Characterizing molecular and synaptic signatures in mouse models of late-onset Alzheimer's disease independent of amyloid and tau pathology.

INTRODUCTION: MODEL-AD (Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease) is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to capture the trajectory and progression of late-onset Alzheimer's disease (LOAD) more accurately. METHODS: We created the LOAD2 model by combining apolipoprotein E4 (APOE4), Trem2*R47H, and humanized amyloid-beta (Aß). Mice were subjected to a control diet or a high-fat/high-sugar diet (LOAD2+HFD). We assessed disease-relevant outcome measures in plasma and brain including neuroinflammation, Aß, neurodegeneration, neuroimaging, and multi-omics. RESULTS: By 18 months, LOAD2+HFD mice exhibited sex-specific neuron loss, elevated insoluble brain Aß42, increased plasma neurofilament light chain (NfL), and altered gene/protein expression related to lipid metabolism and synaptic function. Imaging showed reductions in brain volume and neurovascular uncoupling. Deficits in acquiring touchscreen-based cognitive tasks were observed. DISCUSSION: The comprehensive characterization of LOAD2+HFD mice reveals that this model is important for preclinical studies seeking to understand disease trajectory and progression of LOAD prior to or independent of amyloid plaques and tau tangles. HIGHLIGHTS: By 18 months, unlike control mice (e.g., LOAD2 mice fed a control diet, CD), LOAD2+HFD mice presented subtle but significant loss of neurons in the cortex, elevated levels of insoluble Ab42 in the brain, and increased plasma neurofilament light chain (NfL). Transcriptomics and proteomics showed changes in gene/proteins relating to a variety of disease-relevant processes including lipid metabolism and synaptic function. In vivo imaging revealed an age-dependent reduction in brain region volume (MRI) and neurovascular uncoupling (PET/CT). LOAD2+HFD mice also demonstrated deficits in acquisition of touchscreen-based cognitive tasks.

The effect of diabetes mellitus on perioperative outcomes after colorectal resection: a national cohort study.

BACKGROUND: Diabetes mellitus is a significant modulator of postoperative outcomes and is an important risk factor in the patient selection process. We aimed to investigate the effect of diabetes mellitus and use of insulin on outcomes after colorectal resection using a national cohort. METHODS: Adults with a recorded colorectal resection in England between 2010 and 2020 were identified from Hospital Episode Statistics data linked to the Clinical Practice Research Database. The primary outcome was 90-day mortality. Secondary outcomes included hospital length of stay (LOS) and readmission within 90 days. RESULTS: Of the 106 139 (52 875, 49.8% male) patients included, diabetes mellitus was prevalent in 10 931 (10.3%), 2145 (19.6%) of whom had a record of use of insulin. Unadjusted 90-day mortality risk was 5.7%, with an increased adjusted hazard ratio (aHR) for people with diabetes mellitus (aHR 1.28, 95% confidence interval [CI] 1.19-1.37, P<0.001). This risk was higher in both people with diabetes using insulin (aHR 1.51, 95% CI 1.31-1.74, P<0.001) and not using insulin (aHR 1.22, 95% CI 1.13-1.33, P<0.001), compared with those without diabetes. Ninety-day readmission occurred in 20 542 (19.4%) patients and this was more likely in those with diabetes mellitus (aHR 1.23, 95% CI 1.18-1.29, P<0.001). Median (inter-quartile range) LOS was 8 (5-15) days and was higher in people with diabetes mellitus (adjusted time ratio 1.10, 95% CI 1.08-1.11, P<0.001). CONCLUSIONS: People with diabetes mellitus undergoing colorectal resection are at a higher risk of 90-day mortality, prolonged LOS, and 90-day readmission, with use of insulin associated with additional risk.

The safety and efficacy of direct oral anticoagulants among chronic kidney disease patients on dialysis with non-valvular atrial fibrillation: a meta-analysis.

