Unmet supportive care needs, anxiety and depression in haematology patients during watch-and-wait.

OBJECTIVE: There is growing evidence and awareness of the psychological impact of watch-and-wait in patients with indolent haematological malignancy. However, the need for supportive care is unknown. The aims of this study were to investigate prevalence of unmet needs, their psychological associates, and prevalence of anxiety and depressive symptomatology. METHODS: Adult patients with indolent haematological malignancy, during watch-and-wait (n = 122) were included in this cross-sectional single-centre study. Participants filled out questionnaires on anxiety (Generalised Anxiety Disorder), depression (Patient Health Questionnaire), coping (Acceptance and Action Questionnaire II), distress (distress thermometer), disease-specific quality of life (The European Organisation for Research and Treatment of Cancer quality of life questionnaire) and supportive care needs (Supportive care needs survey - Dutch short version). Multiple linear regression analyses were performed to identify patient-factors associated with unmet needs. RESULTS: The prevalence of anxiety and depressive symptomatology were both 7.3%. Unmet needs were reported by 35% (n = 43) of patients. After controlling for covariates, higher levels of distress (ß = 0.23, p = 0.05), depression (ß = 0.41, p = 0.001), poorer coping (ß = 0.35, p = 0.002) and younger age (ß = -0.16, p = 0.05) were independently associated with more supportive care needs. The highest unmet needs were reported in domain health system, information & patient support (mean = 23.6 ± 23.0) and psychological domain (mean = 18.7 ± 21.8). CONCLUSIONS: One third of indolent haematology patients during watch-and-wait report unmet supportive care needs. Screening for unmet needs and design of interventions is required. A joint approach focused on psychological care, especially on improving psychological flexibility, should be combined with promoting accessibility to health-services and optimising disease education.

Poor health status and distress in cardiac patients: the role of device therapy vs. underlying heart disease.

AIMS: Implantable cardioverter defibrillator (ICD) therapy, which includes the risk of shocks, is considered the primary culprit of reductions in patient reported outcomes (PROs; e.g. health status and distress), thereby negating the role of underlying disease severity. We examined the relative influence of living with an ICD vs. congestive heart failure (CHF) on PROs and compared (i) ICD patients without CHF (ICD only), (ii) CHF patients without an ICD (CHF-only), and (iii) CHF patients with an ICD (ICD + CHF). METHODS AND RESULTS: Separate cohorts of ICD and CHF patients (N = 435; 75% men) completed PROs at baseline, 6 and 12 months. Groups differed on physical health status only at baseline (F((2,415)) = 7.15, P = 0.001) and on anxiety at 12 months (F((2,415)) = 4.04, P = 0.01); ICD + CHF patients had the most impaired physical health status but the lowest anxiety level followed by the ICD only and CHF only patients. Congestive heart failure only patients had the most impaired mental health status and reported the highest level of anxiety as compared to the ICD only (P < 0.001) and ICD + CHF groups (P = 0.009), while the two latter groups did not differ. The effect sizes ranged from very small (0.03) to moderate-large (0.69). Groups did not differ in depression scores. CONCLUSION: Congestive heart failure patients reported worse PROs as compared to ICD patients, although the magnitude of the differences was relatively small. This suggests that the well being of patients is not necessarily negatively influenced by the implantation of an ICD, and that underlying heart disease may have at least an equal if not greater influence on PROs.

What is the use? Application of the short form (SF) questionnaires for the evaluation of treatment effects.

