The effectiveness of intradiscal corticosteroid injection for the treatment of chronic discovertebral low back pain: a systematic review.

OBJECTIVE: Determine the effectiveness of intradiscal corticosteroid injection (IDCI) for the treatment of discovertebral low back pain. DESIGN: Systematic review. POPULATION: Adults with chronic low back pain attributed to disc or vertebral end plate pain, as evidenced by positive provocation discography or Modic 1 or 2 changes on magnetic resonance imaging. INTERVENTION: Fluoroscopically guided or computed tomography-guided IDCI. COMPARISON: Sham/placebo procedure including intradiscal saline, anesthetic, discography alone, or other active treatment. OUTCOMES: Reduction in chronic low back pain reported on a visual analog scale or numeric rating scale and reduction in disability reported by a validated scale such as the Oswestry Disability Index. METHODS: Four reviewers independently assessed articles published before January 31, 2023, in Medline, Embase, CENTRAL, and CINAHL. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The risk of bias in randomized trials was evaluated with the Cochrane Risk of Bias tool (version 2). RESULTS: Of the 7806 unique records screened, 6 randomized controlled trials featuring 603 total participants ultimately met the inclusion criteria. In multiple randomized controlled trials, IDCI was found to reduce pain and disability for 1-6 months in those with Modic 1 and 2 changes but not in those selected by provocation discography. CONCLUSION: According to GRADE, there is low-quality evidence that IDCI reduces pain and disability for up to 6 months in individuals with chronic discovertebral low back pain as evidenced by Modic 1 and 2 changes but not in individuals selected by provocation discography. STUDY REGISTRATION: PROSPERO (CRD42021287421).

Differences in quality of anticoagulation care delivery according to ethnoracial group in the United States: A scoping review.

Anticoagulation therapy is standard for conditions like atrial fibrillation, venous thromboembolism, and valvular heart disease, yet it is unclear if there are ethnoracial disparities in its quality and delivery in the United States. For this scoping review, electronic databases were searched for publications between January 1, 2011 - March 30, 2022. Eligible studies included all study designs, any setting within the United States, patients prescribed anticoagulation for any indication, outcomes reported for ≥ 2 distinct ethnoracial groups. The following four research questions were explored: Do ethnoracial differences exist in 1) access to guideline-based anticoagulation therapy, 2) quality of anticoagulation therapy management, 3) clinical outcomes related to anticoagulation care, 4) humanistic/educational outcomes related to anticoagulation therapy. A total of 5374 studies were screened, 570 studies received full-text review, and 96 studies were analyzed. The largest mapped focus was patients' access to guideline-based anticoagulation therapy (88/96 articles, 91.7%). Seventy-eight articles made statistical outcomes comparisons among ethnoracial groups. Across all four research questions, 79 articles demonstrated favorable outcomes for White patients compared to non-White patients, 38 articles showed no difference between White and non-White groups, and 8 favored non-White groups (the total exceeds the 78 articles with statistical outcomes as many articles reported multiple outcomes). Disparities disadvantaging non-White patients were most pronounced in access to guideline-based anticoagulation therapy (43/66 articles analyzed) and quality of anticoagulation management (19/21 articles analyzed). Although treatment guidelines do not differentiate anticoagulant therapy by ethnoracial group, this scoping review found consistently favorable outcomes for White patients over non-White patients in the domains of access to anticoagulation therapy for guideline-based indications and quality of anticoagulation therapy management. No differences among groups were noted in clinical outcomes, and very few studies assessed humanistic or educational outcomes.

Effectiveness of atropine in managing sialorrhea: A systematic review and meta-analysis.

OBJECTIVES: To describe the efficacy of atropine in controlling salivary flow in patients with sialorrhea or drooling. MATERIALS AND METHODS: We included randomized controlled studies, quasi-randomized trials, case reports, clinical trials, systematic reviews, and meta-analyses assessing the use of atropine in patients with sialorrhea or drooling. The endpoints were reduction in salivary flow rate, amount of saliva secreted, reduction in clinical symptoms of sialorrhea, death rattle intensity, or reduction in drooling intensity as measured by an objective scale such as the drooling intensity scale. RESULTS: A total of 56 studies with 2,378 patients were included in the systematic review. The underlying disease states included brain injury, amyotrophic lateral sclerosis, cerebral palsy, clozapine- and perphenazine-induced sialorrhea, Parkinson's disease, and terminal illness. The routes of atropine administration included sublingual, intravenous, subcutaneous, oral tablet or solution, and direct injection of atropine into parotid glands or at the base of the tongue. The generalized estimated equation regression models showed that sublingual administration is superior to oral and subcutaneous routes. CONCLUSION: Atropine is efficacious in managing sialorrhea in most disease states. Sublingual administration of atropine is superior to other routes of administration in reducing salivary flow in patients with sialorrhea.

