Representative Cohort Of Patients Research Articles

Cost-Effectiveness Analysis of Alirocumab in High Cardiovascular-Risk Patients in Italy

OBJECTIVE: Dyslipidemia, in particular elevated total and low-density lipoprotein cholesterol (LDL-C), results in atherosclerosis and increases the risk of cardiovascular (CV) events. Despite treatment with statins, many patients fail to reduce their LDL-C enough to optimally minimize their risk. Novel therapy alirocumab, on top of background statin therapy, resulted efficacious in lowering CV risk by reducing LDL-C levels. Aim of the present paper is to evaluate the cost-effectiveness of alirocumab in high cardiovascular-risk patients in ItalyMETHODS: A 1-year cycles Markov model was developed to evaluate the cost-effectiveness of statins at maximum dose tolerated plus ezetimibe (MDTS+E) with or without alirocumab. Target population consisted of patients with high baseline risk of CV events. Patients entered the model in stable disease and could experience a non- fatal CV event (acute coronary syndrome, elective revascularization or ischemic stroke) or die. Results from the ODYSSEY trial were used to evaluate CV risk reduction due to alirocumab add-on. Pharmaceutical, CV events, and LDL-C levels’ detection costs are considered in the analysis from the perspective of Italian National Health Service.RESULTS: Simulated cohort was 75 years old on average, 66% male, 42% diabetes mellitus and baseline LDL-C level equal to 121mg/dl. Furthermore, 96% of subjects were hospitalized in the last 12 months. Alirocumab used as an add-on to MDTS+E was more costly (€ 45,358 vs € 13,208) but more effective (8.01LY vs 6.33LY) than MDTS+E, leading to an incremental cost effectiveness ratio of € 19,158 per LY. At a willingness to pay threshold of € 30,000 per LY, alirocumab had 96% probability to be cost effective vs. MDTS+E alone. Results were relatively more favorable in the patient subset with recent CV event (<12 months from index).CONCLUSION: The results indicate that alirocumab in addition to MDTS+E is cost-effective versus MDTS+E alone in a representative cohort of high CV risk patients in Italy.

Perineural invasion as a risk factor for locoregional recurrence of invasive breast cancer

Perineural invasion (PNI) is a pathologic finding observed across a spectrum of solid tumors, typically with adverse prognostic implications. Little is known about how the presence of PNI influences locoregional recurrence (LRR) among breast cancers. We evaluated the association between PNI and LRR among an unselected, broadly representative cohort of breast cancer patients, and among a propensity-score matched cohort. We ascertained breast cancer patients seen at our institution from 2008 to 2019 for whom PNI status and salient clinicopathologic features were available. Fine-Gray regression models were constructed to evaluate the association between PNI and LRR, accounting for age, tumor size, nodal involvement, estrogen receptor (ER), progesterone receptor (PR), HER2 status, histologic tumor grade, presence of lymphovascular invasion (LVI), and receipt of chemotherapy and/or radiation. Analyses were then refined by comparing PNI-positive patients to a PNI-negative cohort defined by propensity score matching. Among 8864 invasive breast cancers, 1384 (15.6%) were noted to harbor PNI. At a median follow-up of 6.3 years, 428 locoregional recurrence events were observed yielding a 7-year LRR of 7.1% (95% CI 5.5–9.1) for those with PNI and 4.7% (95% CI 4.2–5.3; p = 0.01) for those without. On univariate analysis throughout the entire cohort, presence of PNI was significantly associated with an increased risk of LRR (HR 1.39, 95% CI 1.08–1.78, p < 0.01). Accounting for differences in salient clinicopathologic and treatment parameters by multivariable Fine-Gray regression modeling, the association between PNI and LRR was potentiated (HR 1.57, 95% CI 1.2–2.07, p = 0.001). We further conducted propensity score matching to balance clinicopathologic parameters and treatments between the two groups (PNI vs not), again showing a similar significant association between PNI and LRR (HR 1.46, 95% CI 1.03–2.08, p = 0.034). PNI is significantly associated with LRR following the definitive treatment of invasive breast cancer. The excess risk conferred by PNI is similar in magnitude to that observed with LVI, or by ER/PR negativity. Breast cancer prognostication and therapeutic decision-making should consider the presence of PNI among other salient risk factors. Larger studies among more uniform breast cancer presentations may elucidate the extent to which these findings apply across breast cancer subtypes and stages.

Use of incisional preventive negative pressure wound therapy in open incisional hernia repair: Who benefits?

