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Aim: The credibility and value of real-world evidence (RWE) are either supported or undermined by the algorithms (i.e., operational definitions) used. Methods: We conducted a targeted evidence review of key RWE decision makers' published recommendations on RWE algorithms through April 2021. Stakeholders were regulatory bodies, other governmental agencies and payer organizations. Results: Our review identified recommended criteria: relevance, validity, reliability, responsiveness, transparency and replicability, safety, feasibility and quality process. Stakeholders routinely recommended accuracy measures, subgroups evaluation and specific considerations for assessing exposures and covariates and the underlying real-world data (RWD) quality. Conclusion: The importance of stakeholder guidance on fit-for-purpose RWE algorithms is growing. We highlight gaps that future guidance and stakeholder recommendations could address.

Introduction Reliable cost and resource use data for COVID-19 hospitalizations are crucial to better inform local healthcare resource decisions; however, available data are limited and vary significantly. Methods COVID-19 hospital admissions data from the Premier Healthcare Database were evaluated to estimate hospital costs, length of stay (LOS), and discharge status. Adult COVID-19 patients (ICD-10-CM: U07.1) hospitalized in the US from April 1 to December 31, 2020, were identified. Analyses were stratified by patient and hospital characteristics, levels of care during hospitalization, and discharge status. Factors associated with changes in costs, LOS, and discharge status were estimated using regression analyses. Monthly trends in costs, LOS, and discharge status were examined. Results Of the 247,590 hospitalized COVID-19 patients, 49% were women, 76% were aged ≥ 50, and 36% were admitted to intensive care units (ICU). Overall median hospital LOS, cost, and cost/day were 6 days, US$11,267, and $1772, respectively; overall median ICU LOS, cost, and cost/day were 5 days, $13,443, and $2902, respectively. Patients requiring mechanical ventilation had the highest hospital and ICU median costs ($47,454 and $41,510) and LOS (16 and 11 days), respectively. Overall, 14% of patients died in hospital and 52% were discharged home. Older age, Black and Caucasian race, hypertension and obesity, treatment with extracorporeal membrane oxygenation, and discharge to long-term care facilities were major drivers of costs, LOS, and risk of death. Admissions in December had significantly lower median hospital and ICU costs and LOS compared to April. Conclusion The burden from COVID-19 in terms of hospital and ICU costs and LOS has been substantial, though significant decreases in cost and LOS and increases in the share of hospital discharges to home were observed from April to December 2020. These estimates will be useful for inputs to economic models, disease burden forecasts, and local healthcare resource planning. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01887-4.

Abemaciclib is the most recent oral cyclin-dependent kinase 4 and 6 inhibitor (CDK46i) to receive US Food and Drug Administration (FDA) approval to treat hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (MBC). Administrative claims data were used to describe patient characteristics and select clinical and economic outcomes in US patients treated in routine clinical practice. Prior analyses from electronic health records data indicate approximately 25% of patients received either palbociclib or ribociclib for MBC before initiating abemaciclib treatment; this work further explored these findings and associated outcomes.This retrospective study analyzed medical and pharmacy claims from the IBMThis analysis included 454 patients (mean age 57.7 years), with 35.0% (n = 159) in the +F group, 29.3% (n = 133) in the +AI group, 10.4% (n = 47) in the 200 mg Mono group, and 25.3% (n = 115) in the +other group. Prior chemotherapy and CDK 46i use were present in 23.8% and 49.8% of all patients, respectively. Visceral metastases were present at abemaciclib initiation in 50.4% in the +AI group; 49.7% in the +F group; and 55.3% in the 200 mg Mono group. Liver metastases were present in 33.7% of the overall population. Among patients without prior CDK46i use, the median TTD for patients receiving abemaciclib + AI was not reached [95% CI 430-not reached (NR) days], abemaciclib + F [531 days (95% CI 281-NR)], and abemaciclib mono [141 days (95% CI 80-NR)]. Median TTC for abemaciclib + AI and abemaciclib + F groups were not reached and the median TTC for abemaciclib mono was 535 days (95% CI 181-NR). Medication adherence was 88.7% and medication wastage costs among those with at least one dose modification were $808.12 and $452.2 per patient per month based on amount paid and wholesale acquisition cost (WAC), respectively. Mean length of follow-up for all patients was 350 days (SD 187).These real-world data complement clinical trial results by examining abemaciclib use among patients treated in routine clinical practice. The sizeable number of patients treated with prior CDK46i, chemotherapy, and/or visceral metastases at abemaciclib initiation suggest that many patients had very advanced disease and/or were in later stages of their treatment. These data confirm a higher percentage of patients treated with previous CDK46i than reported previously, reinforcing the importance of the ongoing, prospective clinical trials evaluating outcomes following progression on CDK46i.

