Suicidality in Obsessive-Compulsive Disorder: Prevalence and Relation to Symptom Dimensions and Comorbid Conditions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estimating the prevalence of comorbid conditions and their effect on health care costs in patients with diabetes mellitus in Switzerland.

BACKGROUND Estimating the prevalence of comorbidities and their associated costs in patients with diabetes is fundamental to optimizing health care management. This study assesses the prevalence and health care costs of comorbid conditions among patients with diabetes compared with patients without diabetes. Distinguishing potentially diabetes- and nondiabetes-related comorbidities in patients with diabetes, we also determined the most frequent chronic conditions and estimated their effect on costs across different health care settings in Switzerland. METHODS Using health care claims data from 2011, we calculated the prevalence and average health care costs of comorbidities among patients with and without diabetes in inpatient and outpatient settings. Patients with diabetes and comorbid conditions were identified using pharmacy-based cost groups. Generalized linear models with negative binomial distribution were used to analyze the effect of comorbidities on health care costs. RESULTS A total of 932,612 persons, including 50,751 patients with diabetes, were enrolled. The most frequent potentially diabetes- and nondiabetes-related comorbidities in patients older than 64 years were cardiovascular diseases (91%), rheumatologic conditions (55%), and hyperlipidemia (53%). The mean total health care costs for diabetes patients varied substantially by comorbidity status (US$3,203-$14,223). Patients with diabetes and more than two comorbidities incurred US$10,584 higher total costs than patients without comorbidity. Costs were significantly higher in patients with diabetes and comorbid cardiovascular disease (US$4,788), hyperlipidemia (US$2,163), hyperacidity disorders (US$8,753), and pain (US$8,324) compared with in those without the given disease. CONCLUSION Comorbidities in patients with diabetes are highly prevalent and have substantial consequences for medical expenditures. Interestingly, hyperacidity disorders and pain were the most costly conditions. Our findings highlight the importance of developing strategies that meet the needs of patients with diabetes and comorbidities. Integrated diabetes care such as used in the Chronic Care Model may represent a useful strategy.

Obesity and comorbid risk factors for cardiovascular disease among physically inactive patients with musculoskeletal disorders : a targeted intervention for this priority patient group is warranted

Introduction The benefits of physical activity are established and numerous; not the least of which is reduced risk of negative cardiovascular events. While sedentary lifestyles are having negative impacts across populations, people with musculoskeletal disorders may face additional challenges to becoming physically active. Unfortunately, interventions in ambulatory hospital clinics for people with musculoskeletal disorders primarily focus on their presenting musculoskeletal complaint with cursory attention given to lifestyle risk factors; including physical inactivity. This missed opportunity is likely to have both personal costs for patients and economic costs for downstream healthcare funders. Objectives The objective of this study was to investigate the presence of obesity, diabetes, diagnosed cardiac conditions, and previous stroke (CVA) among insufficiently physically active patients accessing (non-surgical) ambulatory hospital clinics for musculoskeletal disorders to indicate whether a targeted risk-reducing intervention is warranted. Methods A sub-group analysis of patients (n=110) who self-reported undertaking insufficient physical activity level to meet national (Australian) minimum recommended guidelines was conducted. Responses to the Active Australia Survey were used to identify insufficiently active patients from a larger cohort study being undertaken across three (non-surgical) ambulatory hospital clinics for musculoskeletal disorders. Outcomes of interest included body mass index, Type-II diabetes, diagnosed cardiac conditions, previous CVA and patients’ current health-related quality of life (Euroqol-5D). Results The mean (standard deviation) age of inactive patients was 56 (14) years. Body mass index values indicated that n=80 (73%) were overweight n=26 (24%), or obese n=45 (49%). In addition to their presenting condition, a substantial number of patients reported comorbid diabetes n=23 (21%), hypertension n=25 (23%) or an existing heart condition n=14 (13%); 4 (3%) had previously experienced a CVA as well as other comorbid conditions. Health-related quality of life was also substantially impacted, with a mean (standard deviation) multi-attribute utility score of 0.51 (0.32). Conclusion A range of health conditions and risk factors for further negative health events, including cardiovascular complications, consistent with physically inactive lifestyles were evident. A targeted risk-reducing intervention is warranted for this high risk clinical group.

