COVID-19 Prevention and Mitigation Decision-Making Processes While Navigating Chronic Disease Care: Perspectives of Black Adults with Heart Failure and Diabetes.

BACKGROUND: Heart failure and diabetes are comorbidities that disproportionately contribute to high morbidity and mortality among Blacks. Further compounding the racial and ethnic disparities in COVID-19 health outcomes, Blacks with cardiometabolic diseases are at high risk of experiencing serious complications or mortality from COVID-19. This study aimed to assess how Blacks with heart failure and diabetes navigated chronic care management during the COVID-19 pandemic. METHODS: A mixed methods study including in-depth interviews and surveys with adults diagnosed with heart failure and diabetes (n = 17) was conducted in 2021-2022. Verbatim transcripts were analyzed using a thematic analysis approach. RESULTS: Participants reported that while the pandemic initially caused delays in access to health services, shifts to telemedicine allowed for continued care despite preferences for in-person appointments. Various sources of information were used in different ways to make decisions on how to best reduce health risks due to COVID-19, but individuals and institutions affiliated with science and medicine, or who promoted information from these sources, were considered to be the most trusted sources of information among those who relied on outside guidance when making health-related decisions. Individuals' self-awareness of their own high-risk status and perceived control over their exposure levels to the virus informed what COVID-19 prevention and mitigation strategies people used. CONCLUSION: Information backed by scientific data was an important health communication tool that alongside other factors, such as fear of mortality due to COVID-19, encouraged individuals to get vaccinated and adopt other COVID-19 prevention and mitigation behaviors.

Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not?

BACKGROUND: Autism spectrum disorder (ASD) is characterized by persistent social interaction impairments and is male-biased in prevalence. We have established naturally occurring low sociality in male rhesus monkeys as a model for the social features of ASD. Low-social male monkeys exhibit reduced social interactions and increased autistic-like trait burden, with both measures highly correlated and strongly linked to low cerebrospinal fluid (CSF) arginine vasopressin (AVP) concentration. Little is known, however, about the behavioral and neurochemical profiles of female rhesus monkeys, and whether low sociality in females is a tractable model for ASD. METHODS: Social behavior assessments (ethological observations; a reverse-translated autistic trait measurement scale, the macaque Social Responsiveness Scale-Revised [mSRS-R]) were completed on N = 88 outdoor-housed female rhesus monkeys during the non-breeding season. CSF and blood samples were collected from a subset of N = 16 monkeys across the frequency distribution of non-social behavior, and AVP and oxytocin (OXT) concentrations were quantified. Data were analyzed using general linear models. RESULTS: Non-social behavior frequency and mSRS-R scores were continuously distributed across the general female monkey population, as previously found for male monkeys. However, dominance rank significantly predicted mSRS-R scores in females, with higher-ranking individuals showing fewer autistic-like traits, a relationship not previously observed in males from this colony. Females differed from males in several other respects: Social behavior frequencies were unrelated to mSRS-R scores, and AVP concentration was unrelated to any social behavior measure. Blood and CSF concentrations of AVP were positively correlated in females; no significant relationship involving any OXT measure was found. LIMITATIONS: This study sample was small, and did not consider genetic, environmental, or other neurochemical measures that may be related to female mSRS-R scores. CONCLUSIONS: Dominance rank is the most significant predictor of autistic-like traits in female rhesus monkeys, and CSF neuropeptide concentrations are unrelated to measures of female social functioning (in contrast to prior CSF AVP findings in male rhesus monkeys and male and female autistic children). Although preliminary, this evidence suggests that the strong matrilineal organization of this species may limit the usefulness of low sociality in female rhesus monkeys as a tractable model for ASD.

Humans' (Homo sapiens), capuchin monkeys' (Sapajus [Cebus] apella), and rhesus macaques' (Macaca mulatta) size judgments shift when stimuli change in frequency.

