Project description:ObjectiveTo determine the effect of heart attack patients' access to intensive treatment on mortality and costs.Data sourcesAdministrative data of 4,920 patients with acute myocardial infarction from the Austrian Social Security Database and the Upper Austrian Sickness Fund for the period 2002-2011.Study designAs treatment intensity in a hospital largely depends on whether it has a catheterization laboratory, we explore the effects of patients' initial admission to such specialized percutaneous coronary intervention (PCI) hospitals. To account for the nonrandom selection of patients into hospitals, we exploit individuals' place of residence as a source of exogenous variation in an instrumental variable framework.Principal findingsWe find that the initial admission to PCI hospitals increases patients' survival chances substantially. The effect on 3-year mortality is -9.5 percentage points. Subgroup analysis shows the strongest effects in relative terms for patients below the age of 65. We do not find significant effects on long-term inpatient costs and only marginal increases in outpatient costs.ConclusionsOur findings suggest that place of residence affects the access of patients to invasive heart attack treatment and therefore their chance of survival. We conclude that that providing more patients immediate access to PCI hospitals should be beneficial.
Project description:IntroductionAwareness of heart attack symptoms and the best response is a national public health priority, especially among those at higher risk of heart disease. Adults with sensory loss are more likely to develop heart disease than those without and may be at risk of poor heart attack knowledge owing to limited patient-provider communication and access to health information. The aim of this study is to examine the association between sensory loss and heart attack knowledge.MethodsCross-sectional, nationally representative data from the 2014 and 2017 National Health Interview Survey were used. Analyses were conducted in 2021. Participants aged ≥20 years were included (N=61,168). Being aware of heart attack symptoms and the best response was considered as recognizing the 5 examined symptoms of heart attacks and the proper emergency response, as defined in the Healthy People 2020 objectives. Functional hearing and vision losses were defined as self-reported difficulty in hearing and seeing.ResultsOverall, 16.2% reported functional hearing loss, and 10.1% reported vision loss. Having vision loss was associated with a lack of knowledge of heart attacks symptoms or the best response (prevalence ratio=1.08, 95% CI=1.06, 1.11). In a separate model, having vision loss only and dual sensory loss (concurrent vision and hearing loss) were associated with not having this knowledge (prevalence ratio=1.09, 95% CI=1.06, 1.12 and PR=1.08, 95% CI=1.01, 1.15, respectively), but having hearing loss only was not (prevalence ratio=1.03, 95% CI=0.99, 1.06).ConclusionsNon-institutionalized adults with sensory loss may represent a group to target for improving the knowledge of heart attacks in the population.
Project description:Mechanotransduction modulates cellular functions as diverse as migration, proliferation, differentiation, and apoptosis. It is crucial for organ development and homeostasis and leads to pathologies when defective. However, despite considerable efforts made in the past, the molecular basis of mechanotransduction remains poorly understood. Here, we have investigated the genetic basis of mechanotransduction in Drosophila. We show that the fly heart senses and responds to mechanical forces by regulating cardiac activity. In particular, pauses in heart activity are observed under acute mechanical constraints in vivo. We further confirm by a variety of in situ tests that these cardiac arrests constitute the biological force-induced response. In order to identify molecular components of the mechanotransduction pathway, we carried out a genetic screen based on the dependence of cardiac activity upon mechanical constraints and identified Painless, a TRPA channel. We observe a clear absence of in vivo cardiac arrest following inactivation of painless and further demonstrate that painless is autonomously required in the heart to mediate the response to mechanical stress. Furthermore, direct activation of Painless is sufficient to produce pauses in heartbeat, mimicking the pressure-induced response. Painless thus constitutes part of a mechanosensitive pathway that adjusts cardiac muscle activity to mechanical constraints. This constitutes the first in vivo demonstration that a TRPA channel can mediate cardiac mechanotransduction. Furthermore, by establishing a high-throughput system to identify the molecular players involved in mechanotransduction in the cardiovascular system, our study paves the way for understanding the mechanisms underlying a mechanotransduction pathway.
