Controlled trial of the impact of a BC adult mental health practice support program (AMHPSP) on primary health care professionals’ management of depression

Background

Depression affects over 400 million people globally. The majority are seen in primary care. Barriers in providing adequate care are not solely related to physicians’ knowledge/skills deficits, but also time constraints, lack of confidence/avoidance, which need to be addressed in mental health-care redesign. We hypothesized that family physician (FP) training in the Adult Mental Health Practice Support Program (AMHPSP) would lead to greater improvements in patient depressive symptom ratings (a priori primary outcome) compared to treatment as usual.

Methods

From October 2013 to May 2015, in a controlled trial 77 FP practices were stratified on the total number of physicians/practice as well as urban/rural setting, and randomized to the British Columbia AMHPSP?a multi-component contact-based training to enhance FPs’ comfort/skills in treating mild-moderate depression (intervention), or no training (control) by an investigator not operationally involved in the trial. FPs with a valid license to practice in NS were eligible. FPs from both groups were asked to identify 3–4 consecutive patients >?18?years old, diagnosis of depression, Patient Health Questionnaire (PHQ-9) score ≥ 10, able to read English, intact cognitive functioning. Exclusion criteria: antidepressants within 5?weeks and psychotherapy within 3?months of enrollment, and clinically judged urgent/emergent medical/psychiatric condition. Patients were assigned to the same arm as their physician. Thirty-six practices recruited patients (intervention n =?23; control n =?13). The study was prematurely terminated at 6?months of enrollment start-date due to concomitant primary health-care transformation by health-system leaders which resulted in increased in-office demands, and recruitment failure. We used the PHQ-9 to assess between-group differences at baseline, 1, 2, 3, and 6?months follow-up. Outcome collectors and assessors were blind to group assignment.

Results

One hundred-and-twenty-nine patients (intervention n =?72; control n =?57) were analysed. A significant improvement in depression scores among intervention group patients emerged between 3 and 6?months, time by treatment interaction, likelihood ratio test (LR) chi2(3)?=?7.96, p =?.047.

Conclusions

This novel skill-based program shows promise in translating increased FP comfort and skills managing depressed patients into improved patient clinical outcomes?even in absence of mental health specialists availability.

Trial registration

#NCT01975948.

     

Antidepressant Use in Canada Has Stopped Increasing

Objective:

Large increases in the use of antidepressants (ADs) were reported in the past 2 decades in many countries, including Canada. Our objective was to determine whether this pattern of increasing use has continued, using data from a 2012 national mental health survey.

Method:

During the past 2 decades, a series of Canadian national health surveys have evaluated AD use in the household population. Some of these surveys have assessed past 2-day use whereas others have assessed self-reported past-month use. We applied meta-regression methods as a methodological strategy to address this heterogeneity and to examine long-term trends, incorporating 2012 data.

Results:

In keeping with prior reports, AD use rapidly increased in the 1990s and early 2000s. However, the 2012 data suggest that these increases have slowed or perhaps even stopped in recent years. A post hoc examination of longitudinal data from the National Population Health Survey reinforced the impression of a levelling off in the use of these medications.

Conclusion:

The frequency of AD use may now be stabilizing in the Canadian population. This emerging steady state may reflect a contemporary balance between the perceived need, perceived effectiveness, and acceptability of these medications in the general population.     

八项肝纤维化血清标志物比较研究

目的比较血清血小板衍生生长因子-BB(PDGF-BB)、转化生长因子-β1(TGF-B1)、基质金属蛋白酶抑制剂-1(TIMP-1)、基质金属蛋白酶-1(MMP-1)、透明质酸(HA)、Ⅲ型前胶原(PC Ⅲ)、Ⅳ型胶原(C Ⅳ)和层黏连蛋白(LN)及外周血单个核细胞(PBMC)内TIMP-1 mRNA、MMP-1 mRNA在肝纤维化中的诊断价值。方法常规肝穿活检、组织病理学诊断；RT-PCR检测PBMCs中MMP-1 mRNA、TIMP-1 mRNA水平；酶标法检测血清PDGF-BB、TGF-β1、TIMP-1和MMP-1含量；放射免疫法检测血清HA、PC Ⅲ、C-Ⅳ和LN含量。结果经ROC曲线分析，血清PDGF-BB、TIMP-1、HA、PC Ⅲ、C-Ⅳ、LN和TIMP-1 mRNA的AUC分别为0．985、0．726、0．318、0．728、0．727、0．583、0．463、0．876；血清PDGF-BB和PBMCs中TIMP-1 mRNA的灵敏度和特异度分别为90％、95％，73．7％、100％；两者联合检测的灵敏度为97．4％，特异度为95．0％。结论八项指标中，血清PDGF-BB的诊断价值最大。在筛选肝纤维化患者时，以血清PDGF-BB、PBMC中TIMP-1 mRNA联合检测最佳。     

