Major Comorbidity In Patients Research Articles

Time-Course of Muscle Mass Loss, Damage, and Proteolysis in Gastrocnemius following Unloading and Reloading: Implications in Chronic Diseases.

BackgroundDisuse muscle atrophy is a major comorbidity in patients with chronic diseases including cancer. We sought to explore the kinetics of molecular mechanisms shown to be involved in muscle mass loss throughout time in a mouse model of disuse muscle atrophy and recovery following immobilization.MethodsBody and muscle weights, grip strength, muscle phenotype (fiber type composition and morphometry and muscle structural alterations), proteolysis, contractile proteins, systemic troponin I, and mitochondrial content were assessed in gastrocnemius of mice exposed to periods (1, 2, 3, 7, 15 and 30 days) of non-invasive hindlimb immobilization (plastic splint, I cohorts) and in those exposed to reloading for different time-points (1, 3, 7, 15, and 30 days, R cohorts) following a seven-day period of immobilization. Groups of control animals were also used.ResultsCompared to non-exposed controls, muscle weight, limb strength, slow- and fast-twitch cross-sectional areas, mtDNA/nDNA, and myosin content were decreased in mice of I cohorts, whereas tyrosine release, ubiquitin-proteasome activity, muscle injury and systemic troponin I levels were increased. Gastrocnemius reloading following splint removal improved muscle mass loss, strength, fiber atrophy, injury, myosin content, and mtDNA/nDNA, while reducing ubiquitin-proteasome activity and proteolysis.ConclusionsA consistent program of molecular and cellular events leading to reduced gastrocnemius muscle mass and mitochondrial content and reduced strength, enhanced proteolysis, and injury, was seen in this non-invasive mouse model of disuse muscle atrophy. Unloading of the muscle following removal of the splint significantly improved the alterations seen during unloading, characterized by a specific kinetic profile of molecular events involved in muscle regeneration. These findings have implications in patients with chronic diseases including cancer in whom physical activity may be severely compromised.

MicroRNA-15b Modulates Molecular Mediators of Blood Induced Arthropathy in Hemophilia Mice.

The development of arthropathy is a major co-morbidity in patients with hemophilia. The present study was designed to study the role of a microRNA biomarker (miR-15b) in the development of joint disease. To investigate the expression profile of miR-15b during the development of arthropathy, we first isolated and studied small RNA from the acute and chronic hemarthrosis model of hemophilia A mice. We observed that miR-15b was consistently repressed (~1- to 4-fold) from the onset of joint bleeding (1, 3, 7 and 24 h) until six bleeding episodes (up to 90 days). To test if reconstitution of miR-15b modulates biomarkers of joint damage in a chronic hemarthrosis model, we administered an adeno-associated virus (AAV) 5-miR-15b vector intra-articularly alone or in combination with systemic administration of AAV2-factor VIII. miR-15b overexpression downregulated markers of angiogenesis and hypoxia (vascular epithelial growth factor α (VEGF-α) and hypoxia inducing factor 2α (HIF-2α), ~70% and ~34%, respectively) in the affected joints. In addition, the co-administration of miR-15b and factor VIII vectors reduced the levels of the chondrodegenerative matrix-metalloproteinases (MMPs) 1, 3, 9 and 14 (~14% to 60%) in the injured joints. These data demonstrate for the first time the role of a miR-15b in the development of hemophilic arthropathy and has implications in development of miR based therapies for joint disease.

Erratum to: Safety and efficacy of dual direct-acting antiviral therapy (daclatasvir and asunaprevir) for chronic hepatitis C virus genotype 1 infection in patients on hemodialysis.