BACKGROUND: Health status has evolved as a clinical outcome measure that is of great interest in medical care. However, there is still debate about the appropriateness of scoring algorithms for the often used short form questionnaires. Therefore, our aim was to evaluate the consequences of the traditional scoring procedure based on orthogonal factor rotation for clinical applications by (a) re-evaluating the results of randomized controlled trials (RCTs) on the effectiveness of antidepressants in improving health status in cardiac patients and (b) comparing empirical evidence on depression and health status using orthogonal and oblique factor rotation (alternative scoring method) in a community sample and a heart failure (HF) sample. METHODS: This is a systematic literature review and cross-sectional analysis among 1,598 community sample participants and 282 HF patients. RESULTS: Orthogonal rotation artificially forces the mental component summary (MCS) and physical component summary (PCS) to be unrelated, which is illustrated in two of the three included RCTs. Two RCTs showed improvements in MCS, but no improvement in PCS over time. Cross-sectional analysis in the two datasets showed that employing the alternative scoring algorithm resulted in higher negative correlations of MCS and PCS with depression, and a gradual decline in MCS with each decile of decline in PCS. CONCLUSION: Our data showed that appropriate carefulness is needed when calculating and interpreting summary scores. The traditional scoring algorithm seems inappropriate to objectively evaluate the effects of interventions on both the MCS and the PCS. Awareness in the design and evaluation of interventions using these outcomes is warranted.

Symptoms of anxiety and cardiac hospitalizations at 12 months in patients with heart failure.

OBJECTIVE: Heart failure (HF) is a leading cause of hospitalization. Clinical and socio-demographic factors have been associated with cardiac admissions, but little is known about the role of anxiety. We examined whether symptoms of anxiety were associated with cardiac hospitalizations at 12 months in HF patients. METHODS: HF outpatients (N = 237) completed the Hospital Anxiety and Depression Scale (HADS) at baseline (i.e., inclusion into the study). A cutoff ≥8 was used to indicate probable clinical levels of anxiety and depression. At 12 months, a medical chart abstraction was performed to obtain information on cardiac hospitalizations. RESULTS: The prevalence of symptoms of anxiety was 24.9% (59/237), and 27.0% (64/237) of patients were admitted for cardiac reasons at least once during the 12-month follow-up period. Symptoms of anxiety were neither significantly associated with cardiac hospitalizations in univariable logistic analysis [OR = 1.13, 95% CI (0.59-2.17), p = 0.72] nor in multivariable analysis [OR = 0.94, 95% CI (0.38-2.31), p = 0.89]. New York Heart Association (NYHA) functional class III [OR = 3.00, 95% CI (1.08-8.12), p = 0.04] and a history of HF-related hospitalizations [OR = 1.18, 95% CI (1.01-1.38), p = 0.03] were independently associated with 12-month cardiac admissions. CONCLUSIONS: The current study found no significant association between symptoms of anxiety and cardiac hospitalizations at 12 months in HF patients. In contrast, clinical indicators (i.e., NYHA class III and a history of HF-related hospitalizations) were significantly associated with admissions due to a cardiac cause. Future studies are warranted to investigate the importance of symptoms of anxiety in HF using a larger sample size and a longer follow-up duration.

Type D personality and course of health status over 18 months in outpatients with heart failure: multiple mediating inflammatory biomarkers.

BACKGROUND: The distressed (Type D) personality is associated with poor health status (HS) and increased inflammatory activation in heart failure (HF). We tested whether multiple inflammatory biomarkers mediated the association between Type D personality and the course of self-reported HS over 18 months. METHODS: HF outpatients (n=228, 80% male, mean age 67.0±8.7 years), filled out the Type D questionnaire (DS14) at inclusion and the Short Form-12 (SF12) and the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 0, 6, 12, and 18 months. Blood samples at inclusion were analyzed for high sensitive C-reactive protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and its soluble receptors (sTNFr1, sTNFr2). A multiple mediation latent growth model was tested using structural equation modeling. RESULTS: Type D personality (prevalence=21%) was associated with poorer HS (all scales p<0.001), deterioration of mental HS (p<0.001), and higher TNF-α and sTNFr2 levels in the full mediation model. A higher inflammatory burden was associated with a poorer baseline level and a deterioration of generic physical, mental and disease-specific HS. No mediating effects were found for the multiple inflammatory biomarkers on the association between Type D and baseline self-reported HS, whereas change in physical HS was significantly mediated by the group of five inflammatory biomarkers (p=0.026). CONCLUSIONS: Only the association between Type D personality and change in self-reported physical health status was significantly mediated by inflammatory biomarkers. Future research should investigate whether the association between Type D personality and poor health status may be explained by other biological or behavioral factors.

