Ability of online drug databases to assist in clinical decision-making with infectious disease therapies

<p>Abstract</p> <p>Background</p> <p>Infectious disease (ID) is a dynamic field with new guidelines being adopted at a rapid rate. Clinical decision support tools (CDSTs) have proven beneficial in selecting treatment options to improve outcomes. However, there is a dearth of information on the abilities of CDSTs, such as drug information databases. This study evaluated online drug information databases when answering infectious disease-specific queries.</p> <p>Methods</p> <p>Eight subscription drug information databases: American Hospital Formulary Service Drug Information (AHFS), Clinical Pharmacology (CP), Epocrates Online Premium (EOP), Facts & Comparisons 4.0 Online (FC), Lexi-Comp (LC), Lexi-Comp with AHFS (LC-AHFS), Micromedex (MM), and PEPID PDC (PPDC) and six freely accessible: DailyMed (DM), DIOne (DIO), Epocrates Online Free (EOF), Internet Drug Index (IDI), Johns Hopkins ABX Guide (JHAG), and Medscape Drug Reference (MDR) were evaluated for their scope (presence of an answer) and completeness (on a 3-point scale) in answering 147 infectious disease-specific questions. Questions were divided among five classifications: antibacterial, antiviral, antifungal, antiparasitic, and vaccination/immunization. Classifications were further divided into categories (e.g., dosage, administration, emerging resistance, synergy, and spectrum of activity). Databases were ranked based on scope and completeness scores. ANOVA and Chi-square were used to determine differences between individual databases and between subscription and free databases.</p> <p>Results</p> <p>Scope scores revealed three discrete tiers of database performance: Tier 1 (82-77%), Tier 2 (73-65%) and Tier 3 (56-41%) which were significantly different from each other (p < 0.05). The top tier performers: MM (82%), MDR (81%), LC-AHFS (81%), AHFS (78%), and CP (77%) answered significantly more questions compared to other databases (p < 0.05). Top databases for completeness were: MM (97%), DM (96%), IDI (95%), and MDR (95%). Subscription databases performed better than free databases in all categories (p = 0.03). Databases suffered from 37 erroneous answers for an overall error rate of 1.8%.</p> <p>Conclusion</p> <p>Drug information databases used in ID practice as CDSTs can be valuable resources. MM, MDR, LC-AHFS, AHFS, and CP were shown to be superior in their scope and completeness of information, and MM, AHFS, and MDR provided no erroneous answers. There is room for improvement in all evaluated databases.</p

Rapid interhemispheric climate links via the Australasian monsoon during the last deglaciation

Recent studies have proposed that millennial-scale reorganization of the ocean-atmosphere circulation drives increased upwelling in the Southern Ocean, leading to rising atmospheric carbon dioxide levels and ice age terminations. Southward migration of the global monsoon is thought to link the hemispheres during deglaciation, but vital evidence from the southern sector of the vast Australasian monsoon system is yet to emerge. Here we present a 230thorium-dated stalagmite oxygen isotope record of millennial-scale changes in Australian–Indonesian monsoon rainfall over the last 31,000 years. The record shows that abrupt southward shifts of the Australian–Indonesian monsoon were synchronous with North Atlantic cold intervals 17,600–11,500 years ago. The most prominent southward shift occurred in lock-step with Heinrich Stadial 1 (17,600–14,600 years ago), and rising atmospheric carbon dioxide. Our findings show that millennial-scale climate change was transmitted rapidly across Australasia and lend support to the idea that the 3,000-year-long Heinrich 1 interval could have been critical in driving the last deglaciation

Prediction of pathological stage in patients with prostate cancer: a neuro-fuzzy model

