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Importance: The Sentinel System is a key component of the US Food and Drug Administration (FDA) postmarketing safety surveillance commitment and uses clinical health care data to conduct analyses to inform drug labeling and safety communications, FDA advisory committee meetings, and other regulatory decisions. However, observational data are frequently deemed insufficient for reliable evaluation of safety concerns owing to limitations in underlying data or methodology. Advances in large language models (LLMs) provide new opportunities to address some of these limitations. However, careful consideration is necessary for how and where LLMs can be effectively deployed for these purposes., Observations: LLMs may provide new avenues to support signal-identification activities to identify novel adverse event signals from narrative text of electronic health records. These algorithms may be used to support epidemiologic investigations examining the causal relationship between exposure to a medical product and an adverse event through development of probabilistic phenotyping of health outcomes of interest and extraction of information related to important confounding factors. LLMs may perform like traditional natural language processing tools by annotating text with controlled vocabularies with additional tailored training activities. LLMs offer opportunities for enhancing information extraction from adverse event reports, medical literature, and other biomedical knowledge sources. There are several challenges that must be considered when leveraging LLMs for postmarket surveillance. Prompt engineering is needed to ensure that LLM-extracted associations are accurate and specific. LLMs require extensive infrastructure to use, which many health care systems lack, and this can impact diversity, equity, and inclusion, and result in obscuring significant adverse event patterns in some populations. LLMs are known to generate nonfactual statements, which could lead to false positive signals and downstream evaluation activities by the FDA and other entities, incurring substantial cost., Conclusions and Relevance: LLMs represent a novel paradigm that may facilitate generation of information to support medical product postmarket surveillance activities that have not been possible. However, additional work is required to ensure LLMs can be used in a fair and equitable manner, minimize false positive findings, and support the necessary rigor of signal detection needed for regulatory activities.

Background: Despite an association between operator volumes and procedural success, there remains an incomplete understanding of the contemporary utilization and procedural volumes for mitral valve transcatheter edge-to-edge repair (MTEER). We aimed to identify annual operator procedural volumes, temporal trends, and geographic variability for MTEER among Medicare patients in the United States (US)., Methods: We queried the National Medicare Provider Utilization and Payment Database for a CPT code (33418) specific for MitraClip device from 2015 through 2019. We analyzed annual operator procedural volumes and incidence and identified longitudinal and geographic trends in MTEER utilization., Results: From 2015 through 2019, a total of 27,034 MTEER procedures were performed among Medicare patients in the US. The nationwide incidence increased from 6.2 per 100,000 patients in 2015 to 23.8 per 100,000 patients in 2019, a 283% increase over the study period ( P trend  < 0.001). The incidence of MTEER by state varied by nearly 900% (range 5.5 to 54.9 per 100,000 person-years). In 2019, the mean annual MTEER operator annual volume was 9.1 MTEER procedures and had grown from 6.2 per year in 2015., Conclusions: In this nationwide study of Medicare beneficiaries in the United States, we identified a significant and sustained increase in the utilization of MTEER devices and operators and growth in annual procedural volumes from 2015 through 2019 with considerable variability in utilization by state. Further studies are needed to understand the clinical impact of variability in utilization and the optimal procedural volumes to ensure high efficacy outcomes and maintain critical access to MTEER therapies., Competing Interests: Zahr reports research grants from Edwards Lifesciences, Medtronic, and Siemens. Sorajja reports service as a consultant for Abbot Vascular, Edwards Lifesciences, Medtronic, Boston Scientific, TriFlo, and VDyne. Reeves reports service as consultant for Edwards Lifesciences and research grants from Edwards Lifesciences, Avicenna, and Ventrix. Song reports service as a consultant for Medtronic and Edwards Lifesciences. Smith reports service as a consultant for Edwards Lifesciences and CryoLife and research grant from Abbott Vascular and Edwards Lifesciences. Chadderdon reports service as an educational consultant for Medtronic and Edwards Lifesciences. Chhatriwalla reports service as a consultant for Abbott Vascular, Edwards Lifesciences, and Medtronic and research grant from Boston Scientific. Golwala reports service as an advisory consultant for Medtronic and Boston Scientific. All other authors declare that they have no conflicts of interest., (Copyright © 2023 Kris Kumar et al.)

To understand the scope and scale of the loss of biodiversity, tools are required that can be applied in a standardized manner to all species globally, spanning realms from land to the open ocean. We used data from the International Union for the Conservation of Nature Red List to provide a synthesis of the conservation status and extinction risk of cetaceans. One in 4 cetacean species (26% of 92 species) was threatened with extinction (i.e., critically endangered, endangered, or vulnerable) and 11% were near threatened. Ten percent of cetacean species were data deficient, and we predicted that 2-3 of these species may also be threatened. The proportion of threatened cetaceans has increased: 15% in 1991, 19% in 2008, and 26% in 2021. The assessed conservation status of 20% of species has worsened from 2008 to 2021, and only 3 moved into categories of lesser threat. Cetacean species with small geographic ranges were more likely to be listed as threatened than those with large ranges, and those that occur in freshwater (100% of species) and coastal (60% of species) habitats were under the greatest threat. Analysis of odontocete species distributions revealed a global hotspot of threatened small cetaceans in Southeast Asia, in an area encompassing the Coral Triangle and extending through nearshore waters of the Bay of Bengal, northern Australia, and Papua New Guinea and into the coastal waters of China. Improved management of fisheries to limit overfishing and reduce bycatch is urgently needed to avoid extinctions or further declines, especially in coastal areas of Asia, Africa, and South America., (© 2023 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Olanzapine is a relatively new antipsychotic agent which appears to be effective in the treatment of both the positive and negative symptoms of schizophrenia. Reported here is the case of a patient who developed symptoms of mania secondary to treatment with olanzapine. Physicians prescribing olanzapine should be aware of this potential complication., (© 1998 American Osteopathic Association.)

