Does race or socioeconomic status predict adverse outcome after out of hospital cardiac arrest: a multi-center study

Objective: To assess whether socioeconomic status (SES) or race is associated with adverse outcome after an out-of-hospital cardiac arrest (OHCA). Methods: A convenience sample of OHCA of presumed cardiac origin from seven suburban cities in Michigan, 1991–1996. Median household income (HHI), utilizing patient home address and 1990 census tract data, was dichotomized above and below 1990 state median income. Patient race was dichotomized as black or white. Outcome was defined as survival to hospital discharge (DC). Multiple logistic regression and Pearson’s χ² values were used for analysis. Results: Of 1317 cases with complete data for analysis, the average age was 67.3±16.0, 939 (71.1%) were white, 587 (44.4%) arrests were witnessed (WIT), and 65 (4.9%) were DC alive. There was no significant difference between races with respect to WIT arrests, V_T/V_F arrest rhythms, and a small difference in EMS response interval. Whites were more likely to be above median HHI (57.1 vs. 26.2%, P<0.001). Adjusted odds ratios for predictors of survival were WIT arrest (OR=3.76, 95% CI (1.7, 8.2)), V_T/V_F (OR=8.74, 95% CI (3.7, 10.8), but not race (OR=0.68, 95% CI (0.3, 1.4)) or SES (OR=1.51,95% CI 0.8, 2.8). Conclusion: In this population, neither race nor SES was independently associated with a worse outcome after OHCA.     

Valuation of Life as outcome and mediator of a depression intervention for older African Americans: the Get Busy Get Better Trial

Objective

Previously, we showed that Get Busy Get Better (GBGB), a 10‐session multicomponent home‐based, behavioral intervention, reduced depressive symptom severity in older African Americans. As appraising the value of life is associated with depressive symptoms, this study examined whether GBGB enhanced positive appraisals of life and if, in turn, this mediated treatment effects on depressive symptoms.

Methods

Data were from a single‐blind parallel randomized trial involving 208 African Americans (≥55 years old) with depressive symptoms (Patient Health Questionnaire, PHQ‐9 ≥5). GBGB involved five components: care management, referral/linkage, stress reduction, depression education, and behavioral activation. A 13‐item Valuation of Life (VOL) scale with two subfactors (optimism and engagement) was examined as an outcome and as mediating GBGB effects on PHQ‐9 scores at 4 months.

Results

Of 208 enrolled African Americans, 180 completed the 4‐month interview (87 = GBGB; 93 = control). At 4 months, compared with wait‐list control group participants, the GBGB group had improved VOL (difference in mean changes from baseline = 4.67, 95% confidence interval 2.53, 6.80). Structural equation models indicated that enhanced VOL mediated a significant proportion of GBGB's impact on depressive symptoms, explaining 71% of its total effect, and its subfactors (optimism, explaining 67%; engagement, 52%).

Conclusion

Valuation of Life appears malleable through an intervention providing resources and activation skills. GBGB's impact on depressive symptoms is attributed in large part to participants' enhanced attachment to life. Attention to VOL as mediator and outcome and the reciprocal relationship between mood and attachment to life is warranted. Copyright © 2017 John Wiley & Sons, Ltd.     

The impact of neurocognitive impairment on occupational recovery of clinically stable patients with bipolar disorder: a prospective study

Bearden CE, Shih VH, Green MF, Gitlin M, Sokolski KN, Levander E, Marusak S, Hammen C, Sugar CA, Altshuler LL. The impact of neurocognitive impairment on occupational recovery of clinically stable patients with bipolar disorder: a prospective study.
Bipolar Disord 2011: 13: 323–333. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objective: Many patients with bipolar disorder do not regain their premorbid level of occupational functioning even after mood episodes have resolved. The reasons for this are not well understood. We evaluated the relationship between neurocognition and occupational function in bipolar disorder patients, following symptomatic recovery. Methods: A total of 79 previously employed adults with bipolar I disorder who achieved symptomatic recovery (i.e., at least six weeks clinically euthymic) following a manic episode underwent a neurocognitive evaluation and assessment of occupational functioning. Study participants were evaluated every three months thereafter for up to nine months. Factor analysis was applied to reduce the initial set of neurocognitive variables to five domains: episodic memory, working memory/attention, executive function, visual scanning, and speed of processing. Multiple logistic regression models were used to examine the joint predictive values of these domains for determining occupational recovery. Results: At the time of symptomatic recovery, four of five neurocognitive factors were significant predictors of concomitant occupational recovery and the fifth, executive function, showed a trend in the same direction. For those not occupationally recovered at baseline, longitudinal analyses revealed that changes between baseline and the three‐month follow‐up timepoint in most cognitive domains were robust and highly significant predictors of occupational recovery at three months. Conclusions: These findings indicate that better neurocognitive function in multiple domains and improvement in these domains over time are strongly predictive of subsequent occupational recovery. Treatments that target cognitive deficit may therefore have potential for improving long‐term vocational functioning in bipolar illness.     

