User-Centered Development of a Patient Decision Aid for Choice of Early Abortion Method: Multi-Cycle Mixed Methods Study.

BACKGROUND: People seeking abortion in early pregnancy have the choice between medication and procedural options for care. The choice is preference-sensitive-there is no clinically superior option and the choice depends on what matters most to the individual patient. Patient decision aids (PtDAs) are shared decision-making tools that support people in making informed, values-aligned health care choices. OBJECTIVE: We aimed to develop and evaluate the usability of a web-based PtDA for the Canadian context, where abortion care is publicly funded and available without legal restriction. METHODS: We used a systematic, user-centered design approach guided by principles of integrated knowledge translation. We first developed a prototype using available evidence for abortion seekers' decisional needs and the risks, benefits, and consequences of each option. We then refined the prototype through think-aloud interviews with participants at risk of unintended pregnancy ("patient" participants). Interviews were audio-recorded and documented through field notes. Finally, we conducted a web-based survey of patients and health care professionals involved with abortion care, which included the System Usability Scale. We used content analysis to identify usability issues described in the field notes and open-ended survey questions, and descriptive statistics to summarize participant characteristics and close-ended survey responses. RESULTS: A total of 61 individuals participated in this study. Further, 11 patients participated in think-aloud interviews. Overall, the response to the PtDA was positive; however, the content analysis identified issues related to the design, language, and information about the process and experience of obtaining abortion care. In response, we adapted the PtDA into an interactive website and revised it to include consistent and plain language, additional information (eg, pain experience narratives), and links to additional resources on how to find an abortion health care professional. In total, 25 patients and 25 health care professionals completed the survey. The mean System Usability Scale score met the threshold for good usability among both patient and health care professional participants. Most participants felt that the PtDA was user-friendly (patients: n=25, 100%; health care professionals: n=22, 88%), was not missing information (patients: n=21, 84%; health care professionals: n=18, 72%), and that it was appropriate for patients to complete the PtDA before a consultation (patients: n=23, 92%; health care professionals: n=23, 92%). Open-ended responses focused on improving usability by reducing the length of the PtDA and making the website more mobile-friendly. CONCLUSIONS: We systematically designed the PtDA to address an unmet need to support informed, values-aligned decision-making about the method of abortion. The design process responded to a need identified by potential users and addressed unique sensitivities related to reproductive health decision-making.

Using shame to extend Martin Conway's self-memory system.

We extend Conway's self-memory system by adding theory and data from shame, an emotion that disrupts the internalised ideals of society needed for a positive self-concept. The event that caused 273 undergraduates their greatest amount of shame was analyzed; 66% were not very negative except for producing shame. Ratings of post-event effects, including two measure of self (self-perceived weakness, and centrality to identity) and four clinical symptoms (intrusions, avoidance, anxiety, and depression), were attributed separately to the remembered event, behaviour during the event, and shame from the event. The effects of shame were generally as large as the those of the event and larger than those of the behaviour, demonstrating the importance of shame's effects. The Tonic Immobility Scale (TIS), which measures tonic immobility (i.e., freezing), was obtained for the event that produced the most tonic immobility but that was not the event that caused the most shame. The post-event symptoms measured on the event that caused the most shame and the TIS correlated highly, suggesting that shame and tonic immobility may belong to a cluster of phylogenetically conserved submissive defensive mechanisms that could account for effects currently attributed to goals in self-memory systems.

Caring for two in the ICU: Pharmacologic management of pregnancy-related complications.

