Treatment Of Low-risk Patients Research Articles

The evolving landscape: magnetic resonance imaging in active surveillance for prostate cancer management

Since overdiagnosis and overtreatment pose significant risks in managing prostate cancer (PCa), active surveillance (AS) is the most common treatment in low-risk patients. However, there is no general agreement yet on the inclusion criteria and the required follow-up. Multiparametric magnetic resonance imaging (mpMRI) of the prostate was born as a useful device in these patients both in diagnosis and follow-up, and it is widely used in daily clinical practice. We reflect on the most current evidence described in the literature on the topic, its results, and our experience.

Management of polycythemia vera: A survey of treatment patterns in Italy.

Polycythemia vera (PV) is an acquired clonal hematopoietic stem cell disorder characterized by the overproduction of red blood cells. It has long been underlined that there are differences in treatment patterns in routine practice. Therapeutic strategies have also expanded, and in recent years the JAK1/JAK2 inhibitor ruxolitinib has emerged as a second-line therapeutic option in patients who are intolerant to or resistant to hydroxyurea. Determining the impact of changes on practice patterns is of interest, especially for aspects that lack detailed guidance for management. To gain insights into treatment patterns by clinicians treating patients with PV in Italy, we carried out a survey of 60 hematologists and transfusion specialists. The questions covered: treatment of low-risk patients, definition of significant leukocytosis, splenomegaly and excessive phlebotomies, resistance/intolerance to hydroxyurea, use of ruxolitinib, cytoreductive therapy, and vaccines. In general, the results of the survey indicate that there is a large heterogeneity in management of patients with PV across these areas. While helping to provide greater understanding of treatment patterns for patients with PV in Italy, our survey highlights the need for additional clinical studies to obtain more precise guidance for the routine care of patients with PV.

A Potential Four-Gene Signature and Nomogram for Predicting the Overall Survival of Papillary Thyroid Cancer.

Background Although the prognosis of papillary thyroid cancer (PTC) is relatively good, some patients experience recurrence or distant metastasis after thyroidectomy and progress to radioactive iodine refractory stage. Therefore, accurate prediction of clinical outlook can aid to screen out the minority of patients with poorer prognosis and avoid excessive treatment in low-risk patients. Methods The RNA-seq and clinical data of PTC patients was downloaded from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. Multivariate and Lasso Cox regression analyses were used to construct a prognostic nomogram to predict overall survival (OS). Thereafter, quantitative RT-PCR and Human Protein Atlas (HPA) database were employed to verify the expression of key genes. Results A four-gene risk score comprising ABI3BP, DPT, MRO, and TENM1 was exhibited strong prognostic value. Moreover, an integrated nomogram was established based on the risk score, age, AJCC (American Joint Commission on Cancer) stage, tumor size, extrathyroidal extension, and history of neoadjuvant treatment, which exhibited significantly better predictive performance than TNM stage system (P < 0.05). GSEA (Gene Set Enrichment Analysis) and GSVA (Gene Set Variation Analysis) revealed that the different tumor-associated hallmarks, biological processes, and pathways were substantially enriched in the poor-prognosis group. In addition, a ceRNA network was constructed by including the four genes (ABI3BP, DPT, MRO, and TENM1), 54 lncRNAs, and 10 miRNAs. Finally, both the relative mRNA and protein expression of ABI3BP, DPT, MRO, and TENM1 were validated. Conclusion The present study identified a four-gene risk signature and developed a novel nomogram, which could be regarded as a reliable prognostic model for PTC patients. The findings also revealed preliminary potential mechanisms that may influence the prognosis outcome. These results can be conducive to design personalized treatment and prognosis management in affected patients.

P326 SURGICAL VERSUS TRANSCATHETER AORTIC VALVE REPLACEMENT WITH NEWER GENERATION DEVICES IN REAL–WORLD PRACTICE: ONE–YEAR OUTCOMES FROM THE ITALIAN OBSERVANT STUDIES

