Objective Recombinant human parathyroid hormone(1-34) [ rhPTH(1-34)] is the unique anabolic substance acting on the skeleton. The efficacy and safety of long-term administration of rhPTH(1-34) in Chinese postmenopausal women have not been evaluated. This study compared the clinical efficacy and safety of rhPTH(1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China. Methods A total of453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH(1-34) 20 μg(200 U) daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine ( L1-4) and femoral neck bone mineral density (BMD), fracture rate, back pain as well as biochemical markers of bone turnover ( serum bone-specific alkaline phosphatase was measured by radioimmunoassay; C-telopeptide/ creatinine ( CTX/ Cr) measured by quantitative sandwich enzyme-linked immunosorbent assay) at 6, 12, and 18 months. Adverse events were recorded. Results rhPTH(1-34) increased lumbar BMD more significantly than that did by elcatonin at 6 months( M6), 12 months (M12), and 18 months(M18; 4. 3% vs 1. 94% , 6. 8% vs 2. 72% , 9. 51% vs 2. 86% , P<0. 01). There was only a small but significant increase of femoral neck BMD at M18(2. 64% , P<0. 01) in rhPTH(1-34) groups. There were greater increases in bone turnover markers in the rhPTH(1-34) group than in the elcatonin group at M6, M12, and M18[serum bone-specific alkaline phosphatase(BSAP) 93. 67% vs -3. 56% , 117. 78% vs -4. 12% , 49. 24% vs-5. 81% , P<0. 01; urinary CTX/ Cr 250% vs -29. 5% , 330% vs -41. 4% , 273 % vs -10. 6% , P<0. 01]. rhPTH (1-34) showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5. 36% (6 / 112) in elcatonin group and 3. 23% ( 11 / 341 ) in rhPTH ( 1-34 ) group ( P = 0. 303 ). Both treatments were well tolerated. Hypercaluria(9. 38% ) and hypercalcemia(7. 04% ) in rhPTH(1-34) group was transient and caused no clinical symptoms. Pruritus(8. 21% vs 2. 68, P=0. 044) and redness of injection site(4. 40% vs 0, P=0. 024) were more frequent in rhPTH(1-34). Nausea / vomiting(16. 07% vs 6. 16% , P = 0. 001) and hot flushes(7. 14% vs 0. 59% , P<0. 001) were more common in elcatonin group. Conclusion rhPTH(1-34) treatment was associated with greater increases in lumbar spine BMD and bone formation markers. It could increase femoral BMD after 18 months treatment. rhPTH(1-34) could ameliorate back pain effectively. The results of the present study indicate that rhPTH(1-34) is an effective, and safe agent in treating postmenopausal women with osteoporosis.

BACKGROUNDElectroconvulsive therapy (ECT) can alleviate the symptoms of treatment-resistant depression (TRD). Functional network connectivity (FNC) is a newly developed method to investigate the brain's functional connectivity patterns. The first aim of this study was to investigate FNC alterations between TRD patients and healthy controls. The second aim was to explore the relationship between the ECT treatment response and pre-ECT treatment FNC alterations in individual TRD patients.

METHODSThis study included 82 TRD patients and 41 controls. Patients were screened at baseline and after 2 weeks of treatment with a combination of ECT and antidepressants. Group information guided-independent component analysis (GIG-ICA) was used to compute subject-specific functional networks (FNs). Grassmann manifold and step-wise forward component selection using support vector machines were adopted to perform the FNC measure and extract the functional networks' connectivity patterns (FCP). Pearson's correlation analysis was used to calculate the correlations between the FCP and ECT response.

RESULTSA total of 82 TRD patients in the ECT group were successfully treated. On an average, 8.50 ± 2.00 ECT sessions were conducted. After ECT treatment, only 42 TRD patients had an improved response to ECT (the Hamilton scores reduction rate was more than 50%), response rate 51%. 8 FNs (anterior and posterior default mode network, bilateral frontoparietal network, audio network, visual network, dorsal attention network, and sensorimotor network) were obtained using GIG-ICA. We did not found that FCPs were significantly different between TRD patients and healthy controls. Moreover, the baseline FCP was unrelated to the ECT treatment response.

CONCLUSIONSThe FNC was not significantly different between the TRD patients and healthy controls, and the baseline FCP was unrelated to the ECT treatment response. These findings will necessitate that we modify the experimental scheme to explore the mechanisms underlying ECT's effects on depression and explore the specific predictors of the effects of ECT based on the pre-ECT treatment magnetic resonance imaging.

Adult ; Brain ; pathology ; physiopathology ; Depression ; physiopathology ; therapy ; Depressive Disorder, Treatment-Resistant ; physiopathology ; therapy ; Electroconvulsive Therapy ; methods ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged

BACKGROUND: Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations. METHODS: In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively. RESULTS: 81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count. CONCLUSIONS In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.