Could distal variants in ALG13 lead to atypical clinical presentation?

Congenital disorders of glycosylation (CDG) represent a wide range of some 150 inherited metabolic diseases, continually expanding in terms of newly identified genes and the heterogeneity of clinical and molecular presentations within each subtype. Heterozygous pathogenic variants in ALG13 are associated with early-onset epileptic encephalopathy, typically in females. The majority of subjects described so far harbour one of the two recurrent pathogenic variants, namely p.(Asn107Ser) and p.(Ala81Thr) in the C-terminal glycosyltransferase domain. We report a novel ALG13 variant (c.1709G > A, p.(Gly570Glu)) in an adult female with unremarkable past developmental and medical history, except for mild kinetic tremor. Our proband presented with acute onset of neurological and psychiatric features, along with liver dysfunction, during pregnancy, all of which gradually resolved after delivery. The proband's newborn baby died at 22 days of life from neonatal liver disease, due to gestational alloimmune liver disease (GALD). Functional assessment on fibroblasts derived from our case showed alterations in 2 of 3 cellular glycosylation markers (LAMP2, Factor IX), suggesting a functional effect of this novel ALG13 variant on glycosylation. This paper raises the possibility that variants outside the glycosyltransferase domain may have a hypomorphic effect leading to atypical clinical manifestations.     

Should beta-blockers be given to patients with heart disease and peanut-induced anaphylaxis? A decision analysis

BACKGROUND: Beta-blocker therapy postmyocardial infarction is generally recommended because it reduces mortality. However, beta-blockers may increase anaphylaxis mortality in the growing population of patients with peanut-induced anaphylaxis. OBJECTIVE: We sought to assess the risks and benefits of beta-blocker therapy among patients with peanut allergy and heart disease. METHODS: We created a Markov model for patients with heart disease at risk for peanut-induced anaphylaxis to compare life expectancy with the following strategies: (1) beta-blocker and (2) no beta-blocker. Meta-analysis and a literature review were used to estimate model parameters. We performed sensitivity analysis to explore parameter uncertainty. RESULTS: For peanut-allergic patients who are postmyocardial infarction or who have congestive heart failure, the heart disease benefit of beta-blockers outweighs the increased likelihood of dying from anaphylaxis, increasing life expectancy by 9.4 and 17.4 months, respectively. Beta-blocker was preferred unless (1) the annual rate of moderate to severe anaphylaxis exceeded 6.0% for postmyocardial infarction and 15% for congestive heart failure patients; (2) beta-blocker therapy increased the incidence of moderate to severe anaphylaxis >2.5-fold for postmyocardial infarction and >5.8-fold for congestive heart failure patients; (3) anaphylaxis case fatality exceeded 6.5% postmyocardial infarction; or (4) beta-blocker therapy increased anaphylaxis case fatality >25-fold postmyocardial infarction. CONCLUSION: Our results suggest that for patients postmyocardial infarction or with congestive heart failure who are at risk for peanut-induced anaphylaxis, beta-blocker use should still improve survival. However, the epidemiology of anaphylaxis and effects of beta-blocker therapy on anaphylaxis incidence and mortality require further study.     

22q13 Microduplication in two patients with common clinical manifestations: a recognizable syndrome?

We report here on two unrelated patients (Patients 1 and 2) with a cryptic microduplication involving a 22q13 segment. Both patients manifested infantile hypotonia, developmental delay, and growth deficiency. In addition, an abnormal signal intensity area was detected in the frontal white matter of Patient 2 by brain MRI. Whole-genome microarray comparative genomic hybridization for Patient 1 and fluorescence in situ hybridization analysis with 22q-subtelomeric probes performed in both patients showed a submicroscopic 22q13 duplication that involved the SHANK3 gene. The duplication in Patient 1 was de novo type, while that in Patient 2 was derived from a familial 17;22 translocation. The presence of common clinical manifestations in the two patients with the common duplicated region led to a conclusion that 22q terminal duplication is a recognizable clinical entity, that is, the 22q13 microduplication syndrome.     

Decreased serum paraoxonase 1 (PON1) activity: an additional risk factor for atherosclerotic heart disease in patients with PCOS?