Abstract Objective To compare the early and 1–year outcomes after transcatheter aortic valve replacement (TAVR) with new–generation devices over surgical replacement (SAVR) among patients with severe aortic stenosis (AS). Background TAVR is gaining acceptance for the treatment of lower risk patients with AS after several randomized and observational studies confirmed comparable early results to SAVR. On the other hand, clinical studies have shown that SAVR is still widely used in intermediate and high risk patients. There is need of data from large clinical registries to demonstrate the efficacy and safety of TAVR in the real–world setting, particularly after the introduction of new TAVR technology. Methods A total of 5706 AS patients who underwent SAVR and 2989 AS patients who underwent TAVR enrolled in the national, prospective OBSERVANT and OBSERVANT II studies, respectively in 2010–2012 and 2016–2018, were analyzed. Outcomes were adjusted using the propensity score matching. The primary outcomes of interest were all–cause mortality, major adverse cardiac and cerebrovascular events (MACCEs) and hospital readmission due to heart failure at 1–year. Secondary outcomes were major adverse events occurring during the index hospitalization. Results Among 1008 propensity score matched pairs, TAVR was associated with significantly lower 30–day mortality (1.8 vs. 3.5%, p = 0.020), stroke (0.8 vs. 2.3%, p = 0.005), acute kidney injury (0.6 vs. 8.2%, p &amp;lt; 0.001), infectious complications (3.8 vs. 6.5%, p = 0.006) and cardiogenic shock (1.4 vs. 5.1%, p &amp;lt; 0.001) compared to SAVR. Moderate–to–severe paravalvular regurgitation (5.9 vs. 2.0%, p &amp;lt; 0.001), major vascular complications requiring invasive treatment (2.2 vs. 0.1%, p &amp;lt; 0.001) and permanent pacemaker implantation (during the index hospitalization, 13.8 vs. 3.3%, p &amp;lt; 0.001) were more frequent after TAVR. At 1–year, TAVR was associated with lower risk of all–cause death (7.9 vs. 11.5%, p = 0.006), MACCE (12.0 vs. 15.8%, p = 0.011), readmission due to heart failure (10.8 vs. 15.9%, p &amp;lt; 0.001) and stroke (3.2 vs. 5.1%, p = 0.033) compared to SAVR. Conclusions In a real–world setting, patients with intermediate operative risk treated with newer generation TAVR devices had a low risk of major adverse events during the index–hospitalization and at 1–year follow–up. TAVR could become the treatment of choice for AS in the elderly provided that its durability is proved by long–term follow–up studies.

Outpatient versus inpatient treatment for acute pulmonary embolism.

Pulmonary embolism (PE) is a common life-threatening cardiovascular condition, with an incidence of 23 to 69 new cases per 100,000 people each year. For selected low-risk patients with acute PE, outpatient treatment might provide several advantages over traditional inpatient treatment, such as reduction of hospitalisations, substantial cost savings, and improvements in health-related quality of life. This is an update of an earlier Cochrane Review. To assess the effects of outpatient versus inpatient treatment in low-risk patients with acute PE. We used standard, extensive Cochrane search methods. The latest search date was 31 May 2021. We included randomised controlled trials (RCTs) of outpatient versus inpatient treatment of adults (aged 18 years and over) diagnosed with low-risk acute PE. We used standard Cochrane methods. Our primary outcomes were short- and long-term all-cause mortality. Secondary outcomes were bleeding, adverse effects, recurrence of PE, and patient satisfaction. We used GRADE to assess certainty of evidence for each outcome. We did not identify any new studies for this update. We included a total of two RCTs involving 453 participants. Both trials discharged participants randomised to the outpatient group within 36 hours of initial triage, and both followed participants for 90 days. One study compared the same treatment regimens in both outpatient and inpatient groups, and the other study used different treatment regimens. There was no clear difference in treatment effect for the outcomes of mortality at 30 days (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.01 to 7.98; 2 studies, 453 participants; low-certainty evidence), mortality at 90 days (RR 0.98, 95% CI 0.06 to 15.58; 2 studies, 451 participants; low-certainty evidence), major bleeding at 14 days (RR 4.91, 95% CI 0.24 to 101.57; 2 studies, 445 participants; low-certainty evidence) and at 90 days (RR 6.88, 95% CI 0.36 to 132.14; 2 studies, 445 participants; low-certainty evidence), minor bleeding (RR 1.08, 95% CI 0.07 to 16.79; 1 study, 106 participants; low-certainty evidence), recurrent PE within 90 days (RR 2.95, 95% CI 0.12 to 71.85; 2 studies, 445 participants; low-certainty evidence), and patient satisfaction (RR 0.97, 95% CI 0.90 to 1.04; 2 studies, 444 participants; moderate-certainty evidence). We downgraded the certainty of the evidence because the CIs were wide and included treatment effects in both directions, the sample sizes and numbers of events were small, and it was not possible to determine the effect of missing data or the presence of publication bias. The included studies did not assess PE-related mortality or adverse effects, such as haemodynamic instability, or adherence to treatment. Currently, only low-certainty evidence is available from two published randomised controlled trials on outpatient versus inpatient treatment in low-risk patients with acute PE. The studies did not provide evidence of any clear difference between the interventions in overall mortality, bleeding, or recurrence of PE.

