Does the type of seizure influence heart rate variability changes?

OBJECTIVE: Heart rate variability (HRV), an index of the autonomic cardiac activity, is decreased in patients with epilepsy, and a low HRV is associated with a higher risk of sudden death. Generalized tonic-clonic seizures are one of the most consistent risk factors for SUDEP, but the influence (and relative risk) of each type of seizure on cardiac function is still unknown. Our objective was to assess the impact of the type of seizure (focal to bilateral tonic-clonic seizure - FBTCS - versus non-FBTCS) on periictal HRV, in a group of patients with refractory epilepsy and both types of seizures. METHODS: We performed a 48-hour Holter recording on 121 patients consecutively admitted to our Epilepsy Monitoring Unit. We only included patients with both FBTCS and non-FBTCS on the Holter recording and selected the first seizure of each type to analyze. To evaluate HRV parameters (AVNN, SDNN, RMSSD, pNN20, LF, HF, and LF/HF), we chose 5-min epochs pre- and postictally. RESULTS: We included 14 patients, with a median age of 36 (min-max, 16-55) years and 64% were female. Thirty-six percent had cardiovascular risk factors, but no previously known cardiac disease. In the preictal period, there were no statistically significant differences in HRV parameters, between FBTCS and non-FBTCS. In the postictal period, AVNN, RMSSD, pNN20, LF, and HF were significantly lower, and LF/HF and HR were significantly higher in FBTCS. From preictal to postictal periods, FBTCS elicited a statistically significant rise in HR and LF/HF, and a statistically significant fall in AVNN, RMSSD, pNN20, and HF. Non-FBTCS only caused statistically significant changes in HR (decrease) and AVNN (increase). SIGNIFICANCE/CONCLUSION: This work emphasizes the greater effect of FBTCS in autonomic cardiac function in patients with refractory epilepsy, compared to other types of seizures, with a significant reduction in vagal tonus, which may be associated with an increased risk of SUDEP.

Real-world treatment patterns and survival outcomes for advanced non-small cell lung cancer in the pre-immunotherapy era in Portugal: a retrospective analysis from the I-O Optimise initiative.

BACKGROUND: As part of the multinational I-O Optimise research initiative, this retrospective cohort study of patients with advanced non-small cell lung cancer (NSCLC) evaluated real-world treatment patterns and survival prior to immunotherapy reimbursement in Portugal. METHODS: This study utilized a database held by IPO-Porto, Portugal's largest oncology hospital. Adult patients diagnosed with stage IIIB or IV NSCLC from January 2012 to December 2016 at IPO-Porto, with follow-up to June 2017, were included. Treatment analyses were performed from 2015 onwards. Kaplan-Meier methods were used for overall survival (OS). Factors associated with OS and systemic anti-cancer therapy (SACT) treatment were assessed using multivariate statistical models. RESULTS: Of 1524 patients diagnosed with NSCLC at IPO-Porto, 1008 patients had advanced disease (stage IIIB: 10.1%, 154/1524, stage IV: 56.0%, 854/1524). For those with advanced disease, median age was 65 years (range: 21-92) and 75.6% (762/1008) were male. Median OS (interquartile range [IQR]) was 11.4 (5.2-26.9) months for stage IIIB and 6.3 (2.4-15.0) months for stage IV. Factors associated with decreased risk of death included female sex and epidermal growth factor receptor gene (EGFR)/anaplastic lymphoma kinase gene (ALK) mutations/rearrangements; factors associated with increased risk of death included older age and stage IV disease. Among patients diagnosed in 2015 or 2016, 75.8% (297/392) received ≥1 line of SACT. Platinum-based chemotherapy was the most common first-line therapy (non-squamous cell carcinoma [NSQ]: 72.9%; squamous cell carcinoma [SQ] 87.3%, 55/63; patients with EGFR/ALK mutations/rearrangements primarily received tyrosine kinase inhibitors). The likelihood of receiving SACT was lower in older patients and those diagnosed with stage IV disease. Patients not receiving SACT had poor survival outcomes (median OS [IQR]: NSQ, 1.8 [1.1-3.1] months; SQ, 2.3 (1.3-3.4) months), while median OS (IQR) in SACT-treated patients was 12.6 (6.1-24.5) months for NSQ and 10.3 (5.7-15.9) months for SQ. CONCLUSIONS: This real-world data analysis from a large Portuguese oncology hospital demonstrates a high disease burden for advanced NSCLC in the pre-immunotherapy era, with nearly one-quarter of patients not receiving SACT. Even in patients receiving SACT, median survival was only about 1 year.

