A Prospective,Longitudinal Study of the Effect of Remission on Cortical Thickness and Hippocampal Volume in Patients with Treatment-Resistant Depression

Background:

Magnetic resonance imaging studies have provided evidence of structural modifications in cortical-limbic regions in major depressive disorder. To date, however, few studies have tracked structural changes in patients during treatment. This prospective, longitudinal imaging study investigated associations between brain structure and clinical responsiveness in a sample of patients with treatment-resistant major depressive disorder during an approximate 1-year follow-up period.

Methods:

FreeSurfer software was used to extract volume or cortical thickness values from 6 regions of interest (hippocampus, rostral middle frontal gyrus, orbitofrontal cortex, rostral and caudal anterior cingulate cortices, and inferior temporal gyrus) in patients (n = 26) and matched healthy controls (n = 28). Regions of interest were selected based on previous evidence of potential associations between morphometric characteristics in these regions and treatment response or remission. Analyses were conducted to compare volume and cortical thickness in patients and controls at baseline imaging, determine whether patients’ brain structure at treatment initiation was associated with response over follow-up, and compare longitudinal changes in volume and cortical thickness in patients who achieved sustained 6-month remission (Montgomery-Åsberg Depression Rating Scale Score ≤12) with nonremitters.

Results:

Patients and controls showed no structural differences at baseline. Among patients, thicker right caudal anterior cingulate cortex at baseline was associated with greater symptom improvement over follow-up. Remitters and nonremitters showed subtle changes in volume and thickness over time in opposing directions, with increased hippocampal volume and cortical thickness in the rostral middle frontal gyrus, orbitofrontal cortex, and inferior temporal gyrus in remitters, and decreased volume or thickness in these regions in nonremitters.

Conclusions:

The results suggest that longitudinal structural trajectories may differ in major depressive disorder patients according to their clinical response to treatment.     

Association between Secure Messaging and Primary Care Face-to-Face Visits and Phone Visits

To study the association between secure message (SM) utilization and the subsequent use of face-to-face and telephone visits. MyHealtheVet is a web-based application allowing Veterans and their Veterans Health Administration (VHA) care team to communicate securely online. SMs may be sent 24 hours, 7 days/week. Two analyses were performed: (1) a retrospective cohort study comparing changes in utilization after initial SM use and (2) a matched cohort difference in difference analysis comparing utilization changes among SM users to non-SM users. Veterans registered in MyHealtheVet, who sent an index SM in calendar year 2016, were identified. A subset of these patients was matched to patients not using SM in calendar year 2016 on the same provider panel. Administrative data were abstracted via the VA Informatics Computing Infrastructure one year prior and after index SM for users and matched non-users. Utilization outcomes included annual primary care face-to-face and telephone visits. Firstly, a paired t test compared the within SM user difference in primary care face-to-face and telephone visits between the pre- and post-periods. Secondly, we matched SM users directly to non-users on the same panel based on age, gender, service-connected percent, and urban-rural designation. Controls were selected within 0.20 standard deviations of predicted propensity of SM use based upon Nosos comorbidity risk score and drive time to the nearest VA clinic. 154,053 Veterans who initiated secure messaging during calendar year 2016 with 25,683 of these matched to controls with no secure messaging use in 2016 (N = 49,266). Compared to the VHA population, SM users were younger (54.4 years vs 62.8) with a higher proportion of females (15.2% vs 8.0%) and urban residents (71.4% vs 63.7%). Among SM users, the annual primary care face-to-face visit rate decreased by 13% from 1.6 to 1.4 visits per SM user per year (P < .001). Similarly, annual telephone visit rates increased by 14%, from 2.7 to 3.1 visits per SM user per year (P < .001). Matched SM users and control samples did not statistically differ by service connection percentage, marital status, rurality, or drive time. However, when comparing cases to controls statistical differences are noted in age (62.3 vs 65.3), female gender (4.2% vs 2.5%), and Nosos comorbidity risk score (0.7 vs 0.6), respectively. Among Veterans in the matched control study, the annual primary care face-to-face visit rate decreased by 16%, or 0.23 visits per SM user per year (P < .001) and 9%, or 0.1 visits (P < .001) for controls. Likewise, the annual telephone visit rate increased by 11%, or 0.27 visits per SM user per year (P < .001) and 4%, or 0.08 visits (P < .001) for controls. For both visit types, the between-group difference was 7% (P < .001). The initiation of secure messaging was associated with a decrease in face-to-face primary care visits and an increase in telephone visits. The association between SM use and reduced face-to-face visits may improve the availability of clinical appointment slots while increasing the impact and time commitment required of non-traditional forms of enhanced access. Department of Veterans Affairs.     

