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Atrial fibrillation (AF) is associated with cognitive impairment, with or without history of stroke. The risk of developing cognitive impairment is increased after clinical stroke. Prospective registries confirm the increased risk of both vascular and Alzheimer's dementia in patients with AF. The purported mechanistic links between AF and cognitive impairment are clinical stroke, subclinical cerebral small-vessel disease, autonomic dysfunction, and systemic and neuroinflammation. Several shared risk factors and genetics also contribute to this interplay. In this review, we explore the evidence bridging cognitive impairment with AF and review the mechanisms and therapeutic targets.

ObjectivesCardiac arrhythmias predict poor outcome after myocardial infarction (MI). We studied if arrhythmia monitoring with an insertable cardiac monitor (ICM) can improve treatment and outcome.DesignBIO|GUARD-MI was a randomized, international open-label study with blinded outcome assessment.SettingTertiary care facilities monitored the arrhythmias, while the follow-up remained with primary care physicians.ParticipantsPatients after ST-elevation (STEMI) or non-ST-elevation MI with an ejection fraction >35% and a CHA2DS2-VASc score ≥4 (men) or ≥5 (women).InterventionsPatients were randomly assigned to receive or not receive an ICM in addition to standard post-MI treatment. Device-detected arrhythmias triggered immediate guideline recommended therapy changes via remote monitoring.Main outcome measuresMACE, defined as a composite of cardiovascular death or acute unscheduled hospitalization for cardiovascular causes.Results790 patients (mean age 71 years, 72% male, 51% non-STEMI) of planned 1,400 pts were enrolled and followed for a median of 31.6 months. At 2 years, 39.4% of the device group and 6.7% of the control group had their therapy adapted for an arrhythmia [hazard ratio (HR) = 5.9, P

Background: Health literacy is a key enabler of effective behavioural modification in chronic diseases. While patient reported outcome measures (PROMs) exists for patient with atrial fibrillation (AF), none address risk factors comprehensively. The aim of the study was to develop and qualitatively validate a disease specific PROM that incorporates knowledge on risk factors and assesses interactive and critical health literacy of people living with AF. Methods: The 47-item Atrial Fibrillation Health Literacy Questionnaire (AFHLQ) was developed and validated through a qualitative research design. Expert and Consumer focus groups, each consisting of seven participants provided opinion. Results: The 47-item questionnaire consists of 5 domains: (1) what is AF, (2) what are the symptoms of AF, (3) why do people get AF, (4) management of AF, and (5) what measures can slow or prevent the progression of AF. Recommendations resulted in several changes to the original 47 item list during the qualitative validation process: 13 original items were removed, and 13 new items were added. The response categories were also simplified from a Likert scale to “yes”, “no” or “don't know”. Conclusion: A 47-item AFHLQ instrument was developed and validated with modifications made through clinical expert and consumer opinion. This tool has a potential to be used to evaluate and guide interventions at a clinical and population level to understand and improve AF health literacy and outcomes.

Blood pressure variability (BPV) impacts brain health by influencing brain structure and cerebrovascular pathologies, though the mechanisms are poorly understood. Changes in the cerebrovasculature may lead to late-onset depression, cognitive impairment, and dementia, however the relationship between BPV with depression and anxiety remains unclear, due to methodological differences and inconsistencies in past research. This review aims to clarify the association between BPV with depression and anxiety in adults to inform understandings of the mechanisms implicating BPV in cognitive health. A systematic search from inception through to January 2024 was performed on Embase, PubMed, PsycINFO, and Web of Science. Studies that assessed BPV quantified by beat-to-beat, 24-hour, or visit-to-visit were eligible if the standardised assessment of depression and/or anxiety were reported as a linear association, or mean differences across control and affect groups. A total of 14 articles reporting on 13 samples and N = 5055 persons met the inclusion criteria (median female proportion = 61 %, range 0 % - 76 %). A meta-analysis was not possible due to methodological heterogeneity in BPV measurements and metrics across studies. Mixed results were observed across depression studies with inconsistencies and variation in the direction, strength of association, and BPV metric. There was weak evidence from only three studies to support a linear association between systolic coefficient of variation and anxiety. Collectively, the findings contribute to understanding the association between BPV and brain health, suggesting that any relationship between BPV and brain structures critical for cognitive function are independent of depression and only modestly implicate anxiety.

