Current prescribing practices for major depressive disorder (MDD) produce limited treatment success. Although pharmacogenomics may improve outcomes by identifying genetically inappropriate ...medications, studies to date were limited in scope. Outpatients (N = 1167) diagnosed with MDD and with a patient- or clinician-reported inadequate response to at least one antidepressant were enrolled in the Genomics Used to Improve DEpression Decisions (GUIDED) trial – a rater- and patient-blind randomized controlled trial. Patients were randomized to treatment as usual (TAU) or a pharmacogenomics-guided intervention arm in which clinicians had access to a pharmacogenomic test report to inform medication selections (guided-care). Medications were considered congruent (‘use as directed’ or ‘use with caution’ test categories) or incongruent (‘use with increased caution and with more frequent monitoring’ test category) with test results. Unblinding occurred after week 8. Primary outcome was symptom improvement change in 17-item Hamilton Depression Rating Scale (HAM-D17) at week 8; secondary outcomes were response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. At week 8, symptom improvement for guided-care was not significantly different than TAU (27.2% versus 24.4%, p = 0.107); however, improvements in response (26.0% versus 19.9%, p = 0.013) and remission (15.3% versus 10.1%, p = 0.007) were statistically significant. Patients taking incongruent medications prior to baseline who switched to congruent medications by week 8 experienced greater symptom improvement (33.5% versus 21.1%, p = 0.002), response (28.5% versus 16.7%, p = 0.036), and remission (21.5% versus 8.5%, p = 0.007) compared to those remaining incongruent. Pharmacogenomic testing did not significantly improve mean symptoms but did significantly improve response and remission rates for difficult-to-treat depression patients over standard of care (ClinicalTrials.gov NCT02109939).
Backgrounds and reflects on themes in two essays contributed by Auckland University medical students, 'Homecoming' by Rebecca Gandhi and 'An unexpected journey' by Thomas Swinburn, about their first ...experiences of dying patients. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Half a million patients are hospitalized with severe dengue every year, many of whom would die without timely, appropriate clinical intervention. The majority of dengue cases are uncomplicated; ...however, 2-5% progress to severe dengue. Severe dengue cases have been reported with increasing frequency over the last 30 years. To discover biomarkers for severe dengue, we used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to analyze dengue virus positive serum samples from the acute phase of infection. Using this method, 16 proteins were identified as candidate biomarkers for severe dengue. From these 16 biomarkers, three candidates were selected for confirmation by enzyme-linked immunosorbent assay and Western blot: vitronectin (Vtn, 55.1 kDa), hemopexin (Hx, 52.4 kDa), and serotransferrin (Tf, 79.2 kDa). Vitronectin, Hx, and Tf best differentiated between dengue and severe dengue.
Loss of empathy has been reported in medical students as they move through the clinical phases of their training. Several researchers have attempted to address this issue by exploring ways of ...heightening students' awareness of the emotional, non-biomedical aspects of illness and the dynamics of the doctor-patient relationship, using a variety of reflective group discussion methods. This pilot project employed the specific group method developed by Michael Balint for general practitioners working in London after the Second World War. The pilot was based on one group of six third-year graduate students, meeting weekly over six weeks. Evaluation includes pre- and post-questionnaires, a 1000-word essay and leaders' observations. The results suggest that the traditional Balint method needs to be modified for students at a point in their training where they have not yet been exposed to patients for long enough to develop meaningful patient relationships. Nevertheless, there was some evidence of a heightened awareness of the dynamics of doctor-patient relationships and the importance of psychological/emotional factors (including their own prejudices) when interacting with a patient. Balint-style groups could be an effective way of encouraging medical students to reflect on the importance of emotions in the doctor-patient relationship.
