Information For Clinical Management Research Articles

How does level of personality functioning inform clinical management and treatment? Implications for ICD-11 classification of personality disorder severity.

The International Classification of Diseases, 11th Edition (ICD-11) classifies personality disturbance according to levels of severity. This article reviews the literature on levels of personality functioning in relation to clinical management and treatment, and proposes how these findings apply to the ICD-11 classification of personality disorders. Findings were primarily derived from studies using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) Level of Personality Functioning Scale (LPFS), Kernberg's Level of Personality Organization, and the general P-factor of personality disorder. Severity of personality dysfunction is related to treatment outcome, risk of dropout, therapeutic alliance, readiness for treatment, risk of harm to self or others, risk of dissociation and psychotic-like breaks, coherence in narrative identity, reflective functioning, and epistemic trust. The overall level of personality disorder severity indicates risk of negative outcomes and may be used as decision tool for 'personalized medicine' and required treatment intensity (e.g., strength of alliance and the need for establishing epistemic trust). Beyond the ICD-11 guidelines for determining personality disorder severity, these implications also apply to practitioners using comparable frameworks such as the DSM-5 LPFS and Kernberg's Level of Personality Organization. Future research should focus on the interaction of severity with trait qualifiers in relation to clinical management.

1718. Respiratory Syncytial Virus (RSV) Surveillance in the Department of Veterans Affairs (VA), 2010-2018

BackgroundRespiratory Syncytial Virus (RSV) is an increasingly recognized cause of acute respiratory illness in older adults, leading to an estimated 177,000 hospitalizations and 14,000 deaths each year in the US. In adult populations, diagnostic testing for RSV has historically been underutilized. Herein, we examine national trends in RSV testing and infection across the Veterans Affairs (VA) healthcare system.MethodsElectronic RSV laboratory testing results, ICD-coded hospitalizations and outpatient encounters were obtained from VA’s Praedico Surveillance System (1/1/2010-12/31/2018). Patients were reviewed for positive results, repeat testing, and demographics. Antibody tests were excluded.ResultsA total of 102,251 RSV results were included. Overall, 4,372 (4.3%) specimens from 4,263 unique individuals were positive with a median age of 67 years (range 0-101) and 90% were male. 1,511 individuals (35.4%) also had an RSV-coded hospitalization. RSV type was specified for only 7.8% of positives (Table). During 2010-2018 there were 2,522 RSV-coded hospitalizations (median length of stay = 4 days) among 2,444 unique individuals, which included 413 ICU stays (16.4%) and 98 deaths (3.9%) during the RSV-coded hospitalization. Approximately 78% of RSV-coded hospitalizations within VA (excluding all non-VA hospitalizations) had a documented positive test result. A greater than 15-fold increase in RSV tests performed, hospitalizations and outpatient encounters was observed from 2010-2018, although the percent testing positive remained relatively stable (Figure, Table).Figure. Testing for Respiratory Syncytial Virus (RSV), Department of Veterans Affairs, 2010-2018. Table. Select RSV Surveillance Metrics, Department of Veterans Affairs, 2010-2018 ConclusionRSV testing and identification of patients with RSV infection increased dramatically during the time period analyzed, likely due to increased availability of PCR-based multi-pathogen panels and duplex assays. While the percentage of tests positive for RSV remained relatively stable, the rise in coded hospitalizations may be due to increased testing for RSV among hospitalized Veterans with severe respiratory infections. These surveillance data may allow for further characterization of RSV disease burden estimates which can help inform clinical management and development of interventions for adults, such as vaccines and antiviral therapies.Disclosures All Authors: No reported disclosures

Molecular Subtypes of Breast Cancer: A Review for Breast Radiologists.

