Introduction: the comprehensive approach

2016 ◽  
Author(s):  
Michael Doherty ◽  
Johannes Bijlsma ◽  
Nigel Arden ◽  
David J. Hunter ◽  
Nicola Dalbeth
Keyword(s):  
Illness Perceptions ◽  
Response To Treatment ◽  
Predictors Of Response ◽  
Wide Range ◽  
Mechanical Factors ◽  
Inflammatory Drugs ◽  
The Individual ◽  
The Impact

This introductory chapter to the section on management of osteoarthritis (OA) emphasizes the need for a full assessment of the patient, not just in terms of joint symptoms and examination findings but a full holistic assessment of the person, including the impact of OA on their life, their illness perceptions of OA, and the presence of comorbidities. An individualized package of care can then be developed. Patients should be fully informed about OA and fully involved in all management decisions. Apart from education, which is an ongoing not one-off process, other core treatments to be considered in every person with OA are exercise (both strengthening and aerobic) and strategies to reduce adverse mechanical factors, including weight loss if overweight or obese. Topical non-steroidal anti-inflammatory drugs are the safest analgesic drug to try first for peripheral joint OA. Other treatments can be selected as required from a wide range of drug and non-pharmacological options, to address the needs of the individual. The patient requires regular follow-up for reassessment and re-adjustment of management as required. Currently there are sparse data on predictors of response to treatment, limiting a stratified medicine approach. Caveats to the research evidence for OA and its transition to clinical practice are discussed, and one way of improving this (reporting overall treatment effect and the proportion attributable to placebo in clinical trials) is presented. Optimizing contextual effects, which are an integral part of any treatment and which may explain the majority of improvement that a patient experiences for their OA, is emphasized as a key aspect of care.

scholarly journals Therapeutic Value of Single Nucleotide Polymorphisms on the Efficacy of New Therapies in Patients with Multiple Sclerosis

2021 ◽  
Vol 11 (5) ◽  
pp. 335
Author(s):  
María José Zarzuelo Romero ◽  
Cristina Pérez Ramírez ◽  
María Isabel Carrasco Campos ◽  
Almudena Sánchez Martín ◽  
Miguel Ángel Calleja Hernández ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mechanism Of Action ◽  
Dimethyl Fumarate ◽  
Response To Treatment ◽  
Nucleotide Polymorphisms ◽  
New Therapies ◽  
Therapeutic Value ◽  
The Impact

The introduction of new therapies for the treatment of multiple sclerosis (MS) is a very recent phenomenon and little is known of their mechanism of action. Moreover, the response is subject to interindividual variability and may be affected by genetic factors, such as polymorphisms in the genes implicated in the pathologic environment, pharmacodynamics, and metabolism of the disease or in the mechanism of action of the medications, influencing the effectiveness of these therapies. This review evaluates the impact of pharmacogenetics on the response to treatment with new therapies in patients diagnosed with MS. The results suggest that polymorphisms detected in the GSTP1, ITGA4, NQO1, AKT1, and GP6 genes, for treatment with natalizumab, ZMIZ1, for fingolimod and dimethyl fumarate, ADA, for cladribine, and NOX3, for dimethyl fumarate, may be used in the future as predictive markers of treatment response to new therapies in MS patients. However, there are few existing studies and their samples are small, making it difficult to generalize the role of these genes in treatment with new therapies. Studies with larger sample sizes and longer follow-up are therefore needed to confirm the results of these studies.

MOBILE APPLICATION REMOVES SOCIETAL BARRIERS TO P4 MEDICINE

2017 ◽  
pp. 1-3
Author(s):  
J.-P. Michel
Keyword(s):  
Cognitive Abilities ◽  
Mobile Application ◽  
New Technologies ◽  
Global Evaluation ◽  
P4 Medicine ◽  
Fertile Ground ◽  
Definition Of ◽  
The Individual ◽  
The Impact

The overlap between one innovative paradigm (P4 medicine: predictive, personalized, participatory and preventive) and another (a new definition of “Healthy ageing”) is fertile ground for new technologies; a new mobile application (app) that could broaden our scientific knowledge of the ageing process and help us to better analyse the impact of possible interventions in slowing the ageing decline. A novel mobile application is here presented as a game including questions and tests will allow in 10 minutes the assessment of the following domains: robustness, flexibility (lower muscle strength), balance, mental and memory complaints, semantic memory and visual retention. This game is completed by specific measurements, which could allow establishing precise information on functional and cognitive abilities. A global evaluation precedes advice and different types of exercises. The repetition of the tests and measures will allow a long follow up of the individual performances which could be shared (on specific request) with family members and general practitioners.

