The effect of lavender aroma for anxiety disorder: a study protocol for a multicenter, double-masked, randomized, placebo-controlled clinical trial.

BACKGROUND: Anxiety disorder is the most prevalent psychiatric disorder. Benzodiazepines, which are often used for anxiety in patients with anxiety disorder, have various side effects. Lavender, one of the most commonly used essential oils in aromatherapy, has the potential to reduce benzodiazepine use for anxiety disorders. METHODS: This study is a multicenter, double-masked, randomized, placebo-controlled clinical trial. The study will recruit patients aged 20-59 years old with generalized anxiety disorder and panic disorder among anxiety disorders. The bottle containing the test solution (lavender aroma essential oil or distilled water) will be given to the patients. Patients will carry the bottles with them in their daily life and use the drops on tissue paper when anxious. The primary endpoint is the number of times anxiolytics used in 28 days. DISCUSSION: If the use of benzodiazepines could be reduced by sniffing lavender aroma, which is inexpensive and safe, it would contribute not only to the risks associated with benzodiazepine use but also to the health care economy and could even be added as a standard treatment. TRIAL REGISTRATION: University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), ID: UMIN000034422 Registered 17 January 2019.

A randomized controlled trial of surgery and postoperative modified FOLFOX6 versus surgery and perioperative modified FOLFOX6 plus cetuximab in patients with KRAS wild-type resectable colorectal liver metastases: EXPERT study.

PURPOSE: To clarify the efficacy of perioperative chemotherapy for the patients with resectable colorectal liver metastases (CLM), we conducted a multicenter randomized phase III trial to compare surgery followed by postoperative FOLFOX regimen with perioperative FOLFOX regimen plus cetuximab in patients with KRAS wild-type resectable CLM. METHODS: Patients who had KRAS wild-type resectable CLM having one to eight liver nodules without extrahepatic disease were randomly assigned to the postoperative chemotherapy group, wherein up-front hepatectomy was performed followed by 12 cycles of postoperative modified FOLFOX6, and the perioperative chemotherapy group (experimental), wherein six cycles of preoperative modified FOLFOX6 plus cetuximab were performed followed by hepatectomy and six cycles of postoperative modified FOLFOX6 plus cetuximab. The primary endpoint was progression-free survival (PFS). RESULTS: There were 37 patients in postoperative chemotherapy group and 40 patients in the perioperative chemotherapy group who were analyzed. Baseline characteristics were well-balanced between groups. The PFS and overall survival (OS) showed no significant difference (PFS, hazard ratio 1.18 [95% confidence interval 0.69-2.01], P = 0.539: OS, 1.03 [0.46-2.29], P = 0.950). In the postoperative chemotherapy group, 35.1% had a 3-year PFS, and 86.5% had a 3-year OS. Meanwhile, in the perioperative chemotherapy group, 30.0% had a 3-year PFS, and 74.4% had a 3-year OS. CONCLUSION: There was no difference in survival found between the group of the perioperative chemotherapy plus cetuximab and that of the postoperative chemotherapy in the cohort of our study. The study was registered in the University Hospital Medical Information Network (UMIN000007787).

Surface contamination of the outer and blister packages of oral anticancer drugs: A multicenter study.

INTRODUCTION: All guidelines necessitate wearing personal protective equipment during dispensing of oral anticancer drugs. This study aims to measure the degree of contamination on the press-through-package strips of oral anticancer drugs in Japan. METHOD: Surface contamination of the external packaging of anticancer drugs was examined by performing wipe tests at four hospitals and two community pharmacies. The following commercially available drugs were examined: Xeloda®, TS-1®, and methotrexate tablets and SA-1® and Rheumatrex® capsules. RESULTS: The wipe tests' results revealed that the contamination levels of Xeloda® and TS-1® tablets and SA-1® capsules were within their detection limits. In some facilities, the contamination levels on the press-through-package strips of Rheumatrex® capsules were 3.27 × 10-1, which is close to its detection limit. However, across all facilities, the contamination level of methotrexate tablets was above its detection limit. CONCLUSION: The results of this study suggested that adherence to oral anticancer drugs may not occur during manufacture or transportation. However, it may be due to the presence of pollutants in the facilities. Prevention of pollution in facilities might eliminate the need to wear personal protective equipment during dispensing of oral anticancer drugs.

