Communicating Through a Brain-Computer Interface: Towards the Assessment of Quality of Life in Minimally Conscious and Covertly Aware Vegetative State Patients

Neuroimaging has been utilized to establish communication, using a brain-computer interface, with select patients with severe brain injuries and profound communication impairments. Due to the severe injuries sustained by these patients, traditional techniques used to develop quality of life instruments cannot be used. The Aware Study used a novel approach to establish the key dimensions for assessing the quality of life of patients who can only communicate using this sophisticated technology. Consensus methodology was employed, with the assistance of a multidisciplinary panel of experts, to collectively decide which dimensions are essential for the inclusion in a quality of life instrument for these unique patients

Towards the assessment of quality of life in patients with disorders of consciousness

© 2019, Springer Nature Switzerland AG. Purpose: To generate foundational knowledge in the creation of a quality-of-life instrument for patients who are clinically diagnosed as being in a vegetative or minimally conscious state but are able to communicate by modulating their brain activity (i.e., behaviourally nonresponsive and covertly aware). The study aimed to identify a short list of key domains that could be used to formulate questions for an instrument that determines their self-reported quality of life. Methods: A novel two-pronged strategy was employed: (i) a scoping review of quality-of-life instruments created for patient populations sharing some characteristics with patients who are behaviourally nonresponsive and covertly aware was done to compile a set of potentially relevant domains of quality of life; and (ii) a three-round Delphi consensus process with a multidisciplinary panel of experts was done to determine which of the identified domains of quality of life are most important to those who are behaviourally nonresponsive and covertly aware. Five expert groups were recruited for this study including healthcare workers, neuroscientists, bioethicists, quality-of-life methodologists, and patient advocates. Results: Thirty-five individuals participated in the study with an average response rate of 95% per round. Over the three rounds, experts reached consensus on 34 of 44 domains (42 domains were identified in the scoping review and two new domains were added based on suggestions by experts). 22 domains were rated as being important for inclusion in a quality-of-life instrument and 12 domains were deemed to be of less importance. Participants agreed that domains related to physical pain, communication, and personal relationships were of primary importance. Based on subgroup analyses, there was a high degree of consistency among expert groups. Conclusions: Quality of life should be a central patient-reported outcome in all patient populations regardless of patients’ ability to communicate. It remains to be determined how covertly aware patients perceive their circumstances and quality of life after suffering a life-altering injury. Nonetheless, it is important that any further dialogue on what constitutes a life worth living should not occur without direct patient input

Development and Testing of Retrieval Augmented Generation in Large Language Models -- A Case Study Report

Purpose: Large Language Models (LLMs) hold significant promise for medical applications. Retrieval Augmented Generation (RAG) emerges as a promising approach for customizing domain knowledge in LLMs. This case study presents the development and evaluation of an LLM-RAG pipeline tailored for healthcare, focusing specifically on preoperative medicine. Methods: We developed an LLM-RAG model using 35 preoperative guidelines and tested it against human-generated responses, with a total of 1260 responses evaluated. The RAG process involved converting clinical documents into text using Python-based frameworks like LangChain and Llamaindex, and processing these texts into chunks for embedding and retrieval. Vector storage techniques and selected embedding models to optimize data retrieval, using Pinecone for vector storage with a dimensionality of 1536 and cosine similarity for loss metrics. Human-generated answers, provided by junior doctors, were used as a comparison. Results: The LLM-RAG model generated answers within an average of 15-20 seconds, significantly faster than the 10 minutes typically required by humans. Among the basic LLMs, GPT4.0 exhibited the best accuracy of 80.1%. This accuracy was further increased to 91.4% when the model was enhanced with RAG. Compared to the human-generated instructions, which had an accuracy of 86.3%, the performance of the GPT4.0 RAG model demonstrated non-inferiority (p=0.610). Conclusions: In this case study, we demonstrated a LLM-RAG model for healthcare implementation. The pipeline shows the advantages of grounded knowledge, upgradability, and scalability as important aspects of healthcare LLM deployment.Comment: N

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

© 2018 The Author(s). Background: Assessments of age-specifc mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Afairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. Methods: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specifc mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in diferent components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. Findings: Globally, 18·7% (95% uncertainty interval 18·4-19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2-59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5-49·6) to 70·5 years (70·1-70·8) for men and from 52·9 years (51·7-54·0) to 75·6 years (75·3-75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5-51·7) for men in the Central African Republic to 87·6 years (86·9-88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3-238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6-42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2-5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. Interpretation: This analysis of age-sex-specifc mortality shows that there are remarkably complex patterns in population mortality across countries. The fndings of this study highlight global successes, such as the large decline in under-5 mortality, which refects signifcant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Early Aggressive Immunotherapy Improves Functional Outcome in Chronic Immune Sensory Polyradiculopathy