Background: Individuals with chronic kidney disease (CKD) on dialysis are at an increased risk of stroke and embolic events especially in the presence of atrial fibrillation (AF). Vitamin K antagonists (VKA), including warfarin, have been used for decades for anticoagulation among CKD patients on dialysis with AF but recent evidence has shown increased bleeding. Direct oral anticoagulants (DOAC) have been emerging as an alternative to VKA which, based on several observational cohort studies, are at least as efficacious and safe as VKA. This meta-analysis looked into the safety and efficacy of DOACs compared to VKA among CKD patients on dialysis with non-valvular AF. Methodology: This study used a random-effects meta-analysis using RevMan 5.4. PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov were searched from their dates of inception to June 2023. The risk of bias was assessed using Cochrane RoB2 and the certainty of evidence was assessed using GRADE. Results: This meta-analysis showed that DOACs when compared to VKA have no significant difference in terms of risk for major bleeding (RR = 0.81, 95% CI 0.46-1.43), ischemic stroke (RR = 0.5, 95% CI 0.19-1.35), and cardiovascular death (RR = 1.34, 95% CI 0.69-2.60). Discussion: This meta-analysis adds to the growing body of evidence supporting that the use of DOACs has similar efficacy and safety outcomes in CKD patients on dialysis with non-valvular AF patients compared to VKA. The findings need to be replicated in larger and more adequately powered clinical trials in order to ascertain its level of evidence.

Risk of Postoperative Venous Thromboembolism After Benign Colorectal Surgery: Systematic Review and Meta-analysis.

BACKGROUND: Venous thromboembolism is a well-established preventable complication after colectomy. Specific guidance on venous thromboembolism prevention after colectomy for benign disease is limited. OBJECTIVE: This meta-analysis aimed to quantify the venous thromboembolism risk after benign colorectal resection and determine its variability. DATA SOURCES: Following Preferred Reporting Items for Systematic Review and Meta-Analysis and Meta-analysis of Observational Studies in Epidemiology Guidelines (PROSPERO: CRD42021265438), Embase, MEDLINE, and 4 other registered medical literature databases were searched from the database inception to June 21, 2021. STUDY SELECTION: Inclusion criteria: randomized controlled trials and large population-based database cohort studies reporting 30-day and 90-day venous thromboembolism rates after benign colorectal resection in patients aged ≥18 years. Exclusion criteria: patients undergoing colorectal cancer or completely endoscopic surgery. MAIN OUTCOME MEASURES: Thirty- and 90-day venous thromboembolism incidence rates per 1000 person-years after benign colorectal surgery. RESULTS: Seventeen studies were eligible for meta-analysis reporting on 250,170 patients. Pooled 30-day and 90-day venous thromboembolism incidence rates after benign colorectal resection were 284 (95% CI, 224-360) and 84 (95% CI, 33-218) per 1000 person-years. Stratified by admission type, 30-day venous thromboembolism incidence rates per 1000 person-years were 532 (95% CI, 447-664) for emergency resections and 213 (95% CI, 100-453) for elective colorectal resections. Thirty-day venous thromboembolism incidence rates per 1000 person-years after colectomy were 485 (95% CI, 411-573) for patients with ulcerative colitis, 228 (95% CI, 181-288) for patients with Crohn's disease, and 208 (95% CI, 152-288) for patients with diverticulitis. LIMITATIONS: High degree of heterogeneity was observed within most meta-analyses attributable to large cohorts minimizing within-study variance. CONCLUSIONS: Venous thromboembolism rates remain high up to 90 days after colectomy and vary by indication for surgery. Emergency resections compared to elective benign resections have higher rates of postoperative venous thromboembolism. Further studies reporting venous thromboembolism rates by type of benign disease need to stratify rates by admission type to more accurately define venous thromboembolism risk after colectomy. REGISTRATION NO: CRD42021265438.

Venous thromboembolism following colectomy for diverticular disease: an English population-based cohort study.

