scholarly journals SARS-CoV-2 Treatment: Current Therapeutic Options and the Pursuit of Tailored Therapy

2021 ◽  
Vol 11 (16) ◽  
pp. 7457
Author(s):  
Gianmarco Marcianò ◽  
Roberta Roberti ◽  
Caterina Palleria ◽  
Davida Mirra ◽  
Vincenzo Rania ◽  
...  
Keyword(s):  
Drug Toxicity ◽  
Scientific Community ◽  
Drug Repurposing ◽  
Drug Efficacy ◽  
Patient Characteristics ◽  
Therapeutic Options ◽  
Tailored Therapy ◽  
New Guidelines ◽  
One Year ◽  
New Compounds

One year on from the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine has made several steps towards increasing the therapeutic options against its treatment. Despite the lack of specific therapies, international societies have introduced new guidelines and launched several trials to test the efficacy of new protocols and drugs. Drug repurposing has been a fundamental strategy to find quick ways to fight the pathogen, even if it is new compounds that are drawing the attention of the scientific community. Tailored therapy should be considered to be a milestone in treatment in order to increase drug efficacy and to reduce drug toxicity. Therefore, both drug characteristics (i.e., pharmacokinetic, pharmacodynamic and safety) and the patient characteristics (i.e., stage of disease, comorbidity, concomitant treatments and the mutation of single nucleotides) could represent the key to achieving this objective. In the present study we performed a narrative review of the pharmacological treatment used to date in the management of coronavirus disease 2019 (COVID-19).

The Probability of A1C Goal Attainment in Patients with Uncontrolled Type-2 Diabetes in a Large Integrated Delivery System: A Prediction Model

2020 ◽  
Author(s):  
Kevin M Pantalone ◽  
Anita D Misra-Hebert ◽  
Todd M Hobbs ◽  
Sheldon X Kong ◽  
Xinge Ji ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Goal Attainment ◽  
Index Date ◽  
Cleveland Clinic ◽  
Patient Characteristics ◽  
Psychiatric Disease ◽  
Lower Probability ◽  
Factors Associated ◽  
One Year

<b>Objective:</b> To assess patient characteristics and treatment factors associated with uncontrolled type 2 diabetes (T2D) and the probability of A1C goal attainment. <p><b>Research Design and Methods</b>: Retrospective cohort study using the electronic health record at Cleveland Clinic. Patients with uncontrolled T2D (A1C>9%) were identified on the index date of 12/31/2016 (n=6,973), grouped by attainment (n=1,653 [24.7%) or non-attainment (n=5,320 [76.3%]) of A1C<8% by 12/31/2017, and subgroups compared on a number of demographic and clinical variables. Based on these variables, a nomogram was created for predicting probability of A1C goal attainment. </p> <p><b>Results:</b> For the entire population, median age at index date was 57.7 years (53.3% male), and the majority were white (67.2%). Median A1C was 10.2%. Obesity (50.6%), cardiovascular disease (46.9%) and psychiatric disease (61.1%) were the most common comorbidities. Metformin (62.7%) and sulfonylureas (38.7%) were the most common anti-diabetes medications. Only 1,653 (24%) patients achieved an A1C <8%. Predictors of increased probability of A1C goal attainment were older age, white/non-Hispanic race/ethnicity, Medicare health insurance, lower baseline A1C, higher frequency of endocrinology/primary care visits, DPP-4i use, thiazolidinedione use, metformin use, GLP-1RA use, and fewer classes of anti-diabetes drugs. Factors associated with lower probability included insulin use and longer time in the T2D database (both presumed as likely surrogates for duration of T2D). </p> <p><b>Conclusions:</b> A minority of patients with an A1C>9% achieved an A1C<8% at one year. While most identified predictive factors are non-modifiable by the clinician, pursuit of frequent patient engagement and tailored drug regimens may help improve A1C goal attainment. </p>

Functional Decline in Emergency Department Patients with Dyspnea; a Register-Based Cohort

2021 ◽  
Author(s):  
Karoline Stentoft Rybjerg Larsen ◽  
Marianne Lisby ◽  
Hans Kirkegaard ◽  
Annemette Krintel Petersen
Keyword(s):  
Emergency Department ◽  
Electronic Patient Record ◽  
Hospital Admissions ◽  
Functional Decline ◽  
Patient Characteristics ◽  
Risk Of Death ◽  
Record Data ◽  
Emergency Department Patients ◽  
One Year ◽  
Historic Cohort