Maternal mortality continues to be an issue globally despite advances in technology and pharmacotherapy. Pregnancy can lead to complications that necessitate immediate action to prevent severe morbidity and mortality. Patients may need escalation to the ICU setting for close monitoring and administration of advanced therapies not available elsewhere. Obstetric emergencies are rare but high-stakes events that require clinicians to have prompt identification and management. The purpose of this review is to describe complications of pregnancy and provide a focused resource of pharmacotherapy considerations that clinicians may encounter. For each disease state, the epidemiology, pathophysiology, and management are summarized. Brief descriptions of non-pharmacological (e.g., cesarean or vaginal delivery of the baby) interventions are provided. Mainstays of pharmacotherapy highlighted include oxytocin for obstetric hemorrhage, methotrexate for ectopic pregnancy, magnesium and antihypertensive agents for preeclampsia and eclampsia, eculizumab for atypical hemolytic uremic syndrome, corticosteroids, and immunosuppressive agents for thrombotic thrombocytopenic purpura, diuretics, metoprolol, and anticoagulation for peripartum cardiomyopathy, and pulmonary vasodilators for amniotic fluid embolism.

Tonic immobility (freezing) during sexual and physical assaults produces stronger memory effects than other characteristics of the assaults.

Tonic immobility (TI) is a phylogenetically conserved, passive, obligatory defense mechanism commonly engaged during sexual and physical assaults. During TI, people become immobile while remaining conscious and later reexperience intrusive memories of both their assault and of its accompanying immobility. Here we show that this well-studied biological process has powerful effects on memory and other processes. Participants had experienced either a serious sexual (n = 234) or physical (n = 137) assault. For both the assault and its accompanying immobility, the standard measure of the peritraumatic severity of TI correlated between .40 and .65 with post-assault effects on memory, including memory of the assault and memory of the immobility, the two memory-based self-concept measures of self-blame and event centrality, and post-assault anxiety and depression. The correlations with TI were much higher than other peritraumatic characteristics commonly used to predict and describe posttraumatic effects in assaults and other traumas. The results suggest that TI should be considered for a broader, more biologically based and ecologically valid understanding of the effects of trauma on memory and memory-based reactions.

Caring for two in the ICU: Pharmacotherapy in the critically ill pregnant patient.

Safe and thoughtful medication management of pregnant patients requiring intensive care unit (ICU) level of care is key to optimizing outcomes for both mother and fetus. Pregnancy induces physiologic alterations that closely mirror the changes expected in a critically ill patient. These changes can be predictable depending on the gestational age and trimester and will directly impact the pharmacokinetic profile of medications commonly used in the ICU; examples include decreased gastric emptying, increased blood and plasma volume, increased glomerular filtration, and increased cardiac output. When pregnant patients require ICU care, the resulting impact on drug absorption, distribution, metabolism, and elimination can be difficult to predict. In addition, there are many nuances of medication metabolism and interface with the placental barrier that should be considered when selecting pharmacotherapy for the pregnant patient. Critical care clinicians need to be aware of medication interactions with the placenta and weigh the risk versus benefit profile of medication use in this patient population. Obstetric critical care admissions have increased over the years, especially during the coronavirus waves. Therefore, understanding the interplay between pregnancy and critical illness to optimize pharmacotherapy selection is crucial to improving health outcomes of mother and fetus. This review highlights pharmacotherapy considerations in the pregnant ICU patient for the following topics: physiologic alterations, categorizing medication risk, supportive care, sepsis, cardiogenic shock, acute respiratory distress syndrome, and venous thromboembolism.

Characterization of Opioid Use in the Intensive Care Unit and Its Impact Across Care Transitions: A Prospective Study.

PURPOSE: The objective of this study is to characterize opioid intensity in the intensive care unit (ICU) and its association with opioid utilization across care transitions. METHODS: This is a prospective cohort study. Medically ill ICU patients with complete medication histories who survived to discharge were included. Opioid intensity was characterized based on IV morphine milligram equivalents (IV MME). Primary outcomes were opioid prescribing upon ICU and hospital discharge. RESULTS: Opioids were prescribed to 34.1% and 31.1% of patients upon ICU and hospital discharge. Within the ≥50 mean IV MME/ICU day cohort, 64.7% of patients received opioids after ICU discharge compared to 45.8% and 13.6% in the 1-49 mean IV MME/ICU day and no opioid groups (P < .05). Within the ≥50 mean IV MME/ICU day cohort, 70.6% of patients were prescribed opioids after hospitalization compared to 37.3% and 13.6% of patients who received less or no opioids. (P < .05). Within the ≥50 mean IV MME/ICU day cohort, 29.4% of patients were opioid naïve and discharged with an opioid, which is over double compared to patients with lower opioid requirements (P < .05). CONCLUSION: Patients with higher mean daily ICU opioid requirements had increased opioid prescribing across care transitions despite preadmission opioid use.