The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre-treatment Prostate-Specific Antigen (PSA) level, the biopsy most common tumor pattern (Primary Gleason pattern) and the second most common tumor pattern (Secondary Gleason pattern) in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer. However, not every patient will return abnormal results in all tests. This significantly influences the capacity to effectively predict the stage of prostate cancer. Herein we have developed a neuro-fuzzy computational intelligence model for classifying and predicting the likelihood of a patient having Organ-Confined Disease (OCD) or Extra-Prostatic Disease (ED) using a prostate cancer patient dataset obtained from The Cancer Genome Atlas (TCGA) Research Network. The system input consisted of the following variables: Primary and Secondary Gleason biopsy patterns, PSA levels, age at diagnosis, and clinical T stage. The performance of the neuro-fuzzy system was compared to other computational intelligence based approaches, namely the Artificial Neural Network, Fuzzy C-Means, Support Vector Machine, the Naive Bayes classifiers, and also the AJCC pTNM Staging Nomogram which is commonly used by clinicians. A comparison of the optimal Receiver Operating Characteristic (ROC) points that were identified using these approaches, revealed that the neuro-fuzzy system, at its optimal point, returns the largest Area Under the ROC Curve (AUC), with a low number of false positives (FPR = 0.274, TPR = 0.789, AUC = 0.812). The proposed approach is also an improvement over the AJCC pTNM Staging Nomogram (FPR = 0.032, TPR = 0.197, AUC = 0.582)

Robotic-assisted laparoscopic prostatectomy

Prostate cancer remains a significant health problem worldwide and is the second highest cause of cancer-related death in men. While there is uncertainty over which men will benefit from radical treatment, considerable efforts are being made to reduce treatment related side-effects and in optimising outcomes. This article reviews the development and introduction of robotic-assisted laparoscopic radical prostatectomy (RALP), the results to date, and the possible future directions of RALP

Effects of small interfering RNAs targeting fascin on human esophageal squamous cell carcinoma cell lines

<p>Abstract</p> <p>Background</p> <p>Fascin induces membrane protrusions and cell motility. Fascin overexpression was associated with poor prognosis, and its downregulation reduces cell motility and invasiveness in esophageal squamous cell carcinoma (ESCC). Using a stable knockdown cell line, we revealed the effect of fascin on cell growth, cell adhesion and tumor formation.</p> <p>Methods</p> <p>We examined whether fascin is a potential target in ESCC using <it>in vitro </it>and <it>in vivo </it>studies utilizing a specific siRNA. We established a stable transfectant with downregulated fascin from KYSE170 cell line.</p> <p>Results</p> <p>The fascin downregulated cell lines showed a slower growth pattern by 40.3% (p < 0.01) and detachment from collagen-coated plates by 53.6% (p < 0.01), compared to mock cells, suggesting that fascin plays a role in cell growth by maintaining cell adhesion to the extracellular matrix. <it>In vivo</it>, the tumor size was significantly smaller in the tumor with fascin knockdown cells than in mock cells by 95% at 30 days after inoculation.</p> <p>Conclusions</p> <p>These findings suggest that fascin overexpression plays a role in tumor growth and progression in ESCC and that cell death caused by its downregulation might be induced by cell adhesion loss. This indicates that targeting fascin pathway could be a novel therapeutic strategy for the human ESCC.</p

Structural basis for terminal loop recognition and stimulation of pri-miRNA-18a processing by hnRNP A1

International audiencePost-transcriptional mechanisms play a predominant role in the control of microRNA (miRNA) production. Recognition of the terminal loop of precursor miRNAs by RNA-binding proteins (RBPs) influences their processing; however, the mechanistic basis for how levels of individual or subsets of miRNAs are regulated is mostly unexplored. We previously showed that hnRNP A1, an RBP implicated in many aspects of RNA processing, acts as an auxiliary factor that promotes the Microprocessor-mediated processing of pri-mir-18a. Here, by using an integrative structural biology approach, we show that hnRNP A1 forms a 1:1 complex with pri-mir-18a where both RNA recognition motifs (RRMs) bind to cognate RNA sequence motifs in the terminal loop of pri-mir-18a. Terminal loop binding induces an allosteric destabilization of base-pairing in the pri-mir-18a stem that promotes its downstream processing. Our results highlight terminal loop RNA recognition by RBPs as a potential general principle of miRNA biogenesis and regulation

Thoracic spine pain in the general population: Prevalence, incidence and associated factors in children, adolescents and adults. A systematic review