To compare the mortality of hospitalized patients with COVID-19 between those that required supplemental oxygen and received dexamethasone with a comparable set of patients who did not receive dexamethasone.We utilized the Premier Health Database to identify hospitalized adult patients with COVID-19 from July 1, 2020-January 31, 2021. Index date was when patients first initiated oxygen therapy. The primary endpoint was in-hospital mortality for patients receiving dexamethasone versus those not receiving dexamethasone 1-day pre- to 1-day post-index period. Secondary endpoints included 28-day mortality, time to in-hospital mortality, progression to invasive mechanical ventilation or death, time to discharge, and proportion discharged alive by day 28. Twenty-three models using weighting, matching, stratification, and regression were deployed through the concept of frequentist model average (FMA) to estimate the effect of dexamethasone on all-cause mortality up to the 28-day hospitalization period.A total of 1,208,881 patients with COVID-19 were screened; as an inpatient 255,216 used oxygen, and 251,536 were included in the analysis. In the dexamethasone group, odds of in-hospital mortality were higher than those of the comparator (FMA: odds ratio [OR] 1.15, 95% CI 1.08, 1.22). Using a best fit model, OR for in-hospital mortality was non-significant for the dexamethasone group compared with the comparator (OR 1.02, 95% CI 0.92, 1.14). Dexamethasone treatment was associated with poorer outcomes versus the comparator group across the majority of secondary endpoints, except for number of days in hospital, which was lower in the dexamethasone group versus the comparator group (mean difference - 2.14, 95% CI - 2.43, - 1.47).Hospitalized adult patients with COVID-19 who required supplemental oxygen and received dexamethasone did not have a survival benefit versus similar patients not receiving dexamethasone. The dexamethasone group was not associated with favorable responses for outcomes such as progression to death or mechanical ventilation and time to in-hospital death.

Early identification of symptoms and comorbidities most predictive of COVID-19 is critical to identify infection, guide policies to effectively contain the pandemic, and improve health systems’ response. Here, we characterised socio-demographics and comorbidity in 3,316,107persons tested and 219,072 persons tested positive for SARS-CoV-2 since January 2020, and their key health outcomes in the month following the first positive test. Routine care data from primary care electronic health records (EHR) from Spain, hospital EHR from the United States (US), and claims data from South Korea and the US were used. The majority of study participants were women aged 18-65 years old. Positive/tested ratio varied greatly geographically (2.2:100 to 31.2:100) and over time (from 50:100 in February-April to 6.8:100 in May-June). Fever, cough and dyspnoea were the most common symptoms at presentation. Between 4%-38% required admission and 1-10.5% died within a month from their first positive test. Observed disparity in testing practices led to variable baseline characteristics and outcomes, both nationally (US) and internationally. Our findings highlight the importance of large scale characterization of COVID-19 international cohorts to inform planning and resource allocation including testing as countries face a second wave.

Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19., Detailed knowledge of the characteristics of COVID-19 patients helps with public health planning. Here, the authors use routinely-collected data from seven databases in three countries to describe the characteristics of >30,000 patients admitted with COVID-19 and compare them with those admitted for influenza in previous years.