Gene expression profiling has reshaped our understanding of breast cancer by identifying four molecular subtypes: (1) luminal A, (2) luminal B, (3) human epidermal growth factor receptor 2 (HER2)-enriched, and (4) basal-like, which have critical differences in incidence, response to treatment, disease progression, survival, and imaging features. Luminal tumors are most common (60%-70%), characterized by estrogen receptor (ER) expression. Luminal A tumors have the best prognosis of all subtypes, whereas patients with luminal B tumors have significantly shorter overall and disease-free survival. Distinguishing between these tumors is important because luminal B tumors require more aggressive treatment. Both commonly present as irregular masses without associated calcifications at mammography; however, luminal B tumors more commonly demonstrate axillary involvement at diagnosis. HER2-enriched tumors are characterized by overexpression of the HER2 oncogene and low-to-absent ER expression. HER2+ disease carries a poor prognosis, but the development of anti-HER2 therapies has greatly improved outcomes for women with HER2+ breast cancer. HER2+ tumors most commonly present as spiculated masses with pleomorphic calcifications or as calcifications alone. Basal-like cancers (15% of all invasive breast cancers) predominate among "triple negative" cancers, which lack ER, progesterone receptor (PR), and HER2 expression. Basal-like cancers are frequently high-grade, large at diagnosis, with high rates of recurrence. Although imaging commonly reveals irregular masses with ill-defined or spiculated margins, some circumscribed basal-like tumors can be mistaken for benign lesions. Incorporating biomarker data (histologic grade, ER/PR/HER2 status, and multigene assays) into classic anatomic tumor, node, metastasis (TNM) staging can better inform clinical management of this heterogeneous disease.

Abstract PR-007: Single-nucleus and spatial transcriptomics of archival pancreatic ductal adenocarcinoma reveals multi-compartment reprogramming after neoadjuvant treatment

Abstract Molecular subtyping of pancreatic ductal adenocarcinoma (PDAC) remains in its nascent stages and does not currently inform clinical management or therapeutic development. Previously identified bulk expression subtypes in the untreated setting were influenced by contaminating stroma whereas single cell RNA-seq (scRNA-seq) of fresh tumors under-represented key cell types. Two consensus subtypes have arisen from these prior efforts: (1) classical-pancreatic, encompassing a spectrum of pancreatic lineage precursors, and (2) basal-like/squamous/quasi-mesenchymal, characterized by loss of endodermal identity and aberrations in chromatin modifiers. Basal-like tumors were associated with poorer responses to chemotherapy and worse survival in the metastatic setting but attempts to refine this binary classification have failed to further stratify patient survival. Recent clinical trials have supported the increasing adoption of neoadjuvant therapy to aggressively address the risk of micro-metastatic spread and to circumvent concerns of treatment tolerance in the postoperative setting. There is an urgent need to understand how preoperative treatment reprograms residual tumor cells to identify additional therapeutic vulnerabilities that can be exploited in combination with neoadjuvant CRT. Here, we developed a robust single-nucleus RNA-seq (snRNA-seq) technique for frozen archival PDAC specimens and used it to study both untreated tumors (n = 15) and those that received neoadjuvant CRT (n = 11). Gene expression programs learned across malignant cell and fibroblast profiles uncovered a clinically relevant molecular taxonomy with improved prognostic stratification (median survival: 11.2 months in highest risk group to 44.7 months in lowest risk group) compared to prior classifications. Moreover, in the neoadjuvant treatment context, there was lower expression of classical-like phenotypes in malignant cells in favor of basal-like phenotypes associated with TNF-NFkB and interferon signaling as well as the presence of novel acinar and neuroendocrine classical-like states, which may be more resilient to cytotoxic treatment. These results suggest that differentiated endodermal phenotypes are only prevalent enough to be detected under treatment selection pressure and when observed in treatment-naïve bulk studies, may reflect normal cell contamination. Spatially-resolved transcriptomics revealed an association between malignant cells expressing basal-like programs and higher immune infiltration with increased lymphocytic content, whereas those exhibiting classical-like programs were linked to sparser macrophage-predominant microniches, perhaps pointing to distinct therapeutic susceptibilities. Our refined molecular taxonomy and spatial resolution may help advance precision oncology in PDAC through informative stratification in clinical trials and insights into differential therapeutic targeting leveraging the immune system. Citation Format: William L. Hwang, Karthik A. Jagadeesh, Jimmy A. Guo, Hannah I. Hoffman, Eugene Drokhlyansky, Nicholas Van Wittenberghe, Samouil Farhi, Denis Schapiro, Jason Reeves, Daniel R. Zollinger, George Eng, Jason M. Schenkel, William A. Freed-Pastor, Clifton Rodrigues, Domenic Abbondanza, Debora Ciprani, Jennifer Y. Wo, Theodore S. Hong, Andrew J. Aguirre, Orit Rozenblatt-Rosen, Mari Mino-Kenudson, Carlos Fernandez-del Castillo, Andrew S. Liss, Tyler E. Jacks, Aviv Regev. Single-nucleus and spatial transcriptomics of archival pancreatic ductal adenocarcinoma reveals multi-compartment reprogramming after neoadjuvant treatment [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PR-007.