Decellularized extracellular matrix in the form of patches and locally injected hydrogels has long been used as therapies in animal models of disease. Here we report the safety and feasibility of an intravascularly infused extracellular matrix as a biomaterial for the repair of tissue in animal models of acute myocardial infarction, traumatic brain injury and pulmonary arterial hypertension. The biomaterial consists of decellularized, enzymatically digested and fractionated ventricular myocardium, localizes to injured tissues by binding to leaky microvasculature, and is largely degraded in about 3 d. In rats and pigs with induced acute myocardial infarction followed by intracoronary infusion of the biomaterial, we observed substantially reduced left ventricular volumes and improved wall-motion scores, as well as differential expression of genes associated with tissue repair and inflammation. Delivering pro-healing extracellular matrix by intravascular infusion post injury may provide translational advantages for the healing of inflamed tissues 'from the inside out'., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Aims: Lipoprotein(a) [Lp(a)] is causally associated with aortic valve stenosis (AS) but Lp(a) testing among AS patients is not broadly incorporated into clinical practice. We evaluated trends in Lp(a) testing in an academic medical center., Methods: Educational efforts and adding Lp(a) to the lipid panel on the electronic medical record (EMR) and pre-procedure order sets were used to increase awareness of Lp(a) as a risk factor in AS. Medical records at University of California San Diego Health (UCSDH) were analyzed from 2010 to 2020 to define the yearly frequency of first time Lp(a) testing in patients with diagnosis codes for AS or undergoing transcatheter aortic valve replacement (TAVR)., Results: Lp(a) testing for any indication increased over 5-fold from 2010 to 2020. A total of 3808 patients had a diagnosis of AS and 417 patients had TAVR. Lp(a) levels >30 mg/dL were present in 37% of AS and 35% of TAVR patients. The rates of Lp(a) testing in AS and TAVR were 14.0% and 65.7%, respectively. In AS, Lp(a) testing increased over time from 8.5% in 2010, peaking at 24.2% in 2017, and declining to 13.9% in 2020 (p < 0.001 for trend). Following implementation of EMR order-sets in 2016, Lp(a) testing in TAVR cases increased to a peak of 88.5% in 2018., Conclusions: Elevated Lp(a) is prevalent in AS and TAVR patients. Implementation of educational efforts and practice pathways resulted in increased Lp(a) testing in patients with AS. This study represents a paradigm that may allow increased global awareness of Lp(a) as a risk factor for AS., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Guidelines for management of Melody transcatheter pulmonary valve (TPV) infective endocarditis (IE) are lacking. We aimed to identify factors associated with surgical valve removal versus antimicrobial therapy in Melody TPV IE. Multicenter retrospective analysis of all patients receiving Melody TPV from 10/2010 to 3/2019 was performed to identify cases of IE. Surgical explants versus non-surgical cases were compared. Of the 663 Melody TPV implants, there were 66 cases of IE in 59 patients (59/663, 8.8%). 39/66 (59%) were treated with IV antimicrobials and 27/66(41%) underwent valve explantation. 26/59 patients (44%) were treated medically without explantation or recurrence with average follow-up time of 3.5 years (range:1-9). 32% of Streptococcus cases, 53% of MSSA, and all MRSA cases were explanted. 2 of the 4 deaths had MSSA. CART analysis demonstrated two important parameters associated with explantation: a peak echo gradient ≥ 47 mmHg at IE diagnosis(OR 10.6, p < 0.001) and a peak echo gradient increase of > 24 mmHg compared to baseline (OR 6.7, p = 0.01). Rates of explantation varied by institution (27 to 64%). In our multicenter experience, 44% of patients with Melody IE were successfully medically treated without valve explantation or recurrence. The degree of valve stenosis at time of IE diagnosis was strongly associated with explantation. Rates of explantation varied significantly among the institutions., (© 2021. The Author(s).)

COVID-19 infection may involve the nervous system and has been associated with a number of neuropsychiatric complications, including impairment of cognition and dementia. Such complications are more likely to occur in (but are not limited to) patients with severe COVID-19 infections and those with concomitant risk factors. In this case report, the authors describe a normally functioning 51-year-old woman who developed cognitive impairment of a degree that rendered her unable to care for herself most likely related to a relatively nonsevere infection with COVID-19 about 2 months earlier. A detailed report of her deficits of different areas of cognitive functioning is provided. This report aims to make clinicians more aware of the potential for cognitive impairment in patients who have suffered from COVID-19, including those with infections that were not severe., (© 2022 Roy R. Reeves and Scott G. Willoughby, published by De Gruyter, Berlin/Boston.)

