Showing papers by "Innlandet Hospital Trust published in 2016"

Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies

Abstract: Objectives To examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of heart failure or hospital admission for heart failure in patients with type 2 diabetes. Design Systematic review and meta-analysis of randomised and observational studies. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov searched up to 25 June 2015, and communication with experts. Eligibility criteria Randomised controlled trials, non-randomised controlled trials, cohort studies, and case-control studies that compared DPP-4 inhibitors against placebo, lifestyle modification, or active antidiabetic drugs in adults with type 2 diabetes, and explicitly reported the outcome of heart failure or hospital admission for heart failure. Data collection and analysis Teams of paired reviewers independently screened for eligible studies, assessed risk of bias, and extracted data using standardised, pilot tested forms. Data from trials and observational studies were pooled separately; quality of evidence was assessed by the GRADE approach. Results Eligible studies included 43 trials (n=68 775) and 12 observational studies (nine cohort studies, three nested case-control studies; n=1 777 358). Pooling of 38 trials reporting heart failure provided low quality evidence for a possible similar risk of heart failure between DPP-4 inhibitor use versus control (42/15 701 v 33/12 591; odds ratio 0.97 (95% confidence interval 0.61 to 1.56); risk difference 2 fewer (19 fewer to 28 more) events per 1000 patients with type 2 diabetes over five years). The observational studies provided effect estimates generally consistent with trial findings, but with very low quality evidence. Pooling of the five trials reporting admission for heart failure provided moderate quality evidence for an increased risk in patients treated with DPP-4 inhibitors versus control (622/18 554 v 552/18 474; 1.13 (1.00 to 1.26); 8 more (0 more to 16 more)). The pooling of adjusted estimates from observational studies similarly suggested (with very low quality evidence) a possible increased risk of admission for heart failure (adjusted odds ratio 1.41, 95% confidence interval 0.95 to 2.09) in patients treated with DPP-4 inhibitors (exclusively sitagliptin) versus no use. Conclusions The relative effect of DPP-4 inhibitors on the risk of heart failure in patients with type 2 diabetes is uncertain, given the relatively short follow-up and low quality of evidence. Both randomised controlled trials and observational studies, however, suggest that these drugs may increase the risk of hospital admission for heart failure in those patients with existing cardiovascular diseases or multiple risk factors for vascular diseases, compared with no use.

Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis

Abstract: Background For more than a century, appendicectomy has been the treatment of choice for appendicitis. Recent trials have challenged this view. This study assessed the benefits and harms of antibiotic therapy compared with appendicectomy in patients with non-perforated appendicitis. Methods A comprehensive search was conducted for randomized trials comparing antibiotic therapy with appendicectomy in patients with non-perforated appendicitis. Key outcomes were analysed using random-effects meta-analysis, and the quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Five studies including 1116 patients reported major complications in 25 (4·9 per cent) of 510 patients in the antibiotic and 41 (8·4 per cent) of 489 in the appendicectomy group: risk difference −2·6 (95 per cent c.i. –6·3 to 1·1) per cent (low-quality evidence). Minor complications occurred in 11 (2·2 per cent) of 510 and 61 (12·5 per cent) of 489 patients respectively: risk difference −7·2 (−18·1 to 3·8) per cent (very low-quality evidence). Of 550 patients in the antibiotic group, 47 underwent appendicectomy within 1 month: pooled estimate 8·2 (95 per cent c.i. 5·2 to 11·8) per cent (high-quality evidence). Within 1 year, appendicitis recurred in 114 of 510 patients in the antibiotic group: pooled estimate 22·6 (15·6 to 30·4) per cent (high-quality evidence). For every 100 patients with non-perforated appendicitis, initial antibiotic therapy compared with prompt appendicectomy may result in 92 fewer patients receiving surgery within the first month, and 23 more experiencing recurrent appendicitis within the first year. Conclusion The choice of medical versus surgical management in patients with clearly uncomplicated appendicitis is value- and preference-dependent, suggesting a change in practice towards shared decision-making is necessary.

Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants

Abstract: BackgroundTreatment with nasal high-flow therapy has efficacy similar to that of nasal continuous positive airway pressure (CPAP) when used as postextubation support in neonates. The efficacy of high-flow therapy as the primary means of respiratory support for preterm infants with respiratory distress has not been proved. MethodsIn this international, multicenter, randomized, noninferiority trial, we assigned 564 preterm infants (gestational age, ≥28 weeks 0 days) with early respiratory distress who had not received surfactant replacement to treatment with either nasal high-flow therapy or nasal CPAP. The primary outcome was treatment failure within 72 hours after randomization. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the chosen margin of noninferiority was 10 percentage points. Infants in whom high-flow therapy failed could receive rescue CPAP; infants in whom CPAP failed were intubated and mechanically ventilated. ResultsTrial recruitment ...

Prognosis after surgical replacement with a bioprosthetic aortic valve in patients with severe symptomatic aortic stenosis: systematic review of observational studies

Abstract: Objective To determine the frequency of survival, stroke, atrial fibrillation, structural valve deterioration, and length of hospital stay after surgical replacement of an aortic valve (SAVR) with a bioprosthetic valve in patients with severe symptomatic aortic stenosis. Design Systematic review and meta-analysis of observational studies. Data sources Medline, Embase, PubMed (non-Medline records only), Cochrane Database of Systematic Reviews, and Cochrane CENTRAL from 2002 to June 2016. Study selection Eligible observational studies followed patients after SAVR with a bioprosthetic valve for at least two years. Methods Reviewers, independently and in duplicate, evaluated study eligibility, extracted data, and assessed risk of bias for patient important outcomes. We used the GRADE system to quantify absolute effects and quality of evidence. Published survival curves provided data for survival and freedom from structural valve deterioration, and random effect models provided the framework for estimates of pooled incidence rates of stroke, atrial fibrillation, and length of hospital stay. Results In patients undergoing SAVR with a bioprosthetic valve, median survival was 16 years in those aged 65 or less, 12 years in those aged 65 to 75, seven years in those aged 75 to 85, and six years in those aged more than 85. The incidence rate of stroke was 0.25 per 100 patient years (95% confidence interval 0.06 to 0.54) and atrial fibrillation 2.90 per 100 patient years (1.78 to 4.79). Post-SAVR, freedom from structural valve deterioration was 94.0% at 10 years, 81.7% at 15 years, and 52% at 20 years, and mean length of hospital stay was 12 days (95% confidence interval 9 to 15). Conclusion Patients with severe symptomatic aortic stenosis undergoing SAVR with a bioprosthetic valve can expect only slightly lower survival than those without aortic stenosis, and a low incidence of stroke and, up to 10 years, of structural valve deterioration. The rate of deterioration increases rapidly after 10 years, and particularly after 15 years.

Introduction to BMJ Rapid Recommendations

Abstract: New BMJ collaboration accelerates evidence into practice to answer the questions that matter quickly and transparently through trustworthy recommendations

Transcatheter or surgical aortic valve replacement for patients with severe, symptomatic, aortic stenosis at low to intermediate surgical risk: a clinical practice guideline

Abstract: In patients with symptomatic severe aortic stenosis but at lower risk of perioperative death, how do minimally invasive techniques compare with open surgery? Prompted by a recent trial, an expert panel produced these recommendations based on three linked rapid systematic reviews

Prevalence of celiac disease in Asia: A systematic review and meta-analysis.

Abstract: Background and Aim Celiac disease (CD) is emerging in Asia. While a few population-based studies from Asia have reported a prevalence of CD from 0.1% to 1.3%, the exact prevalence of CD in Asia is not known. We conducted a systematic review and meta-analysis to estimate the prevalence of CD in Asia. Methods On search of literature, we found 1213 articles, of which 18 articles were included. Diagnosis of CD was based on European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines. Results Pooled sero-prevalence of CD in Asia was 1.6% in 47 873 individuals based on positive anti-tissue transglutaminase and/or anti-endomysial antibodies. Pooled prevalence of biopsy proven CD in Asia was 0.5% in 43 955 individuals. The prevalence of CD among women was higher than in men (0.5% vs 0.4%, P = 0.04). The pooled prevalence of CD was 0.3% in Iran, 0.5% in Turkey, 0.6% in India, and 0.7% in Israel. The pooled prevalence of CD was significantly higher in Israel and India as compared with that in Iran. Conclusions Celiac disease is not uncommon in Asia, and the sero-prevalence and prevalence of CD in Asia are 1.6% and 0.5%, respectively. The prevalence of CD varies with gender and geographic location. There is a need for population-based prevalence studies in many Asian countries to properly estimate the burden of CD in Asia.

Faecal short-chain fatty acids - a diagnostic biomarker for irritable bowel syndrome?