Complex surgery of abdominal wall hernia continues to bear the major concern of wound healing disorders. Technical modifications have not been able to sufficiently prevent wound healing impairments or infections, even in clean elective cases, especially when dealing with large-scale hernia defects. Incisional negative pressure wound therapy (iNPWT) in its intentional use as a preventive tool has recently found its way from theoretical and experimental advantages to the clinical routine. Different indications have been defined but evidence is lacking. We performed a retrospective analysis (1/2014-5/2019) of all ventral hernia repairs (n=386) done in our institution as open sublay mesh reinforcement, partially requiring component separation (CS), receiving iNPWT in selected cases based on single surgeon experience. Pre- and perioperative data included patient and hernia characteristics as well as the employed mesh sizes. Postoperative follow-up (median 38.5months [interquartile range: 23.4, 53.3]) extended beyond patient dismissal and included the rate of re-admission due to wound healing disorders. The primary outcome was the incidence of surgical site occurrences (SSO). Secondary endpoints included wound-related readmissions, reoperations and recurrences. Patients were matched based on propensity scores in a 1:1 ratio. Propensity scores were calculated based on five preoperative variables, including sex, body-mass-index, American Society of Anesthesiology classification, recurrent hernia repair and operation technique, to identify significant parameters. The rate of SSO was 12% (n=46) for all operated cases, and the rate of surgical site infection (SSI) was 8.8% (n=34). In the subgroup of CS (n=40), the rate increased to 15% (n=6). The usage of iNPWT (n=54) led to an in-hospital SSO rate of 14.8% (n=8) but increased to 33.3% (n=18) when including the re-admission rate. The SSI rate for the iNPWT cohort was 14.8% (n=8) with a consecutive need for reoperation (Clavien-Dindo IIIb) in 87.5% (n=7). In the matched-pair analysis, the hernia-size and mesh-size were the main risk factors for SSO. The use of iNPWT significantly reduced this statistical effect (p=0.405). In a large and representative patient cohort, we were able to demonstrate that the advantage of iNPWT used after complex abdominal wall repair does not come first hand. Especially in the follow-up, we found a relevant increase in wound healing problems after dismissal. To proof the benefit of iNPWT in these heterogeneous patients, we could identify hernia size and mesh size as individual risk factors that were nihilated by the use of iNPWT. We found it to be favourable to use iNPWT when mesh-size exceeded 450 cm2 .

Outcomes of COVID-19 in Patients With Cancer: Report From the National COVID Cohort Collaborative (N3C).

Variation in risk of adverse clinical outcomes in patients with cancer and COVID-19 has been reported from relatively small cohorts. The NCATS' National COVID Cohort Collaborative (N3C) is a centralized data resource representing the largest multicenter cohort of COVID-19 cases and controls nationwide. We aimed to construct and characterize the cancer cohort within N3C and identify risk factors for all-cause mortality from COVID-19. We used 4,382,085 patients from 50 US medical centers to construct a cohort of patients with cancer. We restricted analyses to adults ≥ 18 years old with a COVID-19-positive or COVID-19-negative diagnosis between January 1, 2020, and March 25, 2021. We followed N3C selection of an index encounter per patient for analyses. All analyses were performed in the N3C Data Enclave Palantir platform. A total of 398,579 adult patients with cancer were identified from the N3C cohort; 63,413 (15.9%) were COVID-19-positive. Most common represented cancers were skin (13.8%), breast (13.7%), prostate (10.6%), hematologic (10.5%), and GI cancers (10%). COVID-19 positivity was significantly associated with increased risk of all-cause mortality (hazard ratio, 1.20; 95% CI, 1.15 to 1.24). Among COVID-19-positive patients, age ≥ 65 years, male gender, Southern or Western US residence, an adjusted Charlson Comorbidity Index score ≥ 4, hematologic malignancy, multitumor sites, and recent cytotoxic therapy were associated with increased risk of all-cause mortality. Patients who received recent immunotherapies or targeted therapies did not have higher risk of overall mortality. Using N3C, we assembled the largest nationally representative cohort of patients with cancer and COVID-19 to date. We identified demographic and clinical factors associated with increased all-cause mortality in patients with cancer. Full characterization of the cohort will provide further insights into the effects of COVID-19 on cancer outcomes and the ability to continue specific cancer treatments.

The prognostic value of galactosylceramide-sulfotransferase (Gal3ST1) in human renal cell carcinoma

