Association between prescription opioid use and heart failure: Cohort studies and Mendelian randomization analysis.

BACKGROUND: Prescription opioid use (POU) has been shown to lead to cardiovascular disease (CVD), but its association with heart failure has not been well studied. We investigated the potential causal association between POU and HF using cohort studies and Mendelian Randomization (MR) analysis. METHODS: Initially, we examined the longitudinal association between POU and HF using the data from the Health and Retirement Study (HRS) and the UK biobank. Next, we employed a two-sample MR analysis using summary statistics from genome-wide association studies (GWAS) to assess the potential causal associations between POU and HF. RESULTS: During a median of 3.8 and 13.8 years of follow-up, there were 441(8.04 per 1000 person-year) and 16,170 (3.96 per 1000 person-year) HF cases in the HRS and the UK biobank, respectively. After adjusting for covariates, participants who used prescription opioids had a 32% increased risk of developing HF, compared with non-users (HR = 1.32, 95%CI: 1.26-1.38, P < 0.001). In the MR analysis, summary statistics for POU were obtained from 78,808 UK Biobank study participants, and summary data for HF were obtained from 218,792 participants of a European population. A causal effect of genetic liability for POU on an increased risk of HF (OR = 1.16, 95% CI = 1.06, 1.27, P = 0.001) was suggested. The results were generally consistent in the sensitivity analysis, and no pleiotropy or heterogeneity were observed. CONCLUSIONS: POU is associated with a high risk of HF. Our findings provide new insight into prescription opioid use among populations at risk of heart failure. More studies are needed to validate our results and further investigate the underlying mechanisms.

Long-Term Visit-to-Visit Blood Pressure Variability and Cognitive Decline Among Patients With Hypertension: A Pooled Analysis of 3 National Prospective Cohorts.

BACKGROUND: A limited number of studies investigated the association between blood pressure variability (BPV) and cognitive impairment in patients with hypertension. This study aimed to identify the longitudinal association between BPV and cognitive decline and the role of blood pressure (BP) control in this association. METHODS AND RESULTS: Participants with hypertension from the HRS (Health and Retirement Study), the ELSA (English Longitudinal Study of Ageing), and the CHARLS (China Health and Retirement Longitudinal Study) were included. Variation independent of the mean (VIM) was adopted to measure BPV. Cognitive function was measured by standard questionnaires, and a standardized Z score was calculated. Linear mixed-model and restricted cubic splines were adopted to explore the association between BPV and cognitive decline. The study included 4853, 1616, and 1432 eligible patients with hypertension from the HRS, ELSA, and CHARLS, respectively. After adjusting for covariates, per-SD increment of VIM of BP was significantly associated with global cognitive function decline in Z scores in both systolic BP (pooled ß, -0.045 [95% CI, -0.065 to -0.029]) and diastolic BP (pooled ß, -0.022 [95% CI, -0.040 to -0.004]) among hypertensive patients. Similar inverse associations were observed in patients with hypertension taking antihypertensive drugs and in patients with hypertension with well-controlled BP. CONCLUSIONS: High BPV was independently associated with a faster cognitive decline among patients with hypertension, even those with antihypertensive medications or well-controlled BP. Further studies are needed to confirm our results and determine whether reducing BPV can prevent or delay cognitive decline.

The objectively measured walking speed and risk of hypertension in Chinese older adults: a prospective cohort study.

This study aims to investigate the longitudinal association between objectively measured walking speed and hypertension and to explore the potential effect modification of obesity on this association in Chinese older adults. The data from the Chinese Health and Retirement Prospective Cohort Study (CHARLS) during 2011-2015 was used. Walking speed was assessed by measuring the participants' usual gait in a 2.5 m course, and it was divided into four groups according to the quartiles (Q1, Q2, Q3, and Q4). A total of 2733 participants ≥60 years old were eligible for the analyses. After a follow-up of 4 years, 26.9% occurred hypertension. An inverse association was observed between walking speed and the risk of hypertension. There was an interaction between body mass index (BMI) and walking speed for the hypertension risk (P = 0.010). the association of walking speed with hypertension was stronger in overweight and obese participants (Q2, OR: 0.54, 95%CI = 0.34-0.85, P = 0.009; Q3, OR: 0.69, 95%CI = 0.44-1.08, P = 0.106; Q4, OR: 0.62, 95%CI = 0.39-0.98, P = 0.039). However, this association was not significant among lean ones. A similar trend was observed for systolic and diastolic blood pressure. In conclusion, higher walking speed was longitudinally associated with a lower risk of hypertension in Chinese older adults, especially among overweight and obese participants.