Anhedonia is associated with poor health status and more somatic and cognitive symptoms in patients with coronary artery disease.

PURPOSE: The effectiveness of cardiac rehabilitation (CR) in patients with coronary artery disease (CAD) is moderated by negative emotions and clinical factors, but no studies evaluated the role of positive emotions. This study examined whether anhedonia (i.e. the lack of positive affect) moderated the effectiveness of CR on health status and somatic and cognitive symptoms. METHODS: CAD patients (n = 368) filled out the Hospital Anxiety and Depression Scale (HADS) to assess anhedonia at the start of CR, and the Short-Form Health Survey (SF-36) and the Health Complaints Scale (HCS) at the start of CR and at 3 months to assess health status and somatic and cognitive symptoms, respectively. RESULTS: Adjusting for clinical and demographic factors, health status improved significantly during the follow-up (F(1,357) = 10.84, P = .001). Anhedonic patients reported poorer health status compared with non-anhedonic patients, with anhedonia exerting a stable effect over time (F(1,358) = 34.80, P < .001). Somatic and cognitive symptoms decreased over time (F(1,358) = 3.85, P = .05). Anhedonics experienced more benefits in terms of somatic and cognitive symptoms over time (F(1,358) = 13.00, P < .001). CONCLUSION: Anhedonic patients reported poorer health status and higher levels of somatic and cognitive symptoms prior to and after CR. Somatic and cognitive symptoms differed as a function of anhedonia over time, but health status did not. Anhedonia might provide a new avenue for secondary prevention in CAD.

Impact of peripheral arterial disease on health status: a comparison with chronic heart failure.

OBJECTIVE: To further document the experienced burden in patients with peripheral arterial disease (PAD), we compared the health status of patients with PAD and chronic heart failure (CHF). As a secondary aim, we studied clinical and socio-demographic correlates of health status in both conditions. METHODS: We conducted a cross-sectional observational study in four outpatient clinics in the Southern part of The Netherlands, with subjects consisting of ambulatory (346 PAD and 188 CHF) patients. All patients completed the Short-Form 12 to assess their physical and mental health status. Information about socio-demographic, clinical risk factors, and disease severity indices was obtained from patients' medical records. Propensity methodology was applied to enhance comparability between both medical conditions. RESULTS: Type of medical condition explained differences in health status (F = 33.1, P < .0001, Effect Size = 0.27). Impaired physical health status was more often reported in PAD patients (48.4%) compared with CHF patients (17.4%, Odds Ratio [OR] = 4.4, 95% Confidence Interval [CI] 2.3-8.8, P < .0001); impaired mental health status was more noted in CHF patients (43.5% vs. 22.0%, OR = 1.7, 95% CI 1.2-2.6, P = .002). In PAD, younger age (P = .002), low education (P = .02), cardiac history (P = .02), diabetes mellitus (P = .03), and a lower ankle brachial index (P = .003) were associated with worse physical health status; younger age (P = .01) and living without partner (P = .01) were associated with lower mental health status scores. In CHF, patients with comorbid diabetes mellitus (P < .001) and females (P = .001) reported worse physical health, whereas no clinical or socio-demographics were associated with mental health status. CONCLUSIONS: By contrasting PAD patients' health status with another chronic disabling condition, the impact of PAD on patients' physical health status became evident; whereas mental health status was more affected in CHF, patients with PAD reported a greater physical burden as compared with CHF patients. PAD patients who were younger, lower-educated, without a partner or had a cardiac history especially reported a higher disease burden. Clinicians need to be aware of these differences in order to develop tailor-made disease management programs for different groups of cardiovascular patients.

Overlap and distinctiveness of psychological risk factors in patients with ischemic heart disease and chronic heart failure: are we there yet?