Renal cell carcinoma (RCC) is the deadliest primary genitourinary malignancy typically associated with asymptomatic initial presentation and poorly predictable survival. Next to established risk factors, tumor microenvironment may alter metastatic capacity and immune landscape. Due to their high concentrations, sulfoglycolipids (sulfatides) were among the first well-described antigens in RCC that are associated with worse prognosis. As sulfatide detection in routine diagnostics is not possible, we aimed to test the prognostic value of its protein counterpart, sulfatide-producing enzyme Gal3ST1. We performed retrospective long-term follow up analysis of Gal3ST1 expression as prognostic risk factor in a representative RCC patient cohort. We observed differentially regulated Gal3ST1 expression in all RCC types, being significantly more associated with clear cell RCC than to chromophobe RCC (p = 0.001). Surprisingly, in contrast to published observations from in vitro models, we could not confirm an association between Gal3ST1 expression and a malignant clinical behaviour of the RCC. In our cohort, Gal3ST1 did not significantly influence progression-free survival (Hazard Ratio (HR): 1.7 95% CI (0.6–4.9), p = 0.327). Particularly after adjusting for histology, T-stage, N-status and M-status at baseline, we observed no independent prognostic effect (HR = 1.0 95% CI (0.3–3.3), p = 0.96). The analysis of Gal3ST1 mRNA expression in a TCGA dataset supported the results of our cohort. Thus, Gal3ST1 might help to differentiate between chromophobe RCC and other frequent RCC entities but—despite previously published data from cell culture models—does not qualify as a prognostic marker for RCC. Further investigation of regulatory mechanisms of sulfatide metabolism in human RCC microenvironment is necessary to understand the role of this quantitatively prominent glycosphingolipid in RCC progression.

Epigenetic landscape in blood leukocytes following ketosis and weight loss induced by a very low calorie ketogenic diet (VLCKD) in patients with obesity

The molecular mechanisms underlying the potential health benefits of a ketogenic diet are unknown and could be mediated by epigenetic mechanisms. To identify the changes in the obesity-related methylome that are mediated by the induced weight loss or are dependent on ketosis in subjects with obesity underwent a very-low calorie ketogenic diet (VLCKD). Twenty-one patients with obesity (n=12 women, 47.9±1.02yr, 33.0±0.2kg/m2) after 6 months on a VLCKD and 12 normal weight volunteers (n=6 women, 50.3±6.2yrs, 22.7±1.5kg/m2) were studied. Data from the Infinium MethylationEPIC BeadChip methylomes of blood leukocytes were obtained at time points of ketotic phases (basal, maximum ketosis, and out of ketosis) during VLCKD (n=10) and at baseline in volunteers (n=12). Results were further validated by pyrosequencing in representative cohort of patients on a VLCKD (n=18) and correlated with gene expression. After weight reduction by VLCKD, differences were found at 988 CpG sites (786 unique genes). The VLCKD altered methylation levels in patients with obesity had high resemblance with those from normal weight volunteers and was concomitant with a downregulation of DNA methyltransferases (DNMT)1, 3a and 3b. Most of the encoded genes were involved in metabolic processes, protein metabolism, and muscle, organ, and skeletal system development. Novel genes representing the top scoring associated events were identified, including ZNF331, FGFRL1 (VLCKD-induced weight loss) and CBFA2T3, C3orf38, JSRP1, and LRFN4 (VLCKD-induced ketosis). Interestingly, ZNF331 and FGFRL1 were validated in an independent cohort and inversely correlated with gene expression. The beneficial effects of VLCKD therapy on obesity involve a methylome more suggestive of normal weight that could be mainly mediated by the VLCKD-induced ketosis rather than weight loss.

Evaluation of Racial/Ethnic Differences in Treatment and Mortality Among Women With Triple-Negative Breast Cancer

To our knowledge, there is no consensus regarding differences in treatment and mortality between non-Hispanic African American and non-Hispanic White women with triple-negative breast cancer (TNBC). Little is known about whether racial disparities vary by sociodemographic, clinical, and neighborhood factors. To examine the differences in clinical treatment and outcomes between African American and White women in a nationally representative cohort of patients with TNBC and further examine the contributions of sociodemographic, clinical, and neighborhood factors to TNBC outcome disparities. This population-based, retrospective cohort study included 23 123 women who received a diagnosis of nonmetastatic TNBC between January 1, 2010, and December 31, 2015, followed up through December 31, 2016, and identified from the Surveillance, Epidemiology, and End Results data set. The study was conducted from July 2019 to November 2020. The analyses were performed from July 2019 to June 2020. Race and ethnicity, including non-Hispanic African American and non-Hispanic White race. Using logistic regression analysis and competing risk regression analysis, we estimated odds ratios (ORs) of receipt of treatment and hazard ratios (HRs) of breast cancer mortality in African American patients compared with White patients. Of 23 213 participants, 5881 (25.3%) were African American women and 17 332 (74.7%) were White women. Compared with White patients, African American patients had lower odds of receiving surgery (OR, 0.69; 95% CI, 0.60-0.79) and chemotherapy (OR, 0.89; 95% CI, 0.81-0.99) after adjustment for sociodemographic, clinicopathologic, and county-level factors. During a 43-month follow-up, 3276 patients (14.2%) died of breast cancer. The HR of breast cancer mortality was 1.28 (95% CI, 1.18-1.38) for African American individuals after adjustment for sociodemographic and county-level factors. Further adjustment for clinicopathological and treatment factors reduced the HR to 1.16 (95% CI, 1.06-1.25). This association was observed in patients living in socioeconomically less deprived counties (HR, 1.26; 95% CI, 1.14-1.39), urban patients (HR, 1.21; 95% CI, 1.11-1.32), patients having stage II (HR, 1.19; 95% CI, 1.02-1.39) or III (HR, 1.15; 95% CI, 1.01-1.31) tumors that were treated with chemotherapy, and patients younger than 65 years (HR, 1.24; 95% CI, 1.12-1.37). In this retrospective cohort study, African American women with nonmetastatic TNBC had a significantly higher risk of breast cancer mortality compared with their White counterparts, which was partially explained by their disparities in receipt of surgery and chemotherapy.

