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Objectives: Scarce research explores factors of concurrent psychologic distress (prolonged grief disorder [PGD], post-traumatic stress disorder [PTSD], and depression). This study models surrogates' longitudinal, heterogenous grief-related reactions and multidimensional risk factors drawing from the integrative framework of predictors for bereavement outcomes (intrapersonal, interpersonal, bereavement-related, and death-circumstance factors), emphasizing clinical modifiability., Design: Prospective cohort study., Setting: Medical ICUs of two Taiwanese medical centers., Subjects: Two hundred eighty-eight family surrogates., Interventions: None., Measurements and Main Results: Factors associated with four previously identified PGD-PTSD-depressive-symptom states (resilient, subthreshold depression-dominant, PGD-dominant, and PGD-PTSD-depression concurrent) were examined by multinomial logistic regression modeling (resilient state as reference). Intrapersonal: Prior use of mood medications correlated with the subthreshold depression-dominant state. Financial hardship and emergency department visits correlated with the PGD-PTSD-depression concurrent state. Higher anxiety symptoms correlated with the three more profound psychologic-distress states (adjusted odds ratio [95% CI] = 1.781 [1.562-2.031] to 2.768 [2.288-3.347]). Interpersonal: Better perceived social support was associated with the subthreshold depression-dominant state. Bereavement-related: Spousal loss correlated with the PGD-dominant state. Death circumstances: Provision of palliative care (8.750 [1.603-47.768]) was associated with the PGD-PTSD-depression concurrent state. Surrogate-perceived quality of patient dying and death as poor-to-uncertain (4.063 [1.531-10.784]) correlated with the subthreshold depression-dominant state, poor-to-uncertain (12.833 [1.231-133.775]), and worst (12.820 [1.806-91.013]) correlated with the PGD-PTSD-depression concurrent state. Modifiable social-worker involvement (0.004 [0.001-0.097]) and a do-not-resuscitate order issued before death (0.177 [0.032-0.978]) were negatively associated with the PGD-PTSD-depression concurrent and the subthreshold depression-dominant state, respectively. Apparent unmodifiable buffering factors included surrogates' higher educational attainment, married status, and longer time since loss., Conclusions: Surrogates' concurrent bereavement distress was positively associated with clinically modifiable factors: poor quality dying and death, higher surrogate anxiety, and palliative care-commonly provided late in the terminal-illness trajectory worldwide. Social-worker involvement and a do-not-resuscitate order appeared to mitigate risk., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Importance: Improving end-of-life care in the intensive care unit (ICU) is a priority, but clinically modifiable factors of quality of dying and death (QODD) are seldom identified., Objectives: To comprehensively identify factors associated with QODD classes of dying ICU patients, emphasizing clinically modifiable factors based on the integrative framework of factors associated with for bereavement outcomes., Design, Setting, and Participants: This observational cohort study was conducted at medical ICUs of 2 Taiwanese medical centers from January 2018 to March 2020 with follow-up through December 2022. Eligible participants included primary family surrogates responsible for decision making for critically ill ICU patients at high risk of death (Acute Physiology and Chronic Health Evaluation II score >20) but who survived more than 3 days after ICU admission. Data analysis was conducted from July to September 2023., Main Outcomes and Measures: QODD was measured by the 23-item ICU-QODD questionnaire. Factors associated with patient membership in 4 previously determined QODD classes (high, moderate, poor to uncertain, and worst) were examined using a 3-step approach for latent class modeling with the high QODD class as the reference category., Results: A total of 309 family surrogates (mean [SD] age, 49.83 [12.55] years; 184 women [59.5%] and 125 men [40.5%]) were included in the study. Of all surrogates, 91 (29.4%) were the patients' spouse and 66 (53.7%) were the patients' adult child. Patient demographics were not associated with QODD class. Two family demographics (age and gender), relationship with the patient (spousal or adult-child), and length of ICU stay were associated with QODD classes. Patients of surrogates perceiving greater social support were less likely to be in the poor to uncertain (adjusted odds ratio [aOR], 0.89; 95% CI, 0.83-0.94) and worst (aOR, 0.92; 95% CI, 0.87-0.96) QODD classes. Family meetings were associated with the poor to uncertain QODD class (aOR, 8.61; 95% CI, 2.49-29.74) and worst QODD class (aOR, 7.28; 95% CI, 1.37-38.71). Death with cardiopulmonary resuscitation was associated with the worst QODD class (aOR, 7.51; 95% CI, 1.12-50.25). Family presence at patient death was uniformly negatively associated with the moderate QODD class (aOR, 0.16; 95% CI, 0.05-0.54), poor to uncertain QODD class (aOR, 0.21; 95% CI, 0.05-0.82), and worst QODD class (aOR, 0.08; 95% CI, 0.02-0.38). Higher family satisfaction with ICU care was negatively associated with the poor to uncertain QODD class (aOR, 0.93; 95% CI, 0.87-0.98) and worst QODD class (aOR, 0.86; 95% CI, 0.81-0.92)., Conclusions and Relevance: In this cohort study of critically ill patients and their family surrogates, modifiable end-of-life ICU-care characteristics played a more significant role in associations with patient QODD class than did immutable family demographics, preexisting family health conditions, patient demographics, and patient clinical characteristics, thereby illuminating actionable opportunities to improve end-of-life ICU care.