Cost-effectiveness of home-based care of febrile neutropenia in children with cancer.

Home-based treatment of febrile neutropenia (FN) in children with cancer with oral or intravenous antibiotics is safe and effective. There are limited data on the economic impact of this model of care. We evaluated the cost-effectiveness of implementing an FN programme, incorporating home-based intravenous antibiotics for carefully selected patients, in a tertiary paediatric hospital. A decision analytic model was constructed to compare costs and outcomes of the home-based FN programme, with usual in-hospital treatment with intravenous antibiotics. The programme included a clinical decision rule to stratify patients by risk for severe infection and home-based eligibility criteria using disease, chemotherapy and patient-level factors. Health outcomes (quality of life) and probabilities of FN risk classification and home-based eligibility were based on prospectively collected data between 2017 and 2019. Patient-level costs were extracted from hospital administrative records. Cost-effectiveness was expressed as the incremental cost per quality-adjusted life year (QALY). The mean health care cost of home-based FN treatment in low-risk patients was Australian dollars (A$) 7765 per patient compared to A$20,396 for in-hospital treatment (mean difference A$12,632 [95% CI: 12,496-12,767]). Overall, the home-based FN programme was the dominant strategy, being more effective (0.0011 QALY [95% CI: 0.0011-0.0012]) and less costly. Results of the model were most sensitive to proportion of children eligible for home-based care programme. Compared to in-hospital FN care, the home-based FN programme is cost-effective, with savings arising from cheaper cost of caring for children at home. These savings could increase as more patients eligible for home-based care are included in the programme.

Device profile of the SAPIEN 3 transcatheter heart valve in low-risk patients with aortic stenosis: overview of its safety and efficacy

ABSTRACT Introduction Transcatheter aortic valve replacement (TAVR) has become a treatment of reference for patients with symptomatic severe aortic stenosis, and the balloon-expandable SAPIEN 3 and SAPIEN 3 Ultra transcatheter heart valve systems are two of the most broadly used worldwide. Lately, TAVR has progressively expanded toward the treatment of low-risk patients. Areas covered In this review we aimed to describe the main characteristics of the SAPIEN 3 valve, and to delineate the main clinical findings regarding the safety and efficacy associated with this THV system in low-risk patients undergoing TAVR. Expert opinion The approval of THV systems for use in low-risk patients has been a significant step forward in expanding current TAVR indications. Along with procedural refinement and growing operator experience, device iterations implemented in new-generation THV systems have played a vital role in the successful spread of TAVR. The availability of SAPIEN 3 represented an inflection point, as it allows for a predictable positioning and safer navigability while dramatically decreasing the rate of residual paravalvular leakage compared to previous balloon-expandable systems. However, some unresolved issues remain like the relatively high rates of conduction disturbances and the uncertainty about valve performance in the long-term. Future studies are warranted.

Projected Cost Savings of a Plasmic Score-Based Approach to Patients with Suspected Thrombotic Thrombocytopenic Purpura