Mineralization of the deep gray matter with age: a retrospective review with susceptibility-weighted MR imaging

BACKGROUND AND PURPOSE: Susceptibility-weighted imaging (SWI) is an advanced MR imaging sequence that can be implemented at high resolution. This sequence can be performed on conventional MR imaging scanners and is very sensitive to mineralization. The purpose of this study was to establish the course of mineralization in the deep gray matter with age by using SWI.Materials and METHODS: We retrospectively reviewed susceptibility-weighted images of 134 patients (age range, 1 to 88 years). Inclusion criteria comprised a normal conventional MR imaging (T1, T2, and fluid-attenuated inversion recovery sequences). We statistically analyzed the relative signal intensities of the globus pallidus, putamen, substantia nigra, caudate nucleus, red nucleus, and thalamus for correlation with age. The putamen was graded according to a modified scale, based on previous work that described a systematic pattern of mineralization with age. Bands of hypointensity in the globus pallidus, dubbed “waves,” were also evaluated.RESULTS: We documented decreasing intensity (ie, increasing mineralization) with age in all deep gray matter areas analyzed. We confirmed the age-related posterolateral to anteromedial progression of mineralization in the putamen. Characteristic medial and lateral bands of mineralization were exhibited in the globus pallidus in all children and young adults older than 3 years. Finally, an increase in the number of “waves” present in the globus pallidus was associated with increased age by category.CONCLUSION: This study documents the course and pattern of mineralization in the deep gray matter with age, as determined by SWI. These findings may play a role in evaluating diseased brains in the future.

In 1958, Hallgren and Sourander¹ performed some of the earliest work on characterizing brain iron. They studied iron distribution in various tissues, including the deep gray matter, during an autopsy of brains from 98 subjects, excluding those with cerebrovascular or neuropsychiatric disorders. Iron was found to increase with age in most brain tissues. In the globus pallidus, red nucleus, substantia nigra, and dentate nucleus, iron increases rapidly from birth until the end of the second decade, plateaus for several years, and then shows another milder increase after age 60. Iron increases more slowly in the putamen and caudate, levelling off in the fifth or sixth decade. Subsequent iron-staining studies have largely supported the work of Hallgren and Sourander.¹Most brain iron, other than that found in hemoglobin, is protein-bound, nonheme iron. Approximately one third of nonheme iron is postulated to be in the form of ferritin, though this fraction may be higher in certain deep gray matter structures. Other forms include transferrin, lactoferrin, hemosiderin (thought to be degenerated ferritin), ionic iron, and possibly biogenic magnetite.^2,3 The 2 most important compounds in brain-iron regulation are transferrin, which is used in iron transport, and ferritin, which is used in iron storage. Transferrin and ferritin are also thought to be the only forms of nonheme iron that have a high enough concentration in the brain to be detected currently by MR.³ The mechanisms by which iron and other minerals are deposited in the brain are not well understood. Although the bulk of iron required for the metabolic activity of the adult brain is taken up during the neonatal period, experiments with radioactively labeled iron indicate that small amounts continue to be transported into the adult brain.⁴ In particular, the basal ganglia may exhibit increased susceptibility to mineralization because of their high metabolic rate, and the pattern of mineralization may, in part, relate to the functional vascular components of the striatum.^5,6 Mineral deposits may, in turn, restrict blood flow and cause neural tissue injury that leads to further mineralization.It is believed that the destruction of gray matter causes the release of iron, which is then taken up by activated microglia. Studies have linked increased brain mineralization with several diseases (eg, Parkinson, Alzheimer, Huntington, dementia with Lewy bodies, multiple sclerosis, hemochromatosis, Hallervorden-Spatz, Down syndrome, and AIDS). Histochemical analysis of mineralization of the basal ganglia has shown that many other minerals may be present in addition to iron (eg, calcium, manganese, zinc, copper, magnesium, aluminum, potassium, phosphorus).^5,7 It has been found that the accumulation of iron tends to precede the deposition of calcium and other minerals. These discoveries have underlined the need to develop in vivo imaging techniques sensitive to mineralization, particularly iron.Early attempts at developing such techniques have involved CT imaging.^8,9 More recently, with MR imaging, T2 shortening in the gray matter nuclei with age has been well documented.^10–14 A reduction in T2 is thought to be predominantly related to iron deposition, particularly ferritin,^2,11,15 though 1 team¹⁶ reports contrary findings. The drawback of simply using T2 shortening as a measure of mineralization is that it is also affected by factors such as myelin loss and changes in water concentration, which vary with tissue type, presence of disease, and age.^3,11,13,17 Some researchers have worked on minimizing this effect. Bartzokis et al¹¹ used an imaging process called field-dependent relaxation rate increase (FDRI) to extract that portion of T2 shortening that is the result of mineralization. However, this method is logistically difficult because it requires access to 2 MR machines of different magnetic field strengths as well as careful positioning of the patient in order to extract similar sections from high- and low-field sequences for comparison. Gelman et al¹³ also tried to measure susceptibility using gradient-echo sampling of free induction decay and echo (GESFIDE) MR imaging¹⁸ to measure R2′, ie, that part of the transverse relaxation rate resulting from magnetic field inhomogeneities (R2` = R2* − R2, where R2* refers to the actual observed relaxation rate, and R2 refers to the relaxation rate intrinsic to the tissue). They found a correlation between R2` and iron concentration in the brain. However, they experienced problems with significant magnetic field distortions in the region of the sphenoid sinus and nasal cavity.     