Objectives: To examine associations between family surrogates' bereavement outcomes and four previously determined quality of dying and death (QODD) latent classes (high, moderate, poor-to-uncertain, and worst)., Design: Prospective, longitudinal, observational study., Setting: Medical ICUs at two academically affiliated medical centers in Taiwan., Patients/participants: Three hundred nine family surrogates responsible for decision-making for critically ill patients at high risk of death (Acute Physiology and Chronic Health Evaluation II scores > 20) from a disease., Interventions: None., Measurements and Main Results: Participants were assessed by the depression and anxiety subscales of the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, 11 items of the Prolonged Grief Disorder (PGD) scale, and the Medical Outcomes Study 36-Item Short-Form Health Survey at 1, 3, 6, 13, 18, and 24 months post-loss. We simultaneously examined associations of four QODD latent classes with physical and mental health-related quality of life (HRQOL) and symptoms of anxiety, depression, post-traumatic stress disorder (PTSD), and PGD assessed over 24 bereavement months using multivariate hierarchical linear modeling. Surrogates' distinct QODD latent classes assessed at 1-month post-loss were significantly associated with bereavement outcomes, except for physical HRQOL and PGD symptoms. Significantly more depressive symptoms and worse mental HRQOL (β [95% CI]) were reported by bereaved surrogates in the moderate (1.958 [1.144-2.772], -2.245 [-3.961 to -0.529]), poor-to-uncertain (2.224 [1.438-3.010], -7.026 [-8.683 to -5.369]), and worst (2.081 [1.215-2.964], -4.268 [-6.096 to -2.440]) QODD classes than those in the high QODD class. Bereaved surrogates in the moderate (2.095 [1.392-2.798]) and poor-to-uncertain (0.801 [0.123-1.480]) QODD classes reported more anxiety symptoms, whereas those in the poor-to-uncertain QODD class suffered more PTSD symptoms (2.889 [1.005-4.774]) than those in the high QODD class., Conclusions: The four distinct QODD latent classes were significantly associated with ICU family surrogates' bereavement outcomes, suggesting targets to improve end-of-life care quality in ICUs., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Introduction: The deaths from and morbidities associated with snakebites - amputations, loss of function in the limb, visible scarring or tissue damage - have a vast economic, social, and psychological impact on indigenous communities in the Brazilian Amazon, especially children, and represent a real and pressing health crisis in this population. Snakebite clinical and research experts have therefore proposed expanding antivenom access from only hospitals to include the community health centers (CHC) located near and within indigenous communities. However, there are no studies examining the capacity of CHCs to store, administer, and manage antivenom treatment. In response to this gap, the research team calling for antivenom decentralization developed and validated an expert-based checklist outlining the minimum requirements for a CHC to provide antivenom., Methods: The objective of this study was thus to survey a sample of CHCs in indigenous territories and evaluate their capacity to provide antivenom treatment according to this accredited checklist. The checklist was administered to nurses and doctors from 16 CHCs, two per indigenous district in Amazonas/Roraima states., Results: Our results can be conceptualized into three central findings: 1) most CHCs have the capacity to provide antivenom treatment, 2) challenges to capacity are human resources and specialized items, and 3) antivenom decentralization is feasible and appropriate in indigenous communities., Conclusion: Decentralization would provide culturally and contextually appropriate care accessibility to a historically marginalized and underserved population of the Brazilian Amazon. Future studies should examine optimal resource allocation in indigenous territories and develop an implementation strategy in partnership with indigenous leaders. Beyond the indigenous population, the checklist utilized could be applied to community health centers treating the general population and/or adapted to other low-resource settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Acute kidney injury (AKI) is a critical systemic complication caused by Bothrops envenoming, a neglected health problem in the Brazilian Amazon. Understanding the underlying mechanisms leading to AKI is crucial for effectively mitigating the burden of this complication. This study aimed to characterize the urinary protein profile of Bothrops atrox snakebite victims who developed AKI. We analyzed three groups of samples collected on admission: healthy subjects (controls, n = 10), snakebite victims who developed AKI (AKI, n = 10), and those who did not evolve to AKI (No-AKI, n = 10). Using liquid-chromatography tandem mass spectrometry, we identified and quantified (label-free) 1190 proteins. A panel of 65 proteins was identified exclusively in the urine of snakebite victims, with 32 exclusives to the AKI condition. Proteins more abundant or exclusive in AKI's urine were associated with acute phase response, endopeptidase inhibition, complement cascade, and inflammation. Notable proteins include serotransferrin, SERPINA-1, alpha-1B-glycoprotein, and NHL repeat-containing protein 3. Furthermore, evaluating previously reported biomarkers candidates for AKI and renal injury, we found retinol-binding protein, beta-2-microglobulin, cystatin-C, and hepcidin to be significant in cases of AKI induced by Bothrops envenoming. This work sheds light on physiological disturbances caused by Bothrops envenoming, highlighting potential biological processes contributing to AKI. Such insights may aid in better understanding and managing this life-threatening complication., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Brasileiro-Martins et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Context/objectives: The scarce research on factors associated with surrogate decisional regret overlooks longitudinal, heterogenous decisional-regret experiences and fractionally examines factors from the three decision-process framework stages: decision antecedents, decision-making process, and decision outcomes. This study aimed to fill these knowledge gaps by focusing on factors modifiable by high-quality end-of-life (EOL) care., Methods: This observational study used a prior cohort of 377 family surrogates of terminal-cancer patients to examine factors associated with their membership in the four preidentified distinct decisional-regret trajectories: resilient, delayed-recovery, late-emerging, and increasing-prolonged trajectories from EOL-care decision making through the first two bereavement years by multinomial logistic regression modeling using the resilient trajectory as reference., Results: Decision antecedent factors: Financial sufficiency and heavier caregiving burden increased odds for the delayed-recovery trajectory. Spousal loss, higher perceived social support during an EOL-care decision, and more postloss depressive symptoms increased odds for the late-emerging trajectory. More pre- and postloss depressive symptoms increased odds for the increasing-prolonged trajectory. Decision-making process factors: Making an anticancer treatment decision and higher decision conflict increased odds for the delayed-recovery and increasing-prolonged trajectories. Making a life-sustaining-treatment decision increased membership in the three more profound trajectories. Decision outcome factors: Greater surrogate appraisal of quality of dying and death lowered odds for the three more profound trajectories. Patient receipt of anticancer or life-sustaining treatments increased odds for the late-emerging trajectory., Conclusion: Surrogate membership in decisional-regret trajectories was associated with decision antecedent, decision-making process, and decision outcome factors. Effective interventions should target identified modifiable factors to address surrogate decisional regret., (Copyright © 2023 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Currently, antivenoms are the only specific treatment available for snakebite envenoming. In Brazil, over 30% of patients cannot access antivenom within its critical care window. Researchers have therefore proposed decentralizing to community health centers to decrease time-to-care and improve morbidity and mortality. Currently, there is no evidence-based method to evaluate the capacity of health units for antivenom treatment, nor what the absolute minimum supplies and staff are necessary for safe and effective antivenom administration and clinical management., Methods: This study utilized a modified-Delphi approach to develop and validate a checklist to evaluate the minimum requirements for health units to adequately treat snakebite envenoming in the Amazon region of Brazil. The modified-Delphi approach consisted of four rounds: 1) iterative development of preliminary checklist by expert steering committee; 2) controlled feedback on preliminary checklist via expert judge survey; 3) two-phase nominal group technique with new expert judges to resolve pending items; and 4) checklist finalization and closing criteria by expert steering committee. The measure of agreement selected for this study was percent agreement defined a priori as ≥75%., Results: A valid, reliable, and feasible checklist was developed. The development process highlighted three key findings: (1) the definition of community health centers and its list of essential items by expert judges is consistent with the Brazilian Ministry of Health, WHO snakebite strategic plan, and a general snakebite capacity guideline in India (internal validity), (2) the list of essential items for antivenom administration and clinical management is feasible and aligns with the literature regarding clinical care (reliability), and (3) engagement of local experts is critical to developing and implementing an antivenom decentralization strategy (feasibility)., Conclusion: This study joins an international set of evidence advocating for decentralization, adding value in its definition of essential care items; identification of training needs across the care continuum; and demonstration of the validity, reliability, and feasibility provided by engaging local experts. Specific to Brazil, further added value comes in the potential use of the checklist for health unit accreditation as well as its applications to logistics and resource distribution. Future research priorities should apply this checklist to health units in the Amazon region of Brazil to determine which community health centers are or could be capable of receiving antivenom and translate this expert-driven checklist and approach to snakebite care in other settings or other diseases in low-resource settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Serrão-Pinto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This cohort study identified patterns/classes of surrogates' assessment of their relative's quality of dying and death (QODD) and to evaluate their associations with family satisfaction with intensive care unit (ICU) care., Methods: We identified QODD classes through latent class analysis of the frequency component of the QODD questionnaire and examined their differences in summary questions on the QODD and scores of the Family Satisfaction in the ICU questionnaire among 309 bereaved surrogates of ICU decedents., Results: Four distinct classes (prevalence) were identified: high (41.3%), moderate (20.1%), poor-to-uncertain (21.7%) and worst (16.9%) QODD classes. Characteristics differentiate these QODD classes including physical symptom control, emotional preparedness for death, and amount of life-sustaining treatments (LSTs) received. Patients in the high QODD class had optimal physical symptom control, moderate-to-sufficient emotional preparedness for death and few LSTs received. Patients in the moderate QODD class had adequate physical symptom control, moderate-to-sufficient emotional preparedness for death and the least LSTs received. Patients in the poor-to-uncertain QODD class had inadequate physical symptom control, insufficient-uncertain emotional preparedness for death and some LSTs received. Patients in the worst QODD class had poorest physical symptom control, insufficient-to-moderate emotional preparedness for death and substantial LSTs received. Bereaved surrogates in the worst QODD class scored significantly lower in evaluations of the patient's overall QODD, and satisfaction with ICU care and decision-making process than those in the other classes., Conclusions: The identified distinct QODD classes offer potential actionable direction for improving quality of end-of-life ICU care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

This cohort study investigated factors associated with 336 Taiwanese family caregivers' emotional and cognitive preparedness for death of a loved one with terminal cancer. Caregivers' death-preparedness states (no-death-preparedness [as reference], cognitive-death-preparedness-only, emotional-death-preparedness-only, and sufficient-death-preparedness states) were previously identified. Associations of factors with these states were determined by a hierarchical generalized linear model. Financial hardship decreased caregivers' likelihood for the emotional-death-preparedness-only and sufficient-death-preparedness states. Physician prognostic disclosure increased membership in the cognitive-death-preparedness-only and sufficient-death-preparedness states. The better the quality of the patient-caregiver relationship, the higher the odds for the emotional-death-preparedness-only and sufficient-death-preparedness states, whereas the greater the tendency for caregivers to communicate end-of-life issues with their loved one, the lower the odds for emotional-death-preparedness-only state membership. Stronger coping capacity increased membership in the emotional-death-preparedness-only state, but perceived social support was not associated with state membership. Providing effective interventions tailored to at-risk family caregivers' specific needs may facilitate their death preparedness.

Background: Snakebite envenoming (SBE) affects nearly three million people yearly, causing up to 180,000 deaths and 400,000 cases of permanent disability. Brazil's state of Amazonas is a global hotspot for SBE, with one of the highest annual incidence rates per 100,000 people, worldwide. Despite this burden, snake antivenom remains inaccessible to a large proportion of SBE victims in Amazonas. This study estimates the costs, and health and economic benefits of scaling up antivenom to community health centers (CHCs) and hospitals in the state., Methods: We built a decision tree model to simulate three different antivenom scale-up scenarios: (1) scale up to 95% of hospitals, (2) scale up to 95% of CHCs, and (3) scale up to 95% of hospitals and 95% of CHCs. We consider each scenario with and without a 10% increase in demand for antivenom among SBE victims. For each scenario, we model the treatment costs averted, deaths averted, and disability-adjusted life years (DALYs) averted from a societal, health system, and patient perspective relative to the status quo and over a time horizon of one year. For each scenario and perspective, we also calculate the incremental cost per DALY averted and per death averted. We use a willingness to pay threshold equal to the 2022 gross domestic product (GDP) per capita of Brazil., Findings: Scaling up antivenom to 95% of hospitals averts up to 2022 DALYs, costs up to USD $460 per DALY averted from a health system perspective, but results in net economic benefits up to USD $4.42 million from a societal perspective. Scaling up antivenom to 95% of CHCs averts up to 3179 DALYs, costs up to USD $308 per DALY averted from a health system perspective, but results in net economic benefits up to USD $7.35 million from a societal perspective. Scaling up antivenom to 95% of hospitals and CHCs averts up to 3922 DALYs, costs up to USD $328 per DALY averted from a health system perspective, but results in net economic benefits up to USD $8.98 million from a societal perspective., Interpretation: All three antivenom scale up scenarios - scale up to 95% of hospitals, scale up to 95% of CHCs, and scale up to 95% of hospitals and 95% of CHCs - avert a substantial proportion of the SBE burden in Amazonas and are cost-saving from a societal perspective and cost-effective from a health system perspective., Funding: W.M. and J.S. were funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq productivity scholarships). W.M. was funded by Fundação de Amparo à Pesquisa do Estado do Amazonas (PRÓ-ESTADO, call n. 011/2021-PCGP/FAPEAM, call n. 010/2021-CT&I ÁREAS PRIORITÁRIAS, call n. 003/2022-PRODOC/FAPEAM, POSGRAD/FAPEAM) and by the Ministry of Health, Brazil (Proposal No. 733781/19-035). Research reported in this publication was supported by the Fogarty International Center of the National Institutes of Health under Award Number R21TW011944. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., Competing Interests: CJG reports research funding from Ophirex Inc. for other studies., (© 2023 The Authors.)