Does anti-obsessional pharmacotherapy treat so-called comorbid depressive and anxiety states?

Background: Obsessive-compulsive disorder (OCD) is a chronic condition that normally presents high rates of psychiatric comorbidity. Depression, tic disorders and other anxiety disorders are among the most common comorbidities in OCD adult patients. There is evidence that the higher the number of psychiatric comorbidities, the worse the OCD treatment response. However, little is known about the impact of OCD treatment on the outcome of the psychiatric comorbidities usually present in OCD patients. The aim of this study was to investigate the impact of exclusive, conventional treatments for OCD on the outcome of additional psychiatric disorders of OCD patients, detected at baseline. Methods: Seventy-six patients with primary OCD admitted to the treatment protocols of the Obsessive-Compulsive Spectrum Disorders Program between July 2007 and December 2009 were evaluated at pre-treatment and after 12 months. Data were analyzed to verify possible associations between,OCD treatment response and the outcome of psychiatric comorbidities. Results: Results showed a significant association between OCD treatment response and improvement of major depression and dysthymia (p-value = 0.002), other anxiety disorders (generalized anxiety disorder, social phobia, specific phobia, posttraumatic stress disorder, panic disorder, agoraphobia and anxiety disorder not otherwise specified) (p-value = 0.054) and tic disorders (p-value = 0.043). Limitations: This is an open, non-blinded study, without rating scales for comorbid conditions. Further research is necessary focusing on the possible mechanisms by which OCD treatment could improve these specific disorders. Conclusions: Our results suggest that certain comorbid disorders may benefit from OCD-targeted treatment. (C) 2012 Elsevier B.V. All rights reserved.

Abnormal function of monoamine oxidase-A in comorbid major depressive disorder and cardiovascular disease: Pathophysiological and therapeutic implications (Review)

The association between major depressive disorder (MDD) and cardiovascular disease (CVD) is among the best described medical comorbidities. The presence of MDD increases the risk of cardiac admissions and mortality and increases healthcare costs in patients with CVD, and similarly, CVD affects the course and outcome of MDD. The potential shared biological mechanisms involved in these comorbid conditions are not well known. However, the enzyme monoamine oxidase-A (MAO-A), which has a key role in the degradation of catecholamines, has been associated with the pathophysiology and therapeutics of both MDD and CVD. Increased MAO-A activity results in the dysregulation of downstream targets of this enzyme and thus affects the pathophysiology of the two diseases. These deleterious effects include altered noradrenaline turnover, with a direct elevation in oxidative stress parameters, as well as increased platelet activity and cytokine levels. These effects were shown to be reversed by MAO inhibitors. Here, a model describing a key role for the MAO-A in comorbid MDD and CVD is proposed, with focus on the shared pathophysiological mechanisms and the potential therapeutic relevance of agents targeting this enzyme.

Paediatric obesity, physical activity and the musculoskeletal system

The current epidemic of paediatric obesity is consistent with a myriad of health-related comorbid conditions. Despite the higher prevalence of orthopaedic conditions in overweight children, a paucity of published research has considered the influence of these conditions on the ability to undertake physical activity. As physical activity participation is directly related to improvements in physical fitness, skeletal health and metabolic conditions, higher levels of physical activity are encouraged, and exercise is commonly prescribed in the treatment and management of childhood obesity. However, research has not correlated orthopaedic conditions, including the increased joint pain and discomfort that is commonly reported by overweight children, with decreases in physical activity. Research has confirmed that overweight children typically display a slower, more tentative walking pattern with increased forces to the hip, knee and ankle during 'normal' gait. This research, combined with anthropometric data indicating a higher prevalence of musculoskeletal malalignment in overweight children, suggests that such individuals are poorly equipped to undertake certain forms of physical activity. Concomitant increases in obesity and decreases in physical activity level strongly support the need to better understand the musculoskeletal factors associated with the performance of motor tasks by overweight and obese children.