AIM: This study reports venous thromboembolism (VTE) rates following colectomy for diverticular disease to explore the magnitude of postoperative VTE risk in this population and identify high risk subgroups of interest. METHOD: English national cohort study of colectomy patients between 2000 and 2019 using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Stratified by admission type, absolute incidence rates (IR) per 1000 person-years and adjusted incidence rate ratios (aIRR) were calculated for 30- and 90-day post-colectomy VTE. RESULTS: Of 24,394 patients who underwent colectomy for diverticular disease, over half (57.39%) were emergency procedures with the highest VTE rate seen in patients ≥70-years-old (IR 142.27 per 1000 person-years, 95%CI 118.32-171.08) at 30 days post colectomy. Emergency resections (IR 135.18 per 1000 person-years, 95%CI 115.72-157.91) had double the risk (aIRR 2.07, 95%CI 1.47-2.90) of developing a VTE at 30 days following colectomy compared to elective resections (IR 51.14 per 1000 person-years, 95%CI 38.30-68.27). Minimally invasive surgery (MIS) was shown to be associated with a 64% reduction in VTE risk (aIRR 0.36 95%CI 0.20-0.65) compared to open colectomies at 30 days post-op. At 90 days following emergency resections, VTE risks remained raised compared to elective colectomies. CONCLUSION: Following emergency colectomy for diverticular disease, the VTE risk is approximately double compared to elective resections at 30 days while MIS was found to be associated with a reduced risk of VTE. This suggests advancements in postoperative VTE prevention in diverticular disease patients should focus on those undergoing emergency colectomies.

Paxlovid-Induced Tacrolimus Toxicity in the Treatment of COVID-19: A Case Report.

PaxlovidTM (nirmaltrelvir/ritonavir) received emergency use authorization from the Food and Drug Administration (FDA) in December 2021 to treat coronavirus disease 2019 (COVID-19). Given the actions of Paxlovid on cytochrome P450-3A4 (CYP3A4) enzymes, it is imperative to check for potential drug-drug interactions before prescribing. We describe a case in which the common emergency department presentation of generalized weakness was found to be caused by interactions between Paxlovid and a patient's home medications resulting in tacrolimus toxicity.

Discovery of a polymer resistant to bacterial biofilm, swarming, and encrustation.

Innovative approaches to prevent catheter-associated urinary tract infections (CAUTIs) are urgently required. Here, we describe the discovery of an acrylate copolymer capable of resisting single- and multispecies bacterial biofilm formation, swarming, encrustation, and host protein deposition, which are major challenges associated with preventing CAUTIs. After screening ~400 acrylate polymers, poly(tert-butyl cyclohexyl acrylate) was selected for its biofilm- and encrustation-resistant properties. When combined with the swarming inhibitory poly(2-hydroxy-3-phenoxypropyl acrylate), the copolymer retained the bioinstructive properties of the respective homopolymers when challenged with Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. Urinary tract catheterization causes the release of host proteins that are exploited by pathogens to colonize catheters. After preconditioning the copolymer with urine collected from patients before and after catheterization, reduced host fibrinogen deposition was observed, and resistance to diverse uropathogens was maintained. These data highlight the potential of the copolymer as a urinary catheter coating for preventing CAUTIs.

Characterizing Molecular and Synaptic Signatures in mouse models of Late-Onset Alzheimer's Disease Independent of Amyloid and Tau Pathology.

INTRODUCTION: MODEL-AD is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to more accurately mimic LOAD than commonly used transgenic models. METHODS: We created the LOAD2 model by combining APOE4, Trem2*R47H, and humanized amyloid-beta. Mice aged up to 24 months were subjected to either a control diet or a high-fat/high-sugar diet (LOAD2+HFD) from two months of age. We assessed disease-relevant outcomes, including in vivo imaging, biomarkers, multi-omics, neuropathology, and behavior. RESULTS: By 18 months, LOAD2+HFD mice exhibited cortical neuron loss, elevated insoluble brain Aß42, increased plasma NfL, and altered gene/protein expression related to lipid metabolism and synaptic function. In vivo imaging showed age-dependent reductions in brain region volume and neurovascular uncoupling. LOAD2+HFD mice also displayed deficits in acquiring touchscreen-based cognitive tasks. DISCUSSION: Collectively the comprehensive characterization of LOAD2+HFD mice reveal this model as important for preclinical studies that target features of LOAD independent of amyloid and tau.

Where Have All the FLOWERS Gone? A Multicenter Investigation of Frequent Users of Midwest Emergency Department Services During the COVID-19 Stay-at-home Orders.

