Evidence-based Research in Complementary and Alternative Medicine I: History

Contemporary Western medicine has witnessed a fragmentation of our conceptualization of the medical endeavor into ‘traditional medicine’ and ‘non-traditional medicine’. The former is meant to refer to the Western medical tradition, the latter encompasses both ‘complementary’ and ‘alternative’ medical practices. Complementary medicine complements conventional medical treatments, and alternative modes of medical interventions are meant to replace traditional Western medicine. Evidence-based research must be directed at establishing the best available evidence in complementary and alternative medicine. This paper is the first of a set of four ‘lectures’ that reviews the process of evidence-based research, and discusses its implications and applications for the early decades of the 21st century. The purpose of this paper is to introduce the series by examining some of the historical and philosophical foundations of this research endeavor

Evidence-Based Research in Complementary and Alternative Medicine II: The Process of Evidence-Based Research

It is a common practice in contemporary medicine to follow stringently the scientific method in the process of validating efficacy and effectiveness of new or improved modes of treatment intervention. It follows that these complementary or alternative interventions must be validated by stringent research before they can be reliably integrated into Western medicine. The next decades will witness an increasing number of evidence-based research directed at establishing the best available evidence in complementary and alternative medicine (CAM). This second paper in this lecture series examines the process of evidence-based research (EBR) in the context of CAM. We outline the fundamental principles, process and relevance of EBR, and its implication to CAM. We underscore areas of future development in EBR. We note that the main problem of applying EBR to CAM at present has to do with the fact that the contribution of EBR can be significant only to the extent to which studies used in the process of EBR are of good quality. All too often CAM research is not of sufficient quality to warrant the generation of a consensus statement. EBR, nevertheless, can contribute to CAM by identifying current weaknesses of CAM research. We present a revised instrument to assess quality of the literature

25 hydroxyvitamin D deficiency and its relationship to autoimmune thyroid disease in the elderly

Background: Low 25(OH) vitamin D levels have been associated with several autoimmune diseases and recently with autoimmune thyroiditis (AT). The aim of the study was to investigate the association of AT with low 25(OH) vitamin D levels in the elderly. Methods: One hundred sixty-eight elderly subjects (mean age: 81.6 ± 9.4 years) were enrolled. Serum levels of 25(OH) vitamin D, anti-thyroid peroxidase (TPO-Ab), anti-thyroglobulin (TG-Ab) antibodies, free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were measured. Results: The prevalence of AT was significantly higher in subjects with vitamin D deficiency (25(OH) vitamin D < 20 ng/mL) when compared with subjects with normal 25(OH) vitamin D (25(OH) vitamin D ≥ 20 ng/mL) levels (28% vs. 8%, respectively, p = 0.002). Patients with AT and vitamin D deficiency had a comparable hormonal profile compared to patients with AT and vitamin D sufficiency in terms of TSH (p = 0.39), FT3 (p = 0.30), FT4 (p = 0.31), TG-Ab (0.44) and TPO-Ab (0.35). Interestingly, a significant correlation between 25(OH) vitamin D and TPO-Ab (r = −0.27, p = 0.03) and FT3 (r = 0.35, p = 0.006) has been found in subjects with AT while no correlation was found between 25(OH) vitamin D levels and TG-Ab (r = −0.15, p = 0.25), TSH (r = −0.014, p = 0.09) and FT4 (r = 0.13, p = 0.32). Conclusions: These findings suggest that vitamin D deficiency was significantly associated with AT in the elderly. Therefore, the screening for AT should be suggested in subjects with vitamin D deficiency

GEOMETRICAL EVALUATION OF RECTANGULAR FIN MOUNTED IN LATERAL SURFACE OF LID-DRIVEN CAVITY FORCED CONVECTIVE FLOWS

In this work, it is investigated the geometric effect of rectangular fin inserted in a lid-driven square cavity over thermal performance of laminar, incompressible, steady and forced convective flows. This study is performed by applying Constructal Design to maximize the heat transfer between the fin and the cavity flow. For that, the problem is subjected to two constraints: area of the cavity and area of rectangular fin, and two degrees of freedom: height/length ratio of rectangular fin (H1/L1) and its position in upstream surface of the cavity (S/A1/2). It is considered here some fixed parameters, as the ratio between the fin and cavity areas (ϕ = 0.05), the aspect ratio of the cavity dimensions (H/L = 1.0) and Prandtl number (Pr = 0.71). The fin aspect ratio (H1/L1) was varied for three different placements of the fin at the upstream cavity surface (S/A1/2 = 0.1, 0.5 and 0.9) which represents a lower, intermediate and upper positions of the fin. The effects of the fin geometry over the spatial-averaged Nusselt number ( ) is investigated for three different Reynolds numbers (ReH = 10, 102 and 103). The conservation equations of mass, momentum and energy were numerically solved with the Finite Volume Method. Results showed that both degrees of freedom (H1/L1 and S/A1/2) had a strong influence over , mainly for higher magnitudes of Reynolds number. Moreover, the best thermal performance is reached when the fin is placed near the upper surface of the cavity for an intermediate ratio between height and length of rectangular fin, more precisely when (S/A1/2)o = 0.9 and (H1/L1)oo = 2.0