Living alone and the risk of depressive symptoms: a cross-sectional and cohort analysis based on the China Health and Retirement Longitudinal Study.

BACKGROUND: There were a few studies that examined the longitudinal association between living alone and depressive symptoms, and the vast majority of them were conducted in patients with certain diseases, such as heart failure, cancer, and glaucoma. This study aimed to examine the association between living alone and depressive symptoms in a large representative older Chinese population. METHODS: The China Health and Retirement Longitudinal Study (CHARLS) data from 2015 to 2018 were used. Living alone was defined as participants who did not live with others ever or more than 11 months in the past year at baseline. Depressive symptoms were measured using the 10-item Center for Epidemiological Studies-Depression Scale (CES-D10). The multivariate logistic regression was used to estimate the relationship between living alone and depressive symptoms. RESULTS: There were 5,311 and 2,696 participants ≥ 60 years old included in the cross-sectional and cohort analysis, respectively. The risk of depressive symptoms in participants who lived alone was significantly higher than those who lived with others in both cross-sectional (OR:1.33; 95%CI:1.14,1.54) and cohort analysis (OR:1.23; 95%CI:0.97,1.55). There was a significant interaction between financial support and living alone (Pinteraction = 0.008) on the risk of depressive symptoms. Stratified analyses showed that, compared to those who lived with others, the risk of depressive symptoms in participants who lived alone increased by 83% (OR:1.83; 95%CI:1.26,2.65) in participants receiving lower financial support. However, we did not find statistically significant associations in participants with medium (OR:1.10; 95%CI: 0.74,1.63) and higher financial support (OR: 0.87; 95%CI: 0.53,1.41). CONCLUSION: Living alone was associated with a higher risk of depressive symptoms in the Chinese older population, and this association was moderated by the receipt of financial support. Living alone may be an effective and easy predictor for early identification of high-risk populations of depression in the older population.

Associations of pyrethroid exposure with skeletal muscle strength and mass.

This study aimed to examine the associations of pyrethroid exposure with handgrip strength and skeletal muscle mass and potential modification effects in US adults. The data from the National Health and Nutrition Examination Survey was used. Handgrip strength was determined with a handgrip dynamometer, and we quantified muscle mass by using the appendicular skeletal muscle index (ASMI). Urinary 3-Phenoxybenzoic Acid (3-PBA), a validated biomarker for pyrethroid exposure, was used in the primary analysis. After adjusting for other covariates, participants exposed to the highest tertile of 3-PBA exposure had significantly lower handgrip strength (ß = -1.88, 95% CI: -3.29, -0.23, P = 0.026) than those exposed to the lowest tertile of 3-PBA. Similarly, the 3-PBA exposure was marginally significantly associated with ASMI (Tertile 3 vs. Tertile 1: ß = -0.07, 95% CI: -0.14, -0.01, P = 0.056). Significant interactions were found between 3-PBA and body mass index (BMI) on handgrip strength and ASMI (P interaction < 0.05), which indicated a potential moderation effect of BMI on the associations. In conclusion, pyrethroid exposure was adversely associated with handgrip strength and skeletal muscle mass, especially in overweight and obese populations. Further studies are warranted to confirm our results and to explore the potential mechanisms.

Expert consensus on computed tomography-assisted three-dimensional-printed coplanar template guidance for interstitial permanent radioactive 125I seed implantation therapy.