Autonomic dysfunction and exercise intolerance in concussion: a scoping review.

PURPOSE: Concussion commonly results in exercise intolerance, often limiting return to activities. Improved understanding of the underlying mechanisms of post-concussive exercise intolerance could help guide mechanism-directed rehabilitation approaches. Signs of altered cardiovascular autonomic regulation-a potential contributor to exercise intolerance-have been reported following concussion, although it is not clear how these findings inform underlying mechanisms of post-concussive symptoms. Systematic summarization and synthesis of prior work is needed to best understand current evidence, allowing identification of common themes and gaps requiring further study. The purpose of this review was to (1) summarize published data linking exercise intolerance to autonomic dysfunction, and (2) summarize key findings, highlighting opportunities for future investigation. METHODS: The protocol was developed a priori, and conducted in five stages; results were collated, summarized, and reported according to PRISMA guidelines. Studies including injuries classified as mild traumatic brain injury (mTBI)/concussion, regardless of mechanism of injury, were included. Studies were required to include both autonomic and exercise intolerance testing. Exclusion criteria included confounding central or peripheral nervous system dysfunction beyond those stemming from the concussion, animal model studies, and case reports. RESULTS: A total of 3116 publications were screened; 17 were included in the final review. CONCLUSION: There was wide variability in approach to autonomic/exercise tolerance testing, as well as inclusion criteria/testing timelines, which limited comparisons across studies. The reviewed studies support current clinical suspicion of autonomic dysfunction as an important component of exercise intolerance. However, the specific mechanisms of impairment and relationship to symptoms and recovery require additional investigation.

Leaving a lasting legacy: A scoping review of ethical wills.

OBJECTIVES: Palliative care guidelines recommend an interdisciplinary approach to address patients' awareness of mortality and need for end-of-life preparation. An ethical will is a nonlegal way to address mortality by communicating a lasting and intangible legacy of values to others. The aim of this scoping review is to clarify the operationalization of ethical wills across disciplines and map the purposes and outcomes of creating an ethical will. METHODS: We followed the Joanna Briggs Institute methodology for scoping reviews. We searched 14 databases in November 2019 and January 2021 without filtering publication date or type. Two reviewers independently screened 1,948 publications. We extracted frequently used terms describing content, audience, format, purpose, and outcomes identified in ethical will creation. RESULTS: Fifty-one publications met inclusion criteria. Six (11.7%) were research articles. Twenty-four (47.1%) were lay literature published within law, estate, and financial planning. Collectively, our included studies defined an ethical will as a nonlegal way to express values, beliefs, life lessons and experiences, wisdom, love, history, hope for the future, blessings, apology, or forgiveness using any format (e.g., text, audio, video) that is meant to be shared with family, friends, or community. The most common purposes were to be remembered, address mortality, clarify life's meaning, and communicate what matters most. Creation provided opportunity to learn about self, served as a gift to both writer and recipient, and fostered generativity and sense of symbolic immortality. SIGNIFICANCE OF RESULTS: Our findings highlight interdisciplinary utilization and a lack of research of ethical wills. This review provides supportive evidence for ethical wills as a way for patients to address mortality, renew intergenerational connections, solidify self, and promote transcendence before their final days. Ethical wills have potential to be incorporated into interdisciplinary palliative care in the future to address psychological symptoms for patients anticipating the end of life.