INTRODUCTION: In this study we aimed to determine the impact of the mandatory coronavirus disease 2019 (COVID-19) pandemic stay-at-home order on the proportional makeup of emergency department (ED) visits by frequent users and super users. METHODS: We conducted a secondary analysis of existing data using a multisite review of the medical records of 280,053 patients to measure the impact of the COVID-19 pandemic stay-at-home order on ED visits. The primary outcomes included analysis before and during the lockdown in determining ED use and unique characteristics of non-frequent, frequent, and super users of emergency services. RESULTS: During the mandatory COVID-19 stay-at-home order (lockdown), the percentage of frequent users increased from 7.8% (pre-lockdown) to 21.8%. Super users increased from 0.7% to 4.7%, while non-frequent users dropped from 91.5% to 73.4%. Frequent users comprised 23.7% of all visits (4% increase), while super user encounters (4.7%) increased by 53%. Patients who used Medicaid and Medicare increased by 39.3% and 4.6%, respectively, while those who were uninsured increased ED use by 190.3% during the lockdown. CONCLUSION: When barriers to accessing healthcare are implemented as part of a broader measure to reduce the spread of an infectious agent, individuals reliant on these services are more likely to seek out the ED for their medical needs. Policymakers considering future pandemic planning should consider this finding to ensure that vital healthcare resources are allocated appropriately.

Impact of CTLA-4 checkpoint antibodies on ligand binding and Transendocytosis.

Anti-CTLA-4 antibodies have pioneered the field of tumour immunotherapy. However, despite impressive clinical response data, the mechanism by which anti-CTLA-4 antibodies work is still controversial. Two major checkpoint antibodies (ipilimumab and tremelimumab) have been trialled clinically. Both have high affinity binding to CTLA-4 and occupy the ligand binding site, however recently it has been suggested that in some settings such antibodies may not block ligand-CTLA-4 interactions. Here we evaluated blocking capabilities of these antibodies in a variety of settings using both soluble and cell bound target proteins. We found that when ligands (CD80 or CD86) were expressed on cells, soluble CTLA-4-Ig bound in line with affinity expectations and that this interaction was effectively disrupted by both ipilimumab and tremelimumab antibodies. Similarly, cellular CTLA-4 binding to soluble ligands was comparably prevented. We further tested the ability of these antibodies to block transendocytosis, whereby CTLA-4 captures ligands from target cells during a cognate cell-cell interaction. Once again ipilimumab and tremelimumab were similar in preventing removal of ligand by transendocytosis. Furthermore, even once transendocytosis was ongoing and cell contact was fully established, the addition of these antibodies could prevent further ligand transfer. Together these data indicate that the above checkpoint inhibitors performed in-line with predictions based on affinity and binding site data and are capable of blocking CTLA-4-ligand interactions in a wide range of settings tested.

Plcg2M28L Interacts With High Fat/High Sugar Diet to Accelerate Alzheimer's Disease-Relevant Phenotypes in Mice.

Obesity is recognized as a significant risk factor for Alzheimer's disease (AD). Studies have supported the notion that obesity accelerates AD-related pathophysiology in mouse models of AD. The majority of studies, to date, have focused on the use of early-onset AD models. Here, we evaluate the impact of genetic risk factors on late-onset AD (LOAD) in mice fed with a high fat/high sugar diet (HFD). We focused on three mouse models created through the IU/JAX/PITT MODEL-AD Center. These included a combined risk model with APOE4 and a variant in triggering receptor expressed on myeloid cells 2 (Trem2R47H ). We have termed this model, LOAD1. Additional variants including the M28L variant in phospholipase C Gamma 2 (Plcg2M28L ) and the 677C > T variant in methylenetetrahydrofolate reductase (Mthfr 677C > T ) were engineered by CRISPR onto LOAD1 to generate LOAD1.Plcg2M28L and LOAD1.Mthfr 677C > T . At 2 months of age, animals were placed on an HFD that induces obesity or a control diet (CD), until 12 months of age. Throughout the study, blood was collected to assess the levels of cholesterol and glucose. Positron emission tomography/computed tomography (PET/CT) was completed prior to sacrifice to image for glucose utilization and brain perfusion. After the completion of the study, blood and brains were collected for analysis. As expected, animals fed a HFD, showed a significant increase in body weight compared to those fed a CD. Glucose increased as a function of HFD in females only with cholesterol increasing in both sexes. Interestingly, LOAD1.Plcg2M28L demonstrated an increase in microglia density and alterations in regional brain glucose and perfusion on HFD. These changes were not observed in LOAD1 or LOAD1.Mthfr 677C > T animals fed with HFD. Furthermore, LOAD1.Plcg2M28L but not LOAD1.Mthfr 677C > T or LOAD1 animals showed transcriptomics correlations with human AD modules. Our results show that HFD affects the brain in a genotype-specific manner. Further insight into this process may have significant implications for the development of lifestyle interventions for the treatment of AD.

