Retrospective Database Studies Research Articles

P-1949. The Self-Controlled Risk Interval: An Evolving Method for Vaccine Effectiveness Estimation in Complex Real-World Data

Abstract Background Post-marketing assessments of vaccine effectiveness (VE) are critical to informing health policy, understanding real-world vaccine performance, and ensuring confidence in vaccination efforts, though imperfect comparator groups can limit the accuracy of VE assessments. The self-controlled risk interval (SCRI) design, a case-only analytic method historically used in safety studies, controls for time-invariant confounding using within-person comparisons and has recently been used to assess VE. This targeted review identifies and characterizes SCRI’s growing role in VE research.Table 1:Vaccine Effectiveness Studies that Used the Self-Controlled Risk Interval Design Methods Targeted database searches were conducted in Medline, Embase®, Embase Preprints, and BIOSIS Previews®, and the preprint servers: medRxiv, preprints with The Lancet, and Research Square. Key terms (and related variations) included: vaccine effectiveness, COVID-19 vaccines, and self-controlled risk interval. Results Two VE studies that used the SCRI design were identified (Table 1). Both were retrospective database studies (one using electronic health records and the other insurance claims data), evaluated SARS-CoV-2 infection, and used similar post-vaccination control windows, but featured different post-vaccination risk windows and were conducted among notably different populations. An additional 10 identified studies included post-vaccination person-time in the comparison group but did not make within-person comparisons to address important potential confounding, acknowledging that post-vaccination benefits are not appreciated immediately. These studies varied in the study populations, outcomes assessed, comparison group composition, and analytic methods. Conclusion Use of SCRI for VE estimation has been limited; however, the increasing inclusion of post-vaccination control arm person-time in other COVID-19 VE studies merits the broadening of its application. The results of this review suggest that, in the context of COVID-19, SCRI VE evaluation is a promising tool where there are no suitable comparison groups, increasingly complex individual backgrounds (e.g., infection history, number and timing of doses, or heterologous vaccination), or insufficient information for confounding control. Disclosures Jonathan Fix, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Anthony M. Marchese, PhD, Novavax Inc: Employee|Novavax Inc: Stocks/Bonds (Public Company) Hadi Beyhaghi, MD, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Matthew D. Rousculp, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company)

Sugammadex and oral contraceptives.

This review article explores the evidence regarding sugammadex (MSD Australia) and its potential interaction with hormonal contraceptives. The impact of recent clinical trials and review articles is examined. Recent clinical data suggest that the interaction between sugammadex and estrogen and progesterone concentrations may not be clinically significant and may confer some protection against ovulation. There are no clinical trials reporting interactions between sugammadex and the exogenous hormonal compounds found in oral contraceptive pills. The method of contraception is an important consideration, as sugammadex theoretically affects oral and nonoral, and combined versus single agent methods differently. Two large retrospective database studies have reported two cases of pregnancy postoperatively in patients on hormonal contraceptives whose anesthetic included sugammadex. Strong clinical evidence to support or refute claims of a significant impact of sugammadex on contraceptive efficacy in women on contraception is lacking. The existing evidence does not suggest a basis for concern regarding the impact of sugammadex on contraception in the perioperative setting.

Decoding definitions of major bleeding in retrospective observational studies on direct oral anticoagulants for atrial fibrillation: a targeted literature review