Psychometric Testing of the Turkish Version of the Technology Informatics Guiding Educational Reform-Based Assessment of Nursing Informatics Competencies Tool.

Nursing informatics competencies are vital to benefit from information technologies to improve patient outcomes. It is essential to use a reliable and valid instrument for evaluating competencies. The Technology Informatics Guiding Educational Reform-Based Assessment of Nursing Informatics Competencies Tool is a valid and reliable tool used to evaluate nursing informatics competencies in nurses who primarily speak English. This cross-sectional research aimed to evaluate the psychometric properties of a Turkish version of the instrument. Data were collected from 518 nurses working in two university hospitals in Istanbul, Turkey. The tool was translated into Turkish, validated by professional experts, back-translated, and analyzed. Thirty nurses completed the tool twice for test-retest reliability. A four-factor structure identified in exploratory factor analysis (73.64% of the total variance with all items loaded >0.40 [0.44-0.88] for each factor). Cronbach's α reliability coefficients of the subsets were .98 for basic computer skills, .97 for clinical information management, and .98 for information literacy. The total item correlations for subsets were between 0.57 and 0.84. The Turkish version of the Technology Informatics Guiding Educational Reform-Based Assessment of Nursing Informatics Competencies demonstrated sufficient reliability and validity for assessing nursing informatics competencies within Turkish culture.

Clinical Efficacy of Convalescent Plasma Therapy on Treating COVID-19 Patients: Evidence from Matched Study and a Meta-Analysis

Background: COVID-19 has infected tens of millions of people worldwide since its pandemic. CPT is one of the promising treatment methods and is favored by more and more researchers. However, the clinical efficacy and safety of CPT in COVID-19 remains unclear.Methods: We performed a matched control study by PSM analysis (including 163 cases with CPT and 163 controls with the standard treatment) and meta-analysis (including 498 cases and 557 controls) estimate the clinical efficacy and security of CPT and COVID-19, which will help inform clinical management of COVID-19 infection.Results: We found that days of hospital stay in case with CPT groups were significantly higher than matched control group (PConclusions: This study is the first to systematically review and meta-analysis the efficacy and safety of CPT in patients with COVID-19 in the largest sample size. Our results showed that CPT could significantly reduce the mortality rate of COVID-19 patients, and there was no significant increase in the incidence of adverse events. These data provide evidence favoring the efficacy and safety of CPT as a therapeutic agent in COVID-19 patients and provide comprehensive reference for COVID-19 treatment.Funding Statement: This work was supported by Scientific Research Project of Jiangsu Commission of Health (H2019065), Key Foundation of Wuhan Huoshenshan Hospital (2020[18]), Key Research & Development Program of Jiangsu Province (BE2018713), Medical Innovation Project of Logistics Service (18JS005).Declaration of Interests: The authors declare no conflicts of interest with this work.Ethics Approval Statement: The authors were approved by the ethics committee of Huoshenshan hospital, and were conducted in accordance with the tenets of the Declaration of Helsinki and its amendments. All participants provided written informed consent for the collection of samples and their subsequent analysis.

Chest radiograph at admission predicts early intubation among inpatient COVID-19 patients.

ObjectiveThe 2019 Coronavirus (COVID-19) results in a wide range of clinical severity and there remains a need for prognostic tools which identify patients at risk of rapid deterioration and who require critical care. Chest radiography (CXR) is routinely obtained at admission of COVID-19 patients. However, little is known regarding correlates between CXR severity and time to intubation. We hypothesize that the degree of opacification on CXR at time of admission independently predicts need and time to intubation.MethodsIn this retrospective cohort study, we reviewed COVID-19 patients who were admitted to an urban medical center during March 2020 that had a CXR performed on the day of admission. CXRs were divided into 12 lung zones and were assessed by two blinded thoracic radiologists. A COVID-19 opacification rating score (CORS) was generated by assigning one point for each lung zone in which an opacity was observed. Underlying comorbidities were abstracted and assessed for association.ResultsOne hundred forty patients were included in this study and 47 (34%) patients required intubation during the admission. Patients with CORS ≥ 6 demonstrated significantly higher rates of early intubation within 48 h of admission and during the hospital stay (ORs 24 h, 19.8, p < 0.001; 48 h, 28.1, p < 0.001; intubation during hospital stay, 6.1, p < 0.0001). There was no significant correlation between CORS ≥ 6 and age, sex, BMI, or any underlying cardiac or pulmonary comorbidities.ConclusionsCORS ≥ 6 at the time of admission predicts need for intubation, with significant increases in intubation at 24 and 48 h, independent of comorbidities.Key Points • Chest radiography at the time of admission independently predicts time to intubation within 48 h and during the hospital stay in COVID-19 patients. • More opacities on chest radiography are associated with several fold increases in early mechanical ventilation among COVID-19 patients. • Chest radiography is useful in identifying COVID-19 patients whom may rapidly deteriorate and help inform clinical management as well as hospital bed and ventilation allocation. Electronic supplementary materialThe online version of this article (10.1007/s00330-020-07354-y) contains supplementary material, which is available to authorized users.