The Duration and Magnitude of Postdischarge Venous Thromboembolism Following Colectomy.

OBJECTIVE: To assess the impact of current guidelines by reporting weekly postoperative postdischarge venous thromboembolism (VTE) rates. SUMMARY BACKGROUND DATA: Disparity exists between the postoperative thromboprophylaxis duration colectomy patients receive based on surgical indication, where malignant resections routinely receive 28 days extended thromboprophylaxis into the postdischarge period and benign resections do not. METHODS: English national cohort study of colectomy patients between 2010 and 2019 using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Stratified by admission type and surgical indication, absolute incidence rates (IRs) per 1000 person-years and adjusted incidence rate ratios (aIRRs) for postdischarge VTE were calculated for the first 4 weeks following resection and postdischarge VTE IRs for each postoperative week to 12 weeks postoperative. RESULTS: Of 104,744 patients, 663 (0.63%) developed postdischarge VTE within 12 weeks after colectomy. Postdischarge VTE IRs per 1000 person-years for the first 4 weeks postoperative were low following elective resections [benign: 20.66, 95% confidence interval (CI): 13.73-31.08; malignant: 28.95, 95% CI: 23.09-36.31] and higher following emergency resections (benign: 47.31, 95% CI: 34.43-65.02; malignant: 107.18, 95% CI: 78.62-146.12). Compared with elective malignant resections, there was no difference in postdischarge VTE risk within 4 weeks following elective benign colectomy (aIRR=0.92, 95% CI: 0.56-1.50). However, postdischarge VTE risks within 4 weeks following emergency resections were significantly greater for benign (aIRR=1.89, 95% CI: 1.22-2.94) and malignant (aIRR=3.13, 95% CI: 2.06-4.76) indications compared with elective malignant colectomy. CONCLUSIONS: Postdischarge VTE risk within 4 weeks of colectomy is ∼2-fold greater following emergency benign compared with elective malignant resections, suggesting emergency benign colectomy patients may benefit from extended VTE prophylaxis.

Time trends in the incidence rates of venous thromboembolism following colorectal resection by indication and operative technique.

AIM: It is important for patient safety to assess if international changes in perioperative care, such as the focus on venous thromboembolism (VTE) prevention and minimally invasive surgery, have reduced the high post colectomy VTE risks previously reported. This study assesses the impact of changes in perioperative care on VTE risk following colorectal resection. METHOD: This was a population-based cohort study of colectomy patients in England between 2000 and 2019 using a national database of linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Within 30 days following colectomy, absolute VTE rates per 1000 person-years and adjusted incidence rate ratios (aIRRs) using Poisson regression for the per year change in VTE risk were calculated. RESULTS: Of 183 791 patients, 1337 (0.73%) developed 30-day postoperative VTE. Overall, VTE rates reduced over the 20-year study period following elective (relative risk reduction 31.25%, 95% CI 5.69%-49.88%) but not emergency surgery. Similarly, yearly changes in VTE risk reduced following minimally invasive resections (elective benign, aIRR 0.93, 95% CI 0.90-0.97; elective malignant, aIRR 0.94, 95% CI 0.91-0.98; and emergency benign, aIRR 0.96, 95% CI 0.92-1.00) but not following open resections. There was a per year VTE risk increase following open emergency malignant resections (aIRR 1.02, 95% CI 1.00-1.04). CONCLUSION: Yearly VTE risks reduced following minimally invasive surgeries in the elective setting yet in contrast were static following open elective colectomies, and following emergency malignant resections increased by almost 2% per year. To reduce VTE risk, further efforts are required to implement advances in surgical care for those having emergency and/or open surgery.

Mycotic Aortic Aneurysm: A Rare Etiology of Septic Shock.