Hepatitis C virus (HCV) infection is a major comorbidity in patients receiving hemodialysis. Interferon-based antiviral therapy to eradicate HCV is less effective in patients receiving hemodialysis than patients without renal dysfunction. Recently reported combination therapy with two oral direct-acting antiviral drugs, daclatasvir and asunaprevir, both of which are metabolized in the liver and excreted into the bile ducts, reportedly showed a high rate of HCV eradication. We evaluated the safety and efficacy of this therapy in patients receiving hemodialysis. The safety and viral responses were compared among patients infected with HCV genotype 1, between 28 patients receiving hemodialysis, and propensity score-matched 56 patients without renal dysfunction. The reduction in serum HCV RNA levels 1 day after the start of therapy was significantly larger (p = 0.0329) and the disappearance of serum HCV RNA occurred significantly earlier (p = 0.0017) in patients receiving hemodialysis than those without renal dysfunction. The rates of sustained virologic response, i.e., the eradication of HCV, were comparable between two groups; the rate of SVR12 was 100 % in patients receiving hemodialysis and 94.6 % in patients without renal dysfunction. No adverse constitutional events were observed in either of the groups. The elevation of serum alanine aminotransferase levels, a known adverse effect of these drugs, was observed in comparable rate of patients between the two groups. The therapy with daclatasvir and asunaprevir has high antiviral efficacy in patients receiving hemodialysis with a comparable safety profile to patients without renal dysfunction.

Roflumilast inhibits leukocyte–platelet interactions and prevents the prothrombotic functions of polymorphonuclear leukocytes and monocytes

ESSENTIALS: Thrombosis is a major comorbidity in patients with chronic obstructive pulmonary disease (COPD). Roflumilast is a selective phosphodiesterase type-4 (PDE4) inhibitor approved for treatment of severe COPD. PDE4 blockade by roflumilast inhibits prothrombotic functions of neutrophils and monocytes. PDE4 inhibitors may reduce thrombotic risk in COPD as well as in other vascular diseases. Roflumilast, an oral selective phosphodiesterase type 4 inhibitor, is approved for the treatment of severe chronic obstructive pulmonary disease (COPD). A recent meta-analysis of trials on COPD revealed that treatment with roflumilast was associated with a significant reduction in the rate of major cardiovascular events. The mechanisms of this effect remain unknown. We tested the hypothesis that roflumilast N-oxide (RNO), the active metabolite of roflumilast, curbs the molecular mechanisms required for leukocyte-platelet (PLT) interactions and prevents the prothrombotic functions of polymorphonuclear leukocytes (PMNs) and monocytes (MNs). Using well-characterized in vitro models, we analysed the effects of RNO on: (i) PMN adhesiveness; (ii) the release of neutrophil extracellular traps (NETs); and (iii) tissue factor expression in MNs. Key biochemical events underlying the inhibitory effects of RNO were defined. In PMNs, RNO prevented phosphoinositide 3-kinase (PI3K)-dependent phosphorylation of Akt on Ser473, and Src family kinase (SFK)-mediated Pyk2 phosphorylation on Tyr579-580, while inducing protein kinase A-mediated phosphorylation of C-terminal Src kinase, the major negative regulator of SFKs. Modulation of these signaling pathways by RNO resulted in a significant impairment of PMN adhesion to activated PLTs or human umbilical vein endothelial cells, mainly mediated by inhibition of the adhesive function of Mac-1. Moreover RNO curbed SFK/PI3K-mediated NET release by PMNs adherent on fibrinogen-coated surfaces. In MNs interacting with activated PLTs, RNO curbed PI3K-mediated expression of tissue factor. The efficacy of RNO was significantly potentiated by formoterol, a long acting β-adrenergic receptor agonist. This study reveals novel antithrombotic activities by which roflumilast may exert protective effects against cardiovascular comorbodities in COPD.

Cardiovascular Safety of Current and Emerging Glucose-Lowering Therapies.