Abstract Background Functional decline is associated with frequent hospital admissions and elevated risk of death. Presumably patients acutely admitted to hospital with dyspnea have a high risk of functional decline. The aim of this study was to describe patient characteristics, hospital trajectory, and use of physiotherapy services of dyspneic patients in an emergency department. Furthermore, to compare readmission and death among patients with and without a functional decline, and to identify predictors of functional decline. Methods Historic cohort study of patients admitted to a Danish Emergency Department using prospectively collected electronic patient record data from a Business Intelligence Registry of the Central Denmark Region. The study included adult patients that due to dyspnea in 2015 were treated at the emergency department (ED). The main outcome measures were readmission, death, and functional decline. Results In total 2,048 dyspneic emergency treatments were registered. Within 30 days after discharge 20% was readmitted and 3.9% had died. Patients with functional decline had a higher rate of 30-day readmission (31.2% vs. 19.1%, p&lt;0.001) and mortality (9.3% vs. 3.6%, p=0.009) as well as mortality within one year (36.1% vs. 13.4%, p&lt;0.001). Predictors of functional decline were age ≥60 years and hospital stay ≥6 days. Conclusion Patients suffering from acute dyspnea are seen at the ED at all hours. In total one in five patients were readmitted and 3.9% died within 30 days. Patients with a functional decline at discharge seems to be particularly vulnerable.

scholarly journals Drug Repurposing Opportunities in Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 14 (3) ◽  
pp. 280
Author(s):  
Rita Rebelo ◽  
Bárbara Polónia ◽  
Lúcio Lara Santos ◽  
M. Helena Vasconcelos ◽  
Cristina P. R. Xavier
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Pancreatic Ductal Adenocarcinoma ◽  
De Novo ◽  
Drug Repurposing ◽  
Metastatic Tumor ◽  
Therapeutic Options ◽  
Ductal Adenocarcinoma ◽  
Clinical Indication ◽  
Novel Treatments

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis is often possible only in the latter stages of the disease, with patients already presenting an advanced or metastatic tumor. It is also one of the cancers with poorest prognosis, presenting a five-year survival rate of around 5%. Treatment of PDAC is still a major challenge, with cytotoxic chemotherapy remaining the basis of systemic therapy. However, no major advances have been made recently, and therapeutic options are limited and highly toxic. Thus, novel therapeutic options are urgently needed. Drug repurposing is a strategy for the development of novel treatments using approved or investigational drugs outside the scope of the original clinical indication. Since repurposed drugs have already completed several stages of the drug development process, a broad range of data is already available. Thus, when compared with de novo drug development, drug repurposing is time-efficient, inexpensive and has less risk of failure in future clinical trials. Several repurposing candidates have been investigated in the past years for the treatment of PDAC, as single agents or in combination with conventional chemotherapy. This review gives an overview of the main drugs that have been investigated as repurposing candidates, for the potential treatment of PDAC, in preclinical studies and clinical trials.

Atrial Fibrillation and Mortality in the Oldest Old after Surgery for Hip Fractures

Gerontology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Amit Frenkel ◽  
Vladimir Zeldetz ◽  
Roni Gat ◽  
Yair Binyamin ◽  
Asaf Acker ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Risk Factor ◽  
Hip Fractures ◽  
Retrospective Cohort ◽  
Primary Outcome ◽  
Oldest Old ◽  
Postoperative Mortality ◽  
Patient Characteristics ◽  
One Year

Introduction: One-year mortality following hip fractures increases steeply with age, from 2% in the 60- to 69-year-old population up to 28% in the oldest old (older than 90 years). Of the various factors that contribute to hip fractures, atrial fibrillation (AF) is an independent risk factor at any age. Objective: The objective of this study was to assess the association of AF with mortality among the oldest old with hip fractures. Method: This is a retrospective cohort study of 701 persons above age 90 years who underwent orthopedic repair for a hip fracture during 2000–2018. Of them, 218 (31%) had AF at hospital admission. The primary outcome was survival following surgery. We compared patient characteristics and 30-day, 180-day, 1-year, and 3-year survival between patients with and without AF. Results: The adjusted odds ratio for 30-day postoperative mortality for those with AF versus without AF group was 1.03 (95% confidence interval [CI] 0.63–1.66). Survival estimates were higher among those without AF than with AF at 180 days postoperative: 0.85 (95% CI 0.82–0.89) versus 0.68 (95% CI 0.61–0.74), p < 0.001; at 1 year postoperative: 0.68 (95% CI 0.63–0.72) versus 0.48 (95% CI 0.42–0.55), p < 0.001; and at 3 years postoperative: 0.47 (95% CI 0.42–0.52) versus 0.28 (95% CI 0.27–0.34), p < 0.001. Conclusions: Among individuals aged >90 years, operated for hip fractures, mortality was similar for those with and without AF at 30 days postoperative. However, the survival curves diverged sharply after 180 days. Our findings suggest that AF is not an immediate surgical risk factor, but rather confers increased long-term risk in this population.