Project description:Encoding and recognising complex natural sequences provides a challenge for human vision. We found that observers could recognise a previously presented segment of a video of a hearth fire when embedded in a longer sequence. Recognition performance declined when the test video was spatially inverted, but not when it was hue reversed or temporally reversed. Sampled motion degraded forwards/reversed playback discrimination, indicating observers were sensitive to the asymmetric pattern of motion of flames. For brief targets, performance increased with target length. More generally, performance depended on the relative lengths of the target and embedding sequence. Increased errors with embedded sequence length were driven by positive responses to non-target sequences (false alarms) rather than omissions. Taken together these observations favour interpreting performance in terms of an incremental decision-making model based on a sequential statistical analysis in which evidence accrues for one of two alternatives. We also suggest that prediction could provide a means of providing and evaluating evidence in a sequential analysis model.
Project description:Neuropathic pain is a frequent feature of diabetic peripheral neuropathy (DPN) and small fiber neuropathy (SFN). Resolving the genetic architecture of these painful neuropathies will lead to better disease management strategies, counselling and intervention. Our aims were to profile ten sodium channel genes (SCG) expressed in a nociceptive pathway in painful and painless DPN and painful and painless SFN patients, and to provide a perspective for clinicians who assess patients with painful peripheral neuropathy. Between June 2014 and September 2016, 1125 patients with painful-DPN (n = 237), painless-DPN (n = 309), painful-SFN (n = 547) and painless-SFN (n = 32), recruited in four different centers, were analyzed for SCN3A, SCN7A-SCN11A and SCN1B-SCN4B variants by single molecule Molecular inversion probes-Next Generation Sequence. Patients were grouped based on phenotype and the presence of SCG variants. Screening of SCN3A, SCN7A-SCN11A, and SCN1B-SCN4B revealed 125 different (potential) pathogenic variants in 194 patients (17.2%, n = 194/1125). A potential pathogenic variant was present in 18.1% (n = 142/784) of painful neuropathy patients vs. 15.2% (n = 52/341) of painless neuropathy patients (17.3% (n = 41/237) for painful-DPN patients, 14.9% (n = 46/309) for painless-DPN patients, 18.5% (n = 101/547) for painful-SFN patients, and 18.8% (n = 6/32) for painless-SFN patients). Of the variants detected, 70% were in SCN7A, SCN9A, SCN10A and SCN11A. The frequency of SCN9A and SCN11A variants was the highest in painful-SFN patients, SCN7A variants in painful-DPN patients, and SCN10A variants in painless-DPN patients. Our findings suggest that rare SCG genetic variants may contribute to the development of painful neuropathy. Genetic profiling and SCG variant identification should aid in a better understanding of the genetic variability in patients with painful and painless neuropathy, and may lead to better risk stratification and the development of more targeted and personalized pain treatments.
Project description:IntroductionNonfocal transient neurological attacks (TNAs) are associated with an increased risk of future dementia, but it is unclear whether TNAs are also associated with concurrent cognitive impairment. We hypothesized that recent TNAs are related to worse cognitive functioning. We tested our hypothesis in patients with heart failure, as these patients are at risk of cerebral hypoperfusion, which might play a role in the etiology of TNAs.MethodsWe performed neuropsychological testing in all patients with heart failure enrolled in the Heart Brain Connection study. We assessed global cognition, attention-psychomotor speed, executive functioning, memory and language. All patients were interviewed with a standardized questionnaire on the occurrence of TNAs in the preceding 6 months. We studied associations between TNAs and cognitive functioning with linear and logistic regression analyses, adjusted for age, sex and education. We performed additional analyses in patients without previous stroke or TIA and in patients without brain infarction on MRI.ResultsThirty-seven (23%) of 158 patients (mean age 70 years, 67% men) experienced one or more TNAs. Patients with a recent TNA were more likely to be impaired on ≥ 1 cognitive domains than patients without TNAs [41% vs. 18%, adjusted odds ratio 4.6, 95% confidence interval (CI) 1.8-11.8]. Patients with TNAs performed worse than patients without TNAs on global cognition (mean difference in z scores - 0.36, 95% CI - 0.54 to - 0.18), and on the cognitive domains attention-psychomotor speed (mean difference - 0.40, 95% CI - 0.66 to - 0.14), memory (mean difference - 0.57, 95% CI - 0.98 to - 0.15) and language (mean difference - 0.47, 95% CI - 0.79 to - 0.16). These associations were independent of cardiac output and volume of white matter hyperintensities. Subgroup analyses in patients without previous stroke or TIA or brain infarction on MRI (n = 78) yielded comparable results, with the exception of the cognitive domain language, which was no longer different between patients with and without TNAs.ConclusionAmong patients with heart failure, TNAs are associated with cognitive impairment, which warrants the need for more clinical awareness of this problem.