Cardiovascular disease (CVD) remains the most common major comorbidity in patients with diabetes. Individual short-term studies have failed to show that glycemic control over the short term does not have an impact on CVD. However, until recently, it remained uncertain whether the choice of glycemic drug has a beneficial impact on CVD outcomes. A small study suggesting CVD benefit has resulted in the primacy of metformin for glycemic control. Multiplemeta-analyses of studies with sulphonylurea agents have shown either no CVD benefit or potential harm. Despite the common use of insulin and the potential for both cardiovascular and noncardiovascular harm, only 1 study examining the impact of insulin on cardiovascular outcomes, the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial, has been undertaken, and the outcome was neutral. The thiazolidinediones (TZDs) have heterogeneous effects; pioglitazone shows potential cardiac benefit and rosiglizone shows possible harm. After a well-publicized meta-analysis of rosiglitazone studies showed potential harm, the US Food and Drug Administration (FDA) issued safety requirements prior to the licensing of new glycemic medications. Since these requirements were instituted, more than 18 studies have been initiated to study dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter type 2 (SGLT-2) inhibitors. The completed DPP4 and GLP-1 trials meet the safety criteria without improved CVD outcomes. In contrast, the first CVD outcome trial of an SGLT-2 inhibitor, the Empagliflozin Cardiovascular Outcome Event (EMPA-REG) Outcomes trial showed that empagliflozin, in a population of patients with type 2 diabetes and established CVD, reduced CV death and all-cause mortality by 38% and 32%, respectively, and hospitalization for heart failure by 39% in patients with established CVD already treated with metformin. Future guidelines are likely to recommend empagliflozin for patients with type 2 diabetes and CVD. Diabetes confers a substantial risk for the development of atherosclerotic CVD. The life expectancy of a patient with diabetes is 5 to 10 years shorter than that of a person without diabetes (1), largely as a result of the earlier development of coronary heart disease (2). Over the lifetime of a patient with diabetes, there is a greater than 75% chance of developing cardiovascular disease (3), and most patients with diabetes will die as a consequence of CVD. Peripheral vascular disease is common in patients with diabetes, and diabetes is the most common cause for limb amputation. Although patients with diabetes fear blindness, dialysis and amputation, they have a very much greater chance of dying from CVD than suffering one of the feared consequences of diabetes. The risk for CVD increases with the degree of dysglycemia. Both the level of fasting blood glucose and the glucose level after a standard glucose load correlate with the incidence of CVD events (4). The levels of glycated hemoglobin (A1C) predict the incidence of myocardial infarction and mortality (5). However, there is a closer relationship between A1C levels and the development of microvascular events such as nephropathy and retinopathy than is observed for macrovascular CVD events. Over the past 20 years, there has been a marked increase in the number of agents available for glycemic control. Thirty years ago, insulin, first-generation sulphonylureas and phenformin were the only agents available. Subsequently, metformin, glucosidase inhibitors, thiazolidinediones, meglitinides, GLP 1 agonists, DPP4 antagonists and sodium-glucose cotransporter-2 (SGLT2) antagonists have expanded the range of agents for glycemic control. Until recently there was no controlled safety or efficacy data to show whether individual agents had properties beyond glycemic control that were either harmful or beneficial. * St Michael’s Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario M4V 1W5, Canada. E-mail address: fitchettd@smh.ca Can J Diabetes 39 (2015) S176–S182

Characterizing the evolution of perioperative outcomes and costs of endovascular abdominal aortic aneurysm repair

The purpose of this study is to characterize the evolution in perioperative outcomes and costs of endovascular abdominal aortic aneurysm (AAA) repair (EVAR) by detailing changes in adjusted outcomes and costs over time. National Inpatient Sample (2000-2011) data were used to evaluate patient characteristics, outcomes, and perioperative costs for elective EVAR performed for intact AAA. Outcomes were adjusted for patient demographics and comorbidities, and hospital factors by multivariate analysis. Costs were calculated from hospital cost to charge ratio files and adjusted to 2011 dollars. From 2000 to 2011, 185,249 patients underwent elective EVAR for intact AAA. The absolute rates of in-hospital major morbidity, mortality, and procedural costs all decreased significantly over time (P< .0001). The prevalence of major comorbidities in patients undergoing EVAR, including obesity, diabetes, and dyslipidemia, all increased significantly over time. After adjusting for multiple demographics, comorbidities, and hospital-level factors, recent outcomes of EVAR (2009-2011) remain superior to the early experience (2000-2002) with respect to mortality and major complications. From 2000-2011, the perioperative outcomes of EVAR improved significantly despite a higher prevalence of comorbidities among patients undergoing repair. Concurrently, procedure-associated costs declined. Advanced technology is often implicated in escalating healthcare spending, and the value of novel techniques is often questioned. These findings highlight that, in the case of EVAR, procedural outcomes have improved while the initial costs of repair have declined over time. EVAR offers an interesting example for stakeholders to consider in the era of cost-containment pressures and criticism of nascent, expensive technology in healthcare.