scholarly journals Patient characteristics predict patency of early-cannulation arteriovenous grafts

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
David B. Kingsmore ◽  
Karen S. Stevenson ◽  
S. Richarz ◽  
Andrej Isaak ◽  
Andrew Jackson ◽  
...  
Keyword(s):  
Vascular Disease ◽  
Peripheral Vascular Disease ◽  
Vascular Access ◽  
Demographic Data ◽  
Univariate Analysis ◽  
Patient Characteristics ◽  
Peripheral Vascular ◽  
Arteriovenous Grafts ◽  
One Year

AbstractThere is a new emphasis on tailoring appropriate vascular access for hemodialysis to patients and their life-plans, but there is little known about the optimal use of newer devices such as early-cannulation arteriovenous grafts (ecAVG), with studies utilising them in a wide variety of situations. The aim of this study was to determine if the outcome of ecAVG can be predicted by patient characteristics known pre-operatively. This retrospective analysis of 278 consecutive ecAVG with minimum one-year follow-up correlated functional patency with demographic data, renal history, renal replacement and vascular access history. On univariate analysis, aetiology of renal disease, indication for an ecAVG, the number of previous tunnelled central venous catheters (TCVC) prior to insertion of an ecAVG, peripheral vascular disease, and BMI were significant associates with functional patency. On multivariate analysis the number of previous TCVC, the presence of peripheral vascular disease and indication were independently associated with outcome after allowing for age, sex and BMI. When selecting for vascular access, understanding the clinical circumstances such as indication and previous vascular access can identify patients with differing outcomes. Importantly, strategies that result in TCVC exposure have an independent and cumulative association with decreasing long-term patency for subsequent ecAVG. As such, TCVC exposure is best avoided or minimised particularly when ecAVG can be considered.

Divergent patterns of anti-fracture medication use following fracture on therapy: A population-based cohort study

2021 ◽  
Author(s):  
Gregory A Kline ◽  
Suzanne N Morin ◽  
Lisa M Lix ◽  
William D Leslie
Keyword(s):  
Cohort Study ◽  
Medication Adherence ◽  
Vertebral Fracture ◽  
Drug Efficacy ◽  
Population Based ◽  
Duration Of Treatment ◽  
Traumatic Fracture ◽  
Before And After ◽  
One Year

Abstract Context Fracture-on-therapy should motivate better anti-fracture medication adherence. Objective Describe osteoporosis medication adherence in women before and following a fracture. Design Retrospective cohort study. Setting Manitoba BMD Registry (1996-2013). Patients Women who started anti-fracture drug therapy after a DXA-BMD with follow-up for 5 years during which a non-traumatic fracture occurred at least one year after starting treatment. Main Outcome Linked prescription records determined medication adherence (estimated by medication possession ratios, MPR) in one-year intervals. The variable of interest was MPR in the year before and after the year in which the fracture occurred with subgroup analyses according to duration of treatment pre-fracture. We chose an MPR of ≥0.50 to indicate minimum adherence needed for drug efficacy. Results There were 585 women with fracture-on-therapy, 193(33%) had hip or vertebral fracture. Bisphosphonates accounted for 82.2% of therapies. Median MPR the year prior to fracture was 0.89(IQR 0.49-1.0) and 0.69(IQR 0.07-0.96) the year following the year of fracture(p&lt; 0.0001). The percentage of women with MPR ≥ 0.5 pre-fracture was 73.8%, dropping to 57.3% post-fracture(p&lt;0.0001); restricted to hip/vertebral fracture results were similar (58.2% to 33.3%, p &lt;0.002). Among those with pre-fracture MPR &lt;0.5, only 21.7% achieved a post-fracture MPR ≥ 0.5. Conclusions Although fracture-on-therapy may motivate sustained/improved adherence, MPR remains low or even declines after fracture in many. This could reflect natural decline in MPR with time but is paradoxical to expectations. Fracture-on-therapy represents an important opportunity for clinicians to re-emphasize treatment adherence.