Humanities are an integral part of health professions. However, with educational focus shifting gradually toward knowledge, information, evidence-based medicine, and technology, it has taken a back seat and become a part of the “hidden curriculum.” Humanities are hardly ever taught upfront to students of the health profession, let alone its assessment. With the need of its inclusion in health professional education now recognized and established through competency-based education, we need to be aware of the tools and strategies which can be used to teach and assess it. In this article, we share selected tools with relevant readily usable examples for teaching humanities to students of the health profession. Faculty may find it useful to plan sessions around related competencies. Incorporation of such experiential teaching and learning methods can help us achieve the transition from “high-tech” to “high touch” health professions education.

Introduction Atrial fibrillation (AF) is associated with increased risk of stroke, heart failure and death. Health literacy, an aspect that falls within precision health, has been recognised as an important factor. We will be focusing on the impact of these interventions specifically to AF and its health outcomes.Methods and analysis This protocol is informed by the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols. The results will be reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to determine the impacts of health literacy interventions on AF outcomes. Searches will be carried out on databases including MEDLINE, EMBASE, Web of Science, CINAHL, Emcare, Cochrane Library and Google Scholar. Citations will be collected via Endnote 20, then into Covidence for duplicate removal, and article screening. Extraction will occur using a standardised extraction tool and studies will be synthesised using best evidence synthesis. Downs and Black’s checklist will be used for risk of bias and assessment of overall quality of evidence will use the Grading of Recommendations, Assessment, Development and Evaluation approach.Ethics and dissemination Approval from human research ethics committee is not required. Dissemination will occur in peer-reviewed journals and conference presentations.PROSPERO registration number CRD42022304835.

Introduction: Amiodarone is a highly effective antiarrhythmic-drug with well recognized toxic side-effects. The effects of the drug late in patients with atrial fibrillation (AF) is not well described. Methods and results: We present a single centre prospectively collected series of patients with thyrotoxicosis occurring late after the cessation of amiodarone. Between 2006 and 2018, 8 patients were identified with amiodarone induced thyrotoxicosis (AIT). Amiodarone was prescribed for AF in 7 patients and ventricular tachycardia in 1 patient. Mean duration of therapy was 329 [42–1092] days, mean dose of 200 ± 103.5 mg/day. Amiodarone use was short term (

Introduction: Script concordance test (SCT) is an innovativetool to teach and assess the clinical reasoning skills of medicalstudents. It is the key aspect of clinical competency that enablesthe medical graduates to progress from novice to practicinggeneral practitioner. SCT was used the first time in pharmacologyto inculcate clinic reasoning skills in medical students by focusingon the topic of pharmacotherapy.Methods: A SCT with a total of 18 questions, with 15 questionshaving 3 items each, one having four items and two questionshaving two items each was administered to 170 second yearundergraduate medical students in the subject of pharmacologyto assess the clinical reasoning skills. It was an interventionalstudy conducted using convenience sampling technique with asample size of 170. Aggregate scoring method was used to dothe scoring obtained from the answers given by 10 expert-panelmembers in the field of pharmacology, which were used as ananswer key to do the final scoring of the students. Descriptivestatistics were computed using Students t test. SCT conductincluded a small-group feedback session to the students post-SCT. A feedback questionnaire was administered to the studentsone week after the feedback session. Reliability of the SCT andfeedback questionnaire was checked by calculating Cronbachalpha through Siegle reliability calculator. Content validity of thetest as well as feedback questionnaire was done by the panel ofexperts included in the study. Results: Though the mean score of the students (27.68±4.59) wassignificantly lower than the expert panel (40.91±3.52), studentswere highly satisfied as they expressed that SCT enhanced theirperceived clinical reasoning skills (median value=5) and criticalthinking (median value=4). The Cronbach alpha for the test was0.76. The students were also highly satisfied with the feedbackgiven by the teachers after the SCT (median value=4).Conclusion: SCT enhances critical thinking and clinical reasoningskills of the students, as reported by them. With the conductof feedback session post-SCT, it can be used as assessment forlearning tool and can be well used in a para-clinical subject ofpharmacology.

Energy efficiency has recently turned out to be primary issue in wireless sensor networks. Sensor networks are battery powered, therefore become dead after a certain period of time. Thus, improving the data dissipation in energy efficient way becomes more challenging problem in order to improve the lifetime for sensor devices. The clustering and tree based data aggregation for sensor networks can enhance the network lifetime of wireless sensor networks. Hybrid Ant colony optimization (ACO) and particle swarm optimization (PSO) based energy efficient clustering and tree based routing protocol is proposed. Initially, clusters are formed on the basis of remaining energy, then, hybrid ACOPSO based data aggregation will come in action to improve the inter-cluster data aggregation further. Extensive analysis demonstrates that proposed protocol considerably enhances network lifetime over other techniques. Keywords: Wireless sensor networks, Ant colony optimization, Energy efficient, Particle swarm optimization

