Guided self-determination improves life skills with type 1 diabetes and A1C in randomized controlled trial

OBJECTIVE: To report 1-year results of newly developed method, guided self-determination (GSD), applied in group training (GSD-GT) for Type 1 diabetes patients with persistent poor glycaemic control. METHODS: GSD was designed on the basis of qualitative research to help patients develop life skills with diabetes using worksheets filled in at home and coached by nurses in mutual reflection. We randomized 18-49-year-old adults at a Danish university hospital to either 16 h GSD-GT in 2001 or to similar training 1 year later. Inclusion criteria: mean A1C> or =8.0% for at least 2 years, disease onset < or =40 years and insulin treatment from onset. RESULTS: Thirty GSD-GT patients and 20 controls completed the study. GSD-GT patients did better than control patients in terms of (a) increased autonomy support perceived from health professionals (p<0.01); (b) higher frequency of self-monitored blood glucoses (p<0.001); (c) increased perceived competence in managing diabetes (p<0.01); (d) fewer diabetes-related problems (p<0.05); and (e) improved glycaemic control (p<0.01). CONCLUSION: GSD was effective in improving life skills with diabetes, including A1C, over a period of 1 year. PRACTICE IMPLICATIONS: GSD is a worthy candidate for further research. We consider it adjustable to people with type 2 diabetes and other chronic conditions.     

High concentrations of anti-caspase-8 antibodies in Chilean patients with type 1 diabetes

IntroductionDeregulation of apoptosis across the Fas–FasL pathway is an increasingly relevant phenomenon in the pathogenic mechanisms associated with autoimmune diseases. Caspase-8 initiates the activation of the apoptotic process and interacts directly with Fas in the membrane of the T lymphocyte.ObjectivesTo standardize an Elisa essay to measure the concentration of anti-caspase-8 antibodies in plasma of Type 1 Diabetes (T1D) patients and analyze their possible distribution and association with characteristics of the disease.Methods and subjects124 patients newly diagnosed with T1D and 132 controls: children and youngsters. ELISA test was standardized to detect anti-caspase-8 antibodies in plasma. It correlated the concentration of this antibody with classical markers of autoimmunity as anti-IA-2 and anti-GAD65, and the clinical characteristics at onset of diabetes mellitus. The statistical analysis was performed using logistic regression.ResultsPatients with T1D showed a higher concentration of anti-caspase-8 antibodies regarding the controls (87.5 ng/ml versus 24.3 ng/ml, p < 0.0001, values expressed as median). The proportion of patients with T1D and high concentrations of anti-caspase-8 (percentile 50–75) was significantly different from the control group (p < 0.0001). Anti-caspase-8 showed a strong association with positive anti-GAD65 (OR = 3.48, p < 0.035) and ketoacidosis (OR = 10.74, p < 0.0001) events, with glycemia and age at diagnosis as contributing variables.ConclusionThis is the first report in the literature of levels of anti-caspase-8 antibodies in T1D through ELISA. The high concentration in patients with T1D, and its strong correlation with anti-GAD65 auto-antibodies, suggests a potential role of anti-caspase-8 auto-antibodies as surrogate marker autoimmunity in T1D patients.     