Comparison of low-molecular-weight heparins in thromboprophylaxis of major orthopaedic surgery – randomized, prospective pilot study

AimTo compare the clinical effectiveness of the two most commonly used LMWHs, dalteparin (DALT) and enoxaparin (ENOX), in thromboprophylaxis of elective total hip replacement (THR) or total knee replacement (TKR).Material and methodsTo the prospective, randomized study were included 66 adult patients qualified to undergo THR or TKR (age 63 ± 12 years, 44 women). The patients were randomized to daily in-hospital subcutaneous prophylaxis with 5,000 I.U. of DALT or 40 mg of enoxaparin. Clinical and laboratory data were collected before surgery, and on 1st and 5th days after surgery.ResultsThirty-four patients were randomized to prophylaxis with ENOX and 32 with DALT. The groups did not differ significantly in age, sex, creatinine and most of the laboratory parameters. The compared groups had similar surgical parameters, but more patients in the ENOX group received red blood cell infusion (17(50%) vs 8(25%); p < 0.05). The Lee–White coagulation time mildly decreased in ENOX and DALT following the surgery (p = ns). There was a shortening of Duke’s bleeding time in DALT after the surgery and it became significantly quicker than that in ENOX on Day 5 (p = 0.03).ConclusionThe observed difference in Duke’s bleeding time and exceeding blood loss during the surgery on the enoxaparin demands confirmation, as it can be important information for clinical management.

Beyond the Brain: Systematic Review of Extracerebral Phenotypes Associated With Monogenic Cerebral Small Vessel Disease.

An important minority of cerebral small vessel disease (cSVD) is monogenic. Many monogenic cSVD genes are recognized to be associated with extracerebral phenotypes. We assessed the frequency of these phenotypes in existing literature. We performed a systematic review following the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), searching Medline/Embase for publications describing individuals with pathogenic variants in COL4A1/2, TREX1, HTRA1, ADA2, and CTSA genes (PROSPERO 74804). We included any publication reporting on ≥1 individual with a pathogenic variant and their clinically relevant phenotype. We extracted individuals' characteristics and information about associated extracerebral phenotypes and stroke/transient ischemic attack. We noted any novel extracerebral phenotypes and looked for shared phenotypes between monogenic cSVDs. After screening 6048 publications, we included 96 COL4A1 (350 individuals), 32 TREX1 (115 individuals), 43 HTRA1 (38 homozygous/61 heterozygous individuals), 16 COL4A2 (37 individuals), 119 ADA2 (209 individuals), and 3 CTSA (14 individuals) publications. The majority of individuals originated from Europe/North America, except for HTRA1, where most were from Asia. Age varied widely, ADA2 individuals being youngest and heterozygous HTRA1/CTSA individuals oldest. Sex distribution appeared equal. Extracerebral phenotypes were common: 14% to 100% of individuals with a pathogenic variant manifested at least one extracerebral phenotype (14% COL4A2, 43% HTRA1 heterozygotes, 47% COL4A1, 57% TREX1, 91% ADA2, 94% HTRA1 homozygotes, and 100% CTSA individuals). Indeed, for 4 of 7 genes, an extracerebral phenotype was observed more frequently than stroke/transient ischemic attack. Ocular, renal, hepatic, muscle, and hematologic systems were each involved in more than one monogenic cSVD. Extracerebral phenotypes are common in monogenic cSVD with extracerebral system involvement shared between genes. However, inherent biases in the existing literature mean that further data from large-scale population-based longitudinal studies collecting health outcomes in a systematic unbiased way is warranted. The emerging knowledge will help to select patients for testing, inform clinical management, and provide further insights into the underlying mechanisms of cSVD.