Objective: To determine whether natural language processing (NLP) of unstructured medical text can improve identification of ASCVD patients not using high-intensity statin therapy (HIST) due to statin-associated side effects (SASEs) and other reasons., Methods: Reviewers annotated reasons for not prescribing HIST in notes of 1152 randomly selected patients from across the VA healthcare system treated for ASCVD but not receiving HIST. Developers used reviewer annotations to train the Canary NLP tool to detect and extract notes containing one or more of these reasons. Negative predictive value (NPV), sensitivity, specificity and Area Under the Curve (AUC) were used to assess accuracy at detecting documents containing reasons when using structured data, NLP-extracted unstructured data, or both data sources combined., Results: At least one documented reason for not prescribing HIST occurred in 47% of notes. The most frequent reasons were SASEs (41%) and general intolerance (20%). When identifying notes containing any documented reason for not using HIST, adding NLP-extracted, unstructured data significantly ( p <0.05) increased sensitivity (0.69 (95% confidence interval [CI] 0.60-0.76) to 0.89 (95% CI 0.81-0.93)), NPV (0.90 (95% CI 0.87 to 0.93) to 0.96 (95% CI 0.93-0.98)), and AUC (0.84 (95% confidence interval [CI] 0.81-0.88) to 0.91 (95% CI 0.90-0.93)) compared to structured data alone., Conclusions: NLP extraction of data from unstructured text can improve identification of reasons for patients not being on HIST over structured data alone. The additional information provided through NLP of unstructured free text should help in tailoring and implementing system-level interventions to improve HIST use in patients with ASCVD., Competing Interests: Dr. Virani receives research support from the Department of Veterans Affairs, World Heart Federation, Tahir and Jooma Family and honorarium from the American College of Cardiology (Associate Editor for Innovations, acc.org). Dr. Ballantyne: Grant/Research Support- All significant. (All paid to institution, not individual): Abbott Diagnostic, Akcea, Amgen, Esperion, Ionis, Novartis, Regeneron, Roche Diagnostic, NIH, AHA, ADA. Consultant- Abbott Diagnostics, Althera, Amarin*, Amgen, Arrowhead, Astra Zeneca, Corvidia, Denka Seiken*, Esperion, Genentech, Gilead, Matinas BioPharma Inc, New Amsterdam*, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic, Sanofi-Synthelabo*Dr. Turchin: Grant/Research support: Astra Zeneca, Edwards, Eli Lilli, Novo Nordisk, Sanofi. Others: None

Often perceived as environmentally benign, 'green' renewable energy technologies have ecological costs that are often overlooked, especially those occurring below the waterline. After briefly discussing the impacts of hydropower on freshwater and marine organisms, we focus this review on the impacts of marine renewable energy devices (MREDs) on underwater marine organisms, particularly offshore wind farms and marine energy converters (e.g., tidal turbines). We consider both cumulative impacts and synergistic interactions with other anthropogenic pressures, using offshore wind farms and the Taiwanese white dolphin (Sousa chinensis taiwanensis) as an example. While MREDs undoubtedly can help mitigate climate change, variability in the sensitivity of different species and ecosystems means that rigorous case-by-case assessments are needed to fully comprehend the consequences of MRED use., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

The cause of prolonged or recurrent symptoms following the cessation of long-term benzodiazepine use is proposed to be related to downregulation and allosteric decoupling of the γ-aminobutyric acid/benzodiazepine receptor complex. This case series describes 2 patients with prolonged (>2 weeks) recurrent complications during attempted tapering of benzodiazepine doses after long-term treatment. Excited catatonia developed in a 90-year-old woman, and prolonged delirium developed in a 69-year-old woman. Both patients showed improvement of symptoms after resumption of higher doses of benzodiazepine treatment and recurrence of symptoms when the dose was again lowered. Caution should be exercised regarding the long-term use of benzodiazepines in older adults (aged ≥65 years). Tapering of benzodiazepines in older patients after long-term treatment may require slow decreases in dose over long periods. Psychotherapeutic interventions, such as brief cognitive therapy with psychoeducation and motivational enhancement, and osteopathic manipulative treatment to decrease paravertebral muscle tension may be beneficial during the tapering process.

Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for calcific aortic valve stenosis (CAVS) for which transcatheter aortic valve replacement (TAVR) is increasingly utilized as treatment. We evaluated the effect of a program to increase testing of and define the prevalence of elevated Lp(a) among patients undergoing TAVR. Educational efforts and incorporation of a "check-box" Lp(a) order to the preoperative TAVR order set were instituted. Retrospective chart review was performed in 229 patients requiring TAVR between May 2013 and September 2018. Of these patients, 57% had an Lp(a) level measured; testing rates increased from 0% in 2013 to 96% in 2018. Lipoprotein(a) testing occurred in 11% of patients before and in 80% of patients after the "check-box" order set ( P < .001). The prevalence of elevated Lp(a) (≥30 mg/dL) was 35%; these patients had a higher incidence of coronary artery disease requiring revascularization compared with patients with normal Lp(a) (65% vs 47%; P = .047). Patients with Lp(a) ≥30 mg/dL also had higher incidence of paravalvular leak compared with those with normal Lp(a) (13% vs 4%; P = .04). This study defines the prevalence of elevated Lp(a) in advanced stages of CAVS and provides a practice pathway to assess procedural complications and long-term outcomes of TAVR in patients with elevated Lp(a) levels.

