Evidence-based medicine: an update on treatments for peritoneal dialysis-related peritonitis

Peritonitis continues to be a major complication of peritoneal dialysis (PD), and adequate treatment is crucial for a favorable outcome. There is no consensus regarding the optimal therapeutic regimen, and few prospective controlled studies have been published. The objective of this manuscript is to review the results of PD peritonitis treatment reported in narrative reviews, systematic reviews, and proportional meta-analyses. Two narrative reviews, the only existing systematic review and its update published between 1991 and 2014 were included. In addition, we reported the results of a proportional meta-analysis published by our group. Results from systematic reviews of randomized control trials (RCT) and quasi-RCT were not able to identify any optimal antimicrobial treatment, but glycopeptide regimens were more likely to achieve a complete cure than a first generation cephalosporin. Compared to urokinase, simultaneous catheter removal and replacement resulted in better outcomes. Continuous and intermittent IP antibiotic use had similar outcomes. Intraperitoneal antibiotics were superior to intravenous antibiotics in reducing treatment failure. In the proportional meta-analysis of RCTs and the case series, the resolution rate (86%) of ceftazidime plus glycopeptide as initial treatment was significantly higher than first generation cephalosporin plus aminoglycosides (66%) and glycopeptides plus aminoglycosides (75%). Other comparisons of regimens used for either initial treatment or treatment of gram-positive rods or gram-negative rods did not show statistically significant differences. The superiority of a combination of a glycopeptide and a third generation cephalosporin was also reported by a narrative review study published in 1991, which reported an 88% resolution rate.

Thymopoiesis and regulatory T cells in healthy children and adolescents

OBJECTIVES: The purpose of this study was to investigate the association between T cell receptor excision circle levels in peripheral blood mononuclear cells and regulatory T cells that co-express CD25 and Foxp3 in healthy children and adolescents of different ages. MATERIALS AND METHODS: The quantification of signal-joint T-cell receptor excision circle levels in the genomic DNA of peripheral blood mononuclear cells was performed using real-time quantitative PCR. The analysis of CD4, CD8, CD25, and Foxp3 expression was performed using flow cytometry. RESULTS: Ninety-five healthy controls (46 females and 49 males) ranging in age from 1 to 18 years were analyzed. The mean T-cell receptor excision circle count in all individuals was 89.095 +/- 36.790 T-cell receptor excision circles per microgram of DNA. There was an inverse correlation between T-cell receptor excision circles counts and age (r = -0.846; p < 0.001) as well as between the proportion of CD4(+)CD25(+)Foxp3(+) T cells and age (r = -0.467; p = 0.04). In addition, we observed a positive correlation between the amount of CD4(+)CD25(+)Foxp3(+) T cells and the amount of T-cell receptor excision circles per microgram of DNA in individuals of all ages (r = -0.529; p = 0.02). CONCLUSIONS: In this study, we observed a decrease in the thymic function with age based on the fact that the level of T-cell receptor excision circles in the peripheral blood positively correlated with the proportion of regulatory T cells in healthy children and adolescents. These findings indicate that although T-cell receptor excision circles and regulatory T cells levels decrease with age, homeostasis of the immune system and relative regulatory T cells population levels are maintained in the peripheral blood.

Evidence-Based Information on the Clinical Use of Neurofeedback for ADHD

Neurofeedback (NF) is a training to enhance self-regulatory capacity over brain activity patterns and consequently over brain mental states. Recent findings suggest that NF is a promising alternative for the treatment of attention-deficit/hyperactivity disorder (ADHD). We comprehensively reviewed literature searching for studies on the effectiveness and specificity of NF for the treatment of ADHD. In addition, clinically informative evidence-based data are discussed. We found 3 systematic review on the use of NF for ADHD and 6 randomized controlled trials that have not been included in these reviews. Most nonrandomized controlled trials found positive results with medium-to-large effect sizes, but the evidence for effectiveness are less robust when only randomized controlled studies are considered. The direct comparison of NF and sham-NF in 3 published studies have found no group differences, nevertheless methodological caveats, such as the quality of the training protocol used, sample size, and sample selection may have contributed to the negative results. Further data on specificity comes from electrophysiological studies reporting that NF effectively changes brain activity patterns. No safety issues have emerged from clinical trials and NF seems to be well tolerated and accepted. Follow-up studies support long-term effects of NF. Currently there is no available data to guide clinicians on the predictors of response to NF and on optimal treatment protocol. In conclusion, NF is a valid option for the treatment for ADHD, but further evidence is required to guide its use.

