were investigated using a logistic regression model with body mass index (BMI), fasting glucose, total triglyceride, and previous cholecystectomy, with covariates of age and sex. Results: The age- and gender-standardized prevalence (AGS-prevalence) of gallstone diseases was 5.13% (95% CI: 5.11-5.14%). GB, IHD, and EHD stones accounted for 76.3%, 24.3%, and 0.2% of all gallstone cases (concomitant cases were present). GB, IHD, and EHD gallstones presented different patterns by the age, gender, geographic and metabolic factors. Overall, the age-standardized prevalence was higher in women than that in men (5.41% vs. 4.85%, P<0.001). The gender standardized prevalence of all gallstone subtypes apparently increased with age (P<0.001), especially for GB stones from 1.05% (age 18-30) to 11.6% (age ≥70) (P<0.001). There was a marked geographic variation with AGS-prevalence ranging from 3.00% to 8.86% among different provinces. Noticeably, higher BMI, fasting glucose level, or total triglyceride level was associated with a higher prevalence of overall gallstones and GB stones (OR >1), but associated with a lower prevalence of IHD and EHD stones. Conclusions: The prevalence of gallstones in China largely varied in its anatomical location, demographic factors, geographic location, and metabolic factors, suggesting that the etiology of each subtype may be different. Further investigation should be conducted.

A multicentre, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase (MIRROR): 12-month efficacy, safety, immunogenicity, and pharmacokinetic findings during long-term extension of an open-label study.

BACKGROUND: Publications suggest immunomodulation co-therapy improves responder rates in uncontrolled/refractory gout patients undergoing pegloticase treatment. The MIRROR open-label trial showed a 6-month pegloticase + methotrexate co-therapy responder rate of 79%, compared to an established 42% pegloticase monotherapy responder rate. Longer-term efficacy/safety data are presented here. METHODS: Uncontrolled gout patients (serum urate [SU] ≥ 6 mg/dL and SU ≥ 6 mg/dL despite urate-lowering therapy [ULT], ULT intolerance, or functionally-limiting tophi) were included. Patients with immunocompromised status, G6PD deficiency, severe kidney disease, or methotrexate contraindication were excluded. Oral methotrexate (15 mg/week) and folic acid (1 mg/day) were administered 4 weeks before and during pegloticase therapy. Twelve-month responder rate (SU < 6 mg/dL for ≥ 80% during month 12), 52-week change from baseline in SU, and extended safety were examined. Efficacy analyses were performed for patients receiving ≥ 1 pegloticase infusion. Pharmacokinetics (PK)/anti-drug antibodies (ADAs) were examined and related to efficacy/safety findings. RESULTS: Fourteen patients were included (all male, 49.3 ± 8.7 years, 13.8 ± 7.4-year gout history, pre-therapy SU 9.2 ± 2.5 mg/dL). Three patients were non-responders and discontinued study treatment before 24 weeks, one patient exited the study per protocol at 24 weeks (enrolled prior to treatment extension amendment), and 10 remained in the study through week 52. Of the 10, 8 completed 52 weeks of pegloticase + methotrexate and were 12-month responders. The remaining two discontinued pegloticase + methotrexate at week 24 (met treatment goals) and stayed in the study under observation (allopurinol prescribed at physicians' discretion); one remained a responder at 12 months. At 52 weeks, change from baseline in SU was - 8.2 ± 4.1 mg/dL (SU 1.1 ± 2.4 mg/dL, n = 10). Gout flares were common early in treatment but progressively decreased while on therapy (weeks 1-12, 13/14 [92.9%]; weeks 36-52, 2/8 [25.0%]). One patient recovered from sepsis (serious AE). Two non-responders developed high ADA titers; fewer patients had trough concentrations (Cmin) below the quantitation limit (BQL), and the median Cmin was higher (1.03 µg/mL vs. BQL) than pegloticase monotherapy trials. CONCLUSIONS: Pegloticase + methotrexate co-therapy was well-tolerated over 12 months, with sustained SU lowering, progressive gout flare reduction, and no new safety concerns. Antibody/PK findings suggest methotrexate attenuates ADA formation, coincident with higher treatment response rates. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03635957 . Registered on 17 August 2018.

Individualizing Dual Antiplatelet Therapy (DAPT) Duration Based on Bleeding Risk, Ischemic Risk, or Both: An Analysis From the DAPT Study.