Abstract Background Major bleeding is an adverse event associated with using direct oral anticoagulants (DOACs) for treatment of atrial fibrillation (AF). Incidence rates of major bleeding vary notably between randomised controlled trials (RCTs) and real-world evidence (RWE) studies. This may be attributable to inconsistent major bleeding definitions across RWE studies. RCTs commonly use the International Society on Thrombosis and Haemostasis (ISTH) major bleeding definition, including fatal bleeding, critical area/organ bleeding, bleeding requiring a blood transfusion of 2 or more units, and/or reductions in haemoglobin. These parameters may be absent in RWE studies, leading to utilisation of proxy definitions. Thus, the components used to define major bleeding in RWE studies remain unclear. Purpose To examine major bleeding definitions via a targeted literature review of retrospective observational studies on patients with AF receiving DOACs in routine clinical practice. Methods Studies of patients with AF receiving DOACs that were published between 2012 and 2022 were identified using keywords and MeSH terms in PubMed. Retrospective observational studies were screened for inclusion by title and abstract, and subsequently by full text. Articles were assessed for the types of databases and DOAC therapies studied. Components of major bleeding definitions were recorded and compared across database types. Results Of 328 articles screened, 18 retrospective observational studies were included in this analysis. The most common data sources were claims data (n = 10), followed by electronic medical records (n = 4), and registry data (n = 4). Across studies, major bleeding incidence rates varied from 0.59 to 11.4 events per 100 person-years. Of the 6 components of major bleeding definitions identified, requiring hospitalisation (n = 12) was the most frequent (Figure), though is not essential per the ISTH definition. No articles used fatal bleeding as a component to define major bleeding. Approximately half of all articles used the component involvement of critical organ or site (n = 7). Requiring blood transfusion was used in 6 articles and only 4 used reduction in haemoglobin or haematocrit levels (none of these involved claims data). Conclusions This targeted literature review of retrospective database studies of routine clinical practice decodes proxy use of ISTH major bleeding definitions. Claims data were the most common data source but lacked components describing fatal bleeding and haemoglobin levels. Further research is vital to assess the variation in reported major bleeding rates in RWE studies using proxy definitions in place of the ISTH definition.Figure

Transforming diabetes care with continuous glucose monitoring: Rationale for expanded eligibility criteria.

Randomized trials and large retrospective database studies have shown that individuals treated with noninsulin therapies experience the same glycemic benefits from continuous glucose monitoring (CGM) use as those treated with more intensive treatment regimens. However, many policy makers and payers are reluctant to provide CGM coverage for these patients. Although the recent American Diabetes Association guidelines have taken an important first step in recommending that CGM should be offered to all adults treated with basal insulin who are capable of using it, clinicians should consider the acute and long-term consequences of persistent hyperglycemia in all of their patients with diabetes. This article describes how the use of the FreeStyle Libre 2 CGM System (Abbott Diabetes Care, Alameda, CA) improved glycemic outcomes and facilitates personalized diabetes care in two type 2 diabetes patients treated with noninsulin therapies.

A Scoping Review of the Mechanisms Underlying Developmental Anesthetic Neurotoxicity.

Although anesthesia makes painful or uncomfortable diagnostic and interventional health care procedures tolerable, it may also disrupt key cellular processes in neurons and glia, harm the developing brain, and thereby impair cognition and behavior in children. Many years of studies using in vitro, animal behavioral, retrospective database studies in humans, and several prospective clinical trials in humans have been invaluable in discerning the potential toxicity of anesthetics. The objective of this scoping review was to synthetize the evidence from preclinical studies for various mechanisms of toxicity across diverse experimental designs and relate their findings to those of recent clinical trials in real-world settings.

Extranodal extension in laryngeal squamous cell carcinoma.

Although large retrospective database studies have associated extranodal extension (ENE) with worse survival in several head and neck cancers, the prognostic significance of ENE in laryngeal squamous cell carcinoma (LSCC) remains unclear. Our study examines ENE and overall survival (OS) in LSCC. The 2006-2017 National Cancer Database was queried for patients with LSCC undergoing surgical resection and neck dissection, with or without adjuvant therapy. Kaplan-Meier and multivariable Cox regression survival analyses were implemented to identify the independent impacts of pathologic nodal (pN) classification and ENE on OS. Of 4208 patients satisfying inclusion criteria, 2343 (55.7%) were pN0/ENE-negative, 1059 (25.2%) were pN1-2/ENE-negative, and 806 (19.2%) were pN1-2/ENE-positive. The 5-year OS of pN0/ENE-negative, pN1-2/ENE-negative, and pN1-2/ENE-positive patients was 62.8%, 56.7%, and 32.9%, respectively (p < .001). Among pN1-2/ENE-positive patients undergoing no adjuvant therapy, adjuvant radiotherapy alone, and adjuvant chemoradiotherapy, 5-year OS was 24.1%, 30.7%, and 36.7%, respectively (p < .001). After adjusting for patient demographics, clinicopathologic features, and adjuvant therapy, ENE-positivity was associated with worse OS than ENE-negativity (adjusted hazard ratio [aHR] 1.76, 95% confidence interval [CI] 1.53-2.02, p < .001). pN1/ENE-positivity (aHR 1.82, 95% CI 1.31-2.54) and pN2/ENE-positivity (aHR 1.89, 95% CI 1.49-2.40) were associated with worse OS than pN1/ENE-negativity (p < .001). Microscopic (aHR 1.83, 95% CI 1.54-2.18) and macroscopic ENE-positivity (aHR 1.75, 95% 1.35-2.26) were associated with worse OS than ENE-negativity (p < .001). ENE-positivity has prognostic significance in LSCC and is associated with worse OS than ENE-negativity. pN classification did not have prognostic significance independent of ENE. ENE should be carefully considered when determining the prognosis of LSCC and selecting adjuvant therapy. 4.