Treatment of neuromyelitis optica: an evidence based review

Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterized by severe optic neuritis and transverse myelitis, usually with a relapsing course. Aquaporin-4 antibody is positive in a high percentage of NMO patients and it is directed against this water channel richly expressed on foot processes of astrocytes. Due to the severity of NMO attacks and the high risk for disability, treatment should be instituted as soon as the diagnosis is confirmed. There is increasing evidence that NMO patients respond differently from patients with multiple sclerosis (MS), and, therefore, treatments for MS may not be suitable for NMO. Acute NMO attacks usually are treated with high dose intravenous corticosteroid pulse and plasmapheresis. Maintenance therapy is also required to avoid further attacks and it is based on low-dose oral corticosteroids and non-specific immunosuppressant drugs, like azathioprine and mycophenolate mofetil. New therapy strategies using monoclonal antibodies like rituximab have been tested in NMO, with positive results in open label studies. However, there is no controlled randomized trial to confirm the safety and efficacy for the drugs currently used in NMO.

Longitudinal brain volumetric changes during one year in non-elderly healthy adults: a voxel-based morphometry study

Previous cross-sectional magnetic resonance imaging (MRI) studies of healthy aging in young adults have indicated the presence of significant inverse correlations between age and gray matter volumes, although not homogeneously across all brain regions. However, such cross-sectional studies have important limitations and there is a scarcity of detailed longitudinal MRI studies with repeated measures obtained in the same individuals in order to investigate regional gray matter changes during short periods of time in non-elderly healthy adults. In the present study, 52 healthy young adults aged 18 to 50 years (27 males and 25 females) were followed with repeated MRI acquisitions over approximately 15 months. Gray matter volumes were compared between the two times using voxel-based morphometry, with the prediction that volume changes would be detectable in the frontal lobe, temporal neocortex and hippocampus. Voxel-wise analyses showed significant (P < 0.05, family-wise error corrected) relative volume reductions of gray matter in two small foci located in the right orbitofrontal cortex and left hippocampus. Separate comparisons for males and females showed bilateral gray matter relative reductions in the orbitofrontal cortex over time only in males. We conclude that, in non-elderly healthy adults, subtle gray matter volume alterations are detectable after short periods of time. This underscores the dynamic nature of gray matter changes in the brain during adult life, with regional volume reductions being detectable in brain regions that are relevant to cognitive and emotional processes.

Reorganization of secondary and tertiary health care levels: impact on the outcomes of oral cancer screening in the São Paulo State, Brazil

This study presents the strategies for prevention and early detection of oral cancer by means of screening in the elderly population of São Paulo, the richest and the most populous state of Brazil. This research was a retrospective longitudinal study based on the analysis of secondary data. The variables - number of participating cities, coverage of screening, and number of suspicious and confirmed cases of oral cancer - were divided into two periods: 2001-2004 and 2005-2008. Data were analyzed statistically by the chi-square test at 5% significance level. The implementation of a nationwide public oral health policy in 2004 and the reorganization of the secondary and tertiary health care were evaluated as mediator factors able to interfere in the achieved outcomes. From 2001 to 2008, 2,229,273 oral examinations were performed. There was an addition of 205 participating cities by the end of the studied period (p<0.0001). The coverage of oral cancer screening increased from 4.1% to 16% (p<0.0001). There was a decrease in the number of suspicious lesions (from 9% in 2005 to 5% in 2008) (p<0.0001) and in the rate of confirmed oral cancer cases per 100,000 examinations (from 20.89 in 2001 to 10.40 in 2008) (p<0.0001). After 8 years of screening, there was a decrease in the number of suspicious lesions and confirmed cases of oral cancer in the population. The reorganization of secondary and tertiary health care levels of oral care seems to have contributed to modify these numbers, having a positive impact on the outcomes of oral cancer screening in the São Paulo State.