<p>Abstract</p> <p>Background</p> <p>Thoracic spine pain (TSP) is experienced across the lifespan by healthy individuals and is a common presentation in primary healthcare clinical practice. However, the epidemiological characteristics of TSP are not well documented compared to neck and low back pain. A rigorous evaluation of the prevalence, incidence, correlates and risk factors needs to be undertaken in order for epidemiologic data to be meaningfully used to develop evidence-based prevention and treatment recommendations for TSP.</p> <p>Methods</p> <p>A systematic review method was followed to report the evidence describing prevalence, incidence, associated factors and risk factors for TSP among the general population. Nine electronic databases were systematically searched to identify studies that reported either prevalence, incidence, associated factors (cross-sectional study) or risk factors (prospective study) for TSP in healthy children, adolescents or adults. Studies were evaluated for level of evidence and method quality.</p> <p>Results</p> <p>Of the 1389 studies identified in the literature, 33 met the inclusion criteria for this systematic review. The mean (SD) quality score (out of 15) for the included studies was 10.5 (2.0). TSP prevalence data ranged from 4.0–72.0% (point), 0.5–51.4% (7-day), 1.4–34.8% (1-month), 4.8–7.0% (3-month), 3.5–34.8% (1-year) and 15.6–19.5% (lifetime). TSP prevalence varied according to the operational definition of TSP. Prevalence for any TSP ranged from 0.5–23.0%, 15.8–34.8%, 15.0–27.5% and 12.0–31.2% for 7-day, 1-month, 1-year and lifetime periods, respectively. TSP associated with backpack use varied from 6.0–72.0% and 22.9–51.4% for point and 7-day periods, respectively. TSP interfering with school or leisure ranged from 3.5–9.7% for 1-year prevalence. Generally, studies reported a higher prevalence for TSP in child and adolescent populations, and particularly for females. The 1 month, 6 month, 1 year and 25 year incidences were 0–0.9%, 10.3%, 3.8–35.3% and 9.8% respectively. TSP was significantly associated with: concurrent musculoskeletal pain; growth and physical; lifestyle and social; backpack; postural; psychological; and environmental factors. Risk factors identified for TSP in adolescents included age (being older) and poorer mental health.</p> <p>Conclusion</p> <p>TSP is a common condition in the general population. While there is some evidence for biopsychosocial associations it is limited and further prospectively designed research is required to inform prevention and management strategies.</p

Thoracic spine pain in the general population: Prevalence, incidence and associated factors in children, adolescents and adults. A systematic review

<p>Abstract</p> <p>Background</p> <p>Thoracic spine pain (TSP) is experienced across the lifespan by healthy individuals and is a common presentation in primary healthcare clinical practice. However, the epidemiological characteristics of TSP are not well documented compared to neck and low back pain. A rigorous evaluation of the prevalence, incidence, correlates and risk factors needs to be undertaken in order for epidemiologic data to be meaningfully used to develop evidence-based prevention and treatment recommendations for TSP.</p> <p>Methods</p> <p>A systematic review method was followed to report the evidence describing prevalence, incidence, associated factors and risk factors for TSP among the general population. Nine electronic databases were systematically searched to identify studies that reported either prevalence, incidence, associated factors (cross-sectional study) or risk factors (prospective study) for TSP in healthy children, adolescents or adults. Studies were evaluated for level of evidence and method quality.</p> <p>Results</p> <p>Of the 1389 studies identified in the literature, 33 met the inclusion criteria for this systematic review. The mean (SD) quality score (out of 15) for the included studies was 10.5 (2.0). TSP prevalence data ranged from 4.0–72.0% (point), 0.5–51.4% (7-day), 1.4–34.8% (1-month), 4.8–7.0% (3-month), 3.5–34.8% (1-year) and 15.6–19.5% (lifetime). TSP prevalence varied according to the operational definition of TSP. Prevalence for any TSP ranged from 0.5–23.0%, 15.8–34.8%, 15.0–27.5% and 12.0–31.2% for 7-day, 1-month, 1-year and lifetime periods, respectively. TSP associated with backpack use varied from 6.0–72.0% and 22.9–51.4% for point and 7-day periods, respectively. TSP interfering with school or leisure ranged from 3.5–9.7% for 1-year prevalence. Generally, studies reported a higher prevalence for TSP in child and adolescent populations, and particularly for females. The 1 month, 6 month, 1 year and 25 year incidences were 0–0.9%, 10.3%, 3.8–35.3% and 9.8% respectively. TSP was significantly associated with: concurrent musculoskeletal pain; growth and physical; lifestyle and social; backpack; postural; psychological; and environmental factors. Risk factors identified for TSP in adolescents included age (being older) and poorer mental health.</p> <p>Conclusion</p> <p>TSP is a common condition in the general population. While there is some evidence for biopsychosocial associations it is limited and further prospectively designed research is required to inform prevention and management strategies.</p