Association between Extracranial Carotid Artery Plaque and Cognitive Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: Extracranial carotid atherosclerosis has been variably associated with dementia. Prior studies have focused on the association of carotid intima media thickness or carotid stenosis; however, there is evidence that carotid plaque may contribute to dementia, perhaps via microembolic phenomena. OBJECTIVES: We sought to evaluate the role of carotid plaque in contributing to cognitive impairment by performing a systematic review and meta-analysis to summarize the association between extracranial carotid plaque and cognitive dysfunction and dementia. METHODS: We performed a comprehensive literature search evaluating the association of extracranial carotid plaque with cognition. We included studies measuring carotid plaque on ultrasound, computed tomography, or MR and also evaluated cognition through neuropsychological testing. Meta-analyses with assessment of study heterogeneity and publication bias were performed. Results were presented in a forest plot and summarized using a random-effects model. RESULTS: After screening 1,674 studies, we included 40 for systematic review and 16 and 7 studies for two meta-analyses with a total of 19,029 and 27,325 patients, respectively. We found a positive relationship between the presence of extracranial carotid plaque and cognitive dysfunction with a pooled random-effects odds ratio (OR) of 1.83 (95% CI, 1.50, 2.24) and a pooled random-effects hazard ratio (HR) of 1.47 (95% CI, 1.15, 1.89), respectively. A sensitivity analysis of only longitudinal studies found a persistent positive association. Measures of heterogeneity showed moderate heterogeneity in each meta-analysis, respectively (I-squared statistic = 57% and 70%). CONCLUSION: The presence of extracranial carotid plaque is significantly associated with cognitive dysfunction and dementia in both cross-sectional and longitudinal analyses. After further confirmation, our results support carotid plaque being a potentially modifiable risk factor in the development of dementia.

Reactive Balance Responses After Mild Traumatic Brain Injury: A Scoping Review.

OBJECTIVE: Balance testing after concussion or mild traumatic brain injury (mTBI) can be useful in determining acute and chronic neuromuscular deficits that are unapparent from symptom scores or cognitive testing alone. Current assessments of balance do not comprehensively evaluate all 3 classes of balance: maintaining a posture; voluntary movement; and reactive postural response. Despite the utility of reactive postural responses in predicting fall risk in other balance-impaired populations, the effect of mTBI on reactive postural responses remains unclear. This review sought to (1) examine the extent and range of available research on reactive postural responses in people post-mTBI and (2) determine whether reactive postural responses (balance recovery) are affected by mTBI. DESIGN: Scoping review. METHODS: Studies were identified using MEDLINE, EMBASE, CINAHL, Cochrane Library, Dissertations and Theses Global, PsycINFO, SportDiscus, and Web of Science. Inclusion criteria were injury classified as mTBI with no confounding central or peripheral nervous system dysfunction beyond those stemming from the mTBI, quantitative measure of reactive postural response, and a discrete, externally driven perturbation was used to test reactive postural response. RESULTS: A total of 4747 publications were identified, and a total of 3 studies (5 publications) were included in the review. CONCLUSION: The limited number of studies available on this topic highlights the lack of investigation on reactive postural responses after mTBI. This review provides a new direction for balance assessments after mTBI and recommends incorporating all 3 classes of postural control in future research.

In vivo selective inhibition of TRPC6 by antagonist BI 749327 ameliorates fibrosis and dysfunction in cardiac and renal disease.

Transient receptor potential canonical type 6 (TRPC6) is a nonselective receptor-operated cation channel that regulates reactive fibrosis and growth signaling. Increased TRPC6 activity from enhanced gene expression or gain-of-function mutations contribute to cardiac and/or renal disease. Despite evidence supporting a pathophysiological role, no orally bioavailable selective TRPC6 inhibitor has yet been developed and tested in vivo in disease models. Here, we report an orally bioavailable TRPC6 antagonist (BI 749327; IC50 13 nM against mouse TRPC6, t1/2 8.5-13.5 hours) with 85- and 42-fold selectivity over the most closely related channels, TRPC3 and TRPC7. TRPC6 calcium conductance results in the stimulation of nuclear factor of activated T cells (NFAT) that triggers pathological cardiac and renal fibrosis and disease. BI 749327 suppresses NFAT activation in HEK293T cells expressing wild-type or gain-of-function TRPC6 mutants (P112Q, M132T, R175Q, R895C, and R895L) and blocks associated signaling and expression of prohypertrophic genes in isolated myocytes. In vivo, BI 749327 (30 mg/kg/day, yielding unbound trough plasma concentration ∼180 nM) improves left heart function, reduces volume/mass ratio, and blunts expression of profibrotic genes and interstitial fibrosis in mice subjected to sustained pressure overload. Additionally, BI 749327 dose dependently reduces renal fibrosis and associated gene expression in mice with unilateral ureteral obstruction. These results provide in vivo evidence of therapeutic efficacy for a selective pharmacological TRPC6 inhibitor with oral bioavailability and suitable pharmacokinetics to ameliorate cardiac and renal stress-induced disease with fibrosis.