Rhino/enteroviruses in hospitalized children: A comparison to influenza viruses

BackgroundThe relative impact of human rhino/enteroviruses (HRV/EV) compared to influenza viruses on hospitalized children is unknown.ObjectivesThis retrospective study compared the epidemiology and clinical characteristics of hospitalized patients with HRV/EV to patients hospitalized with influenza virus.Study designRespiratory specimens from hospitalized children submitted between January 1, 2009 and December 31, 2009 to Children's Hospital Colorado Virology Laboratory in Aurora, CO were tested by a commercial multiplex PCR for 16 respiratory viruses and subtypes. Patients with specimens positive for HRV/EV or influenza virus without bacterial or viral co-infection were selected for retrospective chart review.ResultsOf the 2299 patients with specimens tested during the study period, 427 (18.6%) were singly positive for HRV/EV and 202 (8.8%) for influenza virus (p < 0.01). Children with HRV/EV were more likely to present with increased work of breathing (67.9% vs. 52.5%, p < 0.01) with crackles (36.3% vs. 23.3%, p < 0.01) and wheezing (41.7% vs. 22.8%, p < 0.01) noted on exam. Children hospitalized with HRV/EV had a shorter median length of stay (2 days vs. 3 days, p < 0.01), duration of fever (1 days vs. 3 days, p < 0.01), and duration of hypoxemia (2 days vs. 3 days, p < 0.01) than children with influenza virus. Similar percentages of children with HRV/EV and influenza virus were admitted to the PICU and required positive pressure ventilation. There were no deaths in children hospitalized with HRV/EV, whereas 6 children with influenza virus expired.ConclusionsHRV/EVs are common pathogens in hospitalized children associated with serious lower respiratory tract disease and significant morbidity, similar to influenza viruses.     

Implementation and outcomes of telephone disclosure of clinical BRCA1/2 test results

ObjectivesWith an increasing demand for genetic services, effective and efficient delivery models for genetic testing are needed.MethodsIn this prospective single-arm communication study, participants received clinical BRCA1/2 results by telephone with a genetic counselor and completed surveys at baseline, after telephone disclosure (TD) and after in-person clinical follow-up.ResultsSixty percent of women agreed to participate; 73% of decliners preferred in-person communication. Anxiety decreased from baseline to post-TD (p = 0.03) and satisfaction increased (p < 0.01). Knowledge did not change significantly from baseline to post-TD, but was higher post-clinical follow-up (p = 0.04). Cancer patients had greater declines in state anxiety and African-American participants reported less increase in satisfaction. 28% of participants did not return for in-person clinical follow-up, particularly those with less formal education, and higher post-disclosure anxiety and depression (p < 0.01).ConclusionsTelephone disclosure of BRCA1/2 test results may not be associated with negative cognitive and affective responses among willing patients, although some subgroups may experience less favorable responses. Some patients do not return for in-person clinical follow-up and longitudinal outcomes are unknown.Practice implicationsFurther evaluation of longitudinal outcomes of telephone disclosure and differences among subgroups can inform how to best incorporate telephone communication into delivery of genetic services.     

Knee laxity of Malaysian adults: Gender differentials,and association with age and anthropometric measures

BackgroundKnee laxity measurements have been shown to be associated with some medical conditions such as chronic joint pain and collagen tissue diseases. The aim of this study was to determine the effects of demographic factors and anthropometric measures on knee laxity.Materials and methodsData were collected from 521 visitors, staffs and students from the University Malaya Medical Centre and University of Malaya between December 2009 and May 2010. Knee laxity was measured using a KT-1000 arthrometer. Multiple regression analysis was used to find the association of knee laxity with age and anthropometric measures.ResultsUsing ANOVA, knee laxity did not show significant differences among ethnic groups for both genders. The average knee laxity in men was 3.47 mm (right) and 3.49 mm (left); while in women were 3.90 mm (right) and 3.67 mm (left). Knee laxity in women was significantly higher (right knee p < 0.01 and left knee p < 0.05) than men. Right knee laxity of men was negatively associated with height (p < 0.05) and BMI (p < 0.05); also a negative association was observed between left knee laxity and BMI (p < 0.05). Overweight and obese men had less knee laxity than normal weight and underweight individuals. Elderly men and women (age 55 and above) had lower knee laxity (p < 0.01) than young adults (ages 21–39).ConclusionThese results suggest that age and body size are important factors in predicting knee laxity.     