3333Contemporary mortality rates in myocardial infarction patients in Sweden: a tale of two registries

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Siverskog ◽  
M Janzon ◽  
L.-Å Levin ◽  
J Alfredsson ◽  
M Henriksson
Keyword(s):  
Myocardial Infarction ◽  
Intensive Care ◽  
Patient Characteristics ◽  
Primary Diagnosis ◽  
Age And Gender ◽  
Quality Registry ◽  
Mortality Outcome ◽  
Mortality Difference ◽  
And Gender ◽  
One Year

Abstract Background Sweden has contributed to the understanding of the long-term prognosis after myocardial infarction (MI) utilising the quality registry SWEDEHEART, including patients admitted to heart intensive care, and the National Patient Registry (PAR), based on administrative records for Swedish hospitals. As registration procedures differ between the registries, and not all MI patients are admitted to heart intensive care, MI patients identified in SWEDEHEART and PAR, respectively, will yield different cohorts of patients. This may result in different epidemiological research findings regarding prognosis after MI. Purpose To study MI populations identified in SWEDEHEART and PAR, respectively, and investigate potential differences in mortality outcome. Methods Patients hospitalised with an MI primary diagnosis (ICD-10 I21) between 2002 and 2015 were identified using SWEDEHEART and PAR. The analysis time started at the date of hospital admission and survivors were followed for 365 days. Kaplan-Meier analysis was used to estimate survival by cohort category controlling for age and gender. Results Excluding cases with invalid data (n=1,905), 225,612 and 282,118 SWEDEHEART and PAR patients, respectively, were identified. We found 213,367 patients in both SWEDEHEART and PAR, whereas 12,245 and 68,751 patients were unique to SWEDEHEART and PAR, respectively. The one-year survival probability after MI in the SWEDEHEART population was 0.841, compared to 0.788 in PAR (Figure). This discrepancy can be explained by high mortality among patients not covered by SWEDEHEART and persists after controlling for age and gender (Table). To what extent differences in registration procedures and other patient characteristics can explain the mortality difference is an area for further research. One-year survival by age and gender Age ± 1 year Male Female PAR S.H. Diff. PAR S.H. Diff. 65 0.922 0.936 0.015 0.919 0.936 0.017 70 0.893 0.909 0.016 0.889 0.908 0.019 75 0.829 0.858 0.029 0.834 0.860 0.026 80 0.743 0.783 0.040 0.768 0.800 0.033 85 0.625 0.677 0.052 0.662 0.705 0.042 One-year survival after MI Conclusion Estimated one-year survival for MI patients differs by up to 5 percentage points depending on the registry used. Although further research is needed to fully understand these differences, epidemiological findings regarding MI prognosis should be interpreted in light of registry type used and population represented. Acknowledgement/Funding Region Östergötland

scholarly journals The Probability of A1C Goal Attainment in Patients with Uncontrolled Type-2 Diabetes in a Large Integrated Delivery System: A Prediction Model

2020 ◽  
Author(s):  
Kevin M Pantalone ◽  
Anita D Misra-Hebert ◽  
Todd M Hobbs ◽  
Sheldon X Kong ◽  
Xinge Ji ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Goal Attainment ◽  
Index Date ◽  
Cleveland Clinic ◽  
Patient Characteristics ◽  
Psychiatric Disease ◽  
Lower Probability ◽  
Factors Associated ◽  
One Year