When making decisions, humans often strive to uphold objective, absolute standards, such as about what is small versus large, blue versus purple, or unfair versus fair, suggesting that our judgments should not be swayed by extraneous factors such as the sequence or frequency of events to be judged. Yet in previous research, when some items (e.g., threatening faces) became less frequent, humans responded by expanding their concept (of "threatening") to include more ambiguous stimuli. We assessed the origins of this perceptual frequency bias by testing 25 capuchins, seven rhesus monkeys, and 102 humans on a computer task in which they had to classify one circle at a time (pulled from a continuum of 50 circle sizes) as either small or large. Small and large circles initially appeared with equal probability but over time small circles either became less frequent, more frequent, or did not change in frequency. All three species showed changes in judgment, but contrary to predictions, they contracted, rather than expanded, their size judgments of the less frequent category. In other words, when small circles became rare, participants were more likely to judge ambiguous circles sizes as large (and vice versa). This may have been due to the immediate explicit feedback, as has recently been found in humans, and we consider possible mechanisms driving our participants' responses. These results suggest that humans' difficulties in maintaining absolute standards are shared with other animals. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Correlates of survival after autoantibody reduction therapy for acute IPF exacerbations.

BACKGROUND: No medical treatment has proven efficacy for acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF), and this syndrome has a very high mortality. Based on data indicating humoral autoimmune processes are involved in IPF pathogenesis, we treated AE-IPF patients with an autoantibody reduction regimen of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin. This study aimed to identify clinical and autoantibody determinants associated with survival after autoantibody reduction in AE-IPF. METHODS: Twenty-four(24) AE-IPF patients received the autoantibody reduction regimen. Plasma anti-epithelial autoantibody titers were determined by HEp-2 indirect immunofluorescence assays in 22 patients. RESULTS: Mean age of the patients was 70 + 7 years old, and 70% were male. Beneficial clinical responses that occurred early during therapy were a favorable prognostic indicator: supplemental O2 flows needed to maintain resting SaO2>92% significantly decreased and/or walk distances increased among all 10 patients who survived for at least one year. Plasma anti-HEp-2 autoantibody titers were ~-three-fold greater in survivors compared to non-survivors (p<0.02). Anti-HEp-2 titers >1:160 were present in 75% of the evaluable one-year survivors, compared to 29% of non-survivors, and 10 of 12 patients (83%) with anti-HEP-2 titers <1:160 died during the observation period (Hazard Ratio = 3.3, 95% Confidence Interval = 1.02-10.6, p = 0.047). CONCLUSIONS: Autoantibody reduction therapy is associated with rapid reduction of supplemental oxygen requirements and/or improved ability to ambulate in many AE-IPF patients. Facile anti-epithelial autoantibody assays may help identify those most likely to benefit from these treatments.

Granulocyte Transfusion: Clinical Updates and a Practical Approach to Transfusion.

Neutrophils are an integral component of the innate immune system and key regulators of cell-mediated defense against bacterial and fungal pathogens. The potential of granulocyte transfusions has been investigated to temporarily replenish innate immune function to prevent and/or treat infections in patients with severe neutropenia or neutrophil dysfunction. However, evidence has been largely theoretical, experimental, and/or inconclusive. Clinical efficacy has yet to be confirmed by large-scale randomized controlled clinical trials. Performing such trials has been hampered by low granulocyte collection yield and poor patient accrual. We provide a practical summary of the current literature surrounding the practice of granulocyte transfusion.

Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys.

BACKGROUND: Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1-3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores. METHODS: Cerebrospinal fluid and blood samples were collected from N = 76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n = 43), samples were collected thrice over a 10-month period. The following statistical tests were used: "Case 2A" intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling. RESULTS: All biological measures (except AKT) showed significant test-retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n = 57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n = 75 of the subjects). CONCLUSIONS: These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys.

Assessment of medical morbidities in a rhesus monkey model of naturally occurring low sociality.