Comparison of Human, Porcine, and Bovine Acellular Dermal Matrix in Prepectoral Breast Reconstruction: A Scoping Review.

OBJECTIVE: The aim of the study is to determine rates of overall complications and failure of prepectoral breast reconstruction between various types of acellular dermal matrices (ADMs). BACKGROUND: Implant-based breast reconstruction is the most common reconstructive technique after mastectomy in the United States. Traditionally, the reconstruction has been performed in the subpectoral plane; however, there has been an emerging interest in prepectoral reconstruction using ADM. Human (hADM), porcine (pADM), and bovine (bADM) ADMs are available for use, but little is known about the benefits and complication profiles of each for prepectoral breast reconstruction. METHODS: Studies examining complications after the use of ADM for prepectoral breast reconstruction were identified using MEDLINE, Embase, the Cochrane Library, LILACS, and the Web of Science from January 2010 to August 2021. Titles and abstracts of 1838 studies were screened, followed by full-text screening of 355 articles. Thirty-three studies were found to meet inclusion criteria. RESULTS: From the 33 studies, 6046 prepectoral reconstructions were examined. Implant loss was comparable across the different types of ADM (pADM, 4.0%; hADM, 4.0%; bADM, 3.7%). Bovine ADM had the highest rate of capsular contracture (6.1%), infection (9.0%), skin flap necrosis (8.3%), dehiscence (5.4%), and hematoma (6.1%) when compared with both hADM and pADM. Human ADM had the highest rate of postoperative seroma (5.3%), followed by pADM (4.6%) and bADM (4.5%). CONCLUSIONS: Among the prepectoral breast reconstruction studies using hADM, pADM, or bADM included in our analysis, complication profiles were similar. Bovine ADM had the highest proportion of breast complications in the following categories: capsular contracture, infection rate, skin flap necrosis, dehiscence, and hematoma. Implant loss was comparable across the cohorts. Overall, prepectoral breast reconstruction using ADM leads to relatively low complication rates with the highest rates within the bADM cohort.

Scaphotrapeziotrapezoid Arthrodesis: Systematic Review.

PURPOSE: Scaphotrapeziotrapezoid (STT) arthrodesis surgery is used for various types of wrist pathologies. The objective of our study was to perform a systematic review of complications and outcomes after STT arthrodesis. METHODS: Several major databases were used to perform a systematic literature review in order to obtain articles reporting complications and outcomes following STT arthrodesis. The primary purpose was to identify rates of nonunion and conversion to total wrist arthrodesis. Secondary outcomes included wrist range of motion, grip strength, and Disabilities of the Arm Shoulder and Hand scores. A multivariable analysis was performed to evaluate factors associated with the primary and secondary outcomes of interest. RESULTS: Out of the 854 records identified in the primary literature search, 30 studies were included in the analysis. A total of 1,429 procedures were performed for 1,404 patients. The pooled nonunion rate was 6.3% (95% CI, 3.5-9.9) and the rate of conversion to total wrist arthrodesis following the index STT was 4.2% (95% CI, 2.2-6.7). The mean pooled wrist flexion was 40.7° (95% CI, 30.8-50.5) and extension was 49.7° (95% CI, 43.5-55.8). At final follow-up, the mean pooled grip strength was 75.9% (95% CI, 69.3-82.5) of the nonsurgical contralateral hand. Compared with all other known indications, Kienbock disease had a statistically significant lower nonunion rate (14.1% vs 3.3%, respectively). Mixed-effects linear regression using patient-level data revealed that increasing age was significantly associated with complications, independent of occupation and diagnosis. CONCLUSIONS: Our study demonstrated a low failure rate and conversion to total wrist arthrodesis after STT arthrodesis and acceptable postoperative wrist range of motion and strength when compared to the contralateral hand. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Sickle cell disease and ventricular myocardial strain: A systematic review.

