Twelve Patients: A Book Review

Twelve Patients weaves the stories of twelve patients to tell the geopolitical stories of Americans, both those born here and elsewhere.  At the epicenter of immigration, New York City and Bellevue Hospital serves as a testament to public health in America over the past century.  It mirrors the challenges new immigrants have, by documenting their health challenges.  Amidst these case studies, Dr. Eric Manheimer offers geopolitical commentary on mental health in America, Latin American geopolitical issues, palliative care, and international infectious disease.   He is a clinical professor of medicine at the New York University School of Medicine, and served as the medical director at Bellevue Hospital for fourteen years.  Fifteen years of handwritten journals of thoughts, incidents, ideas, case studies and conversations culminated into these twelve chapters, focusing on twelve patients

Delirium Rate and Risk Factors in Palliative Care Outpatients and Caregiver Coping Strategies

Background: Delirium causes suffering and in terminal illness undermines important goals to die at home. Improved knowledge about delirium among palliative outpatients can lead to improved patient outcomes through early identification and treatment in the home. Conversely, a missed diagnosis leads to costly hospital admissions, and is the most common reason to seek long-term care placement (Breitbart & Alici, 2008). Medicare stresses the importance by listing it as a common cause of falls among non-reimbursed hospital events. Prior evaluation of outpatient delirium rate was 14% among demented community dwelling elders (Steis, Evans, et al., 2012a). It is hypothesized that frail, palliative care outpatients have high rates of missed delirium, and it is the most common neuropsychiatrie disorder that terminally ill patients face, with prevalence as high as 88% (Breitbart & Alici, 2008). Objectives: To identify the prevalence rate of delirium among palliative care outpatients and correlate patient factors associated with delirium. Caregiver coping strategies associated with the episode were also examined. Methods: This study was a descriptive, correlational study conducted over a three-month period in late 2013. A convenience sample of patient/caregiver dyads were recruited at an urban cancer center. Patients with a life-limiting illness undergoing non-curative therapy consented to a chart review for demographic risk factors. Caregivers were asked to complete two survey instruments at the time of their usual visit. Caregivers were asked to reflect upon the patient\u27s behavior over the past month using the 12 simple yes/no questions on the Family Administered Confusion Assessment Method (FAM-CAM) (Inouye et al., 2011). Risk factors such as age, gender, marital status, medications and diagnosis were correlated with delirium. The Folkman Lazarus Ways of Coping Questionnaire (1988) was also administered to caregivers comparing positive and negative coping techniques. Data was analyzed with ANOVA correlations. Results: The rate of delirium among palliative care outpatients in this sample of 52 patient/caregiver dyads was 27%. The results suggested that opioid use slightly increases the odds for an episode of delirium, and approaches significance (r(50) = .270, p = .052). The majority of caregiver participants reported positive coping styles, however positive reappraisal and emotion-focused coping mechanism were more common in caregivers with a cognitively intact patient. When a patient screened positive for delirium, problem-focused coping was more common than emotional methods among caregivers (m = .22, SD = .073). Implications: Clinicians caring for frail, vulnerable outpatients must promote increased awareness and screening for delirium. Knowledge and communication about these symptoms in the home can increase quality of care and lower costs by increasing safety, quality of life, and lower hospital readmissions. This feasibility study suggests that caregivers cope using an analytic approach during an episode of stress and delirium in the home, which may preclude healthy grief and coping mechanisms. Outpatient delirium screening can improve quality of care and safety by lowering costs and hospital admission rates

A cost analysis of transcription systems

We compare different approaches to transcribing natural history data and summarise the advantages and disadvantages of each approach using six case studies from four different natural history collections. We summarise the main cost considerations when planning a transcription project and discuss the limitations we current have in understanding the costs behind transcription and data quality.Non peer reviewe

Experimental Models of Short Courses of Liposomal Amphotericin B for Induction Therapy for Cryptococcal Meningitis.

Cryptococcal meningoencephalitis is a rapidly lethal infection in immunocompromised patients. Induction regimens are usually administered for 2-weeks. The shortest effective period of induction therapy with liposomal amphotericin B (LAmB) is unknown. The pharmacodynamics of LAmB were studied in murine and rabbit models of cryptococcal meningoencephalitis. The concentrations of LAmB in plasma and brain of mice were measured using HPLC. Histopathological changes were determined. The penetration of LAmB into the brain was determined by immunohistochemistry using an antibody directed to amphotericin B. A dose-dependent decline in fungal burden was observed in the brain of mice with near-maximal efficacy achieved with LAmB 10-20 mg/kg/day. The terminal elimination half-life in brain was 133 hours. The pharmacodynamics of a single dose of 20 mg/kg was the same as 20 mg/kg/day administered for 2 weeks. Changes in quantitative counts were reflected by histopathological changes in the brain. Three doses of LAmB 5 mg/kg/day in rabbits were required to achieve fungicidal activity in cerebrospinal fluid (cumulative AUC 2500 mg.h/L). Amphotericin B was visible in the intra- and perivascular spaces, leptomeninges and choroid plexus. The prolonged mean residence time of amphotericin B in the brain suggest abbreviated induction regimens of LAmB are possible for cryptococcal meningoencephalitis