Abstract: The diagnosis of irritable bowel syndrome (IBS) relies on symptom-based criteria. A valid and reliable biomarker that could confirm the diagnosis is desirable. This study evaluated the properties of faecal short-chain fatty acids (SCFA) as diagnostic biomarkers for IBS. Twenty-five subjects with IBS and 25 controls were included in this explanatory case–control study. Stool samples were analysed for SCFA (acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid) with gas chromatography and reported as mmol/l and molar%. In the search for the best way to distinguish between subjects with and without IBS, the total amount and the amount of each of the SCFA were measured, and the proportions and differences between the SCFA were calculated. In the IBS and control group, the mean age was 46.2 (SD 12.9) and 49.2 (SD 14.6), and the number of females was 13/25 (52 %) and 15/25 (60 %) respectively. The difference between propionic and butyric acid (mmol/l) had the best diagnostic properties, the area under the Receiver Operating Characteristic curve was 0.89 (95 % CI: 0.80–0.98) (p 0.015 mmol/l indicating IBS, the sensitivity, specificity, positive and negative likelihood ratio, and diagnostic odds ratio were 92 %, 72 %, 3.29, 0.11 and 29.6 respectively. Similar diagnostic properties were shown for all the IBS subgroups. The study indicated that faecal SCFA could be a non-invasive, valid and reliable biomarker for the differentiation of healthy subjects from subjects with IBS.

Supplementation with Selenium and Coenzyme Q10 Reduces Cardiovascular Mortality in Elderly with Low Selenium Status. A Secondary Analysis of a Randomised Clinical Trial.

Abstract: Background Selenium is needed by all living cells in order to ensure the optimal function of several enzyme systems. However, the selenium content in the soil in Europe is generally low. Previous reports indicate that a dietary supplement of selenium could reduce cardiovascular disease but mainly in populations in low selenium areas. The objective of this secondary analysis of a previous randomised double-blind placebo-controlled trial from our group was to determine whether the effects on cardiovascular mortality of supplementation with a fixed dose of selenium and coenzyme Q10 combined during a four-year intervention were dependent on the basal level of selenium. Methods In 668 healthy elderly individuals from a municipality in Sweden, serum selenium concentration was measured. Of these, 219 individuals received daily supplementation with selenium (200 μg Se as selenized yeast) and coenzyme Q10 (200 mg) combined for four years. The remaining participants (n = 449) received either placebo (n = 222) or no treatment (n = 227). All cardiovascular mortality was registered. No participant was lost during a median follow-up of 5.2 years. Based on death certificates and autopsy results, all mortality was registered. Findings The mean serum selenium concentration among participants at baseline was low, 67.1 μg/L. Based on the distribution of selenium concentration at baseline, the supplemented group was divided into three groups; 85 μg/L (45 and 90 percentiles) and the remaining participants were distributed accordingly. Among the non-treated participants, lower cardiovascular mortality was found in the high selenium group as compared with the low selenium group (13.0% vs. 24.1%; P = 0.04). In the group with the lowest selenium basal concentration, those receiving placebo or no supplementation had a mortality of 24.1%, while mortality was 12.1% in the group receiving the active substance, which was an absolute risk reduction of 12%. In the middle selenium concentration group a mortality of 14.0% in the non-treated group, and 6.0% in the actively treated group could be demonstrated; thus, there was an absolute risk reduction of 8.0%. In the group with a serum concentration of >85 μg/L, a cardiovascular mortality of 17.5% in the non-treated group, and 13.0% in the actively treated group was observed. No significant risk reduction by supplementation could thus be found in this group. Conclusions In this evaluation of healthy elderly Swedish municipality members, two important results could be reported. Firstly, a low mean serum selenium concentration, 67 μg/L, was found among the participants, and the cardiovascular mortality was higher in the subgroup with the lower selenium concentrations 85 μg/L. Secondly, supplementation was cardio-protective in those with a low selenium concentration, ≤85 at inclusion. In those with serum selenium>85 μg/L and no apparent deficiency, there was no effect of supplementation. This is a small study, but it presents interesting data, and more research on the impact of lower selenium intake than recommended is therefore warranted. Trial Registration Clinicaltrials.gov NCT01443780

Modeling and evaluating evidence-based continuing education program in nursing home dementia care (MEDCED)—training of care home staff to reduce use of restraint in care home residents with dementia. A cluster randomized controlled trial