Caveat Anicula! Beware of the Quiet Little Old Ladies : Demographics, Pharmacotherapy, Survival and Readmissions in a 10 Year Cohort of Heart Failure Patients with Preserved Systolic Function

Objective--To determine whether heart failure with preserved systolic function (HFPSF) has different natural history from left ventricular systolic dysfunction (LVSD). Design and setting--A retrospective analysis of 10 years of data (for patients admitted between 1 July 1994 and 30 June 2004, and with a study census date of 30 June 2005) routinely collected as part of clinical practice in a large tertiary referral hospital.Main outcome measures-- Sociodemographic characteristics, diagnostic features, comorbid conditions, pharmacotherapies, readmission rates and survival.Results--Of the 2961 patients admitted with chronic heart failure, 753 had echocardiograms available for this analysis. Of these, 189 (25%) had normal left ventricular size and systolic function. In comparison to patients with LVSD, those with HFPSF were more often female (62.4% v 38.5%; P = 0.001), had less social support, and were more likely to live in nursing homes (17.9% v 7.6%; P < 0.001), and had a greater prevalence of renal impairment (86.7% v 6.2%; P = 0.004), anaemia (34.3% v 6.3%; P = 0.013) and atrial fibrillation (51.3% v 47.1%; P = 0.008), but significantly less ischaemic heart disease (53.4% v 81.2%; P = 0.001). Patients with HFPSF were less likely to be prescribed an angiotensin-converting enzyme inhibitor (61.9% v 72.5%; P = 0.008); carvedilol was used more frequently in LVSD (1.5% v 8.8%; P < 0.001). Readmission rates were higher in the HFPSF group (median, 2 v 1.5 admissions; P = 0.032), particularly for malignancy (4.2% v 1.8%; P < 0.001) and anaemia (3.9% v 2.3%; P < 0.001). Both groups had the same poor survival rate (P = 0.912). Conclusions--Patients with HFPSF were predominantly older women with less social support and higher readmission rates for associated comorbid illnesses. We therefore propose that reduced survival in HFPSF may relate more to comorbid conditions than suboptimal cardiac management.

Examining the health related quality of life of people with end stage kidney disease living in Hanoi, Vietnam

Background: The prevalence of end-stage kidney disease (ESKD) patients is increasing in Vietnam; however, the impact of ESKD and its treatment on a person’s quality of life (QOL) is not well understood. Objective: This research sought to examine the association between monthly income, comorbidity, length of time on dialysis, social support and health-related quality of life (HRQOL) among Vietnamese ESKD patients. Method: Using a descriptive design, 95 patients who were receiving haemodialysis (HD) and peritoneal dialysis (PD) from one hospital in Hanoi, were conveniently sampled. Results: ESKD patients reported having a moderate level of HRQOL. Factors associated with QOL were social support (r= .268, p<.05), comorbid health conditions (r= –.185, p<.05), and length of time on dialysis (r= .182, p<.05). However, monthly income was not significantly related to HRQOL (p>.05). Conclusion: The results seem to indicate that ESKD patients in Vietnam have a high level of support from family members, friends and significant others. There was also a negative impact of comorbid conditions on the QOL of these patients. Based on the results of this study, nurses ought to develop nursing interventions which will lead to a better QOL for patients, and further research into the QOL for ESKD patients in Vietnam is warranted.

Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2 : prognostic factors and treatment selection based on two large randomized clinical trials

Purpose: Data from two randomized phase III trials were analyzed to evaluate prognostic factors and treatment selection in the first-line management of advanced non-small cell lung cancer patients with performance status (PS) 2. Patients and Methods: Patients randomized to combination chemotherapy (carboplatin and paclitaxel) in one trial and single-agent therapy (gemcitabine or vinorelbine) in the second were included in these analyses. Both studies had identical eligibility criteria and were conducted simultaneously. Comparison of efficacy and safety was performed between the two cohorts. A regression analysis identified prognostic factors and subgroups of patients that may benefit from combination or single-agent therapy. Results: Two hundred one patients were treated with combination and 190 with single-agent therapy. Objective responses were 37 and 15%, respectively. Median time to progression was 4.6 months in the combination arm and 3.5 months in the single-agent arm (p < 0.001). Median survival imes were 8.0 and 6.6 months, and 1-year survival rates were 31 and 26%, respectively. Albumin <3.5 g, extrathoracic metastases, lactate dehydrogenase ≥200 IU, and 2 comorbid conditions predicted outcome. Patients with 0-2 risk factors had similar outcomes independent of treatment, whereas patients with 3-4 factors had a nonsignificant improvement in median survival with combination chemotherapy. Conclusion: Our results show that PS2 non-small cell lung cancer patients are a heterogeneous group who have significantly different outcomes. Patients treated with first-line combination chemotherapy had a higher response and longer time to progression, whereas overall survival did not appear significantly different. A prognostic model may be helpful in selecting PS 2 patients for either treatment strategy. © 2009 by the International Association for the Study of Lung Cancer.