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare but deadly thrombotic microangiopathy (TMA) that is caused by a severe acquired deficiency in the ADAMTS13 enzyme. The PLASMIC clinical scoring system categorizes patients with suspected TTP as being at low (score <5), intermediate (score = 5), or high (score >5) risk of severe ADAMTS13 deficiency. Here we have modeled the potential cost savings of a management approach that incorporates the PLASMIC score to defer testing and treatment for low risk patients and compared this approach to one in which ADAMTS13 testing requests require pre-approval by the blood transfusion service.Methods: We utilized an expanded dataset from the Harvard TMA Research Collaborative, a multi-institutional registry consisting of all consecutive patients with TMA and suspected TTP seen at three large academic medical centers between 2004-2015 (n=372). We leveraged existing differences in practice patterns between participating institutions to identify hospitals that do not regulate ADAMTS13 testing (Group A, N=278) and those that employed a restrictive strategy in which requests for ADAMTS13 testing were subject to approval by the blood transfusion service (Group B, N=94). A decision tree-based cost analysis algorithm was utilized to assess the potential cost savings from utilizing the PLASMIC score to defer ADAMTS13 testing in low-risk patients in Group A. We also compared total TTP-related costs (diagnosis and treatment) between Group A (both the unregulated and PLASMIC-based approach) and Group B.Results: Different practice patterns between Groups A and B provided a “natural experiment” to study the cost implications of different management approaches for TTP. In Group A, we noted a 435% increase in ADAMTS13 assays sent between 2004-2015 (test for trend p<0.0001), driven largely by patients without signs of TMA and/or with low-risk PLASMIC scores. This growth in testing was absent in Group B (test for trend p=0.98). The number of TTP cases per 100,000 admissions did not differ the two groups (p=0.19) and remained unchanged over time (p=0.67 and p=0.31 for Groups A and B, respectively). To assess the cost differences between management approaches, we generated a decision tree containing nodes with important clinical choices such as ADAMTS13 testing, expert consultation, and initiation of therapeutic plasma exchange (TPE). The tree excluded patients without thrombocytopenia or schistocytes at its first branch point. In projecting the number of ADAMTS13 tests through 2025, we found that Group A's TTP-related costs were significantly higher and would result in over $11 million in increased costs between 2004-2025 compared to Group B (Figure 1). Under a PLASMIC score-based approach, patients at Group A institutions with a low risk score would not receive upfront ADAMTS13 testing or downstream care for TTP and instead be closely observed while being worked up for alternative causes of TMA. Considering 2015, the latest year for which complete data are available, applying a PLASMIC-score based approach to the Group A institutions was projected to reduce TTP-related costs from $610,471 to $473,058 (23%) per 100,000 admissions (Table 1). By comparison, in 2015 Group B TTP-related costs were $152,000 per 100,000 admissions. Assuming current trends, a PLASMIC score-based strategy within Group A would result in over $3.2 million (23%) saved between 2004-2025 compared to the current unregulated approach, primarily due to decreased rates of testing, expert consultation, and TPE.Conclusions: Our data suggest that institutions with an unregulated approach to ADAMTS13 testing could potentially realize cost savings by implementing a strategy based on risk stratification of suspected TTP cases by PLASMIC score. In terms of normalized costs, a PLASMIC-score based strategy would be intermediate between an unregulated testing approach and one that employs live oversight of ADAMTS13 testing by the blood transfusion service. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

MO682TAILORING AI-BASED REFERRAL TO INTENSIFIED INTERVENTION PROGRAMS FOR PERITONITIS PREVENTION WITH COST-EFFECTIVENESS SIMULATION

Abstract Background and Aims Peritonitis is a common and potentially severe complication for peritoneal dialysis (PD) patients. It is associated with mortality and technique failure risk and contributes significantly to their healthcare cost. Despite several peritonitis prevention programs based on education and training have been implemented worldwide, it has been reported a large variability of efficacy across patients groups and healthcare settings. In order to avoid unnecessary treatment of low risk patients, healthcare prevention programs should be personalized based on accurate patients’ risk profiling, so that high risk patients may be addressed with intensified prevention programs. However, referral strategy (i.e. defining when risk is too much and deserves special attention) depends the availability, efficacy and cost of medical interventions. In this study, we demonstrate through a program implementation simulator, how different referral strategies to inform peritonitis prevention program among PD patients informed by AI-based risk stratification tools, produce different healthcare and health economics outcomes. In particular, the simulation considers a prevention program characterized by standard of care, which affects all patients as well as an intensive intervention for a subset of high-risk patients (e.g. special training or medical treatment). Method The Peritonitis Risk Score model was trained and validated among 9325 PD patients treated in FMC network (Model accuracy, AUC=0.86). The pharmaco-economic model simulation was performed considering a cohort of 22,900 adult PD patients, treated in Fresenius Medical Care dialysis network between January 1, 2011 and December 31, 2018, for which the Peritonitis Risk Score was computed at a given date. The occurrence of an acute peritonitis in the month after prediction has been registered. We simulated the program outcomes in terms of proportion of referrals to the intensified prevention program, false omission rate, peritonitis risk reduction, overall cost-savings, number needed to treat. We considered the following scenario based on previous cost-effectiveness analysis on peritonitis risk prevention: Results Given the action threshold selected, 5.3% of patients entered the intensified intervention program (PPV=9.5%); the false omission rate was 2.2%. Cost savings for the intensified healthcare where generated when the effect size of the intensified intervention exceeded 1.4 (figure 1A). For that effect size the number needed to treat for each prevented peritonitis was NNT=23.4. Overall, 162 peritonitis/month could be prevented in the whole network (peritonitis with no intervention=592; Peritonitis after intervention=430). When a less conservative threshold was selected, 12.2% of patients entered the intensified prevention program (PPV=7.3%), generating a false omission rate=1.9%. Cost savings were never generated (i.e. the intensified program needed investment to be sustained) but with the same effect size of 1.4 additional 24 peritonitis/months could be saved in the whole network (peritonitis with no intervention=592; Peritonitis after intervention=406). The number needed to treat for the intensified program was NTT=30.4 (figure 1B). Conclusion Cost-effectiveness simulating tool provides a rational evaluation framework for AI-based referral to peritonitis preventive programs. This tool can be easily adapted for any healthcare program based on patient risk score.