Mycotic aneurysm of the aorta is a rare disease with a high mortality rate due to its likelihood of aneurysmal rupture. This syndrome is predominantly seen in patients over age 65 with the most common presenting symptoms being fever and back pain. Our case illustrates a mycotic aneurysm of the aorta presenting in an elderly female with vague abdominal pain, flank pain, and generalized weakness. We review the investigative approach, diagnostic modalities, and treatment options in patient management. This case emphasizes the need for a high index of suspicion of mycotic aneurysms of the aorta in critically ill elderly patients as early antibiotic therapy can be crucial for source control.

Patterns and mechanisms of major trauma injuries during and after the UK Covid-19 Nationwide lockdown: analysis from a UK Major Trauma Centre.

PURPOSE: To compare patterns and mechanisms of injuries during and after the UK Nationwide lockdown during the COVID-19 pandemic. METHODS: This prospective cohort study included all major trauma admissions during the 10-week period of the nationwide lockdown (09/03/2020-18/05/2020), compared with admissions in the 10-weeks following the full lifting of lockdown restrictions (04/07/20-12/09/2020). Differences in the volume, spectrum and mechanism of injuries presenting during and post-lockdown were compared using Fisher's exact and Chi-squared tests as appropriate. The associated risk of 30-day mortality was examined using univariable and multivariable logistic regression. RESULTS: A total of 692 major trauma admissions were included in this analysis. Of these, 237 patients were admitted during the lockdown and 455 patients were admitted post-lockdown. This represented a twofold increase in trauma admission between the two periods. Characteristically, both cohorts had a higher proportion of male patients (73.84% male during lockdown and 72.5% male post-lockdown). There was a noted shift in age groups between both cohorts with an overall more elderly population during lockdown (p = 0.0292), There was a significant difference in mechanisms of injury between the two cohorts. The 3-commonest mechanisms during the lockdown period were: Road traffic accidents (RTA)-31.22%, Falls of less than 2 m-26.58%, and falls greater than 2 m causing 22.78% of major trauma admissions. However, in the post-lockdown period RTAs represented 46.15% of all trauma admissions with falls greater than 2 m causing 17.80% and falls less than 2 m causing 15.16% of major trauma injuries. With falls in the elderly associated with an increased risk of mortality. In terms of absolute numbers, there was a twofold increase in major trauma injuries due to stabbings and shootings, rising from 25 admitted patients during the lockdown to 53 admitted patients post-lockdown. CONCLUSIONS: The lifting of lockdown restrictions resulted in a twofold increase in major trauma admissions that was also associated with significant changes in both the demographic and patterns of injuries with RTA's contributing almost half of all injury presentations. TRIAL REGISTRATION: This study was classed as a service evaluation and registered with the local audit department, registration number: 20-177C.

"His Main Problem Was Not Being in a Relationship With God": Perceptions of Depression, Help-Seeking, and Treatment in Evangelical Christianity.

Some Christian communities may understand mental illness as the result of spiritual causes, such as sin, demons, or a lack of faith. Such perceptions are likely to influence how Christian individuals conceptualise and experience their mental health and enact help-seeking behaviours. This study explores perceptions of depression and mental health help-seeking in evangelical Christianity by using a novel qualitative story completion task. A convenience sample of 110 Christian participants from the United Kingdom completed a third-person, fictional story stem featuring a male with depression who entered his local church. A contextualist-informed thematic analysis illustrated how the disclosure of depression was represented as eliciting negative social reactions, potentially rendering individuals with depression as socially dislocated. Stories suggested that, increasingly, evangelical Christians may perceive a spiritualisation of mental illness, which negates reference to psychological, social, and biomedical representations, as unhelpful. Findings reveal the risks of a solely spiritual aetiology of depression and highlight how existing mental ill-health can be exacerbated if fundamentalist beliefs and approaches to therapeutic care are prioritised over holistic models of care. Methodologically, this study demonstrates the value of a rarely-used tool in psychology-the story completion task-for examining socio-cultural discourses and dominant meanings surrounding stigmatised topics or populations.

Hypokalemic Cardiac Arrest: Narrative Review of Case Reports and Current State of Science.