Homozygous and double heterozygous Factor V Leiden and Factor II G20210A genotypes predispose infants to thromboembolism but are not associated with an increase of foetal loss

2003 ◽  
Vol 90 (10) ◽  
pp. 628-635 ◽  
Author(s):  
Patrick Hundsdoerfer ◽  
Barbara Vetter ◽  
Brigitte Stöver ◽  
Christian Bassir ◽  
Tristess Scholz ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Individual Risk ◽  
Factor V ◽  
Thromboembolic Events ◽  
Foetal Loss ◽  
Asymptomatic Children ◽  
Factor Ii ◽  
The Individual ◽  
The Impact

SummaryProspective and controlled data about the individual risk profile in asymptomatic children with homozygous or double heterozygous risk genotypes for Factor V Leiden (FVL) and factor II (FII) G20210A are currently unavailable. The systematic and prospective observational study presented here was designed to determine the impact of the homozygous and double heterozygous FVL and FII G20210A genotypes on the prenatal and postnatal risk profiles of affected children. Risk infants and heterozygous controls were identified by screening of 85,304 neonates. Follow-up included the comparison of prenatal and postnatal development, ultrasonography of brain and kidneys, and a panel of independent determinants of thrombophilia. The numbers of identified or expected FVL homozygotes and double heterozygotes did not differ significantly (FVL: 116 ver-sus 91, p=0.08; FVL/FII: 94 versus 76, p=0.17), indicating the absence of a prenatal disadvantage. A prenatal advantage was suggested in FII homozygotes, whose identified number far exceeded the expected (19 versus 4, p=0.002). Clinical and/or imaging abnormalities indicated spontaneous thromboembolic events in 4 of 129 risk infants (3%) but in none of the 178 controls (p=0.02). Physical and neurological development was normal in both groups during the first 2 years of life. The risk genotypes appear to confer a significant predisposition for spontaneous thromboembolic events in infancy without impeding development within the first two years of life. Foetal risk genotypes do not cause an increased foetal loss rate. Moreover, homozygous FII G20210A appears to be associated with a prenatal advantage.

Abstract P370: Obesity and Incident Coronary Heart Disease in the Million Women Study: A Prospective, Population-based Cohort Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Dexter Canoy ◽  
Benjamin J Cairns ◽  
Angela Balkwill ◽  
Jayne Green ◽  
Lucy Wright ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Cumulative Risk ◽  
Excess Weight ◽  
Adjusted Relative Risk ◽  
Chd Risk ◽  
Wide Range ◽  
Chd Risk Factors ◽  
The Impact

Background: Higher body-mass index (BMI) has been associated with increased risk for coronary heart disease (CHD) mortality but its association with incident CHD is less investigated, and data for women are limited. Methods: We examined the prospective relation between BMI and incident CHD (first CHD hospitalization or death) in 1.2 million women aged ≥50 years without prior CHD, who were recruited through a national breast screening programme in 1996 to 2001 and followed for an average of 9 years (48,842 events with 10.7 million person-years of follow-up). Absolute and relative risks (using Cox regression) associated with higher BMI were estimated. Results: After excluding the first 4 years of follow-up, there were 32,465 events (5.9 million person-years) including 3,345 CHD deaths. The adjusted relative risk per 5 kg/m 2 BMI difference was 1.24 [95% confidence interval (CI) 1.22 to 1.25]. CHD risk increased linearly across a wide range of BMI, with no apparent excess risk in the lower end of BMI distribution. The relation persisted after excluding current smokers or limiting cases to myocardial infarction only. For women in this cohort, the 20-year cumulative risk of CHD from age 55 to 74 years (95% CI) ranged from 9% (8 to10) to 18% (16 to 20) for women with BMI of 20 to 22.5 kg/m 2 and ≥35 kg/m 2 , respectively. Never smokers with BMI ≥35 kg/m 2 had comparable cumulative risk to current smokers with BMI of 20 to 22.5 kg/m 2 . Conclusion: In this large cohort of women, the impact of excess weight on CHD morbidity and mortality is substantial. Measures to prevent and control excess weight and other CHD risk factors are needed to help reduce CHD burden in women.