Interstitial permanent radioactive seed implantation delivers a high local dose to tumors and sharply drops off at surrounding normal tissues. Radioactive seeds implanted via ultrasound or computed tomography (CT) guidance are minimally invasive and facilitate quick recovery. Transrectal ultrasound-guided 125I seed implantation assisted by a transperineal plane template is standard for early-stage prostate carcinoma, with a highly consistent target volume dose distribution. The postplan dose evaluation is consistent with the preplan evaluation. Until now, there was no workflow for seed implantation elsewhere in the body, and it was difficult to effectively preplan for seed implantation because of patients' position changes, organ movement, and bone structure interference. Along with three-dimensional (3D) printing techniques and seed implantation planning systems for brachytherapy, coplanar and X Y axis coordinate templates were created, referred to as 3D-printed coplanar templates (3D-PCT). 125I seed implantation under CT guidance with 3D-PCT assistance has been very successful in some carcinomas. Preplanning was very consistent with postplanning of the gross tumor volume. All needles are kept parallel for 3D-PCT, with no coplanar needle rearrangement. No standard workflow for 3D-PCT-assisted seed implantation exists at present. The consensus topics for CT-assisted guidance compared to 3D-PCT-assisted guidance for seed implantation are as follows: Indications for seed implantation, preplanning, definition of radiation doses and dosimetry evaluation, 3D-PCT workflow, radiation protection, and quality of staff. Despite current data supporting 125I seed implantation for some solid carcinomas, there is a need for prospectively-randomized multicenter clinical trials to gather strong evidence for using 125I seed implantation in other solid carcinomas.

Clinical application of planar puncture template-assisted computed tomography-guided percutaneous biopsy for small pulmonary nodules.

AIMS: The aims of this study were to evaluate the clinical application of planar puncture template (PPT) in computed tomography (CT)-guided percutaneous needle lung biopsy. SUBJECTS AND METHODS: A total of 56 patients with small pulmonary nodules who received CT-guided percutaneous lung biopsy assisted by PPT were included in the study. Five steps were included in the study: fixing position, CT scanning and designing needle pathway, installing navigation system and template, puncturing fixation needle, and performing biopsy needle insertion and biopsy. The success rate of puncture, pathological results, and complications were analyzed. In addition, the factors that influenced the success rate and complications were analyzed. RESULTS: Biopsy was successfully completed in all 56 patients. The nodule diameter was 0.45-3 cm. The fixation needle technique was applied in 47 cases. Biopsy was performed 1 time in 50% of patients and 2 times in 38% of patients. For pathology, only one case showed no positive result, with a puncture success rate of 98%. The diagnostic rate of malignant tumor was 73%. For complications, the incidence of needle tract bleeding was 68%, the incidence of pneumothorax was 30%, and the thoracic drainage was required in two patients. Hemoptysis was observed in two cases. Univariate analysis: The nodule size was related to both the rate of 1-time biopsy and incidence of complications. Smaller nodule was relevant to lower rate of 1-time biopsy (P = 0.01) and higher incidence of complications (P < 0.05). The fixation needle was related to 1-time biopsy rate. The 1-time biopsy rate was significantly higher in patients with fixation needle than those without fixation needle (P = 0.001). Meanwhile, no significant difference was observed in the incidence of complications in different number of fixation needles (P > 0.05). CONCLUSIONS: PPT-assisted lung biopsy technology can provide high success rate and low complication incidence. It would be helpful to make the puncture procedures more standard for better clinical applications.

Percutaneous computed tomography-guided permanent 125I implantation as therapy for pulmonary metastasis.

PURPOSE: To evaluate intermediate-term outcomes after computed tomography (CT)-guided radioactive 125I seed implantation (CTRISI), and to determine prognostic variables associated with outcomes in patients with pulmonary metastases. MATERIAL AND METHODS: Thoracic surgeons evaluated and performed implantation of 125I radioactive seeds under CT guidance or combined with surgical resection. Patients were monitored in the thoracic surgery clinic for recurrence and survival. RESULTS: Fifty patients (31 men, 19 women; median age, 59 years; range, 16-85) underwent CTRISI. The primary cancer was colorectal in 10 (20%), malignant fibrous histiocytoma in 8 (16%), sarcoma in 5 (10%), renal in 4 (8%), and other in 22 (44%) patients. CTRISI was the sole treatment in 45 patients (90%) and was combined with surgical resection in 5 patients (10%). The actuarial D90 of implanted 125I seeds ranged from 90 to 160 Gy (median, 120 Gy). No procedurally related deaths occurred. At a median follow-up of 41.5 months (range, 7-74 months), 6 patients were alive. The median survival time was 42.1 months (95% confidence interval: 26.5-53.4), and the estimated 1-, 3-, and 5-year overall survival rates were 88.0%, 58.0%, and 26.7%, respectively. Lesion size was an important prognostic variable associated with overall and progression-free survival (p < 0.05). CONCLUSIONS: CTRISI is safe in this group of patients with pulmonary metastases and provides reasonable results. Surgical resection remains the standard for resectable cases, but CTRISI offers an alternative for selected patients or may be used as a feasible approach in combination with surgical resection for selected patients.