Background: Family surrogates experience heterogeneous decisional regret and negative long-lasting postdecision impacts. Cross-sectional findings on the associations between decisional regret and surrogates' bereavement outcomes are conflicting and cannot illustrate the directional and dynamic evolution of these associations. In this study, we sought to longitudinally examine the associations between 4 previously identified decisional-regret trajectories and bereavement outcomes among family surrogates of terminally ill patients with cancer., Patients and Methods: This prospective, longitudinal, observational study included 377 family surrogates. Decisional regret was measured using the 5-item Decision Regret Scale, and 4 decisional regret trajectories were identified: resilient, delayed-recovery, late-emerging, and increasing-prolonged. Associations between bereavement outcomes (depressive symptoms, prolonged grief symptoms, and physical and mental health-related quality of life [HRQoL]) and decisional-regret trajectories were examined simultaneously by multivariate hierarchical linear modeling using the resilient trajectory as a reference., Results: Surrogates in the delayed-recovery, late-emerging, and increasing-prolonged trajectories experienced significantly higher symptoms of prolonged grief (β [95% CI], 1.815 [0.782 to 2.848]; 2.312 [0.834 to 3.790]; and 7.806 [2.681 to 12.931], respectively) and poorer physical HRQoL (-1.615 [-2.844 to -0.386]; -1.634 [-3.226 to -0.042]; and -4.749 [-9.380 to -0.118], respectively) compared with those in the resilient trajectory. Membership in the late-emerging and increasing-prolonged trajectories was associated with higher symptoms of depression (β [95% CI], 2.942 [1.045 to 4.839] and 8.766 [2.864 to 14.668], respectively), whereas only surrogates in the increasing-prolonged decisional-regret trajectory reported significantly worse mental HRQoL (-4.823 [-8.216 to -1.430]) than those in the resilient trajectory., Conclusions: Surrogates who experienced delayed-recovery, unresolved, or late-emerging decisional regret may carry ceaseless doubt, guilt, or self-blame for patient suffering, leading to profound symptoms of prolonged grief, depressive symptoms, and worse HRQoL over their first 2 bereavement years.

Importance: Family surrogates of patients who die in an intensive care unit (ICU) are at risk of cooccurring prolonged grief disorder (PGD), posttraumatic stress disorder (PTSD), and depressive disorder during bereavement, but symptom trajectories are often explored individually., Objectives: To simultaneously examine and determine co-occurrence of PGD, PTSD, and depressive symptom trajectories., Design, Setting, and Participants: This cohort study was conducted in ICUs of 2 Taiwanese medical centers from January 2018 to March 2020, with follow-up through July 2022. Participants included surrogates responsible for decision-making who provided data 6 to 24 months after the death of their loved one. Data were analyzed from August to December 2022., Main Outcomes and Measures: PGD was assessed with the 11 grief symptom items of the PG-13; PTSD, the Impact of Event Scale-Revised; and depressive symptoms, the depression subscale of the Hospital Anxiety and Depression Scale at 6, 13, 18, and 24 months after the death. Latent growth mixture modeling was conducted to identify distinct trajectories, and joint latent class analysis was used to assess joint patterns of trajectories., Results: A total of 303 participants were included, with most younger than 56 years (207 participants [68.3%]), female (177 participants [58.4%]), and married (228 participants [75.2%]), and their relationship with the patient was mostly spouse (88 participants [29.0%]) or adult child (166 participants [54.8%]). Three trajectories were identified each for PGD, PTSD, and depressive symptoms. A resilience trajectory was predominant across PGD (253 participants [83.5%]), PTSD (250 participants [82.5%]), and depressive (200 participants [66.0%]) symptoms. Second most common was a recovery trajectory identified for PGD (36 participants [11.9%]) and PTSD (41 participants [13.5%]) symptoms, while for depressive symptoms, a moderate trajectory (72 participants [23.8%]) signified persistent moderate distress. A chronic trajectory characterized by persistently high distress was identified for PGD (14 participants [4.6%]) and depressive (31 participants [10.2%]) symptoms, whereas a unique delayed-onset trajectory (12 participants [4.0%]) was identified for PTSD symptoms. Most family surrogates (228 participants [75.2%]) experienced cooccurring PGD, PTSD, and depressive symptom trajectories, but multiple patterns were discordant. Symptom trajectories cooccurred in joint patterns: resilient (247 participants [81.5%]), recovered (43 participants [14.1%]), and distressed (14 participants [4.5%]). These patterns were characterized by high conditional probabilities for the resilience (PGD, 0.999; PTSD, 0.999; depressive, 0.804), recovery (PGD, 0.854; PTSD, 0.890; depressive, 0.588), and chronic (PGD, 0.921; PTSD, 0.789; depressive, 0.980) symptom trajectories., Conclusions and Relevance: In this cohort study, grief-related psychological symptoms evolved in complex ways during ICU bereavement, as characterized by heterogeneous trajectories. Some ICU bereaved surrogates experienced persistent elevated PGD, PTSD, and depressive symptoms individually or conjointly, underscoring the importance of early screening to identify this population at high risk of comorbid psychological distress trajectories.

This study investigated the differences in programming novices' intrinsic motivation and performance within a Scratch-based programming learning environment using a pretest-posttest intervention design. Specifically, this study aimed to examine what and how achievement emotions were aroused to impact learners' academic success during Scratch implementation processes by employing regression analyses. One hundred and seventy-two undergraduates (Mage = 20.44, SDage = 1.09, 55.8% female) were voluntarily recruited to participate in a Scratch-based instruction workshop during a 6-week period. The workshop was structured with regard to preparation, Scratch-based programming learning and projects, and assessment activities and questionnaire implemented both before the instructional period and after the workshop. The results suggested that the Scratch-based intervention significantly increased students' overall motivation and examination performance. Concerning achievement emotions, the outcome emotion of hopelessness first negatively predicted students' motivation and performance. Anxiety then replaced hopelessness as a negative predictor, while enjoyment was the strongest predictor of motives and performance. Taking eight emotions together, the arousal of activity and outcome emotions within visual programming environments facilitated students' emotion dynamics that impacted motivation and performance. The discussion and contributions concerning the mechanism behind the effectiveness of visualization and the emotion-performance relationship are presented herein., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Grief-related psychological distress often co-occurs to conjointly impair function during bereavement. Knowledge of comorbid grief-related psychological distress is limited: no longitudinal study has examined dynamic patterns of co-occurring prolonged grief disorder (PGD), posttraumatic stress disorder (PTSD), and depression, and previous assessment time frames have been variable and potentially inadequate given the duration criterion for PGD. Therefore, the purpose of this study was to investigate the transition of distinct symptom states based on the co-occurrence of PGD, PTSD, and depression symptoms for ICU bereaved surrogates over their first two bereavement years., Design: Prospective, longitudinal, observational study., Setting: Medical ICUs at two academically affiliated medical centers in Taiwan., Patients/participants: Three hundred three family surrogates responsible for decision-making for critically ill patients at high risk of death (Acute Physiology and Chronic Evaluation II scores > 20) from a disease., Intervention: None., Measurements and Main Results: Participants were assessed by 11 items of the Prolonged Grief Disorder (PG-13) scale, the Impact of Event Scale-Revised, and the depression subscale of the Hospital Anxiety and Depression Scale at 6, 13, 18, and 24 months postloss. PGD-PTSD-depression-symptom states and their evolution were examined by latent transition analysis. The following four distinct PGD-PTSD-depression-symptom states (prevalence) were initially identified: resilient (62.3%), subthreshold depression-dominant (19.9%), PGD-dominant (12.9%), and PGD-PTSD-depression comorbid (4.9%) states. These PGD-PTSD-depression-symptom states remained highly stable during the first two bereavement years, with transitions predominantly toward resilience. Prevalence for each state at 24 months postloss was 82.1%, 11.4%, 4.0%, and 2.5%, respectively., Conclusions: Four highly stable PGD-PTSD-depression-symptom states were identified, highlighting the importance of screening for subgroups of ICU bereaved surrogates with increased PGD or comorbid PGD, PTSD, and depression symptoms during early bereavement., Competing Interests: Drs. Wen and Chuang disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: The indigenous populations of Brazil present poor health indicators and a disproportionate prevalence and case-fatality rate of neglected tropical diseases, including snakebite envenomations (SBEs). This study aims to estimate access to medical care for SBEs and analyze the barriers that prevent victims from accessing healthcare in indigenous communities in two health districts located in the Western Brazilian Amazon., Methodology/principal Findings: This cross-sectional study used semi-structured interviews to collect data from individuals who experienced SBEs in the Upper Rio Solimões and Upper Rio Negro indigenous health districts. Of the 187 participants, 164 (87.7%) reported that they had access to healthcare and received assistance in a hospital in the urban area of the municipalities. Frequency was 95.4% in the Upper Rio Solimões SIHD, and 69.6% in the Upper Rio Negro SIHD (P<0.0001). The study found that the availability of indigenous medicine as the only choice in the village was the main reason for not accessing healthcare (75%), followed by a lack of financial resources and means of transportation (28.1%). Four deaths were reported from SBEs, resulting in a case-fatality rate of 2.1%., Conclusions/significance: In the study areas, there are records of SBE patients who did not receive medical attention. Availability of pre-hospital emergency transport using motorboats, a greater number of hospitals and better navigability of the Solimões River and its tributaries would make access easier for indigenous people living in the region of the Upper Solimões River. The implementation of cross-cultural hospital care needs to be considered in order to reduce the resistance of indigenous populations in relation to seeking treatment for SBEs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 de Farias et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Context: Regret plays a central role in surrogate decision making. Research on decisional regret in family surrogates is scarce and lacks longitudinal studies to illustrate the heterogenous, dynamic evolution of decisional regret., Objectives: To identify distinct decisional-regret trajectories from end-of-life (EOL) decision making through the first two bereavement years among surrogates of cancer patients., Methods: A prospective, longitudinal, observational study was conducted on a convenience sample of 377 surrogates of terminally ill cancer patients. Decisional regret was measured by the five-item Decision Regret Scale monthly during the patient's last six months and 1, 3, 6, 13, 18, and 24 months post loss. Decisional-regret trajectories were identified using latent-class growth analysis., Results: Surrogates reported substantially high decisional regret (pre- and postloss mean [SD] as 32.20 [11.47] and 29.90 [12.47], respectively). Four decisional-regret trajectories were identified. The resilient trajectory (prevalence: 25.6%) showed a general low decisional-regret level with mild and transient perturbations around the time of patient death only. Decisional regret for the delayed-recovery trajectory (56.3%) accelerated before the patient's death and decreased slowly throughout bereavement. Surrogates in the late-emerging (10.2%) trajectory reported a low decisional-regret level before loss but their decisional regret increased gradually thereafter. The increasing-prolonged trajectory (6.9%) rapidly increased in decisional-regret levels during EOL decision making, peaked one-month post loss, then declined steadily but without a complete resolution., Conclusion: Surrogates heterogeneously suffered decisional regret from EOL decision making through bereavement as evident by four identified distinct decisional-regret trajectories. Early identification and prevention of increasing/prolonged decisional-regret trajectories is warranted., (Copyright © 2023 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background/objective: Facilitating death preparedness is important for improving cancer patients' quality of death and dying. We aimed to identify factors associated with the four death-preparedness states (no-preparedness, cognitive-only, emotional-only, and sufficient-preparedness) focusing on modifiable factors., Methods: In this cohort study, we identified factors associated with 314 Taiwanese cancer patients' death-preparedness states from time-invariant socio-demographics and lagged time-varying modifiable variables, including disease burden, physician prognostic disclosure, patient-family communication on end-of-life (EOL) issues, and perceived social support using hierarchical generalized linear modeling., Results: Patients who were male, older, without financial hardship to make ends meet, and suffered lower symptom distress were more likely to be in the emotional-only and sufficient-preparedness states than the no-death-preparedness-state. Younger age (adjusted odds ratio [95% confidence interval] = 0.95 [0.91, 0.99] per year increase in age) and greater functional dependency (1.05 [1.00, 1.11]) were associated with being in the cognitive-only state. Physician prognostic disclosure increased the likelihood of being in the cognitive-only (51.51 [14.01, 189.36]) and sufficient-preparedness (47.42 [10.93, 205.79]) states, whereas higher patient-family communication on EOL issues reduced likelihood for the emotional-only state (0.38 [0.21, 0.69]). Higher perceived social support reduced the likelihood of cognitive-only (0.94 [0.91, 0.98]) but increased the chance of emotional-only (1.09 [1.05, 1.14]) state membership., Conclusions: Death-preparedness states are associated with patients' socio-demographics, disease burden, physician prognostic disclosure, patient-family communication on EOL issues, and perceived social support. Providing accurate prognostic disclosure, adequately managing symptom distress, supporting those with higher functional dependence, promoting empathetic patient-family communication on EOL issues, and enhancing perceived social support may facilitate death preparedness., (© 2023 John Wiley & Sons Ltd.)