Effects of the home environmental skill-building program on the caregiver-care recipient dyad: 6-month outcomes from the Philadelphia REACH Initiative

PURPOSE: We examine 6-month effects of the Environmental Skill-Building Program on caregiver well-being and care recipient functioning and whether effects vary by caregiver gender, race (White or non-White), and relationship (spouse or nonspouse). DESIGN AND METHODS: We enrolled 255 family caregivers of community-residing persons with Alzheimer's disease or related disorders, of whom 190 participated in a follow-up interview. Caregivers were randomized to a usual care control group or intervention group that received five home contacts and one telephone contact by occupational therapists, who provided education, problem-solving training, and adaptive equipment. Baseline and 6-month follow-up included self-report measures of caregiver objective and subjective burden, caregiver well-being, and care recipient problem behaviors and physical function. RESULTS: Compared with controls (n = 101), intervention caregivers (n = 89) reported less upset with memory-related behaviors, less need for assistance from others, and better affect. Intervention spouses reported less upset with disruptive behaviors; men reported spending less time in daily oversight; and women reported less need for help from others, better affect, and enhanced management ability, overall well-being, and mastery relative to control group counterparts. Statistically significant treatment differences were not found for hours helping with instrumental activities of daily living, upset with providing assistance with instrumental activities of daily living and activities of daily living, perceived change in somatic symptoms, White versus non-White caregivers, or care recipient outcomes. IMPLICATIONS: The Environmental Skill-Building Program reduces burden and enhances caregiver well-being in select domains and has added benefit for women and spouses.     

Structural and biologic characterization of pegylated recombinant IFN-alpha2b.

The type I interferon-alpha (IFN-alpha) family is a family of natural small proteins that have clinically important anti-infective and antitumor activity. We have developed a semisynthetic protein-polymer conjugate of IFN-alpha2b (Intron A) by attaching a 12,000-Da monomethoxypolyethylene glycol (PEG-12000) polymer to the protein. PEG conjugation is thought to increase the serum half-life and thereby prolong patient exposure to IFN-alpha2b without altering the biologic potency to the protein. Matrix-assisted laser desorption ionization/mass spectrometry (MALDI-MS), high-performance size exclusion chromatography (HPSEC), circular dichroism (CD) analysis and tryptic digestion peptide analysis of PEG Intron demonstrated that the IFN-alpha2b protein was approximately 95% monopegylated and that the primary, the secondary, and the tertiary structures were unaltered. Pegylation did not affect the epitope recognition of antibodies used for Intron A quantitation. An extensive analysis of the pegylated positional isomers revealed that approximately 50% of PEG Intron was monopegylated on the His(34) residue of the IFN-alpha2b protein. The highest antiviral activity of the pegylated positional isomers for PEG Intron was associated with the His(34) pegylated isomer. The specific activity for PEG Intron in an antiviral cytopathic protection assay was 28%, relative to Intron A. However, the potency of PEG Intron, defined as bioactivity independent of protein concentration, was comparable to Intron A at both the molecular and cellular levels in a battery of in vitro assays. Equivalent units of PEG Intron and Intron A were indistinguishable for the induction of several key IFN-induced genes, including 2',5'-oligoadenylate synthetase (2',5'-OAS) and protein kinase R (PKR), in Molt 4 cells. The antiviral dose-response curves revealed that there were no significant differences between PEG Intron and Intron A. This demonstrated that the introduction of more IFN-alpha2b protein associated with equivalent unit dosing of PEG Intron did not create any antagonism or agonism in the antiviral assay. In assays for the immune response, PEG Intron and Intron A displayed comparable potency for both natural-killer (NK) and lymphokine-activated killer (LAK) cell cytolytic activity and for the induction of class I major histocompatibility protein. These results demonstrate that PEG Intron maintains an in vitro biologic potency profile for both antiviral and immunotherapeutic activity that is highly comparable to that of Intron A.