T Regulatory Cells in Relapsed/Refractory Chronic Lymphocytic Leukemia Treated with High Dose Methylprednisolone and Rituximab

Higher circulating T regulatory cell (Treg) numbers have been found in untreated patients with chronic lymphocytic leukemia (CLL) compared to healthy subjects and correlated with progressive disease as well as time to first treatment in low-risk patients [1]. Some agents can reduce Treg numbers in CLL patients, but there are no data on the prognostic role of Treg dynamics and patient outcome. We present data from the LT-CLL-001 study, in which the clinical benefit of dose-dense high dose methylprednisolone (HDMP) and rituximab (Rtx) combination in relapsed or refractory high-risk patients with CLL was evaluated [2]. During the study, the change of T regulatory cell frequencies was measured in relation to overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Twenty-nine CLL patients with clinically or biologically high-risk disease were included. Treg frequency was evaluated at screening, after three treatment courses, and at the end of therapy. Significant reduction of the median frequencies of Treg during treatment was observed: median (range) of Treg0-3 after three treatment courses was 2.14% (-1.84%- 9.42%), p &lt; 0.001 and median (range) of Treg0-6 was 1.01% (-2.95%- 8.35%, p = 0.004). Patients with deeper Treg reduction between screening and three treatment courses had significantly better PFS and OS (Table 1 &amp; 2). Our data for the first time show that HDMP and Rtx combination reduces Treg frequency in pretreated CLL patients. Early and deeper Treg reduction is an independent prognostic factor for longer PFS and OS. (ClinicalTrials.gov identifier: NCT005 58181).

Implementing a pharmacogenetic-driven algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics: protocol for a non-randomised clinical trial

IntroductionMinority populations in the USA are disproportionately affected by cardiovascular conditions. Reduced responsiveness to clopidogrel among carriers of CYP2C19 variants has been reported in patients with either coronary artery disease...

Adjuvant and neoadjuvant therapy for breast cancer.

Systemic therapies for operable breast cancer patients have improved outcomes and have thus become standard treatments. Recently, new molecular target drugs and regimens are being developed based on the predicted sensitivity for specific breast cancer histological types. Systemic therapy is selected according to recurrence risk, with the treatment for low-risk patients being de-escalated, while high-risk patients receive aggressive systemic treatment with an adequate dose and duration. Neoadjuvant systemic therapy has a different aim. The efficacy of systemic therapies, based on the sensitivities to drugs, is supported by improvements in the rate of breast-conserving therapy. The response to neoadjuvant systemic therapy is the most important factor for predicting outcomes and selecting the optimal adjuvant therapy. Novel biological markers unique to individual patients allow appropriate targeted therapy, which can achieve optimal efficacy.

Assessment of Utilization of Outpatient Based Treatment for Low Risk Patients with Pulmonary Embolism in Two Community Teaching Hospitals

OBJECTIVE: Several randomized controlled trials and meta-analysis has proven safety and efficacy of outpatient based treatment in appropriately selected low-risk patients with pulmonary embolism (PE). Despite the fact that outpatient treatment has been proven safe, prior studies have shown that it is not commonly practiced. Our current multi-center study focuses on identifying practices of outpatient versus inpatient treatment of low risk PE patients in two community hospitals between 2018-2019. METHODS: A retrospective chart review of the patients in two community hospitals with the principal discharge diagnosis of pulmonary embolism aged 18 years or older was conducted. The study period included February 2018 to February 2019. The high risk patients defined as simplified pulmonary embolism severity index (PESI) score of 1 or above were excluded from the study. Low risk patients were defined as with a simplified PESI score of 0. Criteria were established to determine the appropriateness of inpatient admission for low risk patients with PE. The group of low risk patients with thrombocytopenia (platelets less than 70,000/mm3), glomerular filtration rate (GFR) of less than 30 ml/ minute, international normalized ratio (INR) greater than 1.5, pregnancy, active bleeding as documented in the medical records, total bilirubin greater than 3.0 mg/dl, extreme obesity (weight greater than 150 kg), diagnosis of acute PE while on oral anticoagulation, requiring narcotics for chest pain, need for supplemental oxygen , poor social support or presence of concomitant extensive deep vein thrombosis were deemed appropriate for inpatient treatment. The patients without these baseline characteristics were considered appropriate for outpatient treatment. RESULTS: The cohort comprised of 442 patients in two community hospitals. Among these, 172 patients had a simplified PESI score of 1 or above and were excluded from the study. The remaining 270 patients had a simplified PESI score of 0 and were considered low risk. Based on the study criteria, 54% (145 patients out of 270) of the low risk patients were deemed appropriate for outpatient treatment. Out of these, only 16% (23 patients out of 145) were treated at home. The remaining 84% (122 patients out of 145) of the low risk PE patients considered safe for outpatient treatment were actually treated as inpatient. The mean length of hospital stay for this group of patients was 3 days. Anti-coagulation therapy for those treated on outpatient basis was novel oral anticoagulants in 79% (18 patients out of 23) and low molecular weight heparin or warfarin in 21% (5 patients out of 23). CONCLUSION: Our study demonstrates that majority of low risk PE patients deemed appropriate for outpatient based treatment are treated on inpatient basis. This study shows that there is a need to implement interventions to improve practices of outpatient management of appropriately selected low-risk PE patients. Disclosures No relevant conflicts of interest to declare.