Background: Snakebite envenoming (SBE) is a neglected tropical disease capable of causing both significant disability and death. The burden of SBE is especially high in low- and middle-income countries. The aim of this study was to perform a geospatial analysis evaluating the association of sociodemographics and access to care indicators on moderate and severe cases of SBE in Brazil., Methods: We conducted an ecological, cross-sectional study of SBE in Brazil from 2014 to 2019 using the open access National System Identification of Notifiable Diseases (SINAN) database. We then collected a set of indicators from the Brazil Census of 2010 and performed a Principal Component Analysis to create variables related to health, economics, occupation, education, infrastructure, and access to care. Next, a descriptive and exploratory spatial analysis was conducted to evaluate the geospatial association of moderate and severe events. These variables related to events were evaluated using Geographically Weighted Poisson Regression. T-values were plotted in choropleth maps and considered statistically significant when values were <-1.96 or >+1.96., Results: We found that the North region had the highest number of SBE cases by population (47.83/100,000), death rates (0.18/100,000), moderate and severe rates (22.96/100,000), and proportion of cases that took more than three hours to reach healthcare assistance (44.11%). The Northeast and Midwest had the next poorest indicators. Life expectancy, young population structure, inequality, electricity, occupation, and more than three hours to reach healthcare were positively associated with greater cases of moderate and severe events, while income, illiteracy, sanitation, and access to care were negatively associated. The remaining indicators showed a positive association in some areas of the country and a negative association in other areas., Conclusion: Regional disparities in SBE incidence and rates of poor outcomes exist in Brazil, with the North region disproportionately affected. Multiple indicators were associated with rates of moderate and severe events, such as sociodemographic and health care indicators. Any approach to improving snakebite care must work to ensure the timeliness of antivenom administration., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Isaacson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Scorpion stings in Brazil represent a major public health problem due to their incidence and their potential ability to lead to severe and often fatal clinical outcomes. A better understanding of scorpionism determinants is essential for a precise comprehension of accident dynamics and to guide public policy. Our study is the first to model the spatio-temporal variability of scorpionism across municipalities in São Paulo (SP) and to investigate its relationship with demographic, socioeconomic, environmental, and climatic variables., Methodology: This ecological study analyzed secondary data on scorpion envenomation in SP from 2008 to 2021, using the Integrated Nested Laplace Approximation (INLA) to perform Bayesian inference for detection of areas and periods with the most suitable conditions for scorpionism., Principal Findings: From the spring of 2008 to 2021, the relative risk (RR) increased eight times in SP, from 0.47 (95%CI 0.43-0.51) to 3.57 (95%CI 3.36-3.78), although there has been an apparent stabilization since 2019. The western, northern, and northwestern parts of SP showed higher risks; overall, there was a 13% decrease in scorpionism during winters. Among the covariates considered, an increase of one standard deviation in the Gini index, which captures income inequality, was associated with a 11% increase in scorpion envenomation. Maximum temperatures were also associated with scorpionism, with risks doubling for temperatures above 36°C. Relative humidity displayed a nonlinear association, with a 50% increase in risk for 30-32% humidity and reached a minimum of 0.63 RR for 75-76% humidity., Conclusions: Higher temperatures, lower humidity, and social inequalities were associated with a higher risk of scorpionism in SP municipalities. By capturing local and temporal relationships across space and time, authorities can design more effective strategies that adhere to local and temporal considerations., Competing Interests: The authors declare no competing interests., (Copyright: © 2023 Chiaravalloti-Neto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background/objective: Bereaved family surrogates from intensive care units (ICU) are at risk of comorbid anxiety, depression, and post-traumatic stress disorder (PTSD), but the temporal reciprocal relationships among them have only been examined once among veterans. This study aimed to longitudinally investigate these never-before-examined temporal reciprocal relationships for ICU family members over their first two bereavement years., Methods: In this prospective, longitudinal, observational study, symptoms of anxiety, depression, and PTSD were assessed among 321 family surrogates of ICU decedents from 2 academically affiliated hospitals in Taiwan by the anxiety and depression subscales of the Hospital Anxiety and Depression Scale, and the Impact of Event Scale-Revised, respectively at 1, 3, 6, 13, 18, and 24 months postloss. Cross-lagged panel modeling was conducted to longitudinally examine the temporal reciprocal relationships among anxiety, depression, and PTSD., Results: Examined psychological-distress levels were markedly stable over the first 2 bereavement years: autoregressive coefficients for symptoms of anxiety, depression, and PTSD were 0.585-0.770, 0.546-0.780, and 0.440-0.780, respectively. Cross-lag coefficients showed depressive symptoms predicted PTSD symptoms in the first bereavement year, whereas PTSD symptoms predicted depressive symptoms in the second bereavement year. Anxiety symptoms predicted symptoms of depression and PTSD at 13 and 24 months postloss, whereas depressive symptoms predicted anxiety symptoms at 3 and 6 months postloss while PTSD symptoms predicted anxiety symptoms during the second bereavement year., Conclusions: Different patterns of temporal relationships among symptoms of anxiety, depression, and PTSD over the first 2 bereavement years present important opportunities to target symptoms of specific psychological distress at different points during bereavement to prevent the onset, exacerbation, or maintenance of subsequent psychological distress., (© 2023. The Author(s).)

Objective: Unprecedently investigate associations of prognostic-awareness-transition patterns with (changes in) depressive symptoms, anxiety symptoms, and quality of life (QOL) during cancer patients' last 6 months., Methods: In this secondary analysis study, 334 cancer patients in their last 6 months transitioned between four prognostic-awareness states (unknown and not wanting to know, unknown but wanting to know, inaccurate awareness, and accurate awareness), thus constituting three transition patterns: maintaining-accurate-, gaining-accurate-, and maintaining-inaccurate/unknown prognostic awareness. A multivariate hierarchical linear model evaluated associations of the transition patterns with depressive symptoms, anxiety symptoms, and QOL determined at final assessment and by mean difference between the first and last assessment., Results: At the last assessment before death, the gaining-accurate-prognostic-awareness group reported higher levels of depressive symptoms (estimate [95% confidence interval] = 1.59 [0.35-2.84]) and the maintaining- and gaining-accurate-prognostic-awareness groups suffered more anxiety symptoms (1.50 [0.44-2.56]; 1.42 [0.13-2.71], respectively) and poorer QOL (-7.07 [-12.61 to 1.54]; -11.06 [-17.76 to -4.35], respectively) than the maintaining-inaccurate/unknown-prognostic-awareness group. Between the first and last assessment, the maintaining- and gaining-accurate-prognostic-awareness groups' depressive symptoms (1.59 [0.33-2.85]; 3.30 [1.78-4.82], respectively) and QOL (-5.04 [-9.89 to -0.19]; -8.86 [-14.74 to -2.98], respectively) worsened more than the maintaining-inaccurate/unknown-prognostic-awareness group, and the gaining-accurate-prognostic-awareness group's depressive symptoms increased more than the maintaining-accurate-prognostic-awareness group (1.71 [0.42-3.00])., Conclusions: Unexpectedly, patients who maintained/gained accurate prognostic awareness suffered more depression, anxiety, and poorer QOL at end of life. Promoting accurate prognostic awareness earlier in the terminal-cancer trajectory should be supplemented with adequate psychological care to alleviate patients' emotional distress and enhance QOL., Trial Registration: ClinicalTrials.gov:NCT01912846., (© 2023 John Wiley & Sons Ltd.)

Envenomation caused by venomous animals may trigger significant local complications such as pain, edema, localized hemorrhage, and tissue necrosis, in addition to complications such as dermonecrosis, myonecrosis, and even amputations. This systematic review aims to evaluate scientific evidence on therapies used to target local effects caused by envenomation. The PubMed, MEDLINE, and LILACS databases were used to perform a literature search on the topic. The review was based on studies that cited procedures performed on local injuries following envenomation with the aim of being an adjuvant therapeutic strategy. The literature regarding local treatments used following envenomation reports the use of several alternative methods and/or therapies. The venomous animals found in the search were snakes (82.05%), insects (2.56%), spiders (2.56%), scorpions (2.56%), and others (jellyfish, centipede, sea urchin-10.26%). In regard to the treatments, the use of tourniquets, corticosteroids, antihistamines, and cryotherapy is questionable, as well as the use of plants and oils. Low-intensity lasers stand out as a possible therapeutic tool for these injuries. Local complications can progress to serious conditions and may result in physical disabilities and sequelae. This study compiled information on adjuvant therapeutic measures and underscores the importance of more robust scientific evidence for recommendations that act on local effects together with the antivenom.