Background: Sequentially mapped complex fractionated atrial electrograms (CFAE) and dominant frequency (DF) sites have been targeted during catheter ablation for atrial fibrillation (AF). However, these strategies have yielded variable success and have not been shown to correlate consistently with AF dynamics. Here, we evaluated whether the spatiotemporal stability of CFAE and DF may be a better marker of AF sustenance and termination. Methods: Eighteen sheep with 12 weeks of “one-kidney, one-clip” hypertension underwent open-chest studies. A total of 42 self-terminating (28–100 s) and 6 sustained (>15 min) AF episodes were mapped using a custom epicardial plaque and analyzed in 4-s epochs for CFAE, using the NavX CFE-m algorithm, and DF, using a Fast Fourier Transform. The spatiotemporal stability index (STSI) was calculated using the intraclass correlation coefficient of consecutive AF epochs. Results: A total of 67,733 AF epochs were analyzed. During AF initiation, mean CFE-m and the STSI of CFE-m/DF were similar between sustained and self-terminating episodes, although median DF was higher in sustained AF (p=0.001). During sustained AF, the STSI of CFE-m increased significantly (p=0.02), whereas mean CFE-m (p=0.5), median DF (p=0.07), and the STSI of DF remained unchanged (p=0.5). Prior to AF termination, the STSI of CFE-m was significantly lower (p

BackgroundBesides hypertension, obesity and the metabolic syndrome have recently emerged as risk factors for atrial fibrillation. This study sought to delineate the development of an arrhythmogenic substrate for atrial fibrillation in hypertension with and without concomitant obesity and metabolic syndrome. Methods and ResultsWe compared obese spontaneously hypertensive rats (SHR‐obese, n=7–10) with lean hypertensive controls (SHR‐lean, n=7–10) and normotensive rats (n=7–10). Left atrial emptying function (MRI) and electrophysiological parameters were characterized before the hearts were harvested for histological and biochemical analyses. At the age of 38 weeks, SHR‐obese, but not SHR‐lean, showed increased body weight and impaired glucose tolerance together with dyslipidemia compared with normotensive rats. Mean blood pressure was similarly increased in SHR‐lean and SHR‐obese when compared with normotensive rats (178±9 and 180±8 mm Hg [not significant] versus 118±5 mm Hg, P

Purpose: Conventional diagnostic techniques for detecting Mycobacterium avium infection are far from satisfactory. As serodiagnostic tests for M. avium infection have been shown to be simple and rapid, the present study was carried out to identify and evaluate M. avium secretory protein(s) of diagnostic potential. Materials and Methods: Initially, by differential immunoblotting, a specific protein band of 45-50 kDa was recognized. Anion exchange column chromatography was used for purification of proteins. After fractionation, blast search was carried out. Further immunoreactivity studies were done with M. avium and Mycobacterium tuberculosis infected mice sera. Clinical utilization was confirmed by conducting indirect enzyme-linked immunosorbent assay (ELISA) with serum samples from mycobacterial infected patients. Results: A complex of three proteins (Aro-Tal-AST) of molecular weight ~48 kDa, shown to be Aro A homologue (Aro), transaldolase (Tal) and aspartate transaminase (AST) by blast search was separated. Immunoreactivity studies of purified complex protein with mice sera confirmed it to be specific for M. avium infection. Indirect ELISA with patient samples further confirmed it to be M. avium infection specific. Conclusion: Aro-Tal-AST protein is specifically recognized by patients infected with M. avium and can be used as a marker for simple and rapid ELISA based tests for differential diagnosis of M. avium infection in patients with M. avium complex (MAC).

During the last decade, despite increased investment in drug research and development related activity, stagnation in new drug discovery has been documented. Despite a 70% increase in investment in research and development-related activities, a 40% fall in launch of new chemical entities was seen during 1994-2004. A steep rise in the attrition rate of drug development has complicated the matter. Rising cost and increased attrition rates proved major barriers to investment in higher risk drugs or in therapies for uncommon diseases or diseases that predominantly afflict the poor. This prompted Food and Drug Administration (FDA) to highlight this problem in a 2004 white paper classified as "Critical Path Initiative" (CPI) and to initiate steps to target stagnation and rise in attrition rates. Many new drug development projects have started worldwide taking cue from CPI; adopting microdosing, adaptive designs and taking advantage of newly developed biomarkers under the CPI. This review discusses the various strategies adopted under CPI to decrease attrition rate and stagnation of new drug development, and the challenges and controversies associated with CPI.

