Utilization,Patient Characteristics,and Longitudinal Improvements among Patients from a Provincially Funded Transdiagnostic Internet-delivered Cognitive Behavioural Therapy Program: Observational Study of Trends over 6 Years

Objective:There is strong evidence supporting internet-delivered cognitive behaviour therapy (iCBT) and consequently growing demand for iCBT in Canada. Transdiagnostic iCBT that addresses both depression and anxiety is particularly promising as it represents an efficient method of delivering iCBT in routine care. The Online Therapy Unit, funded by the Saskatchewan government, has been offering transdiagnostic iCBT for depression and anxiety since 2013. In this article, to broadly inform implementation efforts, we examined trends in utilization, patient characteristics, and longitudinal improvements for patients receiving transdiagnostic iCBT over 6 years.Methods:Patients who completed telephone screening between November 2013 and December 2019 were included in this observational study. Patients provided demographics and mental health history at screening and completed measures at pre-treatment, post-treatment and at 3- to 4-month follow-up. Treatment engagement and satisfaction were assessed.Results:A total of 5,321 telephone screenings were completed and 4,283 of patients were accepted for treatment over the 6-year period (80.5% acceptance). The most common reason for referral to another service was high suicide risk/severe symptoms (47.1%). Examination of trends showed growing use of transdiagnostic iCBT over time (37% increase per year). There was remarkable stability in patient characteristics across years. Most patients were concurrently using medication (57.3%) with 11.9% reporting using iCBT while on a waiting list for face-to-face treatment highlighting the importance of integrating iCBT with other services. Consistent across years, large improvements in depression and anxiety symptoms were found and maintained at 3- to 4-month follow-up. There was strong patient engagement with iCBT and positive ratings of treatment experiences.Conclusions:As there is growing interest in iCBT in Canada, this large observational study provides valuable information for those implementing iCBT in terms of likely user characteristics, patterns of use, and improvements. This information has potential to assist with resource allocation and planning in Canada and elsewhere.     

Restriction of cell lysis by homologous complement: II. Protection of erythrocytes against lysis by newly activated complement

Our previous work revealed that homologous complement (C) was ineffective in lysing antibody-sensitized erythrocytes (EA) even at high concentrations. It was also shown that activation of complement on homologous EA resulted in the binding of C9 and the formation of EA bearing complement proteins C1 through C9 (EAC1-9), yet few hemolytic sites were formed. Instead, as shown here, the formation of homologous EAC1-9 caused the cells to become resistant to lysis even by heterologous complement during a second incubation. In contrast, when homologous EAC1-8 were produced by incubating EA with C9-depleted serum, such intermediates were not protected against lysis by heterologous complement during a second incubation. Furthermore, homologous C9 on EAC1-9 was able to reduce the hemolytic efficiency of heterologous complement without blocking C activation and the formation of new C5b-9 complexes. Protection was not modified when homologous EAC1-9 were produced in one step, by incubation of EA with serum, or sequentially by adding C9 to EAC1-8. The minimum number of 9-sites required to confer a protective effect on EAC1-9 was less than 200 per cell. Thus, in addition to its known effect in heterologous cell killing, homologous C9 is capable of protecting homologous cells against inadvertent complement lysis.     

Zinc protoporphyrin in anemia of chronic disorders

Hematofluorometric determination of zinc protoporphyrin (ZPP) is a screening method for the assessment of iron deficiency (ID). Chronic disorders are frequently accompanied by anemias of unclear origin, most probably caused by an impairment of iron metabolism. We investigated the relevance of ZPP for the detection of derangements of iron metabolism in anemias of chronic disorders (ACD). In 19 patients with ACD caused by chronic inflammatory non-neoplastic diseases, ZPP was determined and correlated with ferritin, transferrin saturation, and hemoglobin (Hb). Marrow sideroblast counts and semiquantitative grading of the marrow hemosiderin were performed in all patients to exclude ID and to show the decreased iron bioavailability. In all ACD patients who exhibited the typical laboratory findings of disturbed iron metabolism, such as hypoferremia, decreased transferrin saturation, decreased bone marrow sideroblasts, and increased marrow hemosiderin, strongly elevated ZPP levels were found (131 +/- 23 mumol/mol heme). ZPP returned to normal after successful treatment of the underlying disease. This is shown in three patients with polymyalgia rheumatica. We conclude that the fluorometric determination of ZPP allows detection and quantification of derangements of iron metabolism associated with chronic inflammatory disorders. By recording the derangements quantitatively, ZPP allows monitoring of therapy of chronic inflammatory diseases.     

Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium

Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor.     

碱性成纤维细胞生长因子对大鼠脑血肿周围组织和海马bax及bcl-2基因表达的调节

目的:观察碱性成纤维细胞生长因子对大鼠脑出血后出血灶周围脑组织和出血侧海马bax、bcl-2基因表达的影响,探讨神经营养因子对神经细胞调亡的调控。方法:实验于2006-01/10在广西医科大学医学科学实验中心完成。①取成年清洁级Wistar大鼠72只,雌雄各半,体质量250g左右。②采用脑内囊注射胶原酶建立大鼠脑出血模型,动物于苏醒后按Bederson法进行神经病学评分,评分>3分后入选本实验,入选72只大鼠随机抽签法分为3组,每组24只。碱性成纤维细胞生长因子组按8μg/kg剂量肌肉注射,1次/d;生理盐水组肌肉注射等剂量的生理盐水,1次/d;模型组不作任何干预。③每组分别于干预后1,3,7d随机抽取8只大鼠,麻醉状态下取出血灶周围脑组织和出血侧海马,采用半定量反转录-聚合酶链反应检测调亡调控基因bax mRNA,bcl-2mRNA的表达。结果:在建立脑出血模型中共5只大鼠死亡,随后对死亡动物进行解剖,发现脑内血肿量过大,致脑疝形成而导致死亡,后随机补充动物。72只大鼠进入结果分析。①血肿周围脑组织bax mRNA表达:干预后3d,7d,碱性成纤维细胞生长因子组血肿周围脑组织bax mRNA表达比生理盐水组明显减少(3d:0.54±0.19,0.76±0.23,P<0.05;7d:0.45±0.19,0.71±0.16,P<0.01)。②血肿周围脑组织bcl-2mRNA表达:干预后3d,7d,碱性成纤维细胞生长因子组的血肿周围脑组织bcl-2mRNA表达比生理盐水组明显增高(3d:0.68±0.25,0.39±0.19,P<0.05;7d:0.80±0.21,0.48±0.18,P<0.01)。③出血侧海马bax mRNA表达:干预后3d和7d,碱性成纤维细胞生长因子组的出血侧海马bax mRNA表达比生理盐水组均明显减少(3d:0.54±0.18,0.70±0.11;7d:0.43±0.24,0.69±0.18,P均<0.05)。④出血侧海马bcl-2mRNA表达:干预后3d和7d,碱性成纤维细胞生长因子组的出血侧海马bcl-2mRNA表达比生理盐水组均明显增多(3d:0.66±0.11,0.50±0.15;7d:0.72±0.12,0.52±0.22,P均<0.05)。结论:碱性成纤维细胞生长因子能调节凋亡相关基因,提高大鼠脑出血后大脑脑组织和海马bcl-2mRNA的表达,降低bax mRNA的表达。     

A clinical and pharmacological study of 5-fluorouracil,leucovorin and interferon alfa in advanced colorectal caner

Modulation of 5-fluorouracil (FUra) using leucovorin (LV) is a standard treatment approach in patients with metastatic colorectal cancer. Modulation of FUra with interferon alfa has also shown some promise. Laboratory data have demonstrated increased cytotoxicity when FUra is combined with both LV and interferon. The current study examined the effects of double modulation of FUra using LV and interferon. Patients with measurable advanced colorectal cancer received bolus FUra 375 mg/m² plus LV 20 mg/m² daily for 5 days, repeated every 28 days. Recombinant human interferon alfa-2a, 3 million IU/m² subcutaneously, was given daily on the days of chemotherapy then three times weekly. There was one complete response and nine partial responses (10/41) seen for an overall response rate of 24% (95% CI 12.0–40.0%). Overall, 70% of patients experienced one or more episodes of nonhematologic toxicity of grade 3 or more. Weight loss was common, with a mean decrease of 2.9 kg over the first two months (P<0.0001). Improvements in tumor-related symptoms were balanced by increased fatigue and a deterioration in body weight and performance status. There was no evidence of progressive changes in FUra metabolism from interferon usage.This work was supported in part by a grant from Hoffman LaRoche Canada