Remote areas, such as the Amazon Forest, face unique geographical challenges of transportation-based access to health services. As transportation to healthcare in most of the Amazon Forest is only possible by rivers routes, any travel time and travel distance estimation is limited by the lack of data sources containing rivers as potential transportation routes. Therefore, we developed an approach to convert the geographical representation of roads and rivers in the Amazon into a combined, interoperable, and reusable dataset. To build the dataset, we processed and combined data from three data sources: OpenStreetMap, HydroSHEDS, and GloRiC. The resulting dataset can consider distance metrics using the combination of streets and rivers as a transportation route network for the Amazon Forest. The created dataset followed the guidelines and attributes defined by OpenStreetMap to leverage its reusability and interoperability possibilities. This new data source can be used by policymakers, health authorities, and researchers to perform time-to-care analysis in the International Amazon region., (© 2023. The Author(s).)

Background: Fatigue in patients on hemodialysis varies based on disease and treatment situations. Most studies have assessed the effectiveness of interventions based on average fatigue during the past week. However, two different types of fatigue are identified: post-dialysis fatigue and continuous fatigue. Identifying different types of fatigue and related factors may facilitate the development of more-effective, type-specific measures to reduce patient fatigue., Purpose: The purpose of this study was to explore fatigue patterns and predictors in patients on hemodialysis during their eight-day dialysis cycle., Methods: A perspective, observational research design was adopted. One hundred and two patients were recruited from three hospitals and one hemodialysis clinic in New Taipei City. During the dialysis, patients answered a structured questionnaire that included a demographic datasheet, Taiwanese depression questionnaire, hemodialysis social support scale, trait anxiety inventory, Pittsburgh sleep quality index, and fatigue visual analogy scale. After dialysis on each day, patients completed the fatigue visual analogy scale for a period of eight consecutive days every morning, noon, and night. Biochemical data and inter-dialysis weight gain were collected from medical charts., Results: This study found three distinct fatigue status groups: fatigue adaptation, rapid change and continuous fatigue. After the day of dialysis, fatigue level was the lowest in the fatigue adaptation group, followed by the continuous fatigue group. The rapid change group reported the highest level of fatigue. With regard to the degree of increase in fatigue after dialysis (fatigue score after dialysis minus fatigue score before dialysis), the rapid change group had the highest average increase in score after dialysis, while the continuous fatigue group had the lowest. Sleep quality, trait anxiety, and health caregiver support were also found to be predictors of group affiliation., Conclusions: Nurses can provide individual social support interventions and methods to improve sleep quality and alleviate anxiety to reduce fatigue in patients on hemodialysis.

Background: In the Brazilian Amazon, snakebite envenomings (SBE) disproportionately affect indigenous peoples. Communication between indigenous and biomedical health sectors in regards to SBEs has never been explored in this region. This study aims to build an explanatory model (EM) of the indigenous healthcare domain for SBE patients from the perspective of the indigenous caregivers., Methodology/principal Findings: This is a qualitative study involving in-depth interviews of eight indigenous caregivers who are representatives of the Tikuna, Kokama and Kambeba ethnic groups, in the Alto Solimões River, western Brazilian Amazon. Data analysis was carried out via deductive thematic analysis. A framework was built containing the explanations based on three explanatory model (EM) components: etiology, course of sickness, and treatment. To indigenous caregivers, snakes are enemies and present conscience and intention. Snakebites have a natural or a supernatural cause, the last being more difficult to prevent and treat. Use of ayahuasca tea is a strategy used by some caregivers to identify the underlying cause of the SBE. Severe or lethal SBEs are understood as having been triggered by sorcery. Treatment is characterized by four components: i) immediate self-care; ii) first care in the village, mostly including tobacco smoking, chants and prayers, combined with the intake of animal bile and emetic plants; iii) a stay in a hospital, to receive antivenom and other treatments; iv) care in the village after hospital discharge, which is a phase of re-establishment of well-being and reintroduction into social life, using tobacco smoking, massages and compresses to the affected limb, and teas of bitter plants. Dietary taboos and behavioral interdictions (avoiding contact with menstruating and pregnant women) prevent complications, relapses, and death, and must be performed up to three months after the snakebite. Caregivers are in favor of antivenom treatment in indigenous areas., Conclusions/significance: There is a potential for articulation between different healthcare sectors to improve the management of SBEs in the Amazon region, and the aim is to decentralize antivenom treatment so that it occurs in indigenous health centers with the active participation of the indigenous caregivers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 de Farias et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Snakebite envenoming is currently considered a neglected tropical disease, which affects over 5 million people worldwide, and causes almost 150 000 deaths every year, as well as severe injuries, amputations and other sequelae. Snakebite envenoming in children, although proportionally less frequent, is generally more severe, and represents an important challenge for pediatric medicine, since they often result in worse outcomes. In Brazil, given its ecological, geographic and socioeconomic characteristics, snakebites are considered an important health problem, presenting approximately 30 000 victims per year, approximately 15% of them in children. Even with low snakebite incidence, children tend to have higher snakebite severity and complications due to the small body mass and same venom volume inoculated in comparison to adults, even though, due to the lack of epidemiological information about pediatric snakebites and induced injuries, it is difficult to measure the treatment effectiveness, outcomes and quality of emergency medical services for snakebites in children. In this review, we report how Brazilian children are affected by snakebites, describing the characteristics of this affected population, clinical aspects, management, outcomes and main challenges., (© The Author(s) [2023]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: The present study used a hierarchical generalized linear model to explore the effects of physical and mental health and occupational categories on occupational injuries and diseases., Methods: The data were obtained from the Registry for Beneficiaries of the 2002-2013 National Health Insurance Research Database. The benefit categories involved adults with occupational injuries and diseases. Six major occupational categories and 28 subcategories were used. The main analysis methods were binary logistic regression (BLR) and hierarchical generalized linear model (HGLM)., Results: After adjustment for relevant factors, the three major occupation subcategories most likely to develop occupational injuries and diseases were Subcategory 12 "employees with fixed employers" of Category 1 "civil servants, employees in public or private schools, laborers, and self-employed workers"; Subcategory 2 "employees in private organizations" of Category 1; and "sangha and religionists" of Category 6 "other citizens." Conditions such as mental disorders and obesity increased the risk of occupational injuries and diseases., Conclusion: A portion of the occupational categories had a higher risk of occupational injuries and diseases. Physical and mental health issues were significantly correlated with occupational injuries and diseases. To the authors' knowledge, this is the first study to use HGLM to analyze differences in occupational categories in Taiwan.

With the advancements in therapeutics and available treatment options, almost all deaths and permanent disabilities from snakebite envenoming (SBE) are preventable. The challenge lies in implementing these evidence-based treatments and practices across different settings and populations. This study aims to compare data on provider perceptions of SBE care across health systems and cultural contexts to inform potential implementation science approaches. We hypothesize different health systems and cultural contexts will influence specific perceived needs to provide adequate snakebite care within central tenets of care delivery (e.g., cost, access, human resources). We previously conducted exploratory descriptive studies in the US and Brazil in order to understand the experience, knowledge, and perceptions of health professionals treating SBE. In the US, in-depth interviews were performed with emergency physicians from January 2020 to March 2020. In BR, focus group discussions were conducted with health professionals from community health centers at the end of June 2021. The focus group discussions (BR) were originally analyzed through an inductive thematic analysis approach. We conducted a secondary qualitative analysis in which this codebook was then applied to the interviews (US) in a deductive content analysis. The analysis concluded in August 2022. Brazil participants were physicians (n=5) or nurses (n=20) from three municipalities in the State of Amazonas with an average of three years of professional experience. US participants were emergency physicians (n=16) with an average of 15 years of professional experience. Four main themes emerged: 1) barriers to adequate care on the patient and/or community side and 2) on the health system side, 3) perceived considerations for how to address SBE, and 4) identified needs for improving care. There were 25 subthemes within the four themes. These subthemes were largely the same across the Brazil and US data, but the rationale and content within each shared subtheme varied significantly. For example, the subtheme "role of health professionals in improving care" extended across Brazil and the US. Brazil emphasized the need for task-shifting and -sharing amongst health care disciplines, whereas the US suggested specialized approaches geared toward increasing access to toxicologists and other referral resources. Despite similar core barriers to adequate snakebite envenoming care and factors to consider when trying to improve care delivery, health professionals in different health systems and sociocultural contexts identified different needs. Accounting for, and understanding, these differences is crucial to the success of initiatives intended to strengthen snakebite envenoming care. Implementation science efforts, with explicit health professional input, should be applied to develop new and/or adapt existing evidence-based treatments and practices for SBE., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Charles J Gerardo reports financial support was provided by National Institutes of Health. Wuelton Monteiro, Jacqueline Sachett, and Flavia Regina Ramos report financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico. Wuelton Monteiro reports financial support was provided by Fundação de Amparo à Pesquisa do Estado do Amazonas and the Brazilian Ministry of Health. Felipe Murta reports financial support was provided by Fiocruz. Wuelton Monteiro and Joao RN Vissoci have served in an editorial capacity for Toxicon:X., (© 2022 Published by Elsevier Ltd.)