An adaptive case management system to support integrated care services: Lessons learned from the NEXES project

BackgroundExtensive deployment and sustainability of integrated care services (ICS) constitute an unmet need to reduce the burden of chronic conditions. The European Union project NEXES (2008–2013) assessed the deployment of four ICS encompassing the spectrum of severity of chronic patients.ObjectiveThe current study aims to (i) describe the open source Adaptive Case Management (ACM) system (Linkcare®) developed to support the deployment of ICS at the level of healthcare district; (ii) to evaluate its performance; and, (iii) to identify key challenges for regional deployment of ICS.MethodsWe first defined a conceptual model for ICS management and execution composed of five main stages. We then specified an associated logical model considering the dynamic runtime of ACM. Finally, we implemented the four ICS as a physical model with an ICS editor to allow professionals (case managers) to play active roles in adapting the system to their needs. Instances of ICS were then run in Linkcare®. Four ICS provided a framework for evaluating the system: Wellness and Rehabilitation (W&R) (number of patients enrolled in the study (n) = 173); Enhanced Care (EC) in frail chronic patients to prevent hospital admissions, (n = 848); Home Hospitalization and Early Discharge (HH/ED) (n = 2314); and, Support to remote diagnosis (Support) (n = 7793). The method for assessment of telemedicine applications (MAST) was used for iterative evaluation.ResultsLinkcare® supports ACM with shared-care plans across healthcare tiers and offers integration with provider-specific electronic health records. Linkcare® successfully contributed to the deployment of the four ICS: W&R facilitated long-term sustainability of training effects (p < 0.01) and active life style (p < 0.03); EC showed significant positive outcomes (p < 0.05); HH/ED reduced on average 5 in-hospital days per patient with a 30-d re-admission rate of 10%; and, Support, enhanced community-based quality forced spirometry testing (p < 0.01). Key challenges for regional deployment of personalized care were identified.ConclusionsLinkcare® provided the required functionalities to support integrated care adopting an ACM model, and it showed adaptive potential for its implementation in different health scenarios. The research generated strategies that contributed to face the challenges of the transition toward personalized medicine for chronic patients.     

Physicians’ decision-making style and psychosocial outcomes among cancer survivors

ObjectiveWe evaluated pathways linking physicians’ decision-making style with cancer survivors’ health-related quality of life (HRQOL).MethodsWe analyzed survey data from 623 survivors diagnosed with leukemia, colorectal, or bladder cancer in Northern California, 2–5 years prior to the study. Of these, 395 reported making a medical decision in the past 12 months and were asked about their physician's decision-making style. We evaluated the association of physician style with proximal communication outcomes (trust and participation self-efficacy), intermediate cognitive outcomes (perceived control and uncertainty), and distal health outcomes (physical and mental HRQOL).ResultsOverall, 54% of survivors reported a sub-optimal decision-making style for their physician. With the exception of physical health, physician style was associated with all proximal, intermediate, and distal outcomes (p ≤ 0.01). We identified two significant pathways by which a participatory physician style may be associated with survivors’ mental health: (1) by increasing survivors’ participation self-efficacy and thereby enhancing their perceptions of personal control (p < 0.01); (2) by enhancing survivors’ level of trust and thereby reducing their perceptions of uncertainty (p < 0.05).ConclusionA participatory physician style may improve survivors’ mental health by a complex two-step mechanism of improving survivors’ proximal communication and intermediate cognitive outcomes.Practice implicationsPhysicians who adopt a participatory decision-making style are likely to facilitate patient empowerment and enhance patients’ HRQOL.     