Gene Expression-Based Diagnosis of Infections in Critically Ill Patients-Prospective Validation of the SepsisMetaScore in a Longitudinal Severe Trauma Cohort.

Early diagnosis of infections is pivotal in critically ill patients. Innovative gene expression-based approaches promise to deliver precise, fast, and clinically practicable diagnostic tools to bedside. This study aimed to validate the SepsisMetaScore, an 11-gene signature previously reported by our study group, in a representative longitudinal cohort of trauma patients. Prospective observational cohort study. Surgical ICUs of the University Medical Center Goettingen, Germany. Critically ill patients with severe traumatic injuries. None. Paired box gene (PAXgene) RNA blood tubes were drawn at predefined time points over the course of disease. The performance of the SepsisMetaScore was tested using targeted polymerase chain reaction and compared with Procalcitonin using area under the receiver operating characteristics analyses. The SepsisMetaScore showed significant differences between infected and noninfected patients (n = 52). It was able to accurately discriminate infectious from noninfectious acute inflammation with an area under the receiver operating characteristics of 0.92 (95% CI, 0.85-0.99) and significantly outperformed Procalcitonin (area under the receiver operating characteristics curve = 0.53; 95% CI, 0.42-0.64) early in the course of infection (p = 0.014). We demonstrated the clinical utility for diagnosis of infections with higher accuracy using the SepsisMetaScore compared with Procalcitonin in a prospective cohort of severe trauma patients. Future studies should assess whether the SepsisMetaScore may substantially improve clinical practice by accurate differentiation of infections from sterile inflammation and identification of patients at risk for sepsis. Our results support further investigation of the SepsisMetaScore for the development of tailored precision treatment of critically ill patients.

Protocol for the UK cohort study to investigate the prevention of parastomal hernia (the CIPHER study).

Abdominal surgery sometimes necessitates the creation of a stoma, which can cause future complications including parastomal hernia (PSH), an incisional hernia adjacent to and related to the stoma. PSH affects approximately 40% of patients within 2years of stoma formation. Complications of PSH reduce a patient's quality of life and can be severe (e.g. bowel obstruction). PSHs are difficult to manage and can recur after surgical repair. Therefore, it is very important to prevent a PSH. Surgeons create stomas in different ways and both patient and surgical factors are believed to influence the development of PSH. The aim of the CIPHER study is to investigate the influence of different surgical techniques on the development of PSH. The UK cohort study to investigate the prevention of parastomal hernia (the CIPHER study) aims to recruit 4000 patients undergoing elective or expedited surgery with the intention of forming an ileostomy or colostomy, irrespective of the primary indication for the planned surgery. For each patient, surgeons will describe their methods of trephine formation, mesh reinforcement of the stoma trephine, use of the stoma as a specimen extraction site and wound closure. The primary outcome will be incident PSH during follow-up, defined as symptoms of PSH (custom-designed questionnaire) and anatomical PSH, ascertained by independent reading of usual care CT scans. Secondary outcomes will include surgical site infection, the Comprehensive Complication Index, quality of life (EQ-5D-5L and SF-12), PSH repair and use of NHS resources. Results of the study will be submitted for publication in peer-reviewed journals. All publications relating to the results of CIPHER will use a corporate authorship, 'The CIPHER Study Investigators' with named writing committee members. The CIPHER study will be the first to investigate detailed surgical methods of stoma formation in a large, representative cohort of patients with a range of primary indications, both cancer and noncancer.

Variability of computed tomography angiography coverage of lung parenchyma in acute stroke