People with autism spectrum disorder (ASD) exhibit a variety of medical morbidities at significantly higher rates than the general population. Using an established monkey model of naturally occurring low sociality, we investigated whether low-social monkeys show an increased burden of medical morbidities compared to their high-social counterparts. We systematically reviewed the medical records of N = 152 (n = 73 low-social; n = 79 high-social) rhesus macaques (Macaca mulatta) to assess the number of traumatic injury, gastrointestinal, and inflammatory events, as well as the presence of rare medical conditions. Subjects' nonsocial scores, determined by the frequency they were observed in a nonsocial state (i.e., alone), and macaque Social Responsiveness Scale-Revised (mSRS-R) scores were also used to test whether individual differences in social functioning were related to medical morbidity burden. Medical morbidity type significantly differed by group, such that low-social monkeys incurred higher rates of traumatic injury compared to high-social monkeys. Nonsocial scores and mSRS-R scores also significantly and positively predicted traumatic injury rates, indicating that monkeys with the greatest social impairment were most impacted on this health measure. These findings from low-social monkeys are consistent with well-documented evidence that people with ASD incur a greater number of traumatic injuries and receive more peer bullying than their neurotypical peers, and add to growing evidence for the face validity of this primate model. LAY SUMMARY: People with autism exhibit multiple medical problems at higher rates than the general population. We conducted a comprehensive medical record review of monkeys that naturally exhibit differences in sociality and found that low-social monkeys are more susceptible to traumatic injuries than high-social monkeys. These results are consistent with reports that people with autism also incur greater traumatic injury and peer bullying and add to growing evidence for the validity of this monkey model.

Potential impact of a delayed ADAMTS13 result in the treatment of thrombotic microangiopathy: an economic analysis.

BACKGROUND: A pre-plasma exchange ADAMTS13 measurement differentiates thrombotic thrombocytopenic purpura (TTP) from other forms of thrombotic microangiopathy (TMA). Given that many hospitals do not perform the ADAMTS13 assay in-house and that the turnaround time (TAT) differs among reference laboratories, we performed an analysis investigating the potential impact of a delay in obtaining the results on the healthcare system. METHODS: An economic model was developed to estimate the impact of a delay in obtaining the pretreatment ADAMTS13 results on patients admitted with TMA with cost (US dollars) as the primary outcome. Incremental cost-effectiveness ratio (ICER) as a composite outcome was calculated from both cost and life days [LDs], an effectiveness surrogate marker. Model parameters were gathered from the medical literature, except for the institutional cost of the ADAMTS13 test. RESULTS: In patients with TMA, during the 6-day study period, the incremental cost to the healthcare system ranged from approximately $4155 to $5123 for every 1-day delay in obtaining the pre-exchange ADAMTS13 results with virtually no change in the effectiveness marker. The ICER composite outcome established the cost-effectiveness of having a fast TAT for pre-exchange ADAMTS13 results. Probabilistic sensitivity analyses also confirmed the robustness of the model. CONCLUSIONS: In patients with clinical presentations of TMAs, having a rapid TAT for pre-exchange ADAMTS13 measurement appeared to be cost-effective. If testing cannot be performed in-house, then our findings support the necessity of contracting with a reference laboratory that can reliably provide the result, preferably within 1 day of admission.

An economic analysis of different treatments for bleeding in patients with acquired haemophilia.

BACKGROUND: Acquired haemophilia A (AHA), with potentially high risk of morbidity and mortality, occurs as a result of inhibitors against factor VIII. Bleeding due to AHA can be treated with activated prothrombin complex concentrate (aPCC), recombinant activated factor VII (rFVIIa) or recently, recombinant porcine-sequence factor VIII (rpFVIII). We extended our previous cost-effectiveness analysis (CEA) comparing rpFVIII against the available traditional options. METHODS: For high-titred, haemorrhaging AHA patients treated with either aPCC, rFVIIa or rpFVIII, over the course of 6-days, a Markov simulation was conducted to evaluate the outcomes when these patients transitioned into any of the four following health states: (1) continuous bleeding, (2) thrombosis, (3) stop bleeding and (4) death, with states (2), (3) and (4) modelled as absorbing states. All model parameters were obtained from the medical literature, except the costs of aPCC, rFVIIa and the factor VIII assay, which came from our institutional data. RESULTS: Excluding the cost of the initial treatment on day 0, the total subsequent treatment cost of rFVIIa was substantially more than the costs of aPCC and rpFVIII ($13 925 vs. $1778 vs. $6957, respectively). The average quality-adjusted life days (QALDs) gained from rpFVIII was lowest (4·89 vs. 4·9 for rFVIIa and 4·91 for aPCC). Overall, aPCC dominated the other two treatments. The model was determined to be robust across the tested ranges for all input variables. CONCLUSION: Based on this economic model, for AHA patients with high titres who were bleeding, aPCC was the most cost-effective treatment option and may be considered for use if there is no clinical contraindication.