Real-world treatment patterns, resource use and cost burden of multiple myeloma in Portugal.

OBJECTIVE: We provide a real-world overview of multiple myeloma (MM) treatment patterns, outcomes and healthcare resource use (HRU) in Portugal. METHODS: Data were collected retrospectively from consecutive patients diagnosed/treated at the Portuguese Oncology Institute of Porto (IPO-Porto) between 2012 and 2015. Primary objectives were progression-free survival (PFS) and overall survival (OS), with treatment patterns and HRU secondary. Analysis was by line of therapy (LOT), and post hoc by age (<65/≥65 years). RESULTS: 165, 73 and 32 patients received first, second and third LOTs respectively (N = 187). OS probabilities were 91.5%, 83.2% (<65 years) and 86.6%, 65.3% (≥65 years) at 12, 24 months respectively. PFS decreased from the start of each LOT for both age groups and was less for patients ≥65 years. Younger patients received more combination treatment (immunomodulatory drugs + proteasome inhibitors) and stem cell transplants, and had higher mean costs than older patients (€81,213 vs. €36,864 where three LOTs were received). Cost drivers were medications, transplantations and hospitalisations. CONCLUSION: Our results suggest divergence between younger and older MM patients. Older patients had lower OS and PFS probabilities, HRU costs and fewer stem cell transplantations. The treatment patterns in each LOT may differ from other countries' findings, suggesting treatment heterogeneity.

Development of a benchmark tool for cancer centers; results from a pilot exercise.

BACKGROUND: Differences in cancer survival exist between countries in Europe. Benchmarking of good practices can assist cancer centers to improve their services aiming for reduced inequalities. The aim of the BENCH-CAN project was to develop a cancer care benchmark tool, identify performance differences and yield good practice examples, contributing to improving the quality of interdisciplinary care. This paper describes the development of this benchmark tool and its validation in cancer centers throughout Europe. METHODS: A benchmark tool was developed and executed according to a 13 step benchmarking process. Indicator selection was based on literature, existing accreditation systems, and expert opinions. A final format was tested in eight cancer centers. Center visits by a team of minimally 3 persons, including a patient representative, were performed to verify information, grasp context and check on additional questions (through semi-structured interviews). Based on the visits, the benchmark methodology identified opportunities for improvement. RESULTS: The final tool existed of 61 qualitative and 141 quantitative indicators, which were structured in an evaluative framework. Data from all eight participating centers showed inter-organization variability on many indicators, such as bed utilization and provision of survivorship care. Subsequently, improvement suggestions for centers were made; 85% of which were agreed upon. CONCLUSION: A benchmarking tool for cancer centers was successfully developed and tested and is available in an open format. The tool allows comparison of inter-organizational performance. Improvement opportunities were successfully identified for every center involved and the tool was positively evaluated.

A comparison of in-hospital acute myocardial infarction management between Portugal and the United States: 2000-2010.

OBJECTIVE: To compare healthcare in acute myocardial infarction (AMI) treatment between contrasting health systems using comparable representative data from Europe and USA. DESIGN: Repeated cross-sectional retrospective cohort study. SETTING: Acute care hospitals in Portugal and USA during 2000-2010. PARTICIPANTS: Adults discharged with AMI. INTERVENTIONS: Coronary revascularizations procedures (percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) surgery). MAIN OUTCOME MEASURES: In-hospital mortality and length of stay. RESULTS: We identified 1 566 601 AMI hospitalizations. Relative to the USA, more hospitalizations in Portugal presented with elevated ST-segment, and fewer had documented comorbidities. Age-sex-adjusted AMI hospitalization rates decreased in USA but increased in Portugal. Crude procedure rates were generally lower in Portugal (PCI: 44% vs. 47%; CABG: 2% vs. 9%, 2010) but only CABG rates differed significantly after standardization. PCI use increased annually in both countries but CABG decreased only in the USA (USA: 0.95 [0.94, 0.95], Portugal: 1.04 [1.02, 1.07], odds ratios). Both countries observed annual decreases in risk-adjusted mortality (USA: 0.97 [0.965, 0.969]; Portugal: 0.99 [0.979, 0.991], hazard ratios). While between-hospital variability in procedure use was larger in USA, the risk of dying in a high relative to a low mortality hospital (hospitals in percentiles 95 and 5) was 2.65 in Portugal when in USA was only 1.03. CONCLUSIONS: Although in-hospital mortality due to an AMI improved in both countries, patient management in USA seems more effective and alarming disparities in quality of care across hospitals are more likely to exist in Portugal.

HIV patients have impaired diastolic function that is not aggravated by anti-retroviral treatment.

PURPOSE: Recent studies have shown that HIV infection is independently associated with heart failure. Diastolic dysfunction (DD) is frequent in HIV patients, but it is unclear whether this is an effect of the HIV infection itself or of the anti-retroviral therapy (ART). Our aim was to compare diastolic function in HIV treatment-naïve, HIV-ART patients and controls. METHODS: We prospectively enrolled 206 consecutive patients with HIV-1 infection and 30 controls, selected by frequency matching for age and sex. HIV patients were divided in two subgroups: ART-naïve (n = 88) and ART (n = 118). Diastolic function was assessed and graded by echocardiography, according to modern consensus criteria and using tissue Doppler analysis. RESULTS: Compared to controls, ART-naïve patients had lower E' velocities (E' septal: 10.2 ± 2.4 vs 11.9 ± 2.6 cm/s, p = 0.02), higher E/E' ratio (7.8 ± 1.9 vs 6.9 ± 1.6,p = 0.02) and higher prevalence of DD (19 % vs 3.3 %,p = 0.05). HIV patients under ART also had worse diastolic function compared to controls (E' septal: 10.3 ± 2.5 cm/s;p < 0.01; E/E'ratio: 8.0 ± 2.0,p < 0.01; DD prevalence: 23 %;p = 0.01), but no significant differences were found between ART-naïve and ART HIV subgroups. In multivariable logistic regression analysis, age and body mass index were the only independent predictors of reduced diastolic reserve in HIV patients. Regarding systolic function, there were no significant differences in ejection fraction or S' velocities between controls and HIV subgroups. CONCLUSIONS: HIV treatment-naïve patients have reduced diastolic reserve that is not worsened by ART. These data reinforce the association of diastolic dysfunction with the HIV infection itself and not with the anti-retroviral therapy.

Cost-utility analysis of endoscopic surveillance of patients with gastric premalignant conditions.

BACKGROUND: Progression of extensive gastric premalignant conditions to cancer might warrant surveillance programms. Recent guidelines suggest a 3-yearly endoscopic follow-up for these patients. Our aim was to determine the cost utility of endoscopic surveillance of patients with extensive gastric premalignant conditions such as extensive atrophy or intestinal metaplasia. MATERIALS AND METHODS: A cost-utility economic analysis was performed from a societal perspective in Portugal using a Markov model to compare two strategies: surveillance versus no surveillance. Clinical data were collected from a systematic review of the literature, costs from published national data, and community utilities derived from a population study by the EuroQol questionnaire in terms of quality-adjusted life years (QALY). Population started at age 50, for a time horizon of 25 years and an annual discount rate of 3% was used for cost and effectiveness. Primary outcome was the incremental cost-effectiveness ratio (ICER) of a 3-yearly endoscopic surveillance versus no surveillance for a base case scenario and in deterministic and probabilistic sensitivity analysis. Secondary outcomes were ICER of 5- and 10-yearly endoscopic surveillance versus no surveillance. RESULTS: Endoscopic surveillance every 3 years provided an ICER of € 18,336, below the adopted threshold of € 36,575 which corresponds to the proposed guideline limit of USD 50,000 and this strategy dominated surveillance every 5 or 10 years. Utilities for endoscopic treatment were relevant in deterministic analysis, while probabilistic analysis showed that in 78% of cases the model was cost-effective. CONCLUSIONS: Endoscopic surveillance every 3 years of patients with premalignant conditions is cost-effective.

Determinants of clinical improvement after surgical replacement or transcatheter aortic valve implantation for isolated aortic stenosis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement (SAVR) in patients with aortic stenosis (AS) and high surgical risk. Hemodynamic performance after TAVI is superior, but the impact of reverse remodeling on clinical improvement is controversial. We aim to address the differences in hemodynamic changes between SAVR and TAVI, and its correlation with LV remodeling and clinical improvement at 6 months follow-up. METHODS: Forty-two patients treated by TAVI were compared with 45 SAVR patients with a stented bioprosthesis. Clinical, 2D and 3D echocardiographic data were prospectively obtained before and six months after intervention. RESULTS: Patients had similar distribution for sex, body surface area and AS severity. TAVI patients were older, more symptomatic and had more comorbidities. They also had higher LV filling pressures, larger 3D indexed left atrium volume, but similar 3D indexed LV mass. At 6 months, TAVI patients had greater clinical improvement and higher effective orifice area index (EAOI), but only SAVR patients already had a significant decrease in 3D indexed LV mass and diastolic volume. In univariate analysis older age, NYHA class ≥ III, increase in EAOI and TAVI were related with functional class improvement. After multivariate analysis only NYHA class ≥ III (OR 8.81, CI:2.13-36.52; p=0.003) and an increase in EAOI ≥ 105% (OR 3.87, CI:1.02-14.70; p=0.04) were predictors of clinical improvement. CONCLUSIONS: At 6 months, functional class improvement was greater after TAVI. Higher initial NYHA class and an increase in EAOI ≥ 105% were independently associated with functional enhancement. It is debatable if left ventricular remodeling is determinant for functional class improvement.

Screening for gastric cancer and surveillance of premalignant lesions: a systematic review of cost-effectiveness studies.

BACKGROUND: Cost-effectiveness studies are highly dependent on the models, settings, and variables used and should be based on systematic reviews. We systematically reviewed cost-effectiveness studies that address screening for gastric cancer and/or surveillance of precancerous conditions and lesions. MATERIALS AND METHODS: A systematic review of cost-effectiveness studies was performed by conducting a sensitive search in seven databases (PubMed, Scopus, Web of Science, Current Contents Connect, Centre for Reviews and Dissemination, Academic Search Complete, and CINAHL Plus), independently evaluated by two investigators. Articles were evaluated for type of study, perspective, model, intervention, incremental cost-effectiveness ratio, clinical or cost variables, and quality, according to published guidelines. RESULTS: From 2395 abstracts, 23 articles were included: 19 concerning population screening and 4 on following up premalignant lesions. Studies on Helicobacter pylori screening concluded that serology was cost-effective, depending on cancer incidence and endoscopy cost (incremental cost-effectiveness ratio: 6264-25,881), and eradication after endoscopic resection was also cost-effective (dominant) based on one study. Studies on imaging screening concluded that endoscopy was more cost-effective than no screening (incremental cost-effectiveness ratio: 3376-26,836). Articles on follow-up of premalignant lesions reported conflicting results (incremental cost-effectiveness ratio: 1868-72,519 for intestinal metaplasia; 18,600-39,800 for dysplasia). Quality assessment revealed a unanimous lack of a detailed systematic review and fulfillment of a median number of 23 items (20-26) of 35 possible ones. CONCLUSIONS: The available evidence shows that Helicobacter pylori serology or endoscopic population screening is cost-effective, while endoscopic surveillance of premalignant gastric lesions presents conflicting results. Better implementation of published guidelines and accomplishment of systematic detailed reviews are needed.

Rosuvastatin slows the development of diastolic dysfunction in calcific aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: The study aims were to test the effect of rosuvastatin on the progression of left ventricular (LV) diastolic function in patients with aortic stenosis (AS), and to evaluate the use of beta-natriuretic-peptide (BNP) as a marker of diastolic dysfunction in this condition. METHODS: Sixty-one hypercholesterolemic, consecutive new referrals with moderate AS were administered rosuvastatin (Crestor) 20 mg/day for 18 months, while a further 60 subjects with normal cholesterol levels remained untreated. The LV diastolic function was determined using conventional Doppler echocardiography, tissue Doppler imaging (TDI); BNP plasma levels were monitored when subjects entered the study and then assessed prospectively at six-month intervals until the study end. RESULTS: After an 18-month (mean 73 +/- 24 weeks) period of treatment with rosuvastatin (Tx group), patients showed a significantly better diastolic function than untreated subjects (uTx group), as indicated by an isovolumic relaxation time (IVRT) (Tx 102.0 +/- 42.8 versus 97.2 +/- 19.1; p < 0.001; uTx 99.7 +/- 21.7 versus 95.2 +/- 21.8 ms; p = 0.032), E/A ratio (Tx 1.0 +/- 0.6 versus 0.9 +/- 0.3, p = 0.52; uTx 1.2 +/- 0.40 versus 0.9 +/- 0.30 versus, p = 0.006), and E/E' ratio (Tx 11.4 +/- 1.5 versus 11.4 +/- 1.8, p = 0.19; uTx 15.4 +/- 1.2 versus 12.3 +/- 1.5, p < 0.001). Similarly, at study end, plasma levels of BNP were significantly lower in the Tx group than in the uTx group [median (1st-3rd quartiles): 37.0 pg/ml (20.1-65.2 pg/ml) versus 57.1 pg/ml (46.9-98.2 pg/ml); p = 0.017]. CONCLUSION: The results of this prospective follow up study of asymptomatic patients showed that rosuvastatin treatment delays the progression of diastolic dysfunction in moderate AS when assessed using hemodynamic echocardiographic parameters or by the release of plasma physiological markers. Hence, the benefits of statin treatment in AS, which are known to affect the valve endothelium, also extend to changes affecting myocardial function itself.

Long-term outcomes of primary cardiovascular prevention: A retrospective study at a referral center in Portugal.

INTRODUCTION AND OBJECTIVES: Lifestyle changes are frequently insufficient to reduce cardiovascular (CV) risk in patients with dyslipidemia. This study aims to characterize the long-term evolution of lipid profile and CV risk of patients under primary prevention. METHODS: A retrospective study was performed of outpatients at a Portuguese cardiovascular risk clinic with ≥2 CV risk factors, followed for ≥2 years between 1995 and 2015. Statin therapy had been initiated early, in accordance with the clinic's practice. After written informed consent was obtained, sociodemographic and clinical characteristics were collected from medical charts, at baseline and last visit. Changes in lipid profile and CV risk scores were estimated. Associations between HDL-C or LDL-C changes and gender, age, observation time and treatments were assessed through bivariate analysis and multiple linear regression models. RESULTS: Out of 516 participants with mean follow-up of 11.4±4.3 years, 56.6% were female and 91.5% received statins. Lipid profile showed statistically significant improvement, including median changes in LDL-C and HDL-C of -77.0 mg/dl and +19 mg/dl, respectively. CV risk also showed statistically significant improvements according to all scores. Statin therapy resulted in a mean HDL-C increase of 7.4 mg/dl (independently of gender and other treatments) and a mean LDL-C reduction of 51.8 mg/dl (irrespective of age and other treatments). CONCLUSION: Results from this long-term real-life study indicate that primary prevention, specifically early and continuous therapy with intermediate-intensity statins as an add-on to lifestyle interventions, was important in obtaining consistent and adequate metabolic correction in patients with additional risk factors.

Prognostic implications of fibrosis in low risk aortic stenosis patients.

INTRODUCTION AND OBJECTIVES: Among patients with aortic stenosis (AS), interstitial fibrosis has been associated with progression to heart failure and is a marker of poorer prognosis. We aimed to assess the impact of myocardial fibrosis on clinical events after aortic valve replacement (AVR) in low risk, severe AS. METHODS: We prospectively followed 56 severe AS patients with ejection fraction >40%, who underwent AVR with simultaneous myocardial biopsies and collagen volume fraction (CVF) determination. Baseline and follow-up echocardiographic parameters were assessed. Outcomes were all-cause death and the combined endpoint of all-cause death or non-fatal cardiovascular hospitalization. RESULTS: Patients were predominantly women (67.9%) and mean age was 66±12 years. At follow-up, there was a significant decrease in transaortic gradients and wall stress, as well as regression in indexed LV mass. Patients who suffered a fatal event or the combined endpoint had a higher degree of fibrosis (27.1±20.7% vs. 15.4±11.8%, p=0.035; 24.0±18.2% vs. 15.3±12.0%, p=0.038, respectively). Patients with CVF≥15.4% had higher rates of all-cause death (37.5% vs. 97.0%, p=0.001) and lower survival free of the combined endpoint of all-cause death or non-fatal cardiovascular hospitalization (0% vs. 91.2%, p<0.001). CVF was the only independent predictor of all-cause death (hazard ratio (HR) 1.88; 95% confidence interval (CI): 1.08-3.29 for each 10% increase; p=0.026) and all-cause death or cardiovascular hospitalization (HR 1.73; 95% CI: 1.03-2.911 for each 10% increase; p=0.038). CONCLUSIONS: In low risk AS patients, higher levels of fibrosis are independent predictors of all-cause death and the composite of all-cause death or non-fatal cardiovascular hospitalization. Further advances in anti-fibrotic therapies in AS are needed.

Antithrombotic therapy in nonvalvular atrial fibrillation: a narrative review.

Atrial fibrillation (AF) is an important and potentially modifiable cause of stroke. It has been known since 1989 that oral anticoagulant drugs, such as warfarin, lead to a dramatic decrease in stroke associated with AF. The best risk-benefit ratio is obtained with intensity of oral anticoagulant treatment for an INR of 2-3, even in the elderly. Given the risks of anticoagulant therapy, including bleeding, individual thromboembolic risk must be assessed in patients with AF. In 2009, dabigatran was shown to be a reasonable alternative to vitamin K antagonists, establishing itself as a major alternative to warfarin in AF patients. Rivaroxaban and apixaban have subsequently also been shown to be alternatives to warfarin. When there are contraindications to vitamin K antagonists, antiplatelet agents can produce a therapeutic effect, although much less than oral anticoagulants. Apixaban may be a better alternative to aspirin in this setting. Patients with low-risk atrial fibrillation (no risk factors) have not been the subjects of specific clinical trials. It is unclear what would be the best therapeutic choice for these patients.

The addition of neoadjuvant pertuzumab for the treatment of HER2+ breast cancer: a cost estimate with real-world data.

BACKGROUND: Breast cancer (BC) is largely prevalent worldwide. HER2-positive BC account for roughly 20-25% of all BC cases and has an overall survival lower than other BC. Innovation on BC therapeutics is a constant, but novel therapies have higher costs. Therefore, cost-effectiveness research is essential to provide healthcare decision-makers with solid foundations for a resource allocation. This study aims to estimate the average direct medical costs/patient and cost-effectiveness of adding pertuzumab in neoadjuvant treatment (NeoT) for HER2-positive breast cancer (BC). METHODS: Two retrospective real-world consecutive cohorts of ≥18yo female patients diagnosed with HER2-positive BC treated with NeoT at the Breast Clinic of IPO-Porto were studied. The AC-DH regimen (2012-2015) comprised 8 cycles of neoadjuvant therapy (4 cycles of doxorubicin + cyclosphosphamide followed by 4 cycles ofdocetaxel + trastuzumab), while the AC-DHP regimen (2015-2017) included also pertuzumab as NeoT. NeoT was followed by surgery and adjuvant trastuzumab. Micro-costing technique and a bottom-up approach was used comprising all medical direct costs from the hospital perspective. Unit costs were obtained from government official prices or from IPO-Porto costing system. Costs were adjusted to 2017 and are expressed in euros. Multivariable logistic regression models were used for effectiveness assessment, while generalized linear models with gamma distribution were used for costs. ICER was calculated using the pathological complete response (pCR) as the preferential measure of effectiveness. Sensitivity analysis was also performed. RESULTS: AC-DHP (n = 40) and AC-DH (n = 54) cohorts had heterogenous patient profiles (median age 43y/53y; 67.5%/59.3% positive HR; 60.0%/27.8% operable; 25.0%/24.1% inflammatory, respectively). The AC-DHP average total cost/patient was 56,375€, with pertuzumab accounting for 13,978€ (24.79%) and increasing in 15,982€ the average cost/patient (p < 0.001). Clinical staging and hormone receptors (HR) were significantly associated with pCR. ICER was 1.370€ per percentage point of pCR. CONCLUSIONS: ICER was more favourable in stage III HR negative BC patients compared to other patient profiles. Innovative treatments access is critical to deliver high-quality healthcare, but sustainability must be considered. These results suggest the importance of establishing a cost-effectiveness profile of Pertuzumab in NeoT for HER2-positive BC.