Expert consensus statement on computed tomography-guided 125I radioactive seeds permanent interstitial brachytherapy.

The aim of this study is to develop expert consensus statement for recommendations of patient selection criteria, prescription dose, and procedure of computed tomography (CT)-guided 125I radioactive seeds permanent interstitial brachytherapy. Members of Chinese medical association radiation oncology branch, Chinese medical association radiation therapy professional committee, Chinese cancer society minimally invasive surgery branch seed therapy group, Chinese geriatric cancer society minimally invasive surgery branch, Beijing medical association radiation oncology professional committee, China northern radioactive seeds brachytherapy group formed a committee, which consists of physician members who come from the department of radiation oncology, surgery, intervention, internal medicine, ultrasound, and nuclear medicine. The leader of the group organized experts to write the first draft based on clinical experience and literature review and then sent the draft to the commissioner for consultation, finally reached a consensus. Guidelines for patient selection criteria, prescription dose of 125I seed for different kinds of carcinomas, activity of per seed, and workflow of CT-guided permanent interstitial radioactive seed implantation (RSI) are presented in this study. The procedure of CT-guided RSI comprised eight steps: indication selection, preoperative preparation, preoperative CT simulation and position setup, preplan, intraoperative needle insertion, RSI, postoperative dosimetric evaluation, and follow-up. Patient selection criteria are developed. Guidelines for prescription dose of 125I seed for different kinds of carcinomas, activity of per seed, and workflow of CT-guided permanent interstitial RSI are provided.

125I inhibited the NSCLC both in vivo and in vitro.

Lung cancer is the main reason of cancer-linked death all over the world. Non-small cell lung cancer (NSCLC) patients always have an extremely poor prognosis. It is urgent to find novel treating methods. It was previously showed that 125I brachytherapy had been applied to the lung cancer treatment. However, fundamental researches are limited. In the present study, we first explored the mechanism by which 125I radiation induced arrest or apoptosis of the cell cycle and relevant protein expression. Furthermore, we explored its effect on the invasion. We found that 125I significantly induced cell apoptosis through mitochondrial pathway, triggered S phase arrest via regulating cyclinA2, p21 and CDK6 expressions. Meanwhile, 125I could inhibit invasion of NSCLC cells by altering the expression level of vimentin, N-cadherin and MMP-9. Furthermore, we confirmed the effects of 125I on NSCLC cell growth in vivo. The results indicated that 125I obviously inhibited the tumor growth. Thus, we determined that 125I brachytherapy remarkably restrained NSCLC cellular growth and intrusion by inducing apoptosis, S phase arrest and corresponding protein expression.

All-fiber mode converter based on long-period fiber gratings written in few-mode fiber.

We investigated an all-fiber mode converter based on long-period fiber gratings (LPFGs) written in the few-mode fiber. Mode conversion between the fundamental core mode and different higher-order core modes (LP11, LP21, and LP02 modes) can be realized via a single LPFG with an efficiency of 99% at the resonance wavelength. Moreover, optimized mode conversion between the LP01 and LP21 modes can be realized by cascading two LPFGs with different grating pitches. The maximum conversion efficiency is estimated to be ∼99.5% at 1553 nm. The orbital angular momentum states with different topological charges (±1,±2) are demonstrated experimentally. The all-fiber LPFG mode converters could have promising applications in the mode-division multiplexing optical communications.

Expert consensus workshop report: Guideline for three-dimensional printing template-assisted computed tomography-guided 125I seeds interstitial implantation brachytherapy.