The Burden of Urinary Tract Infections on Quality of Life and Healthcare in Patients with Interstitial Cystitis.

Interstitial cystitis/bladder pain syndrome (IC/BPS) patients are more susceptible to urinary tract infections (UTIs), likely worsening pre-existing symptoms. However, this receives limited attention in guidelines. This study aimed to explore the burden of UTIs on IC/BPS patients' quality of life and their healthcare. Two quantitative retrospective database studies were conducted in cystoscopically proven IC/BPS patients: one compiled existing patient survey data (n = 217) from July 2021 to examine physical and emotional UTI burden, and the other used a patient file database (n = 100) from January 2020 to May 2022, focusing on UTI prevalence, healthcare use, urine cultures and antibiotic resistance. A delay in diagnosis was seen in 70% of patients, due to doctors confusing IC/BPS symptoms with UTIs. The UTI prevalence was over 50%; these patients also report anxiety for new UTIs (70%) and worsening of IC/BPS symptoms (60%). Additionally, for UTI+ patients, healthcare consumption was significantly increased in both studies. Antibiotic resistance (80% of cultures) and prophylactic antibiotic use were common. These findings highlight the burden of UTIs on quality of life in IC/BPS patients and the healthcare system. These results emphasize the need for improved UTI guidelines concerning diagnosis, management and prevention for IC/BPS patients to improve quality of life and care.

The Anterior Versus Posterior Approach for Interbody Fusion in Patients Who Are Classified as Obese: A Retrospective Cohort Study of 9,021 Patients From a National Database.

Introduction Lumbar spine interbody fusions have been performed to relieve back pain and improve stability due to various underlying pathologies.Anterior interbody fusion and posterior interbody fusion approaches are two main approaches that are classically compared.In an attempt to compare these two approaches to the spine, large retrospective national database reviews have been performed to compare and predict 30-day postoperative outcomes; however, they have conflicting findings.Obesity, defined as having a body mass index (BMI) over 30kg/m2, may also contribute to the extent of spine pathology and isassociated withincreased rates of postoperative complications. Complication rates in patients who are obese have yet to be thoroughly investigated using a large national database.Our present investigation aims to make this comparison using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database.The goal of the present study is to utilize a nationwide prospective database to determine short-term differences in postoperative outcomes between posterior and anterior lumbar fusion in patients with obesity and relate these findings to previous studies in the general population. Methods A retrospective cohort analysis was conducted on 9,021 patientdata from the ACS-NSQIP database from 2015 to 2019 who underwent an elective, single-level fusion via anterior or posterior surgical approach. This database captures over 150 clinical variables on individual patient cases, including demographic data, preoperative risk factors and laboratory values, intraoperative data, and significant events up to postoperative day 30. All outcome measures were included in this analysis with special attentionto rates of deep venous thrombosis (DVT) and pulmonary embolism (PE), prolonged length of stay (LOS), reoperation, and operation time. Results Multivariable analysis controlling for age, BMI, sex, race, functional status, American Society of Anesthesiologists (ASA) class, and selected comorbidities with P < 0.05 demonstrated that the anterior approach was an independent predictor for all significant outcomes except prolonged length of stay. Compared to the posterior approach, the anterior approach had a shorter total operation time (B = -13.257, 95% confidence interval (CI) [-17.522, -8.992], P< 0.001), higher odds of deep vein thrombosis (odds ratio (OR) = 2.210, 95% CI [1.211, 4.033], P= 0.010), and higher odds of pulmonary embolism (OR = 2.679, 95% CI [1.311, 5.477], P= 0.007) and was protective against unplanned reoperation (OR = 0.702, 95% CI [0.548, 0.898],P= 0.005). Conclusions The obese population makes up a large and growing demographic of those undergoing spine surgery, and as such, it is pertinent to investigate the differences, advantages, and disadvantages of lumbar fusion approaches in this group. While anterior approachesmaybe protective of longer operation time and unplanned reoperation, this benefit may not be clinically significant when considering an increased risk of DVT and PE. Given the short-term nature of this dataset and the limitations inherent in large de-identified retrospective database studies, these findings are interpreted with caution. Longer-term follow-up studies accounting for confounding variables with spine-centered outcomes will be necessary to further elucidate these nuances.