Impact of diabetes on mortality and complications after coronary artery by-pass graft operation in patients with left main coronary artery disease

PurposeLeft main disease (LMD) is a severe form of coronary artery disease (CAD). Fifty percent of patients with LMD treated conservatively die within 3–5 years of diagnosis. The aim of the study was to assess the influence of type 2 diabetes on early and late (2-year) prognosis and the risk of complications after coronary artery by-pass graft (CABG) surgery in patients with LMD.Material/methodsWe enrolled 257 patients diagnosed with LMD. 169 (67%) underwent CABG, 19 (8%) percutaneous coronary intervention (PCI) without left main stem protection. 30 (12%) patients had CABG previously. Patients treated with CABG were divided into two groups – with and without diabetes. There were 43 (25.4%) patients with diabetes and 126 (74.6%) without diabetes.ResultsWe observed more complications with wound healing (40.5% vs. 12.8%, p < 0.001) and sternal dehiscence (23.8% vs. 4.0%, p < 0.001) after CABG in patients with diabetes. There were no differences in 7-day, 30-day, 3-month and 1-year mortality. 2-Year mortality was also similar in both groups (11.6% vs. 11.1%, p = 0.928). Patients with diabetes were more frequently hospitalized due to other reasons than angina (39.5% vs. 20.6%, p = 0.014).ConclusionsPatients with diabetes and LMD had more often complications with wound healing and sternal dehiscence after CABG than patients without diabetes. Type 2 diabetes did not influence early and late mortality in patients with LMD treated with cardiac surgery, but the presence of diabetes was associated with more frequent hospitalizations.     

The role of patient education and physician support in self-efficacy for skin self-examination among patients with melanoma

ObjectiveThis project aims to elucidate the relationships between skin self-examination (SSE), perceived physician support of SSE, and self-efficacy for SSE among melanoma patients.MethodsA longitudinal study of patients diagnosed with melanoma was conducted over the span of 18 months. Participants filled out questionnaires at four assessment points and participated in an SSE education about the early signs of melanoma.ResultsAmong the 242 patients enrolled, the level of self-efficacy for SSE was 23% higher immediately after the educational intervention (p < .001) and the increase was retained three months (p < .001) and twelve months later (p < .001). Additionally, a one-way repeated measures ANOVA revealed that the perceived physician support of SSE positively corresponded to the level of patient self-efficacy with higher patient-reported physician support being related to higher self-efficacy (p = .001).ConclusionPatient education and perceived physician support of SSE are positively associated with patients’ level of self-efficacy.Practice implicationsPhysicians caring for melanoma survivors should be aware that, both SSE education and patients’ perception of high physician support of SSE may be associated with higher self-efficacy for checking one’s own skin for signs of cancer recurrence.     

High seroprevalence against hepatitis E virus in patients with chronic hepatitis C virus infection

BackgroundHepatitis E virus (HEV) genotype 3 is endemic in Europe. Superinfection with HEV in patients with underlying chronic liver disease can cause hepatic decompensation leading to increased morbidity and mortality.ObjectivesThe prevalence of anti-HEV antibodies was investigated in 204 patients with chronic hepatitis C virus (HCV) infection and different stages of fibrosis.Study designSera were analyzed for anti-HEV IgG, IgM and HEV RNA.ResultsThe median age of the patients was 55 years (IQR 40–62 years); 126 (62%) were men. Ninety-eight (48%) patients had a METAVIR fibrosis stage F2 or higher. The prevalence of anti-HEV IgG was 30% (62/204), which was significantly higher than among Swedish blood donors (17%, p < 0.01). The prevalence of anti-HEV antibodies was associated with higher age (OR 1.08 (1.05–1.11); p < 0.01). It was also higher for patients with a prior history of blood transfusion (48%) as compared to intravenous drug use (IDU; 26%) as the risk factor for acquisition of the HCV infection (OR 2.72 (1.2–6.19); p < 0.02). The prevalence of anti-HEV IgG was also significantly higher in patients with significant fibrosis, i.e. ≥F2 (38%; OR 2.04 (1.11–3.76); p = 0.02) and/or neoplasm (72%; OR 7.27 (2.46–21.44); p < 0.01).ConclusionsWhen adjusted for age, the prevalence of anti-HEV antibodies was significantly higher in patients with previous or current malignant liver disease compared to blood donors. The lack of significant correlation between HCV and HEV infections indicate low level of transmission of HEV by IDU. HEV infections warrant more attention, especially in patients with preexisting liver disease.     