Prognostic significance of thrombocytosis in idiopathic sideroblastic anemia

In order to determine the prognostic significance of thrombocytosis in idiopathic sideroblastic anemia, the clinical courses of 17 patients were reviewed. Six patients (36%) had thrombocytosis, and none developed acute leukemia. Nine patients (53%) had normal platelet counts, and one developed acute leukemia. Two patients (12%) were thrombocytopenic, and one died of acute leukemia. There was little correlation between survival and platelet count. Sixty-three additional case reports of idiopathic sideroblastic anemia were collected from the literature. Analysis of those patients and the patients in the present study documented transformation to acute leukemia in 5 of 9 (56%) thrombocytopenic patients, 4 of 54 (7.4%) patients with normal platelet counts, and 0 of 17 patients with thrombocytosis (p less than 0.05). Therefore patients with idiopathic sideroblastic anemia and thrombocytosis appear to have a decreased likelihood of leukemic transformation.     

Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization

Human factor VIII(FVIII) inhibitors are pathologic, circulating antibodies that inactivate FVIII. We have examined the location of epitopes on the FVIII protein for inhibitors from hemophilia A and nonhemophilic individuals. The inhibitors were of type I or type II in the kinetics of their inactivation of FVIII. A cDNA clone of human FVIII was used to express defined FVIII protein fragments in Escherichia coli for immunoblotting with inhibitor plasma. An epitope for 18 heavy-chain inhibitors was localized to the aminoterminal 18.3 Kd of the A2 domain. Two of these inhibitors also recognized an epitope located between A1 and A2 domains. Similarly, an epitope for 23 light- chain inhibitors was localized to the C2 domain. Weaker epitopes for 13 of the same inhibitors within the C1 and C2 domains were also observed. Four of the 23 inhibitors in addition bound strongly to the A3 domain. Most inhibitors (22 of 23) were neutralized in vitro only by the FVIII fragments to which they bound on immunoblots; however, one inhibitor that was neutralized by a fragment containing the A1 domain did not bind to it on immunoblots. Conversely, 3 of 3 inhibitors that bound to the A3 domain and 5 of 15 that bound to the A2 domain were not neutralized by the corresponding fragments. The epitope specificity of an inhibitor did not depend on its source or type. Our results show that FVIII inhibitors bind to limited areas within the heavy and light chains of FVIII. Some inhibitor plasmas contain additional antibodies that may not be inhibitory.     

Expression studies of catalytic antibodies.

We have examined the positive influence of human constant regions on the folding and bacterial expression of active soluble mouse immunoglobulin variable domains derived from a number of catalytic antibodies. Expression yields of eight hybridoma- and myeloma-derived chimeric Fab fragments are compared in both shake flasks and high density fermentations. In addition the usefulness of this system for the generation of in vivo expression libraries is examined by constructing and expressing combinations of heavy and light chain variable regions that were not selected as a pair during an immune response. A mutagenesis study of one of the recombinant catalytic Fab fragments reveals that single amino acid substitutions can have dramatic effects on the expression yield. This system should be generally applicable to the production of Fab fragments of catalytic and other hybridoma-derived antibodies for crystallographic and structure-function studies.     

Use of porcine factor VIII in the treatment of patients with acquired hemophilia

Data have been collected from 47 centers in Europe and North America on the treatment with porcine factor VIII concentrate of 74 acute bleeding episodes in 65 patients with acquired hemophilia. The median initial anti-human factor VIII auto-antibody inhibitor level was 38 Bethesda unit (BU)/mL (range 1.2 to 1,024) whereas that against porcine was 1 BU/mL (range 0 to 15). The mean initial dose of porcine factor VIII infused was 84 IU/kg, which increased the plasma factor VIII:C activity by 0.85 IU/mL. Therapy was continued for a mean of 8.5 days during which time the average number of infusions was 11. Objective clinical responses were rated as good or excellent in 78% of recipients. Side effects were uncommon; only one patient experienced a severe anaphylactic reaction necessitating the discontinuation of porcine FVIII therapy. After therapy, no increase in the median level of anti- human FVIII or anti-porcine antibody was noted in the group as a whole, although 13 patients showed individual increases in either anti-human or anti-porcine antibody levels or both of more than 10 BU/mL. Of the 7 patients who subsequently rebled, 5 were successfully re-treated and 2 did not respond to further porcine factor VIII treatment. Porcine factor VIII is safe and clinically effective treatment for bleeding episodes associated with acquired hemophilia and should be considered as first-line therapy for patients whose acquired anti-factor VIII:C antibody cross-reacts with porcine factor VIII:C at low levels.     

Rapid prenatal diagnosis of beta thalassemia using DNA amplification and nonradioactive probes

We used in vitro DNA amplification by the polymerase chain reaction and nonradioactive probes for prenatal diagnosis of beta thalassemia in Chinese from the Guangdong province. Exact molecular diagnoses were made in all 20 fetuses studied over a 6-month period. We conclude that this method of prenatal diagnosis for beta thalassemia is a viable approach in many parts of the world where this disease is common.