412. Host Response Biomarkers Predict Clinical Failure in Patients with Staphylococcus aureus Bacteremia (SAB) Treated with Flucloxacillin (FLU) or Vancomycin (VAN)

BackgroundImbalance among innate mediators such as IL-1β, IL-10, and TNF-α portends poor outcomes of persistence and death in patients with SAB. Previous studies did not consider the role of antibiotic treatment in this important host–pathogen relationship. In this study of SAB, we determined cytokine signatures that correlate with the composite endpoint of clinical failure (bacteremia duration >4 days or 30-day mortality) in Australian patients treated with FLU or VAN.MethodsSera from 86 patients with SAB (24.4% MRSA) were obtained from a clinical study of patients treated with FLU or VAN. All of the patient samples were collected at clinical presentation (day 0 or day 1 of infection) and were treated with FLU or VAN throughout. Patients were classified into either clinical success (CS = 68) or clinical failure (CF = 18), defined as death or prolonged bacteremia >4 days. Patient demographic and infection characteristics were collected. A 10-multiplex TH1/TH2 cytokine analysis was performed using electrochemoluminescence with the Meso-Scale Discovery platform analyzed by Mann–Whitney U.ResultsPatients’ median values were significantly elevated and above the normal range in CF for IL-1β (P = 0.029), IL-10 (P = 0.018), TNF-α (P = 0.042), and IL-6 (P = 0.006) (figure). Epidural abscess source was associated with CF, but no other host or pathogen characteristics correlated to outcome. Patients infected with isolates with VAN MIC = 2 mg/L (by Etest and broth dilution) had lower concentrations of IL-1β and IL-10 (P = 1.5 mg/L. In ROC analysis, IL-1β, IL-10, TNF, and IL-6 were higher sensitivity and specificity predictors of CF (AUC 0.65–0.71; P = 0.05).ConclusionA suboptimal host immune response to SAB at presentation predicts adverse clinical outcomes. IL-10, TNF-α, and IL-6 serum concentrations appear to reflect immunopathology in patients with SAB. These predictive markers may be considered in therapeutic clinical decision-making, such as escalation of alternative therapies in high-risk patients and/or de-escalation treatment in low-risk patients. These data offer steps toward further refining therapeutic precision for patients with SAB beyond the standard clinical or microbiological metrics that are employed in current practice. Disclosures All authors: No reported disclosures.

Pulmonary Embolism

Pulmonary embolism (PE) is a life-threatening disease and the third most frequent cardiovascular cause of death after stroke and myocardial infarction. The annual incidence is increasing. The individual risk for PE-related complications and death increases with the number of comorbidities and severity of right ventricular dysfunction. Using clinical, laboratory and imaging parameters, patients with PE can be stratified to four risk classes (high, intermediate-high, intermediate-low and low risk). This risk stratification has concrete therapeutic consequences ranging from out-of-hospital treatment of low-risk patients to reperfusion treatment of (intermediate-) high-risk patients. For haemodynamically unstable patients, a treatment decision should preferable be made in interdisciplinary "Pulmonary Embolism Response Teams" (PERT). Being comparably efficient and due to a preferable safety profile compared to vitamin-K antagonists (VKAs), non-vitamin K-dependent oral anticoagulants (NOACs) are increasingly considered to be the treatment of choice for initial and prolonged anticoagulation of patients with pulmonary embolism. The use of low molecular weight heparins (LMWHs) is recommended for PE patients with cancer; however, recent studies indicate that treatment with factor Xa-inhibitors may be effective and safe (in patients without gastrointestinal cancer). Only prolonged anticoagulation (in reduced dosage) will ensure reduction of VTE recurrence and thus should be considered for all patients with unprovoked events.