OBJECTIVE: Growing evidence supports the importance of psychological factors in the etiology and progression of cardiovascular disease (CVD). However, this research has been criticized due to overlap between psychological constructs. We examined whether psychological questionnaires frequently used in cardiovascular research assess distinct constructs in a mixed group of ischemic heart disease (IHD) and chronic heart failure (CHF) patients. METHODS: 565 patients with CHF (n=118) or IHD (n=447) completed the Type D scale (DS14), Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI), and State Trait Anxiety Inventory (STAI). Pearson product moment correlations were computed to determine the interrelatedness between psychological constructs. Principal component analyses (PCA) were conducted on both scale scores and items to determine higher-order constructs and distinctiveness of psychological questionnaires. RESULTS: Two higher-order constructs were identified, namely negative affect and social inhibition. PCA on all 69 items showed that anxiety, depression, negative affectivity, and social inhibition were distinct constructs. The original structure of the DS14 was confirmed, whereas items of the HADS and BDI loaded more diffusely; items of the STAI reflected two different components. CONCLUSION: The use of multiple questionnaires in cardiac patients is justified, as the higher order construct negative affect comprised different facets. Social inhibition was also shown to be a distinct construct, indicating that it may timely for cardiovascular research to look at the role of inhibition in addition to negative emotions. Future studies are warranted to determine whether these findings are replicable in other cardiac samples and to specify the unique prognostic value of these psychological facets.

Health-related quality of life following vertical banded gastroplasty.

BACKGROUND: Morbid obesity is associated with increased risks of morbidity and mortality as well as poor quality of life (QoL). Therefore, the goal of bariatric surgery should not only be reducing weight and treatment of comorbid conditions, but also improving QoL. Moreover, enhanced QoL may motivate patients to adhere to adequate health behavior in order to maintain the surgically established weight loss. METHODS: We evaluated early postoperative health-related quality of life (HRQoL) over time. Preoperatively as well as 6, 12, and 24 months after vertical banded gastroplasty (VBG), 107 patients were psychologically assessed using a semistructured interview and the RAND 36-item Health Survey (RAND-36). RESULTS: Over time, we found significant changes in weight: 2 years after surgery, excess weight loss (EWL) was 58.4%. HRQoL showed significant improvements over time, especially in the physical domains. Two years after surgery, 74% of patients were satisfied with the results of the operation and 94.1% would opt for surgery again. CONCLUSIONS: VBG not only leads to considerable weight loss, but also to significant improvements in HRQoL. However, some of the initially reported improvements lessened over time and not all patients appeared to profit in the same way.

Beyond Type D personality: reduced positive affect (anhedonia) predicts impaired health status in chronic heart failure.

OBJECTIVE: Type D personality has been associated with impaired health status in chronic heart failure (CHF), but other psychological factors may also be important. AIM: To determine whether non-Type D patients with low positive affect and Type D patients report lower health status, compared with non-Type D patients with high positive affect at 12-month follow-up in chronic heart failure. METHODS: Consecutive CHF outpatients (n = 276) filled out the Short Form-12 (health status) and Health Complaints Scale (disease-specific complaints) at inclusion and 12-month follow-up, and the DS14 (Type D personality) and positive affect (Global Mood Scale) at inclusion. Three groups were composed: non-Type D patients without anhedonia, non-Type D patients with anhedonia, and Type D patients. RESULTS: After controlling for demographic and clinical confounders, and scores at inclusion, anhedonic non-Type D patients reported lower mental health status (beta = -.19, P < .004), and more feelings of disability (beta = .10, P = .04), marginally lower physical health status (beta = -.11, P = .07), and equal levels of cardiac symptoms (beta = .04, P = .43), when compared with non-Type D's without anhedonia. Type D patients reported lower levels of impaired mental health status, more cardiac symptoms and feelings of disability (-.31 < beta < .17, all Ps < .05). A trend was shown for physical health status (beta = -.11, P = .09). CONCLUSION: Non-Type D patients low on positive affect and Type D patients report lower levels of health status in CHF, compared with non-Type D patients with high positive affect. Future studies need to determine whether lack of positive affect is associated with impaired clinical outcome.

