scholarly journals Drug Response Pharmacogenetics for 200,000 UK Biobank Participants

2020 ◽  
Author(s):  
Gregory McInnes ◽  
Russ B Altman
Keyword(s):  
Drug Response ◽  
Clinical Decision Making ◽  
Optimal Dose ◽  
Clinical Decision ◽  
Uk Biobank ◽  
Gene Associations ◽  
The Uk ◽  
The Right ◽  
Normal Clinical Practice ◽  
Novel Associations

Pharmacogenetics studies how genetic variation leads to variability in drug response. Guidelines for selecting the right drug and right dose to patients based on their genetics are clinically effective, but are still widely unused. For some drugs, the normal clinical decision making process may lead to the optimal dose of a drug that minimizes side effects and maximizes effectiveness. Without measurements of genotype, physicians and patients may observe and adjust dosage in a manner that reflects the underlying genetics. The emergence of genetic data linked to longitudinal clinical data in large biobanks offers an opportunity to confirm known pharmacogenetic interactions as well as discover novel associations by investigating outcomes from normal clinical practice. Here we use the UK Biobank to search for pharmacogenetic interactions among 200 drugs and 9 genes among 200,000 participants. We identify associations between pharmacogene phenotypes and drug maintenance dose as well as side effect incidence. We find support for several known drug-gene associations as well as novel pharmacogenetic interactions.

scholarly journals Contextualizing genetic risk score for disease screening and rare variant discovery

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dan Zhou ◽  
Dongmei Yu ◽  
Jeremiah M. Scharf ◽  
Carol A. Mathews ◽  
Lauren McGrath ◽  
...  
Keyword(s):  
Complex Traits ◽  
Genetic Basis ◽  
Clinical Decision Making ◽  
Genetic Risk Score ◽  
Sufficient Conditions ◽  
Clinical Decision ◽  
Generative Models ◽  
Variant Discovery ◽  
Models Of Disease ◽  
The Uk

AbstractStudies of the genetic basis of complex traits have demonstrated a substantial role for common, small-effect variant polygenic burden (PB) as well as large-effect variants (LEV, primarily rare). We identify sufficient conditions in which GWAS-derived PB may be used for well-powered rare pathogenic variant discovery or as a sample prioritization tool for whole-genome or exome sequencing. Through extensive simulations of genetic architectures and generative models of disease liability with parameters informed by empirical data, we quantify the power to detect, among cases, a lower PB in LEV carriers than in non-carriers. Furthermore, we uncover clinically useful conditions wherein the risk derived from the PB is comparable to the LEV-derived risk. The resulting summary-statistics-based methodology (with publicly available software, PB-LEV-SCAN) makes predictions on PB-based LEV screening for 36 complex traits, which we confirm in several disease datasets with available LEV information in the UK Biobank, with important implications on clinical decision-making.

scholarly journals Factors Influencing Physicians' Clinical Decision-making at Upazila Health Complexes in Bangladesh

2020 ◽  
Vol 3 (4) ◽  
pp. 125-133
Author(s):  
M. Aminul Islam ◽  
M. Abdul Awal
Keyword(s):  
Decision Making ◽  
Social Networks ◽  
Clinical Decision Making ◽  
Average Length ◽  
Clinical Decision ◽  
Primary Data ◽  
Decision Making Process ◽  
Cross Sectional ◽  
The Right ◽  
Consultation Session