BackgroundComputed tomography angiography (CTA) of the head and neck during acute ischemic stroke (AIS) usually includes visualization of lung apices. The possibility to evaluate for pulmonary changes, e.g. peripheral ground-glass and consolidative opacities suggestive of coronavirus disease 2019 (COVID-19)–related pneumonia, depends on the area of the lung covered by CTA.MethodsWe performed an analysis of a real-world scenario assessing the variability of lung coverage on CTA in patients presenting with AIS to a comprehensive stroke center (CSC) or to one of eight primary stroke centers (PSC) within a teleradiological network covered by the comprehensive stroke center in 2019.ResultsOur final analysis included n = 940 CTA, and in n = 573 (61%) merely lung apices were covered. In 19/940 (2%) of patients no lung tissue was covered by CTA. CTA scanning protocols in the CSC began significantly more frequently at the level of the ascending aorta (CSC: n = 180 (38.2%), PSC: n = 127 (27.1%), p-value < 0.001) and the aortic arch (CSC: n = 140 (29.7%), PSC: n = 83 (17.7%), p-value < 0.001), and by this covered less frequently the lower lobes compared to CTA acquired in one of the PSC.ConclusionsIn our pre-COVID-19 pandemic representative stroke patient cohort, CTA for AIS covered most often only lung apices. In 37% of the patients CTA visualized at least parts of the lower lobes, the lingula or the middle lobe allowing for a more extensive assessment of the lungs.

Sex differences in health resource utilization, costs and mortality during hospitalization for infective endocarditis in the United States

BackgroundFew studies have assessed the association between sex and outcomes among patients with infective endocarditis. The aim of the study was to better understand the association between biologic sex, clinical outcomes and surgical treatment patterns among a contemporary cohort of patients admitted to hospital with infective endocarditis. MethodsWe used the National Inpatient Sample dataset from the Health Care Utilization Project to identify adult patients admitted for infective endocarditis between January and December 2016. We compared outcomes between men and women including inpatient hospital mortality, direct hospital costs, length of stay, and inpatient surgical treatment patterns. Multivariable analyses were performed with adjustment for age, socioeconomic status, and comorbidity burden. ResultsAmong 18,702 patients with infective endocarditis, there were 8730 (46.7%) women and 1753 (8.4%) in-hospital deaths. In multivariable analysis, female sex was associated with a trend toward lower in-hospital mortality (adjusted odds ratio (OR) 0.90; 95% confidence interval (CI) 0.80 to 1.01, p = 0.06). Additionally, female sex was associated with significantly shorter hospital length of stay (−0.5 days; 95% CI −0.88 to −0.12, p = 0.009) and lower hospital costs (−$3035; 95% CI −$4277 to −$1792; p < 0.001). Notably, women were less likely to undergo surgical intervention (adjusted OR 0.59; 95% CI 0.52 to 0.67, p < 0.001). ConclusionsIn a contemporary, nationally representative cohort of patients admitted for IE in the United States, there were sex-specific differences in management and in-hospital outcomes. Possible sex-based bias in treatment patterns and access to inpatient surgical intervention for infective endocarditis warrants further study.

Calcium scoring using virtual non-contrast images from a dual-layer spectral detector CT: comparison to true non-contrast data and evaluation of proportionality factor in a large patient collective

ObjectiveDetermination of coronary artery calcium scoring (CACS) in non-contrast computed tomography (CT) images has been shown to be an important prognostic factor in coronary artery disease (CAD). The objective of this study was to evaluate the accuracy of CACS from virtual non-contrast (VNC) imaging generated from spectral data in comparison to standard (true) non-contrast (TNC) imaging in a representative patient cohort with clinically approved software.MethodsOne hundred three patients referred to coronary CTA with suspicion of CAD were investigated on a dual-layer spectral detector CT (SDCT) scanner. CACS was calculated from both TNC and VNC images by software certified for medical use. Patients with a CACS of 0 were excluded from analysis.ResultsThe mean age of the study population was 61 ± 11 years with 48 male patients (67%). Inter-quartile range of clinical CACS was 22–282. Correlation of measured CACS from true- and VNC images was high (0.95); p < 0.001. The slope was 3.83, indicating an underestimation of VNC CACS compared to TNC CACS by that factor. Visual analysis of the Bland-Altman plot of CACS showed good accordance with both methods after correction of VNC CACS by the abovementioned factor.ConclusionsIn clinical diagnostics of CAD, the determination of CACS is feasible using VNC images generated from spectral data obtained on a dual-layer spectral detector CT. When multiplied by a correction factor, results were in good agreement with the standard technique. This could enable radiation dose reductions by obviating the need for native scans typically used for CACS.Key Points• Calcium scoring is feasible from contrast-enhanced CT images using a dual-layer spectral detector CT scanner.• When multiplied by a correction factor, calcium scoring from virtual non-contrast images shows good agreement with the standard technique.• Omitting native scans for calcium scoring could enable radiation dose reduction.

Association of the 2012 American Urological Association Vasectomy Guidelines with National Trends in Vasectomy Followup in the United States.

