Disease management for co-morbid depression and anxiety in diabetes mellitus: design of a randomised controlled trial in primary care

BACKGROUND: Depression and anxiety are common co-morbid health problems in patients with type 2 diabetes. Both depression and anxiety are associated with poor glycaemic control and increased risk of poor vascular outcomes and higher mortality rates. Results of previous studies have shown that in clinical practice, treatment of depression and anxiety is far from optimal as these symptoms are frequently overlooked and undertreated. METHODS/DESIGN: This randomised controlled trial will examine the effectiveness of a disease management programme treating symptoms of depression and anxiety in primary care patients with Type 2 diabetes. Patients will be randomized on patient level in 1:1 ratio. Random block sizes of 2 and 4 are used. The disease management programme consists of screening, stepped treatment and monitoring of symptoms (n = 80). This will be compared to care as usual (n = 80). DISCUSSION: The disease management model for co-morbid depression and anxiety in primary care patients with diabetes is expected to result in reduced symptoms of depression and anxiety, improved quality of life, reduced diabetes specific distress and improved glyceamic control, compared to care as usual. TRIAL REGISTRATION: Dutch Trial Register NTR262

2,2′-[4,10-Bis(carb­oxy­meth­yl)-4,10-diaza-1,7-diazo­niacyclo­dodecane-1,7-di­yl]diacetate dihydrate

In the title compound, C16H28N4O8·2H2O, the 12-membered macrocycle has twofold crystallographic symmetry and the asymmetric unit comprises one half-mol­ecule. The four carbox­yl/carboxyl­ate groups reside on the same side of the macrocycle. The mol­ecule is a double zwitterion with two of the carb­oxy­lic acid H atoms transferred to the two N atoms on the opposite sides of the macrocycle, resulting in both N atoms having positive charges and leaving the two resulting carboxyl­ate groups with negative charges. The two remaining carb­oxy­lic acid groups and the carboxyl­ate groups form O—H⋯O hydrogen bonds with the crystal water mol­ecules. The H atoms bound to the N atoms within the macrocyle are engaged in two equivalent hydrogen bonds with the adjacent N atoms

Internet-based cognitive behavioural therapy for subthreshold depression in people over 50 years old:a randomized controlled clinical trial

Background. Subthreshold depression is a highly prevalent condition and a risk factor for developing a major depressive episode. Internet-based cognitive behaviour therapy may be a promising approach for the treatment of subthreshold depression. The current study had two aims: (1) to determine whether an internet-based cognitive behaviour therapy intervention and a group cognitive behaviour therapy intervention are more effective than a waiting-list control group; and (2) to determine whether the effect of the internet-based cognitive behaviour therapy differs from the group cognitive behaviour therapy intervention. Method. A total of 191 women and 110 men with subthreshold depression were randomized into internet-based treatment, group cognitive behaviour therapy (Lewinsohn's Coping With Depression course), or a waiting-list control condition. The main outcome measure was treatment response after 10 weeks, defined as the difference in pre- and post-treatment scores on the Beck Depression Inventory (BDI). Missing data, a major limitation of this study, were imputed using the Multiple Imputation (MI) procedure Data Augmentation. Results. In the waiting-list control group, we found a pre- to post-improvement effect size of 0.45, which was 0.65 in the group cognitive behaviour therapy condition and 1.00 within the internet-based treatment condition. Helmert contrasts showed a significant difference between the waiting-list condition and the two treatment conditions (p=0.04) and no significant difference between both treatment conditions (p=0.62). Conclusions. An internet-based intervention may be at least as effective as a commonly used group cognitive behaviour therapy intervention for subthreshold depression in people over 50 years of age. © 2007 Cambridge University Press

Rationale and design of WEBCARE: A randomized, controlled, web-based behavioral intervention trial in cardioverter-defibrillator patients to reduce anxiety and device concerns and enhance quality of life

Background: The implantable cardioverter defibrillator (ICD) is generally well accepted, but 25-33% of patients experience clinical levels of anxiety, depression, and impaired quality of life (QoL) following implantation. Few trials in ICD patients have investigated whether behavioral intervention may mitigate the development of these adjustment problems. We present the rationale and study design of the WEB-based distress management program for implantable CARdioverter dEfibrillator patients (WEBCARE) trial.Methods: WEBCARE is a multi-center, multi-disciplinary, randomized, controlled behavioral intervention trial designed to examine the effectiveness of a web-based approach in terms of reducing level

Is self-guided internet-based cognitive behavioural therapy (iCBT) harmful? : An individual participant data meta-analysis