Future Directions. Transcatheter Aortic Valve Implantation for Low-risk Patients: Inevitable Evolution or a Step Too Far?

Transcatheter aortic valve replacement has become the treatment of choice for inoperable and high-risk patients with symptomatic aortic stenosis, and is becoming more and more common as the first choice for intermediate-risk patients as well. The next step in this evolution would be the expansion of treatment indications to low-risk patients. Successful treatment of this patient population will require setting new standards in terms of clinical outcomes and cost effectiveness. In this review, we present the main challenges that need to be addressed before transcatheter aortic valve replacement can be applied as a standard treatment for low-risk patients.

Outpatient versus inpatient treatment for acute pulmonary embolism.

Pulmonary embolism (PE) is a common life-threatening cardiovascular condition, with an incidence of 23 to 69 new cases per 100,000 people each year. For selected low-risk patients with acute PE, outpatient treatment might provide several advantages over traditional inpatient treatment, such as reduction of hospitalisations, substantial cost savings, and improvements in health-related quality of life. This is an update of the review first published in 2014. To compare the efficacy and safety of outpatient versus inpatient treatment in low-risk patients with acute PE for the outcomes of all-cause and PE-related mortality; bleeding; adverse events such as haemodynamic instability; recurrence of PE; and patients' satisfaction. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers, to 26 March 2018. We also undertook reference checking to identify additional studies. We included randomised controlled trials of outpatient versus inpatient treatment of adults (aged 18 years and over) diagnosed with low-risk acute PE. Two review authors selected relevant trials, assessed methodological quality, and extracted and analysed data. We calculated effect estimates using risk ratio (RR) with 95% confidence intervals (CIs), or mean differences (MDs) with 95% CIs. We used standardised mean differences (SMDs) to combine trials that measured the same outcome but used different methods. We assessed the quality of the evidence using GRADE criteria. One new study was identified for this 2018 update, bringing the total number of included studies to two and the total number of participants to 451. Both trials discharged patients randomised to the outpatient group within 36 hours of initial triage and both followed participants for 90 days. One study compared the same treatment regimens in both outpatient and inpatient groups, and the other study used different treatment regimes. There was no clear difference in treatment effect for the outcomes of short-term mortality (30 days) (RR 0.33, 95% CI 0.01 to 7.98, P = 0.49; low-quality evidence), long-term mortality (90 days) (RR 0.98, 95% CI 0.06 to 15.58, P = 0.99, low-quality evidence), major bleeding at 14 days (RR 4.91, 95% CI 0.24 to 101.57, P = 0.30; low-quality evidence) and at 90 days (RR 6.88, 95% CI 0.36 to 132.14, P = 0.20; low-quality evidence), minor bleeding (RR 1.08, 95% CI 0.07 to 16.79; P = 0.96, low-quality evidence), recurrent PE within 90 days (RR 2.95, 95% CI 0.12 to 71.85, P = 0.51, low-quality evidence), and participant satisfaction (RR 0.97, 95% CI 0.90 to 1.04, P = 0.39; moderate-quality evidence). We downgraded the quality of the evidence because the CIs were wide and included treatment effects in both directions, the sample sizes and numbers of events were small, and because the effect of missing data and the absence of publication bias could not be verified. PE-related mortality, and adverse effects such as haemodynamic instability and compliance, were not assessed by the included studies. Currently, only low-quality evidence is available from two published randomised controlled trials on outpatient versus inpatient treatment in low-risk patients with acute PE. The studies did not provide evidence of any clear difference between the interventions in overall mortality, bleeding and recurrence of PE.

Future Therapy for Low-Risk Patients With Severe Aortic Stenosis—A Provider Survey

With the expansion of transcatheter aortic valve replacement in low-risk patients, we sought to explore current implanters' predictions on the future of this therapy by sending a survey to a sample of 8,261 healthcare professionals using Internet-based software. The survey contained six questions regarding physician specialty and experience, transcatheter aortic valve replacement age cutoff, optimal treatment for low-risk patients, transcatheter aortic valve replacement valve sequence, and transcatheter aortic valve replacement concerns. The majority, 29% percent, of all respondents felt that transcatheter aortic valve replacement will become the first-choice therapy for all patients, regardless of age and 70% felt that the optimal treatment would be transcatheter aortic valve replacement, with transcatheter aortic valve replacement valve-in-valve if the first valve degenerates. Regarding the sequence of transcatheter aortic valve replacement valves, 78% preferred the Edwards Sapien 3 valve (ES-3) as the first transcatheter aortic valve replacement valve followed by either a second ES-3 or Medtronic Evolut valve. Despite the high acceptance of transcatheter aortic valve replacement, many respondents (56%) felt that surgical aortic valve replacement might still remain the preferred treatment in low-risk patients due to an unknown durability of transcatheter aortic valve replacement valves. A majority of implanters see transcatheter aortic valve replacement followed by valve-in-valve transcatheter aortic valve replacement as the first-line therapy for low-risk patients with severe aortic stenosis, but long-term durability of transcatheter aortic valve replacement is an unanswered concern.