The American Urological Association Vasectomy Guidelines published in 2012 defined vasectomy success as either azoospermia or rare nonmotile sperm (≤100,000 nonmotile sperm/ml). We sought to characterize nationwide practice patterns surrounding vasectomy followup before and after publication of the guidelines. Data were collected using the MarketScan® database. We identified men 18 to 64 years old undergoing vasectomy between 2007 and 2015 with at least 12 months of followup to track post-vasectomy semen analysis claims. Demographic data including age, vasectomy provider type and regionality were also queried. We compared the likelihood of men obtaining multiple post-vasectomy semen analyses before vs after the guidelines release with multivariate logistic regression. Linear regression was used examine time to first post-vasectomy semen analysis association with observed post-vasectomy semen analysis frequency trends. We identified a total of 87,201 patients who underwent vasectomy between 2007 and 2015 and had at least 1 post-vasectomy semen analysis claim. Men undergoing vasectomy in the post-guideline years of 2013 to 2015 were at lower risk for requiring any repeat post-vasectomy semen analysis (OR 0.68, 95% CI 0.66-0.71) and less likely to have had ≥3 post-vasectomy semen analyses (OR 0.82, 95% CI 0.77-0.88) than those in the pre-guideline (2007 to 2012) cohort. Mean time to first post-vasectomy semen analysis was shorter in men who submitted multiple analyses (p <0.001). Within a nationally representative patient cohort, men required fewer repeat post-vasectomy semen analyses after publication of the 2012 guidelines. Further research on patient and provider characteristics affecting variations in vasectomy followup patterns and guideline adherence is needed.

Triple negative breast cancer in Bulgaria: epidemiological data and treatment patterns based on real world evidence and patient registries

Breast cancer is the most common oncologic disease among women worldwide. Survival rates vary significantly and depend on early diagnosis practice and access to treatment. Triple negative breast cancer (TNBC) accounts for 12–15% of all breast cancers. We performed a one-year real-life retrospective study on the patho-histological status and treatment of a representative cohort of patients with TNBC in Bulgaria. We collected anonymised data for TNBC patients from the electronic artificial intelligence platform Sqilline - Danny Platform. Demographic characteristics, data on biomarkers, TNM (Tumor, Nodule, Metastasis) stage, therapeutic regime, line and changes in treatment were chronologically analysed for all patients. The results were processed through descriptive statistics. For the observed period, Jan 2019–Dec 2019, 6880 breast cancer patients from eight major oncology hospitals were included in the database. The average age of the women was 60 y; 234 (3.4%) of them were diagnosed with TNBC; 10% had unknown TNM stage. The majority of the patients were assigned to chemotherapy (84%) of which 35% were on adjuvant. Most changes in the therapy were observed in the neo-adjuvant group).The results from this study provide evidence that the treatment patterns of TNBC, and changes in therapy are in compliance with international guidelines. We identified less patients with TNBC than the frequencies reported in international epidemiological studies. This might be attributed to lack of funding of necessary tests or insufficient data in patients record. The study confirms that dynamic patient registers are important for performing a real-world studies of treatment patterns.

PCV20 Cost-Effectiveness Analysis of Alirocumab in High Cardiovascular-Risk Patients in Italy

Dyslipidemia, in particular elevated total and low-density lipoprotein cholesterol (LDL-C), results in atherosclerosis and increases the risk of cardiovascular (CV) events. Despite treatment with statins, many patients fail to reduce their LDL-C enough to optimally minimize their risk. Aim of this study was to evaluate the cost-effectiveness of alirocumab on top of statins at maximum dose tolerated plus ezetimibe (MDTS+E). A 1-year cycles Markov model with lifetime model horizon, was developed. Target population consisted of patients with high baseline risk of CV events; specifically, patients with acute coronary syndrome, myocardial infarction or unstable angina. Baseline characteristics were obtained from a national primary care database analysis. Patients entered the model in stable disease and could experience a non- fatal CV event (acute coronary syndrome, elective revascularization or ischemic stroke) or die. Results from the ODYSSEY trial (for the LDL-C>100 mg/dl subgroup) were used to evaluate CV risk reduction due to alirocumab add-on. Only pharmaceutical, CV events, and LDL-C levels’ detection costs are considered in the analysis from the perspective of Italian National Health Service. According to national database analysis, simulated cohort was 75 years old on average, 66% male, 42% diabetes mellitus and baseline LDL-C level equal to 121 mg/dl. Alirocumab used as an add-on to MDTS+E was more costly (€45,294 vs €13,123 for MDTS+E) but more effective (8.01 LY vs 6.33 LY for MDTS+E) leading to an ICER of €19,171 per LY (95%CI €11,617 31,496). At a willingness to pay threshold of €30,000 per LY, alirocumab had 96% probability to be cost effective vs. MDTS+E alone. Results were relatively more favorable in the patient subset with recent CV event (<12 months from index). The results indicate that alirocumab in addition to MDTS+E is cost-effective versus MDTS+E alone in a representative cohort of high CV risk patients in Italy.

