The Michigan Genomics Initiative: a biobank linking genotypes and electronic clinical records in Michigan Medicine patients

The recent wave of biobank repositories linking individual-level genetic data with dense clinical health history has introduced a dramatic paradigm shift in phenotyping for human genetic studies. The mechanism by which biobanks recruit participants can vary dramatically according to factors such as geographic catchment and sampling strategy. These enrollment differences leave an imprint on the cohort, defining the demographics and the utility of the biobank for research purposes. Here we introduce the Michigan Genomics Initiative (MGI), a rolling enrollment, single health system biobank currently consisting of >85,000 participants recruited primarily through surgical encounters at Michigan Medicine. A strong ascertainment effect is introduced by focusing recruitment on individuals in Southeast Michigan undergoing surgery. MGI participants are, on average, less healthy than the general population, which produces a biobank enriched for case counts of many disease outcomes, making it well suited for a disease genetics cohort. A comparison to the much larger UK Biobank, which uses population representative sampling, reveals that MGI has higher prevalence for nearly all diagnosis-code-based phenotypes, and larger absolute numbers of cases for many phenotypes. GWAS of these phenotypes replicate many known findings, validating the genetic and clinical data and their proper linkage. Our results illustrate that single health-system biobanks that recruit participants through opportunistic sampling, such as surgical encounters, produce distinct patient profiles that provide an ideal resource for exploring the genetics of complex diseases.

Costs and mortality associated with HIV: a machine learning analysis of the French national health insurance database

Background: The objective is to characterise the economic burden to the healthcare system of people living with HIV (PLWHIV) in France and to help decision makers in identifying risk factors associated with high-cost and high mortality profiles.Design and Method: The study is a retrospective analysis of PLWHIV identified in the French National Health Insurance database (SNDS). All PLWHIV present in the database in 2013 were identified. All healthcare resource consumption from 2008 to 2015 inclusive was documented and costed (for 2013 to 2015) from the perspective of public health insurance. High-cost and high mortality patient profiles were identified by a machine learning algorithm.Results: In 2013, 96,423 PLWHIV were identified in the SNDS database, including 3,373 incident cases. Overall, 3,224 PLWHIV died during the three-year follow-up period (mean annual mortality rate: 1.1%). The mean annual per capita cost incurred by PLWHIV was € 14,223, corresponding to a total management cost of HIV of € 1,370 million in 2013. The largest contribution came from the cost of antiretroviral medication (M€ 870; 63%) followed by hospitalisation (M€ 154; 11%). The costs incurred in the year preceding death were considerably higher. Four specific patient profiles were identified for under/over-expressing these costs, suggesting ways to reduce them.Conclusion: Even though current therapeutic regimens provide excellent virological control in most patients, PLWHIV have excess mortality. Other factors such as comorbidities, lifestyle factors and screening for cancer and cardiovascular disease, need to be targeted in order to lower the mortality and cost associated with HIV infection.

Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person

Homocysteine (Hcy) metabolism is crucial for regulating methionine availability, protein homeostasis, and DNA-methylation presenting, therefore, key pathways in post-genomic and epigenetic regulation mechanisms. Consequently, impaired Hcy metabolism leading to elevated concentrations of Hcy in the blood plasma (hyperhomocysteinemia) is linked to the overproduction of free radicals, induced oxidative stress, mitochondrial impairments, systemic inflammation and increased risks of eye disorders, coronary artery diseases, atherosclerosis, myocardial infarction, ischemic stroke, thrombotic events, cancer development and progression, osteoporosis, neurodegenerative disorders, pregnancy complications, delayed healing processes, and poor COVID-19 outcomes, among others. This review focuses on the homocysteine metabolism impairments relevant for various pathological conditions. Innovative strategies in the framework of 3P medicine consider Hcy metabolic pathways as the specific target for in vitro diagnostics, predictive medical approaches, cost-effective preventive measures, and optimized treatments tailored to the individualized patient profiles in primary, secondary, and tertiary care.

Real-world evidence data on the monoclonal antibody erenumab in migraine prevention: perspectives of treating physicians in Germany