Ketamine in Critically Ill Patients: Use, Perceptions, and Potential Barriers.

Objective: To evaluate practitioner use of ketamine and identify potential barriers to use in acutely and critically ill patients. To compare characteristics, beliefs, and practices of ketamine frequent users and non-users. Methods: An online survey developed by members of the Society of Critical Care Medicine (SCCM) Clinical Pharmacy and Pharmacology Section was distributed to physician, pharmacist, nurse practitioner, physician assistant and nurse members of SCCM. The online survey queried SCCM members on self-reported practices regarding ketamine use and potential barriers in acute and critically ill patients. Results: Respondents, 341 analyzed, were mostly adult physicians, practicing in the United States at academic medical centers. Clinicians were comfortable or very comfortable using ketamine to facilitate intubation (80.0%), for analgesia (77.9%), procedural sedation (79.4%), continuous ICU sedation (65.8%), dressing changes (62.4%), or for asthma exacerbation and status epilepticus (58.8% and 40.4%). Clinicians were least comfortable with ketamine use for alcohol withdrawal and opioid detoxification (24.7% and 23.2%). Most respondents reported "never" or "infrequently" using ketamine preferentially for continuous IV analgesia (55.6%) or sedation (61%). Responses were mixed across dosing ranges and duration. The most common barriers to ketamine use were adverse effects (42.6%), other practitioners not routinely using the medication (41.5%), lack of evidence (33.5%), lack of familiarity (33.1%), and hospital/institutional policy guiding the indication for use (32.3%). Conclusion: Although most critical care practitioners report feeling comfortable using ketamine, there are many inconsistencies in practice regarding dose, duration, and reasons to avoid or limit ketamine use. Further educational tools may be targeted at practitioners to improve appropriate ketamine use.

Review of Hematological and Oncological Emergencies.

Patients with hematological malignancies, both treated and untreated, or solid tumors undergoing treatment are at risk of life-threatening complications, which may present in the emergency department (ED). Such emergencies are diverse in etiology and often require prompt treatment. Traditional complications, such as febrile neutropenia, have had recent guideline updates, which incorporate new evidence and a new validated risk stratification tool. In addition, newer approaches to treatment, such as chimeric antigen receptor (CAR) T-cell therapy, are becoming more widely available and have unique associated toxicities. This review discusses the management of the following hematological and oncological emergencies likely to be encountered in the ED: febrile neutropenia, CAR T-cell toxicities, differentiation syndrome, tumor lysis syndrome, hypercalcemia of malignancy, and hyponatremia.

Asystole Following Concomitant Intravenous Administration of Neostigmine and Dexmedetomidine in a Patient With Acute Colonic Pseudo-Obstruction.

Acute colonic pseudo-obstruction (ACPO) is a condition characterized by acute dilation of the large bowel without evidence of mechanical obstruction that occurs in a variety of hospitalized patients with many predisposing factors. Management includes supportive care and limitation of offending medications with mainstays of treatment of neostigmine administration and colonic decompression. We report the case of a critically ill patient with ACPO who experienced bradycardia and a brief episode of asystole when receiving concomitant dexmedetomidine and neostigmine infusions but who later remained hemodynamically stable when receiving propofol and neostigmine infusions. The bradycardia and associated hemodynamic instability experienced while on dexmedetomidine and neostigmine infusions were rapidly corrected with atropine and cessation of offending agents. Because ACPO is encountered frequently and the use of dexmedetomidine as a sedative agent in the ICU is increasing, practitioners should be aware of the additive risk of bradycardia and potential for asystole with the combination of neostigmine and dexmedetomidine. Electronic drug interaction databases should be updated and drug information sources should include a drug-drug interaction between dexmedetomidine and neostigmine to reduce the likelihood of concomitant administration.