PURPOSE: Hypokalemic cardiac arrest is an uncommon occurrence in the emergency department. Electrocardiogram findings related to hypokalemic cardiac arrest include prolonged QT, U waves, and preventricular contractions leading to Torsades de Pointes and then arrest. Literature evaluating the prevalence of hypokalemic cardiac arrest is scarce, and its management is lacking. This review provides a summary of current literature, recommendations from current guidelines, and proposed management strategies of hypokalemic cardiac arrest. SUMMARY: Intravenous potassium administration is the treatment for hypokalemic cardiac arrest. Although the treatment for hypokalemic cardiac arrest is known, there is limited evidence on the proper procedure for administering intravenous potassium appropriately and safely. Owing to the time-sensitive nature of treating hypokalemic cardiac arrest, rapid administration of intravenous potassium (10 mEq/100 mL of potassium chloride over 5 minutes) is warranted. Concerns regarding rapid potassium administration are not without merit; however, a risk-benefit analysis and potential mitigation strategies for unwanted side effects need to be considered if hypokalemic cardiac arrest is to remain a reversible cause. It is imperative to identify hypokalemia as the cause for arrest as soon as possible and administer potassium before systemic acidosis, ischemia, and irreversible cell death. CONCLUSIONS: More evidence is necessary to support treatment recommendations for hypokalemic cardiac arrest; however, it is the authors' opinion that, if identified early during cardiac arrest, intravenous potassium should be administered to treat a reversible cause for cardiac arrest.

"It's easy to dismiss it as simply a spiritual problem." Experiences of mental distress within evangelical Christian communities: A qualitative survey.

Evidence suggests that faith communities can support psychological wellbeing but can also potentially diminish wellbeing through stigma, imposed spiritualization, and marginalization. In particular, for evangelical Christianity, whose theological praxis typically accentuates literalist spiritual onto-etiologies, including the belief that mental distress can be treated solely through spiritual intervention (prayer, fasting, and deliverance), there may be negative implications for Christians with mental distress. The current qualitative survey examined the responses of 293 self-identified evangelical Christians, concerning their experiences of mental distress in relation to their church community. An inductive thematic analysis revealed five themes: 1) Tensions between Faith and Suffering; 2) Cautions about a Reductive Spiritualization; 3) Feeling Othered and Disconnected; 4) Faith as Alleviating Distress; and 5) Inviting an Integrationist Position. Findings reveal stigma and the totalizing spiritualization of mental distress can be experienced as both dismissive and invalidating and can problematize secular help-seeking. This lends support to previous research which has suggested that evangelical Christian communities tend to link mental distress to spiritual deficiencies, which can hold potentially negative consequences for their wellbeing. Nevertheless, a degree of complexity and nuance emerged whereby spiritual explanations and interventions were also experienced as sometimes helpful in alleviating suffering. Overall, findings suggest evangelical communities are increasingly adopting integrationist understandings of mental distress, whereby spiritual narratives are assimilated alongside the biopsychosocial. We argue that church communities and psychotherapeutic practitioners should support movement from a position of dichotomizing psychological suffering (e.g., spiritual vs. biopsychosocial) towards a spiritually syntonic frame, which contextualizes distress in terms of the whole person. Considerations for psychotherapeutic practice and further research are made.

Qualitative Investigation into Therapists' Experiences of Online Therapy: Implications for Working Clients.

Online therapy has increasingly been utilised during the COVID-19 pandemic by many, including working populations. However, few qualitative studies have explored how online therapy is experienced in practice and discussed its implications for those working clients. Semi-structured interviews attended by nine integrative psychotherapists practising in California, the United States, were conducted. Thematic analysis of the transcripts identified three themes: (i) 'Positive experiences of online therapy', (ii) 'Challenges experienced by therapists and clients in online therapy', and (iii) 'Preparation and training for online therapy'. Online therapy was assessed as being helpful, particularly in terms of mitigating against previous geographical and temporal barriers to uptake. However, due to technological disruptions and potential blurring of professional boundaries, online therapy may detract from the emotional salience of therapy, negatively impacting the therapeutic relationship and containment. Considering these positive experiences, participants expected that the demand for online therapy would continue to increase. Particularly in the occupational context, online therapy can offer interventions without fostering shame regarding mental health. The findings provide preliminary qualitative evidence that online therapy can be a useful adjunct to traditional forms of face-to-face therapy. However, therapists require more explicit training in implementing online therapy. Results are discussed in particular regarding the utility of this therapy for working clients.