Cardiac disease is the primary cause of death in sickle cell disease (SCD). Cardiac abnormalities begin in childhood and progress throughout life. Right and left ventricular (RV, LV) myocardial strain are early markers of systolic dysfunction but are not well investigated among individuals with SCD. The objectives of this review were to (1) identify all published studies that have evaluated ventricular myocardial strain, (2) summarize their values, and (3) compare findings with those obtained from controls. From search results of four electronic databases-Medline, Embase, Scopus, and Web of Science-42 potential articles were identified, of which 18 articles and 17 studies met eligibility criteria for inclusion. The evaluated studies demonstrate that RV and LV myocardial strain are generally abnormal in individuals with SCD compared with controls, despite having normal ejection/shortening fraction. Myocardial strain has been inconsistently evaluated in this population and should be considered any time an echocardiogram is performed.

Borrowing trouble? The impact of a systematic review service on interlibrary loan borrowing in an academic health sciences library.

BACKGROUND: With the mandate to review all available literature in the study's inclusion parameters, systematic review projects are likely to require full-text access to a significant number of articles that are not available in a library's collection, thereby necessitating ordering content via interlibrary loan (ILL). The aim of this study is to understand what effect a systematic review service has on the copyright royalty fees accompanying ILL requests at an academic health sciences library. CASE PRESENTATION: The library created a custom report using ILLiad data to look specifically at 2018 ILL borrowing requests that were known to be part of systematic reviews. This subset of borrowing activity was then analyzed to determine its impact on the library's copyright royalty expenditures for the year. In 2018, copyright eligible borrowing requests that were known to be part of systematic reviews represented only approximately 5% of total filled requests that involved copyright eligible borrowing. However, these systematic review requests directly or indirectly caused approximately 10% of all the Spencer S. Eccles Library copyright royalty expenditures for 2018 requests. CONCLUSION: Based on the sample data set, the library's copyright royalty expenditures did increase, but the overall financial impact was modest.

Patient satisfaction with physician assistant/associate care: an international scoping review.

BACKGROUND: As the role of the physician assistant/associate grows globally, one question is: what is the level of patient satisfaction with PAs? Driven by legislative enactments to improve access to care, the PA has emerged as a ready and able medical professional to address workforce shortages. The aim of this study was to review the literature on patient satisfaction of PAs. OBJECTIVES: The basis for this review was to clarify working definitions, synthesize the evidence, and establish conceptual boundaries around the topic of patient satisfaction with PAs. The intent was to identify gaps in the literature and offer suggested undertakings for more clarification on the subject. METHODS: A scoping review was undertaken. Literature from 1968 to 2019 was searched and filtered for eligibility. Those that met criteria were categorized by date, method, geography, themes, and design. RESULTS: In total, there were 987 papers or reports that were identified through bibliography database searching. Additional articles found through snowball methodology-reviewing references (n = 11). Only English language articles emerged for analysis. From this effort, 25 articles surfaced from the filtering process for final inclusion. Most (72%) of the articles came from the United States of America, three from the United Kingdom, and one each from Ireland, the Netherlands, and New Zealand. Most articles were descriptive in nature. Some variations in methods emerged. CONCLUSION: PAs are operational in 15 nations; their acceptance appears successful and satisfaction with their care largely indistinguishable from physicians. Findings from this analysis highlight one theory that when patient's needs are met, satisfaction is high regardless of the medical provider. Areas for further research are identified.

Cross-Leg Flaps for Lower Extremity Salvage: A Scoping Review.