BACKGROUND: Patients with polycystic ovary syndrome (PCOS) may have an increased risk for the development of hypertension and atherosclerotic heart disease (AHD), the pathophysiological mechanisms of which are not clear. Paraoxonase1 (PON1) is a high-density lipoprotein-associated enzyme that prevents oxidative modification of low-density lipoprotein. The aim of this study was to measure the serum levels of PON1 activity in patients with PCOS and to compare with those of regularly cycling controls. METHODS: Serum lipid parameters, malondialdehyde (MDA) levels and PON1 activity, were measured in PCOS patients (n = 23) and regularly cycling, age-, body mass index- and smoking status-matched controls (n = 23). All patients had normal glucose tolerance test as assessed by a 75 g oral glucose tolerance test. None of the patients had clinically evident hypertension or AHD. RESULTS: Apart from the mean serum PON1 activity, all parameters in the lipid profile including serum MDA levels were comparable between the two groups. There were no significant differences in respect to fasting glucose (4.64 +/- 0.5 versus 4.43 +/- 0.83 mmol/l) and fasting glucose insulin ratio (11.06 +/- 8.26 versus 11.49 +/- 4.90) among the two groups (P > 0.05). However, HOMA insulin resistance index was significantly higher in patients with PCOS compared with the controls (2.06 +/- 0.86 versus 1.51 +/- 0.49; P = 0.01). Also, mean serum PON1 activity was significantly lower in the PCOS group compared with the controls (151.2 +/- 90.8 versus 217.7 +/- 101.6, respectively; P = 0.027). CONCLUSIONS: Reduced serum PON1 activity might contribute to the increased susceptibility for the development of AHD in women with PCOS.     

Everolimus,a promising medical therapy for coronary heart disease?

Coronary heart disease is mainly caused by atherosclerosis, which is a multifactotial and systemic disease. Lipid metabolism disorder and chronic inflammation are two well accepted mechanisms leading to atherosclerosis. The key initiating process in athrogenesis is lipid retention in subendothelium. Inflammatory activity plays an important role in the whole pathogenesis of atherosclerosis. Recent investigations have demonstrated that rapamycin reduces lipid retention by increasing adipose-tissue lipase activity and decreasing lipoprotein lipase activity. Rapamycin also reduce intracellular lipid accumulation in smooth muscle cells and macrophages. Since rapamycin is a definite immunosuppressive agent, and inflammatory process has been involved in atherosclerosis, the compound would have effect on the progression of atherosclerosis through reducing inflammatory activity. Moreover, rapamycin would protect plaque from rupture by selectively clearing macrophages without affecting vascular smooth muscle cells.     

Effect of atorvastatin in patients with chronic heart failure – insights from randomized clinical trials

Introduction

Recent large clinical trials have yielded disappointing results of rosuvastatin in the chronic heart failure (CHF) population. The question that remains is whether these results of rosuvastatin studies could be extended to other statins. Therefore, we performed a meta-analysis based on all currently available randomized controlled trials (RCTs) to evaluate the clinical efficacy of atorvastatin in CHF patients.

Material and methods

The published literature was scanned by formal searches of electronic databases up to January 2010. RCTs were eligible for inclusion if they compared atorvastatin versus placebo treatment in patients with CHF and reported the clinical outcomes.

Results

Pre-specified criteria were met by 7 trials involving 540 patients. The primary endpoint, all-cause mortality, was significantly reduced with atorvastatin therapy compared with placebo in CHF patients (odds ratio [OR] 0.39, P = 0.002), with similar results in cardiovascular mortality (OR 0.28, P = 0.002) and sudden cardiac death (OR 0.24, P = 0.01). There was also a significant decrease in hospitalization for worsening CHF with atorvastatin therapy compared with placebo (OR 0.30, P < 0.001).

Conclusions

This meta-analysis suggests the effectiveness of atorvastatin treatment in reducing the risks of all-cause mortality and worsening CHF hospitalization in patients with CHF. Further large, well-conducted randomized trials are needed to confirm the benefits of atorvastatin or other statins for CHF relative to placebo or rosuvastatin.     

Are psychoeducational smoking cessation interventions for coronary heart disease patients effective? Meta‐analysis of interventions

Purpose . This systematic review aimed to assess the effectiveness of psychoeducational smoking cessation interventions for coronary heart disease (CHD) patients; and to examine behaviour change techniques used in interventions and their suitability to change behavioural determinants. Methods . Multiple bibliographic databases and references of retrieved articles were searched for relevant randomized controlled studies. One reviewer extracted and a second reviewer checked data from included trials. Random effects meta‐analyses were conducted to estimate pooled relative risks for smoking cessation and mortality outcomes. Behaviour change techniques used and their suitability to change behavioural determinants were evaluated using a framework by Michie, Johnston, Francis, Hardeman, and Eccles. Results . A total of 14 studies were included. Psychoeducational interventions statistically significantly increased point prevalent (RR 1.44, 95% CI, 1.20–1.73) and continuous (RR 1.51, 95% CI, 1.18–1.93) smoking cessation, and statistically non‐significantly decreased total mortality (RR 0.73, 95% CI, 0.46–1.15). Included studies used a mixture of theories in intervention planning. Despite superficial differences, interventions appear to deploy similar behaviour change techniques, targeted mainly at motivation and goals, beliefs about capacity, knowledge, and skills. Conclusions . Psychoeducational smoking cessation interventions appear effective for patients with CHD. Although questions remain about what characteristics distinguish an effective intervention, analysis indicates similarities between the behaviour change techniques used in such interventions.     