Towards a Roadmap for Advancing the Catalogue of the World’s Natural History Collections

Natural history collections are the foundations upon which all knowledge of natural history is constructed. Biological specimens are the best documentation of variation within each species, increasingly serve as curated sources for reference DNA, and are frequently our only evidence for historical species distribution. Collections represent an enormous multigenerational investment in research infrastructure for the biological sciences, but despite this importance most of the holdings of these institutions remain invisible on the Internet, inaccessible to taxonomists from other countries and hidden from computational biodiversity research.Although comprehensive digitisation of the complete holdings of each natural history collection is the long-term goal, this is an expensive and labor-intensive task and will not be completed in the near future for all collections. However, many benefits could quickly be achieved by publishing high-quality metadata on each collection to increase its visibility, provide the foundations for further digitisation and enable researchers to discover and communicate with collections of interest.This paper summarises the results from a consultation activity carried out in 2020 as part of the SYNTHESYS+ (Synthesys of Systematic Resources), “Developing implementation roadmaps for priority infrastructure areas as part of cooperative RI for biodiversity” project. This consultation was primed through an ideas paper, and introductory webinars and conducted as a facilitated two-week online multilingual discussion around 26 topics grouped under four broad headings (Users, Content, Technology and Governance). The results of these discussions are summarised here, along with the wider context of existing and planned initiatives

Pharmacodynamics of the Orotomides against Aspergillus fumigatus: New Opportunities for Treatment of Multidrug-Resistant Fungal Disease.

F901318 is an antifungal agent with a novel mechanism of action and potent activity against Aspergillus spp. An understanding of the pharmacodynamics (PD) of F901318 is required for selection of effective regimens for study in phase II and III clinical trials. Neutropenic murine and rabbit models of invasive pulmonary aspergillosis were used. The primary PD endpoint was serum galactomannan. The relationships between drug exposure and the impacts of dose fractionation on galactomannan, survival, and histopathology were determined. The results were benchmarked against a clinically relevant exposure of posaconazole. In the murine model, administration of a total daily dose of 24 mg/kg of body weight produced consistently better responses with increasingly fractionated regimens. The ratio of the minimum total plasma concentration/MIC (Cmin/MIC) was the PD index that best linked drug exposure with observed effect. An average Cmin (mg/liter) and Cmin/MIC of 0.3 and 9.1, respectively, resulted in antifungal effects equivalent to the effect of posaconazole at the upper boundary of its expected human exposures. This pattern was confirmed in a rabbit model, where Cmin and Cmin/MIC targets of 0.1 and 3.3, respectively, produced effects previously reported for expected human exposures of isavuconazole. These targets were independent of triazole susceptibility. The pattern of maximal effect evident with these drug exposure targets was also apparent when survival and histopathological clearance were used as study endpoints. F901318 exhibits time-dependent antifungal activity. The PD targets can now be used to select regimens for phase II and III clinical trials.IMPORTANCE Invasive fungal infections are common and often lethal. There are relatively few antifungal agents licensed for clinical use. Antifungal drug toxicity and the emergence of drug resistance make the treatment of these infections very challenging. F901318 is the first in a new class of antifungal agents called the orotomides. This class has a novel mechanism of action that involves the inhibition of the fungal enzyme dihydroorotate dehydrogenase. F901318 is being developed for clinical use. A deep understanding of the relationship between dosages, drug concentrations in the body, and the antifungal effect is fundamental to the identification of the regimens to administer to patients with invasive fungal infections. This study provides the necessary information to ensure that the right dose of F901318 is used the first time. Such an approach considerably reduces the risks in drug development programs and ensures that patients with few therapeutic options can receive potentially life-saving antifungal therapy at the earliest opportunity

Replacement of Enterococcus faecalis by Enterococcus faecium as the predominant enterococcus in UK bacteraemias