<b>Objective:</b> To assess patient characteristics and treatment factors associated with uncontrolled type 2 diabetes (T2D) and the probability of A1C goal attainment. <p><b>Research Design and Methods</b>: Retrospective cohort study using the electronic health record at Cleveland Clinic. Patients with uncontrolled T2D (A1C>9%) were identified on the index date of 12/31/2016 (n=6,973), grouped by attainment (n=1,653 [24.7%) or non-attainment (n=5,320 [76.3%]) of A1C<8% by 12/31/2017, and subgroups compared on a number of demographic and clinical variables. Based on these variables, a nomogram was created for predicting probability of A1C goal attainment. </p> <p><b>Results:</b> For the entire population, median age at index date was 57.7 years (53.3% male), and the majority were white (67.2%). Median A1C was 10.2%. Obesity (50.6%), cardiovascular disease (46.9%) and psychiatric disease (61.1%) were the most common comorbidities. Metformin (62.7%) and sulfonylureas (38.7%) were the most common anti-diabetes medications. Only 1,653 (24%) patients achieved an A1C <8%. Predictors of increased probability of A1C goal attainment were older age, white/non-Hispanic race/ethnicity, Medicare health insurance, lower baseline A1C, higher frequency of endocrinology/primary care visits, DPP-4i use, thiazolidinedione use, metformin use, GLP-1RA use, and fewer classes of anti-diabetes drugs. Factors associated with lower probability included insulin use and longer time in the T2D database (both presumed as likely surrogates for duration of T2D). </p> <p><b>Conclusions:</b> A minority of patients with an A1C>9% achieved an A1C<8% at one year. While most identified predictive factors are non-modifiable by the clinician, pursuit of frequent patient engagement and tailored drug regimens may help improve A1C goal attainment. </p>

scholarly journals Reviewing drug package inserts available in United Arab Emirates for USFDA recommended pharmacogenomic information

2017 ◽  
Vol 2 (1) ◽  
Keyword(s):  
Enzyme Activity ◽  
Genetic Variation ◽  
United Arab Emirates ◽  
Drug Toxicity ◽  
Therapeutic Response ◽  
Drug Efficacy ◽  
Brand Names ◽  
Package Inserts ◽  
Metabolizing Enzyme ◽  
Direct Genetic Evidence

Pharmacogenomics aims to characterize the contribution of genetic polymorphisms to variability in therapeutic response and toxicity. The USFDA has issued a list of drugs which exhibit polymorphism and relevant sections in the package inserts for providing pharmacogenomic information and their biomarkers to reduce the risk of drug toxicity. A total of 67 Package inserts of 41 drugs in 5 therapeutic areas, available in UAE under various brand names, were thoroughly reviewed for direct and indirect pharmacogenomic information and compared with FDA recommendations. It was observed that only 26 package inserts of 17 drugs (41%) prescribed provided direct genetic evidence and information on the type of polymorphism influencing drug efficacy and toxicity. Indirect indicators describing genetic variation in metabolizing enzyme activity was present in 20 inserts (30%)., It was concluded that incorporating the necessary pharmacogenomic information, as recommended by the USFDA, in the package inserts of drugs available in UAE will help in enhancing drug efficacy, safety and awareness among the physicians, pharmacists and patients.

scholarly journals Integrative pharmacogenomics to infer large-scale drug taxonomy

2016 ◽  
Author(s):  
Nehme El-Hachem ◽  
Deena M.A. Gendoo ◽  
Laleh Soltan Ghoraie ◽  
Zhaleh Safikhani ◽  
Petr Smirnov ◽  
...  
Keyword(s):  
Drug Targets ◽  
Large Scale ◽  
Prior Information ◽  
Structural Information ◽  
Drug Efficacy ◽  
Basic Drug ◽  
Flexible Tool ◽  
Experimental Drugs ◽  
New Compounds ◽  
Novel Drug

ABSTRACTIdentification of drug targets and mechanism of action (MoA) for new and uncharacterlzed drugs is important for optimization of drug efficacy. Current MoA prediction approaches largely rely on prior information including side effects, therapeutic indication and/or chemo-informatics. Such information is not transferable or applicable for newly identified, previously uncharacterlzed small molecules. Therefore, a shift in the paradigm of MoA predictions is necessary towards development of unbiased approaches that can elucidate drug relationships and efficiently classify new compounds with basic input data. We propose a new integrative computational pharmacogenomlc approach, referred to as Drug Network Fusion (DNF), to infer scalable drug taxonomies that relies only on basic drug characteristics towards elucidating drug-drug relationships. DNF is the first framework to integrate drug structural information, high-throughput drug perturbation and drug sensitivity profiles, enabling drug classification of new experimental compounds with minimal prior information. We demonstrate that the DNF taxonomy succeeds in identifying pertinent and novel drug-drug relationships, making it suitable for investigating experimental drugs with potential new targets or MoA. We highlight how the scalability of DNF facilitates identification of key drug relationships across different drug categories, and poses as a flexible tool for potential clinical applications in precision medicine. Our results support DNF as a valuable resource to the cancer research community by providing new hypotheses on the compound MoA and potential insights for drug repurposlng.

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