Abstract: Objective The aim of this study was to evaluate the effectiveness of a tailored 7-month training intervention “Trust Before Restraint,” in reducing use of restraint, agitation, and antipsychotic medications in care home residents with dementia. Methods This is a single-blind cluster randomized controlled trial in 24 care homes within the Western Norway Regional Health Authority 2011–2013. Results From 24 care homes, 274 residents were included in the study, with 118 in the intervention group and 156 in the control group. Use of restraint was significantly reduced in both the intervention group and the control group despite unexpected low baseline, with a tendency to a greater reduction in the control group. There was a significant reduction in Cohen-Mansfield Agitation Inventory score in both the intervention group and the follow-up group with a slightly higher reduction in the control group, although this did not reach significance and a small nonsignificant increase in use of antipsychotics (14.1–17.7%) and antidepressants (35.9–38.4%) in both groups. Conclusions This study reports on the statistically significant reduction in use of restraint in care homes, both prior and during the 7-month intervention periods, in both intervention and control groups. When interpreted within the context of the current climate of educational initiatives to reduce restraint and a greater focus on the importance of person-centered care, the study also highlights the potential success achieved with national training programs for care staff and should be further evaluated to inform future training initiatives both in Norway and internationally. Copyright © 2015 John Wiley & Sons, Ltd.

Stronger and More Vulnerable: A Balanced View of the Impacts of the NICU Experience on Parents

Abstract: For parents, the experience of having an infant in the NICU is often psychologically traumatic. No parent can be fully prepared for the extreme stress and range of emotions of caring for a critically ill newborn. As health care providers familiar with the NICU, we thought that we understood the impact of the NICU on parents. But we were not prepared to see the children in our own families as NICU patients. Here are some of the lessons our NICU experience has taught us. We offer these lessons in the hope of helping health professionals consider a balanced view of the NICU's impact on families.

Neuroimmune Interface in the Comorbidity between Alcohol Use Disorder and Major Depression

Abstract: Bidirectional communication links operate between the brain and the body. Afferent immune-to-brain signals are capable of inducing changes in mood and behavior. Chronic heavy alcohol drinking, typical of alcohol use disorder (AUD), is one such factor that provokes an immune response in the periphery that, by means of circulatory cytokines and other neuroimmune mediators, ultimately causes alterations in the brain function. Alcohol can also directly impact the immune functions of microglia, the resident CNS immune cell. Several lines of research have established the contribution of specific inflammatory mediators in the development and progression of depressive illness. Much of the available evidence in this field stems from cross-sectional data on the immune interactions between isolated AUD and major depression (MD). Given their heterogeneity as disease entities with overlapping symptoms and shared neuroimmune correlates, it is no surprise that systemic and CNS inflammation could be a critical determinant of the frequent comorbidity between AUD and MD. This review presents a summary and analysis of the extant literature on neuroimmune interface in the AUD-MD comorbidity.

Treatment strategies in Alzheimer’s disease: a review with focus on selenium supplementation

Abstract: Alzheimer’s disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (Aβ) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce Aβ production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral Aβ plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.

Living cumulative network meta-analysis to reduce waste in research: A paradigmatic shift for systematic reviews?

Abstract: In a recent research article in BMC Medicine, Crequit and colleagues demonstrate how published systematic reviews in lung cancer provide a fragmented, out-of-date picture of the evidence for all treatments. The results and conclusions drawn from this study, based on cumulative network meta-analyses (NMA) of evidence from randomized clinical trials over time, are quite compelling. The inherent waste of research resulting from incomplete evidence synthesis has wide-reaching implications for a range of target groups including developers of systematic reviews and guidelines and their end-users, health care professionals and patients at the point of care. Building on emerging concepts for living systematic reviews and NMA, the authors propose "living cumulative NMA" as a potential solution and paradigmatic shift. Here we describe how recent innovations within authoring, dissemination, and updating of systematic reviews and trustworthy guidelines may greatly facilitate the production of living NMA. Some additional challenges need to be solved for NMA in general, and for living cumulative NMA in particular, before a paradigmatic shift for systematic reviews can become reality.