Evidence-based clinical use of insulin premixtures

Brazil is expected to have 19.6 million patients with diabetes by the year 2030. A key concept in the treatment of type 2 diabetes mellitus (T2DM) is establishing individualized glycemic goals based on each patient’s clinical characteristics, which impact the choice of antihyperglycemic therapy. Targets for glycemic control, including fasting blood glucose, postprandial blood glucose, and glycated hemoglobin (A1C), are often not reached solely with antihyperglycemic therapy, and insulin therapy is often required. Basal insulin is considered an initial strategy; however, premixed insulins are convenient and are equally or more effective, especially for patients who require both basal and prandial control but desire a more simplified strategy involving fewer daily injections than a basal-bolus regimen. Most physicians are reluctant to transition patients to insulin treatment due to inappropriate assumptions and insufficient information. We conducted a nonsystematic review in PubMed and identified the most relevant and recently published articles that compared the use of premixed insulin versus basal insulin analogues used alone or in combination with rapid-acting insulin analogues before meals in patients with T2DM. These studies suggest that premixed insulin analogues are equally or more effective in reducing A1C compared to basal insulin analogues alone in spite of the small increase in the risk of nonsevere hypoglycemic events and nonclinically significant weight gain. Premixed insulin analogues can be used in insulin-naïve patients, in patients already on basal insulin therapy, and those using basal-bolus therapy who are noncompliant with blood glucose self-monitoring and titration of multiple insulin doses. We additionally provide practical aspects related to titration for the specific premixed insulin analogue formulations commercially available in Brazil.

Tradition, Change and Variation : Past and Present Trends in Public Old-age Care

The general aim of this dissertation is to describe and analyse how public old-age care in Sweden has developed and changed during the last century. The study applies a provider perspective on how care has been planned and professionally carried out. A broader social policy perspective, studying old-age care at central/national as well as local/municipal level, is also developed. A special focus is directed at the large local variation in care and services for the elderly. The empirical base is comprised of official documents and other public sources, survey data from interviews with elderly recipients of public old-age care, and official statistics on publicly financed and controlled old-age care and services. Study I addresses the development of old-age care in Sweden during the twentieth century by studying an important occupation in this field – the supervisors and their professional roles, tasks and working conditions. Throughout, the roles of supervisors have followed the prevailing official policy on the proper way to provide care for elderly people in Sweden; from poor relief at the beginning of the 1900s, via a generous level of services in the 1960s and 1970s, to today’s restricted and economy-controlled mode of operation. Study II describes and compares two main forms of public old-age care in Sweden today, home help services and institutional care. The care-load found in home-based care was comparable to and sometimes even larger than in service-homes and other institutions, indicating that large care needs among elderly people in Sweden today can be met in their homes as well as in institutional settings. Studies III and IV analyse the local variation in public old-age care in Sweden. During the last decades there has been an overall decline in home help services. The coverage of home help for elderly people shows large differences between municipalities throughout this period, and the relative variation has increased. The local disparity seems to depend more on historical factors, e.g., previous coverage rates, than on the present municipal situation in levels of need or local economy and politics. In an introductory part the four papers are linked together by an outline of the demographic situation and the social policy model for old-age care in Sweden. Trends that have been apparent over time, e.g. professionalisation and market orientation, are traced and discussed. Conflicts between prevailing ideologies are analysed, in regards to for instance home-based and institution-based care, social and medical culture, and local and central levels of decision-making. ’Welfare municipality’, ‘path dependency’, and ‘decentralisation’ are suggested as a conceptual framework for describing the large and increasing local variations in old-age care. Finally, implications of the four studies with regard to old-age care policy and further research are discussed.

Critical incident monitoring in paediatric and adult critical care: from reporting to improved patient outcomes?