Background: In the last 30 years concepts in pharmacology have moved from Essential Medicines (EM) to P-drugs via the Rational Use of Medicines (RUM), but no structured study has evaluated the level of understanding among the working clinicians about these concepts. Aim: The present study was designed to assess the attitude and knowledge of clinical practitioners about the concepts of RUM, EM, P-drugs, and sources of drug-information, across North India. Materials and Methods: A cross-sectional study was carried out in and around the teaching hospitals attached to Medical Colleges, enrolling 504 clinicians from six centers across North India to fill-up a questionnaire containing 25 questions. Statistical Analysis: The results were compiled using percentages and averages. Univariate analysis, which explores each variable in a data set separately, was carried out by using the Fisher′s exact test. Results: Only one-fourth of the participants claimed that they always prescribed Essential Medicine; no one could correctly count the number of drugs / drug combinations in the Indian Essential Drug list; only 15.1% of the clinicians wrote the generic names of drugs on the prescription slip; about one-third of clinicians were not fully aware about the adverse effects, drug interactions, and contraindications of the drugs they prescribed; about 83% of physicians admitted to relying on information from Medical Representatives and an interest in research activities seemed to be lost. Conclusion: Results show a sorry state of affairs among clinicians, as far as the level of understanding about EM, P-drugs, and RUM is concerned, and it points toward arranging more continuing medical education (CME) for clinicians with regard to these concepts.

Delirium tremens is recognized as a potentially fatal and debilitating complication of alcohol withdrawal. Use of sedatives, particularly benzodiazepines, is the cornerstone of therapy for delirium tremens. But sometimes, very heavy doses of benzodiazepines are required to control delirious symptoms. We are reporting one such case of delirium tremens, which required very heavy doses of benzodiazepines and was ultimately controlled by using infusion of propofol. Thus propofol should always be considered as an option to treat patients with resistant delirium tremens.

Arias et al in the article 'A narrow QRS complex tachycardia with an apparently concentric retrograde atrial activation sequence' describe a case with spontaneous intra atrial block along the mitral isthmus to explain the change in atrial activation [1]. This phenomenon has been described during radiofrequency ablation while ablating along the lateral mitral annulus for a left free wall pathway [2-4]. Mitral isthmus block is very difficult to achieve even after repeated RF lesions [5]. We feel there is a simpler explanation to their finding. We have two points to make. First, in figure 1 CS 3-4 has a good A but hardly any V. Authors themselves have admitted to difficulty in advancing the CS catheter. We strongly feel that CS 34 was more into atrium and not in the CS. This could have resulted in the mistaken assumption of concentric activation. Advancing the catheter further into the CS would have confirmed this. Secondly, a change in activation can often be due to the presence of another tachycardia. To ascribe the change in activation to a mitral isthmus block, we must demonstrate that the tachycardia cycle length and VA in the HIS remained the same. Also, only if the concentric activation is persisting at the time of ablation, the final successful ablating site at the lateral mitral isthmus having the earliest A confirms that the block at the mitral isthmus was the cause of concentric activation. Further more advancing the CS catheter further into the CS during the time of apparent concentric activation would have confirmed the mechanism. If the CS 3-4 was out of the CS, the deeper insertion would have made the activation eccentric. If spontaneous isthmus block was actually present, double potentials along the line of block with sudden change in activation beyond it would have confirmed.

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Abstract In this research work, optimized nebivolol-loaded lecithin-chitosan hybrid nanoparticles (NEB-LCNPs) were prepared using sequential screening and optimization designs. The design of experiments software (DoE) was used to obtain a robust formulation that can improve ocular delivery of the NEB in the treatment of glaucoma. The optimized NEB-LCNPs had a mean particle size of 170.5 ± 5.3 nm and drug loading of 10.5 ± 1.2%. These were further loaded in a dual-responsive in situ gel, designed and reported previously by our group. The NEB-LCNPs loaded in situ gel (NEB-LCNPs-ISG) was characterized for physicochemical properties, rheological behavior, stability, in vitro dissolution, and ocular in vivo studies. The ocular pharmacokinetics showed that NEB-LCNPs-ISG had two-fold higher aqueous humor exposure with AUC0–tlast of 375.4 ng × h/mL and sustained drug concentrations for longer durations (1.7-folds higher duration with a mean residence time of 10.6 h) in comparison to a conventional aqueous suspension of NEB (NEB-Susp). Similarly, the pharmacodynamic study showed that NEB-LCNPs-ISG resulted in a higher percentage reduction in intraocular pressure (% ΔIOP) of 28.1 ± 1.8% × h, which was 2.2-times higher reduction compared to NEB-Susp (74.2 ± 3.2% × h). In addition, the pharmacodynamic effect was more sustained with a mean response time of 11.3 ± 0.2 h, a 2.8-times higher response time compared to NEB-Susp (4.06 ± 0.3 h). These results suggest that NEB-LCNPs-ISG was more effective than the conventional aqueous suspension of NEB in the treatment of glaucoma.

