Effect of moderate or intensive disease management program on outcome in patients with heart failure: Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH)

BACKGROUND: Heart failure (HF) disease management programs are widely implemented, but data about their effect on outcome have been inconsistent. METHODS: The Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH) was a multicenter, randomized, controlled trial in which 1023 patients were enrolled after hospitalization because of HF. Patients were assigned to 1 of 3 groups: a control group (follow-up by a cardiologist) and 2 intervention groups with additional basic or intensive support by a nurse specializing in management of patients with HF. Patients were studied for 18 months. Primary end points were time to death or rehospitalization because of HF and the number of days lost to death or hospitalization. RESULTS: Mean patient age was 71 years; 38% were women; and 50% of patients had mild HF and 50% had moderate to severe HF. During the study, 411 patients (40%) were readmitted because of HF or died from any cause: 42% in the control group, and 41% and 38% in the basic and intensive support groups, respectively (hazard ratio, 0.96 and 0.93, respectively; P = .73 and P = .52, respectively). The number of days lost to death or hospitalization was 39 960 in the control group, 33 731 days for the basic intervention group (P = .81), and 34 268 for the intensive support group (P = .49). All-cause mortality occurred in 29% of patients in the control group, and there was a trend toward lower mortality in the intervention groups combined (hazard ratio, 0.85; 95% confidence interval, 0.66-1.08; P = .18). There were slightly more hospitalizations in the 2 intervention groups (basic intervention group, P = .89; and intensive support group, P = .60). CONCLUSIONS: Neither moderate nor intensive disease management by a nurse specializing in management of patients with HF reduced the combined end points of death and hospitalization because of HF compared with standard follow-up. There was a nonsignificant, potentially relevant reduction in mortality, accompanied by a slight increase in the number of short hospitalizations in both intervention groups. Clinical Trial Registry http://trialregister.nl Identifier: NCT 98675639.     

For better and for worse: Quality of life impaired in HF patients as well as in their partners.

BACKGROUND: Quality of Life (QOL) is known to be impaired in patients with Heart Failure (HF). The involvement of a key person, most often the spouse, enables the HF patient to manage the medical regimen and therefore to sustain Quality of Life (QOL). Yet little is known on the impact of caring for an HF patient on the QOL of the caregiving partner. This study aims to explore the QOL of partners of HF patients compared to the QOL of the patients. METHODS: The study population consisted of 38 couples of hospitalized HF patients and their partners. The Cantril Ladder of Life was used to rate QOL during hospitalization, with regard to the month prior to hospitalization and as projected 3 years in the future. Demographic and clinical variables were collected by patient interview and chart review. RESULTS: On a scale from 0-10, QOL scores of partners varied from 5.9 to 6.4. At some point the QOL score of partners was even lower than the QOL scores of HF patients. In the month prior to hospital admission the QOL of partners was significantly higher in comparison to the QOL of HF patients (6.1 vs. 4.9, respectively). However, this reversed during hospital admission, with QOL scores of partners being significantly lower compared to QOL scores of HF patients (5.9 vs. 6.8, respectively), even after correcting for age and gender. CONCLUSION: In our study the QOL of partners of HF patients was low. Whether this is explicitly due to having to live with a HF patient is not clear. Further research on what partners actually do and the relationship between being a caregiver and QOL is necessary in order to support these partners in giving optimal care and support.     

Brain Activation During Emotional Memory Processing Associated with Subsequent Course of Depression

Major depressive disorder (MDD) is characterized by a heterogeneous course and identifying patients at risk for an unfavorable course is difficult. Neuroimaging studies may identify brain predictors of clinical course and may help to further unravel the neurobiological processes underlying an unfavorable course. We investigated whether brain activation during an emotional memory paradigm is associated with depressive course. To this end, we followed 74 MDD patients and 45 healthy controls (HCs) for 2 years. At baseline, participants performed an emotional word-encoding and -recognition task during functional magnetic resonance imaging. Activation patterns were compared between patients with fast remission (n=22), remission with recurrence (n=23), non-remission (n=29), and HCs. Additionally, linear relations of brain activation and time to remission during the follow-up period were investigated across patients. We observed that during encoding of negative words, non-remitters showed higher activation of the left insula than HCs. Groups also differed in activation of the right hippocampus and left amygdala during negative encoding, with a trend for higher activation in non-remitters compared with HCs. Furthermore, hippocampal activation during negative word encoding was significantly and positively correlated with time to remission, irrespective of illness severity. Our findings suggest that higher activation in the left insula could serve as a neural marker of a naturalistic non-remitting course, whereas higher hippocampal activation is associated with delayed remission. Longitudinal analyses should clarify whether abnormal activation progresses further as a function of time with depression or may serve as load-independent markers of MDD course.     