Objectives: To assess the long-term safety and efficacy of robotic percutaneous coronary revascularization for use in complex coronary lesions., Background: Robotically assisted percutaneous coronary intervention (PCI) is safe and feasible in simple coronary lesions and has excellent short-term procedural and clinical outcomes for complex lesions; however, long-term safety and efficacy outcomes are unknown., Methods: A total of 103 consecutive patients underwent a total of 108 robotic (R)-PCI procedures (age 68.1; 78.3% male) over 18 months, and 210 patients underwent a total of 226 manual (M)-PCI procedures (age 67.5; 78.1% male) during the same period. Patients were subsequently followed and both 6-month and 12-month major adverse cardiovascular events (MACE), comprised of any death, stroke, myocardial infarction, or target vessel revascularization, are reported and compared., Results: There was no difference between the two groups with regard to overall MACE at 6 months (R-PCI 5.8% vs. M-PCI 3.3%, P = 0.51) or at 12 months (R-PCI 7.8% vs. M-PCI 8.1%, P = 0.92). There was no difference between the individual components of the primary combined endpoint at either time point. No access site complications occurred in either cohort that met BARC III or higher criteria., Conclusions: At the 6- and 12-month time points following R-PCI, no difference in clinical outcomes or safety measures was observed as compared to M-PCI., (© 2018 Wiley Periodicals, Inc.)

Pressure to optimise land use and to maximise the economic viability of land has had a detrimental impact on wetlands worldwide. Rehabilitating wetlands has been identified by resource managers as increasingly important to enhance environmental values and restore ecosystem functions that may have been lost through developments effecting wetlands. This paper investigates rehabilitating a geothermally influenced wetland that had been drained and used for grazing stock. The Waikite Wetland (New Zealand) is a relatively unique wetland because the primary water source to the wetland has a significant geothermal water component. This results in the area hosting populations of rare flora and fauna that are significant to New Zealand. A range of management actions that included diverting a geothermal stream back into the wetland, blocking drains, pest control, weed control, native plantings, fencing and building a weir to increase water levels were used to rehabilitate the wetland. This was done to promote thermotolerant vegetation growth, restore wetland water levels and minimise pest plant species re-establishing while minimising the effects on geothermal surface features and allowing indigenous wetland vegetation to re-establish. Physical, chemical and vegetation monitoring show that management actions have increased thermotolerant vegetation growth in the wetland while having a small potential impact on geothermal discharges into the wetland. Increasing the water level in the wetland appears to be helping control plant pest species close to the weir, but has also made sensitive vegetation growing close to the waterways more susceptible to flooding caused by high-intensity rainfall events., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Global warming is significantly altering arctic marine ecosystems. Specifically, the precipitous loss of sea ice is creating a dichotomy between ice-dependent polar bears and pinnipeds that are losing habitat and some cetaceans that are gaining habitat. While final outcomes are hard to predict for the many and varied marine mammal populations that rely on arctic habitats, we suggest a simplified framework to assess status, based upon ranking a population's size, range, behavior, and health. This basic approach is proposed as a means to prioritize and expedite conservation and management efforts in an era of rapid ecosystem alteration., Competing Interests: The authors have declared that no competing interests exist.

Background: A number of studies suggest that bivalirudin (BIV) is associated with similar efficacy but reduced bleeding when compared with unfractionated heparin (UFH) in patients undergoing peripheral vascular interventions (PVI)., Methods: A comprehensive literature search was conducted with the electronic databases MEDLINE, EMBASE and CENTRAL. These were queried to identify studies comparing BIV with UFH in PVI. Study endpoints included total bleeding events, major and minor bleeding events and procedural success. Random-effects meta-analysis method was used to pool endpoint odds ratios (OR) for both UFH and BIV with 95% confidence intervals (CI)., Results: A total of 12,335 patients (70.6 years; 59.7% male) were included from seven observational cohort studies (two prospective and five retrospective) comparing outcomes between BIV and UFH during PVI between January 2000 and May 2017. Compared with BIV, UFH was associated with significantly higher total bleeding, (OR 1.52 with 95% CI 1.11 to 2.09, p = 0.009), major bleeding (OR 1.38 with 95% CI 1.13 to 1.68, p = 0.002), and minor bleeding (OR 1.51 with 95% CI 1.09 to 2.08, p = 0.01). Procedural success rates were not different between the two groups (BIV vs HEP: OR 0.90 with 95% CI 0.49 to 1.64, p = 0.72) CONCLUSION: Compared with BIV, UFH was associated with more bleeding when used during PVI. There was no significant difference in procedural success between the two anticoagulation strategies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Stroke is the most feared complication of atrial fibrillation (AF). Although oral anticoagulation with non-vitamin K antagonist and non-vitamin K antagonist oral anticoagulants (NOACs) have been established to significantly reduce risk of stroke, real-world use of these agents are often suboptimal due to concerns for adverse events including bleeding from both patients and clinicians. Particularly in patients with previous serious bleeding, oral anticoagulation may be contraindicated. Left atrial appendage occlusion (LAAO), mechanically targeting the source of most of the thrombi in AF, holds an immense potential as an alternative to OAC in management of stroke prophylaxis. In this focused review, we describe the available evidence of various LAAO devices, detailing data regarding their use in patients with a contraindication for oral anticoagulation. Although some questions of safety and appropriate use of these new devices in patients who cannot tolerate anticoagulation remain, LAAO devices offer a significant step forward in the management of patients with AF, including those patients who may not be able to be prescribed OAC at all. Future studies involving patients fully contraindicated to OAC are warranted in the era of LAAO devices for stroke risk reduction.