Snakebite envenomations (SBEs) in pregnant women can result in adverse maternal or neonatal effects, such as abortion, placental abruption, preterm labor, fetal malformations, and maternal, fetal or neonatal deaths. Despite the high incidence of SBEs in the Brazilian Amazon, there is no literature on the impact of SBEs on pregnancy outcomes. The objective of this study was to describe clinical epidemiology and outcomes associated with SBEs in women of childbearing age and pregnant women in the state of Amazonas, Western Brazilian Amazon, from 2007 to 2021. Information on the population was obtained from the Reporting Information System (SINAN), Mortality Information System (SIM) and Live Birth Information System (SINASC) for the period from 2007 to 2021. A total of 36,786 SBEs were reported, of which 3,297 (9%) involved women of childbearing age, and 274 (8.3%) involved pregnant women. Severity (7.9% in pregnant versus 8.7% in non-pregnant women) (P = 0.87) and case-fatality (0.4% in pregnant versus 0.3% in non-pregnant women) rates were similar between groups (P = 0.76). Pregnant women who suffered snakebites were at higher risk for fetal death (OR: 2.17, 95%CI: 1.74-2.67) and neonatal death (OR = 2.79, 95%CI: 2.26-3.40). This study had major limitations related to the completeness of the information on the pregnancy outcomes. Although SBE incidence in pregnant women is low in the Brazilian Amazon, SBEs increased the risk of fetal and neonatal deaths., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Nascimento et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Brazilian Amazon has high rates of snakebite envenomings (SBEs), with ∼90% caused by Bothrops atrox. Envenomings by this species can trigger local and systemic effects, such as acute kidney injury (AKI). Our aim was to identify predictors of AKI in Bothrops SBEs in patients from Manaus, Western Brazilian Amazon. A total of 127 patients were enrolled, with a predominance of men between 16 and 45 years old from rural areas. Of the 127 patients, 38.6% developed AKI, with 61.2% presenting stage I, 34.7% presenting stage II and 4.1% presenting stage III severity. The age groups 0-10 years and ≥60 years presented a significantly higher frequency of AKI compared to the 11-40 years group. Moderate/severe edema in the affeccted limb was significantly associated with lower risk of AKI [p = 0.01; OR = 0.11 (95%CI 0.02-0.53)]. Nausea [p = 0.01; OR = 54.44 (95%CI = 3.26-909.27)] and high blood urea levels [p = 0.01; OR = 5.38 (95%CI = 2.12-13.66)] were risk factors for AKI. There was a significant positive correlation between circulating venom levels and the highest creatinine serum values during the hospital stay (p = 0.03) and with the difference between the maximum creatinine levels and the creatinine levels on admission (p = 0.02). A positive correlation between serum venom concentrations and creatinine levels suggests a direct or indirect dose-dependent participation of the venom toxins in the pathogenesis of AKI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Bereaved ICU family surrogates are at risk of comorbid prolonged grief disorder (PGD), posttraumatic stress disorder (PTSD), and depression. Knowledge about temporal relationships between PGD, PTSD, and depression is limited by a lack of relevant studies and diverse or inappropriate assessment time frames given the duration criterion for PGD. We aimed to determine the temporal reciprocal relationships between PGD, PTSD, and depressive symptoms among ICU decedents' family surrogates during their first 2 bereavement years with an assessment time frame reflecting the PGD duration criterion., Methods: This prospective, longitudinal, observational study examined PGD, PTSD, and depressive symptoms among 303 family surrogates of ICU decedents from two academic hospitals using 11 items of the Prolonged Grief Disorder-13, the Impact of Event Scale-Revised, and the depression subscale of the Hospital Anxiety and Depression Scale, respectively, at 6, 13, 18, and 24 months post-loss. Cross-lagged panel modeling was conducted: autoregressive coefficients indicate variable stability, and cross-lagged coefficients indicate the strength of reciprocal relationships among variables between time points., Results: Symptoms (autoregressive coefficients) of PGD (0.570-0.673), PTSD (0.375-0.687), and depression (0.591-0.655) were stable over time. Cross-lagged standardized coefficients showed that depressive symptoms measured at 6 months post-loss predicted subsequent symptoms of PGD (0.146) and PTSD (0.208) at 13 months post-loss. PGD symptoms did not predict depressive symptoms. PTSD symptoms predicted subsequent depressive symptoms in the second bereavement year (0.175-0.278). PGD symptoms consistently predicted subsequent PTSD symptoms in the first 2 bereavement years (0.180-0.263), whereas PTSD symptoms predicted subsequent PGD symptoms in the second bereavement year only (0.190-0.214). PGD and PTSD symptoms are bidirectionally related in the second bereavement year., Conclusions: PGD, PTSD, and depressive symptoms can persist for 2 bereavement years. Higher PGD symptoms at 6 months post-loss contributed to the exacerbation of PTSD symptoms over time, whereas long-lasting PTSD symptoms were associated with prolonged depression and PGD symptoms beyond the first bereavement year. Identification and alleviation of depression and PGD symptoms as early as 6 months post-loss enables bereaved surrogates to grieve effectively and avoid the evolution of those symptoms into long-lasting PGD, PTSD, and depression., (© 2022. The Author(s).)

Snakebite envenomings (SBEs) and other envenomings triggered by venomous animals (VAEs) represent a significant disease burden in Brazil, with 29,152 SBEs reported in 2021 alone with nearly half of those occurring in the remote Brazilian Amazon. In 2021, Brazil recorded 240,294 envenomings from snakes, scorpions, spiders, and caterpillars. Therefore, there is an unequal distribution of SBEs with high morbidity and mortality in the Brazilian Amazon. The severity of SBEs increases when patients require more than 6 h to access antivenom treatment, a common issue for the rural and indigenous populations. Understanding currently available resources and practices in Amazon remote areas of Brazil can serve to inform future interventions and guide health care policies. This study aims to develop a resource map of existing healthcare resources for the Brazilian Amazon's clinical management of VAEs with emphasis in SBEs, which will aid future strategic interventions. Data collection included a literature review, secondary data collected by government departments and organizational records, GIS mapping activities, and expert input. Our framework was guided by the three levels of healthcare service ecosystem analysis (macro, meso, and micro). Our resource map lays out a comprehensive overview of antivenom access, the distribution landscape, differences in patient transportation, and barriers to access healthcare that face populations in the Brazilian Amazon., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background/purpose: The purpose of this secondary-analysis study was to identify never-before-examined factors associated with distinct depressive-symptom trajectories among family caregivers from end-of-life caregiving through the first 2 bereavement years., Participants/methods: Participants (N=661) were family caregivers who provided end-of-life caregiving for terminally ill cancer patients. Multinomial logistic regressions were conducted to identify modifiable factors associated with caregivers ' seven previously identified depressive-symptom trajectories: minimal-impact resilience, recovery, preloss-depressive-only, delayed symptomatic, relief, prolonged symptomatic, and chronically persistent distressed. Drawing from the stress-appraisal-coping model, modifiable time-varying factors associated with distinct depressive-symptom trajectories were examined in three domains: (1) stressors, (2) stress appraisal, and (3) available resources (internal coping capacity and external social support)., Results: Profound objective caregiving demands were associated with caregivers' increased likelihood of belonging to more distressing depressive-symptom trajectories than to the minimal-impact-resilience trajectory. But, stronger negative appraisal of end-of-life caregiving increased odds of caregiver membership in preloss-depressive-only and relief trajectories over the recovery, delayed, and prolonged-symptomatic trajectories. Stronger internal coping capacity and perceived social support buffered the tremendous stress of end-of-life caregiving and permanent loss of a relative, as evidenced by higher odds of being in the minimal-impact-resilience and recovery trajectories., Conclusion: Family caregivers' distinct depressive-symptom trajectories were linked to their preloss caregiving demands, appraisal of negative caregiving impact, personal coping capacity, and perceived social support. Our results highlight actionable opportunities to improve end-of-life-care quality by boosting family caregivers' coping capacity and enhancing their social support to help them adequately manage daily caregiving loads/burdens thus relieving the emotional toll before patient death and throughout bereavement., (© 2022. The Author(s).)

Objective: Preparing family surrogates for patient death and end-of-life (EOL) decision making may reduce surrogate decisional conflict and regret. Preparedness for patient death involves cognitive and emotional preparedness. We assessed the associations of surrogates' death-preparedness states (that integrate both cognitive and emotional preparedness for patient death) with surrogates' decisional conflict and regret., Methods: Associations of 173 surrogates' death-preparedness states (no, cognitive-only, emotional-only, and sufficient preparedness states) with decisional conflict (measured by the Decision Conflict Scale) and heightened decisional regret (Decision Regret Scale scores >25) were evaluated using hierarchical linear modeling and hierarchical generalized linear modeling, respectively, during a longitudinal observational study at a medical center over cancer patients' last 6 months., Results: Surrogates reported high decisional conflict (mean [standard deviation] = 41.48 [6.05]), and 52.7% of assessments exceeded the threshold for heightened decisional regret. Surrogates in the cognitive-only preparedness state reported a significantly higher level of decisional conflict (β = 3.010 [95% CI = 1.124, 4.896]) than those in the sufficient preparedness state. Surrogates in the no (adjusted odds ratio [AOR] [95% CI] = 0.293 [0.113, 0.733]) and emotional-only (AOR [95% CI] = 0.359 [0.149, 0.866]) preparedness states were less likely to suffer heightened decisional regret than those in the sufficient preparedness state., Conclusions: Surrogates' decisional conflict and heightened decisional regret are associated with their death-preparedness states. Improving emotional preparedness for the patient's death among surrogates in the cognitive-only preparedness state and meeting the specific needs of those in the no, emotional-only, and sufficient preparedness states are actionable high-quality EOL-care interventions that may lessen decisional conflict and decisional regret., (© 2022 John Wiley & Sons Ltd.)