Colostral antibody protection and interference with immunity in lambs born from sheep vaccinated with an inactivated Bluetongue serotype 8 vaccine

Widespread vaccination programmes against Bluetongue virus serotype 8 (BTV-8), using inactivated vaccines, are being carried out across many countries in northern, western and southern Europe. This study investigates the extent and length of colostral antibody protection, as well as the degree of colostral antibody induced interference of the immune response to BTV-8, in sheep. Significantly lower titres of neutralising antibodies were transferred in colostrum to lambs born from sheep vaccinated once as opposed those vaccinated twice (single vaccine in the first year and a booster vaccine in the second year). On BTV-8 challenge, lambs born from sheep vaccinated on two occasions, with the second booster vaccine given approximately 1 month prior to lambing, were protected from clinical disease for up to 14 weeks. BTV-8 was isolated from 5 of the 22 challenged lambs, although only one of these lambs showed a transient rise in body temperature with no other clinical signs. Lambs born from ewes given a second booster vaccine 1 month prior to lambing, are likely to be protected from clinical disease for at least 14 weeks, whereas lambs born from ewes vaccinated once are likely to be protected for a shorter time. Colostral antibodies present in the 13–14-week-old lambs appeared to interfere with the humoral response to challenge virus. These results suggest that colostral antibodies may interfere with vaccination in lambs up to at least 14 weeks of age.     

The Accelerating Access Initiative: experience with a multinational workplace programme in Africa

Problem

A multinational company with operations in several African countries was committed to offer antiretroviral treatment to its employees and their dependants.

Approach

The Accelerating Access Initiative (AAI), an initiative of six pharmaceutical companies and five United Nations’ agencies, offered the possibility of obtaining brand antiretroviral drugs (ARVs) at 10% of the commercial price. PharmAccess, a foundation aimed at removing barriers to AIDS treatment in Africa, helped to establish an HIV policy and treatment guidelines, and a workplace programme was rolled out from September 2001.

Local setting

Private sector employers in Africa are keen to take more responsibility in HIV prevention and AIDS care. An important hurdle for African employers remains the price and availability of ARVs.

Relevant changes

The programme encountered various hurdles, among them the need for multiple contracts with multiple companies, complex importation procedures, taxes levied on ARVs, lack of support from pharmaceutical companies in importation and transportation, slow delivery of the drugs, lack of institutional memory in pharmaceutical companies and government policies excluding the company from access to ARVs under the AAI.

Lessons learned

The launch of the AAI enabled this multinational company to offer access to ARVs to its employees and dependants. The private sector should have access to these discounted drugs under the AAI. A network of local AAI offices should be created to assist in logistics of drugs ordering, purchase and clearance. No taxes should be levied on ARVs.     

Excretory urography with iohexol: evaluation in children

A multicenter clinical study was conducted using iohexol, a second-generation nonionic contrast medium, for excretory urography performed in 130 children. Doses of iohexol (300 mg iodine/ml) ranged between 150 and 660 mgI/kg (0.5 and 2.2 ml/kg). Iohexol was tolerated well, and no significant adverse reactions occurred. Sixty-five iohexol urograms were evaluated to determine the minimum dose for adequate visualization of the kidneys and collecting systems. A dose greater than 300 mgI/kg (1.0 ml/kg) always resulted in a urogram of diagnostic quality, while visualization was insufficient for diagnosis in 10% of studies done with doses of 150-300 mgI/kg (0.5-1.0 ml/kg). Another 65 iohexol urograms were compared in a blinded manner with a similar number of studies performed using iothalamate meglumine at comparable iodine concentration and dose. Visualization of calyces and pelvoinfundibular structures achieved with iohexol was rated better with statistical significance, but there was no difference in visualization of the renal parenchyma or ureters. Use of iohexol in excretory urography may be advantageous in children who are at greatest risk for an adverse reaction to contrast media or in those most likely to benefit from use of a low osmolality contrast agent.     

Dilemmas of'Crosscultural Psychotherapy Supervision'

Crosscultural psychotherapy supervision is defined as a specific three-way interaction. The influences of bilingual and cross-cultural differences between the therapistpatient dyad and the therapist-supervisor dyad on the therapeutic and supervisory processes are described. The limitations and advantages of a traditional psychoanalytical model of supervision within a transcultural setting are also explored.     

BAFF mediates survival of peripheral immature B lymphocytes

B cell maturation is a very selective process that requires finely tuned differentiation and survival signals. B cell activation factor from the TNF family (BAFF) is a TNF family member that binds to B cells and potentiates B cell receptor (BCR)-mediated proliferation. A role for BAFF in B cell survival was suggested by the observation of reduced peripheral B cell numbers in mice treated with reagents blocking BAFF, and high Bcl-2 levels detected in B cells from BAFF transgenic (Tg) mice. We tested in vitro the survival effect of BAFF on lymphocytes derived from primary and secondary lymphoid organs. BAFF induced survival of a subset of splenic immature B cells, referred to as transitional type 2 (T2) B cells. BAFF treatment allowed T2 B cells to survive and differentiate into mature B cells in response to signals through the BCR. The T2 and the marginal zone (MZ) B cell compartments were particularly enlarged in BAFF Tg mice. Immature transitional B cells are targets for negative selection, a feature thought to promote self-tolerance. These findings support a model in which excessive BAFF-mediated survival of peripheral immature B cells contributes to the emergence and maturation of autoreactive B cells, skewed towards the MZ compartment. This work provides new clues on mechanisms regulating B cell maturation and tolerance.     