The Relation Between Liver Dysfunction and Gastrointestinal Bleeding in Patients with Ventricular Assist Devices

The Relation Between Liver Dysfunction and Gastrointestinal Bleeding in Patients with Ventricular Assist Devices

246. Intra-Articular Gene Transfer of miR-15b Attenuates Molecular Mediators of Hemophilic Arthropathy in a Murine Model of Hemophilia

Hemophilic arthropathy is a major co-morbidity in patients with hemophilia and caused by recurrent bleeds (hemarthrosis) in the joints. Despite the availability of protein replacement therapy, newer and targeted strategies are required to prevent the onset of blood-induced arthropathy, particularly in patients who develop inhibitors. Thus, a thorough understanding of the molecular mediators contributing to joint damage becomes pivotal to not only pinpoint mechanisms but also reveal biomarkers of the disease and targets for further intervention. Recently, in a murine model of hemophilia A, we identified that nuclear factor (NF)-kB and its associated factors-hypoxia inducing factor (HIF)-1/2α, vascular epithelial growth factor (VEGF)-α and matrix metallo proteinases(MMP) 3, contribute to the development of arthropathy [J Thromb Haemost 2013; 11:293-306]. In addition, several microRNA (miR) were also differentially expressed following an episodic bleeding. One of these, miR-15b is known to modulate expression of hypoxic and pro-angiogeneic genes. To document the expression pattern of miR-15b during development of arthropathy, the acute hemarthrosis model of hemophhilia A was studied on 1,3,7 and 24h after a single-injury and the chronic hemarthrosis model was studied at 60, 75 and 90 days after multiple injury. We then measured miR-15b levels by qPCR at each one of these time points. miR-15b was downregulated (~1 to 4 fold) from 3hrs after a single bleeding episode to the 90-day time point where the animals have 2 to 6 bleedings into the joint cavity. The maximal down regulation (-4 fold) of miR-15b was observed at 60 days. These data suggest that miR-15b is consistently and progressively repressed from the onset of synovitis to the development of arthropathy in the murine model of hemophilia A. To test if intra-articular overexpression of this miR modulates the molecular biomarkers of joint disease, we administered an adeno-associated virus (AAV)5 vector encoding miR15b into the joints of a chronic model of hemarthrosis. Our results demonstrate that miR15b over-expression downregulates markers such as VEGF-α, HIF 2α (~70% and ~34% respectively) in affected joints. In addition, co-administration of AAV5-miR15b intra-articularly and AAV2-factor VIII intravenously, attenuated the expression of MMPs 1, 3, 9 and 14 (~14% to 60%). Sixty days after intra-articular gene therapy, there was a considerable decrease in the joint scores of animals treated intra-articularly with AAV5-miR-15b when compared to the control AAV5-luc vector (1.6 Vs 2.6). These data provide the first evidence that targeted and local AAV mediated gene delivery of miRs can be potentially used as therapeutic agent to ameliorate hemophilic arthropathy.

Statin Helps Endothelial Function in COPD Subgroup

Statin Helps Endothelial Function in COPD Subgroup

Epidemiology and clinical impact of major comorbidities in patients with COPD.

Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival. There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes. Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD. Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication. The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities. Unfortunately, comorbidities are often under-recognized and under-treated. This review focuses on the epidemiology of ten major comorbidities in patients with COPD. Further, we emphasize the clinical impact upon prognosis and management considerations. This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD.

SAT0134 Prevalence of Cardiovascular Risk Factors and Cardiovascular Disease in Rheumatoid Arthritis Patients across International Regions: A Comparison of the Corrona International and Corrona US Registries

BackgroundCardiovascular disease (CVD) is a major comorbidity in patients (pts) with rheumatoid arthritis (RA). We explored variations in the prevalence of cardiovascular (CV) risk factors and CVD among RA pts...

The Problem of Renal Function Monitoring in Patients Treated With the Novel Antiretroviral Drugs