European Sea Bass (Dicentrarchus labrax) immune status and disease resistance are impaired by arginine dietary supplementation

Infectious diseases and fish feeds management are probably the major expenses in the aquaculture business. Hence, it is a priority to define sustainable strategies which simultaneously avoid therapeutic procedures and reinforce fish immunity. Currently, one preferred approach is the use of immunostimulants which can be supplemented to the fish diets. Arginine is a versatile amino acid with important mechanisms closely related to the immune response. Aiming at finding out how arginine affects the innate immune status or improve disease resistance of European seabass (Dicentrarchus labrax) against vibriosis, fish were fed two arginine-supplemented diets (1% and 2% arginine supplementation). A third diet meeting arginine requirement level for seabass served as control diet. Following 15 or 29 days of feeding, fish were sampled for blood, spleen and gut to assess cell-mediated immune parameters and immune-related gene expression. At the same time, fish from each dietary group were challenged against Vibrio anguillarum and survival was monitored. Cell-mediated immune parameters such as the extracellular superoxide and nitric oxide decreased in fish fed arginine-supplemented diets. Interleukins and immune-cell marker transcripts were down-regulated by the highest supplementation level. Disease resistance data were in accordance with a generally depressed immune status, with increased susceptibility to vibriosis in fish fed arginine supplemented diets. Altogether, these results suggest a general inhibitory effect of arginine on the immune defences and disease resistance of European seabass. Still, further research will certainly clarify arginine immunomodulation pathways thereby allowing the validation of its potential as a prophylactic strategy.European Union's Seventh Framework Programme AQUAEXCEL (Aquaculture Infrastructures for Excellence in European Fish Research) [262336]; AQUAIMPROV [NORTE-07-0124-FEDER-000038]; North Portugal Regional Operational Programme (ON. 2 - O Novo Norte) , under the National Strategic Reference Framework, through the European Regional Development Fund; North Portugal Regional Operational Programme (ON. 2 - O Novo Norte), under the National Strategic Reference Framework through the COMPETE - Operational Competitiveness Programme; Fundacao para a Ciencia e Tecnologia; Fundacao para a Ciencia e Tecnologia [SFRH/BD/89457/2012, SFRH/BPD/77210/2011]; Generalitat Valenciana through the project REVIDPAQUA [ISIC/2012/003]; [PEst-C/MAR/LA0015/2013]; [UID/Multi/04423/2013]info:eu-repo/semantics/publishedVersio

Circadian Modulation of Gene Expression, but not Glutamate Uptake, in Mouse and Rat Cortical Astrocytes

Circadian clocks control daily rhythms including sleep-wake, hormone secretion, and metabolism. These clocks are based on intracellular transcription-translation feedback loops that sustain daily oscillations of gene expression in many cell types. Mammalian astrocytes display circadian rhythms in the expression of the clock genes Period1 (Per1) and Period2 (Per2). However, a functional role for circadian oscillations in astrocytes is unknown. Because uptake of extrasynaptic glutamate depends on the presence of Per2 in astrocytes, we asked whether glutamate uptake by glia is circadian.We measured glutamate uptake, transcript and protein levels of the astrocyte-specific glutamate transporter, Glast, and the expression of Per1 and Per2 from cultured cortical astrocytes and from explants of somatosensory cortex. We found that glutamate uptake and Glast mRNA and protein expression were significantly reduced in Clock/Clock, Per2- or NPAS2-deficient glia. Uptake was augmented when the medium was supplemented with dibutyryl-cAMP or B27. Critically, glutamate uptake was not circadian in cortical astrocytes cultured from rats or mice or in cortical slices from mice.We conclude that glutamate uptake levels are modulated by CLOCK, PER2, NPAS2, and the composition of the culture medium, and that uptake does not show circadian variations

Cost-effectiveness of microendoscopic discectomy versus conventional open discectomy in the treatment of lumbar disc herniation: a prospective randomised controlled trial [ISRCTN51857546]