BACKGROUND: Lower extremity trauma with soft tissue loss presents a challenge to the reconstructive surgeon. Cross-leg flaps, first described by Hamilton in 1854, are still used to salvage traumatized lower extremities in patients not suitable for free tissue transfer, or those who are receiving care in locations with limited resources. METHODS: A scoping review methodology was used to examine the evidence supporting the use of cross-leg flaps in modern healthcare. RESULTS: There have been 409 cases of cross-leg flaps reported in the modern literature, with the majority of flap cases occurring outside the United States in Turkey, India, and Japan. The most common indication was trauma, mentioned in 93.2% of patients (n = 353 of 379), and anatomic limitation, including inadequate vasculature, was the main reason for not performing free tissue transfer (52.8% of patients; n = 170 of 322). The majority are cross-leg fasciocutaneous flaps (85.8%, n = 273 of 318), based off the posterior tibial artery (27.5%, n = 50 of 182) and peroneal artery (26.9%, n = 49 of 182) and, covering defects of the distal third of the leg (55.5%, n = 151 of 272), or the foot (27.9%, n = 76 of 272). The pedicles are typically divided at 3 weeks (mean 20.9 days) after external fixation is used as the immobilization method (57.7%, n = 184 of 319). Flap survival was 100% across all publications except one (n = 349 of 350 patients), making cross-leg flaps a robust and reliable reconstructive option. CONCLUSION: In resource-limited environments or in patients who are unsuitable for microvascular free tissue transfer, the cross-leg flap remains an impactful and reliable option for limb salvage.

Scoping Review and Meta-analysis of Hyperbaric Oxygen Therapy for Radiation-Induced Hemorrhagic Cystitis.

PURPOSE OF REVIEW: To critically review and summarize existing literature assessing the effectiveness of hyperbaric oxygen therapy (HBOT) for the treatment of radiation-induced urologic injury. RECENT FINDINGS: Though 5 of the included 13 studies were published in the last 2-3 years, the only randomized controlled study was performed in 2012. Recent studies have confirmed the safety and efficacy of HBOT as well as identified risk factors for success vs. failure of HBOT for hemorrhagic radiation cystitis (HRC). Of the 602 patients that received HBOT for HRC, 84% had a partial or complete resolution. In the 7 studies that utilized RTOG/EORTC, 75% of patients saw an improvement in hematuria of at least one grade (out of possible 5 total). Of the 499 patients with documented follow-up, 14% experienced recurrence, with a median time to recurrence of 10 months (6 to 16.5 months).

Graduate Medical Education in Pathology: A Scoping Review.

CONTEXT.­: Pathologists have produced a substantial body of literature on graduate medical education (GME). However, this body of literature is diverse and has not yet been characterized. OBJECTIVE.­: To chart the concepts, research methods, and publication patterns of studies on GME in pathology. DATA SOURCES.­: This was a systematic scoping review covering all literature produced since 1980 in the PubMed and Embase databases. CONCLUSIONS.­: Research on GME in pathology is evenly dispersed across educational topics. This body of literature would benefit from research based on theory, stronger study designs, and studies that can provide evidence to support decisions on educational policies.

Incorporating social determinants of health into transmission modeling of COVID-19 vaccine in the US: a scoping review.

During COVID-19 in the US, social determinants of health (SDH) have driven health disparities. However, the use of SDH in COVID-19 vaccine modeling is unclear. This review aimed to summarize the current landscape of incorporating SDH into COVID-19 vaccine transmission modeling in the US. Medline and Embase were searched up to October 2022. We included studies that used transmission modeling to assess the effects of COVID-19 vaccine strategies in the US. Studies' characteristics, factors incorporated into models, and approaches to incorporate these factors were extracted. Ninety-two studies were included. Of these, 11 studies incorporated SDH factors (alone or combined with demographic factors). Various sets of SDH factors were integrated, with occupation being the most common (8 studies), followed by geographical location (5 studies). The results show that few studies incorporate SDHs into their models, highlighting the need for research on SDH impact and approaches to incorporating SDH into modeling. Funding: This research was funded by the Centers for Disease Control and Prevention (CDC).

Evaluation of phosphatidylinositol-4-kinase IIIα as a hepatitis C virus drug target.