Introduction

2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jonas Grethlein ◽  
Luuk Huitink ◽  
Aldo Tagliabue
Keyword(s):  
Aesthetic Experience ◽  
Rhetorical Theory ◽  
The Novel ◽  
Ancient Greek ◽  
Reading Habits ◽  
Theoretical Frameworks ◽  
Early Christian ◽  
Wide Range ◽  
The Individual

This volume aims to pursue a new approach to ancient Greek narrative beyond the taxonomies of structuralist narratologies, focusing on the phenomenal and experiential dimension of our response to narrative and triangulating ancient narrative with ancient criticism and cognitive approaches. The introductory chapter offers an overview of the theoretical frameworks in play and briefly encapsulates how each chapter seeks to contribute to a multifaceted picture of narrative and aesthetic experience. Immersion and embodiment emerge as central concepts and common threads throughout, helping to establish a more comprehensive understanding of ancient narrative and ancient reading habits, as manifested in Greek criticism and rhetorical theory, though the individual chapters tackle a wide range of narrative genres, broadly understood, from epic, historiography, and the novel to tragedy and early Christian texts, and other media, such as dance and sculpture.

1156Coronary artery bypass grafting vs. FFR-guided PCI in diabetic patients with multivessel disease

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G Di Gioia ◽  
N Soto Flores ◽  
D Franco ◽  
I Colaiori ◽  
J Sonck ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Artery Bypass ◽  
Diabetic Patients ◽  
Bypass Grafting ◽  
Fractional Flow ◽  
Artery Bypass Grafting ◽  
The Individual ◽  
The Impact

Abstract Background In diabetic patients with multivessel coronary disease (MVD), coronary artery bypass grafting (CABG) has shown long-term benefits in mortality over percutaneous coronary revascularization (PCI). Nevertheless, the impact of fractional flow reserve (FFR)-guided PCI on clinical outcomes has never been investigated in these patients. Purpose To evaluate the long-term (5-year) clinical outcome of diabetic patients with MVD treated with FFR-guided PCI compared to CABG. Methods From February 2010 to February 2018, all diabetic patients undergoing coronary angiography in one centre (n=4622) were screened for inclusion. The inclusion criterion was presence of at least two-vessels CAD defined as with diameters stenosis ≥50%. In case of intermediate coronary stenosis (%DS 30–70%), FFR was performed at the discretion of the operator. Revascularization was performed when FFR ≤0.80. Exclusion criteria were ST-elevation myocardial infarction, prior CABG, and moderate or severe valvular heart dysfunction. To account for confounders, we compared outcomes by calculating an adjusted Kaplan-Meier estimator using inverse probability of treatment weighting (IPTW). Propensity score variables included age, sex, smoking habit, hypertension, hyperlipidemia, insulin therapy, family history of CAD, chronic obstructive pulmonary disease (COPD), glomerular filtration rate (GFR), prior myocardial infarction, peripheral vascular disease (PVD), admission for NSTEMI, ejection fraction, number of angiographic stenotic vessels. Odds ratios were calculated using generalized linear models (GLM). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), defined as all-cause death, myocardial infarction and stroke. Secondary endpoints were the individual component of MACCE and any repeated revascularization. Results A total of 538 diabetic patients with MVD were included in the analysis. Among them, 317 (59%) patients underwent CABG and 221 (41%) FFR-guided PCI. Patients treated with FFR-guided PCI had more often COPD as compared to patients in the CABG-group, but patients treated with CABG had lower GFR, more PVD, higher number of angiographic stenotic vessels (2.8±0.4 vs. 2.5±0.5; p<0.01) and higher Syntax score (20±7 vs. 14±6; p<0.01) as compared to the FFR-guided PCI group. Clinical follow-up was obtained in 95% of the patients at a median follow-up of 5 years. The incidence of MACCE was similar in the CABG and in the FFR-guided PCI group [27% vs. 29%; OR (95% CI) 1.05 (0.68–1.63); p=0.74]. No differences were found in the individual components of MACCE. Repeat revascularization was more frequent in the FFR-guided PCI group than in the CABG group [27% vs. 7%; OR (95% CI) 4.3 (2.35–7.9); p<0.01]. Conclusions In diabetic patients with MVD undergoing FFR-guided PCI, no differences in major adverse events were observed at a median follow-up of 5 years compared with CABG.

