Продукты ограниченного протеолиза: подходы к обнаружению и диагностические возможности в оценке тяжести патологии при эндогенной интоксикации

ПРОДУКТЫ ОГРАНИЧЕННОГО ПРОТЕОЛИЗАПРОТЕИНАЗО-ИНГИБИТОРНАЯ СИСТЕМАОТРАВЛЕНИЕ /ДИАГН /ОСЛЭНДОГЕННАЯ ИНТОКСИКАЦИЯ /ДИАГН /ОСЛСРЕДНЕМОЛЕКУЛЯРНАЯ ПЕПТИДНАЯ ФРАКЦИЯПАТОЛОГИЧЕСКИЕ ПРОЦЕССЫЛАБОРАТОРНЫЕ МЕТОДЫ И ПРОЦЕДУРЫБЕЛКОВО-ПЕПТИДНЫЕ КОМПОНЕНТ

Primacy of effective communication and its influence on adherence to artemether-lumefantrine treatment for children under five years of age: a qualitative study.

BACKGROUND\ud \ud Prompt access to artemesinin-combination therapy (ACT) is not adequate unless the drug is taken according to treatment guidelines. Adherence to the treatment schedule is important to preserve efficacy of the drug. Although some community based studies have reported fairly high levels of adherence, data on factors influencing adherence to artemether-lumefantrine (AL) treatment schedule remain inadequate. This study was carried-out to explore the provider's instructions to caretakers, caretakers' understanding of the instructions and how that understanding was likely to influence their practice with regard to adhering to AL treatment schedule.\ud \ud METHODS\ud \ud A qualitative study was conducted in five villages in Kilosa district, Tanzania. In-depth interviews were held with providers that included prescribers and dispensers; and caretakers whose children had just received AL treatment. Information was collected on providers' instructions to caretakers regarding dose timing and how to administer AL; and caretakers' understanding of providers' instructions.\ud \ud RESULTS\ud \ud Mismatch was found on providers' instructions as regards to dose timing. Some providers' (dogmatists) instructions were based on strict hourly schedule (conventional) which was likely to lead to administering some doses in awkward hours and completing treatment several hours before the scheduled time. Other providers (pragmatists) based their instruction on the existing circumstances (contextual) which was likely to lead to delays in administering the initial dose with serious treatment outcomes. Findings suggest that, the national treatment guidelines do not provide explicit information on how to address the various scenarios found in the field. A communication gap was also noted in which some important instructions on how to administer the doses were sometimes not provided or were given with false reasons.\ud \ud CONCLUSIONS\ud \ud There is need for a review of the national malaria treatment guidelines to address local context. In the review, emphasis should be put on on-the-job training to address practical problems faced by providers in the course of their work. Further research is needed to determine the implication of completing AL treatment prior to scheduled time

Identification and Validation of Leucine-rich α-2-glycoprotein 1 as a Noninvasive Biomarker for Improved Precision in Prostate Cancer Risk Stratification.

BACKGROUND: More accurate risk assessments are needed to improve prostate cancer management. OBJECTIVE: To identify blood-based protein biomarkers that provided prognostic information for risk stratification. DESIGN SETTING AND PARTICIPANTS: Mass spectrometry was used to identify biomarker candidates from blood, and validation studies were performed in four independent cohorts retrospectively collected between 1988 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome objectives were progression-free survival, prostate cancer-specific survival (PCSS), and overall survival. Statistical analyses to assess survival and model performance were performed. RESULTS AND LIMITATION: Serum leucine-rich α-2-glycoprotein 1 (LRG1) was found to be elevated in fatal prostate cancer. LRG1 provided prognostic information independent of metastasis and increased the accuracy in predicting PCSS, particularly in the first 3 yr. A high LRG1 level is associated with an average of two-fold higher risk of disease-progression and mortality in both high-risk and metastatic patients. However, our study design, with a retrospective analysis of samples spanning several decades back, limits the assessment of the clinical utility of LRG1 in today's clinical practice. Thus, independent prospective studies are needed to establish LRG1 as a clinically useful biomarker for patient management. CONCLUSIONS: High blood levels of LRG1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer, and LRG1 increased the accuracy of risk stratification of prostate cancer patients. PATIENT SUMMARY: High blood levels of leucine-rich α-2-glycoprotein 1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer

Long-term follow-up of disability pensioners having musculoskeletal disorders

<p>Abstract</p> <p>Background</p> <p>Previously we have conducted a randomised controlled trial (RCT) to evaluate the effect of a brief cognitive behavioural program with a vocational approach aiming to return disability pensioners with back pain to work, as compared to no intervention. One year after the intervention, 10 participants (22%) who received the program and 5 (11%) in the control group reported to have entered a return to work process. The aims of this study were to evaluate long-term effects of the intervention, and compare this effect to 2 reference populations not participating in the original trial.</p> <p>Methods</p> <p>Three groups of disability pensioners were investigated: 1) Disability pensioners having back pain (n = 89) previously participating in the RCT (randomized to either a brief cognitive behavioural intervention or to a control group), 2) 342 disability pensioners having back pain, but refusing to participate in the study and 3) 449 disability pensioners having other musculoskeletal disorders than back pain. Primary outcome was return to work, defined as a reduction in payment of disability pension.</p> <p>Results</p> <p>Only 2 of 89 (2.3%) participants from the RCT had reduced disability pension at 3-years follow-up, both from the control group. None of the participants that had been in a process of returning to work after 1 year had actually gained employment at 3-years follow-up. In the 2 groups not participating in the previous RCT, only 4 (1.2%) and 8 (1.6%) had returned to work after 3 years respectively.</p> <p>Conclusion</p> <p>The number of pensioners who returned to work was negligible in all groups regardless of having participated in a cognitive behavioural intervention or not.</p

Estimating Long-Term Survival of Critically Ill Patients: The PREDICT Model

BACKGROUND: Long-term survival outcome of critically ill patients is important in assessing effectiveness of new treatments and making treatment decisions. We developed a prognostic model for estimation of long-term survival of critically ill patients. METHODOLOGY AND PRINCIPAL FINDINGS: This was a retrospective linked data cohort study involving 11,930 critically ill patients who survived more than 5 days in a university teaching hospital in Western Australia. Older age, male gender, co-morbidities, severe acute illness as measured by Acute Physiology and Chronic Health Evaluation II predicted mortality, and more days of vasopressor or inotropic support, mechanical ventilation, and hemofiltration within the first 5 days of intensive care unit admission were associated with a worse long-term survival up to 15 years after the onset of critical illness. Among these seven pre-selected predictors, age (explained 50% of the variability of the model, hazard ratio [HR] between 80 and 60 years old = 1.95) and co-morbidity (explained 27% of the variability, HR between Charlson co-morbidity index 5 and 0 = 2.15) were the most important determinants. A nomogram based on the pre-selected predictors is provided to allow estimation of the median survival time and also the 1-year, 3-year, 5-year, 10-year, and 15-year survival probabilities for a patient. The discrimination (adjusted c-index = 0.757, 95% confidence interval 0.745-0.769) and calibration of this prognostic model were acceptable. SIGNIFICANCE: Age, gender, co-morbidities, severity of acute illness, and the intensity and duration of intensive care therapy can be used to estimate long-term survival of critically ill patients. Age and co-morbidity are the most important determinants of long-term prognosis of critically ill patients

Impact of previous sepsis on the accuracy of procalcitonin for the early diagnosis of blood stream infection in critically ill patients

<p>Abstract</p> <p>Background</p> <p>Blood stream infections (BSI) are life-threatening infections in intensive care units (ICU), and prognosis is highly dependent on early detection. Procalcitonin levels have been shown to accurately and quickly distinguish between BSI and noninfectious inflammatory states in critically ill patients. It is, however, unknown to what extent a recent history of sepsis (namely, secondary sepsis) can affect diagnosis of BSI using PCT.</p> <p>Methods</p> <p>review of the medical records of every patient with BSI in whom PCT dosage at the onset of sepsis was available between 1^stSeptember, 2006 and 31^stJuly, 2007.</p> <p>Results</p> <p>179 episodes of either primary (<it>n </it>= 117) or secondary (<it>n </it>= 62) sepsis were included. Procalcitonin levels were found to be markedly lower in patients with secondary sepsis than in those without (6.4 [9.5] vs. 55.6 [99.0] ng/mL, respectively; <it>p </it>< 0.001), whereas the SOFA score was similar in the two groups. Although patients in the former group were more likely to have received steroids and effective antibiotic therapy prior to the BSI episode, and despite a higher proportion of candidemia in this group, a low PCT value was found to be independently associated with secondary sepsis (Odd Ratio = 0.33, 95% Confidence Interval: 0.16–0.70; <it>p </it>= 0.004). Additional patients with suspected but unconfirmed sepsis were used as controls (<it>n </it>= 23). Thus, diagnostic accuracy of PCT as assessed by the area under the receiver-operating characteristic curves (AUROCC) measurement was decreased in the patients with secondary sepsis compared to those without (AUROCC = 0.805, 95% CI: 0.699–0.879, vs. 0.934, 95% CI: 0.881–0.970, respectively; <it>p </it>< 0.050).</p> <p>Conclusion</p> <p>In a critically ill patient with BSI, PCT elevation and diagnosis accuracy could be lower if sepsis is secondary than in those with a first episode of infection.</p

Avanços recentes em nutrição de larvas de peixes

Os requisitos nutricionais de larvas de peixes são ainda mal compreendidos, o que leva a altas mortalidades e problemas de qualidade no seu cultivo. Este trabalho pretende fazer uma revisão de novas metodologias de investigação, tais como estudos com marcadores, genómica populacional, programação nutricional, génomica e proteómica funcionais, e fornecer ainda alguns exemplos das utilizações presentes e perspectivas futuras em estudos de nutrição de larvas de peixes