Chronic kidney disease (CKD) is currently considered a major comorbidity in patients affected by HIV infection. In addition, new generation antiretroviral drugs that interact with creatinine transporters were recently introduced. Rilpivirine, dolutegravir, and cobicistat, with different mechanisms, inhibit the amount of tubular secretion of creatinine causing a slight increase in serum creatinine levels and consensual eGFRcreatreduction. This will require an unprecedented attention to renal issues, because the new drugs can also be associated to old antiretroviral drugs that may exert renal toxic effects. Owing to the interference of these drugs with creatinine secretion, an alternative way of estimating GFR would be desirable. At the moment, methods of direct GFR measurement have a high impact on the patient, are not readily available, or are not reliable in HIV patients. Consequently, use of classic formulas to estimate GFR is still recommended, considering the apparent reduction of eGFRcreat due to these drugs. Tubular function needs to be carefully monitored with simple tests such as proteinuria, phosphatemia, urinary excretion of phosphate, normoglycemic glycosuria, and excretion of uric acid. More specific and sensitive markers of tubular damage are still not readily available in all clinical labs. HIV patients treated by the novel drugs need to be monitored on a monthly basis for the first 3 months. Subsequent monitoring should be performed on a quarterly basis or guided by comorbidities.

Are MMSE and HDS-R neuropsychological tests adequate for screening HIV-associated neurocognitive disorders?

HIV-associated neurocognitive disorders (HAND) are one of major comorbidities in patients with HIV-1 infection. There are currently no standardized tests for screening HAND in such patients. The sensitivity of the cognitive function tests routinely used in clinical practice, such as the Mini-Mental State Examination and the Revised Hasegawa's Dementia Scale, is inadequate to rule out HAND, even in patients with clear abnormal behavior. We report a 41-year-old man with HIV-associated dementia, the most severe form of HAND, in whom the simplified methods did not show abnormal results, and a comprehensive battery of neuropsychological tests which covering several cognitive domains was needed to detect cognitive impairment.

Beneficial effect of successful HCV treatment in patients with inherited bleeding disorders, assessed by liver stiffness measurements

Hepatitis C infection is a major comorbidity in patients with inherited bleeding disorders. Successful antiviral treatment leads to a reduction in liver fibrosis, as shown by liver biopsies. Liver stiffness measurement (LSM) is a non-invasive method of assessing liver fibrosis. The aim of this cohort study was to evaluate the long-term effect of successful antiviral treatment, using LSM, in HCV-infected patients with inherited bleeding disorders. The LSM were performed in 2005 (LSM 1) and 2009 (LSM 2) in 39 patients who were successfully treated for HCV. The change in liver fibrosis between LSM 1 and 2 was assessed. The median duration of HCV infection was 28.8 years. A total of 22 patients (56%) underwent successful antiviral treatment before LSM 1 (group 1), and 17 patients between LSM 1 and LSM 2 (group 2). The median time since antiviral treatment was 8.8 years in group 1 and 2.5 years in group 2. In group 1, the median results of LSM 1 and 2 were similar (6.0 vs. 5.6 kPa, P-value 0.36), so overall, patients remained stable. In three patients in this group, all treated more than 15 years ago, an increase of liver stiffness was shown. Group 2 showed a significant improvement in median LSM results (10.3 vs. 6.1 kPa, P-value <0.01), with decrease of liver stiffness in 82%. Even after a long HCV infection duration, successful antiviral treatment led to a significant improvement of fibrosis, measured by LSM, mainly in the first few years after completing treatment.

Liver stiffness measurements to assess progression of fibrosis in HCV‐infected patients with inherited bleeding disorders

Hepatitis C is a major co-morbidity in patients with inherited bleeding disorders, leading to progressive liver fibrosis and eventually cirrhosis. Liver stiffness measurement (LSM) is a non-invasive way of assessing the extent of liver fibrosis. This article describes our experience with serial LSM to assess prospectively progression of fibrosis in a cohort of patients with inherited bleeding disorders and chronic hepatitis C. A total of 84 patients underwent serial LSMs, with a median interval of 3.7 years. The change in LSM results over time was assessed. Overall, there was no significant difference between the median results of LSM 1 and LSM 2. The median result of LSM 2 was low (6.6 kPa), after a median duration of infection of 37 years. On the individual level, deterioration of LSM results of more than 2 kPa was seen in 13 patients (16%), 44 patients (52%) remained stable and 27 patients (32%) showed improvement of LSM results of more than 2 kPa. These results are comparable with those of paired liver biopsy studies. LSM appears to be a good alternative for liver biopsies in patients with hepatitis C and inherited bleeding disorders, although the interpretation of the unexpected improvement we found in some of our patients is not straightforward. LSMs will be repeated in our patient population in a few years to be able to better assess the value of serial LSM.