Psychological predictors of prognosis in chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is an increasingly prevalent condition with high mortality and morbidity rates. This review examines the role of depression, anxiety, and social support on prognosis in CHF. METHOD AND RESULTS: Prospective studies that examined mortality as an outcome, and assessed depression, anxiety, or social support as associates were included. Methodological qualities were evaluated. In total, 25 studies were identified. Concerning depression, 6 of 15 studies of inpatients, 10 of 11 studies of outpatients, and 1 study of a mixed sample found associations between depression and prognosis, with greater associations rendered by depressive symptomatology in outpatients. Anxiety was not associated with prognosis in one inpatient study and one outpatient study. There was a univariable trend in one outpatient study for anxiety to be associated with prognosis. In two of six studies of inpatients and in two of four studies of outpatients, social support was associated with prognosis. On the basis of methodological quality, studies on depression showed mixed results, no conclusions could be drawn for anxiety because this association was not investigated soundly, and the quality of the social network was not associated with outcome. CONCLUSION: Evidence suggests that depressive symptoms and social support might be associated with prognosis in CHF outpatients, independently of biomedical risk factors. With respect to anxiety, no conclusions can be drawn. Future studies are warranted to disentangle associations with psychological factors.

Psychosocial functioning, personality, and body image following vertical banded gastroplasty.

BACKGROUND: In addition to increased risks of morbidity and mortality, extreme obesity is substantially associated with psychosocial problems. Therefore, the ultimate goal of bariatric surgery should not only be reducing weight and counteracting comorbid conditions but also improving psychosocial functioning. In addition to being an important goal of bariatric surgery, enhanced psychosocial functioning may motivate patients to adhere to adequate health behavior to maintain the surgically established weight loss. METHODS: We evaluated early postoperative psychosocial functioning in several domains over time. Preoperatively as well as 6, 12, and 24 months after vertical banded gastroplasty, 104 patients were psychologically assessed using a semi-structured interview and psychological questionnaires focusing on psychosocial functioning, personality, and body image. RESULTS: Over time, we found significant changes in weight: 2 years excess weight loss was 58.6%. In addition, most aspects of psychosocial functioning showed significant improvements over time. However, initial improvements in depressive symptoms, sleeping problems, and neuroticism did not last. With respect to personality features, only short-term changes in self-esteem were found. The most robust improvements were seen in the case of body image. Finally, within the patient group, there was a wide variability in changes. CONCLUSION: Vertical banded gastroplasty not only leads to considerable weight loss but also to significant improvements in psychosocial functioning. However, some improvements waned over time, and successful postoperative functioning did not apply to all patients.

Type D patients report poorer health status prior to and after cardiac rehabilitation compared to non-type D patients.

BACKGROUND: Type D personality is an emerging risk factor in coronary artery disease (CAD). Cardiac rehabilitation (CR) improves outcomes, but little is known about the effects of CR on Type D patients. PURPOSE: We examined (1) variability in Type D caseness following CR, (2) Type D as a determinant of health status, and (3) the clinical relevance of Type D as a determinant of health status compared to cardiac history. METHODS: CAD patients (n = 368) participating in CR completed the Type D Scale, the Short-Form Health Survey 36 pre- and post-CR, and the Hospital Anxiety and Depression Scale pre-CR, to assess health status and depressive and anxious symptomatology, respectively. RESULTS: The prevalence of Type D decreased from 26.6% to 20.7% (p = 0.012) following CR, but Type D caseness remained stable in 81% of patients. Health status significantly improved following CR [F(1,359) = 17.48, p < 0.001], adjusting for demographic and clinical factors and anxious and depressive symptoms. Type D patients reported poorer health status [F(1,359) = 10.40, p = 0.001], with the effect of Type D being stable over time [F(1,359) = 0.49, p = 0.48]. Patients with a cardiac history benefited less from CR [F(1,359) = 5.76, p = 0.02]. The influence of Type D on health status was larger compared to that for cardiac history, as indicated by Cohen's effect size index. CONCLUSIONS: Type D patients reported poorer health status compared to non-Type D patients pre- and post-CR. In the majority of patients, CR did not change Type D caseness, with Type D being associated with a stable and clinically relevant effect on outcome. These high-risk patients should be identified in clinical practice and may require adjunctive interventions.