Impact of Proteinuria and Kidney Function Decline on Health Care Costs and Resource Utilization in Adults With IgA Nephropathy in the United States: A Retrospective Analysis

Among patients with IgA nephropathy (IgAN), proteinuria and decline in kidney function may be associated with increased economic burden. This study aimed to provide current information on the epidemiology and economic burden of IgAN in the United States. Retrospective cohort study. Overall, 9,984 patients in the Optum's Market Clarity database identified by the presence of at least 2 natural language processing-derived IgAN signs and disease and symptoms terms; 813 with linked claims data included in a health care resource utilization/cost subcohort. High-risk proteinuria (≥1g/d), chronic kidney disease (CKD) stage. Standardized prevalence, health care resource utilization, costs. Descriptive statistics for categorical and continuous variables. Direct standardization for prevalence estimation. Generalized linear models for health care resource utilization/costs, reported as per-patient-per-month (PPPM) costs in 2020 US dollars. The estimated standardized US prevalence of IgAN (2016-2020) was 329.0 per 1,000,000 persons. High-risk proteinuria (≥1 vs<1 g/d) was associated with a higher mean PPPM number of outpatient visits (3.49 vs 1.74; P=0.01) and pharmacy claims (3.79 vs 2.41; P=0.01), contributing to higher mean total costs PPPM ($3,732 vs $1,457; P=0.01). Furthermore, higher CKD stage was also associated with higher health care resource utilization (number of outpatient visits PPPM, number of pharmacy claims PPPM, proportion of patients with inpatient visits and emergency department visits; P<0.001) and mean total cost PPPM (from $2,111 CKD stage 1 to $10,703 CKD stage 5/kidney failure; P<0.001). Generalizability outside of the catchment group for the database, missing data/errors inherent in retrospective database studies, relatively small sample size, use of Optum Market Clarity standardized pricing algorithms, exclusion of out-of-pocket costs. Health care resource utilization and costs were higher for IgAN patients with high-risk proteinuria and worsening kidney function. Treatments that reduce proteinuria and slow CKD disease progression may reduce the economic burden associated with IgAN. Immunoglobulin A nephropathy (IgAN) is a rare kidney disease. Over time, the kidneys may leak protein into the urine (proteinuria). IgAN can lead to kidney failure. Because IgAN is rare, it is hard to know how many people have it. This study used electronic health records to estimate the number of patients with IgAN in the United States, describe the characteristics of patients, and understand their treatments and the costs. The number of patients with IgAN increased between 2016 and 2020. The researchers think this is because doctors learned more about IgAN. Patients with severe disease used more health care resources and had higher costs. The authors believe treatments that slow kidney damage may reduce the cost of treating IgAN.

76-LB: Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA)–Experienced Adults with Type 2 Diabetes (T2D) Switching to Once-Weekly (OW) Semaglutide in a Real-World Setting—SURE Program Post Hoc Analysis