Chronic immune sensory polyradiculopathy (CISP) is an uncommon and treatable inflammatory disorder of the proximal sensory nerve roots. Patients typically present with severe sensory ataxia, normal motor examination, unsteady gait, and normal nerve conduction studies (NCS). We describe an elderly man who presented with a two-week history of progressive numbness of both legs and recurrent falls. He had hyporeflexia, normal strength, severe proprioceptive, and vibration sense loss in both lower limbs and was unable to stand or walk because of severe sensory ataxia. The NCS and MR scan of the spine were normal. Tibial somatosensory evoked potentials revealed proximal conduction defect and localized the pathology to the lumbar sensory nerve roots proximal to the dorsal root ganglion. Cerebrospinal fluid showed cytoalbuminergic dissociation suggestive of inflammation. CISP was diagnosed; he was given aggressive immunotherapy consisting sequentially of corticosteroids with mycophenolate mofetil and three cycles of intravenous immunoglobulin after which he regained independent mobility. Unlike previous reports where patients presented months-years after symptom onset and improved after single-line immunotherapy, our patient presented fairly acutely and made dramatic improvement only after aggressive combination therapy. We urge physicians to recognize this uncommon neurologic cause of sensory ataxia where early aggressive treatment is crucial for better functional outcomes

Palliative Care for Cancer Patients Near End of Life in Acute-Care Hospitals across Canada: A Look at the Inpatient Palliative Care Code

Hospitals play an important role in the care of patients with advanced cancer: nearly half of all cancer deaths occur in acute-care settings. The need for increasing access to palliative care and related support services for patients with cancer in acute-care hospitals is therefore growing. Here, we examine how often and how early in their illness patients with cancer might be receiving palliative care services in the 2 years before their death in an acute-care hospital in Canada. The palliative care code from inpatient administrative databases was used as a proxy for receiving, or being referred for, palliative care. Currently, the palliative care code is the only data element routinely collected from patient charts that allows for the tracking of palliative care activity at a pan-Canadian level. Our findings suggest that most patients with cancer who die in an acute-care hospital receive a palliative designation; however, many of those patients are identified as palliative only in their final admission before death. Of the patients who received a palliative designation before their final admission, nearly half were identified as palliative less than 2 months before death. Findings signal that delivery of services within and between jurisdictions is not consistent, that the palliative care needs of some patients are being missed by physicians, and that palliative care is still largely seen as end-of-life care and is not recognized as an integral component of cancer care. Measuring the provision of system-wide palliative care remains a challenge because comprehensive national data about palliative care are not currently reported from all sectors. To advance measurement and reporting of palliative care in Canada, attention should be focused on collecting comparable data from regional and provincial palliative care programs that individually capture data about palliative care delivery in all health care sectors

Assessing and Improving the Knowledge of Sexually Transmitted Infections among High School Adolescents

Background. According to the Center for Disease Control and Prevention (CDC), half of the 20 million new sexually transmitted infections (STIs) occur annually in youth aged 15 to 24. It is critical for dermatologists to be able to provide young patients with accessible education about how to identify, prevent, and treat these conditions. Our pilot study sought to assess the impact of a live presentation about STIs in high school students and to evaluate students’ baseline and acquired knowledge about common STIs using a before and after survey. Methods. This survey study was conducted as part of the health education curriculum at a suburban high school. An interactive scenario-based presentation about STIs was given to participants. Identical, deidentified preintervention and postintervention surveys were completed by subjects to assess their baseline and acquired knowledge of STIs. Each question was worth 1 point, for a total of 8 points. Results. 74 high school students were surveyed. Overall, there was a mean improvement of 1.85 points in the posttest score in comparison to pretest score with a standard deviation of 1.58 (p<0.0001). Among all participants, the mean pretest score was 1.07 (SD = 0.75) and the mean posttest score was 2.92 (SD = 1.59). Conclusions. This study demonstrated that many young adults are unaware of the common types of STIs, symptoms, and potential complications. While our scenario-based presentation was effective at providing understandable content to help improve students’ knowledge regarding STIs, additional educational resources in varied formats could likely further these gains

Nosocomial treatment-induced neuropathy of diabetes : an important cause of painful and autonomic neuropathy in hospitalized diabetes mellitus patients

Treatment-induced neuropathy of diabetes (TIND) is an acute painful autonomic small-fiber neuropathy that develops following an abrupt improvement in glycaemia control. Recent reports suggest TIND is a significant problem in tertiary neuropathy clinics. TIND in hospitalized patients with poor initial glycaemia control, that we refer to as nosocomial TIND, has not been well-studied. We describe the demographic, clinical features and indices of glycaemia control in 5 consecutive nosocomial TIND patients. TIND was defined using recently published criteria. Pre-meal capillary blood glucose recordings performed during the period of HbA1c decline was used to calculate glycaemic variability. All the nosocomial TIND patients were hospitalized for prolonged periods for serious medical conditions that warranted good glycaemia control, namely severe sepsis, diabetic ketoacidosis, stroke, heart failure and traumatic head injury. They had raised, double-digit, HbA1c levels at admission that subsequently dropped precipitously with tight in-patient glycaemia control protocols. These patients had multiple, largely asymptomatic, hypoglycaemic episodes. Glycaemic variability also appeared to be high in this cohort. TIND may be a significant cause of morbidity in hospitalized diabetic patients with poor glycaemia control. Not all patients developed both autonomic and painful neuropathies, raising the possibility of forme-fruste TIND.Published versio