Smell and taste dysfunction following minor stroke: A case report

Smell (olfactory) and taste (gustatory) are key senses in the regulation of nourishment and individual safety. Olfactory and gustatory dysfunctions have been infrequently reported together in patients following stroke (Landis et al., 2006; Leopold et al., 2006). This case report details two patients who experienced smell and taste dysfunction following minor stroke events. Symptoms reported included hyposmia (diminished sense of smell) and anosmia (complete loss of smell), and dysgeusia (distorted taste). Patients' sense of smell and taste were assessed in an ambulatory care stroke prevention clinic eight months following their strokes. Patient A presented with minor stroke due to a lesion in the anterior circulation, patient B with a lesion in the posterior circulation. Both patients reported intense olfactory and gustatory dysfunction immediately following their strokes. Examination revealed a general inability to detect subtle odours and the ability to identify only 'sweet' tastes for both patients. In addition, both patients reported heavily salting or sweetening their food to mask the distorted and unpleasant taste, which also impacted comorbid conditions such as hypertension and diabetes. Patients and their spouses reported a decrease in their appreciation of family-related activities due to the patients' olfactory and gustatory dysfunction. Patients reported weight loss, lack of energy and strength, likely due to poor nutrition. Olfactory and gustatory dysfunctions are potentially deleterious outcomes following minor stroke and should be assessed by health care professionals prior to patient discharge. Assistance may be required to promote the health and well-being of patients and their carers if smell and taste are impacted by the stroke event.

Impact of a stroke unit on length of hospital stay and in-hospital case fatality

Background and Purpose Randomized trials have demonstrated reduced morbidity and mortality with stroke unit care; however, the effect on length of stay, and hence the economic benefit, is less well-defined. In 2001, a multidisciplinary stroke unit was opened at our institution. We observed whether a stroke unit reduces length of stay and in-hospital case fatality when compared to admission to a general neurology/medical ward. Methods A retrospective study of 2 cohorts in the Foothills Medical Center in Calgary was conducted using administrative databases. We compared a cohort of stroke patients managed on general neurology/medical wards before 2001, with a similar cohort of stroke patients managed on a stroke unit after 2003. The length of stay was dichotomized after being centered to 7 days and the Charlson Index was dichotomized for analysis. Multivariable logistic regression was used to compare the length of stay and case fatality in 2 cohorts, adjusted for age, gender, and patient comorbid conditions defined by the Charlson Index. Results Average length of stay for patients on a stroke unit (n=2461) was 15 days vs 19 days for patients managed on general neurology/medical wards (n=1567). The proportion of patients with length of stay >7 days on general neurology/medical wards was 53.8% vs 44.4% on the stroke unit (difference 9.4%; P<0.0001). The adjusted odds of a length of stay >7 days was reduced by 30% (P<0.0001) on a stroke unit compared to general neurology/medical wards. Overall in-hospital case fatality was reduced by 4.5% with stroke unit care. Conclusions We observed a reduced length of stay and reduced in-hospital case-fatality in a stroke unit compared to general neurology/medical wards.