Surface-Enhanced, Laser-Desorption & Ionization, Time-Of-Flight Mass Spectrometry (SELDI-TOF MS) permits the study of the protein/peptide content of complex biological fluids such as serum, plasma, ...urine, cell lysates and tissue extracts. This high throughput proteomic platform has been used to identify biomarkers for a wide range of inflammatory, infectious and neoplastic conditions. The promising results obtained in these varied conditions raised the possibility that SELDI could be applied to dengue virus (DV) infection to develop urgently needed diagnostic tests. Plasma from pediatric Thai patients with either primary (1°) dengue fever (DF) (n=12) or dengue hemorrhagic fever (DHF) (n=9) as well as patients with either secondary (2°) DF (n=24) or DHF (n=27) were available for the Discovery Study. In addition, 15 samples from Thai patients admitted to hospital with other febrile illnesses (OFI) were analyzed as controls. Validation was accomplished using sera samples from 30 confirmed 2° DF, 54 2° DHF and 30 OFI cases from Puerto Rico (PR). SELDI peaks that discriminated between patients with DV infection and those with OFI were considered potential diagnostic biomarkers. SELDI peaks that differed between uncomplicated DV infection and DHF early in the course of infection were considered to be potential prognostic biomarkers. For both cases, an initial p-value ≤ 0.05 and a 0.30 ≥ ROC-value ≥ 0.70 were used in screening potential biomarkers. Of these, only the peaks that showed an intensity ratio between the two groups being compared of at least 2 and followed the same pattern (i.e. either up- or down-regulated) in PR and Thai samples were considered as candidate biomarkers. Following these criteria, 33 peaks were selected that differentiated 2°DV from OFI and 4 peaks between 2°DF and 2°DHF. Using Biomarker Pattern Software (BPS), an algorithm was developed and tested using two independent data sets (i.e. PR as the learning set and Thai as the testing set). A specificity and sensitivity ≥ 89% for diagnostic purposes was achieved. Unfortunately, no algorithm for prognostic purposes with a specificity and sensitivity ≥70% using a single or a combination of the 4 selected peaks was achieved. Guided by these results, the most promising candidate biomarkers were identified using SDS-PAGE gels and tandem MS. More than 30 proteins were identified, five of which were detected in samples from both countries (i.e. α2-macroglobulin, complement component C3, plasma protease (C1) inhibitor, serotransferrin inhibitor, serum albumin, and vitronectin precursor). The last, vitronectin (Vn) precursor protein, was selected for further, in depth study. Vn is an acute phase glycoprotein thought to be involved in vascular inflammation and complement activation. Since hemorrhages and plasma leakage are hallmarks of severe DV infection, it may be relevant that Vn also plays a role in the fibrinolytic pathway. By binding and stabilizing type 1 plasminogen activator inhibitor (PAI-1), it inhibits fibrinolysis. In Thai subjects, we found that Vn precursor could differentiate between 1°DF and more severe DV infection (e.g.: DHF and dengue shock syndrome). The Vn precursor was readily found by Western blot in serum/plasma from healthy children as well as patients with OFI or 1°DF but it was not detectable in patients with 1°DHF, 2° DF, or 2° DHF. Surprisingly, these results could not be confirmed in the Puerto Rican samples although Vn does seem to be a biomarker if we consider the concentration of Vn found in both set of samples. The genetic background of the individuals studied and/or of the viral strains may account for these differences. The total Vn plasma concentration was lower in 2°DHF (about 20% Vn of normal plasma content) than in 2°DF samples (70% Vn of normal plasma) or in OFI and healthy samples with a p-value < 0.01. PR samples followed the same trend (2°DF > 2°DHF) with a significance of p-value<0.001. Although clinical manifestations of a 1° and 2°DV infection is clinically indistinguishable, more than 100 candidate biomarkers were found in Thai specimen that differentiated between the 1° and 2° DV infection proteomes. This suggests that the plasma proteome of patients with a 1° infection is markedly different than that of a patient with a 2° infection and that perhaps the underlying disease mechanism might differ in subtle ways. This study demonstrates the potential for high-throughput proteomics to develop useful diagnostic and prognostic tests for DF/DHF. Additionally, such biomarker studies may give unique insight into the mechanisms underlying the different manifestations of DV infection.
Multi-center, cross-sectional, observational study. STUDY CENTER(S): Multiple centers in India. NUMBER OF PARTICIPANTS: 1,000. PRIMARY RESEARCH OBJECTIVE: To characterize patients and treatment ...utilized for orthopedic patients presenting to both private and public hospital centers in India with knee pain and symptoms suggestive of knee arthritis.
All patients 18 years of age or older who present to a recruiting hospital for treatment of knee pain will be eligible for participation. The subjects must be able to understand and complete the questionnaire.
Patients with total knee replacement, open wound or evidence of recent surgery, or with a current or a history of tumor and/or fracture in the tibial plateau, femoral condyle or patella, in the affected knee are not eligible.
This study aims to characterize the following: general demographics of patients presenting with knee pain, severity of knee symptoms at time of presentation, severity of knee pathology at time of presentation, factors associated with the decision to seek medical care, previous treatments and health care contacts, planned treatment, and gaps in treatment perceived by the patient and treating surgeons.
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