PRS29 Cost-Utility Analysis of Fixed Dose Combination (FDC) of Indacaterol Acetate (IND) and Mometasone Furoate (MF) As a Maintenance Treatment of Asthma in Patients not Adequately Controlled with Inhaled Corticosteroids and Inhaled Short Acting beta2-Agonists

To evaluate the cost-utility of IND/MF FDC low-high dose relative to low–high dose of MF or salmeterol/fluticasone (SF) in not adequately controlled asthma patients 12 years or older, from the Italian National Health Service (NHS) perspective. A two-state and four-week cycle Markov model was used to estimate lifetime clinical outcomes and costs. Patients entered the model in stable disease and could experience a non-fatal exacerbation event. The exacerbation rate is dependent upon the therapy a patient is receiving, as per the IND/MF clinical trials. The impact of each type of exacerbation is accounted by applying a utility decrement, obtained from literature, and a treatment cost. Utility values were obtained from the EQ-5D questionnaires in the IND/MF clinical trials. Lifetime costs considered in the analysis were drugs and exacerbation management. Probabilistic sensitivity analyses were carried out, with the aim of evaluating impact of uncertainty around model assumptions. IND/MF-low dose is associated with higher quality of life (+0.533 QALY) than MF-low dose, with an incremental cost of €1,900.09. The incremental cost-utility ratio (ICUR) results of €3,565 per QALY. IND/MF-medium dose is associated with higher quality of life (+0.609 QALY) than MF-medium dose, with an incremental cost of €436.57. ICUR results of €717 per QALY. IND/MF-high dose is associated with higher quality of life (+0.350 QALY) than MF-high dose, with an incremental cost of -€1,297.80, which is a dominant treatment strategy. IND/MF-high dose is associated with higher quality of life (+0.102 QALY) than SF, with an incremental cost of -€1,719.01, which is also dominant. At a threshold of €5,000 per QALY, IND/MF has nearly 100% of probability of being cost-effective compared to all 3 doses of MF. The results indicate that IND/MF is cost-effective among the considered comparisons in a representative cohort of asthma patients 12 years or older in Italy.

PRS33 Three YEARS Follow up of a Representative Cohort of COPD Patients in Bulgaria

At the end of 2015, 426 patients from Bulgaria were recruited by pneumologists across the country to participate in a prospective cohort study of Chronic Obstructive Pulmonary Disease (COPD) and were followed for 3 year period. Here we report data for patient status, pharmacotherapy changes, mortality, as well as costs. This is a prospective, multi-center, observational, randomized, representative, and comparative real-life study of previously diagnosed patients with COPD from 5 main regions - North-east Bulgaria [NEB], North-West Bulgaria [NWB], South-east Bulgaria [SEB]. South-west Bulgaria [SWB] including Sofia city. Patient characteristics, therapy costs and outcomes were analyzed and compared to results from 2016-2017. Statistics was done through MedCalc software version 14.8.1 At the end of year three, 406 patients remained in the study. Patients distribution according to severity of COPD are: GOLD A – 31 (7.38%); GOLD B – 145 (34.76%); GOLD C – 63 (15.24%); GOLD D – 161 (42.62%) for 2018, vs 30,149,65, and 182 in 2015, respectively. 22 patients had died, with 20 of them being in GOLD D. Median age was 66 years (65-68 years 95%CI) with 132 patients (31.36%) experiencing a change to pharmacotherapy compared to previous years, with 35 recorded instances of improvement and 44 instances of worsening of COPD symptoms. Average number of exacerbations was 2.10 (1.94-2.27 95%CI) with no significant change. Median monthly costs of pharmacotherapy were: 59.63 BGN paid by the NHIF (43.41-59.63 96%CI) and 13.08 per patient as co-pay. The cost of group C decreased due to deceased patients, cost in group A and B remain constant, and cost in group C increased. The main cost driver appears to be the severity and mortality of patients with insignificant changes in other health care resources used and significant changes in pharmacotherapy.

PRS15 Cost-Utility Analysis of Fixed Dose Combination (FDC) of Indacaterol Acetate (IND) Glycopyrronium Bromide (GLY) and Mometasone Furoate (MF) As a Maintenance Treatment in Adult Asthma Patients not Adequately Controlled with a Maintenance Combination of a long-Acting beta2-Agonist and a High Dose of an Inhaled Corticosteroid who Experienced One or More Asthma Exacerbations in the Previous Year