The COVID-19 pandemic caused by the severe acute syndrome virus 2 (SARS-CoV-2) has been around since November 2019. As of early June 2022, more than 527 million cases were diagnosed, with more than 6.0 million deaths due to this disease. Coronaviruses accumulate mutations and generate greater diversity through recombination when variants with different mutations infect the same host. Consequently, this virus is predisposed to constant and diverse mutations. The SARS-CoV-2 variants of concern/interest (VOCs/VOIs) such as Alpha (B.1.1.7), Beta (B.1.351), Gamma (B.1.1.28/P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) have quickly spread across the world. These VOCs and VOIs have accumulated mutations within the spike protein receptor-binding domain (RBD) which interacts with the angiotensin-2 converting enzyme (ACE-2) receptor, increasing cell entry and infection. The RBD region is the main target for neutralizing antibodies; however, other notable mutations have been reported to enhance COVID-19 infectivity and lethality. Considering the urgent need for alternative therapies against this virus, an anti-SARS-CoV-2 equine immunoglobulin F(ab') 2 , called ECIG, was developed by the Butantan Institute using the whole gamma-irradiated SARS-CoV-2 virus. Surface plasmon resonance experiments revealed that ECIG binds to wild-type and mutated RBD, S1+S2 domains, and nucleocapsid proteins of known VOCs, including Alpha, Gamma, Beta, Delta, Delta Plus, and Omicron. Additionally, it was observed that ECIG attenuates the binding of RBD (wild-type, Beta, and Omicron) to human ACE-2, suggesting that it could prevent viral entry into the host cell. Furthermore, the ability to concomitantly bind to the wild-type and mutated nucleocapsid protein likely enhances its neutralizing activity of SARS-CoV-2. We postulate that ECIG benefits COVID-19 patients by reducing the infectivity of the original virus and existing variants and may be effective against future ones. Impacting the course of the disease, mainly in the more vulnerable, reduces infection time and limits the appearance of new variants by new recombination., Competing Interests: AC-T is co-author of the patent “Processo de produção de um antígeno, correspondente aos vírus SARS-CoV-2 inativado e seus usos”. BR1020200166689, (2020). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Andrade, Batalha-Carvalho, Curi, Wen, Covas, Chudzinski-Tavassi and Moro.)

Objective: To determine whether distinctive prolonged-grief-disorder- (PGD) and depressive-symptom states emerge among family caregivers of cancer patients over their first 2 years of bereavement. This may extend cross-sectional evidence that PGD and major depressive disorder (MDD) symptoms can co-occur/occur independently and validate their construct distinctiveness., Methods: In this secondary-analysis study, PGD symptoms and depressive symptoms were measured over 666 caregivers using 11 grief symptom items of the Prolonged Grief-13 scale and 16 items of the Center for Epidemiologic Studies-Depression scale, respectively. Distinct PGD/depressive-symptom states were identified by latent transition analysis with dichotomous indicators (presence/absence) of PGD or depressive symptoms., Results: Four distinct PGD/depressive-symptom states emerged. The resilient and subthreshold depression-dominant states showed low and moderate probabilities of the presence of majority of depressive symptoms, respectively, with no PGD symptoms having a greater than moderate probability of presence. The depression-dominant state was marked by a high probability of the presence for 9 of 16 depressive symptoms, with moderate probabilities for almost all PGD symptoms. The PGD-depression comorbid state was characterized by a high probability of presence of all PGD symptoms and depressive symptoms, except for moderate probabilities of presence of two depressive symptoms., Conclusion: Our longitudinal identification of a predominantly depressive state but absence of a PGD-dominant state provides further evidence that PGD and MDD are related but distinct constructs that can occur independently or concurrently as the PGD-depression comorbid state. When PGD is suspected, bereaved individuals should be assessed for the potential comorbidity of MDD., (© 2022 John Wiley & Sons Ltd.)

Purpose: Cancer patients heterogeneously develop prognostic awareness, and end-of-life cancer care has become increasingly aggressive to the detriment of patients and healthcare sustainability. We aimed to explore the never-before-examined associations of prognostic-awareness-transition patterns with end-of-life care., Methods: Prognostic awareness was categorized into four states: (1) unknown and not wanting to know; (2) unknown but wanting to know; (3) inaccurate awareness; and (4) accurate awareness. We examined associations of our previously identified three prognostic-awareness-transition patterns during 334 cancer patients' last 6 months (maintaining accurate prognostic awareness, gaining accurate prognostic awareness, and maintaining inaccurate/unknown prognostic awareness) and end-of-life care (cardiopulmonary resuscitation, intensive care unit care, mechanical ventilation, chemotherapy/immunotherapy, and hospice care) in cancer patients' last month by multivariate logistic regressions., Results: Cancer patients in the maintaining-accurate-prognostic-awareness and gaining-accurate-prognostic-awareness groups had significantly lower odds of cardiopulmonary resuscitation (adjusted odds ratio [95% confidence interval]: 0.22 [0.06-0.78]; and 0.10 [0.01-0.97], respectively) but higher odds of hospice care (3.44 [1.64-7.24]; and 3.28 [1.32-8.13], respectively) in the last month than those in the maintaining inaccurate/unknown prognostic awareness. The maintaining-accurate-prognostic-awareness group had marginally lower odds of chemotherapy or immunotherapy received than the gaining-accurate-prognostic-awareness group (0.58 [0.31-1.10], p = .096]). No differences in intensive care unit care and mechanical ventilation among cancer patients in different prognostic-awareness-transition patterns were observed., Conclusion: End-of-life care received in cancer patients' last month was associated with the three distinct prognostic-awareness-transition patterns. Cancer patients' accurate prognostic awareness should be facilitated earlier to reduce their risk of receiving aggressive end-of-life care, especially for avoiding chemotherapy/immunotherapy close to death., Trial Registration: ClinicalTrials.gov:NCT01912846., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: Patients can prepare for end of life and their forthcoming death to enhance the quality of dying., Objectives: We aimed to longitudinally evaluate the never-before-examined associations of cancer patients' death-preparedness states by conjoint cognitive prognostic awareness and emotional preparedness for death with psychological distress, quality of life (QOL), and end-of-life care received., Methods: In this cohort study, we simultaneously evaluated associations of four previously identified death-preparedness states (no-death-preparedness, cognitive-death-preparedness-only, emotional-death-preparedness-only, and sufficient-death-preparedness states) with anxiety symptoms, depressive symptoms, and QOL over 383 cancer patients' last six months and end-of-life care received in the last month using multivariate hierarchical linear modeling and logistic regression modeling, respectively. Minimal clinically important differences (MCIDs) have been established for anxiety- (1.3-1.8) and depressive- (1.5-1.7) symptom subscales (0-21 Likert scales)., Results: Patients in the no-death-preparedness and cognitive-death-preparedness-only states reported increases in anxiety symptoms and depressive symptoms that exceed the MCIDs, and a decline in QOL from those in the sufficient-death-preparedness state. Patients in the emotional-death-preparedness-only state were more (OR [95% CI]=2.38 [1.14, 4.97]) and less (OR [95% CI]=0.38 [0.15, 0.94]) likely to receive chemotherapy/immunotherapy and hospice care, respectively, than those in the sufficient-death-preparedness state. Death-preparedness states were not associated with life-sustaining treatments received in the last month., Conclusion: Conjoint cognitive and emotional preparedness for death is associated with cancer patients' lower psychological distress, better QOL, reduced anti-cancer therapy, and increased hospice-care utilization. Facilitating accurate prognostic awareness and emotional preparedness for death is justified when consistent with patient circumstances and preferences., (Copyright © 2022 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Accidents caused by scorpions are considered a neglected condition and represent a major health problem in most tropical countries, especially for children and elderly people. In Brazil, scorpionism is recurrent in the southeast region, mainly in the state of São Paulo, due to the progressive increase in scorpions found in urban habitats. Thus, our study aimed to provide better insights into the geographic and epidemiological characteristics of scorpion envenomation in São Paulo state and identify the environmental factors that are associated with these accidents. This is an ecological and retrospective study with secondary data on scorpion accidents in the state of São Paulo from 2008 to 2018 obtained from the Notifiable Disease Information System. The SatScan software was used to identify the higher- and lower-risk spatiotemporal clusters. A total of 145,464 scorpion sting cases were recorded in the state of São Paulo, between 2008 and 2018; there was a four-fold increase in the incidence rate. Accidents occurred more frequently in the spring season, wherein higher-risk clusters were in the north and northwest regions of the state. High temperatures, low precipitation, and poor natural vegetation are associated with higher risk areas. Our study mapped vulnerable areas for scorpion accidents that can aid in the design of efficient public health policies, which should be intensified during the spring season., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Snakebite envenoming (SBE) is a neglected tropical disease with significant global morbidity and mortality. Even when antivenom is available in low-resource areas, health workers do not receive adequate training to manage SBEs. This study aims to develop and validate a clinical practice guideline (CPG) for SBE management across Brazil. A panel of expert judges with academic and/or technical expertise in SBE management performed content validation. The content validity index (CVI) score was 90% for CPG objectives, 89% for structure and presentation and 92% for relevance and classified the CPG as valid. A semantic validation was performed by analyzing focus group discussions with doctors and nurses from three municipalities of the Brazilian Amazon, after a 5-day meeting during which the CPG was presented. Two central themes emerged: knowledge acquired during the meeting and recommendations for improving the CPG. Based on these results, the CPG was revised into a final version. This study presents the successful development and validation process of a CPG for SBE management, which is targeted to a specific low-resource, high-burden setting. This development and validation process can be adapted to other settings and/or other neglected tropical diseases.

Background/objective: Bereaved ICU family surrogates' psychological distress, e.g., anxiety, depression, and post-traumatic stress disorder (PTSD), is usually examined independently, despite the well-recognized comorbidity of these symptoms. Furthermore, the few studies exploring impact of psychological distress on development of prolonged grief disorder (PGD) did not consider the dynamic impact of symptom evolution. We identified surrogates' distinct patterns/states of comorbid psychological distress and their evolution over the first 3 months of bereavement and evaluated their associations with PGD at 6-month postloss., Methods: A longitudinal observational study was conducted on 319 bereaved surrogates. Symptoms of anxiety, depression, PTSD, and PGD were measured by the anxiety and depression subscales of the Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised scale, and the PGD-13, respectively. Distinct psychological-distress states and their evolution were examined by latent transition analysis. Association between psychological-distress states and PGD symptoms was examined by logistic regression., Results: Three distinct comorbid psychological-distress states (prevalence) were initially identified: no distress (56.3%), severe-depressive/borderline-anxiety distress (30.5%), and severe-anxiety/depressive/PTSD distress (13.3%). Except for those in the stable no-distress state, surrogates tended to regress to states of less psychological distress at the subsequent assessment. The proportion of participants in each psychological-distress state changed to no distress (76.8%), severe-depressive/borderline-anxiety distress (18.6%), and severe-anxiety/depressive/PTSD distress (4.6%) at 3-month postloss. Surrogates in the severe-depressive/borderline-anxiety distress and severe-anxiety/depressive/PTSD-distress state at 3-month postloss were more likely to develop PGD at 6-month postloss (OR [95%] = 14.58 [1.48, 143.54] and 104.50 [10.45, 1044.66], respectively)., Conclusions: A minority of family surrogates of ICU decedents suffered comorbid severe-depressive/borderline-anxiety distress and severe-anxiety/depressive/PTSD symptoms during early bereavement, but they were more likely to progress into PGD at 6-month postloss., (© 2022. The Author(s).)