Objectives To review temporal changes in the proportions of different Enterococcus species recorded in two UK bacteraemia surveillance systems. Antibiotic resistance trends were also considered. Methods We reviewed data for enterococci from 2001 to 2019 in: (a) the BSAC Resistance Surveillance Programme, which collected up to 7–10 bloodstream enterococci every year from each of 23–39 hospitals in the UK and Ireland and tested these centrally; and (b) PHE bacteraemia surveillance, using routine results from NHS microbiology laboratories in England. Results BSAC surveillance, based upon 206–255 enterococci each year (4486 in total), indicated that the proportion of Enterococcus faecium rose from 31% (212/692) in the period 2001–3 to 51% (354/696) in the period 2017–19, balanced by corresponding falls in the proportion of Enterococcus faecalis. PHE surveillance provided a larger dataset, with >5000 enterococcus reports per year; although its identifications are less precise, it too indicated a rise in the proportion of E. faecium. BSAC surveillance for E. faecium indicated no consistent trends in resistance to ampicillin (≥86% in all years), vancomycin (annual rates 19%–40%) or high-level resistance to gentamicin (31%–59%). Resistance to vancomycin remained <4% in E. faecalis in all years, whilst high-level resistance to gentamicin fell, perhaps partly reflecting the decline of two initially prevalent gentamicin- and ciprofloxacin-resistant clones. Conclusions Both surveillance systems indicate a growing proportion of E. faecium in enterococcal bloodstream infections. This is important because fewer therapeutic options remain against this frequently multiresistant species than against E. faecalis

A single oral dose of citalopram increases interoceptive insight in healthy volunteers

Rationale Interoception is the signalling, perception, and interpretation of internal physiological states. Many mental disorders associated with changes of interoception, including depressive and anxiety disorders, are treated with selective serotonin reuptake inhibitors (SSRIs). However, the causative link between SSRIs and interoception is not yet clear. Objectives To ascertain the causal effect of acute changes of serotonin levels on cardiac interoception. Methods Using a within-participant placebo-controlled design, forty-seven healthy human volunteers (31 female, 16 male) were tested on and off a 20 mg oral dose of the commonly prescribed SSRI, citalopram. Participants made judgements on the synchrony between their heartbeat and auditory tones and then expressed confidence in each judgement. We measured three types of interoceptive cognition. Results Citalopram increased cardiac interoceptive insight, measured as correspondence of self-reported confidence to the likelihood that interoceptive judgements were actually correct. This effect was driven by enhanced confidence for correct interoceptive judgements and was independent of measured cardiac and reported subjective effects of the drug. Conclusions An acute change of serotonin levels can increase insight into the reliability of inferences made from cardiac interoceptive sensations

A benchmark dataset of herbarium specimen images with label data

More and more herbaria are digitising their collections. Images of specimens are made available online to facilitate access to them and allow extraction of information from them. Transcription of the data written on specimens is critical for general discoverability and enables incorporation into large aggregated research datasets. Different methods, such as crowdsourcing and artificial intelligence, are being developed to optimise transcription, but herbarium specimens pose difficulties in data extraction for many reasons. To provide developers of transcription methods with a means of optimisation, we have compiled a benchmark dataset of 1,800 herbarium specimen images with corresponding transcribed data. These images originate from nine different collections and include specimens that reflect the multiple potential obstacles that transcription methods may encounter, such as differences in language, text format (printed or handwritten), specimen age and nomenclatural type status. We are making these specimens available with a Creative Commons Zero licence waiver and with permanent online storage of the data. By doing this, we are minimising the obstacles to the use of these images for transcription training. This benchmark dataset of images may also be used where a defined and documented set of herbarium specimens is needed, such as for the extraction of morphological traits, handwriting recognition and colour analysis of specimens

Cross-validation of a semantic segmentation net-work for natural history collection specimens

Semantic segmentation has been proposed as a tool to accelerate the processing of natural history collection images. However, developing a flexible and resilient segmentation network requires an approach for adaptation which allows processing different datasets with minimal training and validation. This paper presents a cross-validation approach designed to determine whether a semantic segmentation network possesses the flexibility required for application across different collections and institutions. Consequently, the specific objectives of cross-validating the semantic segmentation network are to (a) evaluate the effectiveness of the network for segmenting image sets derived from collections different from the one in which the network was initially trained on; and (b) test the adaptability of the segmentation network for use in other types of collections. The resilience to data variations from different institutions and the portability of the network across different types of collections are required to confirm its general applicability. The proposed validation method is tested on the Natural History Museum semantic segmentation network, designed to process entomological microscope slides. The proposed semantic segmentation network is evaluated through a series of cross-validation experiments designed to test using data from two types of collections: microscope slides (from three institutions) and herbarium sheets (from seven institutions). The main contribution of this work is the method, software and ground truth sets created for this cross-validation as they can be reused in testing similar segmentation proposals in the context of digitization of natural history collections. The cross-validation of segmentation methods should be a required step in the integration of such methods into image processing workflows for natural history collections