Weight loss and eating behavior following vertical banded gastroplasty.

BACKGROUND: Bariatric surgery is the treatment of choice for patients with morbid obesity. In addition to surgery, postoperative dietary behavior is an important mediator of weight loss and, therefore, critical in influencing outcome. Surgical treatment of obesity is not an alternative to dieting but a method to enforce dieting. METHODS: We evaluated early weight loss and postoperative eating behavior over time. Preoperatively as well as 6 months, 1 and 2 years after vertical banded gastroplasty (VBG), 91 patients were psychologically assessed using a semi-structured interview and a psychological questionnaire focusing on eating behavior. RESULTS: Over time, we found significant changes in weight, mostly in the 1st postoperative year (EWL= 52.0%); at 2 years, EWL was 61.5%. Patients reported substantial changes in feelings of hunger, appetite, satiety, and eating behavior; however, most improvements waned over time. In addition, there was a wide variability in changes within our patient group, and changes in weight loss appeared to be related to changes in restrained eating. CONCLUSION: VBG not only leads to considerable weight loss, but also to significant improvements in eating behavior, at least within 2 years. However, most improvements wane over time and not all patients profit in the same way.

Symptoms of fatigue in chronic heart failure patients: clinical and psychological predictors.

OBJECTIVE: To examine the role of clinical and psychological characteristics as predictors of fatigue in CHF. BACKGROUND: Little is known about predictors of fatigue in CHF. Next to heart failure characteristics, depressive symptoms and type-D personality may explain individual differences in fatigue. METHODS: At baseline, 136 CHF outpatients (age

Psychosocial functioning following bariatric surgery.

Morbid obesity is associated with an increased risk of morbidity and mortality as well as psychosocial problems and poor quality of life. The ultimate goal of bariatric surgery is not only reduced weight and reduction of co-morbidities, but also improved psychosocial functioning and quality of life. However, not all patients are successful. A systematic literature search of recent articles identified relevant variables reflecting postoperative psychosocial functioning. Most studies showed that bariatric surgery does not only lead to substantial weight reduction, but also to improvement or cure of physical as well as psychological co-morbidities. Although most studies are optimistic and report broad psychosocial improvement, a significant minority of patients do not benefit psychologically from surgery. Although there are mixed results, the overall improvements in psychosocial functioning provide additional justification for surgical treatment of morbid obesity.

Positive affect, anhedonia, and compliance with self-care in patients with chronic heart failure.

OBJECTIVE: Optimal self-care is crucial in patients with chronic heart failure (HF). While the focus of research has been on negative mood states, adequate psychological resources may be required to successfully engage in HF self-care. Therefore, the longitudinal associations of multiple positive affect measures in explaining HF self-care including consulting behavior were examined while adjusting for depressive symptoms and potential covariates (e.g., disease severity). METHODS: In this prospective cohort study, 238 patients (mean age: 66.9 ± 8.6 years, 78% men), with chronic HF completed questionnaires at baseline and 1-year follow-up. Positive affect was assessed with the Positive and Negative Affect Schedule (PANAS) and the Global Mood Scale (GMS). Anhedonia, i.e. diminished interest or pleasure, was assessed with a subscale of the Hospital Anxiety and Depression Scale (HADS). The 9-item European Heart Failure Self-care Behaviour scale was completed to assess HF self-care including consultation behavior. RESULTS: Linear mixed modeling results showed that anhedonia was most strongly associated with both poor self-care (estimate=-.72, P<.001) and consulting behavior (estimate=-.44, P<.001) over time, after adjustment for covariates and depressive symptoms. GMS positive affect was related to better HF self-care adjusting for standard depressive symptoms but not when adjusting for anhedonia. PANAS positive affect was not independently related to self-care. CONCLUSION: Anhedonia was associated with worse compliance with self-care among chronic HF patients over time, irrespective of disease severity and depression. Associations between positive affect and self-care were dependent on the measures used in multivariable analyses.