Retrospective database studies have shown that switching between some GLP-1RAs may be associated with additional benefits on glycemic control and body weight (BW). This prospective post hoc analysis of pooled data from the SURE real-world program (9 ~30 week studies in 10 countries) investigated outcomes associated with switching to OW semaglutide from another GLP-1RA in adults with T2D. Endpoints included change in HbA1c and BW from baseline to end of study, percentage achieving HbA1c &amp;lt;7% (when baseline HbA1c ≥7%) or BW change ≥5%, and safety. For change in HbA1c and BW, a random coefficient-adjusted mixed analysis for repeated measures was used, regardless of semaglutide treatment status. In total 651 participants (mean age 60 years; 53% male) switched to OW semaglutide: 64% from liraglutide, 31% from dulaglutide. Significant changes were observed in HbA1c and BW (Figure); 33% of participants with baseline HbA1c ≥7% achieved HbA1c &amp;lt;7%, and 28% reduced BW by ≥5%. No new safety concerns were identified; 3% discontinued due to AEs, 2% reported ≥1 hypoglycemic episode (blood glucose &amp;lt;54 mg/dL) and 8/11 participants with ≥1 level 2 hypoglycemic episode were on insulin. In adults with T2D previously treated with GLP-1RAs, switching to OW semaglutide may provide additional benefits with convenient OW dosing. Disclosure G. Rudofsky: Consultant; AstraZeneca, Eli Lilly and Company, Speaker's Bureau; Abbott Diabetes, Bayer Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Sanofi. M. Menzen: Advisory Panel; Boehringer Ingelheim Pharma GmbH&amp;Co. KG, Novo Nordisk A/S, Ascensia Diabetes Care, Eli Lilly and Company, Novartis, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Santis, Boehringer Ingelheim Pharma GmbH&amp;Co. KG, Novo Nordisk A/S, Bayer Inc., Eli Lilly and Company, Novartis. L. Potier: Consultant; Lilly Diabetes, Novo Nordisk, Sanofi, AstraZeneca, Boehringer Ingelheim Inc. A. Catarig: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. A. Clark: Employee; Novo Nordisk A/S. P. Priyadarshini: None. C. Abreu: Speaker's Bureau; Lilly, Novo Nordisk. Funding Novo Nordisk

Integrating the evidence in allergen immunotherapy: Why real-world data should be important for the practicing clinician?

Data obtained from controlled clinical trials are the gold standard for evaluation of allergen immunotherapy (AIT) efficacy and safety. Less prone to biases (with a strong internal validity), they allow their use and external validation in the real world. The quantity and diversity of real-world data has increased exponentially, and access to large cohorts and electronic medical records have made this information increasingly accessible and useful for research and regulatory purposes. New retrospective database studies have confirmed the sustained benefits of grass, birch pollen, and house dust mite AIT for both allergic rhinitis and asthma symptom and medication scores, the prevention of asthma (when used in nonasthmatic rhinitics), and the real rate of adverse systemic reactions. They also have addressed clinical practice issues not elsewhere analyzed, including the management of polysensitized patients with respiratory allergies and adherence to AIT. Real-world evidence has its own biases and limits that need to be taken into account. In this article we present a concise summary of the literature about the role of real-world evidence in AIT.

A Systematic Review of Head and Neck Cancer Health Disparities: A Call for Innovative Research.

(1) Describe the existing head and neck cancer health disparities literature. (2) Contextualize these studies by using the NIMHD research framework (National Institute on Minority Health and Health Disparities). (3) Explore innovative ideas for further study and intervention. Ovid MEDLINE, Embase, Web of Science, and Google Scholar. Databases were systematically searched from inception to April 20, 2020. The PRISMA checklist was followed (Preferred Reporting Items for Systematic Reviews and Meta-analyses). Two authors reviewed all articles for inclusion. Extracted data included health disparity population and outcomes, study details, and main findings and recommendations. Articles were also classified per the NIMHD research framework. There were 148 articles included for final review. The majority (n = 104) focused on health disparities related to at least race/ethnicity. Greater than two-thirds of studies (n = 105) identified health disparities specific to health behaviors or clinical outcomes. Interaction between the individual domain of influence and the health system level of influence was most discussed (n = 99, 66.9%). Less than half of studies (n = 61) offered specific recommendations or interventions. There has been extensive study of health disparities for head and neck cancer, largely focusing on individual patient factors or health care access and quality. This review identifies gaps in this research, with large numbers of retrospective database studies and little discussion of potential contributors and explanations for these disparities. We recommend shifting research on disparities upstream toward a focus on community and societal factors, rather than individual, and an evaluation of interventions to promote health equity.

The Importance of Appropriate Dosing of Nonvitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Patients with Atrial Fibrillation

Preventing thromboembolic events, while minimizing bleeding risks, remains challenging when managing patients with atrial fibrillation (AF). Several factors contribute to current dosing patterns of nonvitamin K antagonist oral anticoagulants (NOACs), including patient characteristics, comorbidities, and physician judgment. Application of NOAC doses inconsistent with the drug labels may cause patients to receive either subtherapeutic (increasing stroke risk) or supratherapeutic (increasing bleeding risk) anticoagulant levels. In clinical practice, under- or over-dosing of NOACs in patients with AF is not uncommon. This analysis of prospective and retrospective registry and database studies on NOAC use in patients with AF (with at least 250 patients in each treatment arm) showed that under-dosing may be associated with reduced effectiveness for stroke prevention, with similar or even increased bleeding than with the standard dose. This may reflect underlying conditions and patient factors that increase bleeding despite NOAC dose reduction. Such factors could drive the observed overuse of reduced NOAC dosages, often making the prescription of reduced-dose NOAC an intentional label deviation. In contrast, over-dosing more likely occurs accidentally; instead of providing benefits, it may be associated with worse safety outcomes than the standard dose, including increased bleeding risk and higher all-cause mortality rates. This review summarizes the main findings on NOAC doses usually prescribed to patients with AF in clinical practice.