The pivotal role of plaster of Paris (POP) cast as an immobilization tool to promote healing in complex and/or other types of fractures is irrefutable. We clearly know that Antonius Mathysen extensively applied plaster cast during Crimea and/or other wars and reportedly saved thousands of lives. However, the exact origin of using POP in orthopedic cast is yet to be clear. In his famous report from Bandar-e Rig, a city in Iran, William Eton paved the way for the conclusion that POP cast might have originated from the Persian Empire. In this paper, we provide more supporting evidences which make the aforementioned claim more probable.

FDA-approved prescribing information (also known as product labeling or labels) contain critical safety information for health care professionals. Drug labels have often been criticized, however, for being overly complex, difficult to read, and rife with overwarning, leading to high cognitive load. In this project, we aimed to improve the usability of drug labels by increasing the ‘signal-to-noise ratio’ and providing meaningful information to care providers based on patient-specific comorbidities and concomitant medications. In the current paper, we describe the design process and resulting web application, known as myDrugLabel. Using the Structured Product Label documents as a base, we describe the process of label personalization, readability improvements, and integration of diverse evidence sources, including the medical literature from PubMed, pharmacovigilance reports from FDA adverse event reporting system (FAERS), and social media signals directly into the label.

Breast cancer is one of the most common forms of cancer observed in women and endogenous estrogens are thought to play a major role in its development. Tamoxifen is a selective estrogen receptor (ER) modulator which is widely used to treat and prevent breast cancer. Tamoxifen is an ER antagonist in the breast but an ER agonist in cardiovascular system (CVS) and some other tissues. Many patients experience resistance to tamoxifen. Several studies have indicated various mechanisms in tamoxifen resistance. Growth factors and their receptors, extracellular proteins, transcription factors, cell-cycle regulators, and signal-transduction molecules have been identified as being potentially involved in tamoxifen resistance. The aim of the present hypothesis is to provide evidences that may lead to this suggestion that renin–angiotensin system (RAS) may have a role in tamoxifen resistance. It has been established in numerous studies that RAS play a role in the progression of various cancers such as breast cancer. Besides, other studies have indicated that estrogen has an inhibitory effect on the RAS components levels in CVS and various tissues such as the adrenal and the pituitary. Therefore, it can be suggested that tamoxifen may increase RAS components levels in the breast tissue by its antagonistic effect on ER and causes resistance. Confirmation of this theory by experimental investigations may lead to this suggestion that combination of angiotensin-converting enzyme inhibitors or angiotensin receptor-1 blockers with tamoxifen may have a preventive effect on development of acquired tamoxifen resistance.

Breast cancer is the prevalent cancer worldwide. Excessive exposure to endogenous estrogen across a woman's lifespan contributes to and may be a causal factor in breast cancer. Tamoxifen is a mixed estrogen agonist and antagonist, which is used in treatment and prevention of breast cancer as an estrogen antagonist. Many patients experience resistance to tamoxifen for which many mechanisms have been suggested. Endothelin-1 acts as a mitogen for human breast fibroblasts and it affects tumor cell proliferation, invasion, angiogenesis, neovascularization, mitogenesis, and apoptosis inhibition. Previous studies have shown that estradiol is effective in inhibiting endothelin synthesis in breast tissue and cardiovascular system. Tamoxifen as an estrogen receptor (ER) agonist in cardiovascular system has a cardioprotective effect and decreases endothelin level as a vasoconstrictor in cardiovascular system. But in breast tissue tamoxifen acts as an ER antagonist. According to the role of endothelin in breast cancer and inhibitory effect of estrogen on endothelin, we hypothesized that tamoxifen causes increasing in endothelin level or endothelin receptors probably by inhibitory effect on ER in breast tissue, leading to tamoxifen resistance. Therefore a combination of tamoxifen with endothelin antagonist seems to be a reasonable therapeutic strategy.