Frequency of Alterations in Apheresis-Related Abstracts Prior to Publications as Peer-Reviewed Articles.

High-quality evidence supporting clinical practice is lacking in apheresis. A potential source of evidence is provided by abstracts submitted to the Annual Meetings of the American Association of Blood Banks (AABB) and the American Society for Apheresis (ASFA). However, there is potential for study conclusions to be altered significantly following abstract presentations prior to publications in peer-reviewed journals. Therefore, we evaluated the discordance rate between apheresis-related meeting abstracts and their corresponding published articles. Abstracts accepted to either AABB or ASFA Annual Meetings from 2005 to 2012 and corresponding PubMed-indexed peer-reviewed articles' abstracts published prior to 9/2014 were reviewed for altered methods, results, and conclusions. When present, changes were evaluated for clinical significance. During the 8-year period, 198 out of 1152 abstracts were published as peer-reviewed articles. Of these, 36 (18.2%) presented discordant results, six of which (16.7%) were potentially clinically significant. An alteration in results (58.3%) was the leading reason for discordance. The discordance rate for ASFA abstracts was significantly higher (HR = 4.69, P = 0.0028) than the AABB ones. However, clinically significant alterations occurred more frequently among AABB abstracts (P = 0.025). Approximately 18% of meeting abstracts demonstrated alterations prior to publication in peer-reviewed journals. Given that approximately one in six changes represented clinically significant alterations, potentially affecting clinical practice, we recommend caution when modifying one's clinical practice based on abstract presentations at Annual Meetings. Future studies involving abstracts from both the International Society for Apheresis and the World Apheresis Association should also be performed.

Monitoring Fondaparinux in the Setting of Antithrombin Deficiency.

Heparin-induced thrombocytopenia (HIT) is a not-uncommon adverse effect of heparin exposure, with potentially serious and/or fatal thrombotic consequences. Recent studies looking at the off-label use of fondaparinux for HIT show similar efficacy and adverse-effect profiles, as well as improved costs, compared with some commonly used direct thrombin inhibitors. Although routine laboratory monitoring of fondaparinux-specific anti-Xa levels typically is not recommended, we present a case report that suggests fondaparinux monitoring may be needed in patients with hepatic impairment causing acquired antithrombin deficiency. We performed daily assessment of antithrombin- and fondaparinux-specific anti-Xa levels in a 50-year-old female of unknown ethnicity to ensure that fondaparinux dosing was maintained within an acceptable range. With this management strategy, the patient experienced no thrombotic or hemorrhagic complications during the hospital admission or the following 2 months in outpatient treatment.

aPCC vs. rFVIIa for the treatment of bleeding in patients with acquired haemophilia - a cost-effectiveness model.

BACKGROUND: Acquired haemophilia A (AHA) is an autoimmune bleeding disorder with significant morbidity and mortality. Bleeding AHA patients with high titre inhibitors can be treated with either activated prothrombin complex concentrate (aPCC) or recombinant activated factor VII (rFVIIa). Given that both replacement therapies have inherent benefits and limitations, a cost-effectiveness analysis (CEA) was performed in this population to compare rFVIIa with aPCC. METHODS: In high-titered AHA patients with bleeding treated with either aPCC or rFVIIa, during a 5-day study period, a Markov model was developed such that these patients were transitioned into four different health states: (1) continuous bleeding, (2) thrombosis, (3) stop bleeding and (4) death, with states (2), (3) and (4) modelled as absorbing states. Model parameters, including probabilities, health utility index and costs, were gathered from the medical literature, except for the costs of aPCC and rFVIIa, which were obtained from our institutional data. RESULTS: During the 5-day period, the total treatment cost of rFVIIa was substantially more than the cost of aPCC ($13 635 vs. $1741). The average quality-adjusted life days (QALDs) gained for rFVIIa were slightly lower compared to aPCC (4·08 vs. 4·09). Overall, aPCC prevailed over rFVIIa. Sensitivity analysis confirmed the robustness of the model across tested ranges of all input variables. CONCLUSION: In high-titered AHA patients with bleeding, aPCC is a cost-effective treatment option when compared to rFVIIa. Thus, aPCC may be considered in these patients, if available, and provided there is no clinical contraindication.