ABSTRACT Introduction Selecting the most appropriate treatment for each patient is the key activity in patient-physician encounters and providing healthcare services. Achieving desirable clinical goals mostly depends on making the right decision at the right time in any healthcare setting. But little is known about physicians' clinical decision-making in the primary care setting in Bangladesh. Therefore, this study explored the factors that influence decisions about prescribing medications, ordering pathologic tests, counseling patients, average length of patient visits in a consultation session, and referral of patients to other physicians or hospitals by physicians at Upazila Health Complexes (UHCs) in the country. It also explored the structure of physicians' social networks and their association with the decision-making process. Methods This was a cross-sectional descriptive study that used primary data collected from 85 physicians. The respondents, who work at UHCs in the Rajshahi Division, were selected purposively. The collected data were analyzed with descriptive statistics including frequency, percentage, one-way analysis of variance, and linear regression to understand relationships among the variables. Results The results of the study reveal that multiple factors influence physicians' decisions about prescribing medications, ordering pathologic tests, length of visits, counseling patients, and referring patients to other physicians or hospitals at the UHCs. Most physicians prescribe drugs to their patients, keeping in mind their purchasing capacity. Risk of violence by patients' relatives and better management are the two key factors that influence physicians' referral decisions. The physicians' professional and personal social networks also play an influential role in the decision-making process. It was found that physicians dedicate on average 16.17 minutes to a patient in a consultation session. The length of visits is influenced by various factors including the distance between the physicians' residence and their workplace, their level of education, and the number of colleagues with whom they have regular contact and from whom they can seek help. Conclusion The results of the study have yielded some novel insights about the complexity of physicians' everyday tasks at the UHCs in Bangladesh. The results would be of interest to public health researchers and policy makers.

The value of a consultant physiotherapist within a primary care musculoskeletal interface service: part of the spinal multidisciplinary team

2021 ◽  
Vol 28 (1) ◽  
pp. 1-10
Author(s):  
Michelle L Angus ◽  
Victoria Dickens ◽  
Naveed Yasin ◽  
James Greenwood ◽  
Irfan Siddique
Keyword(s):  
Primary Care ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Tertiary Referral Centre ◽  
Allied Health Professionals ◽  
Convenience Sample ◽  
Surgical Services ◽  
Pain Pathway ◽  
The Uk ◽  
Case Based

Background/aims The national low back pain pathway in the UK suggests practitioners managing patients with spinal pathology should be specifically trained to do so and have the ability to link with tertiary spinal services when required. The aim of this study was to ensure referrals through to a tertiary spinal surgical centre are appropriate and patients get the correct advice early in their management pathway. Methods A retrospective review of 700 cases were discussed at a spinal case-based discussion meeting in a primary care interface service, compared to services without this model. A convenience sample of cases were analysed with the consultant physiotherapist and those referred from other allied health professionals into the tertiary spinal surgical centre. Case-based team discussion took place before every referral into the tertiary spinal service, with spinal surgical discussion where required. Results Patients referred from other interface services were more likely to require further work-up such as investigations, or be discharged from clinic on their first attendance than those who had been through the case-based discussion. Conclusions A consultant physiotherapist working as part of the spinal team of a tertiary referral centre can help advanced practitioners with their clinical decision making to help prevent unnecessary referrals to spinal surgical services.

LPA and APOE are associated with statin selection in the UK Biobank

2020 ◽  
Author(s):  
Adam Lavertu ◽  
Gregory McInnes ◽  
Yosuke Tanigawa ◽  
Russ B Altman ◽  
Manuel A. Rivas
Keyword(s):  
Statin Therapy ◽  
High Intensity ◽  
Drug Response ◽  
Association Studies ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Treatment Decisions ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
The Uk

AbstractGenetics plays a key role in drug response, affecting efficacy and toxicity. Pharmacogenomics aims to understand how genetic variation influences drug response and develop clinical guidelines to aid clinicians in personalized treatment decisions informed by genetics. Although pharmacogenomics has not been broadly adopted into clinical practice, genetics influences treatment decisions regardless. Physicians adjust patient care based on observed response to medication, which may occur as a result of genetic variants harbored by the patient. Here we seek to understand the genetics of drug selection in statin therapy, a class of drugs widely used for high cholesterol treatment. Genetics are known to play an important role in statin efficacy and toxicity, leading to significant changes in patient outcome. We performed genome-wide association studies (GWAS) on statin selection among 59,198 participants in the UK Biobank and found that variants known to influence statin efficacy are significantly associated with statin selection. Specifically, we find that carriers of variants in APOE and LPA that are known to decrease efficacy of treatment are more likely to be on atorvastatin, a stronger statin. Additionally, carriers of the APOE and LPA variants are more likely to be on a higher intensity dose (a dose that reduces low-density lipoprotein cholesterol by greater than 40%) of atorvastatin than non-carriers (APOE: p(high intensity) = 0.16, OR = 1.7, P = 1.64 × 10−4, LPA: p(high intensity) = 0.17, OR = 1.4, P = 1.14 × 10−2). These findings represent the largest genetic association study of statin selection and statin dose association to date and provide evidence for the role of LPA and APOE in statin response, furthering the possibility of personalized statin therapy.