Review Article: Gastrointestinal Bleeding Risk with Direct Oral Anticoagulants.

Although direct oral anticoagulants (DOACs) are associated with an overall favourable safety profile, the risk of gastrointestinal bleeding with DOACs compared with vitamin K antagonists (VKAs) remains controversial. Accordingly, we aimed to provide a focused overview of the risk of gastrointestinal bleeding associated with dabigatran, rivaroxaban, apixaban and edoxaban and its management. We reviewed published studies reporting on DOACs with gastrointestinal bleeding as an outcome, including randomised controlled trials (RCTs), retrospective database studies and large-scale prospective cohort studies. Cumulative evidence confirms no notable difference in major gastrointestinal bleeding risk between DOACs and VKAs. Moreover, gastrointestinal bleeding in DOAC-treated patients seems less severe and requires less intensive management. The main cause of upper gastrointestinal bleeding in DOAC-treated patients appears to be gastroduodenal ulcers, whereas lower gastrointestinal bleedings are mainly due to diverticula followed by angiodysplasia and haemorrhoids. The lack of head-to-head RCTs with DOACs precludes drawing conclusions on the DOAC with the lowest gastrointestinal bleeding risk. Prescribing physicians should be aware of risk factors for DOAC-related gastrointestinal bleeding (e.g. age > 65, heavy alcohol use, uncontrolled hypertension, hepatic or renal dysfunction, active cancer, anaemia) and adopt preventive measures accordingly. Management of DOAC-associated major gastrointestinal bleeding involves temporary discontinuation of the DOAC, investigation of the bleeding source and treatment of bleeding with fluid resuscitation combined with transfusion and endoscopic haemostasis. DOACs as a class do not increase the risk of major gastrointestinal bleeding compared to VKAs, which supports their continued use for different anticoagulant indications.

Benefits and Harms of Low-Dose Rivaroxaban in Asian Patients With Atrial Fibrillation: A Systematic Review and Meta-analysis of Real-World Studies

Background: Low-dose prescription of rivaroxaban was common among patients with atrial fibrillation (AF) in Asia. However, the benefits and harms of rivaroxaban at a low dosage in Asian patients with AF remains unclear. Accordingly, we aimed to collect and summarize all available evidence to fill this important knowledge gap. Methods: In this systematic review and meta-analysis, we systematically searched databases of MEDLINE, EMBASE, and Cochrane Library for relevant studies from inception until February 23, 2021. Eligible retrospective nationwide or health insurance database studies or prospective registration studies that reported efficacy (stroke/systemic embolism), safety (major bleeding, intracranial hemorrhage, gastrointestinal bleeding), or other outcomes (myocardial infarction, death) of low-dose rivaroxaban in comparison with warfarin in AF patients were enrolled. Data extraction and study quality assessment were conducted by two authors independently. Low dosing of rivaroxaban (15/10 mg) was defined as the received dose lower than the recommended dose (20 mg) approved in most districts. Hazard ratio (HR) with 95% confidence intervals (95% CIs) was pooled using a random-effect model. Subgroup analyses were conducted according to different dose regimens. Sensitivity analyses were conducted by sequential elimination of each study from the pool. Since potential effect modifiers (patient demographics, differences of each study, and others) may lead to bias in primacy outcomes, we performed a meta-regression analysis to explore the influence of these factors on the primary efficacy and safety outcomes. Results: Totally, 12 studies involving 292,815 Asian patients with AF were included. All studies were detected as low to moderate risk bias. Low-dose rivaroxaban treatment in Asian AF patients was associated with a reduced risk of stroke/systemic embolism (HR: 0.76, 95% CI: 0.70–0.84, I 2: 57.8%), major bleeding (HR: 0.72, 95% CI: 0.62–0.84, I 2: 81.5%), and all-cause death (HR: 0.65, 95% CI: 0.58–0.73, I 2: 81.7%) when compared with warfarin. Furthermore, consistent results were observed among different dose regimens (10/15/20 mg) in all the clinical outcomes (P interaction > 0.05 for each outcome). Meta-regression analysis failed to detect any potential confounding to impact the primacy outcomes. Conclusion: Insights from the present meta-analysis, we found that low-dose rivaroxaban, even at a dosage of 10 mg daily, was associated with a reduced risk of stroke/SE and bleeding than warfarin in Asian AF patients. However, owing to considerable heterogeneity among included studies, further prospective studies are required to confirm these findings.