Project description:Background Racially and ethnically minoritized groups, people with lower income, and rural communities have worse access to percutaneous coronary intervention (PCI) than their counterparts, but PCI hospitals have preferentially opened in wealthier areas. Our study analyzed disparities in PCI access, treatment, and outcomes for patients with acute myocardial infarction based on the census-derived Area Deprivation Index. Methods and Results We obtained patient-level data on 629 419 patients with acute myocardial infarction in California between January 1, 2006 and December 31, 2020. We linked patient data with population characteristics and geographic coordinates, and categorized communities into 5 groups based on the share of the population in low or high Area Deprivation Index neighborhoods to identify differences in PCI access, treatment, and outcomes based on community status. Risk-adjusted models showed that patients in the most advantaged communities had 20% and 15% greater likelihoods of receiving same-day PCI and PCI during the hospitalization, respectively, compared with patients in the most disadvantaged communities. Patients in the most advantaged communities also had 19% and 16% lower 30-day and 1-year mortality rates, respectively, compared with the most disadvantaged, and a 15% lower 30-day readmission rate. No statistically significant differences in admission to a PCI hospital were observed between communities. Conclusions Patients in disadvantaged communities had lower chances of receiving timely PCI and a greater risk of mortality and readmission compared with those in more advantaged communities. These findings suggest a need for targeted interventions to influence where cardiac services exist and who has access to them.
Project description:Painless bleeding in a patient presenting from the community with elevated coagulation studies rarely makes the physicians suspect superwarfarin or rodenticide poisoning. Although a significant number of superwarfarin exposure cases are diagnosed every year, we believe there appears to be delay in diagnosis and confusion in determining what is the ideal way to treat and monitor these patients during the management. This is the first thorough literature review of all the reported cases of superwarfarin poisoning which also studied the clinical presentation, management and follow-up patterns. We present a 70-year-old man who presented to the emergency room with epistaxis, melena, cola-colored urine with elevated prothrombin time (PT), activated partial thromboplastin time (aPTT) and international normalized ratio (INR). Mixing studies showed complete correction of coagulopathy indicative of factor deficiency. Additional history revealed that the patient had arguments with family member at home and made us suspect superwarfarin exposure. Qualitative brodifacoum testing was positive and was managed with fresh frozen plasma and high doses of vitamin K1 (phytomenadione) with serial monitoring of INR and clinical symptoms. Superwarfarin poisoning should be considered in the differential diagnosis of a patient who presents with above clinical and laboratory profile especially in the absence of any history of coagulopathy or anticoagulant use. We want to raise public and especially physician awareness that history taking, early diagnosis and managing in right clinical setting play a significant role in survival of these patients.
Project description:Aberrantly truncated immature O-glycosylation in proteins occurs in essentially all types of epithelial cancer cells, which was demonstrated to be a common feature of most adenocarcinomas and strongly associated with cancer proliferation and metastasis. Although extensive efforts have been made toward the development of anticancer antibodies targeting MUC1, one of the most studied mucins having cancer-relevant immature O-glycans, no anti-MUC1 antibody recognises carbohydrates and the proximal MUC1 peptide region, concurrently. Here we present a general strategy that allows for the creation of antibodies interacting specifically with glycopeptidic neoepitopes by using homogeneous synthetic MUC1 glycopeptides designed for the streamlined process of immunization, antibody screening, three-dimensional structure analysis, epitope mapping and biochemical analysis. The X-ray crystal structure of the anti-MUC1 monoclonal antibody SN-101 complexed with the antigenic glycopeptide provides for the first time evidence that SN-101 recognises specifically the essential epitope by forming multiple hydrogen bonds both with the proximal peptide and GalNAc linked to the threonine residue, concurrently. Remarkably, the structure of the MUC1 glycopeptide in complex with SN-101 is identical to its solution NMR structure, an extended conformation induced by site-specific glycosylation. We demonstrate that this method accelerates dramatically the development of a new class of designated antibodies targeting a variety of "dynamic neoepitopes" elaborated by disease-specific O-glycosylation in the immunodominant mucin domains and mucin-like sequences found in intrinsically disordered regions of many proteins.