To evaluate the cost-utility of FDC of IND/GLY/MF relative to a combination of salmeterol/fluticasone (SF) and tiotropium (Tio) or SF or IND/MF in adult asthma patients, from the Italian Health Service (NHS) perspective. A two-state and four-week cycle Markov model was used to estimate lifetime clinical outcomes and costs. Patients entered the model in stable disease and could experience a non-fatal exacerbation event. The exacerbation rate is dependent upon the therapy a patient is receiving, as per the IND/GLY/MF clinical trials. The impact of each type of exacerbation is accounted by applying a utility decrement, obtained from literature, and a treatment cost. Utility values were obtained from the EQ-5D questionnaires in the IND/GLY/MF clinical trials. Lifetime costs considered in the analysis were drugs and exacerbation management. Probabilistic sensitivity analyses were carried out, with the aim of evaluating impact of uncertainty in input parameters. IND/GLY/MF is associated with higher quality of life (+0.254 QALY) than SF+Tio, with an incremental cost of -€3,213.90. The incremental cost-utility ratio (ICUR) indicates dominance. At a threshold of €5,000 per QALY, IND/GLY/MF has nearly 100% probability of being cost-effective. IND/GLY/MF is associated with higher quality of life (+0.214 QALY) than SF, with an incremental cost of €2,547.76. ICUR results in €11,897 per QALY. At a threshold of €20,000 per QALY, IND/GLY/MF has nearly 100% probability of being cost-effective. IND/GLY/MF is associated with higher quality of life (+0.337 QALY) than IND/MF, with an incremental cost of €4,745.91. ICUR results of €14,088. At a threshold of €20,000 per QALY, IND/GLY/MF has nearly 100% probability of being cost-effective. The results indicate that IND/GLY/MF is cost-effective among the considered comparisons in a representative cohort of adult asthma patients in Italy.

Abstract 16496: Longitudinal Outcomes After Implantation of a Subcutaneous or Transvenous Implantable Cardioverter Defibrillator in Older Patients: A Report From the National Cardiovascular Data Registry

Introduction: The subcutaneous (S-) implantable cardioverter defibrillator (ICD) is an alternative to the transvenous (TV-) ICD that is increasingly implanted in younger patients. However, data on the safety and effectiveness of the S-ICD in older patients are lacking. Methods: We compared S-ICD and single chamber TV-ICD implants in Medicare beneficiaries (≥65yrs) using National Cardiovascular Data Registry ICD Registry data from 9/28/2012 through 12/31/2017. We excluded patients with prior pacemaker or ICD, an indication for pacing or resynchronization, and those undergoing implant in an acute setting. Mortality status was determined using the Medicare master summary beneficiary file. Cox regression analyses with overlap weights were used to compare all-cause mortality. Mean cumulative counts of all-cause readmissions were compared among for Fee for Service beneficiaries. Results: A total of 23,717 patients met inclusion criteria [mean age 72.7±5.8 years, 29% female, 69% ischemic heart disease, 33% atrial arrhythmias, 49% NYHA II, 31.7% NYHA III, ejection fraction (EF) 28±9%, 3% dialysis dependent, 20% with prior ventricular tachycardia]. Compared to TV-ICD patients (n=22,264), S-ICD patients (n=1,453, 6% overall) were more often male, black, diabetic, dialysis dependent and were less likely to have atrial or ventricular arrhythmias or ischemic heart disease. There was no difference in age or EF between the 2 groups. In adjusted analyses, during a median follow-up of 2.3 years (IQR: 1.2 - 3.5), there was no difference between the 2 groups in all-cause mortality (HR 1.04, CI 0.91-1.17, Figure A ) or readmissions (based on overlap of confidence intervals, Figure B ). Conclusions: In a large representative cohort of older patients undergoing ICD implant, all-cause mortality and readmission were similar among S-ICD and TV-ICD recipients. These findings support use of the S-ICD for the prevention of sudden cardiac death in appropriately selected older patients.

Long term results of liver transplantation for alpha-1 antitrypsin deficiency

IntroductionLiver transplantation (LT) is the therapeutic option for end-stage liver disease associated with alpha1 antitrypsin (A1AT) deficiency. The aim of the present retrospective study was to report on long-term outcomes following LT for A1AT deficiency. MethodsThe medical records of 90 pediatric and adult patients transplanted between 1982 and 2017 in France and Geneva (Switzerland) were reviewed. ResultsThe study population consisted of 32 adults and 58 children; median age at transplant was 13.0 years (range: 0.2–65.1), and 65 were male (72.2%). Eighty-two patients (94.8% of children and 84.4% of adults) had the PI*ZZ genotype/phenotype and eight patients (8.9%) had the Pi*SZ genotype/phenotype. Eighty-four patients (93.3%) were transplanted for end-stage liver disease and six (all Pi*ZZ adults) for HCC. Median follow-up after LT was 13.6 years (0.1–31.7). The overall cumulative patient survival rates post-transplant were 97.8% at 1 year, and 95.5%, 95.5%, 92.0%, 89.1% at 5, 10, 15, 20 years respectively. The overall cumulative graft survival rates were 92.2% at 1 year, and 89.9%, 89.9%, 84.4%, 81.5% at 5, 10, 15 and 20 years, respectively. ConclusionsIn a representative cohort of patients having presented with end-stage-liver disease or HCC secondary to A1AT, liver transplantation offered very good patient and graft survival rates.