Anti-Tax antibody levels in asymptomatic carriers,oligosymptomatic carriers,patients with rheumatologic disease or with HAM/TSP do not correlate with HTLV-1 proviral load

BackgroundHTLV-1 infects millions of people around the world and induces myelopathy (HAM/TSP), adult T-cell leukemia (ATL) or other inflammatory or rheumatologic diseases. The host–virus interaction causes asymptomatic carriers to develop HAM/TSP. Biomarkers are needed to predict patients who are at risk for HAM/TSP. Tax is highly immunogenic and is a major target protein recognized by cytotoxic T lymphocytes. Anti-Tax antibodies are involved in HAM/TSP pathogenesis.ObjectivesTo assess anti-Tax IgG reactivity with a flow cytometry assay (FCA) using an infection/transfection system with Vaccinia virus and pLW44/Tax-expressing Tax and to correlate the anti-Tax response and the HTLV-1 proviral load.Study design: We enrolled 81 individuals: 9 HTLV-1 seronegative (NP) and 72 HTLV-1 positive (23 HTLV-1 asymptomatic carriers (AC), 12 oligosymptomatic patients (OL), 7 with rheumatologic diseases (DR) and 30 with HAM/TSP (HT)). Anti-Tax reactivity was assessed by FCA, and HTLV-1 proviral load was measured with real time PCR.ResultsThe HT and DR groups showed greater anti-Tax IgG reactivity (p < 0.001 and p < 0.05 comparing HT to the OL and AC group, respectively; p < 0.05 comparing DR to the OL group), and the reactivity in the DR + HT group was significantly different when compared to the AC group (p < 0.05) and to the OL group (p < 0.001). The proviral load was higher in the HT group compared to the OL (p < 0.001) and in the HT + DR group compared to OL (p < 0.001). There was no correlation between anti-Tax IgG reactivity and proviral load in any of the HTLV-1-infected groups.ConclusionThese findings suggest that although anti-Tax IgG reactivity and the HTLV-1 proviral load are important markers of the development of HTLV-1-associated diseases, their levels are not correlated.     

The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency

Background and ObjectiveHereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) causes disturbances in the complement system. However, the influence of HAE-C1-INH on the lectin pathway of complement is unresolved. Thus, we studied the main initiator molecules, enzymes and regulators in the lectin pathway in patients with HAE-C1-INH.MethodsThe serum concentrations of ficolin-2, ficolin-3, MBL, MASP-2, MASP-3, and MAP-1 were measured during symptom-free periods in 91 patients with HAE-C1-INH, and in 100 healthy controls using sandwich ELISAs.ResultsCompared with controls, the levels of ficolin-2 (p < 0.0001) and MASP-2 (p = 0.0238) were reduced, while the levels of MBL and MASP-3 were elevated (p = 0.0028 and p < 0.0001, respectively) in HAE-C1-INH patients. Ficolin-3 and MAP-1 levels did not differ significantly between the two groups. Ficolin-2 correlated with MASP-3 in patients (r = 0.3443, p = 0.0008), while these parameters showed an opposite relationship in controls (r = −0.4625, p < 0.0001). In the patients, ficolin-3 correlated with MASP-2 (r = 0.3698, p = 0.001). Ficolin-2, -3, and MAP-1 correlated negatively with the annual requirement of plasma derived C1-INH concentrate (r = −0.2863, p = 0.0059; r = −0.2654, p = 0.0110 and r = −0.2501, p = 0.0168, respectively). Ficolin-3 showed a negative correlation with the annual number of attacks (r = −0.2478, p = 0.0179).ConclusionsWe found significant differences between patients and controls in the levels of some of the molecules belonging to the lectin complement pathway. Low concentrations of particularly ficolin-2 and -3 were inversely correlated with the severity of HAE-C1-INH, while this was not observed for MBL. This suggests a previously unrecognized involvement of the ficolin-dependent lectin complement pathway in the pathophysiology of HAE-C1-INH.     

Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease

BackgroundAlloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization.Study designTwo-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT–HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression.ResultsWhile only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p = 0.02), -DQ3 (p = 0.02) and -DQ5 (p = 0.01) alleles were significantly higher in non-alloimmunized patients, likely behaving as protective alleles. In addition, multiple logistic regression analysis showed both HLA-DQ2/6 (p = 0.01) and HLA-DQ5/5 (p = 0.03) combinations constitute additional predictor of protective status.ConclusionOur data suggest that particular HLA-DQ alleles influence the clinical course of RBC transfusion in patients with SCD, which could pave the way towards predictive strategies.     

Specifying the effects of physician's communication on patients’ outcomes: A randomised controlled trial

ObjectiveTo experimentally test the effects of physician's affect-oriented communication and inducing expectations on outcomes in patients with menstrual pain.MethodsUsing a 2 × 2 RCT design, four videotaped simulated medical consultations were used, depicting a physician and a patient with menstrual pain. In the videos, two elements of physician's communication were manipulated: (1) affect-oriented communication (positive: warm, emphatic; versus negative: cold, formal), and (2) outcome expectation induction (positive versus uncertain). Participants (293 women with menstrual pain), acting as analogue patients, viewed one of the four videos. Pre- and post video participants’ outcomes (anxiety, mood, self-efficacy, outcome expectations, and satisfaction) were assessed.ResultsPositive affect-oriented communication reduced anxiety (p < 0.001), negative mood (p = 0.001), and increased satisfaction (p < 0.001) compared to negative affect-oriented communication. Positive expectations increased feelings of self-efficacy (p < 0.001) and outcome expectancies (p < 0.001), compared to uncertain expectations, but did not reduce anxiety. The combination of positive affect-oriented communication and a positive expectation reduced anxiety (p = 0.02), increased outcome expectancies (p = 0.01) and satisfaction (p = 0.001).ConclusionBeing empathic and inducing positive expectations have distinct and combined effects, demonstrating that both are needed to influence patients’ outcomes for the best.Practice implicationsContinued medical training is needed to harness placebo-effects of medical communication into practice.     

Polymyositis/dermatomyositis and nasopharyngeal carcinoma: The Epstein–Barr virus connection?

BackgroundPolymyositis (PM) and dermatomyositis (DM) are associated with high risk of nasopharyngeal carcinoma (NPC) in Asian countries. Epstein–Barr virus (EBV) might induce autoimmunity and malignancies in susceptible individuals.ObjectivesTo investigate the association of EBV with PM/DM and NPC in PM/DM patients.Study designSerum levels of anti-EBV viral capsid antigens (VCA) and anti-EBV-coded nuclear antigens-1 (EBNA-1) antibodies were measured by ELISA, and EBV DNA loads were determined using real-time PCR for 98 PM/DM patients, 94 systemic lupus erythematosus (SLE) patients and 370 healthy controls (HC). Anti-transfer-RNA synthetase antibodies (ASA) were determined by radioimmunoprecipitation for PM/DM patients.ResultsThirteen (13.3%) of PM/DM patients vs. none of SLE patients had detectable NPC. ASA were detectable in 31.7% of PM/DM without malignancy, while lack of ASA in any PM/DM patient with NPC. IgA anti-EBNA-1 were detectable in 30.6% of PM/DM patients and 31.9% of SLE patients, but only in 4.1% of HC (odds ratio [OR] 10.44 and 11.12 respectively, both p < 0.001). Significantly higher positivity for IgA anti-EBNA-1 were observed in PM/DM with NPC than in those without malignancy (OR 44.7, p < 0.01). Significantly higher positivity for EBV genome were observed in PM/DM with NPC than in those without malignancy (OR 43.9, p < 0.01), in SLE patients (OR 13.2, p < 0.05) and in HC (OR 99.4, p < 0.001). EBV DNA loads were significantly higher in PM/DM with NPC compared with those without malignancy and HC.ConclusionsOur results showed a positive association of EBV with PM/DM and NPC. PM/DM patients who have IgA anti-EBNA-1 or increased EBV DNA loads should be highly suspected to have occult NPC.     