BACKGROUND: Little is known about potential harmful effects as a consequence of self-guided internet-based cognitive behaviour therapy (iCBT), such as symptom deterioration rates. Thus, safety concerns remain and hamper the implementation of self-guided iCBT into clinical practice. We aimed to conduct an individual participant data (IPD) meta-analysis to determine the prevalence of clinically significant deterioration (symptom worsening) in adults with depressive symptoms who received self-guided iCBT compared with control conditions. Several socio-demographic, clinical and study-level variables were tested as potential moderators of deterioration. METHODS: Randomised controlled trials that reported results of self-guided iCBT compared with control conditions in adults with symptoms of depression were selected. Mixed effects models with participants nested within studies were used to examine possible clinically significant deterioration rates. RESULTS: Thirteen out of 16 eligible trials were included in the present IPD meta-analysis. Of the 3805 participants analysed, 7.2% showed clinically significant deterioration (5.8% and 9.1% of participants in the intervention and control groups, respectively). Participants in self-guided iCBT were less likely to deteriorate (OR 0.62, p < 0.001) compared with control conditions. None of the examined participant- and study-level moderators were significantly associated with deterioration rates. CONCLUSIONS: Self-guided iCBT has a lower rate of negative outcomes on symptoms than control conditions and could be a first step treatment approach for adult depression as well as an alternative to watchful waiting in general practice

Efficacy of Self-guided Internet-Based Cognitive Behavioral Therapy in the Treatment of Depressive Symptoms : A Meta-analysis of Individual Participant Data

IMPORTANCE Self-guided internet-based cognitive behavioral therapy (iCBT) has the potential to increase access and availability of evidence-based therapy and reduce the cost of depression treatment. OBJECTIVES To estimate the effect of self-guided iCBT in treating adults with depressive symptoms compared with controls and evaluate the moderating effects of treatment outcome and response. DATA SOURCES A total of 13 384 abstracts were retrieved through a systematic literature search in PubMed, Embase, PsycINFO, and Cochrane Library from database inception to January 1, 2016. STUDY SELECTION Randomized clinical trials in which self-guided iCBT was compared with a control (usual care, waiting list, or attention control) in individuals with symptoms of depression. DATA EXTRACTION AND SYNTHESIS Primary authors provided individual participant data from 3876 participants from 13 of 16 eligible studies. Missing data were handled using multiple imputations. Mixed-effects models with participants nested within studies were used to examine treatment outcomes and moderators. MAIN OUTCOMES AND MEASURES Outcomes included the Beck Depression Inventory, Center for Epidemiological Studies-Depression Scale, and 9-item Patient Health Questionnaire scores. Scales were standardized across the pool of the included studies. RESULTS Of the 3876 study participants, the mean (SD) age was 42.0 (11.7) years, 2531 (66.0%) of 3832 were female, 1368 (53.1%) of 2574 completed secondary education, and 2262 (71.9%) of 3146 were employed. Self-guided iCBT was significantly more effective than controls on depressive symptoms severity (ß =-0.21; Hedges g = 0.27) and treatment response (ß = 0.53; odds ratio, 1.95; 95% CI, 1.52-2.50; number needed to treat, 8). Adherence to treatment was associated with lower depressive symptoms (ß =-0.19; P =.001) and greater response to treatment (ß = 0.90; P <.001). None of the examined participant and study-level variables moderated treatment outcomes. CONCLUSIONS AND RELEVANCE Self-guided iCBT is effective in treating depressive symptoms. The use of meta-analyses of individual participant data provides substantial evidence for clinical and policy decision making because self-guided iCBT can be considered as an evidence-based first-step approach in treating symptoms of depression. Several limitations of the iCBT should be addressed before it can be disseminated into routine care

Is self-guided internet-based cognitive behavioural therapy (iCBT) harmful? An individual participant data meta-analysis

Background Little is known about potential harmful effects as a consequence of self-guided internet-based cognitive behaviour therapy (iCBT), such as symptom deterioration rates. Thus, safety concerns remain and hamper the implementation of self-guided iCBT into clinical practice. We aimed to conduct an individual participant data (IPD) meta-analysis to determine the prevalence of clinically significant deterioration (symptom worsening) in adults with depressive symptoms who received self-guided iCBT compared with control conditions. Several socio-demographic, clinical and study-level variables were tested as potential moderators of deterioration. Methods Randomised controlled trials that reported results of self-guided iCBT compared with control conditions in adults with symptoms of depression were selected. Mixed effects models with participants nested within studies were used to examine possible clinically significant deterioration rates. Results Thirteen out of 16 eligible trials were included in the present IPD meta-analysis. Of the 3805 participants analysed, 7.2% showed clinically significant deterioration (5.8% and 9.1% of participants in the intervention and control groups, respectively). Participants in self-guided iCBT were less likely to deteriorate (OR 0.62, p < 0.001) compared with control conditions. None of the examined participant- and study-level moderators were significantly associated with deterioration rates. Conclusions Self-guided iCBT has a lower rate of negative outcomes on symptoms than control conditions and could be a first step treatment approach for adult depression as well as an alternative to watchful waiting in general practice.This work was funded by the European Commission’s Seventh Framework Program (grant 603098 for the E-COMPARED project). At the time of the study, Dr K. Griffiths was supported by National Health & Medical Research Counselling Fellowship 1059620

Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR?=?1.022, 95%CI 1.007?1.038 and OR?=?1.025, 95%CI 1.001?1.051, respectively), while thromboprophylaxis use was protective (OR?=?0.199, 95%CI 0.061?0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR?=?1.062, 95%CI 1.017-1.109 and OR?=?2.438, 95%CI 1.023-5.813, respectively). CONCLUSIONS: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration

COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated

The evolving landscape of COVID‐19 and post‐COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations