Several Subgroups Of Patients Research Articles

Clinical Challenges in Treating Cancer Associated Thrombosis: A Clinically Oriented Review.

Managing cancer associated thrombosis (CAT) is a significant clinical challenge due to several factors such as increased bleeding tendency, frailty, and drug - drug interactions. For many years, the drug of choice for treating CAT was low molecular weight heparin (LMWH); Recently, direct oral anticoagulants (DOACs) entered to the therapeutic milieu of CAT. However, due to the large diversity among patients with CAT in clinical and laboratory characteristics not all patients will equally benefit from treatment with DOACs. Furthermore, several subgroups of patients with CAT have specific characteristics that influence the anticoagulant decision-making process. In this review, we present four different theoretical clinical case scenarios, each representing a different challenge that is associated with thrombosis management; brain metastasis, malignancies of the gastrointestinal tract, drug-drug interactions (DDI) and thrombocytopenia. By reviewing current literature, we suggest our clinical approach for managing these cases in the era of DOACs. (1) The management of patients with brain tumors and CAT is challenging due to increased risk for both intracranial hemorrhage and recurrent venous thromboembolism (VTE). Both LMWH and DOACs are optional treatment in this setting. (2) There are conflicting data regarding the bleeding risk in patients with GI malignancies. Treatment with LMWH should be considered specifically in patients with advanced disease and unresectable tumors. (3) There is a paucity of data regarding DDI in patients with CAT. However, caution should be exercised when prescribing DOACs to patients receiving concurrent medications that either affect DOAC metabolism or influence bleeding risk. (4) The management of patients with CAT and thrombocytopenia depends on the severity of thrombocytopenia and the timing of the thrombotic event.

Hypothyroidism Revisited: Defining the Subgroups on Optimal Thyroxine Replacement Who Have Persisting Symptoms

Hypothyroid patients on optimal replacement but with persisting symptoms continue to be a challenge for their treating physicians. This commentary is based on a substantial clinical experience with this subpopulation. With the focus on laboratory tests to achieve a diagnosis, aspects of the traditional clinical examination have been overlooked. In particular the routine testing of tendon reflexes has lapsed. A delay in the relaxation phase of tendon reflexes (hypothyroid hyporeflexia), once known as a positive Woltman’s sign, has long been the hallmark sign of overt hypothyroidism. The majority will do well when treated with appropriate thyroxine replacement. This sign is also positive in those patients on thyroxine (T4) with normal T4 and Thyrotropin (TSH) levels if they have symptomatic intracellular Triiodothyronine (T3) deficiency. These patients will respond promptly to combination therapy (T4+T3). This subgroup accounts for more than half of the thyroxine-dissatisfied population. They should be described as having T3-hypothyroidism. The remaining symptomatic patients with normal reflexes have unrelated conditions. A small clearly defined subgroup with autoimmune symptoms and very high anti-Thyroperoxidase (anti-TPO) antibodies (>10 times the upper limit of normal) will respond to total thyroidectomy with a marked improvement that is maintained for 3-5 years. They can be categorised as having TPO-toxic hypothyroidism. Many patients can have persistent symptoms because of psycho-social issues and the burden of having a chronic disease. They have in-denial-hypothyroidism. There are very rare cases of thyroxine allergy. This nomenclature should assist physicians in their diagnosis and management of the several subgroups of patients on thyroxine with persistent symptoms.

Cognitive disturbances basic symptoms in help-seeking patients with borderline personality disorder: Characteristics and association with schizotypy.

Although the presence of psychotic symptoms has been widely recognized in Borderline Personality Disorder (BPD), no study previously investigated cognitive Basic Symptoms (BS) and their clinical implications in patients with BPD. This cross-sectional study specifically examined the prevalence of COGDIS (cognitive disturbances) BS criteria in 93 help-seeking outpatients with BPD by using the Schizophrenia Proneness Instrument-Adult Version (SPI-A). We then explored associations of COGDIS with personality traits, functioning and core psychopathological features of BPD. The prevalence rates of COGDIS criterion were 62.4%. BPD patients meeting COGDIS criteria reported higher levels of schizotypal personality traits, dissociative experiences and work/social functional impairment compared to individuals without COGDIS criteria. Furthermore, the number of cognitive BSs showed a positive correlation with severity levels of schizotypy. Cognitive BS are common in BPD. Cognitive disturbances are associated with schizotypal personality traits and specific clinical features. The presence of cognitive BSs may identify a more severe subgroup of patients with BPD, potentially vulnerable to psychotic symptoms and reliably identifiable through assessment of schizotypal traits.

Decreased progenitor TCF1 + T-cells correlate with COVID-19 disease severity

COVID-19, caused by SARS-CoV-2, can lead to a severe inflammatory disease characterized by significant lymphopenia. However, the underlying cause for the depletion of T-cells in COVID-19 patients remains incompletely understood. In this study, we assessed the presence of different T-cell subsets in the progression of COVID-19 from mild to severe disease, with a focus on TCF1 expressing progenitor T-cells that are needed to replenish peripheral T-cells during infection. Our results showed a preferential decline in TCF1+ progenitor CD4 and CD8+ T-cells with disease severity. This decline was seen in various TCF1+ subsets including naive, memory and effector-memory cells, and surprisingly, was accompanied by a loss in cell division as seen by a marked decline in Ki67 expression. In addition, TCF1+ T-cells showed a reduction in pro-survival regulator, BcL2, and the appearance of a new population of TCF1 negative caspase-3 expressing cells in peripheral blood from patients with severe disease. The decline in TCF1+ T-cells was also seen in a subgroup of severe patients with vitamin D deficiency. Lastly, we found that sera from severe patients inhibited TCF1 transcription ex vivo which was attenuated by a blocking antibody against the cytokine, interleukin-12 (IL12). Collectively, our findings underscore the potential significance of TCF1+ progenitor T-cells in accounting for the loss of immunity in severe COVID-19 and outline an array of markers that could be used to identify disease progression.

Long-term outcomes and risk factors for reoperation after subaortic stenosis resection in children and adults

Abstract Background Sub-valvular aortic stenosis (SAS) is an extremely heterogeneous form of left ventricular outflow tract (LVOT) obstruction, which can lead to aortic valve damage. Although corrective surgery is considered the most effective treatment, rates of recurrence and reoperation are still high. Previous studies have focused on predictors of reoperation in several subgroups of patients with SAS, but rarely in the whole population of patients with SAS. Purpose We sought to describe long-term outcomes after SAS resection and to determine the predictors of reoperation after successful primary resection. Methods We retrospectively reviewed the records of patients who underwent SAS resection between 1994 and 2021 at our institution with at least 12 months’ follow-up. Patients with a single-ventricle physiology and idiopathic hypertrophic cardiomyopathy were excluded. Demographic, surgical and echocardiographic data were analyzed. Outcomes were reoperation after successful primary resection, death and morbidities, including postoperative complete heart block and aortic regurgitation (AR) grade at latest follow-up. Results Seventy-six patients (paediatric, n = 72 and adult, n = 4) who underwent SAS resection were included in the analysis. Median length of postoperative follow-up was 11.1 years (IQR range: 7.3 – 15.7 years), with two late deaths. Reoperation due to recurrent obstruction or severe AR occurred in 24 patients (31.6%). Median time to reoperation was 7.5 years (IQR range: 3.6 – 11 years). Overall freedom from reoperation at 5 years and 10 years was 84.6% and 69.1% respectively. Gender and association with other cardiac defects did not differ significantly between those with reoperation and those without. In multivariate analysis, independent predictors of reoperation were age at first surgery younger than 5 years (HR 3.54, 95% CI 1.06 – 11.83; P = 0.040) and tunnel-type lesions (HR 4.42, 95% CI 1.70 – 11.51; P = 0.002). Three patients (3.9%) had complete heart block and required placement of an implantable pacemaker. Following SAS resection, progression of AR was common (39/68, 57.3%) but only 5 patients (7.3%) developed sufficient regurgitation to require surgical repair or replacement. Conclusions Reoperation is not infrequent after surgical relief of SAS and reaches a plateau after 10 years. Younger age at first surgery and tunnel-type SAS independently predict reoperation. Progression of AR after corrective surgery of SAS is common, but fortunately only a minority of patients develop hemodynamically significant AR requiring reintervention.

Patient-level outcomes of patients undergoing resorbable magnesium scaffold (RMS) implantation stratified according to different subgroups: a post-hoc analysis of SHERPA MAGIC study

Abstract Background The SHERPA-MAGIC is an investigator-driven, multicenter, prospective, single-arm study that enrolled patients undergoing resorbable magnesium scaffold (RMS) implantation in 18 Italian centers. The results from the first 543 patients supported the safety and long-term performance of RMS in a real-world population. Purpose The present post-hoc analysis aimed to assess differences in adverse events at patient-level (patient-oriented composite endpoints, POCE, defined as the composite of all-cause death, myocardial infarction -MI- and ischemia-driven coronary revascularization) at the longest follow-up between different subgroups of the final study population (n=543). Methods We identified the subgroups according to different variables: age, sex, cardiovascular risk factors, clinical presentation, left ventricle ejection fraction, multivessel disease, multivessel PCI, and antiplatelet therapy. If the analysis highlighted a subgroup of patients at higher risk of adverse events, to understand if this finding is related to RMS implantation or to the characteristic itself, a propensity score matched analysis was conducted comparing patients of the SHERPA-MAGIC study with a matched cohort of patients receiving second generation drug eluting stent. The endpoint for the comparison between the two matched cohorts was POCE. Results The mean age of the final study population was 56±9 years. 433 (78%) patients were men, and the most common clinical presentation was MI (n=402, 74%). At the median follow-up of 3.5 [2.6-4.3] years, the cumulative occurrence of the primary endpoint (vessel-oriented composite endpoints, VOCE, including cardiac death, target vessel MI, and ischemia-driven target vessel revascularization) was 37 (5.8%, 95%CI 4.1%-7.9%) and 54 (9.9%, 95% CI 7.5%-12.7%) patients met criteria for POCE. There was no significant difference among POCE in the subgroup analysis (Figure 1), with the exception of patients with MI as clinical presentation. As compared to patients admitted for chronic coronary syndrome, MI patients showed a significantly higher POCE rate (11.4 vs 5.6%, CI 8.5-14.9, p=0.04). Therefore, a propensity score matched analysis was conducted comparing MI patients of the SHERPA-MAGIC study with a matched cohort of MI patients from the Acute coRonary sYndrOmes proSpective regisTry Of Ferrara (ARYOSTO) study (NCT02438085) treated with second-generation DES. We did not find significant differences in the cumulative occurrence of POCE between SHERPA MAGIC and ARYOSTO (11.4% vs. 12.5% respectively, p=0.71) (Figure 2). Conclusions The present analysis confirmed the safety and effectiveness of RMS across several subgroups of patients stratified by clinical and procedural characteristics. We found that MI patients had an higher occurrence of POCE, but this was not related to RMS implantation. Indeed, a similar MI population treated with second generation DES showed the same long-term outcome.Fig 1POCE difference between subgroupsFig 2Propensity matched MI populations

A functional variant in the RAD51 3′ UTR is associated with survival of hepatocellular carcinoma patients

The RAD51 gene plays an important role in DNA repair by homologous recombination, and is involved in the development and progression of multiple cancers. Single nucleotide polymorphisms in RAD51 have been previously described to impact the prognosis of patients with cancers, however, it is still unclear whether this is also true for hepatocellular carcinoma (HCC). This study therefore aimed to identify genetic variants in RAD51 and determine the effect on the survival of patients with HCC. In this study, we performed genotyping assays for RAD51 polymorphisms in a cohort of 368 patients with HCC who had underwent hepatectomy. Using multivariate cox proportional hazards model and Kaplan-Meier analyses with log-rank tests, we compared the survival of patients with HCC according to RAD51 SNP genotypes. We identified one potential functional variant, rs12593359, located in a microRNA (miRNA) binding site in the RAD51 3′ untranslated region, to be an independent predictor of overall survival of patients with HCC in the dominant model. Patients carrying GT/TT genotypes had a significantly increased risk of death when compared with those carrying GG genotype (adjusted hazard ratio = 1.34, 95 % confidence interval = 1.02–1.76, P = 0.035). Kaplan-Meier curve analysis showed a markedly shorter survival time for patients with HCC carrying GT/TT genotypes of SNP rs12593359 (19.0 months vs 36.0 months; Plog-rank = 0.012). Notably, this effect was particularly pronounced in several subgroups of patients (e.g., males, Hepatitis B virus-positive patients, patients with a single tumor nodule, patients with alpha-fetoprotein (AFP) < 400 ng/ml, or patients who were cancer embolus-free). Additional expression analysis of quantitative trait loci showed that SNP rs12593359 was significantly associated with RAD51 mRNA expression levels in 483 cell-cultured fibroblasts (P = 1.1 × 10-4). These findings provide evidence that RAD51 rs12593359 is associated with HCC survival and may serve as a promising predictor of survival in patients with HCC.

0083 A Thermoregulated Pillow Improves Sleep: Results from Real-Life Data

Abstract Introduction Sleep is regulated by homeostatic mechanisms and circadian rhythms.Thermal environment is one of the most important factors that can affect human sleep. This real-life study aims to evaluate the effects of temperature regulation on sleep quality using a thermoregulated pillow. Methods The Moona device has been used to control the temperature of a pillow pad from 64°F to 95°F. Users with more than 7 uses of the device and who completed the initial questionnaire (18 profile questions) participated in this study from October 2019 to July 2021. Participants rated their sleep quality on a scale of 1 to 5. Comparison between the sleep quality before the first use and the average of the last seven uses of the device has been done. A survey has been sent to all users from June to November 2021. To date, 206 answers have been collected including 32 users who reported having been diagnosed with insomnia. Improvement of their insomnia has been assessed by a 5-point scale (from ‘much better’ to ‘much worse’). Statistical analyses have been performed on Python 3.7. Mean comparisons have been measured by student t-test. Results The sleep quality significantly increased with the use of the device from 2.6/5 to 3.7/5 (p&amp;lt;0.001) in the general population (N=620). This significant difference has been also measured in several subgroups who have temperature issues. That is the case for overweight/obese users (N=321, from 2.6/5 to 3.7/5, p&amp;lt;0.001), women over 45 (N=97, from 2.4/5 to 3.6/5, p&amp;lt;0.001) and users who feel hot during the night more than several times a week (N=523, from 2.5/5 to 3.8/5, p&amp;lt;0.001). Moreover, 30 out of 32 insomniacs have reported an improvement of their insomnia since using this active cooling pillow pad. Conclusion The present study findings showed that an active thermoregulated pillow could improve sleep of insomnia patients and several subgroups of patients with issues at controlling temperature at night. Support (If Any)

Chronic aspirin use and survival following sepsis—A propensity-matched, observational cohort study

ObjectivesThe use of antiplatelet agents is postulated to lead to improved outcomes in sepsis. We aimed to evaluate whether chronic, pre-hospitalization aspirin use leads to improved outcomes in patients with sepsis. MethodsWe conducted an observational cohort study among patients with sepsis, hospitalized in internal medicine wards in a single university-affiliated medical center. A propensity-score model was used to match and compare patients on chronic aspirin use to non-users. Patients with established cardiovascular disease were excluded. The primary outcome was survival rates at 30 days. Secondary outcomes included survival rates at 90 days, days of fever, length of hospital stay, and hospital readmission within 90 days. ResultsA total of 1671 patients fulfilled the inclusion criteria. 533 chronic aspirin users were matched to 533 aspirin non-users. Survival rates were significantly higher among patients on chronic aspirin use (hazard ratio (HR) 0.67; 95% CI, 0.51–0.89)). This effect was highlighted in several subgroups of patients, as patients with chronic obstructive pulmonary disease (COPD) or those with chronic use of beta blockers showed the greatest survival benefit with aspirin use. Patients in the aspirin group also showed significantly higher 90 days survival rates (HR 0.69; 95% CI, 0.57–0.92; p = 0.006) and experienced less days of fever in comparison to the control group. DiscussionPre-hospitalization treatment with aspirin for patients without established cardiovascular disease may be associated with mortality reduction, as shown in this is hypothesis-generating single center observational study.

Weighted Cox regression for the prediction of heterogeneous patient subgroups

BackgroundAn important task in clinical medicine is the construction of risk prediction models for specific subgroups of patients based on high-dimensional molecular measurements such as gene expression data. Major objectives in modeling high-dimensional data are good prediction performance and feature selection to find a subset of predictors that are truly associated with a clinical outcome such as a time-to-event endpoint. In clinical practice, this task is challenging since patient cohorts are typically small and can be heterogeneous with regard to their relationship between predictors and outcome. When data of several subgroups of patients with the same or similar disease are available, it is tempting to combine them to increase sample size, such as in multicenter studies. However, heterogeneity between subgroups can lead to biased results and subgroup-specific effects may remain undetected.MethodsFor this situation, we propose a penalized Cox regression model with a weighted version of the Cox partial likelihood that includes patients of all subgroups but assigns them individual weights based on their subgroup affiliation. The weights are estimated from the data such that patients who are likely to belong to the subgroup of interest obtain higher weights in the subgroup-specific model.ResultsOur proposed approach is evaluated through simulations and application to real lung cancer cohorts, and compared to existing approaches. Simulation results demonstrate that our proposed model is superior to standard approaches in terms of prediction performance and variable selection accuracy when the sample size is small.ConclusionsThe results suggest that sharing information between subgroups by incorporating appropriate weights into the likelihood can increase power to identify the prognostic covariates and improve risk prediction.

LUNA3 Phase III Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of the Oral BTK Inhibitor Rilzabrutinib in Adults and Adolescents with Persistent or Chronic Immune Thrombocytopenia

LUNA3 Phase III Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of the Oral BTK Inhibitor Rilzabrutinib in Adults and Adolescents with Persistent or Chronic Immune Thrombocytopenia

Surface-Guided Radiotherapy Feedback: Improvement and Change of Practices

Surface imaging systems are becoming a reference in radiotherapy treatments to improve patient setup. Thanks to an important database of patient positioning, a clinical retrospective evaluation of the system has been realized. For this evaluation, three relevant endpoints have been identified and analyzed: the time-saving setup, the accuracy setup, the number of additional X-Ray images performed to validate the patient setup.Two groups of patients have been defined including all localizations except head & neck treatments. Patients have been all treated on the same Linac following the same positioning and imaging protocol. The first group, the reference one, includes 700 patients with a treatment positioning based on skin marks using lasers. The second group includes 250 patients with treatment positioning based on surface imaging system. In parallel, clinical data (BMI, age, localization etc.) and treatment data (immobilizing system, treatment technique etc.) have been extracted from the Hospital Information System (HIS) and Treatment Planning System (TPS) databases thanks to homemade program. Afterwards, statistical analyses have been carried out for both groups in order to correlate the clinical and technical data with the three defined endpoints.Different correlations have been pointed out. First results confirm that the surface imaging system gives relevant and better set-up information for different sub-groups (breast, skinny pelvis etc.). Nevertheless, for others sub-groups, no correlation nor improvements have been observed (pelvic high BMI etc.) in comparison to laser positioning.Different changes in our patient positioning practices have been defined with the help of surface imaging system. For many patients, we improved our imaging workflow efficiency. For several sub-groups of patients, we still have to investigate the system and its best use.

Progression Rates by Age, Sex, Treatment, and Disease Activity by AASLD and EASL Criteria: Data for Precision Medicine

Antiviral treatment criteria are based on disease progression risk, and hepatocellular carcinoma (HCC) surveillance recommendations for patients with chronic hepatitis B (CHB) without cirrhosis is based on an annual incidence threshold of 0.2%. However, accurate and precise disease progression estimate data are limited. Thus, we aimed to determine rates of cirrhosis and HCC development stratified by age, sex, treatment status, and disease activity based on the 2018 American Association for the Study of Liver Diseases and 2017 European Association for the Study of the Liver guidelines. We analyzed 18,338 patients (8914 treated, 9424 untreated) from 6 centers from the United States and 27 centers from Asia-Pacific countries. The Kaplan-Meier method was used to estimate annual progression rates to cirrhosis or HCC in person-years. The cohort was 63% male, with a mean age of 46.19 years, with baseline cirrhosis of 14.3% and median follow up of 9.60 years. By American Association for the Study of Liver Diseases criteria, depending on age, sex, and disease activity, annual incidence rates ranged from 0.07% to 3.94% for cirrhosis, from 0.04% to 2.19% for HCC in patients without cirrhosis, and from 0.40% to 8.83% for HCC in patients with cirrhosis. Several subgroups of patients without cirrhosis including males younger than 40 years of age and females younger than 50 years of age had annual HCC risk near or exceeding 0.2%. Similar results were found using European Association for the Study of the Liver criteria. There is great variability in CHB disease progression rates even among "lower-risk" populations. Future CHB modeling studies, public health planning, and HCC surveillance recommendation should be based on more precise disease progression rates based on sex, age, and disease activity, plus treatment status.

Predictors of Response to an Evidence-Based Behavioral Cancer Pain Management Intervention: An Exploratory Analysis From a Clinical Trial

ContextInterventions that teach patients cognitive and behavioral strategies for managing cancer pain have demonstrated effectiveness. Systematic reviews of such interventions call for research to inform their implementation in practice, including investigations into which patients are most likely to benefit. ObjectivesWe aimed to identify predictors of response to an evidence-based behavioral intervention for cancer pain, pain coping skills training (PCST). MethodsWe conducted an exploratory secondary analysis of a randomized noninferiority trial comparing in-person to videoconference-based PCST. Using modified Poisson regression, we estimated the adjusted associations of patient characteristics with clinically meaningful reductions (≥30%) in pain severity and pain interference. ResultsOf the 178 patients who were randomized, 135 completed at least one follow-up assessment and were included in this analysis. Proportions of patients experiencing reductions in pain severity and pain interference were 34% and 46%, respectively. In multivariable analysis, education level was associated with a reduction in pain severity (adjusted relative risk, some college or technical school vs. college or higher: 0.49, 95% CI: 0.26-0.93). Patients with colorectal cancer were 61% more likely to experience a reduction in pain interference than patients with breast cancer (95% CI:1.21-2.34). Marital status was also statistically significantly associated with pain interference reduction, with married patients less likely to experience a reduction in pain interference (adjusted relative risk, married vs. not: 0.69, 95% CI: 0.49-0.98). ConclusionOur findings elucidate several subgroups of patients who may be especially likely to benefit from PCST, informing both targeted implementation efforts and opportunities to improve delivery for diverse patients.

Impact of Hormone Receptor Status on the Behaviour of HER2+ Breast Cancer.

The study aimed to evaluate differences in the overall survival of HER2+ breast cancer patients treated with regard to their hormone receptors negativity or positivity. We evaluated a cohort of patients treated with trastuzumab in the Czech Republic. The present study is a retrospective analysis of patients whose data were recorded in a nationwide non-interventional, post-authorisation database BREAST. After propensity score matching of data, the cohort included 4,532 patients. A significant difference in overall survival (OS) of the entire cohort was found between patients with and without hormone dependence. The OS was significantly higher in the group of patients with hormone receptor-positive (HR+) tumours in the following cohorts: patients treated with neoadjuvant therapy, patients with advanced disease, G2 tumours, stage III and IV and in patients with stage II and III of G2 tumours. Increased OS rates were found in several subgroups of patients with HR+/HER2+ tumours compared to those with HR-/HER2+ tumours. Better outcomes of HR+/HER2+ patients were only observed in the first four/five years of follow-up, and the differences disappeared over time.

PND20 HEALTH TECHNOLOGY ASSESSMENTS OF DISEASE-MODIFYING THERAPIES FOR THE TREATMENT OF RELAPSING- REMITTING MULTIPLE SCLEROSIS CHALLENGES IN NICE TECHNOLOGY APPRAISALS

NICE has encountered various evidential, clinical and methodological challenges during its Health Technology Assessments (HTAs) of disease-modifying therapies (DMTs) for the treatment of relapsing–remitting multiple sclerosis (RRMS). NICE guidance published in 2002 did not recommend the use of beta interferons and glatiramer acetate in the NHS because there was insufficient evidence to show their cost effectiveness over a 20-year time horizon. The NHS and the manufacturers of the DMTs agreed to create the RRMS RSS to make these treatments available. The use of data from this scheme to inform a subsequent review of NICE guidance is examined. Substantial advances in the treatment of RRMS have led to the approval of a range of new DMTs and the identification of several subgroups of patients with RRMS who may benefit from certain DMTs. The definitions of these subgroups often come from clinical trials, which are subject to change as clinical understanding of the role of DMTs improves. The definition of clinically relevant groups can vary between trials, creating challenges with generalising evidence when assessing DMTs. Efforts from NICE to ensure its guidance reflects this changing landscape and provides clinicians with clear and relevant recommendations are discussed. NICE has identified several areas of uncertainty, which may drive cost-effectiveness results in HTAs of DMTs for RRMS. These include the costs associated with different health states, the long-term effectiveness of DMTs and different approaches to modelling the mortality rates of people with RRMS. The HTA appraisal committee’s judgements about these uncertainties is discussed, along with recommendations for future research.

Interatrial blocks prevalence and risk factors for human immunodeficiency virus-infected persons.

BackgroundInteratrial blocks are considered a new important risk factor for atrial fibrillation and cerebrovascular events. Their prevalence and clinical implications have been reported in general population and several subgroups of patients but no data from HIV-infected populations, with a non-negligible prevalence of atrial fibrillation, has been previously reported.MethodsWe conducted a cross-sectional study in a previously enrolled cohort of randomly selected middle-aged HIV-infected patients who attended our hospital and were clinically stable.Patients underwent both a 12-lead rest electrocardiogram and clinical questionnaires while epidemiological, clinical and HIV-related variables were obtained from electronic medical records and interviews with the patients. Electrocardiograms were then analyzed and codified using a standardized form by two trained members of the research team who were blinded to clinical variables.ResultsWe obtained electrocardiograms from 204 patients with a mean age of 55.22 years, 39 patients (19.12%) presented an interatrial block, 9 (4.41%) advanced and 30 (14.71%) partial. Patients with interatrial block had a lower nadir lymphocyte CD4 count (124 vs 198 cells, p = 0.02) while advanced interatrial blocks were associated to older age (62.16 vs. 54.95 years, p = 0.046) and hypertension (77.8% vs. 32.3%, p = 0.009). We did not find differences regarding baseline CD4 lymphocyte count or CD4/CD8 lymphocyte ratio. Clinical variables and functional capacity among patients with or without interatrial block were similar.ConclusionsIn a cohort of clinically stable HIV infected patients the prevalence of interatrial blocks, specially advanced, is high and associated to previously known factors (age, hypertension) and novel ones (nadir CD4 lymphocyte count).

The Efficacy of Chest Compressions in the Bell 407

ObjectiveThe Air Medical industry is fraught with obstacles to patient care and providers can recognize that several sub-groups of patients can provide very challenging scenarios while in flight. However, the patient experiencing cardiac arrest in flight is, by its very nature, one that poses the most severe risk to the patient and provider. This study seeks to explore the capability of a highly trained emergency medical provider to provide adequate chest compressions while in a Bell 407 helicopter. Methods59 participants were evaluated in two separate scenarios. Scenario A consisted of 2 rounds of of 200 chest compressions performed on a flat, uncrowded surface. Scenario B consisted of 200 chest compressions performed in the cabin of a Bell 407. Participants performed 2 rounds of 200 chest compressions. The results were then compared to each other and to the AHA 2010 CPR guidelines. ResultsThe findings of the study show that compressions performed in the aircraft do not meet AHA guidelines for chest compressions in regard to depth and duration of compressions. The deviation from guideline in regard to rate was found to be not statistically significant. ConclusionChest compressions performed in a Bell 407 helicopter do not meet AHA guidelines.