High expression of OX40 (CD134) and 4-1BB (CD137) molecules on CD4+CD25high cells in children with type 1 diabetes

PurposeDespite the rapidly rising incidence of diabetes in children, with the highest rise in children < 5 years of age, data on mechanisms that trigger severe beta-cells damage are limited. The aim of the study was to assess the frequency of OX40 (CD134) or 4-1BB (CD137) positive cells in the peripheral blood of children with newly diagnosed type 1 diabetes (T1D) in comparison to healthy controls.Material/methodsThe study included 33 children (mean age 7.3 ± 5.4 years) with newly diagnosed T1D and 39 age-matched healthy controls. Separate analysis was performed in children < 5 years. Flow cytometric analysis was performed using the following markers: CD4, CD25, CD137, and CD134. Fasting C-peptide level was assessed as well.ResultsThe frequency of CD4⁺CD25^highOX40⁺ was higher in T1D children than in controls (median value 3.58% vs. 1.1%, respectively; p = 0.003). Moreover, T1D children had higher frequency of CD4⁺CD25^high4-1BB⁺ cells than healthy subjects (median value 5.76% vs. 3.74%, respectively; p = 0.037). A significant correlation was noted between the age of diabetic children and the C-peptide level (r = 0.54, 95% CI [0.19–0.77], p = 0.004). In comparison with age-matched controls, children < 5 years had higher frequency of CD4⁺CD25^highOX40⁺ (p = 0.004) and CD4⁺CD25^high4-1BB⁺ cells (p = 0.079).ConclusionsOur study showed higher frequency of both OX40 and 4-1BB positive cells in T1D children in comparison to controls. It seems that observed differences might be more pronounced in children < 5 years of age than in older subjects. Further clinical studies are needed to determine the age-related differences in the immune system, in the pathogenesis of T1D.     

Serum paraoxonase 1 activity and oxidant/antioxidant status in Saudi women with polycystic ovary syndrome

Oxidative stress is considered to be implicated in the pathophysiology of polycystic ovary syndrome (PCOS). This study was designed to evaluate the paraoxonase 1 (PON1) activity and oxidant/antioxidant status in Saudi women with PCOS and its contribution to the risk of atherosclerosis.Lipid profile, hormonal parameters, serum PON1 activity and oxidant (malondialdehyde)/antioxidant (total antioxidant capacity (TAC) levels were analyzed in 35 patients with PCOS and 30 healthy controls using a spectrophotometric method; correlation analysis was made between these variables. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR).Women with PCOS had significantly higher fasting insulin, HOMA-IR and LH levels than controls. Lipid profiles and free androgen index (FAI) were significantly higher in women with PCOS when compared with controls. Serum PON1 activity was lower in the PCOS group (161.2 ± 6.1 U/l vs. 217.6 ± 9.3 U/l, p < 0.001) compared with controls, whereas malondialdehyde levels were higher in the PCOS group (4.26 ± 0.18 nmol/ml vs. 1.37 ± 0.12 nmol/ml, p < 0.001) compared with controls. Total antioxidant capacity was lower in the PCOS group (0.88 ± 0.10 mmol Trolox/l vs. 1.63 ± 0.17 mmol Trolox/l, p < 0.001) compared with controls. In PCOS group, serum PON1 was positively correlated with HDL-C (r = 0.425, p < 0.05) and TAC (r = 0.582, p < 0.01) but inversely correlated with HOMA-R (r = ?0.54, p < 0.01), testosterone (r = ?0.672, p < 0.01), FAI (r = ?0.546, p < 0.01) and malondialdehyde (r = ?0.610, p < 0.01).In conclusion, our data indicate that PON1 activity and antioxidant status were significantly decreased in Saudi women with PCOS. Lower serum PON1 activity might contribute to the increased susceptibility for the development of atherosclerosis risk in Saudi women with PCOS. Therefore, measurement of serum PON1 activity may be of value in assessment of women at higher risk for development of atherosclerosis risk in PCOS. However, further studies with larger sample size are needed to verify these results, and to assess the efficacy of antioxidant therapy on these patients.     