Meeting the National Service Framework for coronary heart disease: which patients have untreated high blood pressure?

BACKGROUND: The National Service Framework for coronary heart disease requires primary care teams to identify patients who are at high risk of cardiovascular events and treat those with high blood pressure. However, there are no data on how many must be assessed, how much cardiovascular disease can be prevented or which patients are most likely to benefit. AIM: To estimate the potential number of patients who are eligible for blood pressure assessment, the number of preventable cardiovascular disease events and the relative efficiency of the strategy in different age groups. DESIGN OF STUDY: Modelling exercise. SETTING: Hypothetical population of 100,000. METHOD: The age-sex specific prevalence of cardiovascular risk factors and of current anti-hypertensive treatment were obtained from published sources and combined with published estimates of the effectiveness of anti-hypertensive treatment. From these data were calculated numbers of persons eligible for assessment and treatment, and numbers of preventable cardiovascular events. RESULTS: There were 79,607 persons eligible for assessment and 5888 eligible for treatment. Treatment could prevent between 101 and 139 cardiovascular events annually. There were 11,571 persons aged over 65 years and eligible for assessment and 4655 eligible for treatment. Treatment could prevent 85 to 117 cardiovascular events annually. No cardiovascular events are prevented in persons aged under 45 years. CONCLUSION: Confining assessment to the 16% who are aged over 65 years prevents 85% of the population's avoidable cardiovascular disease. Primary care teams should assess and treat persons aged over 65 years before assessing younger patients. No health benefit results from assessing persons aged under 45 years.     

Do patients with different psychiatric disorders show altered social decision-making? A systematic review of ultimatum game experiments in clinical populations

Background: Impairments in social functioning are a common feature of psychiatric disorders. Game paradigms pose a unique way for studying how people make decisions in interpersonal contexts. In the last decade, researchers have started to use these paradigms to study social decision-making in patients with psychiatric disorders.

Purpose: The aim of this systematic literature review is to summarise the currently available evidence on the behaviour of patients with psychiatric disorders in the commonly used Ultimatum Game (UG).

Method: A systematic literature search including MEDLINE, PsycINFO, PSYNDEXplus Tests, PSYNDEXPLUS Literature, EBM Reviews—Cochrane Central Register of Controlled Trials, Embase and PASCAL was performed via the Ovid interface.

Results: We found evidence for alterations in UG behaviour for patients with frontotemporal dementia, schizophrenia, affective disorders, alcohol, cocaine, heroin and 3,4-methylenedioxymethamphetamine consumption, alcohol dependence, anxiety disorders, borderline personality disorder, autism, Tourette syndrome and oppositional defiant disorder.

Conclusion: There is some evidence that different psychiatric disorders might go along with alterations in social decision-making. However, in general, data are currently limited and studies are hard to compare due to differences in methodologies.     

Randomized clinical trial of computerized PAINRelieveIt® for patients with sickle cell disease: PAINReportIt® and PAINUCope®

ObjectiveTo compare effects of a tailored multimedia education program versus usual-care on barriers to pain management of adult patients with SCD.MethodsPretest/posttest randomized controlled trial (RCT) of 228 outpatients with SCD randomized to the tablet-based PAINUCope intervention focused on barriers to pain management, pain, and analgesic adherence or selection of games (control). Outcomes were barriers to pain management, pain, and analgesic adherence.ResultsThe barriers to pain management and pain scores did not change significantly from pretest to posttest for either condition. Changes in analgesic adherence rates from pretest to posttest were statistically significant for the intervention group (p = .046) but not for the usual care group (p = .419). The group difference was not statistically significant.ConclusionsThis first RCT of a tailored multimedia education intervention with adult patients with SCD did not significantly reduce the outcomes of interest compared to the control group. Findings provide insights for improving intervention delivery and reinforcement of patient behaviors.Practice implicationsStudy redesign is warranted with modifications that include theoretical and methodological approaches and patient-centered delivery of the intervention that take advantage of recent technology developments.