氯化钐、氯化镨对大鼠肝脏形态及LPO、SOD活性的影响

本实验采用不同途径给予断乳Ｗｉｓｔａｒ大鼠小剂量（０．０５ｍｇ／ｋｇ、０．０２５ｍｇ／ｋｇ）氯化角钐（ＳｍＣｌ３）、氯化镨（ＰｒＣｌ３）后，测定了肝脏中过氧化脂质（ＬＰＯ）和超氧化物歧化酶（ＳＯＤ）的含量，观察了肝脏的超微结构。结果表明：ＳｍＣｌ３和ＰｒＣｌ３均使肝脏中ＬＰＯ活性降低、ＳＯＤ活性升高，二者比较ＰｒＣｌ３的作用更为明显，肝脏未见明显形态学改变。     

A benefit of spinal manipulation as adjunctive therapy for acute low-back pain: a stratified controlled trial

Fifty-four subjects volunteered to participate in a controlled study contrasting spinal manipulation with spinal mobilization without the rotational forces and leverage required to move facet joints. All suffered from regional low-back pain for less than 1 month, were ages 18-40, had never previously undergone any form of spinal manipulation, and denied a prior episode of backache within the previous 6 months. Randomization was stratified at outset into those who suffered for less than 2 weeks and those whose discomfort had persisted for 2-4 weeks. Outcome was monitored by a questionnaire assessing functional impairment. A treatment effect of manipulation was demonstrated only in the strata with more prolonged illness at entry. In the first week following manipulation, these patients improved to a greater degree (P = .009, t test) and more rapidly (P less than .025, Wilcoxon rank-sum test).     

Analysis of interrupted time series mortality trends: an example to evaluate regionalized perinatal care.

Interrupted time series designs are frequently employed to evaluate program impact. Analysis strategies to determine if shifts have occurred are not well known. The case where statistical fluctuations (errors) may be assumed independent is considered, and a segmented regression methodology presented. The method discussed ia applied to the assessment of changes in local and state perinatal postneonatal mortality to identify historical trends and will be used to evaluate the impact of the North Carolina Regionalized Perinatal Care Program when seven years of post-program mortality data become available. The perinatal program region is contrasted with a control region to provide a basis for interpretation of differences noted. Relevant segmented regression models provided good fits to the data and highlighted mortality trends over the last 30 years. Considerable racial differences in these trends were identified, particularly for postneonatal mortality. Segmented regression is considered relevant for the analysis of interrupted time series designs in other applications when errors can be taken to be independent. Thus, the methodology may be regarded as a general statistical tool for evaluation purposes.     

Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam

The Observer's Assessment of Alertness/Sedation (OAA/S) Scale was developed to measure the level of alertness in subjects who are sedated. This scale was tested in 18 subjects in a three-period crossover study to assess its reliability and its criterion, behavioral, and construct validity. After receiving either placebo or a titrated dose of midazolam to produce light or heavy sedation, each subject was administered two sedation scales (OAA/S Scale and a Visual Analogue Scale) and two performances tests (Digit Symbol Substitution Test and Serial Sevens Subtraction). Two raters individually evaluated the subject's level of alertness on each of the two sedation scales. The results obtained on the OAA/S Scale were reliable and valid as measured by high correlations between the two raters and high correlations between the OAA/S Scale and two of the three standard tests used in this study. The OAA/S Scale was sensitive to the level of midazolam administered; all pairwise comparisons were significant (p less than 0.05) for all three treatment levels at both test periods.     

Serotonergic mechanisms in addiction-related memories

Drug-associated memories are a hallmark of addiction and a contributing factor in the continued use and relapse to drugs of abuse. Repeated association of drugs of abuse with conditioned stimuli leads to long-lasting behavioral responses that reflect reward-controlled learning and participate in the establishment of addiction. A greater understanding of the mechanisms underlying the formation and retrieval of drug-associated memories may shed light on potential therapeutic approaches to effectively intervene with drug use-associated memory. There is evidence to support the involvement of serotonin (5-HT) neurotransmission in learning and memory formation through the families of the 5-HT(1) receptor (5-HT(1)R) and 5-HT(2)R which have also been shown to play a modulatory role in the behavioral effects induced by many psychostimulants. While there is a paucity of studies examining the effects of selective 5-HT(1A)R ligands, the available dataset suggests that 5-HT(1B)R agonists may inhibit retrieval of cocaine-associated memories. The 5-HT(2A)R and 5-HT(2C)R appear to be integral in the strong conditioned associations made between cocaine and environmental cues with 5-HT(2A)R antagonists and 5-HT(2C)R agonists possessing potency in blocking retrieval of cocaine-associated memories following cocaine self-administration procedures. The complex anatomical connectivity between 5-HT neurons and other neuronal phenotypes in limbic-corticostriatal brain structures, the heterogeneity of 5-HT receptors (5-HT(X)R) and the conflicting results of behavioral experiments which employ non-specific 5-HT(X)R ligands contribute to the complexity of interpreting the involvement of 5-HT systems in addictive-related memory processes. This review briefly traces the history of 5-HT involvement in retrieval of drug-cue associations and future targets of serotonergic manipulation that may reduce the impact that drug cues have on addictive behavior and relapse.