Airway Management in Surgical Patients With Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder, and the difficult airway is perhaps the anesthesiologists' quintessential concern. OSA and the difficult airway share certain similar anatomical, morphological, and physiological features. Individual studies and systematic reviews of retrospective, case-control, and large database studies have shown a likely association between patients with OSA and the difficult airway; OSA patients have a 3- to 4-fold higher risk of difficult intubation, difficult mask ventilation, or a combination of both. The presence of OSA should initiate proactive perioperative management in anticipation of a difficult airway. Prudent intraoperative management comprises the use of regional anesthesia where possible and considering an awake intubation technique where there is the presence of notable difficult airway predictors and risk of rapid desaturation following induction of general anesthesia. Familiarity with difficult airway algorithms, cautious extubation, and appropriate postoperative monitoring of patients with OSA are necessary to mitigate perioperative risks.

Axillary Primary and Breast Cancer Management

Axillary primary breast cancer, also known as occult primary breast cancer, is a rare entity representing less than 1% of all breast cancers. The surgical management of the axilla in breast cancer has changed significantly, with implications for the management of axillary primary breast cancer. Much of the data is limited by era, small cohorts, or large retrospective database studies. The purpose of this review is to reinforce the diagnostic work up of occult breast cancer, review updated management strategies of the axilla and breast, and summarize changes and updates in practice management and outcomes. Pathologic confirmation of breast primary disease and MRI are critical for the diagnostic work up of axillary primary breast cancer. A recent axillary primary specific meta-analyses and several National Cancer Database studies (NCDB) have reinforced that mastectomy versus breast conservation with whole breast radiation has equivalent outcomes. Surgical axillary management is under evolution, with multiple large trials reporting the role of neoadjuvant chemotherapy to downstage the node-positive axilla and decrease the morbidity of axillary lymph node dissection by allowing accurate sentinel node biopsy. Use of neoadjuvant chemotherapy and adjuvant radiation therapy is increasingly used, although no prospective data exists specifically in occult primary breast cancer. Appropriate diagnostic work up includes MRI to identify possible primary breast lesions in all patients with metastatic axillary disease and negative exam, mammography, and ultrasound. Axillary primary breast cancer should be treated with contemporary management strategies as other anatomic stage II breast cancers. Appropriate management strategies based on recent trial data suggest the use of neoadjuvant chemotherapy to downstage the axilla and allow for less morbid axillary surgery. Outcomes are equivalent with mastectomy or whole breast radiation.

Household presentation of influenza and acute respiratory illnesses to a primary care sentinel network: retrospective database studies (2013\u20132018)

BackgroundDirect observation of the household spread of influenza and respiratory infections is limited; much of our understanding comes from mathematical models. The study aims to determine household incidence of influenza-like illness (ILI), lower (LRTI) and upper (URTI) respiratory infections within a primary care routine data and identify factors associated with the diseases’ incidence.MethodsWe conducted two five-year retrospective analyses of influenza-like illness (ILI), lower (LRTI) and upper (URTI) respiratory infections using the England Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care sentinel network database; a cross-sectional study reporting incident rate ratio (IRR) from a negative binomial model and a retrospective cohort study, using a shared gamma frailty survival model, reporting hazard ratios (HR). We reported the following household characteristics: children < 5 years old, each extra household member, gender, ethnicity (reference white), chronic disease, pregnancy, and rurality.ResultsThe IRR where there was a child < 5 years were 1·62 (1·38–1·89, p < 0·0001), 2·40 (2.04–2.83, p < 0·0001) and 4·46 (3.79–5.255, p < 0·0001) for ILI, LRTI and URTI respectively. IRR also increased with household size, rurality and presentations and by female gender, compared to male. Household incidence of URTI and LRTI changed little between years whereas influenza did and were greater in years with lower vaccine effectiveness.The HR where there was a child < 5 years were 2·34 (95%CI 1·88–2·90, p < 0·0001), 2·97 (95%CI 2·76–3·2, p < 0·0001) and 10·32 (95%CI 10.04–10.62, p < 0·0001) for ILI, LRTI and URTI respectively. HR were increased with female gender, rurality, and increasing household size.ConclusionsPatterns of household incidence can be measured from routine data and may provide insights for the modelling of disease transmission and public health policy.