Irritable bowel syndrome in the general population : epidemiology, comorbidity and societal costs

Background: Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder characterised by abdominal pain and abnormal bowel function. It is associated with a high rate of healthcare consumption and significant health care costs. The prevalence and economic burden of IBS in Finland has not been studied before. The aims of this study were to assess the prevalence of IBS according to various diagnostic criteria and to study the rates of psychiatric and somatic comorbidity in IBS. In addition, health care consumption and societal costs of IBS were to be evaluated. Methods: The study was a two-phase postal survey. Questionnaire I identifying IBS by Manning 2 (at least two of the six Manning symptoms), Manning 3 (at least three Manning symptoms), Rome I, and Rome II criteria, was mailed to a random sample of 5 000 working age subjects. It also covered extra-GI symptoms such as headache, back pain, and depression. Questionnaire II, covering rates of physician visits, and use of GI medication, was sent to subjects fulfilling Manning 2 or Rome II IBS criteria in Questionnaire I. Results: The response rate was 73% and 86% for questionnaires I and II. The prevalence of IBS was 15.9%, 9.6%, 5.6%, and 5.1% according to Manning 2, Manning 3, Rome I, and Rome II criteria. Of those meeting Rome II criteria, 97% also met Manning 2 criteria. Presence of severe abdominal pain was more often reported by subjects meeting either of the Rome criteria than those meeting either of the Manning criteria. Presence of depression, anxiety, and several somatic symptoms was more common among subjects meeting any IBS criterion than by controls. Of subjects with depressive symptoms, 11.6% met Rome II IBS criteria compared to 3.7% of those with no depressiveness. Subjects meeting any IBS criteria made more physician visits than controls. Intensity of GI symptoms and presence of dyspeptic symptoms were the strongest predictors of GI consultations. Presence of dyspeptic symptoms and a history of abdominal pain in childhood also predicted non-GI visits. Annual GI related individual costs were higher in the Rome II group (497 ) than in the Manning 2 group (295 ). Direct expenses of GI symptoms and non GI physician visits ranged between 98M for Rome II and 230M for Manning 2 criteria. Conclusions: The prevalence of IBS varies substantially depending on the criteria applied. Rome II criteria are more restrictive than Manning 2, and they identify an IBS population with more severe GI symptoms, more frequent health care use, and higher individual health care costs. Subjects with IBS demonstrate high rates of psychiatric and somatic comorbidity regardless of health care seeking status. Perceived symptom severity rather than psychiatric comorbidity predicts health care seeking for GI symptoms. IBS incurs considerable medical costs. The direct GI and non-GI costs are equivalent to up to 5% of outpatient health care and medicine costs in Finland. A more integral approach to IBS by physicians, accounting also for comorbid conditions, may produce a more favourable course in IBS patients and reduce health care expenditures.

Non-small cell lung cancer : studies on pathogenesis, tumour targeting and treatment outcomes

Lung cancer accounts for more cancer-related deaths than any other cancer. In Finland, five-year survival ranges from 8% to 13%. The main risk factor for lung cancer is long-term cigarette smoking, but its carcinogenesis requires several other factors. The aim of the present study was to 1) evaluate post-operative quality of life, 2) compare clinical outcomes between minimally invasive and conventional open surgery, 3) evaluate the role of oxidative stress in the carcinogenesis of non-small lung cancer (NSCLC), and 4) to identify and characterise targeted agents for therapeutic and diagnostic use in surgery. For study I, pneumonectomy patients replied to 15D quality of life and baseline dyspnea questionnaires. Study III involved a prospective quality of life assessment using the 15D questionnaire after lobectomy or bi-lobectomy. Study IV was a retrospective comparison of clinical outcomes between 212 patients treated with open thoracotomy and 116 patients who underwent a minimally invasive technique. Study II measured parameters of oxidative metabolism (myeloperoxidase activity, glutathione content and NADPH oxidase activity) and DNA adducts. Study V employed the phage display method and identified a core motif for homing peptides. This method served in cell-binding, cell-localisation, and biodistribution studies. Following both pneumonectomy and lobectomy, NSCLC patients showed significantly decreased long-term quality of life. No significant correlation was noted between post-operative quality of life and pre-operative pulmonary function tests. Women suffered more from increased dyspnea after pneumonectomy which was absent after lobectomy or bi-lobectomy. Patients treated with video-assisted thoracoscopy showed significantly decreased morbidity and shorter periods of hospitalization than did open surgery patients. This improvement was achieved even though the VATS patients were older and suffered more comorbid conditions and poorer pulmonary function. No significant differences in survival were noted between these two groups. An increase in NADPH oxidase activity was noted in tumour samples of both adenocarcinoma and squamous cell carcinoma. This increase was independent from myeloperoxidase activity. Elevated glutathione content was noted in tumour tissue, especially in adenocarcinoma. After panning the clinical tumour samples with the phage display method, an amino acid sequence of ARRPKLD, the Thx, was chosen for further analysis. This method proved selective of tumour tissue in both in vitro and in vivo cell-binding assay, and biodistribution showed tumour accumulation. Because of the significantly reduced quality of life following pneumonectomy, other operative strategies should be implemented as an alternative (e.g. sleeve-lobectomy). To treat this disease, implementation of a minimally invasive surgical technique is safe, and the results showed decreased morbidity and a shorter period of hospitalisation than with thoracotomy. This technique may facilitate operative treatment of elderly patients with comorbid conditions who might otherwise be considered inoperable. Simultaneous exposure to oxidative stress and altered redox states indicates the important role of oxidative stress in the pathogenesis and malignant transformation of NSCLC. The studies showed with great specificity and with favourable biodistribution that Thx peptide is specific to NSCLC tumours. Thx thus shows promise in imaging, targeted therapy, and monitoring of treatment response.