scholarly journals Clinical decision making in the provision of audiovisual care for upper limb trauma: a survey of UK experiences

Hand Therapy ◽  
2020 ◽  
pp. 175899832097213
Author(s):  
Emily McMullen ◽  
Megan Robson ◽  
Mark Paul Brewin ◽  
Poonam Valand ◽  
Leela Sayed ◽  
...  
Keyword(s):  
Decision Making ◽  
Upper Limb ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Service Planning ◽  
Cross Sectional Survey ◽  
Visual Technology ◽  
Limb Trauma ◽  
The Uk ◽  
Decision Making Tool

Introduction For many patients, audio-visual appointments have provided a timely and efficient way of seeking advice, assessment and treatment for their hand injuries during the NHS response to COVID-19. This study aimed to explore the experience of hand units across the UK in determining the safe and judicious use of audio-visual outpatient care for the management of acute upper limb trauma. Methods An online cross-sectional survey was sent to the therapy leads of hand units across the UK. Questions focused on the experience of using audio-visual technology in the management of upper limb trauma, and the relevant factors in determining its appropriate use. A deductive mixed methods analysis was used to identify both common themes and capture community experience and characteristics. Results A total of 51 out of 76 hand therapy units completed the survey; a response rate of 67%. Of these, 82% (42/51) reported using audio-visual technology to manage upper limb trauma during the UK COVID-19 lockdown. When determining patient suitability for audio-visual consultations, 73% (37/51) of respondents reported the use of COVID-19 guidelines, but only 35% (18/51) reported the use of a clinical decision-making tool. In agreement with our experience at Salisbury Hospital Foundation Trust, 92% (47/51) had concerns relating to the use of audio-visual care. Conclusion The choice of safely managed remote care or in-person consultation has, to date, largely relied on the discretion of the clinician. A carefully designed clinical decision-making tool for the management of upper limb trauma is needed for use both in clinical practice and in future service planning.

scholarly journals Complexity of Clinical Decision Making: Consent, Capacity, and Ethics

2019 ◽  
Vol 40 (03) ◽  
pp. 162-169 ◽  
Author(s):  
Annette Askren ◽  
Paula Leslie
Keyword(s):  
Decision Making ◽  
Clinical Decision Making ◽  
Negative Charge ◽  
Clinical Decision ◽  
Informed Consent Process ◽  
Thickened Liquids ◽  
Medical Decisions ◽  
Social Media Platforms ◽  
The Right ◽  
Right To Refuse

AbstractSpeech–language pathologists (SLPs), and really their patients, are often faced with challenging clinical decisions to be made. Patients may decline interventions recommended by the SLP and are often inappropriately labeled “noncompliant.” The inappropriateness of this label extends beyond the negative charge; the patient's right to refuse is, in fact, protected by law. Anecdotal exchanges, social media platforms, and American Speech-Language-Hearing Association forums have recently revealed that many SLPs are struggling with the patient's right to decline. Many are not comfortable with the informed consent process and what entails patients' capacity to make their own medical decisions. Here, we discuss the basics of clinical decision-making ethics with intent to minimize the clinician's discomfort with the right to refuse those thickened liquids and eliminate the practice of defensive medicine.