PURPOSE OF REVIEW: Critical incident reporting alone does not necessarily improve patient safety or even patient outcomes. Substantial improvement has been made by focusing on the further two steps of critical incident monitoring, that is, the analysis of critical incidents and implementation of system changes. The system approach to patient safety had an impact on the view about the patient's role in safety. This review aims to analyse recent advances in the technique of reporting, the analysis of reported incidents, and the implementation of actual system improvements. It also explores how families should be approached about safety issues. RECENT FINDINGS: It is essential to make as many critical incidents as possible known to the intensive care team. Several factors have been shown to increase the reporting rate: anonymity, regular feedback about the errors reported, and the existence of a safety climate. Risk scoring of critical incident reports and root cause analysis may help in the analysis of incidents. Research suggests that patients can be successfully involved in safety. SUMMARY: A persisting high number of reported incidents is anticipated and regarded as continuing good safety culture. However, only the implementation of system changes, based on incident reports, and also involving the expertise of patients and their families, has the potential to improve patient outcome. Hard outcome criteria, such as standardized mortality ratio, have not yet been shown to improve as a result of critical incident monitoring.

Antibiotic use in adult outpatients in Switzerland in relation to regions, seasonality and point of care tests

The use of antibiotics is highest in primary care and directly associated with antibiotic resistance in the community. We assessed regional variations in antibiotic use in primary care in Switzerland and explored prescription patterns in relation to the use of point of care tests. Defined daily doses of antibiotics per 1000 inhabitants (DDD(1000pd) ) were calculated for the year 2007 from reimbursement data of the largest Swiss health insurer, based on the anatomic therapeutic chemical classification and the DDD methodology recommended by WHO. We present ecological associations by use of descriptive and regression analysis. We analysed data from 1 067 934 adults, representing 17.1% of the Swiss population. The rate of outpatient antibiotic prescriptions in the entire population was 8.5 DDD(1000pd) , and varied between 7.28 and 11.33 DDD(1000pd) for northwest Switzerland and the Lake Geneva region. DDD(1000pd) for the three most prescribed antibiotics were 2.90 for amoxicillin and amoxicillin-clavulanate, 1.77 for fluoroquinolones, and 1.34 for macrolides. Regions with higher DDD(1000pd) showed higher seasonal variability in antibiotic use and lower use of all point of care tests. In regression analysis for each class of antibiotics, the use of any point of care test was consistently associated with fewer antibiotic prescriptions. Prescription rates of primary care physicians showed variations between Swiss regions and were lower in northwest Switzerland and in physicians using point of care tests. Ecological studies are prone to bias and whether point of care tests reduce antibiotic use has to be investigated in pragmatic primary care trials.

Evidence-based management of bullous pemphigoid

Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease typically affecting the elderly. Although different therapeutic regimens have been proposed, a review of the evidence is needed to aid clinicians in their decision making and management. Systemic therapies such as corticosteroids and adjuvants are effective in BP but are plagued with adverse effects, and potent topical steroids are an alternative treatment. This article reviews the evidence supporting different therapeutic options in the management of BP.

Evidence Based Development of a Novel Lateral Fibula Plate (VariAx Fibula) Using a Real CT Bone Data Based Optimization Process During Device Development

Development of novel implants in orthopaedic trauma surgery is based on limited datasets of cadaver trials or artificial bone models. A method has been developed whereby implants can be constructed in an evidence based method founded on a large anatomic database consisting of more than 2.000 datasets of bones extracted from CT scans. The aim of this study was the development and clinical application of an anatomically pre-contoured plate for the treatment of distal fibular fractures based on the anatomical database. 48 Caucasian and Asian bone models (left and right) from the database were used for the preliminary optimization process and validation of the fibula plate. The implant was constructed to fit bilaterally in a lateral position of the fibula. Then a biomechanical comparison of the designed implant to the current gold standard in the treatment of distal fibular fractures (locking 1/3 tubular plate) was conducted. Finally, a clinical surveillance study to evaluate the grade of implant fit achieved was performed. The results showed that with a virtual anatomic database it was possible to design a fibula plate with an optimized fit for a large proportion of the population. Biomechanical testing showed the novel fibula plate to be superior to 1/3 tubular plates in 4-point bending tests. The clinical application showed a very high degree of primary implant fit. Only in a small minority of cases further intra-operative implant bending was necessary. Therefore, the goal to develop an implant for the treatment of distal fibular fractures based on the evidence of a large anatomical database could be attained. Biomechanical testing showed good results regarding the stability and the clinical application confirmed the high grade of anatomical fit.