Heart rate variability in patients with refractory epilepsy: The influence of generalized convulsive seizures.

OBJECTIVE: Patients with epilepsy, mainly drug-resistant, have reduced heart rate variability (HRV), linked to an increased risk of sudden death in various other diseases. In this context, it could play a role in SUDEP. Generalized convulsive seizures (GCS) are one of the most consensual risk factors for SUDEP. Our objective was to assess the influence of GCS in HRV parameters in patients with drug-resistant epilepsy. METHODS: We prospectively evaluated 121 patients with refractory epilepsy admitted to our Epilepsy Monitoring Unit. All patients underwent a 48-hour Holter recording. Only patients with GCS were included (n = 23), and we selected the first as the index seizure. We evaluated HRV (AVNN, SDNN, RMSSD, pNN50, LF, HF, and LF/HF) in 5-min epochs (diurnal and nocturnal baselines; preictal - 5 min before the seizure; ictal; postictal - 5 min after the seizure; and late postictal - >5 h after the seizure). These data were also compared with normative values from a healthy population (controlling for age and gender). RESULTS: We included 23 patients, with a median age of 36 (min-max, 16-55) years and 65% were female. Thirty percent had cardiovascular risk factors, but no previously known cardiac disease. HRV parameters AVNN, RMSSD, pNN50, and HF were significantly lower in the diurnal than in the nocturnal baseline, whereas the opposite occurred with LF/HF and HR. Diurnal baseline parameters were inferior to the normative population values (which includes only diurnal values). We found significant differences in HRV parameters between the analyzed periods, especially during the postictal period. All parameters but LF/HF suffered a reduction in that period. LF/HF increased in that period but did not reach statistical significance. Visually, there was a tendency for a global reduction in our patients' HRV parameters, namely AVNN, RMSSD, and pNN50, in each period, comparing with those from a normative healthy population. No significant differences were found in HRV between diurnal and nocturnal seizures, between temporal lobe and extra-temporal-lobe seizures, between seizures with and without postictal generalized EEG suppression, or between seizures of patients with and without cardiovascular risk factors. SIGNIFICANCE/CONCLUSION: Our work reinforces the evidence of autonomic cardiac dysfunction in patients with refractory epilepsy, at baseline and mainly in the postictal phase of a GCS. Those changes may have a role in some SUDEP cases. By identifying patients with worse autonomic cardiac function, HRV could fill the gap of a lacking SUDEP risk biomarker.

B-type natriuretic peptide is related to cardiac function and prognosis in hospitalized patients with decompensated cirrhosis.

BACKGROUND: B-type natriuretic peptide (BNP) concentrations are high in cirrhosis, possibly related to volume status and cirrhotic cardiomyopathy. The prognostic significance of BNP in cirrhosis is unknown. AIMS: We aimed to evaluate (i) the influence of haemodynamic parameters and volaemia, assessed by impedance cardiography (ICG), in BNP levels, (ii) the performance of BNP as a prognostic marker, in a cohort of cirrhotic patients. METHODS: Patients consecutively hospitalized with decompensated cirrhosis during 1 year were evaluated. At admission, ICG and BNP measurements were performed in 83 patients (median age 56 years; median Child-Pugh score=10). The 70 patients discharged were followed for the occurrence of death within 6 months. RESULTS: Median BNP levels were 130.3 (65.2-363.3) pg/ml. Independent BNP predictors in multivariate linear regression analysis were cardiac output, age and haemoglobin (R(2)=36.7%). The 24 patients with cardiac systolic dysfunction, defined by low cardiac output, had higher BNP concentrations than the other patients (230.8 vs 98.5 pg/ml, P=0.003). BNP levels above median were associated with an increased occurrence of death within 6 months of discharge (log rank P=0.023). Cardiac output and BNP were predictors of survival in univariate Cox regression analysis. Only BNP remained independently related to the outcome in multivariate analysis [hazard ratio=2.86 (1.11-7.38), P=0.03]. CONCLUSIONS: BNP levels in cirrhosis reflect cardiac systolic function and non-cardiac variables that should be considered in their interpretation. BNP is an independent predictor of medium-term survival in advanced cirrhosis, suggesting its utility in risk stratification of decompensated cirrhotic patients.