Prevalence and Diagnosis of Diabetic Cardiovascular Autonomic Neuropathy in Beijing, China: A Retrospective Multicenter Clinical Study.

Cardiovascular autonomic neuropathy (CAN) is a debilitating condition occurring among diabetic patients especially those with long duration of disease. Whereas incidences and treatment of CAN has been well described for Western populations, fewer studies have been conducted among the Chinese. This study, therefore, aimed to assess the prevalence of CAN among sampled Chinese diabetic patients. Accordingly, 2,048 participants with a history of type 1 diabetes mellitus (T1DM, 73) and type 2 diabetes mellitus (T2DM, 1975) were randomly sampled from 13 hospitals. Patients' biodata were recorded, and autonomic nervous system function tests performed to aid in the preliminary diagnosis of CAN. The final CAN diagnosis was based on the Ewing's test in which heart rate variation (HRV) values were evaluated through deep-breathing (DB), lying-to-standing (LS), and Valsalva (V) tests. Systolic blood pressure (SBP) variation values were also evaluated through LS. In the T1DM group, 61.6% patients were diagnosed with CAN and no differences were observed in the baseline and clinical data between this group and those without CAN (P > 0.05). In the T2DM group, 62.6% patients were diagnosed with CAN and statistically significant differences were found between the CAN and non- CAN group with regards to age, duration of diabetes, metformin treatment, retinopathy, and hypertension history (P < 0.05). The most common manifestations of CAN included weakness (28.6%), dizziness (23.4%), frequent urination (19.6%), upper body sweating (18.3%), and nocturia (15.9%). Additionally, duration of disease and age were independent risk factors for CAN in T1DM and T2DM, respectively. On diagnosis, a combination of the V test + LS test provided the highest sensitivity of detecting CAN among T1DM group (sensitivity = 97.6%, AUC = 0.887) while for T2DM category, DB test had the highest sensitivity (83.6%), and maximal AUC (0.856) was found with V test + DB test. The overall prevalence of diabetes with CAN in the study was up to 63%.

Preoperative and postoperative predictors of long-term outcome after endovascular treatment of poor-grade aneurysmal subarachnoid hemorrhage.

OBJECTIVE An increasing number of patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) have received endovascular treatment. Endovascular treatment of poor-grade aSAH, however, is based on single-center retrospective studies, and predictors of long-term outcome have not been well defined. Using results from a multicenter prospective registry, the authors aimed to develop preoperative and postoperative prognostic models to predict poor outcome after endovascular treatment of poor-grade aSAH. METHODS A Multicenter Poor-grade Aneurysm Study (AMPAS) was a prospective and observational registry of consecutive patients with poor-grade aSAH. From October 2010 to March 2012, 366 patients were enrolled in the registry, and 136 patients receiving endovascular treatment were included in this study. Outcome was assessed by modified Rankin Scale (mRS) score at 12 months, and poor outcome was defined as an mRS score of 4, 5, or 6. Prognostic models were developed in multivariate logistic regression models. The area under receiver operating characteristic curves (AUC) was used to assess the model's discriminatory ability, and Hosmer-Lemeshow goodness-of-fit tests were used to assess the calibration. RESULTS At 12 months, 64 patients (47.0%) had a poor outcome: 9 (6.6%) had an mRS score of 4, 6 (4.4%) had an mRS score of 5, and 49 (36.0%) had died. Univariate analyses showed that older age (p = 0.001), female sex (p = 0.044), lower Glasgow Coma Scale score (p < 0.001), a World Federation of Neurosurgical Societies (WFNS) grade of V (p < 0.001), higher Fisher grade (p < 0.001), modified Fisher grade (p < 0.001), and wider neck aneurysm (p = 0.026) were associated with a poor outcome. There was a trend toward a worse outcome in patients with anterior communicating artery aneurysms (p = 0.080) and in those with incompletely occluded aneurysms (p = 0.063). After endovascular treatment, the presence of cerebral infarction (p = 0.039), symptomatic vasospasm (p = 0.039), and pneumonia (p = 0.006) were associated with a poor outcome. Multivariate analyses showed that the preoperative prognostic model including age, a WFNS grade of V, modified Fisher grade, and aneurysm neck size had excellent discrimination with an AUC of 0.86 (95% CI 0.80-0.92, p < 0.001), and a postoperative model that included these predictors as well as postoperative pneumonia had excellent discrimination (AUC = 0.87, 95% CI 0.81-0.93, p < 0.001). Both models had good calibration (p = 0.941 and p = 0.653, respectively). CONCLUSIONS Older age, WFNS Grade V, higher modified Fisher grade, wider neck aneurysm, and postoperative pneumonia were independent predictors of poor outcome after endovascular treatment of poor-grade aSAH. The preoperative model had almost the same discrimination as the postoperative model. Endovascular treatment should be carefully considered in patients with poor-grade aSAH with ruptured wide-neck aneurysms. ▪ CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort trial; evidence: Class I.