Nebivolol hydrochloride (NEB), a 3rd-generation beta-blocker, was recently explored in managing open-angle glaucoma due to its mechanism of action involving nitric oxide release for the vasodilation. To overcome the issue of low ocular bioavailability and the systemic side effects associated with conventional ocular formulation (aqueous suspension), we designed and optimized polycaprolactone polymeric nanoparticles (NEB-PNPs) by applying design of experiments (DoE). The particle size and drug loading of the optimized NEB-PNPs were 270.9 ± 6.3 nm and 28.8 ± 2.4%, respectively. The optimized NEB-PNPs were suspended in a dual-sensitive in situ gel prepared using a mixture of P407 + P188 (as a thermo-sensitive polymer) and κCRG (as an ion-sensitive polymer), reported previously by our group. The NEB-PNPs-loaded in situ gel (NEB-PNPs-ISG) formulation was characterized for its rheological behavior, physical and chemical stability, in vitro drug release, and in vivo efficacy. The NEB-PNPs-loaded in situ gel, in ocular pharmacokinetic studies, achieved higher aqueous humor exposure (AUC0–t = 329.2 ng × h/mL) and for longer duration (mean residence time = 9.7 h) than compared to the aqueous suspension of plain NEB (AUC0–t = 189 ng × h/mL and mean residence time = 6.1 h) reported from our previous work. The pharmacokinetic performance of NEB-PNPs-loaded in situ gel translated into a pharmacodynamic response with 5-fold increase in the overall percent reduction in intraocular pressure by the formulation compared to the aqueous suspension of plain NEB reported from our previous work. Further, the mean response time of NEB-PNPs-loaded in situ gel (12.4 ± 0.6 h) was three times higher than aqueous suspension of plain NEB (4.06 ± 0.3 h).

Neratinib maleate (NM), a tyrosine kinase inhibitor, is used in the treatment of breast cancer. NM is orally administered at a high dose of 290 mg due to its low solubility and poor dissolution rate at pH > 3, as well as gut-wall metabolism limiting its bioavailability. Self-emulsifying drug delivery systems (SEDDSs) of NM were developed in the current study to improve its oral bioavailability. The oily vehicle (clove oil) was selected based on the solubility of NM, while the surfactant and the cosurfactant were selected based on the turbidimetric analysis. Three different sets were screened for surfactant selection in the preparation of SEDDS formulations, the first set containing Cremophor® EL alone as the surfactant, the second set containing a mixture of Cremophor® EL (surfactant) and Caproyl® PGMC (cosurfactant), and the third set containing a mixture of Cremophor® EL (surfactant) and Capmul® MCM C8 (cosurfactant). Propylene glycol was used as the cosolubilizer in the preparation of SEDDSs. A series of studies, including the construction of ternary phase diagrams to determine the zone of emulsification, thermodynamic stability studies (involving dilution studies, freeze-thaw, and heating–cooling studies), turbidimetric analysis, and physicochemical characterization studies were conducted to identify the two most stable combinations of SEDDSs. The two optimized SEDDS formulations, TP16 and TP25, consisted of clove oil (45% w/w) and propylene glycol (5% w/w) in common but differed with respect to the surfactant or surfactant mixture in the formulations. TP16 was prepared using a mixture of Cremophor® EL (surfactant) and Caproyl® PGMC (cosurfactant) in a 4:1 ratio (50% w/w), while TP25 contained only Cremophor® EL (50% w/w). The mean globule sizes were 239.8 ± 77.8 nm and 204.8 ± 2.4 nm for TP16 and TP25, respectively, with an emulsification time of p < 0.05) and 2.24 (p < 0.01), respectively.

The article discusses the use of Bexarotene gel as the new topical therapy Alopecia areata (AA). It notes that AA is an autoimmune disease chracterized by discrete patches of nonscarring hair loss, and is also called spot baldness as it mostly causes bald spots on the scalp. It states that the hair loss is triggered by perifollicular and intrafollicular mononuclear cell infiltrates, composed primarily of activated CD4+ and CD8+ T cells. It mentions that Bexarotene is a member of retinoids subclass that selectively activate retinoid X receptors (RXRs), and has been approved orally for the treatment of refractory cutaneous T-cell lymphomas (CTCL). Moreover, Bexarotene gel 1% is indicated for the topical treatment of cutaneous lesions in patients with refractory or persistent CTCL.