Discontinuing prophylactic transfusions increases the risk of silent brain infarction in children with sickle cell disease: data from STOP II.

In the STOP II trial, discontinuation of prophylactic transfusions in high risk children with sickle cell disease (SCD) resulted in a high rate of reversion to abnormal blood-flow velocities on transcranial Doppler (TCD) ultrasonography and strokes. We analyzed data from STOP II to determine the effect of discontinuing transfusions on the development or progression of silent brain infarcts on magnetic resonance imaging (MRI). At study entry, 21 of 79 (27%) patients had evidence of silent infarcts. There were no statistically significant differences in baseline characteristics between patients with normal brain MRI or silent infarcts at study entry. At study end, 3 of 37 (8.1%) patients in the continued-transfusion group developed new brain MRI lesions compared with 11 of 40 (27.5%) in the transfusion-halted group (P = .03). The total number of lesions remained essentially unchanged decreasing from 25 to 24 in the continued-transfusion group while increasing from 27 to 45 in transfusion-halted patients. Thus, discontinuation of transfusions in children with SCD and abnormal TCD who revert to low-risk increases the risk of silent brain infarction. Together with data from STOP, these findings demonstrate that transfusions prevent the development of silent infarcts in patients with SCD and abnormal TCD but normal MRA.

Effect of transfusion therapy on transcranial Doppler ultrasonography velocities in children with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) and abnormal transcranial Doppler (TCD) ultrasonography have a high risk of stroke, but this risk is greatly reduced when chronic transfusion therapy is administered. The change in TCD velocities during chronic transfusion therapy and rate and frequency of normalization of TCD findings have not been studied extensively. PROCEDURES: Using data from children with SCD enrolled as potential subjects in the Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) trial, we characterized the change in TCD velocities on transfusion therapy and identified predictors of developing a normal TCD. RESULTS: Among 88 children with serial TCD data after starting transfusions for abnormal TCD 46 (52%) converted to normal TCD after a mean of 4.3 months (median 3.0; range 0.85-14.3 months) of transfusions. TCD studies remained abnormal in 19/88 (21.6%) after a mean of 2.4 years of transfusion. The median TCD velocity was lowered by 38 cm/sec within 3 months of initiating transfusions, followed by a more gradual decline then stabilization of velocities, although with significant individual variation. Factors associated with conversion to normal TCD included lower initial TCD velocity, younger age, and higher pre-transfusion hemoglobin level during transfusion therapy. CONCLUSION: Younger children with higher pre-transfusion hemoglobin levels and lower abnormal TCD velocities are most likely to have rapid normalization of TCD on transfusions. Long-term follow-up of children with persistently abnormal exams or worsening velocities on transfusion is needed to determine if these children are at higher risk of stroke.

Immune complexes containing modified lipoproteins are related to the progression of internal carotid intima-media thickness in patients with type 1 diabetes.

Modified lipoproteins induce autoimmune responses including the synthesis of autoantibodies with pro-inflammatory characteristics. Circulating modified lipoprotein autoantibodies combine with circulating antigens and form immune complexes (IC). We now report the results of a study investigating the role of circulating IC containing modified lipoproteins in the progression of carotid intima-media thickness (IMT) in patients enrolled in the Epidemiology of Diabetes Interventions and Complications (EDIC) Trial, a follow-up study of the Diabetes Control and Complications Trial (DCCT). This cohort includes 1229 patients with type 1 diabetes in whom B-mode ultrasonography of internal and common carotid arteries was performed in 1994-1996 and in 1998-2000. Conventional CHD risk factors, antibodies against modified forms of LDL and modified lipoprotein IC were determined in 1050 of these patients from blood collected in 1996-1998. Cholesterol and apolipoprotein B content of IC (surrogate markers of modified ApoB-rich lipoproteins) were significantly higher in patients who showed progression of the internal carotid IMT than in those showing no progression, regression or mild progression. Multivariate linear and logistic regression modeling using conventional and non-conventional risk factors showed that the cholesterol content of IC was a significant positive predictor of internal carotid IMT progression. In conclusion these data demonstrate that increased levels of modified ApoB-rich IC are associated with increased progression of internal carotid IMT in the DCCT/EDIC cohort of type 1 diabetes.

Continuation electroconvulsive therapy vs pharmacotherapy for relapse prevention in major depression: a multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE).