Sustained remission of rheumatoid arthritis with a specific serotonin reuptake inhibitor antidepressant: a case report and review of the literature

IntroductionThe mainstay of pharmacologic therapy for rheumatoid arthritis includes the use of disease-modifying agents like sulfasalazine and methothrexate, and more recently, anti-tumor necrosis factor-α agents. Depression remains a major co-morbidity in patients with rheumatoid arthritis and is thought to contribute to disability and mortality in these patients. Evidence now suggests that a biologic link exists between substrates responsible for inflammatory conditions and mood disorders. Most of this evidence comes from preclinical studies. Nevertheless, more research into this area is helping us to understand the possible mechanisms through which these conditions interact with each other.Case presentationWe describe a 60-year-old Indian man with rheumatoid arthritis diagnosed 15 years ago who had minimal response to multiple therapies with disease-modifying agents and whose arthritis symptoms surprisingly remitted when he was started on a specific serotonin reuptake inhibitor antidepressant, three years ago, for co-morbid major depression. This remission has been maintained with this medication, and the patient is currently not taking any antirheumatoid medications.ConclusionPossible mechanisms linking substrates of mood disorders and inflammation are reviewed in this case report, particularly the serotonergic system. Evidence seems to suggest a significant interaction between the serotonergic systems and inflammation. This interaction seems to be bidirectional. An understanding of this relation is most important to gain insight not only into pathophysiological mechanisms underlying this condition, but also into how treatments for these conditions may complement each other and possibly provide greater therapeutic options in both of these disabling conditions.

P01-380 - Correlates of depression and quality of life in patients with inflammatory arthritides

Depression is a major co-morbidity in patients with inflammatory arthritides. In addition to the inflammatory processes, factors like pain, quality of life and trait emotional intelligence or the awareness on one's emotion and the ability to regulate these effectively may be associated with the presence of depression in this population.AimsThe aims of the present study were to determine the rates of depression in patients with psoriatic (PsA) and rheumatoid arthritis (RA) attending a tertiary referral centre, and to investigate possible factors that are associated with depression in this population.MethodsInterim data pertaining to depression (HADS), pain (British Pain Society Pain scale), quality of life (EuroQoL), physical function (HAQ-DI), inflammation (CRP) and emotional intelligence (Trait Emotional Intelligence Questionnaire - TEIQue-SF) were analysed from data from 100 patients (50 PsA and 50 RA).ResultsUpto 30% of patients with PsA and RA were found to be depressed. Similarly, upto 25% of patients with PsA and RA fulfilled the criteria for caseness on the HADS A subscale.None of these patients were on therapeutic doses of an antidepressant. There was significant correlation between depression scores and scores on quality of life, disability and emotional intelligence. Together, they explained almost 50% of the variance in depression scores.ConclusionThe prevalence of depression is high in people with inflammatory arthritides. Disability, Quality of life and trait emotional intelligence seems to be important factors associated with inflammation and presence of depression in this population.

Metabolic risk factors are a major comorbidity in patients with cirrhosis independent of the presence of hepatocellular carcinoma

Recent studies have identified cases of hepatocellular carcinoma (HCC) arising in cryptogenic cirrhosis and proposed that many of them may be attributable to nonalcoholic fatty liver disease (NAFLD). To evaluate the prevalence of NAFLD-associated metabolic risk factors among HCC patients to determine whether NAFLD could have played a role in the development of HCC. Patients with HCC in the setting of hepatic cirrhosis and age-matched, sex-matched, and Child-Pugh-matched cirrhotic patients were included in this study. A verbal interview regarding family and personal history of metabolic risk factors; a complete physical examination, including morphometric measurements; and a blood analysis evaluating liver function and cirrhosis etiology were conducted with each patient. Seventy HCC patients and 64 tumor-free cirrhotics were included. Sixty-six patients (49%) were overweight and 37 (28%) obese, with a median body mass index of 27.6 (range: 19-41). Fifty-six patients (42%) had central adiposity, 62 (46%) had hypertension, 46 (34%) had type 2 diabetes, seven (5%) had coronary artery disease, and 48 (36%) had dyslipidemia. There were no significant differences in the distribution of metabolic risk factors between the groups. The main cause of cirrhosis was HCV in 83 patients (62%). In only two patients (1.4%), no cirrhosis etiology could be determined; both of them had HCC and metabolic risk factors. Metabolic risk factors are a major health issue in patients with liver disease, regardless of the presence of HCC. Metabolic factors may have been risk factors for the development of liver disease and cirrhosis, even when other established causes of cirrhosis were present.