Background: Robotically-assisted percutaneous coronary intervention (R-PCI) is feasible for simple coronary lesions., Objectives: To determine the frequency and reasons for partial manual assistance or manual conversion during R-PCI in clinical practice., Methods: The CorPath 200 System (Corindus, Waltham, MA) enables the operator to sit in a radiation-shielded cockpit and remotely control intracoronary devices including guidewires, balloons, and stents. Consecutive R-PCI procedures performed over 18months were analyzed to identify reasons for planned or unplanned manual assistance or manual conversion, and categorized as due to 1) adverse event; 2) technical limitation of the robotic platform; or 3) limited guide catheter/wire support., Results: During the study period, 108 R-PCI procedures (68.1±11.0years, 77.8% men, 69.4% elective PCI, 78.3% type B2/C lesions, and 50.3% left anterior descending/left main target lesion segment) were performed. High robotic technical success (91.7%) and clinical procedural success (99.1%) were achieved. Twenty procedures (18.5%) required either planned partial manual assistance (3.7%), unplanned partial manual assistance (7.4%), or manual conversion (7.4%). Among these procedures, manual assistance/conversion was required in 3 procedures for an adverse event (15%), 8 for technical limitation of the robotic platform (40%), and 9 for guide catheter/wire support issues (45%)., Conclusions: High clinical success with R-PCI for a complex lesion cohort is possible with only occasional partial manual assistance or manual conversion. The majority of procedures requiring manual assistance/conversion were due to limited guide catheter/wire support or robotic platform limitations, rather than occurrence of adverse events., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The scientific study of death across animal taxa-comparative thanatology-investigates how animals respond behaviourally, physiologically and psychologically to dead conspecifics, and the processes behind such responses. Several species of cetaceans have been long known to care for, attend to, be aroused by, or show interest in dead or dying individuals. We investigated patterns and variation in cetacean responses to dead conspecifics across cetacean taxa based on a comprehensive literature review. We analysed 78 records reported between 1970 and 2016, involving 20 of the 88 extant cetacean species. We adopted a weighted comparative approach to take observation effort into account and found that odontocetes (toothed cetaceans) were much more likely than mysticetes (baleen whales) to attend to dead conspecifics. Dolphins (Delphinidae) had the greatest occurrence of attentive behaviour (92.3% of all records), with a weighed attendance index 18 times greater than the average of all other cetacean families. Two dolphin genera, Sousa and Tursiops, constituted 55.1% of all cetacean records (N=43) and showed the highest incidence of attentive behaviour. Results of analyses intended to investigate the reasons behind these differences suggested that encephalisation may be an important predictor, consistent with the "social brain" hypothesis. Among attending individuals or groups of known sex (N=28), the majority (75.0%) were adult females with dead calves or juveniles (possibly their own offspring, with exceptions), consistent with the strong mother-calf bond, or, in a few cases, with the bond between mothers and other females in the group. The remaining records (25.0%) involved males either showing sexual interest in a dead adult or subadult, or carrying a dead calf in the presence of females. Because an inanimate individual is potentially rescuable, responses to dead conspecifics-especially by females-can be explained at least in part by attempts to revive and protect, having a clear adaptive value. In some cases such responses are followed by apparently maladaptive behaviour such as the long-term carrying of, or standing by, a decomposed carcass, similar to observations of certain terrestrial mammals. Among the possible explanations for the observed cetacean behavioural responses to dead conspecifics are strong attachment resulting in a difficulty of "letting go"-possibly related to grieving-or perhaps individuals failing to recognise or accept that an offspring or companion has died. Our current understanding is challenged by small sample size, incomplete descriptions, and lack of information on the physiology and neural processes underpinning the observed behaviour. We provide research recommendations that would improve such understanding., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Renal artery stenosis (RAS) is a prevalent cause of secondary hypertension. Elderly patients with atherosclerosis and young women with fibromuscular dysplasia (FMD) are particularly at risk. Blood pressure screening is often key to this diagnosis, although the reliability of clinical screening has been questioned, and ambulatory blood pressure monitoring (ABPM) likely offers superior ability to diagnose poorly controlled hypertension. In patients with RAS, medical management should be the primary means of therapy; however, in a select group of these patients, renal revascularization may be considered, and has been shown to reduce blood pressure and stabilize chronic kidney disease. In this report, we present a patient diagnosed with RAS due to FMD, found to have significant hypertension via ABPM, and treated successfully with percutaneous renal artery angioplasty; importantly, continuous 24-hr ambulatory monitoring after pressure gradient guided renal angioplasty confirmed reduction in blood pressure., (© 2017 Wiley Periodicals, Inc.)