Scandinavian clinical practice guideline on fluid and drug therapy in adults with acute respiratory distress syndrome

Abstract: Background The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on fluid and drug therapy in adults with acute respiratory distress syndrome (ARDS) was to provide clinically relevant, evidence-based treatment recommendations according to standards for trustworthy guidelines. Methods The guideline was developed according to standards for trustworthy guidelines, including a systematic review of the literature and use of the GRADE methodology for assessment of the quality of evidence and for moving from evidence to recommendations. Results A total of seven ARDS interventions were assessed. We suggest fluid restriction in patients with ARDS (weak recommendation, moderate quality evidence). Also, we suggest early use of neuromuscular blocking agents (NMBAs) in patients with severe ARDS (weak recommendation, moderate quality evidence). We recommend against the routine use of other drugs, including corticosteroids, beta2 agonists, statins, and inhaled nitric oxide (iNO) or prostanoids in adults with ARDS (strong recommendations: low- to high-quality evidence). These recommendations do not preclude the use of any drug or combination of drugs targeting underlying or co-existing disorders. Conclusion This guideline emphasizes the paucity of evidence of benefit – and potential for harm – of common interventions in adults with ARDS and highlights the need for prudence when considering use of non-licensed interventions in this patient population.

Strength training improves cycling performance, fractional utilization of VO2max and cycling economy in female cyclists.

Abstract: The purpose of this study was to investigate the effect of adding heavy strength training to well-trained female cyclists' normal endurance training on cycling performance. Nineteen female cyclists were randomly assigned to 11 weeks of either normal endurance training combined with heavy strength training (E+S, n = 11) or to normal endurance training only (E, n = 8). E+S increased one repetition maximum in one-legged leg press and quadriceps muscle cross-sectional area (CSA) more than E (P < 0.05), and improved mean power output in a 40-min all-out trial, fractional utilization of VO2 max and cycling economy (P < 0.05). The proportion of type IIAX-IIX muscle fibers in m. vastus lateralis was reduced in E+S with a concomitant increase in type IIA fibers (P < 0.05). No changes occurred in E. The individual changes in performance during the 40-min all-out trial was correlated with both change in IIAX-IIX fiber proportion (r = -0.63) and change in muscle CSA (r = 0.73). In conclusion, adding heavy strength training improved cycling performance, increased fractional utilization of VO2 max , and improved cycling economy. The main mechanisms behind these improvements seemed to be increased quadriceps muscle CSA and fiber type shifts from type IIAX-IIX toward type IIA.

The prevalence of anemia and iron deficiency is more common in breastfed infants than their mothers in Bhaktapur, Nepal

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Problem gambling and the five-factor model of personality: a large population-based study.

Abstract: BACKGROUND AND AIMS Knowledge of the personality characteristics of individuals who develop gambling problems is important for designing targeted prevention efforts. Previous studies of the relationship between the five-factor model of personality and gambling problems were based on small samples not representative of the general population. We estimated differences in neuroticism, extroversion, intellect, agreeableness and conscientiousness between non-problem gamblers and individuals with low, moderate and severe gambling problems. DESIGN Cross-sectional survey. SETTING Norway. PARTICIPANTS A total of 10 081 (51.5% female) individuals aged 16-74 years (mean age 46.5 years). MEASURES The Problem Gambling Severity Index, The Mini-International Personality Item Pool and demographic variables. Differences between groups of gamblers were analysed by ordinary least-squares regression models separately for each personality trait adjusting for gender, age, cohabitation, level of education and work status. FINDINGS Gamblers with low, moderate and severe levels of gambling problems differed significantly from non-problem gamblers in neuroticism (b = 0.16, 0.34 and 0.66, respectively, all P < 0.001) and conscientiousness (b = -0.13, -0.28 and -0.44, respectively, all P < 0.001). Moderate and severe problem gamblers differed from non-problem gamblers in agreeableness (b = -0.21, P < 0.001 and b = -0.20, P = 0.028, respectively). In addition, gambling problems were much more prevalent among men than women, and more prevalent among those who live alone, individuals without tertiary education and among those who are unemployed or on disability pension. CONCLUSIONS A higher level of problem gambling severity appears to be associated with higher scores on neuroticism, and with lower scores on conscientiousness and agreeableness in the Mini-International Personality Item Pool.

Multi-psychotropic drug prescription and the association to neuropsychiatric symptoms in three Norwegian nursing home cohorts between 2004 and 2011.