scholarly journals Earth-based observations of impact phenomena

1996 ◽  
Vol 156 ◽  
pp. 81-109
Author(s):  
Philip D. Nicholson
Keyword(s):  
Hubble Space Telescope ◽  
Common Pattern ◽  
Mid Infrared ◽  
Wide Range ◽  
Impact Phenomena ◽  
Infrared Wavelengths ◽  
Positive Correlations ◽  
The Individual ◽  
The Impact ◽  
Size Estimates

Earth-based observations at near- and mid-infrared wavelengths were obtained for at least 15 of the SL9 impacts, ranging from the spectacular G, K and L events to the barely-detected N and V impacts. Although there were a few exceptions, most of the IR lightcurves fit a common pattern of one or two relatively faint precursor flashes, followed several minutes later by the main infrared event as the explosively-ejected plume crashed down onto the jovian atmosphere. Correlations with the impact times recorded by the Galileo spacecraft and plumes imaged by the Hubble Space Telescope lead to an interpretation of the twin precursors in terms of (i) the entry of the bolide into the upper atmosphere, and (ii) the re-appearance of the rising fireball above Jupiter's limb. Positive correlations are observed between the peak IR flux observed during the splashback phase and both pre-impact size estimates for the individual SL9 fragments and the scale of the resulting ejecta deposits. None of the fragments observed to have moved off the main train of the comet by May 1994 produced a significant impact signature. Earth-based fireball temperature estimates are on the order of 750 K, 30-60 sec after impact. For the larger impacts, the unexpectedly protracted fireball emission at 2.3 μm remains unexplained. A wide range of temperatures has been inferred for the splashback phase, where shocks are expected to have heated the re-entering plume material at least briefly to several thousand K, and further modelling is required to reconcile these data.

The Impact of Cannabis in the Early Stages of Schizophrenia: A 3-Year Longitudinal Study on Cannabis Influence on Relapse Rates

2017 ◽  
Vol 41 (S1) ◽  
pp. S196-S197
Author(s):  
M. Gomez Revuelta ◽  
M. Juncal Ruiz ◽  
O. Porta Olivares ◽  
V. Gajardo Galan ◽  
G. Pardo de Santayana Jenaro ◽  
...  
Keyword(s):  
Intervention Program ◽  
Response To Treatment ◽  
Rank Test ◽  
First Episode ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Early Stages ◽  
Increased Risk ◽  
The Impact

IntroductionThe first five years after the onset of a first episode of psychosis (FEP) are crucial for long term outcome. In this period, the risk of relapse is particularly high. Consequences of relapse include an increased risk of neurotoxicity, chronicity, hospitalization, decreased response to treatment, increased economic burden and functional impairment.ObjectivesTo discern the influence of cannabis on relapse as it may contribute to adopt specific measures in patients during early stages of the illness.Material and methodsPAFIP is an early intervention program for patients with a FEP. Between January 2005 and January 2011, 163 patients were recruited for this study. They were followed-up during 3 years at intervals of three months. The sample was divided into three groups: (1) those non-cannabis users neither before the FEP nor during follow-up (nn), (2) consumers before the FEP and during follow-up (ss) and (3) consumers before the FEP that gave up consumption during follow-up (sn).ResultsNo statistically significant differences between the three groups were observed but a trend (P = 0.057) towards a more enduring survival in Group 3 (sn). (Kaplan–Meier curve and detailed Log Rank Test results will be included in the final poster).ConclusionsCannabis has a detrimental effect on schizophrenia. The interruption of its use could contribute to improve the outcome of the disease, as the results of our study suggest.Disclosure of interestThe authors have not supplied their declaration of competing interest.