Ordering CT pulmonary angiography to exclude pulmonary embolism: defense versus evidence in the emergency room

To identify reasons for ordering computed tomography pulmonary angiography (CTPA), to identify the frequency of reasons for CTPA reflecting defensive behavior and evidence-based behavior, and to identify the impact of defensive medicine and of training about diagnosing pulmonary embolism (PE) on positive results of CTPA.

Quantitative assessment of urea generation and elimination in healthy dogs and in dogs with chronic kidney disease

BACKGROUND: Kinetic assessment of urea, the main end product of protein metabolism, could serve to assess protein catabolism in dogs with chronic kidney disease (CKD). Protein malnutrition and catabolism are poorly documented in CKD and they often are neglected clinically because of a lack of appropriate evaluation tools. HYPOTHESIS: Generation and excretion of urea are altered in dogs with CKD. ANIMALS: Nine dogs with spontaneous CKD (IRIS stages 2-4) and 5 healthy research dogs. METHODS: Endogenous renal clearance (Clrenal) of urea and creatinine was measured first. Exogenous plasma clearance (Clplasma, total body clearance) of the 2 markers then was determined by an IV infusion of urea (250-1,000 mg/kg over 20 minutes) and an IV bolus of creatinine (40 mg/kg). Extrarenal clearance (Clextra) was defined as the difference between Clplasma)and Clrenal. Endogenous urea generation was computed assuming steady-state conditions. RESULTS: Median Clrenal and Clextra of urea were 2.17 and 0.21 mL/min/kg in healthy dogs and 0.37 and 0.28 mL/min/kg in CKD dogs. The proportion of urea cleared by extrarenal route was markedly higher in dogs with glomerular filtration rate<1 mL/kg/min than in normal dogs, reaching up to 85% of the total clearance. A comparable pattern was observed for creatinine excretion, except in 1 dog, Clextra remained<20% of Clplasma. CONCLUSION: Extrarenal pathways of urea excretion are predominant in dogs with advanced CKD and justify exploring adjunctive therapies based on enteric nitrogen excretion in dogs. A trend toward increased urea generation may indicate increased catabolism in advanced CKD.

Current Changes in the Lifestyle and Mental Health of Teenagers

The group studied 1,253 students from various types of schools chosen randomly from those in Prague and Budejovice in order to evaluate the life styles, prevailing value standards, attitudes and behavioural patterns of Czech adolescents. The respondents (including 614 men and 639 women with an average age of 16.4 years) completed questionnaires containing standard scales focusing on feelings about social life, conservative and authoritarian tendencies, levels of self-esteem, general health, eating attitudes and behaviour The adolescents showed a relatively high level of conformity with authoritarian, conservative tendencies and with a dictate of power, rigid conventionality, ethnocentrism and low inner tolerance of differences, their scores being higher than those found in Western European countries. These tendencies were stronger among students outside Prague and those attending vocational schools. As the level of education rose, the sense of fatality and social determination decreased, indicating a higher share of responsibility for events in the surrounding world. When changes of life style were considered, adolescents can be expected to adapt more easily to more risky, socially attractive and manifest models of attitudes and behaviour. On the one hand, adolescents were often involved in sports, and young women in particular often showed a extreme concern and care for their own bodies. On the other hand, one quarter of respondents smoked, one fifth reported serious problems with alcohol and one quarter had already had some experience with drugs. One third of young men and one quarter of young women reported regular consumption of alcohol, and 6.5 percent of men and 3.6 percent of women regularly smoked marihuana or hashish. For the majority of adolescents, life conditions and conformity seem to be more important than the sense of active choice and responsibility for one's own life.