Effectiveness and Safety of Twice- Versus Thrice-Daily Subcutaneous Heparin for Venous Thromboembolism Prophylaxis at a Large Academic Medical Center.

BACKGROUND: Dosing variation of subcutaneous unfractionated heparin (UFH) exist for venous thromboembolism prophylaxis (VTEP). OBJECTIVE: The purpose of this study was to compare the safety and effectiveness of thrice-daily (TID) versus twice-daily (BID) administration of UFH during a heparin shortage for VTEP. METHODS: A single-center retrospective analysis was conducted in patients with orders for BID subcutaneous UFH during a heparin shortage from September 1, 2019, to February 4, 2020. These patients were matched to patients with TID subcutaneous UFH orders from January 1, 2019, to May 31, 2019. The primary outcome was the incidence of deep-vein thrombosis or pulmonary embolism confirmed by imaging during hospitalization. The secondary outcome was the incidence of major or clinically relevant nonmajor bleeding events as defined by International Society on Thrombosis and Haemostasis (ISTH) definitions. RESULTS: A total of 277 patients with orders for BID UFH and meeting inclusion criteria were evaluated and matched to patients who received TID UFH. After the exclusion criteria were implemented, 510 patients remained in the TID group. The primary outcome occurred in 4% of patients in the BID group and 3% in the TID group (P = 0.645). Major bleeding or clinically relevant nonmajor bleeding events occurred in 10% of patients in the BID group and 8% in the TID group (P = 0.310). CONCLUSION AND RELEVANCE: There was no difference in effectiveness or safety of TID versus BID subcutaneous UFH for VTEP. During a heparin shortage, transitioning patients to BID UFH for VTEP to conserve supply may be considered.

Development and implementation of a clinical decision support-based initiative to drive intravenous fluid prescribing.

OBJECTIVE: Studies suggest superior outcomes with use of intravenous (IV) balanced fluids compared to normal saline (NS). However, significant fluid prescribing variability persists, highlighting the knowledge-to-practice gap. We sought to identify contributors to prescribing variation and utilize a clinical decision support system (CDSS) to increase institutional balanced fluid prescribing. MATERIALS AND METHODS: This single-center informatics-enabled quality improvement initiative for patients hospitalized or treated in the emergency department included stepwise interventions of 1) identification of design factors within the computerized provider order entry (CPOE) of our electronic health record (EHR) that contribute to preferential NS ordering, 2) clinician education, 3) fluid stocking modifications, 4) re-design and implementation of a CDSS-integrated IV fluid ordering panel, and 5) comparison of fluid prescribing before and after the intervention. EHR-derived prescribing data was analyzed via single interrupted time series. RESULTS: Pre-intervention (3/2019-9/2019), balanced fluids comprised 33% of isotonic fluid orders, with gradual uptake (1.4%/month) of balanced fluid prescribing. Clinician education (10/2019-2/2020) yielded a modest (4.4%/month, 95% CI 1.6-7.2, p = 0.01) proportional increase in balanced fluid prescribing, while CPOE redesign (3/2020) yielded an immediate (20.7%, 95% CI 17.7-23.6, p < 0.0001) and sustained increase (72% of fluid orders in 12/2020). The intervention proved most effective among those with lower baseline balanced fluids utilization, including emergency medicine (57% increase, 95% CI 0.7-1.8, p < 0.0001) and internal medicine/subspecialties (18% increase, 95% CI 14.4-21.3, p < 0.0001) clinicians and substantially reduced institutional prescribing variation. CONCLUSION: Integration of CDSS into an EHR yielded a robust and sustained increase in balanced fluid prescribing. This impact far exceeded that of clinician education highlighting the importance of CDSS.