On Compressor Station Layout

2003 ◽  
Author(s):  
Rainer Kurz ◽  
Sebouh Ohanian ◽  
Matt Lubomirsky
Keyword(s):  
Gas Turbine ◽  
Electric Motor ◽  
Operating Conditions ◽  
Performance Characteristics ◽  
General Context ◽  
Operational Flexibility ◽  
Gas Engine ◽  
Wide Range ◽  
The Individual ◽  
The Impact

This paper discusses issues that influence the decision on the arrangement of compressors and the type of equipment in gas pipeline compressor stations. Different concepts such as multiple small units versus single large units are considered, both regarding their impact on the individual station and the overall pipeline. The necessity of standby units is discussed. Various concepts for drivers (gas turbine, gas motor and electric motor) and compressors (centrifugal and reciprocating) are analyzed. The importance of considering all possible operating conditions is stressed. With the wide range of possible operating conditions for the pipeline in mind, the discussion will be brought into the general context of operational flexibility, availability, reliability, installation issues, remote control, and operability of gas turbine driven centrifugal compressors compared to other solutions such as electric motor driven compressors or gas engine driven reciprocating compressors. The impact of different concepts on emissions and fuel cost is discussed. Among the assumptions in this paper are the performance characteristics of the compressor. It will be outlined how these performance characteristics influence the conclusions.

The association of D4, 3-keto-abi (D4A) and response to abiraterone in castration-resistant prostate cancer (CRPC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 245-245
Author(s):  
Hamid Emamekhoo ◽  
Mohammad Alyamani ◽  
Zhenfei Li ◽  
Paul Elson ◽  
Petros Grivas ◽  
...  
Keyword(s):  
Median Time ◽  
Specific Antigen ◽  
Response To Treatment ◽  
Multiple Time ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Receptor Antagonist ◽  
Duration Of Response ◽  
Multiple Time Points ◽  
The Impact

245 Background: Abiraterone (Abi), a potent inhibitor of 17α-hydroxylase/17,20-lyase (CYP17A1), is a standard treatment for men with metastatic CRPC. Abi is converted to D4A by 3β-hydroxysteroid dehydrogenase (3βHSD). D4A inhibits CYP17A1, 3βHSD, and steroid-5α-reductase (SRD5A) and has direct androgen receptor antagonist activity, which together make it a more potent agent than Abi in xenograft models. It is not known if conversion to D4A in patients (pts) correlates with response or resistance to Abi. Methods: Blood was collected (single time point on Abi) from CRPC pts who started Abi during 2011-2015. Abi and D4A were extracted from serum and analyzed by mass spectrometry. The purpose of this ongoing study is to assess the potential correlation between D4A and response to treatment. Results: 32 patients with CRPC had blood collected. 4 pts (12.5%) received ketoconazole and 6 (18.8%) chemotherapy prior to Abi. Median pre-Abi prostate-specific antigen (PSA) was 14.3 ng/ml (0.6-646.1). Median time from initiation of androgen deprivation therapy (ADT) to CRPC was 34.3 months (m) (6-129.6) and median time from CRPC to Abi initiation was 4.8 m (0-14.9). PSA decline > 50% (PSA50) on Abi was seen in 68% (12/31) and 73% (19/26) of pts at 3 and 6 m, respectively. Treatment with Abi was ongoing in 23/32 pts (74%), and discontinued in 8 pts (26%) due to disease progression (no follow up data on 1 pt) with median duration of Abi treatment 14.6 m (2.9-44.4 m) at last follow up. As the absolute concentration of detected levels of Abi and D4A varied significantly among pts, the percentage of the total extracted metabolites was used to assess correlation with response. Abi and D4A comprised 94.3% (73.8-97.4%) and 5.7% (2.6-26.2%), respectively, of total levels. Conclusions: Abi absorption and metabolism significantly vary among pts. Most of these pts had prolonged duration of response to Abi (74% ongoing treatment and median treatment duration 13.3 m in 8 pts that came off treatment). Longer follow up, accrual of pts with shorter duration of response, and sampling at multiple time points on Abi and at progression is ongoing to further evaluate the impact of D4A on treatment response.

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