Denosumab: a cost-effective alternative for older men with osteoporosis from a Swedish payer perspective.

OBJECTIVE: To assess the cost-effectiveness of denosumab versus other treatments in men with osteoporosis who are ≥75years old from a payer perspective in Sweden. METHODS: A lifetime cohort Markov model was developed with seven health states: well, hip fracture, vertebral fracture, other osteoporotic fracture, post-hip fracture, post-vertebral fracture, and dead. During each cycle, patients could have a fracture, remain healthy, remain in a post-fracture state or die. Background fracture risks, mortality rates, persistence rates, utilities, medical and drug costs were derived using published sources. Estimates of fracture efficacy were drawn from available studies in post-menopausal osteoporotic (PMO) women as BMD improvements have been shown to be similar across male osteoporosis (MOP) and PMO populations, and a recent clinical trial suggested that the fracture risk reduction from bisphosphonate therapy in men is similar to that seen in women in comparable studies. Lifetime expected costs and quality-adjusted life-years (QALYs) were estimated for denosumab, generic alendronate, generic risedronate, ibandronate, zoledronate, strontium ranelate and teriparatide. On average, patients in the model were 78years old, with bone mineral density T-score at the femoral neck of -2.12. Prevalent vertebral fractures were present in 23% of patients. In the base-case, the model assumed that patients would experience treatment-related effects up to 2years after discontinuation. Costs and QALYs were discounted at 3% annually. Extensive sensitivity analyses were conducted. RESULTS: Total lifetime costs for denosumab, alendronate, strontium ranelate, zoledronate, risedronate, ibandronate and teriparatide were €31,004, €33,731, €34,788, €34,796, €34,826, €35,983 and €37,461, respectively. Total QALYs were 5.23, 5.15, 5.15, 5.17, 5.13, 5.12 and 5.22, respectively. Compared to other treatments, denosumab had the lowest costs and highest QALYs. In the one-way sensitivity analyses, when compared to alendronate (next least expensive strategy), the ICER for denosumab was most sensitive to the relative risk of hip fracture on denosumab. The probability of denosumab being cost-effective compared to the other treatments at a threshold of €66,000/QALY was 96.1%. CONCLUSION: Denosumab dominated all comparators, including generic bisphosphonates, in the treatment of osteoporosis in men who were ≥75years old in Sweden.

Clinical observation on the treatment of 69 patients with diabetic neurogenic bladder with acupoint injection therapy / 国际中医中药杂志

Objective To investigate an effective therapy to cure Diabetic Neurogenic Bladder (DNB).Methods By adopting multi-center,random,comparative and single-blind clinical experiments,138 patients with DNB from three centers were divided equally into two groups,namely a control group and a therapy group.Patients in the therapy group were treated with acupoint injection therapy with Astragalus injection,while others were treated by western medical based therapy.After four weeks,the effectiveness was collected.Results After the treatment,the TCM syndrome integral of the treatment group and the control group was (18.47± 1.67) and (23.19±2.82) respectively,both reduced than that before the treatment[(29.25±2.12) and (29.13 ± 1.69) respectively]; the difference between the two groups after treatment was statistically significant (P＜0.05) ; bladder residual urine volume in the treatment group and the control group was (88.47± 16.7) ml and (143.19±28.2)ml respectively,both reduced than that before the therapy [(308.90±22.6)ml and (305.90± 20.8)ml respectively],the difference between the two groups after treatment was statistically significant (P＜0.05) ;The total effective rate was 88.4％ and 72.5％ in the treatment group and the control group respectively,showing statistical difference(P＜0.05).Conclusion It is confirmed that acupoint injection therapy with Astragalus injection is an effective curative method for DNB.