Phosphatidylinositol-4-kinase IIIα (PI4KIIIα) is an essential host cell factor for hepatitis C virus (HCV) replication. An N-terminally truncated 130-kDa form was used to reconstitute an in vitro biochemical lipid kinase assay that was optimized for small-molecule compound screening and identified potent and specific inhibitors. Cell culture studies with PI4KIIIα inhibitors demonstrated that the kinase activity was essential for HCV RNA replication. Two PI4KIIIα inhibitors were used to select cell lines harboring HCV replicon mutants with a 20-fold loss in sensitivity to the compounds. Reverse genetic mapping isolated an NS4B-NS5A segment that rescued HCV RNA replication in PIK4IIIα-deficient cells. HCV RNA replication occurs on specialized membranous webs, and this study with PIK4IIIα inhibitor-resistant mutants provides a genetic link between NS4B/NS5A functions and PI4-phosphate lipid metabolism. A comprehensive assessment of PI4KIIIα as a drug target included its evaluation for pharmacologic intervention in vivo through conditional transgenic murine lines that mimic target-specific inhibition in adult mice. Homozygotes that induce a knockout of the kinase domain or knock in a single amino acid substitution, kinase-defective PI4KIIIα, displayed a lethal phenotype with a fairly widespread mucosal epithelial degeneration of the gastrointestinal tract. This essential host physiologic role raises doubt about the pursuit of PI4KIIIα inhibitors for treatment of chronic HCV infection.

Quality improvement approaches to heparin-induced thrombocytopenia: a scoping review.

Background: Heparin-induced thrombocytopenia (HIT) is a relatively uncommon condition characterized by 2 exceedingly common phenomena in hospitalized patients: thrombocytopenia and heparin exposure. Consequently, HIT is frequently overdiagnosed and inappropriately treated. These issues are the focus of many quality improvement (QI) initiatives. Objectives: In this scoping review, we identified and characterized all published QI studies on improving the diagnosis and management of HIT. Methods: We conducted a systematic literature search through April 2022 for studies reporting on QI interventions regarding the diagnosis, treatment, and/or prevention of HIT. Results: Thirty studies were included in the final review. Studies were separated into 5 groups based on the focus of the interventions: increasing HIT recognition, reducing HIT incidence, reducing HIT overdiagnosis, promoting safer HIT management, and creating HIT task forces. Nine studies focused on the implementation of 4Ts score calculator into electronic medical record orders for HIT testing, while only 1 evaluated the impact of reducing unfractionated heparin use in favor of low-molecular-weight heparin. Six studies focused on the implementation of direct thrombin inhibitor management protocols, while none evaluated the use of alternative anticoagulants in HIT management. Conclusion: The bulk of published HIT QI research focused on reducing overdiagnosis and promoting safer direct thrombin inhibitor therapy, while minimal attention has been devoted to HIT prevention and the use of evidence-based alternative HIT therapies.

Exploring the intersections of college student poverty, grief, and racial/ethnic identity: a scoping review protocol.

BACKGROUND: College students who experience the negative impact of poverty, such as food, financial, and housing insecurity, are at higher risk for poor academic performance. One recent study examined grief in a college student sample and found students with a diverse racial or ethnic background were more likely to experience prolonged grief disorder, however, did not examine poverty in their sample. To date, no known reviews have examined poverty by racial and ethnic identity and the experience of grief due to the death of a family member or friend, and no reviews have examined how these three factors relate to interventions designed to support student academic performance and degree completion. METHODS: Our aim is to map the primary literature reporting on college students of any age who identify or are identified as non-white racial or ethnic groups who experience poverty and grief due to the death of a family member or friend. The mapping strategy includes extracting the various types of interventional support of academic performance and degree completion delivered from campus or community services in any geographic setting worldwide. We will conduct our scoping review with guidance from the latest version of the JBI Manual for Evidence Synthesis. Utilizing the framework as outlined by Arksey and O'Malley, we will conduct our scoping review with Arksey's five stages: (1) identifying the research question, (2) identifying relevant studies, (3) study selection, (4) charting the data, and (5) collating, summarizing, and reporting the results. For transparency and reproducibility, we will adhere to the PRISMA reporting guidelines. DISCUSSION: The purpose of this scoping review is to map the primary literature reporting college students, regardless of their age, who belong to non-white racial or ethnic groups and face poverty and grief resulting from the loss of a family member or friend. This analysis includes mapping the various types of intervention and support available both on and off campus, in any global setting, with the aim of enhancing academic performance and facilitating degree completion. The results of this review may inform the further research needed in this area to help prevent poor academic performance and dropout for many vulnerable college students. The results may be of value, particularly to college administrators developing prevention and interventional programs to support college student success. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework ( https://osf.io/enuwt ).