Are there socio-economic inequalities in utilization of predictive biomarker tests and biological and precision therapies for cancer? A systematic review and meta-analysis

BackgroundNovel biological and precision therapies and their associated predictive biomarker tests offer opportunities for increased tumor response, reduced adverse effects, and improved survival. This systematic review determined if there are socio-economic inequalities in utilization of predictive biomarker tests and/or biological and precision cancer therapies.MethodsMEDLINE, Embase, Scopus, CINAHL, Web of Science, PubMed, and PsycINFO were searched for peer-reviewed studies, published in English between January 1998 and December 2019. Observational studies reporting utilization data for predictive biomarker tests and/or cancer biological and precision therapies by a measure of socio-economic status (SES) were eligible. Data was extracted from eligible studies. A modified ISPOR checklist for retrospective database studies was used to assess study quality. Meta-analyses were undertaken using a random-effects model, with sub-group analyses by cancer site and drug class. Unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed for each study. Pooled utilization ORs for low versus high socio-economic groups were calculated for test and therapy receipt.ResultsAmong 10,722 citations screened, 62 papers (58 studies; 8 test utilization studies, 37 therapy utilization studies, 3 studies on testing and therapy, 10 studies without denominator populations or which only reported mean socio-economic status) met the inclusion criteria. Studies reported on 7 cancers, 5 predictive biomarkers tests, and 11 biological and precision therapies. Thirty-eight studies (including 1,036,125 patients) were eligible for inclusion in meta-analyses. Low socio-economic status was associated with modestly lower predictive biomarker test utilization (OR 0.86, 95% CI 0.71–1.05; 10 studies) and significantly lower biological and precision therapy utilization (OR 0.83, 95% CI 0.75–0.91; 30 studies). Associations with therapy utilization were stronger in lung cancer (OR 0.71, 95% CI 0.51–1.00; 6 studies), than breast cancer (OR 0.93, 95% CI 0.78–1.10; 8 studies). The mean study quality score was 6.9/10.ConclusionsThese novel results indicate that there are socio-economic inequalities in predictive biomarker tests and biological and precision therapy utilization. This requires further investigation to prevent differences in outcomes due to inequalities in treatment with biological and precision therapies.

Minimum volume standards in day surgery: a systematic review

BackgroundThe aim was to find out if and for what indications are minimum volume standards (MVS) applied in the day surgery setting and whether the application of MVS improves patient relevant outcomes.MethodsWe conducted a comprehensive systematic literature search in seven databases on July 12th, 2019. Concerning effectiveness and safety, the data retrieved from the selected studies were systematically extracted into data-extraction tables. Two independent researchers (MS, CS) systematically assessed the quality of evidence using the quality assessment tool for individual studies of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) called Task Force Checklist for Quality Assessment of Retrospective Database Studies. No instances of disagreement occurred. No further data processing was applied.ResultsThe systematic literature search, together with hand search, yielded 595 hits. No prospective or controlled studies were found. Data from eight retrospective studies were used in the analysis of clinical effectiveness and safety on seven indications: anterior cruciate ligament reconstruction, cataract surgery, meniscectomy, thyroidectomy, primary hip arthroscopy, open carpal tunnel release, and rotator cuff repair. All interventions (except for carpal tunnel release and thyroidectomy) confirmed a volume-outcome relationship (VOR) with relation to surgeon/hospital volume, however, none established MVS for the respective interventions. Safety related data were reported without its relationship to surgeon/hospital volume.ConclusionsThis present paper provides some evidence in favor of the VOR, however, it based on low quality retrospective data-analyses. The present results cannot offer any clear-cut MVS thresholds for the day surgery setting and so the simple transition from inpatient results (that support MVS) to the day surgery setting is questionable. Further quality assuring policy approaches should be considered.