Background: Elevated fibrinogen is associated with short-term major adverse cardiovascular events (MACE) after percutaneous coronary intervention, but the relation with late MACE is unknown., Methods and Results: Baseline demographics and 2-year MACE were recorded among subjects undergoing nonemergent percutaneous coronary intervention. A total of 332 subjects (66.6±19.5 years, 69.9% male, 25.3% acute coronary syndrome) were enrolled. Two-year MACE (periprocedural myocardial infarction 9.0%, rehospitalization 6.3%, revascularization 12.7%, non-periprocedural myocardial infarction 4.5%, stent thrombosis 0.9%, stroke 1.8%, and death 0.6%) were associated with higher fibrinogen (352.8±123.4 mg/dL versus 301.6±110.8 mg/dL; P <0.001), longer total stent length (40.1±25.3 mm versus 32.1±19.3 mm; P =0.004), acute coronary syndrome indication (38.7% versus 17.8%; P <0.001), number of bare-metal stents (0.5±1.1 versus 0.2±0.5; P =0.002), and stent diameter ≤2.5 mm (55.8% versus 38.4%, P =0.003). No relation between platelet reactivity and 2-year MACE was observed. Fibrinogen ≥280 mg/dL (odds ratio [OR] 3.0, confidence interval [CI], 1.6-5.4, P <0.001), total stent length ≥32 mm (OR 2.2, CI, 1.3-3.8, P <0.001), acute coronary syndrome indication (OR 4.1, CI, 2.3-7.5, P <0.001), any bare-metal stents (OR 3.2, CI, 1.6-6.1, P <0.001), and stent diameter ≤2.5 mm (OR 2.0, CI, 1.2-3.5, P =0.010) were independently associated with 2-year MACE. Following a landmark analysis excluding periprocedural myocardial infarction, fibrinogen ≥280 mg/dL remained strongly associated with 2-year MACE (37.0% versus 17.4%, log-rank P <0.001)., Conclusions: Elevated baseline fibrinogen level is associated with 2-year MACE after percutaneous coronary intervention. Acute coronary syndrome indication for percutaneous coronary intervention, total stent length implanted, and use of bare-metal stents or smaller-diameter stents are also independently associated with 2-year MACE, while measures of on-thienopyridine platelet reactivity are not., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Robotic technology has been utilized in cardiovascular medicine for over a decade, and over that period, its use has been expanded to percutaneous coronary and peripheral vascular interventions. The safety and feasibility of robotically assisted percutaneous cardiovascular interventions has been demonstrated in studies including simple to complex coronary lesions, and both iliac and femoropopliteal lesions. These reports have shown that robotically assisted PCI significantly reduces operator exposure to harmful ionizing radiation without a detrimental effect on procedural success or clinical efficacy. Additionally, the use of robotics has the intuitive benefit of alleviating the risk of orthopedic injuries faced by interventional operators. In addition to the interventional operator benefits, robotically assisted intervention has the potential for patient level benefit by allowing more accurate lesion length measurement, precise stent placement, and lower patient radiation exposure. However, further investigation is required to fully elucidate these potential benefits., (© 2017 Wiley Periodicals, Inc.)

Introduction: The fundamental technique of performing percutaneous cardiovascular (CV) interventions has remained unchanged and requires operators to wear heavy lead aprons to minimize exposure to ionizing radiation. Robotic technology is now being utilized in interventional cardiology partially as a direct result of the increasing appreciation of the long-term occupational hazards of the field. This review was undertaken to report the clinical outcomes of percutaneous robotic coronary and peripheral vascular interventions. Areas covered: A systematic literature review of percutaneous robotic CV interventions was undertaken. The safety and feasibility of percutaneous robotically-assisted CV interventions has been validated in simple to complex coronary disease, and iliofemoral disease. Studies have shown that robotically-assisted PCI significantly reduces operator exposure to harmful ionizing radiation without compromising procedural success or clinical efficacy. In addition to the operator benefits, robotically-assisted intervention has the potential for patient advantages by allowing more accurate lesion length measurement, precise stent placement and lower patient radiation exposure. However, further investigation is required to fully elucidate these potential benefits. Expert commentary: Incremental improvement in robotic technology and telecommunications would enable treatment of an even broader patient population, and potentially provide remote robotic PCI.

The authors demonstrate that device manipulation during percutaneous coronary intervention can result in "noise," which can be perceived as an arrhythmia resulting in an inappropriate shock. Although rare, this possibility should be considered when an operator encounters a difficult to traverse lesion in a patient with an ICD.