BACKGROUND: Guidelines recommend individualization of dual antiplatelet therapy (DAPT) duration. Whether to guide decisions based on bleeding risk, ischemic risk or a combination is not known. AIMS: To compare a bleeding prediction model, an ischemic prediction model, and the DAPT score in guiding DAPT duration. METHODS: 11,648 patients in the DAPT Study were categorized into higher and lower risk using a bleeding model, an ischemic model, and the DAPT score. Effect of 30 vs. 12 months of DAPT on bleeding events, ischemic events, and the combination (net-adverse clinical events [NACE]) was assessed. RESULTS: Among patients stratified with the bleeding model, 30 vs. 12 months of DAPT resulted in similar ischemic and bleeding event rates. With the ischemic model, however, higher risk patients had a greater reduction in ischemic events with extended duration of DAPT (difference in risk differences [DRD]: -2.6%, 95% CI: -3.9 to -1.3%; p < 0.01), and a smaller increase in bleeding (DRD: -1.0%, 95% CI: -2.1-0.0%; p = 0.04). Similarly, high DAPT score patients had a greater reduction in ischemic events with extended DAPT duration (DRD: -2.4%, 95%: CI: -3.6 to -1.1%; p < 0.01) and a smaller increase in bleeding (DRD: -1.2%, 95%: CI: -2.2-0.0%; p = 0.02). Although NACE was similar for bleeding risk groups, NACE was significantly reduced with extended DAPT in the higher ischemic risk and high DAPT score groups. CONCLUSIONS: In this low-bleeding risk population, stratifying patients based on predicted ischemic risk and the DAPT score best discerned benefit versus harm of extended DAPT duration on ischemic events, bleeding events, and NACE. CONDENSED ABSTRACT: Duration of dual antiplatelet therapy (DAPT) should be guided by an individualized risk assessment. Bleeding risk tools have emerged to identify patients at high bleeding risk for whom truncated DAPT therapy may be safest. In a lower bleeding risk population, however, whether DAPT duration should be guided by bleeding risk, ischemic risk, or a combination is unknown. In this analysis, implementation of a score based on ischemic risk prediction and the DAPT score (a combination of ischemic and bleeding risk) best predicted ischemic events, bleeding events, and net-adverse clinical events (NACE).

Predictors of blood pressure response to ultrasound renal denervation in the RADIANCE-HTN SOLO study.

The blood pressure (BP) lowering response to renal denervation (RDN) remains variable with about one-third of patients not responding to ultrasound or radiofrequency RDN. Identification of predictors of the BP response to RDN is needed to optimize patient selection for this therapy. This is a post-hoc analysis of the RADIANCE-HTN SOLO study. BP response to RDN was measured by the change in daytime ambulatory systolic blood pressure (dASBP) at 2 months post procedure. Univariate regression was used initially to assess potential predictors of outcome followed by multivariate regression analysis. In the univariate analysis, predictors of response to RDN were higher baseline daytime ambulatory diastolic blood pressure (dADBP), the use of antihypertensive medications at screening, and presence of orthostatic hypertension (OHTN) whilst the presence of untreated accessory arteries was a negative predictor of response. Multivariate analysis determined that dADBP and use of antihypertensive medications were predictors of response to RDN with a trend for OHTN to predict response. Obese females also appeared to be better responders to RDN in an interaction model. RDN is more effective in patients with elevated baseline dADBP and those with OHTN, suggesting increased peripheral vascular resistance secondary to heightened sympathetic tone. These assessments are easy to perform in clinical setting and may help in phenotyping patients who will respond better to RDN.

Radiofrequency thermocoagulation of trigeminal nerve assisted by nerve bundle extraction and image fusion based on hamilton-jacobi equation.

BACKGROUND AND OBJECTIVE: Radiofrequency thermocoagulation is an effective method for treating classic trigeminal neuralgia. However, the accurate positioning of thermocoagulation is difficult. The purpose of this study was to design an optimal strategy for performing adjuvant surgery. METHODS: A total of 60 patients with trigeminal neuralgia were divided into two groups. One group received conventional computed tomography (CT) guided treatment (CT group). In the other group, neural fiber bundles were firstly extracted based on the Hamilton-Jacobi equation. Then, the MRI, CT, and fiber bundle images were fused to visualize the relationship among semilunar ganglion, trigeminal nerve, and puncture needle (fusion group). RESULTS: Trigeminal fiber bundles were extracted quickly by the contour tracking method, and different types of image fusion were realized for radiofrequency surgery navigation. In the fusion group, 13.3% of patients could not reach semilunar ganglion, and 76.9% of the remaining cases reached the ideal damage area. In the CT group, the preoperative design shows that 26.7% of patients may have puncture difficulty, and 54.5% of remaining cases reached the ideal damage area. CONCLUSION: The technique of neural bundle extraction and image fusion based on the Hamilton-Jacobi equation can be used to plan the personalized puncture path targeting the semilunar ganglion.