Benefits and Harms of Antihypertensive Treatment in Low-Risk Patients With Mild Hypertension

Evidence to support initiation of pharmacologic treatment in low-risk patients with mild hypertension is inconclusive, with previous trials underpowered to demonstrate benefit. Clinical guidelines across the world are contradictory. To examine whether antihypertensive treatment is associated with a low risk of mortality and cardiovascular disease (CVD) in low-risk patients with mild hypertension. In this longitudinal cohort study, data were extracted from the Clinical Practice Research Datalink, from January 1, 1998, through September 30, 2015, for patients aged 18 to 74 years who had mild hypertension (untreated blood pressure of 140/90-159/99 mm Hg) and no previous treatment. Anyone with a history of CVD or CVD risk factors was excluded. Patients exited the cohort if follow-up records became unavailable or they experienced an outcome of interest. Prescription of antihypertensive medication. Propensity scores for likelihood of treatment were constructed using a logistic regression model. Individuals treated within 12 months of diagnosis were matched to untreated patients by propensity score using the nearest-neighbor method. The rates of mortality, CVD, and adverse events among patients prescribed antihypertensive treatment at baseline, compared with those who were not prescribed such treatment, using Cox proportional hazards regression. A total of 19 143 treated patients (mean [SD] age, 54.7 [11.8] years; 10 705 [55.9%] women; 10 629 [55.5%] white) were matched to 19 143 similar untreated patients (mean [SD] age, 54.9 [12.2] years; 10 631 [55.5%] female; 10 654 [55.7%] white). During a median follow-up period of 5.8 years (interquartile range, 2.6-9.0 years), no evidence of an association was found between antihypertensive treatment and mortality (hazard ratio [HR], 1.02; 95% CI, 0.88-1.17) or between antihypertensive treatment and CVD (HR, 1.09; 95% CI, 0.95-1.25). Treatment was associated with an increased risk of adverse events, including hypotension (HR, 1.69; 95% CI, 1.30-2.20; number needed to harm at 10 years [NNH10], 41), syncope (HR, 1.28; 95% CI, 1.10-1.50; NNH10, 35), electrolyte abnormalities (HR, 1.72; 95% CI, 1.12-2.65; NNH10, 111), and acute kidney injury (HR, 1.37; 95% CI, 1.00-1.88; NNH10, 91). This prespecified analysis found no evidence to support guideline recommendations that encourage initiation of treatment in patients with low-risk mild hypertension. There was evidence of an increased risk of adverse events, which suggests that physicians should exercise caution when following guidelines that generalize findings from trials conducted in high-risk individuals to those at lower risk.

ACOG Committee Opinion No. 753: Assessment and Treatment of Pregnant Women With Suspected or Confirmed Influenza.

Pregnant and postpartum women are at high risk of serious complications of seasonal and pandemic influenza infection. Pregnancy itself is a high-risk condition, making the potential adverse effects of influenza particularly serious in pregnant women. If a pregnant woman has other underlying health conditions, the risk of adverse effects from influenza is even greater. Antiviral treatment is necessary for all pregnant women with suspected or confirmed influenza, regardless of vaccination status. Obstetrician-gynecologists and other obstetric care providers should promptly recognize the symptoms of influenza, adequately assess severity, and readily prescribe safe and effective antiviral therapy for pregnant women with suspected or confirmed influenza. Over-the-phone treatment for low-risk patients is preferred to help reduce the spread of disease among other pregnant patients in the office. Obstetrician-gynecologists and other obstetric care providers should treat pregnant women with suspected or confirmed influenza with antiviral medications presumptively based on clinical evaluation, regardless of vaccination status or laboratory test results. Pregnant women with suspected or confirmed influenza infection should receive antiviral treatment with oseltamivir or zanamivir based on the current resistance patterns. Treatment within 48 hours of the onset of symptoms is ideal but treatment should not be withheld if the ideal window is missed. Because of the high potential for morbidity and mortality for pregnant and postpartum patients, the Centers for Disease Control and Prevention advises that postexposure antiviral chemoprophylaxis can be considered for pregnant women and women who are up to 2 weeks postpartum (including after pregnancy loss) who have had close contact with infectious individuals.