Robotic technology has been used in cardiovascular medicine for over a decade, and over that period its use has been expanded to interventional cardiology and percutaneous coronary and peripheral vascular interventions. The safety and feasibility of robotically assisted interventions has been demonstrated in multiple studies ranging from simple to complex coronary lesions, and in the treatment of iliofemoral and infrapopliteal disease. These studies have shown a reduction in operator exposure to harmful ionizing radiation, and the use of robotics has the intuitive benefit of alleviating the occupational hazard of operator orthopedic injuries. In addition to the interventional operator benefits, robotically assisted intervention has the potential to also be beneficial for patients by allowing more accurate lesion length measurement, stent placement, and patient radiation exposure; however, more investigation is required to elucidate these benefits fully.

Large bore vascular access is becoming increasingly common for a range of interventional cardiovascular procedures. In the vast majority, percutaneous closure is preplanned and successfully achieved. However, for patients with percutaneous closure failure, or those requiring prolonged hemodynamic support, alternatives to percutaneous closure are required. Currently there are no approved vascular closure devices for delayed removal of large bore sheaths and therefore, manual hemostasis or surgical closure remains the only options. In this case series we present an endovascular approach to achieve delayed large bore vascular hemostasis, using either the contralateral femoral arterial access or radial arterial access., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Pericardiocentesis with drain placement provides relief of symptomatic pericardial tamponade. The use of a pericardial sheath preserves access to the pericardial space in the event a drain may need to be replaced or manipulated. Although rare, sheath fracture and migration into the pericardial space may be a complication of prolonged sheath maintenance. Prompt action may allow percutaneous retrieval of the foreign body and avoid the need for surgical exploration. We report a case of successful percutaneous retrieval of a fractured pericardial sheath. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

The North Atlantic right whale (NARW) (Eubalaena glacialis) is one of the world's most threatened whales. It came close to extinction after nearly a millennium of exploitation and currently persists as a population of only approximately 500 individuals. Setting appropriate conservation targets for this species requires an understanding of its historical population size, as a baseline for measuring levels of depletion and progress toward recovery. This is made difficult by the scarcity of records over this species' long whaling history. We sought to estimate the preexploitation population size of the North Atlantic right whale and understand how this species was distributed across its range. We used a spatially explicit data set on historical catches of North Pacific right whales (NPRWs) (Eubalaena japonica) to model the relationship between right whale relative density and the environment during the summer feeding season. Assuming the 2 right whale species select similar environments, we projected this model to the North Atlantic to predict how the relative abundance of NARWs varied across their range. We calibrated these relative abundances with estimates of the NPRW total prewhaling population size to obtain high and low estimates for the overall NARW population size prior to exploitation. The model predicted 9,075-21,328 right whales in the North Atlantic. The current NARW population is thus <6% of the historical North Atlantic carrying capacity and has enormous potential for recovery. According to the model, in June-September NARWs concentrated in 2 main feeding areas: east of the Grand Banks of Newfoundland and in the Norwegian Sea. These 2 areas may become important in the future as feeding grounds and may already be used more regularly by this endangered species than is thought., (© 2015 Society for Conservation Biology.)

Peripheral arterial disease (PAD) involving the lower extremity is a major source of morbidity and mortality. Clinical manifestations of PAD span the spectrum from lifestyle limiting claudication to ulceration and gangrene leading to amputation. Advancements including balloon angioplasty, self-expanding stents, drug-eluting stents, and atherectomy have resulted in high technical success rates for endovascular therapy in patients with PAD. However, these advances have been limited by somewhat high rates of clinical restenosis and clinically driven target lesion revascularization. The recent introduction of drug-coated balloon technology shows promise in limiting neointimal hyperplasia induced by vascular injury after endovascular therapies. This review summarizes the contemporary clinical data in the emerging area of drug-coated balloons.

Reported here is the case of a 41-year-old female who developed paranoia and delusions. Physical examination, laboratory studies, and neuroimaging were unremarkable. She was diagnosed with schizophrenia and treated with risperidone, ultimately at a dose of 3 mg daily, with improvement. Her EEG showed bursts of 30-40 Hz gamma activity in the frontal regions, a finding sometimes noted on the resting EEGs of patients with schizophrenia. This report discusses gamma activity as well as other EEG abnormalities that may occur on the resting EEG of patients with schizophrenia. Additionally discussed is recent research suggesting that 35-45 Hz gamma activity associated with active information processing and cognition may be decreased in patients with schizophrenia compared to normal individuals. The role of gamma activity, both in the resting state and during cognitive activity, could be an area of importance for future research in schizophrenia and possibly other disorders.

Myofascial trigger points (TPs) are a poorly understood phenomenon involving the myofascial system and its related neural, lymphatic, and circulatory elements. Compression or massage of a TP causes localized pain and may cause referred pain and autonomic phenomena. The authors describe a 58-year-old woman who experienced precipitation of substantial psychological symptoms directly related to her treatment for a lower abdominal TP. Her symptoms resolved after 2 weeks of receiving high-velocity, low-amplitude manipulation and soft tissue massage. Particularly in the abdomen, TPs may be associated with psychological reactions as well as physical aspects of bodily function.