Vitamin C for Sepsis and Septic Shock.

BACKGROUND: Sepsis remains a leading cause of death in the critically ill. The combination of thiamine, vitamin C, and hydrocortisone has recently emerged as a potential adjunctive therapy and supportive care for patients with sepsis and septic shock. AREAS OF UNCERTAINTY: Several randomized and observational controlled trials evaluated the role of vitamin C in sepsis and septic shock. However, there are variabilities in the findings of these studies that led to a substantial global debate on incorporating vitamin C therapy in clinical practice. DATA SOURCES: A PubMed and Embase English language literature search through April 2021 was performed using the following terms: ascorbic acid, vitamin C, corticosteroid, hydrocortisone, thiamine, HAT, sepsis, and shock. Citations, including controlled trials, observational studies, review articles, guidelines, and consensus statements, were reviewed. The risk of bias for each clinical study was systematically evaluated. Relevant clinical data focusing on efficacy, safety, and special considerations regarding the use of vitamin C with and without thiamine and hydrocortisone in sepsis and septic shock were narratively summarized. RESULTS: The most commonly used vitamin C dosing in sepsis and septic shock is 1.5 g every 6 hours with and without thiamine and hydrocortisone. Current literature is limited because of heterogeneity in vitamin C regimen used, initiation time, and duration of treatment. This limitation led to variability in outcomes evaluated. Vitamin C decreases proinflammatory mediators and slows the progression of endothelial injury in severe sepsis. There is an inconsistency between randomized controlled trials and observational controlled trials regarding mortality, resolution in organ failure, hospital and intensive care unit length of stay findings with the use of vitamin C in septic shock. Vitamin C seems to be safe in comparison with placebo. CONCLUSIONS: Future studies with consistent end points, initiation time with an emphasis on early initiation, and standard vitamin C dosing regimen are needed to determine the overall benefit of vitamin C in sepsis.

Effectiveness and Safety of Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation and Weighing ≥ 120 Kilograms versus 60-120 Kilograms.

BACKGROUND: Direct oral anticoagulants (DOACs) have become favorable choices for anticoagulation due to their fixed-dose schedule, limited need for monitoring, and non-inferiority or superiority to warfarin. DOACs are currently not recommended in patients with a body weight ≥ 120 kg or body mass index ≥ 40 kg/m2 due to limited data regarding safety and efficacy. OBJECTIVE: The aim of this study was to compare the safety and efficacy of DOACs in patients with nonvalvular atrial fibrillation (NVAF) and weighing ≥ 120 kg with those weighing < 120 kg. METHODS: A single-center, retrospective study was conducted in patients weighing ≥ 120 kg who received either apixaban, dabigatran, or rivaroxaban for stroke risk reduction in NVAF, and matched to patients who weighed < 120 kg. The primary outcome was the incidence of stroke, deep vein thrombosis, pulmonary embolism, or myocardial infarction, while the safety outcome was the incidence of major or clinically relevant non-major bleeding based on the International Society on Thrombosis and Haemostasis (ISTH) definitions. RESULTS: A total of 318 patients weighing ≥ 120 kg with NVAF and meeting the inclusion criteria were evaluated and matched with 318 patients weighing < 120 kg. The primary outcome occurred in 2.5% of patients in the ≥ 120 kg group and in 3.1% of patients in the < 120 kg group (p = 0.632). The safety outcome occurred in 5.3% and 6.6% of patients in these respective groups (p = 0.503). CONCLUSION: Apixaban, dabigatran, or rivaroxaban may be well-tolerated and effective anticoagulant options in patients with NVAF weighing ≥ 120 kg.

Major publications in the critical care pharmacotherapy literature: 2019.