Scorpion envenomation is a significant public health concern in São Paulo, Brazil, and its incidence and mortality have increased in recent decades. The present study analyzed documented scorpion envenomation notifications from 2008 to 2018 throughout the 645 municipalities of São Paulo. Annual incidence and mortality rates were calculated and stratified according to sex and age. The local empirical Bayesian method and Getis-Ord Gi* statistic were used to represent standardized incidence rates in the municipalities and to identify high- and low-risk agglomerates. The incidence rate of scorpion envenomation quintupled between 2008 and 2018. Overall, the risk was higher for man, and increased with age. Deaths due to envenomation, however, were concentrated almost entirely in children 0-9 years of age. Incidence maps showed that the risk of envenomation increased in almost all regions and municipalities of São Paulo throughout the study period. The highest incidence rates were found in the western, northwestern and northern regions of the state, in contrast to the São Paulo metropolitan area and southern and coastal regions. Hot spots were identified in the Presidente Prudente, Barretos, São José do Rio Preto, and Araçatuba regional health districts, which over time formed a single high-risk cluster. In spatial terms, however, deaths were randomly distributed. In this study, we identified areas and populations at risk of scorpion envenomation and associated-fatalities, which can be used to support decision-making by health services to reduce human contact with these arachnids and avoid fatalities, especially in children., Competing Interests: The authors have declared that no competing interests exist.

Objective: Depression and prolonged grief disorder (PGD) are related but distinct constructs with different risk factors and treatments. We aimed to determine commonality and differences in factors predicting membership in depressive- and PGD-symptom trajectories to highlight uniqueness of each construct to guide further care and treatments., Methods: We previously identified four shared trajectories for depressive- and PGD-symptom trajectories (endurance, transient-reaction, resilience, and prolonged-symptomatic) with unique trajectories of chronically distressed and potential recurrence for depressive and PGD symptoms, respectively. This secondary-analysis study examined pre- and postloss factors predisposing 849 bereaved caregivers of cancer patients to membership in depressive- and PGD-symptom trajectories from the integrative framework of predictors for bereavement outcomes by a multinomial logistic regression model (the "endurance" trajectory as reference)., Results: Common factors predicted membership in depressive- and PGD-symptom trajectories: higher postloss personal coping capacity protected from more distressing symptom trajectories, spousal relationship with the patient predicted membership in the transient-reaction trajectory, while financial hardship and preloss depressive symptoms predicted for the resilience trajectory. Yet, accurate prognostic awareness protected caregivers from more distressing depressive-symptom trajectories only. Higher preloss subjective caregiving burden protected caregivers from the four more distressing depressive-symptom trajectories but only from the transient-reaction and resilience trajectories for PGD symptoms., Conclusion: Commonality and differences in factors predicting membership in PGD- and depressive-symptom trajectories confirm that PGD and depression are related but distinct constructs. Interventions should be tailored to caregivers' unique risk profile for depressive- and PGD-symptom trajectories to reduce the likelihood of suffering both or individual symptom trajectories., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Snakebite envenomings are considered a global health problem. The specific therapy for these envenomings consists of administering animal-derived antivenoms aiming to neutralize the venom toxins. Antivenoms have been used effectively to treat snakebites for more than a century; however, their administration may result in early and/or late adverse reactions. The present study presents the prevalence of early adverse reactions (EARs) towards Bothrops antivenom therapy in a health tertiary unit in the Brazilian Amazon and explores if specific plasma cytokines and chemokines from envenomed patients could be used as predictors of EARs. A cohort of patients bitten by Bothrops atrox was followed-up at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), from 2014 to 2016. Patients were treated with the Brazilian Bothrops antivenom and CXCL-8, CCL-5, CXCL-9, CCL-2, CXCL-10, IL-6, TNF, IL-2, IL-10, IFN-y, IL-4, and IL-17A were evaluated in patients' plasma samples before and after antivenom administration. From the total of patients (n = 186), mostly were male (82.3%), inhabiting rural areas (87.1%), with an average age of 35 years. Most of the patients (83.8%) were admitted to the hospital within 6 h after the accident, 26 (14%) reported having suffered a previous snakebite, and 97 (52.1%) received between 7 and 9 antivenom vials. The frequency of antivenom-induced EARs was 11.8% (22), resulting mostly of mild reactions. Urticaria was the major EAR manifestation (46.4%). Interestingly, CXCL-8 and IL-2 showed significantly lower levels in patients who progressed to EARs, although IL-2 levels might not represent biological relevance due the small magnitude difference between groups. This study reveals that CXCL-8 and IL-2 could play a role in the onset of EARs in pit viper envenomings., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The new outbreak of coronavirus disease 2019 (COVID-19) has infected and caused the death of millions of people worldwide. Intensive efforts are underway around the world to establish effective treatments. Immunoglobulin from immunized animals or plasma from convalescent patients might constitute a specific treatment to guarantee the neutralization of the virus in the early stages of infection, especially in patients with risk factors and a high probability of progressing to severe disease. Worldwide, a few clinical trials using anti-SARS-CoV-2 immunoglobulins from horses immunized with the entire spike protein or fragments of it in the treatment of patients with COVID-19 are underway. Here, we describe the development of an anti-SARS-CoV-2 equine F(ab') 2 immunoglobulin using a newly developed SARS-CoV-2 viral antigen that was purified and inactivated by radiation. Cell-based and preclinical assays showed that the F(ab') 2 immunoglobulin successfully neutralizes the virus, is safe in animal models, and reduces the severity of the disease in a hamster model of SARS-CoV-2 infection and disease., (© 2022. The Author(s).)

Objective: Death preparedness involves cognitive prognostic awareness and emotional acceptance of a relative's death. Effects of retrospectively assessed cognitive prognostic awareness and emotional preparedness for patient death have been individually investigated among bereaved family caregivers. We aimed to prospectively examine associations of caregivers' death-preparedness states, determined by conjoint cognitive prognostic awareness and emotional preparedness for death, with bereavement outcomes., Methods: Associations of caregivers' death-preparedness states (no-death-preparedness, cognitive-death-preparedness-only, emotional-death-preparedness-only, and sufficient-death-preparedness states) at last preloss assessment with bereavement outcomes over the first two bereavement years were evaluated among 332 caregivers of advanced cancer patients using hierarchical linear models with the logit-transformed posterior probability for each death-preparedness state., Results: Caregivers with a higher logit-transformed posterior probability for sufficient death-preparedness state reported less prolonged-grief symptoms, lower likelihoods of severe depressive symptoms and heightened decisional regret, and better mental health-related quality of life (HRQOL). Caregivers with a higher logit-transformed posterior probability for no-death-preparedness state reported less prolonged-grief symptoms, a lower likelihood of severe depressive symptoms, and better mental HRQOL. A higher logit-transformed posterior probability for cognitive-death-preparedness-only state was associated with bereaved caregivers' higher likelihood of heightened decisional regret, whereas that for emotional-death-preparedness-only state was not associated with caregivers' bereavement outcomes., Conclusions: Caregivers' bereavement outcomes were associated with their preloss death-preparedness states, except for physical health-related QOL. Interventions focused on not only cultivating caregivers' accurate prognostic awareness but also adequately preparing them emotionally for their relative's forthcoming death are actionable opportunities for high-quality end-of-life care and are urgently warranted to facilitate caregivers' bereavement adjustment., (© 2021 John Wiley & Sons Ltd.)

Background/objective: Preparing family caregivers, cognitively, emotionally, and behaviorally, for their relative's death is an actionable component of high-quality end-of-life care. We aimed to examine the never-before-examined associations of conjoint cognitive prognostic awareness and emotional preparedness for death with caregiving outcomes and end-of-life care received by cancer patients., Design/setting/participants/main Measures: For this longitudinal study, associations of death-preparedness states (no-death-preparedness, cognitive-death-preparedness-only, emotional-death-preparedness-only, and sufficient-death-preparedness states) with subjective caregiving burden, depressive symptoms, and quality of life (QOL) and patients' end-of-life care (chemotherapy and/or immunotherapy, cardiopulmonary resuscitation, intensive care unit care, intubation, mechanical ventilation support, vasopressors, nasogastric tube feeding, and hospice care) were evaluated using multivariate hierarchical linear and logistic regression modeling, respectively, for 377 caregivers in cancer patients' last 6 months and 1 month, respectively., Key Results: Caregivers in the cognitive-death-preparedness-only state experienced a higher level of subjective caregiving burden than those in the sufficient-death-preparedness state. Caregivers in the no-death-preparedness and cognitive-death-preparedness-only states reported significantly more depressive symptoms and worse QOL than those in the sufficient-death-preparedness state. Cancer patients with caregivers in the sufficient-death-preparedness state were less likely to receive chemotherapy and/or immunotherapy, intubation, mechanical ventilation, and nasogastric tube feeding than patients with caregivers in other death-preparedness states. However, patients' receipt of hospice care was not associated with their caregivers' death-preparedness states., Conclusion: Family caregivers' death-preparedness states were associated with caregiving outcomes and their relative's end-of-life care. Cultivating caregivers' accurate prognostic awareness and improving their emotional preparedness for their relative's death may facilitate more favorable end-of-life-caregiving outcomes and may limit potentially nonbeneficial end-of-life care., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)