BACKGROUND: Although electroconvulsive therapy (ECT) has been shown to be extremely effective for the acute treatment of major depression, it has never been systematically assessed as a strategy for relapse prevention. OBJECTIVE: To evaluate the comparative efficacy of continuation ECT (C-ECT) and the combination of lithium carbonate plus nortriptyline hydrochloride (C-Pharm) in the prevention of depressive relapse. DESIGN: Multisite, randomized, parallel design, 6-month trial performed from 1997 to 2004. SETTING: Five academic medical centers and their outpatient psychiatry clinics. PATIENTS: Two hundred one patients with Structured Clinical Interview for DSM-IV-diagnosed unipolar depression who had remitted with a course of bilateral ECT. INTERVENTIONS: Random assignment to 2 treatment groups receiving either C-ECT (10 treatments) or C-Pharm for 6 months. MAIN OUTCOME MEASURE: Relapse of depression, compared between the C-ECT and C-Pharm groups. RESULTS: In the C-ECT group, 37.1% experienced disease relapse, 46.1% continued to have disease remission at the study end, and 16.8% dropped out of the study. In the C-Pharm group, 31.6% experienced disease relapse, 46.3% continued to have disease remission, and 22.1% dropped out of the study. Both Kaplan-Meier and Cox proportional hazards regression analyses indicated no statistically significant differences in overall survival curves and time to relapse for the groups. Mean +/- SD time to relapse for the C-ECT group was 9.1 +/- 7.0 weeks compared with 6.7 +/- 4.6 weeks for the C-Pharm group (P = .13). Both groups had relapse proportions significantly lower than a historical placebo control from a similarly designed study. CONCLUSIONS: Both C-ECT and C-Pharm were shown to be superior to a historical placebo control, but both had limited efficacy, with more than half of patients either experiencing disease relapse or dropping out of the study. Even more effective strategies for relapse prevention in mood disorders are urgently needed.

Therapist adherence and competence with manualized cognitive-behavioral therapy for PTSD delivered via videoconferencing technology.

Using secondary analyses from a randomized trial comparing the effectiveness of manualized cognitive-behavioral therapy for posttraumatic stress disorder, we compared ratings of therapist competency and adherence between two service delivery modes: telepsychiatry (TP) and same room (SR). Patients were 38 male treatment-seeking veterans recruited from a veterans affairs medical center. Domains of therapist competence and adherence included structuring sessions, implementing session activities, providing feedback, dealing with difficulties, developing rapport, and conveying empathy. Only one difference emerged between the two treatment conditions, with more favorable ratings on this item in the TP condition. Findings suggest that therapist competence and adherence to cognitive-behavioral therapy is similar whether the treatment is delivered via TP or by traditional means, and TP does not compromise therapists' ability to effectively structure sessions or build rapport with patients. These data further support the use of TP to address shortages in access to mental health care.

A randomized trial of telepsychiatry for post-traumatic stress disorder.

We compared the efficacy of telepsychiatry and same-room treatment of combat-related post-traumatic stress disorder (PTSD) using cognitive behavioural therapy in 14 weekly, 90-min treatment sessions. Of 97 patients referred for study participation, 38 were randomized (17 into telepsychiatry, 21 into same-room), and approximately 25 (the number differed by instrument) had at least one post-baseline assessment. Measures of clinical and process outcomes were examined. No group differences were found on clinical outcomes at three-month follow-up. Satisfaction with treatment ratings was similar in both groups, with 'strong satisfaction' indicated by veterans in both modalities. Attendance and drop-out were similar in the two groups. The same-room group reported more comfort in talking with their therapist at post-treatment and had better treatment adherence. The results provide preliminary support for the use of telepsychiatry in the treatment of PTSD to improve access to care.

Ischemic stroke subtypes and migraine with visual aura in the ARIC study.

OBJECTIVE: To investigate the association among migraine, ischemic stroke, and stroke subtypes in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: In this ongoing, prospective, longitudinal community-based cohort study, participants were given an interview ascertaining migraine history in 1993-1995, and were followed for all vascular events, including stroke. All stroke events over the subsequent 20 years were adjudicated and classified into stroke subtypes by standard definitions. Cox proportional hazards models adjusted for stroke risk factors were used to study the relationship between migraine and ischemic stroke, overall, as well as stroke subtypes (cardioembolic, lacunar, or thrombotic). RESULTS: We identified 1,622 migraineurs among 12,758 participants. Mean age of the study population at the 3rd clinical visit was 59 years. When compared to nonheadache participants, there was a significant association between migraine with visual aura and ischemic stroke (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.2-2.6, p = 0.008). Migraine without visual aura was not significantly associated with ischemic stroke (HR 1.2, CI 1.0-1.8, p = 0.28) when compared to nonheadache participants. Among the 3 subtypes of ischemic stroke evaluated, migraine with visual aura was significantly associated only with cardioembolic stroke (HR 3.7, 95% CI 1.6-8.7, p = 0.003). CONCLUSION: In participants with migraine with visual aura in late middle age, increased risk of cardioembolic stroke was observed. Migraine with visual aura was linked to increased stroke risk, while migraine without visual aura was not, over the period of 20 years. These results are specific to older migraineurs.

Patients' reports of traumatic or harmful experiences within the psychiatric setting.