BACKGROUND: Open discectomy is the standard surgical procedure in the treatment of patients with long-lasting sciatica caused by lumbar disc herniation. Minimally invasive approaches such as microendoscopic discectomy have gained attention in recent years. Reduced tissue trauma allows early ambulation, short hospital stay and quick resumption of daily activities. A comparative cost-effectiveness study has not been performed yet. We present the design of a randomised controlled trial on cost-effectiveness of microendoscopic discectomy versus conventional open discectomy in patients with lumbar disc herniation. METHODS/DESIGN: Patients (age 18–70 years) presenting with sciatica due to lumbar disc herniation lasting more than 6–8 weeks are included. Patients with disc herniation larger than 1/3 of the spinal canal diameter, or disc herniation less than 1/3 of the spinal canal diameter with concomitant lateral recess stenosis or sequestration, are eliglible for participation. Randomisation into microendoscopic discectomy or conventional unilateral transflaval discectomy will take place in the operating room after induction of anesthesia. The length of skin incision is equal in both groups. The primary outcome measure is the functional assessment of the patient, measured by the Roland Disability Questionnaire for Sciatica, at 8 weeks and 1 year after surgery. We will also evaluate several other outcome parameters, including perceived recovery, leg and back pain, incidence of re-operations, complications, serum creatine kinase, quality of life, medical consumption, absenteeism and costs. The study is a randomised prospective multi-institutional trial, in which two surgical techniques are compared in a parallel group design. Patients and research nurses are kept blinded of the allocated treatment during the follow-up period of 2 years. DISCUSSION: Currently, open discectomy is the golden standard in the surgical treatment of lumbar disc herniation. Whether microendoscopic discectomy is more cost-effective than unilateral transflaval discectomy has to be determined by this trial

High Degree of Heterogeneity in Alzheimer's Disease Progression Patterns

There have been several reports on the varying rates of progression among Alzheimer's Disease (AD) patients; however, there has been no quantitative study of the amount of heterogeneity in AD. Obtaining a reliable quantitative measure of AD progression rates and their variances among the patients for each stage of AD is essential for evaluating results of any clinical study. The Global Deterioration Scale (GDS) and Functional Assessment Staging procedure (FAST) characterize seven stages in the course of AD from normal aging to severe dementia. Each GDS/FAST stage has a published mean duration, but the variance is unknown. We use statistical analysis to reconstruct GDS/FAST stage durations in a cohort of 648 AD patients with an average follow-up time of 4.78 years. Calculations for GDS/FAST stages 4–6 reveal that the standard deviations for stage durations are comparable with their mean values, indicating the presence of large variations in the AD progression among patients. Such amount of heterogeneity in the course of progression of AD is consistent with the existence of several sub-groups of AD patients, which differ by their patterns of decline

Calculating Stage Duration Statistics in Multistage Diseases

Many human diseases are characterized by multiple stages of progression. While the typical sequence of disease progression can be identified, there may be large individual variations among patients. Identifying mean stage durations and their variations is critical for statistical hypothesis testing needed to determine if treatment is having a significant effect on the progression, or if a new therapy is showing a delay of progression through a multistage disease. In this paper we focus on two methods for extracting stage duration statistics from longitudinal datasets: an extension of the linear regression technique, and a counting algorithm. Both are non-iterative, non-parametric and computationally cheap methods, which makes them invaluable tools for studying the epidemiology of diseases, with a goal of identifying different patterns of progression by using bioinformatics methodologies. Here we show that the regression method performs well for calculating the mean stage durations under a wide variety of assumptions, however, its generalization to variance calculations fails under realistic assumptions about the data collection procedure. On the other hand, the counting method yields reliable estimations for both means and variances of stage durations. Applications to Alzheimer disease progression are discussed

Adherence to antibiotic treatment guidelines and outcomes in the hospitalized elderly with different types of pneumonia

Background: Few studies evaluated the clinical outcomes of Community Acquired Pneumonia (CAP), Hospital-Acquired Pneumonia (HAP) and Health Care-Associated Pneumonia (HCAP) in relation to the adherence of antibiotic treatment to the guidelines of the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) in hospitalized elderly people (65 years or older). Methods: Data were obtained from REPOSI, a prospective registry held in 87 Italian internal medicine and geriatric wards. Patients with a diagnosis of pneumonia (ICD-9 480-487) or prescribed with an antibiotic for pneumonia as indication were selected. The empirical antibiotic regimen was defined to be adherent to guidelines if concordant with the treatment regimens recommended by IDSA/ATS for CAP, HAP, and HCAP. Outcomes were assessed by logistic regression models. Results: A diagnosis of pneumonia was made in 317 patients. Only 38.8% of them received an empirical antibiotic regimen that was adherent to guidelines. However, no significant association was found between adherence to guidelines and outcomes. Having HAP, older age, and higher CIRS severity index were the main factors associated with in-hospital mortality. Conclusions: The adherence to antibiotic treatment guidelines was poor, particularly for HAP and HCAP, suggesting the need for more adherence to the optimal management of antibiotics in the elderly with pneumonia