PURPOSE: To summarize selected meta-analyses and trials related to critical care pharmacotherapy published in 2019. MATERIALS AND METHODS: The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 36 journals monthly for impactful articles and reviewed 113 articles during 2019 according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. RESULTS: Articles with a 1A grade, including three clinical practice guidelines, six meta-analyses, and five original research trials are reviewed here from those included in the monthly CCPLU. Clinical practice guidelines on the use of polymyxins and antiarrhythmic drugs in cardiac arrest as well as meta-analyses on antipsychotic use in delirium, stress ulcer prophylaxis (SUP), and vasoactive medications in septic shock and cardiac arrest were summarized. Original research trials evaluated delirium, sedation, neuromuscular blockade, SUP, anticoagulation reversal, and hemostasis. CONCLUSION: This clinical review and expert opinion provides summary and perspectives of clinical practice impact on influential critical care pharmacotherapy publications in 2019.

Porphyria cutanea tarda associated with elevated serum ferritin, iron overload, and a bone morphogenetic protein 6 genetic variant.

A man aged 51 years was referred to dermatology for hand dermatitis. The dorsal hands and fingers had superficial erosions with pale pink shallow scars and milia suggestive of porphyria cutanea tarda (PCT). Urine and fecal studies were typical of PCT. The patient had daily alcohol use and was found to have elevated serum ferritin, aspartate aminotransferase, and alanine transaminase. Genetic testing for common hemochromatosis genetic variants (HFE C282Y and H63D) was normal. He underwent next-generation sequencing analysis using the 16-gene hyperferritinemia gene panel for genes known to be associated with hereditary hyperferritinemia, iron overload, or both and was discovered to have a genetic variant in bone morphogenetic 6 (BMP6, c.287T> C, p.Leu96Pro). The skin lesions improved with phlebotomy therapy.

Prolonged Zika Virus RNA Detection in Semen of Immunosuppressed Patient.

Zika virus RNA has been detected in semen samples collected <370 days after symptom onset. We report unusual persistence of Zika virus RNA in semen, confirmed by sequencing at 515 days after symptom onset and detectable for >900 days, in a patient with immunosuppression.

Gastrointestinal dysfunction in patients and mice expressing the autism-associated R451C mutation in neuroligin-3.

Gastrointestinal (GI) problems constitute an important comorbidity in many patients with autism. Multiple mutations in the neuroligin family of synaptic adhesion molecules are implicated in autism, however whether they are expressed and impact GI function via changes in the enteric nervous system is unknown. We report the GI symptoms of two brothers with autism and an R451C mutation in Nlgn3 encoding the synaptic adhesion protein, neuroligin-3. We confirm the presence of an array of synaptic genes in the murine GI tract and investigate the impact of impaired synaptic protein expression in mice carrying the human neuroligin-3 R451C missense mutation (NL3R451C ). Assessing in vivo gut dysfunction, we report faster small intestinal transit in NL3R451C compared to wild-type mice. Using an ex vivo colonic motility assay, we show increased sensitivity to GABAA receptor modulation in NL3R451C mice, a well-established Central Nervous System (CNS) feature associated with this mutation. We further show increased numbers of small intestine myenteric neurons in NL3R451C mice. Although we observed altered sensitivity to GABAA receptor modulators in the colon, there was no change in colonic neuronal numbers including the number of GABA-immunoreactive myenteric neurons. We further identified altered fecal microbial communities in NL3R451C mice. These results suggest that the R451C mutation affects small intestinal and colonic function and alter neuronal numbers in the small intestine as well as impact fecal microbes. Our findings identify a novel GI phenotype associated with the R451C mutation and highlight NL3R451C mice as a useful preclinical model of GI dysfunction in autism. Autism Res 2019, 12: 1043-1056. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism commonly experience gastrointestinal problems, however the cause is unknown. We report gut symptoms in patients with the autism-associated R451C mutation encoding the neuroligin-3 protein. We show that many of the genes implicated in autism are expressed in mouse gut. The neuroligin-3 R451C mutation alters the enteric nervous system, causes gastrointestinal dysfunction, and disrupts gut microbe populations in mice. Gut dysfunction in autism could be due to mutations that affect neuronal communication.