Depressive symptoms in outpatients with heart failure: importance of inflammatory biomarkers, disease severity and personality.

OBJECTIVE: Depressive symptoms are highly prevalent in heart failure (HF) patients, however the underlying etiology of depression in HF patients remains yet unclear. Hence, the goal is to examine the relative importance of inflammation, disease severity and personality as predictors of depression in HF patients. DESIGN: Depressive symptoms (Hospital Anxiety and Depression Scale, depression subscale) were assessed at baseline and one-year follow-up in 268 HF patients (75.6% men; mean age = 66.7 ± 8.7). Markers of inflammation (TNFα, sTNFr1, sTNFr2, IL-6 and IL-10), disease severity (e.g. New York Heart Association (NYHA) classification) and personality (Type D personality, loneliness) were assessed at baseline. RESULTS: At baseline, NYHA class, body mass index, educational level, Type D personality and loneliness were significantly associated with depression. Higher NYHA class (B = 2.25; SE = .83), higher educational level (B = 1.41; SE = .48), Type D personality (B = 2.56; SE = .60) and loneliness (B = .19; SE = .05) were also independently associated with higher depression levels at one-year follow-up (all p-values < .005). Inflammation, brain natriuretic peptide and left ventricular ejection fraction were not related to depression over time. CONCLUSIONS: Personality factors, but not inflammation, were independent concomitants of depressive symptoms in patients with HF. Gaining more insight into the etiology of depression in HF patients is important in order to identify potential targets for novel interventions.

Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Macrolide resistance is an increasing problem; there is therefore debate about when to implement maintenance treatment with macrolides in patients with chronic obstructive pulmonary disease (COPD). We aimed to investigate whether patients with COPD who had received treatment for three or more exacerbations in the previous year would have a decrease in exacerbation rate when maintenance treatment with azithromycin was added to standard care. METHODS: We did a randomised, double-blind, placebo-controlled, single-centre trial in The Netherlands between May 19, 2010, and June 18, 2013. Patients (≥18 years) with a diagnosis of COPD who had received treatment for three or more exacerbations in the previous year were randomly assigned, via a computer-generated randomisation sequence with permuted block sizes of ten, to receive 500 mg azithromycin or placebo three times a week for 12 months. Randomisation was stratified by use of long-term, low-dose prednisolone (≤10 mg daily). Patients and investigators were masked to group allocation. The primary endpoint was rate of exacerbations of COPD in the year of treatment. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00985244. FINDINGS: We randomly assigned 92 patients to the azithromycin group (n=47) or the placebo group (n=45), of whom 41 (87%) versus 36 (80%) completed the study. We recorded 84 exacerbations in patients in the azithromycin group compared with 129 in those in the placebo group. The unadjusted exacerbation rate per patient per year was 1·94 (95% CI 1·50-2·52) for the azithromycin group and 3·22 (2·62-3·97) for the placebo group. After adjustment, azithromycin resulted in a significant reduction in the exacerbation rate versus placebo (0·58, 95% CI 0·42-0·79; p=0·001). Three (6%) patients in the azithromycin group reported serious adverse events compared with five (11%) in the placebo group. During follow-up, the most common adverse event was diarrhoea in the azithromycin group (nine [19%] patients vs one [2%] in the placebo group; p=0·015). INTERPRETATION: Maintenance treatment with azithromycin significantly decreased the exacerbation rate compared with placebo and should therefore be considered for use in patients with COPD who have the frequent exacerbator phenotype and are refractory to standard care. FUNDING: SoLong Trust.