Values based psychiatry

2011 ◽  
Vol 26 (S2) ◽  
pp. 2128-2128
Author(s):  
B.K.W.M. Fulford
Keyword(s):  
Mental Health ◽  
Clinical Decision Making ◽  
Clinical Skills ◽  
Clinical Decision ◽  
Evidence Based ◽  
Involuntary Treatment ◽  
New Approach ◽  
Health Values ◽  
Potential Partner ◽  
The Uk

Values-based Practice is a new approach to working with complex and conflicting values in medicine. The approach is derived from work in analytic philosophy on the logic of values. As a practical approach, it is based primarily on learnable clinical skills. Values-based Practice has been developed particularly in mental health, through a number of programmes involving both voluntary sector and government organisations in the UK and internationally. Two examples of these programmes will be presented: one related to the use of involuntary treatment in psychiatry; the other arising from a government-sponsored programme on diagnosis and assessment in mental health. Values-based Practice is currently being extended into other areas of medicine as a potential partner to evidence-based practice in clinical decision making

scholarly journals Comparison of Cortisol, Androstenedione and Metanephrines to Assess Selectivity and Lateralization of Adrenal Vein Sampling in Primary Aldosteronism

2021 ◽  
Vol 10 (20) ◽  
pp. 4755
Author(s):  
Giulio Ceolotto ◽  
Giorgia Antonelli ◽  
Brasilina Caroccia ◽  
Michele Battistel ◽  
Giulio Barbiero ◽  
...  
Keyword(s):  
Decision Making ◽  
Primary Aldosteronism ◽  
Inferior Vena ◽  
Clinical Decision Making ◽  
Vena Cava ◽  
Clinical Decision ◽  
Selectivity Index ◽  
Adrenal Vein ◽  
Adrenal Vein Sampling ◽  
The Right

Success of adrenal vein sampling (AVS) is verified by the selectivity index (SI), i.e., by a step-up of cortisol levels between the adrenal vein and the infrarenal inferior vena cava samples, beyond a given cut-off. We tested the hypothesis that androstenedione, metanephrine, and normetanephrine, which have higher gradients than cortisol, could increase the rate of AVS studies judged to be bilaterally successful and usable for the clinical decision making. We prospectively compared within-patient, head-to-head, the selectivity index of androstenedione (SIA), metanephrine (SIM), and normetanephrine (SINM), and cortisol (SIC) in consecutive hypertensive patients with primary aldosteronism submitted to AVS. Main outcome measures were rate of bilateral success, SI values, and identification of unilateral PA. We recruited 136 patients (55 + 10 years, 35% women). Compared to the SIC, the SIA values were 3.5-fold higher bilaterally, and the SIM values were 7-fold and 4.4-fold higher on the right and the left side, respectively. With the SIA and the SIM the rate of bilaterally successful AVS increased by 14% and 15%, respectively without impairing the identification of unilateral PA. We concluded that androstenedione and metanephrine outperformed cortisol for ascertaining AVS success, thus increasing the AVS studies useable for the clinical decision making.

scholarly journals Management of Cancer-Associated Thrombosis: An Evolving Area

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2999
Author(s):  
Corinne Frere ◽  
Jean M. Connors ◽  
Dominique Farge
Keyword(s):  
Cancer Patient ◽  
Clinical Decision Making ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Clinical Decision ◽  
Patient Centered ◽  
Patient Values ◽  
The Individual ◽  
The Right ◽  
Cancer Associated Thrombosis

The management of cancer-associated thrombosis (CAT) is an evolving area. With the use of direct oral anticoagulants as a new option in the management of CAT, clinicians now face several choices for the individual cancer patient with venous thromboembolism. A personalized approach, matching the right drug to the right patient, based on drug properties, efficacy and safety, side effect profile of each drug, and patient values and preference, will probably supplant the one size fits all approach of use of only low-molecular-weight heparin in the near future. We herein present eight translational, clinical research, and review articles on recent advances in the management of CAT published in the Special Issue “Treatment for Cancer-Associated Thrombosis” of Cancers. For now, a multidisciplinary patient-centered approach involving a close cooperation between oncologists and other specialists is warranted to guide clinical decision making and optimize the treatment of VTE in cancer patient.

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