Radioactive 125I seeds (RIS) interstitial implantation brachytherapy has been a first-line treatment for early-stage cancer of the prostate gland. However, its poor accuracy and homogeneity has limited its indication and hampered its popularization for a long time. Intriguingly, scholars based in China introduced computed tomography (CT)-guided technology to improve the accuracy and homogeneity of RIS implantation and broadened the indications. Then, they creatively designed and introduced three-dimensional printing coplanar template (3D-PCT) and 3D printing noncoplanar template (3D-PNCT) into the practice of RIS implantation. Use of such templates makes RIS implantation more precise and efficacious and aids preoperative planning, real-time dose optimization, and postoperative planning. However, studies on the standard workflow for 3D-PT-assisted CT-guided RIS implantation have not been published. Therefore, the China Northern Radioactive Seeds Brachytherapy Group organized multidisciplinary experts to formulate the guideline for this emerging treatment modality. This guideline aims at standardizing 3D-PT-assisted CT-guided RIS implantation procedures and criteria for selecting treatment candidates and assessing outcomes and for preventing and managing postoperative complications.

Implantation of computed tomography-guided Iodine-125 seeds in combination with chemotherapy for the treatment of stage III non-small cell lung cancer.

PURPOSE: We investigated the role of computed tomography (CT)-guided Iodine-125 (125I) seed implantation in combination with chemotherapy for the treatment of stage III non-small cell lung carcinoma (NSCLC). MATERIAL AND METHODS: The data from 182 patients with stage III NSCLC who were treated with radioactive 125I seed implantation between June 2002 and June 2009, and who received sequential platinum-based combination chemotherapy using the most common combination of platinum and gemcitabine, were retrospectively reviewed. The 182 patients received a prescribed dose of 110.0 Gy, with a median radioactivity of 0.70 mCi (range, 0.64-0.78 mCi, 2.37-3.26 × 107 Bq). The median number of 125I seeds was 38 pellets (range, 6-105 pellets). The median post-operation dose covering 100% of the target volume (D100) was 94.5 Gy (range, 54.6-125.5 Gy). The median D90 was 143.0 Gy (range, 121.6-184.0). RESULTS: The 1-, 3-, and 5-year overall survival rates were 83.35%, 25.57%, and 11.34%, respectively; the median survival time was 24.76 months. At 1, 3, and 5 years, the local control rates were 92.01%, 86.51%, and 76.45%, respectively; the median local control time was 25.28 months. For patients with stage IIIA and IIIB NSCLC, the median survival times were 26.67 and 24.59 months, respectively (p = 0.2). Pre-treatment hemoglobin level, tumor volume, and postoperative D100 were significantly associated with survival. A total of 24 patients experienced pneumothorax (incidence rate, 13.20%), and 17 patients experienced hemothorax (incidence rate, 5.0%). CONCLUSIONS: CT-guided 125I seed implantation combined with chemotherapy is an effective, minimally invasive method for the treatment of stage III NSCLC. Furthermore, hemoglobin levels before treatment, D100, and the maximum diameter of the tumor may be prognostic factors in patients with NSCLC treated sequentially with radiotherapy and chemotherapy.

Effectiveness and safety of CT-guided (125)I seed brachytherapy for postoperative locoregional recurrence in patients with non-small cell lung cancer.

PURPOSE: To retrospectively evaluate the effectiveness and safety of CT-guided (125)I seed brachytherapy (CTISB) in 38 non-small cell lung cancer (NSCLC) patients with locoregional recurrence (LRR). METHODS AND MATERIALS: In total, we analyzed 38 NSCLC patients with LRR treated with percutaneous CTISB in our hospital between 2001 and 2008; among them, 15 also received combined chemotherapy: 1-6 cycles (median, 2) of platinum-based regimens. The change in tumor volume was evaluated based on followup contrast material-enhanced CT or positron emission tomography scans. RESULTS: The median Day 0 dosimetry was as follows: The volume treated with the prescription dose (V100) was 96.3% (90.1-123.5%), and the minimum dose received by at least 90% of the tumor volume (D90) was 124.8 Gy (116.0-130.7 Gy). The median duration of the followup period calculated from the first CTISB treatment was 22.5 months (range, 8-98 months). Two months after CTISB, complete response, partial response, and progressive disease were observed in 50%, 37%, and 8% of patients, respectively. Median overall survival (OS) after CTISB was 21 months (95% confidence interval, 7.4-34.6), and the rates of 2-year OS, progression-free survival, and local control were 47.4%, 39.5%, and 83.5%, respectively. Both univariate and multivariate analysis indicated that D90 was significant prognostic factors for OS and progression-free survival. CONCLUSION: For selected NSCLC patients with limited LRR, CTISB is effective and can provide a high rate of local cancer control with minimal trauma.