Rat Poisoning: A Challenging Diagnosis With Clinical and Psychological Implications.

Rat poisoning should be considered in the differential diagnosis of a patient presenting with signs and symptoms of vitamin K deficiency without a more likely explanation. However, confirming this diagnosis may be difficult due to the varying sensitivities of available assays. A 40-year-old Caucasian woman presented to our hospital with chronic abdominal pain, hematuria, and a history of diarrhea of unknown etiology, despite an extensive work-up. Her laboratory evaluation results were consistent with vitamin K deficiency. Because she reported that she had not ingested warfarin, rat poisoning was suspected; however, the results of the first assay were negative. A second specimen was sent to another reference laboratory with a more sensitive assay, and the diagnosis of brodifacoum poisoning was confirmed. The patient was treated with oral vitamin K. If a patient presents with unexplained signs and symptoms of vitamin K deficiency, toxicological evaluation should be performed and repeat testing may be warranted, depending on the sensitivity of the original testing method.

Management of chronic myeloid leukemia in the setting of pregnancy: when is leukocytapheresis appropriate? A case report and review of the literature.

BACKGROUND: Chronic myeloid leukemia (CML) is a common hematologic malignancy; however, its occurrence during pregnancy is unusual due to its low prevalence in females of childbearing age. There are conflicting reports of how to best manage CML in pregnancy, particularly in the setting of leukocytosis. HEMAPHERESIS: A 30-year-old female was diagnosed with CML at 18 weeks' estimated gestational age. On initial presentation she reported fatigue, night sweats, and early satiety, and was found to have a white blood cell (WBC) count of 69.3 × 109 /L and platelet count of 366 × 109 /L. Her disease was managed during pregnancy using interferon-α alone despite persistent leukocytosis. CONCLUSION: CML may be effectively managed during pregnancy, even in the setting of leukocytosis, without the application of leukocytapheresis. Management relies not only upon the coordination of drug therapy and fetal monitoring, but requires close communication between multiple medical disciplines. Leukocytapheresis has been safely performed during pregnancy and may be a suitable adjunct management strategy in pregnant patients diagnosed with CML with specific clinical presentations, such as hyperleukocytosis (WBC count > 150 × 109 /L) and/or symptomatic leukostasis.

ADAMTS13 test and/or PLASMIC clinical score in management of acquired thrombotic thrombocytopenic purpura: a cost-effective analysis.

BACKGROUND: The ADAMTS13 test distinguishes thrombotic thrombocytopenic purpura (TTP) from other thrombotic microangiopathies (TMAs). The PLASMIC score helps determine the pretest probability of ADAMTS13 deficiency. Due to inherent limitations of both tests, and potential adverse effects and cost of unnecessary treatments, we performed a cost-effectiveness analysis (CEA) investigating the benefits of incorporating an in-hospital ADAMTS13 test and/or PLASMIC score into our clinical practice. STUDY DESIGN AND METHODS: A CEA model was created to compare four scenarios for patients with TMAs, utilizing either an in-house or a send-out ADAMTS13 assay with or without prior risk stratification using PLASMIC scoring. Model variables, including probabilities and costs, were gathered from the medical literature, except for the ADAMTS13 send-out and in-house tests, which were obtained from our institutional data. RESULTS: If only the cost is considered, in-house ADAMTS13 test for patients with intermediate- to high-risk PLASMIC score is the least expensive option ($4,732/patient). If effectiveness is assessed as measured by the number of averted deaths, send-out ADAMTS13 test is the most effective. Considering the cost/effectiveness ratio, the in-house ADAMTS13 test in patients with intermediate- to high-risk PLASMIC score is the best option, followed by the in-house ADAMTS13 test without the PLASMIC score. CONCLUSIONS: In patients with clinical presentations of TMAs, having an in-hospital ADAMTS13 test to promptly establish the diagnosis of TTP appears to be cost-effective. Utilizing the PLASMIC score further increases the cost-effectiveness of the in-house ADAMTS13 test. Our findings indicate the benefit of having a rapid and reliable in-house ADAMTS13 test, especially in the tertiary medical center.