Background Erenumab, the first-in-class fully human monoclonal antibody targeting the calcitonin gene-related peptide receptor, was shown to be efficacious and safe for the prophylactic treatment of migraine in adults in randomized clinical trials. Large-scale, real-world evidence in multi-centre settings is still needed to confirm these results. Erenumab patient profiles outside clinical trials and physicians’ treatment patterns, as well as data from patients treated in Germany, a severely impacted population, are not published yet. Methods TELESCOPE was a multi-centre survey gathering real-world data from 45 German headache centres between July 2019 and December 2019. The project consisted of two parts. In the first part, treating physicians shared their experiences on current erenumab treatment with regard to patient profiles, treatment patterns and treatment responses. In the second part, a retrospective chart review was conducted of 542 migraine patients treated with erenumab for at least three months. Treatment responses focused on various aspects of patients’ quality of life. Results The analysis of 542 patients’ charts revealed that three-month treatment with erenumab significantly reduced monthly headaches, migraine and acute medication days. Furthermore, headache intensity and frequency were reduced in over 75 % and accompanying aura in 35 % of patients. The clinical global impression scale revealed a general improvement in 91 % of patients. According to the treating physicians’ professional judgement, 83 % of patients responded to erenumab and 80 % were satisfied with the treatment. Physicians evaluated restricted quality of life, the number of monthly migraine days and previous, prophylactic treatments as the main components of the current patient profile for monoclonal antibody recipients. Based on the assessment of physicians, erenumab reduced migraine symptoms in 65 % and increased quality of life in more than 75 % of their patients. Conclusions TELESCOPE confirms positive treatment responses with erenumab shown in clinical trials in a real-world multi-centre setting. The results show consistently positive experiences of physicians utilizing erenumab in clinical practice and underline that therapy with this monoclonal antibody is effective in migraine patients, particular in those, who have failed several prophylactic therapies.

Impact of Immunoscore on the Management of Stage II Colon Cancer Patients: A Physician Survey

Background: Adjuvant chemotherapy use in stage II colon cancer is controversial. Current prognostic risk factors do not take the tumor immune microenvironment into account. Consideration of the Immunoscore, which measures the host immune response at the tumor site, may assist clinicians in reducing adjuvant chemotherapy use in patients who are unlikely to benefit from it. This study sought to determine the potential clinical utility of the Immunoscore, via its effect on medical oncologists’ recommendations for management of patients with stage II colon cancer. Methods: De-identified vignettes of 10 patients with stage II colon cancer were presented to 25 practicing medical oncologists. Each participant completed surveys indicating recommendations for adjuvant chemotherapy and surveillance strategies. An educational session was subsequently conducted, and the same patient profiles were re-presented but included immunoscore results. Participants were again asked to provide their recommendations. A participant was counted as influenced if their responses were altered after immunoscore test results were provided. Results: All but one participant (96%) altered a management recommendation for ≥1 case. For individual cases, a mean of 55% (range, 40–80%) of participants altered their recommendations for adjuvant chemotherapy and/or surveillance. For the immunoscore-high cases (low-risk of recurrence), recommendations for adjuvant chemotherapy use decreased from 60% to 31%. Conclusions: These results indicate a willingness by oncologists to integrate immunoscore information into clinical practice recommendations. Incorporation of immunoscore data resulted in the reduction of nonvalue care in the simulated population. Confirmation in prospective studies is planned.

Application of self-assessment triage tool in COVID-19 pandemic (Preprint)

BACKGROUND (-) OBJECTIVE COVID-19 pandemic has sped up the implementation of telehealth solutions in medicine. This paper demonstrates our experiences with the COVID-19 Risk Assessment Tool. We tried to determine who is the user of the web-based COVID-19 triage application and compare this group with the patients of the infectious diseases ward’s admission room to evaluate who could benefit from implementing the COVID-19 online symptom checker as a remote triage solution. METHODS We have analyzed the answers of more than 650 000 people interacting with an online WHO-based triage tool for assessing the probability of SARS-CoV-2 infection. Based on the presented symptoms, risk factors, and demographics, the tool has assessed if the user’s answers are suggestive of COVID-19 and recommended appropriate action. Subsequently, we have compared “patient profiles” of tool users with patients admitting to the Infectious Diseases Admission Room. RESULTS COVID-19 Risk Assessment tool tended to be used by asymptomatic or oligosymptomatic individuals, which constituted 70.58% of all users. The majority of users were young (67.30% were below 40 years of age) and without significant comorbidities. On the contrary, most admission room patients were symptomatic - symptoms like fever, cough and dyspnea were prevalent in both covid positive and negative patients. COVID-suspected patients in the self-assessment tool presented similar COVID-19 symptoms as those who presented to the admission room. These were: cough (66.51% in self-assessment tool, 59.48% in the admission room, P=.03), fever (57.79% in the self-assessment tool, 62,93% in the admission room, P=.13), and shortness of breath (8.73% in the self-assessment tool vs. 37.50% in the admission room, P<.001). CONCLUSIONS The self-assessment COVID-19 tool, as it served as the means of screening and self-education, did not substitute for the consultation in the admission room for symptomatic patients. It seems that these types of solutions may serve as health information hubs for oligosymptomatic individuals, as well as a way of identifying and advising patients at risk. It fulfils the idea of remote, pre-clinical triage, however, the accuracy and influence on healthcare must be examined in the clinical setting.