Therapeutic Drug Monitoring by Pharmacists: Does It Reduce Costs.

Therapeutic drug monitoring (TDM) has as its main objective to ensure that the plasma drug concentration remains within the appropriate range. Regarding the economic dimension of TDM, it is known that there are gains in health outcomes; however, there is still little evidence for the benefit of this procedure performed by pharmacists within the hospital context. With this project, we aimed to create a matrix of cost avoidance associated with TDM performed by pharmacists and to quantify the total avoided costs in 1 year, by implementing a TDM process in a tertiary hospital. For the studied period, we collected 362 pharmaceutical interventions related to TDM of antibiotics performed in adults. As a result, considering these data, the total cost avoidance in 1 year was 371,018 ($416,584.58) at one medical center. We conclude that TDM is highly cost-avoidant and that the implementation costs by pharmaceutical services is clearly lower than the benefit achieved.

Outcomes Management in a Real-World Evidence Context: The Case of Abiraterone and Enzalutamide in the Treatment of Metastatic Castration-Resistant Prostate Cancer.

At present, for patients with metastatic and castration-resistant prostate cancer, European Society for Medical Oncology and National Comprehensive Cancer Network guidelines recommend enzalutamide (E) or abiraterone (A). There are still a few studies comparing both drugs in a real-world setting, thus, in this article, we discuss an outcomes management methodology, supporting the follow-up of patients. This involves measuring relevant baseline traits and outcomes, such as overall survival (OS), treatment duration, patient-reported outcomes, and adverse events. We include 38 men in the A group and 15 in the E group. When comparing the survival of both drugs, both present similar OS. Regarding the quality-of-life analysis (QoL) with EPIC26, reported Standard QoL score was 58.3% in our patients, which was in line with the European Organization for the Research and Treatment of Cancer reference. As a result, by showing that we can capture the distinctive clinical benefits of A and E, and that patient-reported outcomes can be systematically collected for more than 2 years per living patient, we can now incorporate these findings in clinical discussions, risk-sharing agreements, or policy-level arguments.

cTnI, BNP and CRP profiling after seizures in patients with drug-resistant epilepsy.

PURPOSE: To profile serum levels of high sensitivity Troponin I (hs-cTnI), B-Type Natriuretic Peptide (BNP), and high sensitivity C Reactive Protein (hs-CRP), after epileptic seizures in patients with focal drug-resistant epilepsy, relating the results to the revised SUDEP-7 inventory. METHODS: We prospectively evaluated patients admitted to our Epilepsy Monitoring Unit. hs-cTnI, BNP, and hs-CRP were measured at admission and after the first seizure. The revised SUDEP-7 Risk Inventory was calculated. The statistical significance level was set at 0.05. RESULTS: Fifty-eight patients were included (53.4 % female). The index seizure was a focal to bilateral tonic-clonic seizure (FBTCS) in 25.9 % of the patients, and 17.5 % had post-ictal generalized EEG suppression (PGES). After the seizure, 25.9 % had a significant (above 50 %) increase in hs-cTnI, 23.3 % in BNP, and 4.3 % in hs-CRP. About 40 % had cardiovascular risk factors (CRF), without known cardiac disease. The elevation of one biomarker did not compel the elevation of another. hs-cTnI increase was associated with FBTCS, PGES, longer seizures, maximal ictal heart rate, and HR change. Increases in BNP were associated with CRF. hs-CRP increase was associated with PGES. We found no significant association between SUDEP-7 and any biomarker increase. SIGNIFICANCE: Several patients had increases in biomarkers of myocardial necrosis/dysfunction after seizures, without significant association with the SUDEP-7 inventory. Different patterns of biomarkers' elevations point to multifactorial pathophysiologies hypothetically associated with incipient myocardial lesions. A larger cohort with follow-up data could help to clarify the clinical relevance of these findings.