OBJECTIVE: This study examined the frequency and associated distress of potentially traumatic or harmful experiences occurring within psychiatric settings among persons with severe mental illness who were served by a public-sector mental health system. METHODS: Participants were 142 randomly selected adult psychiatric patients who were recruited through a day hospital program. Participants completed a battery of self-report measures to assess traumatic and harmful events that occurred during the course of their mental health care, lifetime trauma exposure, and symptoms of posttraumatic stress disorder. RESULTS: Data revealed high rates of reported lifetime trauma that occurred within psychiatric settings, including physical assault (31 percent), sexual assault (8 percent), and witnessing traumatic events (63 percent). The reported rates of potentially harmful experiences, such as being around frightening or violent patients (54 percent), were also high. Finally, reported rates of institutional measures of last resort, such as seclusion (59 percent), restraint (34 percent), takedowns (29 percent), and handcuffed transport (65 percent), were also high. Having medications used as a threat or punishment, unwanted sexual advances in a psychiatric setting, inadequate privacy, and sexual assault by a staff member were associated with a history of exposure to sexual assault as an adult. CONCLUSIONS: Findings suggest that traumatic and harmful experiences within psychiatric settings warrant increased attention.

Relationship between somatization and remission with ECT.

Patients treated with electroconvulsive therapy (ECT) were divided into those with less severe depression and those with more severe depression. In the less severely depressed group, high somatic anxiety and hypochondriasis predicted a low likelihood of sustained remission with ECT. In the more severely depressed group, these traits were not predictive of ECT outcome.

Cognitive function, behavioral problems, and physical function in long-term care insurance beneficiaries with dementia in South Korea: comparison of home care and institutional care services.

OBJECTIVES: To examine, in beneficiaries with long-term care (LTC) insurance (LTCI) with dementia in Korea, changes in cognitive function, behavioral symptoms, and physical function over time in relation to LTCI service type and to determine the 2-year effects of service type on those health outcomes. DESIGN: Secondary analyses of the existing LTCI data set from 2008 to 2010. SETTING: South Korea. PARTICIPANTS: LTCI beneficiaries with dementia aged 65 and older (N=31,319). Participants were divided according to the service type that they were receiving home care (HC), institutional care (IC), and combined care (CC). MEASUREMENTS: A LTC approval checklist was used to determine the level of LTCI coverage of each participant and to assess cognitive function, behavioral symptoms, and physical function. Linear mixed models and multiple regression models were used. RESULTS: There were significant differences in cognitive function, behavioral symptoms, and physical function at baseline between individuals receiving the three service types (P<.001) and overall improvements in those outcomes over 2 years in the three groups (P<.001). After limiting the sample to those who had received LTCI services for the full 2 years (2008-2010) and adjusting for baseline characteristics, individuals receiving HC were more likely to have better cognitive and physical function than those receiving IC or CC but were likely to have more behavioral symptoms 2 years after the LTCI enrollment (P<.001). CONCLUSION: LTCI service type (HC, IC, CC) predicted cognitive function, behavioral symptoms, and physical function at 2-year follow-up in beneficiaries with dementia. Further research is necessary to examine the effect of LTC services on health outcomes in a longer observational cohort.

Increased methionine sulfoxide content of apoA-I in type 1 diabetes.

Cardiovascular disease is a major cause of morbidity and premature mortality in diabetes. HDL plays an important role in limiting vascular damage by removing cholesterol and cholesteryl ester hydroperoxides from oxidized low density lipoprotein and foam cells. Methionine (Met) residues in apolipoprotein A-I (apoA-I), the major apolipoprotein of HDL, reduce peroxides in HDL lipids, forming methionine sulfoxide [Met(O)]. We examined the extent and sites of Met(O) formation in apoA-I of HDL isolated from plasma of healthy control and type 1 diabetic subjects to assess apoA-I exposure to lipid peroxides and the status of oxidative stress in the vascular compartment in diabetes. Three tryptic peptides of apoA-I contain Met residues: Q(84)-M(86)-K(88), W(108)-M(112)-R(116), and L(144)-M(148)-R(149). These peptides and their Met(O) analogs were identified and quantified by mass spectrometry. Relative to controls, Met(O) formation was significantly increased at all three locations (Met(86), Met(112), and Met(148)) in diabetic patients. The increase in Met(O) in the diabetic group did not correlate with other biomarkers of oxidative stress, such as N(epsilon)-malondialdehyde-lysine or N(epsilon)-(carboxymethyl)lysine, in plasma or lipoproteins. The higher Met(O) content in apoA-I from diabetic patients is consistent with increased levels of lipid peroxidation products in plasma in diabetes. Using the methods developed here, future studies can address the relationship between Met(O) in apoA-I and the risk, development, or progression of the vascular complications of diabetes.

Are there racial differences in the experience of harmful or traumatic events within psychiatric settings?

The current study examined racial differences in the reported frequency and distress associated with potentially harmful or traumatic experiences occurring within psychiatric settings. One hundred and forty-two (109 African-American; 32 Caucasian) randomly selected adult consumers recruited from a community psychosocial day program completed a battery of self-report measures to assess experiences in the psychiatric setting, lifetime trauma exposure, PTSD severity, and were the subject of a chart review. A subset of participants (20%) also completed a qualitative interview exploring their perceptions of events occurring in psychiatric settings. Few racial differences were noted in the reported frequency or distress associated with particular events in the psychiatric setting. However, we found differential patterns of association between adverse psychiatric events and lifetime trauma history, and racial differences in diagnosis and medications prescribed by the mental health center. These racial differences merit further attention to better understand their meaning and to improve mental health services provided to both African-Americans and Caucasian public-sector psychiatric patients.