Survival Curves and Behavioral Profiles ofFemale 3xTg-AD Mice Surviving to18-Months of Age as Compared toMicewith Normal Aging.

New evidence reveals a high degree of heterogeneity in Alzheimer’s disease (AD) clinical and temporal patterns, supporting the existence of several subgroups of patients. Prognosticators of end-of-life dementia specific to elderly patients are necessary to address this heterogeneity. Among 3xTg-AD mice, a widely-used model for AD, a very small number of animals overcome advanced neuropathological stages of disease beyond 18 months of age. They are usually females, which reach longevity in spite of worse neuropathological status as compared to males (the morbidity/mortality paradox). We posit that 3xTg-AD long-term survivors could serve to model end-of-life dementia but also aware about the mortality selection bias. In the present study, we performed behavioral and functional phenotype in long-term survivors, 18-month-old female 3xTg-AD mice and age-matched wildtype undergoing normal aging. Animals were followed up until natural death to correlate survival with phenotype assessments. Strong similarity of their behavioral profiles in all the variables analyzed (e.g. reflexes, sensorimotor functions, locomotion, exploration, emotionality, and anxiety-like behaviors) was found, with the exception of memory impairment, which was a salient trait in old 3xTg-AD survivors. The two groups showed similar mean life expectancy and had behavioral correlates among lifespan, neophobia and long-term memory in common, with some distinctions in 3xTg-AD, supporting recent studies in end-of-life patients. In spite of the small sample size, this brief report presents an interesting scenario to further study heterogeneity and survival in Alzheimer’s disease. 3xTg-AD survivors may be a model to gain insight into the frailty/survival paradigm in normal and pathological aging.

Prognostic value of histone chaperone FACT subunits expression in breast cancer.

Understanding the underlying reasons for tumor aggressiveness, such as why some tumors grow slowly and locally, while others rapidly progress to a lethal metastatic disease, is still limited. This is especially critical in breast cancer (BrCa) due to its high prevalence and also due to the possibility that it can be detected early. Several oncogenes and tumor suppressors have been identified and are used in the prognosis and treatment of BrCa. However, even with these markers, the outcome within BrCa subtypes is highly variable. Chromatin organization has long been acknowledged as a factor that plays an important role in tumor progression, but molecular mechanisms defining chromatin dynamics are largely missing. We have recently found that histone chaperone FACT (facilitates chromatin transcription) is overexpressed in ~18–20% of BrCa cases. FACT is elevated upon transformation of mammary epithelial cells and is essential for viability of tumor cells. BrCa cells with high FACT have a more aggressive transcriptional program than those with low FACT cells. Based on this we propose that FACT may be a marker of aggressive BrCa. In this study, we aimed to comprehensively characterize the pattern of FACT expression in BrCa in relation to other molecular and clinical prognostic markers. We developed and tested an assay for the detection and quantitation of protein levels of both FACT subunits, SSRP1, and SPT16, in clinical samples. We compared the value of mRNA and protein as potential markers of disease aggressiveness using a large cohort of patients (n=1092). We demonstrated that only SSRP1 immunohistochemical staining is a reliable indicator of FACT levels in tumor samples. High SSRP1 correlated with known markers of poor prognosis, such as negative hormone receptor status, presence of Her2, high-grade tumors, and tumors of later clinical stage. At the same time, no strong correlation between SSRP1 expression and survival was detected when all samples were analyzed together. Clear trend toward longer survival of patients with low or no SSRP1 expression in tumor samples was seen in several subgroups of patients, and most importantly significant association of high SSRP1 expression with shorter disease-free survival was detected in patients with early-stage and low-grade BrCa, the category of patients with the highest demand in predictive marker of disease progression.