Objectives: This study sought to determine radiation exposure across the cranium of cardiologists and the protective ability of a nonlead, XPF (barium sulfate/bismuth oxide) layered cap (BLOXR, Salt Lake City, Utah) during fluoroscopically guided, invasive cardiovascular (CV) procedures., Background: Cranial radiation exposure and potential for protection during contemporary invasive CV procedures is unclear., Methods: Invasive cardiologists wore an XPF cap with radiation attenuation ability. Six dosimeters were fixed across the outside and inside of the cap (left, center, and right), and 3 dosimeters were placed outside the catheterization lab to measure ambient exposure., Results: Seven cardiology fellows and 4 attending physicians (38.4 ± 7.2 years of age; all male) performed diagnostic and interventional CV procedures (n = 66.2 ± 27 cases/operator; fluoroscopy time: 14.9 ± 5.0 min). There was significantly greater total radiation exposure at the outside left and outside center (106.1 ± 33.6 mrad and 83.1 ± 18.9 mrad) versus outside right (50.2 ± 16.2 mrad; p < 0.001 for both) locations of the cranium. The XPF cap attenuated radiation exposure (42.3 ± 3.5 mrad, 42.0 ± 3.0 mrad, and 41.8 ± 2.9 mrad at the inside left, inside center, and inside right locations, respectively) to a level slightly higher than that of the ambient control (38.3 ± 1.2 mrad, p = 0.046). After subtracting ambient radiation, exposure at the outside left was 16 times higher than the inside left (p < 0.001) and 4.7 times higher than the outside right (p < 0.001). Exposure at the outside center location was 11 times higher than the inside center (p < 0.001), whereas no difference was observed on the right side., Conclusions: Radiation exposure to invasive cardiologists is significantly higher on the left and center compared with the right side of the cranium. Exposure may be reduced similar to an ambient control level by wearing a nonlead XPF cap. (Brain Radiation Exposure and Attenuation During Invasive Cardiology Procedures [BRAIN]; NCT01910272)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Alexithymia is characterized by impairment of an individual's ability to experience, identify, and express emotions, and is associated with impaired emotional intelligence and an externally oriented cognitive style. There has been increasing interest in the phenomenon, with numerous peer-reviewed articles published recently. Alexithymia may occur in patients with many psychiatric disorders, and more severe alexithymia is related to worse outcome. However, many clinicians remain unaware of the issue. The current article discusses alexithymia and its importance in the field of mental health., (Copyright 2015, SLACK Incorporated.)

The potential for abuse of medications that are controlled substances is well known. Abuse of certain noncontrolled prescription drugs and over-the-counter medications also may occur. To some degree, any medication that exerts psychoactive effects may be abused if taken in high enough doses or by means that result in high serum or cerebrospinal fluid levels. Many clinicians may be unaware of the potential for abuse of these medications. This review examines evidence of the possibility of abuse of several common medications that theoretically do not have abuse potential, including cough and cold preparations, antihistamines, anticholinergics, antipsychotics, antidepressants, anticonvulsants, skeletal muscle relaxants, and antiemetics. Means by which such medications may be abused and biochemical and physiological mechanisms fostering their abuse also are discussed.

Objectives: To characterize the prevalence of thrombus burden, collateral vessels to the infarct-related artery, epicardial coronary artery flow, and myocardial perfusion in patients with angiographically confirmed definite stent thrombosis (ST), and to define their relationship with associated treatments and outcomes., Background: Angiographic characteristics of ST are not well defined., Methods: All cases of angiographically determined ST at five academic hospitals from 2005 to 2012 were reviewed. Demographic, procedural, and angiographic characteristics were recorded. In-hospital and 1-year follow-up data were obtained., Results: Among 205 cases of angiographic definite ST (60 ± 8 years; 87% male), the majority presented with late/very late ST (69%) and STEMI (66%). High-risk angiographic findings at presentation included thrombus grade 4-5 (87%), absence of collateral vessels (76%), and reduced initial TIMI 3 flow (90%). Final TIMI 3 flow was achieved in 90% of patients and was associated with greater use of aspiration thrombectomy (60% vs. 25%; P = 0.003), glycoprotein IIb/IIIa inhibitors (80% vs. 30%, P < 0.001), and repeat stenting (67% vs. 10%, P < 0.001). A final myocardial perfusion grade of 2-3 was achieved in 79% of patients and was associated with greater use of aspiration thrombectomy (61% vs. 36%, P = 0.003). After multivariable logistic regression, aspiration thrombectomy (AOR 2.6, 95% CI 1.3-5.2) and implantation of a new stent (AOR 2.1, 95% CI 1.1-4.3) were associated with optimal combined epicardial flow and myocardial perfusion. At 1-year follow-up, significantly lower risk of repeat ST (HR 0.1; 95% CI 0.1,0.2; P < 0.001) among patients with initial TIMI 3 flow at index ST was observed., Conclusions: The majority of ST patients present with late/very late ST with high thrombus burden and STEMI. Presence of collateral vessels and low thrombus burden is cardioprotective, while reduced initial TIMI flow is associated with larger infarct size and recurrent ST. Aspiration thrombectomy and repeat stenting are associated with improved epicardial coronary artery flow and myocardial perfusion among patients treated for ST. © 2014 Wiley Periodicals, Inc., (© 2014 Wiley Periodicals, Inc.)