Peginterferon α-2a and ribavirin treatment of patients with haemophilia and hepatitis C virus infection: a single-centre study of 367 cases

Chronic hepatitis C virus infection (HCV) is a major comorbidity in patients with haemophilia. Peginterferon alpha and ribavirin is current standard anti-HCV therapy but there is little information about safety and efficacy of peginterferon alpha-2a and ribavirin combination therapy in these patients. In an open-label single-treatment arm cohort study, 367 haemophilia patients seronegative for hepatitis B and human immunodeficiency virus markers and chronically infected with HCV (HCV RNA>50 IU/ml for at least 6 months) received 180 microg of Pegasys and 800-1200 mg of ribavirin according to body weight. Genotypes 1 and 4, mixed and untypable infections were treated for 48 weeks, while genotypes 2 and 3 were treated for 24 weeks. The efficacy of therapy was expressed as sustained virological response (SVR). Two hundred and twenty-five subjects [61%, 95% confidence interval (CI) 56-66] achieved SVR, 66 patients relapsed and 30 subjects did not respond and nine patients developed breakthrough during treatment. In a multivariate logistic regression model, age<24 odds ratio (OR)=1.8 (95% CI 1.1-3.1), genotype non-1 OR=1.8 (95% CI 1.1-3.2), BMI<25 OR=2.1 (95% CI 1.3-3.3) and HCV RNA<600 000 IU/ml OR=1.7 (95% CI 1.1-3.2) were independent predictors of SVR. Eight patients discontinued the treatment because of persistent neutropaenia and 22 subjects were dropped out because of intractable side effects. Furthermore, two patients died during treatment and five were lost to follow-up after treatment cessation. Peginterferon alpha-2a in combination with weight-based ribavirin has SVR rate of 51% for genotype 1 and 71% for genotype non-1 infections in haemophilia patients. Age<24, BMI<25, viral load<600 000 IU/ml and genotype non-1 are the major determinants of SVR achievement in these patients.

Comorbidities and clinical determinants of outcome in children with spastic quadriplegic cerebral palsy

The objective of this study was to determine the major comorbidities in patients with spastic quadriplegic (SQ) cerebral palsy (CP) and their possible clinical associations. Medical records of patients with SQ CP from a pediatric neurology practice over a 14-year period were retrospectively and systematically reviewed. Variables examined included demographics, prenatal, perinatal, and postnatal risk factors. Comorbidities documented included those involving hearing, vision, feeding status, and epilepsy. Binomial logistic regression analyses were applied to identify clinical associations of the comorbidities. Ninety-two children were included in this study of whom 39 were born preterm. Mean age of presentation was 2 months (SD 3.5) and males comprised 60% of the group. A total of 57% had a Gross Motor Function Classification Score (GMFCS) of Level IV or V. The four documented comorbidities occurred at a high frequency: 66 out of 83 children (80%) had a visual impairment with 13 (21%) having a substantial impairment; 37 out of 86 children (40%) had a hearing deficit; 43 out of 92 children (47%) had epilepsy; and 29 (33%) required assisted feeding. A GMFCS Level of IV or V and documented microcephaly was associated with the need for assisted feeding (odds ratio [OR] 8.1; 95% confidence interval [CI] 2.1-29.8, p=0.002 and OR 4.9, 95% CI 1.7-14.8, p=0.004 respectively). Epilepsy was associated with the occurrence of neonatal encephalopathy (OR 2.3, 95% CI 1.0-55; p=0.05), microcephaly (OR 4.9, 95% CI 1.6-14.8; p=0.004), periventricular leukomalacia (OR 7.4, 95% CI 1.6-35.0; p=0.012), and perinatal asphyxia (OR 3.6, 95% CI 1.5-8.9; p=0.005). There is a high frequency of comorbidity in the setting of SQ CP which can impact on quality of life and burdens of care. Few clinical associations of this burden appear, thus necessitating systematic programmatic follow-up of these children to facilitate early identification and intervention.