组织工程细胞支架的免疫原性研究

目的：以组织工程血管脱细胞支架和仿生髓核组织工程细胞支架、周围神经去细胞神经基膜管为例,介绍组织工程脱细胞支架的免疫原性研究情况. 方法：应用计算机检索Medline 1997-01/2007-03关于免疫原性的文章.检索词“Immunotoxicology”并限定文章的语种类为English.同时利用计算机检索中国期刊全文数据库1997-01/2007-03的相关文章,限定文章语言种类为中文,检索词“组织工程,免疫原性”. 结果：主要组织相容性复合体Ⅰ免疫组织化学方法能够检测血管脱细胞支架的免疫原性;组织学观察及反转录-聚合酶链反应检测γ-干扰素、白细胞介素2、白细胞介素4、白细胞介素10 mRNA表达,可以反映仿生髓核组织工程支架的免疫原性;主要组织相容性复合体Ⅱ抗原可以反映出经过化学萃取后的去细胞预变性神经基膜血管结构保留较完整,免疫原性低. 结论：脱细胞可以极大地降低组织工程支架的免疫原性,从而使得组织工程产品有更广阔的使用前景.     

Demographic characteristics and prevalence of serologic markers among donors who use the confidential unit exclusion process: the Retrovirus Epidemiology Donor Study

BACKGROUND: Most blood centers utilize a confidential unit exclusion (CUE) process, intended to reduce the risk of transfusion-associated infectious diseases by allowing high-risk donors confidentially to exclude their blood from use for transfusion. The effectiveness of this method remains controversial. STUDY DESIGN AND METHODS: Confirmatory or supplemental test results for antibodies to human immunodeficiency virus, human T-lymphotropic virus type I, and hepatitis C virus, as well as hepatitis B surface antigen and syphilis and screening test results for antibodies to hepatitis B core (antigen) and alanine aminotransferase levels were obtained for approximately 1.8 million units donated during 1991 and 1992 at five blood centers within the United States. The prevalences of these infectious disease markers in units that the donors confidentially excluded (CUE+) and units that the donors did not exclude (CUE-) were calculated and examined within demographic subgroups. RESULTS: Units that were CUE+ were 8 to 41 times more likely to be seropositive for antibodies to human immunodeficiency virus and hepatitis C virus, hepatitis B surface antigen, and syphilis and three to four times more likely to react for antibody to hepatitis B core (antigen) or to have elevated alanine aminotransferase levels than units that were CUE- (p < 0.001). The positive predictive value of CUE (the percentage of CUE+ units that were confirmed seropositive for any marker) was 3.5 percent, and the sensitivity of CUE (the percentage of confirmed-seropositive units that were CUE+) was 2.3 percent. CONCLUSION: The current CUE process has low sensitivity and apparently low positive predictive value, and in many cases, it appeared that donors misunderstood it. Yet, CUE was not a “random process,” as CUE+ units were more likely to be seropositive for any infectious disease marker than CUE- units. This suggests that efforts to improve the CUE system may be warranted. As risk factors for transfusion-transmitted infection become more difficult to identify by history-based screening, however, such efforts may have limited effect.     

Increasing the safety-promoting behaviors of abused women

OVERVIEW: Despite an epidemic of intimate-partner violence against women, and general agreement that women should be screened for it, few assessment and intervention protocols have been evaluated in controlled studies. To test a telephone intervention intended to increase the "safety-promoting behavior" of abused women, 75 women received six telephone calls over a period of eight weeks in which safety-promoting behaviors were discussed. A control group of 75 women received usual care. Women in both groups received follow-up calls to assess safety-promoting behaviors at three, six, 12, and 18 months after intake. Analysis showed that the women in the intervention group practiced significantly (P < 0.01) more safety-promoting behaviors than women in the control group at each assessment. On average, women in the intervention group practiced almost two more safety-promoting behaviors than they had at time of intake and nearly two more than women in the control group; the additional behaviors were practiced for 18 months. This nursing intervention requires only 54 minutes to complete (six nine-minute telephone calls) and can be integrated into any health care setting. Because less than one hour of professional nursing time is involved, the cost of the intervention is minimal. Future research should determine whether the adoption of safety-promoting behaviors by abused women averts trauma and its subsequent health care costs.