Valve surgery in active infective endocarditis: a simple score to predict in-hospital prognosis

Aims Surgery for infective endocarditis (IE) is associated with high mortality. Our objectives were to describe the experience with surgical treatment for IE in Spain, and to identify predictors of in-hospital mortality. Methods Prospective cohort of 1000 consecutive patients with IE. Data were collected in 26 Spanish hospitals. Results Surgery was performed in 437 patients (43.7%). Patients treated with surgery were younger and predominantly male. They presented fewer comorbid conditions and more often had negative blood cultures and heart failure. In-hospital mortality after surgery was lower than in the medical therapy group (24.3 vs 30.7%, p = 0.02). In patients treated with surgery, endocarditis involved a native valve in 267 patients (61.1%), a prosthetic valve in 122 (27.9%), and a pacemaker lead with no clear further valve involvement in 48 (11.0%). The most common aetiologies were Staphylococcus (186, 42.6%), Streptococcus (97, 22.2%), and Enterococcus (49, 11.2%). The main indications for surgery were heart failure and severe valve regurgitation. A risk score for in-hospital mortality was developed using 7 prognostic variables with a similar predictive value (OR between 1.7 and 2.3): PALSUSE: prosthetic valve, age ≥ 70, large intracardiac destruction, Staphylococcus spp, urgent surgery, sex [female], EuroSCORE ≥ 10. In-hospital mortality ranged from 0% in patients with a PALSUSE score of 0 to 45.4% in patients with PALSUSE score > 3. Conclusions The prognosis of IE surgery is highly variable. The PALSUSE score could help to identify patients with higher in-hospital mortality.

Cognitive, global, and functional benefits of donepezil in Alzheimer's disease and vascular dementia:results from large-scale clinical trials

Alzheimer's disease (AD) and vascular dementia (VaD) are both associated with deficits in cholinergic neurotransmission that are amenable to therapeutic intervention. The cholinesterase inhibitor, donepezil, is clinically effective in both AD and VaD. Results from a 10-study metaanalysis of donepezil (5 or 10 mg/day) in AD and a two-study combined analysis of donepezil (5 or 10 mg/day) in VaD are presented to compare patient characteristics and donepezil treatment outcomes. The analyzed studies were randomized, placebo-controlled, and of up to 24 weeks duration. In both AD and VaD, donepezil provided significant benefits compared with placebo on measures of cognition and global function. Placebo-treated AD patients showed a decline in cognition and global function, whereas placebo-treated VaD patients remained stable, suggesting treatment effects of donepezil in VaD were driven by improvement rather than stabilization or reduced decline. More VaD patients than AD patients received concomitant medications. Cardiovascular adverse events were more common in VaD than AD patients but were not increased by donepezil. In conclusion, although there are differences between AD and VaD patients in comorbid conditions and concomitant medications, donepezil is effective and well tolerated in both types of dementia.