Abstract: Neuropsychiatric symptoms, such as affective symptoms, psychosis, agitation, and apathy are common among nursing home patients with and without dementia. Treatment with one or more psychotropic drug is often without explicit clinical indication, despite low treatment efficacy, and potential side effects. We aim to investigate the multi-psychotropic drug use to identify factors and patient characteristics associated with multi-use. We analysed three cohorts from 129 Norwegian nursing homes, collected between 2004 and 2011. Patients (N = 4739) were assessed with the Neuropsychiatric Inventory – Nursing Home version (NPI-NH), Clinical Dementia Rating scale, and Physical Self Maintenance Scale. We used ordinal logistic regression to analyse associations between psychotropics (antidepressants, antipsychotics, anxiolytics, hypnotics, and anti-dementia drugs), patient characteristics, and neuropsychiatric symptoms. Patients used on average 6.6 drugs; 27 % used no psychotropics, 32 % one, and 41 % multiple psychotropic drugs (24 % two, 17 % ≥3). Thirty-nine percent were prescribed antidepressants, 30 % sedatives, 24 % anxiolytics, and 20 % antipsychotics. The total NPI-NH score was associated with multi-use (OR 1.02, 95 % CI 1.02–1.03), and increased from a mean of 13.5 (SD 16.3) for patients using none, to 25.5 (21.8) for patients using ≥3 psychotropics. Affective symptoms (depression and anxiety) were most strongly associated with multi-psychotropic drug use (OR 1.10, 95 % CI: 1.09–1.12). Female gender, independency in daily living, younger age, dementia, and many regular drugs were also associated with multi-use. Forty-one percent were exposed to multi-psychotropic drug prescriptions. Contrary to current evidence and guidelines, there is an extensive use of multiple psychotropic drugs in patients with severe NPS and dementia.

Patient values and preferences on transcatheter or surgical aortic valve replacement therapy for aortic stenosis: a systematic review

Abstract: Objective To investigate patients9 values and preferences regarding aortic valve replacement therapy for aortic stenosis. Setting Studies published after transcatheter aortic valve insertion (TAVI) became available (2002). Participants Adults with aortic stenosis who are considering or have had valve replacement, either TAVI or via surgery (surgical aortic valve replacement, SAVR). Outcome measures We sought quantitative measurements, or qualitative descriptions, of values and preferences. When reported, we examined correlations between preferences and objective (eg, ejection fraction) or subjective (eg, health-related quality of life) measures of health. Results We reviewed 1348 unique citations, of which 2 studies proved eligible. One study of patients with severe aortic stenosis used a standard gamble study to ascertain that the median hypothetical mortality risk patients were willing to tolerate to achieve full health was 25% (IQR 25–50%). However, there was considerable variability; for mortality risk levels defined by current guidelines, 130 participants (30%) were willing to accept low-to-intermediate risk (≤8%), 224 (51%) high risk (>8–50%) and 85 (19%) a risk that guidelines would consider prohibitive (>50%). Study authors did not, however, assess participants9 understanding of the exercise, resulting in a potential risk of bias. A second qualitative study of 15 patients identified the following factors that influence patients to undergo assessment for TAVI: symptom burden; expectations; information support; logistical barriers; facilitators; obligations and responsibilities. The study was limited by serious risk of bias due to authors9 conflict of interest (5/9 authors industry-funded). Conclusions Current evidence on patient values and preferences of adults with aortic stenosis is very limited, and no studies have enrolled patients deciding between TAVI and SAVR. On the basis of the data available, there is evidence of variability in individual values and preferences, highlighting the importance of well-informed and shared decision-making with patients facing this decision. Trial registration number PROSPERO CRD42016041907.

Cytokine Changes following Acute Ethanol Intoxication in Healthy Men: A Crossover Study.

Abstract: Alcohol is a known modulator of the innate immune system. Owing to the absence of human studies, alcohol’s effect on circulating cytokine profile remains unclear. We investigated the effect of acute high dose alcohol consumption on systemic cytokine release. After an overnight fasting, alcohol-experienced healthy male volunteers ( ) aged 25–45 years were given oral ethanol in the form of vodka (4.28 mL/kg) which they drank over a period of 30 minutes reaching peak blood alcohol concentration of 0.12% (SD 0.028). Blood samples were obtained prior to alcohol intake as well as 2, 7, and 12 hours thereafter. Serum levels of the inflammatory cytokines IL-1β, IL-1Ra, IL-6, IL-10, IL-17, IFN-γ, MCP-1, and TNF-α were determined by the multibead-based assay. Baseline cytokine levels were not related to BMI, hepatic parameters, electrolytes, glucose, or morning cortisol levels. Within 2 hours of alcohol intake, levels of IL-1Ra were elevated and remained so throughout the assessment period ( for trend = 0.015). In contrast, the levels of the chemokine MCP-1 dropped acutely followed by steadily increasing levels during the observation period ( ). The impact of sustained elevated levels of MCP-1 even after the clearance of blood alcohol content deserves attention.

Aberrant Resting-State Functional Connectivity in the Salience Network of Adolescent Chronic Fatigue Syndrome.

Abstract: Neural network investigations are currently absent in adolescent chronic fatigue syndrome (CFS). In this study, we examine whether the core intrinsic connectivity networks (ICNs) are altered in adolescent CFS patients. Eighteen adolescent patients with CFS and 18 aged matched healthy adolescent control subjects underwent resting-state functional magnetic resonance imaging (rfMRI). Data was analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic connectivity was evaluated in the default mode network (DMN), salience network (SN), and central executive network (CEN). Associations between network characteristics and symptoms of CFS were also explored. Adolescent CFS patients displayed a significant decrease in SN functional connectivity to the right posterior insula compared to healthy comparison participants, which was related to fatigue symptoms. Additionally, there was an association between pain intensity and SN functional connectivity to the left middle insula and caudate that differed between adolescent patients and healthy comparison participants. Our findings of insula dysfunction and its association with fatigue severity and pain intensity in adolescent CFS demonstrate an aberration of the salience network which might play a role in CFS pathophysiology.

Vitamin status among breastfed Infants in Bhaktapur, Nepal

Abstract: Vitamin deficiencies are known to be common among infants residing in low- and middle-income countries but relatively few studies have assessed several biochemical parameters simultaneously. The objective of the study was to describe the status of vitamins (A, D, E, B6, B12 and folate) in breastfed infants. We measured the plasma concentrations of trans retinol, 25 hydroxy vitamin D, α-tocopherol, pyridoxal 5′-phosphate, cobalamin, folate, methylmalonic acid, homocysteine, hemoglobin and C-reactive protein from 467 randomly selected infants. One in five (22%) was deficient in at least one vitamin. Mean (SD) plasma folate concentration was 73 (35) nmol/L, and no infant in the sample was folate deficient. Vitamin B6 deficiency and vitamin B12 deficiency was found in 22% and 17% of the infants, respectively. Elevated plasma methylmalonic acid or total homocysteine concentration was found in 82% and 62% of infants, respectively. Fifteen percent of infants were vitamin A deficient and 65% were marginally deficient in vitamin A. Fewer than 5% of infants had low plasma vitamin D concentration or vitamin E concentration (α-tocopherol <9.3 µmol/L). Our results illustrate the importance of continued supplementation campaigns and support the expansion of food fortification and dietary diversification programs that target children and women in Nepal.

Right ventricular function in long-term adult survivors of childhood lymphoma and acute lymphoblastic leukaemia.

Abstract: Aims Little is known about right ventricular (RV) function in survivors of childhood cancer, although both anthracyclines and radiotherapy represent potentially cardiotoxic treatment. We hypothesized that adult survivors of childhood malignant lymphoma or acute lymphoblastic leukaemia would have impaired RV function. Methods and results We examined RV dimensions and function by echocardiography in 246 survivors, mean 21.7 years after diagnosis, and in 211 matched controls. Of the survivors, 84% had been exposed to anthracyclines, mediastinal radiotherapy, or both. Compared with controls, all mean measures of RV function were lower in the survivor group: fractional area change (44.5 vs. 48.6%, P < 0.001), tricuspid annular plane systolic excursion (2.24 vs. 2.49 cm, P < 0.001), peak systolic tricuspid annular velocity (12.1 vs. 13.0 cm/s, P < 0.001), and free wall strain (−26.5 vs. −28.4%, P < 0.001). In contrast, there were little differences in RV diastolic dimensions. Lower measures of RV function were found in all survivor subgroups having received cardiotoxic treatment, but not in the 16% of survivors unexposed to anthracyclines or mediastinal radiotherapy. Signs of RV systolic dysfunction were found in 30% of the survivors, and more than 3 times more often in survivors with left ventricular dysfunction. Conclusion Long-term survivors of childhood lymphoma or acute lymphoblastic leukaemia frequently have impaired RV function compared with controls. As this is associated with increased risk of heart failure and death in many other conditions, we recommend increased attention to RV function in childhood survivors. Whether RV dysfunction impairs prognosis in this patient group should be examined in longitudinal studies.