A distinct salivary secretory response mediated by the esophago-salivary reflex in patients with Barrett's esophagus: Its potential pathogenetic implications

PurposeA significantly compromised epidermal growth factor (EGF) secretion by basal parotid saliva may contribute to the development of Barrett's esophagus (BE). The rate of secretion of EGF as well as a wide spectrum of protective factors in total basal and stimulated saliva in BE patients remains to be explored. We therefore studied the rate of secretion of salivary buffers, glycoconjugate, protein, EGF, transforming growth factor α (TGFα) and prostaglandin E₂ (PGE₂), evoked by esophago-salivary reflex, in patients with BE and controls (CTRL).Material/methodsSalivary secretion was collected during basal condition, mastication, and intraesophageal mechanical and chemical stimulations respectively, mimicking the natural gastroesophageal reflux scenario.ResultsSalivary pH in BE was significantly lower than in controls during mechanical (p < 0.001) and chemical stimulations (p < 0.001). Bicarbonate and protein outputs in BE were significantly lower during mechanical (p < 0.05) and chemical stimulations (p < 0.01). The non-bicarbonate and glycoconjugate outputs in BE were lower during chemical stimulation (p < 0.05) and during mechanical (p < 0.05) and chemical stimulations (p < 0.05) respectively. The rate of salivary EGF output in BE was significantly lower during mechanical stimulation (p < 0.05). We observed a higher TGFα output during mastication (p < 0.05) and PGE₂ secretion during basal and masticatory condition (p < 0.05) in BE.ConclusionsPatients with BE demonstrated significantly compromised salivary pH and rate of secretion of bicarbonate, non-bicarbonate, glycoconjugate, protein and EGF. This impairment could potentially predispose to the development of accelerated esophageal mucosal injury. Potential restoration of this impairment by masticatory stimulation of salivary secretion using sugarless chewing gum justifies further clinical exploration.     

Evaluation of a 3D serious game for advanced life support retraining

ObjectiveAdvanced life support (ALS) knowledge and skills decrease in as little as three months, but only a few ALS providers actually attend retraining courses. We assess the effectiveness of a 3D serious game as a new tool for frequent ALS retraining.MethodsWe developed a 3D serious game for scenario-based ALS retraining. The serious game, called EMSAVE, was designed to promote self-correction while playing. We organized a retraining course in which 40 ALS providers played two cardiac arrest scenarios with EMSAVE and took a test with 38 multiple-choice questions before and after playing. We administered the same test again 3 months later to evaluate retention. Participants also rated EMSAVE and the overall retraining experience.ResultsAfter using EMSAVE, the number of correct answers per participant increased by 4.8 (95%CI +3.4, +6.2, p < 0.001) and all but one participant improved. After 3 months, despite an expected decrease in ALS knowledge and skills (?1.9 correct answers, 95%CI ?0.6, ?3.3, p < 0.01), there was a significant retention benefit (+2.9 correct answers per participant, 95%CI +1.5, +4.2, p < 0.001). Moreover, all but one participant regarded EMSAVE as a valuable tool to refresh ALS knowledge and skills, and 85% of participants were also willing to devote 1 h/month to retrain with the serious game.ConclusionsA 3D serious game for scenario-based retraining proved effective to retrain in ALS and supported retention of acquired knowledge and skills at 3 months. EMSAVE also positively engaged and motivated participants.