P52 A baseline review of the activity of the PICU pharmacists using electronically captured data

AimTo date there are no metrics for the clinical pharmacist service to PICU. It is accepted that use of a Clinical Information Management System (CIMS) has a role in medication safety,1 however there are few studies that review the information potential of a CIMS for collecting pharmacist activity.2MethodAdditional fields and custom reports were configured in the CIMS to enable PICU pharmacists to record their activity in the following areas:Medicines reconciliation within 72 hours of admission to PICUDischarge kardex reviewAnalgesia and sedation (A&amp;S) reviewClinical pharmacy reviewOther interventions &amp; medication error reporting continued as per normal practice. Data was analysed using Microsoft Excel®.ResultsComplete data was available from July 2017 to end of 2018.There were 1274 medicines reconciliations by a pharmacist within 72 hours of admission (78% admissions). 14% of discharge kardexes had been reviewed prior to discharge to the ward. There was an average of 190 pharmacy reviews per 100 bed days. A total of 780 Pharmacist A&amp;S Plans were documented by the clinical pharmacists – an average of 2 per working day, and 48% of admissions.Comparisons between each six month period showed a significant increase in the number of pharmacists medicines reconciliations (p&lt;0.001). No other differences were found.ConclusionThis study has shown that electronic tracking of pharmacist ward activity is possible. It has the potential to demonstrate compliance with external or internal standards and audits. This data continues to be collected, and therefore these results will be used as a baseline to compare future activity. The findings of this study may encourage other units to replicate, providing data that can be used for comparison. Further configuration of the CIMS to capture other metrics such as TDM, and document discrepancies in medicines reconciliation is planned.ReferencesForni A, Chu H, Fanikos J. Technology Utilization to Prevent Medication Errors. Current Drug Safety. 2010;5:13–18.Nelson S, Poikonen J, Reese T, El Halta D, Weir C. The pharmacist and the EHR. Journal of the American Medical Informatics Association. 2016;24:193–197.Health and Information Quality Authority. Guidance for health and social care providers; Principles of good practice in medication reconciliation. Dublin: HIQA; 2014

The clinical, histologic, and genotypic spectrum of SEPN1-related myopathy: A case series.

To clarify the prevalence, long-term natural history, and severity determinants of SEPN1-related myopathy (SEPN1-RM), we analyzed a large international case series. Retrospective clinical, histologic, and genetic analysis of 132 pediatric and adult patients (2-58 years) followed up for several decades. The clinical phenotype was marked by severe axial muscle weakness, spinal rigidity, and scoliosis (86.1%, from 8.9 ± 4 years), with relatively preserved limb strength and previously unreported ophthalmoparesis in severe cases. All patients developed respiratory failure (from 10.1±6 years), 81.7% requiring ventilation while ambulant. Histopathologically, 79 muscle biopsies showed large variability, partly determined by site of biopsy and age. Multi-minicores were the most common lesion (59.5%), often associated with mild dystrophic features and occasionally with eosinophilic inclusions. Identification of 65 SEPN1 mutations, including 32 novel ones and the first pathogenic copy number variation, unveiled exon 1 as the main mutational hotspot and revealed the first genotype-phenotype correlations, bi-allelic null mutations being significantly associated with disease severity (p = 0.017). SEPN1-RM was more severe and progressive than previously thought, leading to loss of ambulation in 10% of cases, systematic functional decline from the end of the third decade, and reduced lifespan even in mild cases. The main prognosis determinants were scoliosis/respiratory management, SEPN1 mutations, and body mass abnormalities, which correlated with disease severity. We propose a set of severity criteria, provide quantitative data for outcome identification, and establish a need for age stratification. Our results inform clinical practice, improving diagnosis and management, and represent a major breakthrough for clinical trial readiness in this not so rare disease.

Prospective performance of clear cell likelihood scores (ccLS) in renal masses evaluated with multiparametric magnetic resonance imaging.

Solid renal masses have unknown malignant potential with commonly utilized imaging. Biopsy can offer a diagnosis of cancer but has a high non-diagnostic rate and complications. Reported use of multiparametric magnetic resonance imaging (mpMRI) to diagnose aggressive histology (i.e., clear cell renal cell carcinoma (ccRCC)) via a clear cell likelihood score (ccLS) was based on retrospective review of cT1a tumors. We aim to retrospectively assess the diagnostic performance of ccLS prospectively assigned to renal masses of all stages evaluated with mpMRI prior to histopathologic evaluation. In this retrospective cohort study from June 2016 to November 2019, 434 patients with 454 renal masses from 2 institutions with heterogenous patient populations underwent mpMRI with prospective ccLS assignment and had pathologic diagnosis. ccLS performance was assessed by contingency table analysis. The association between ccLS and ccRCC was assessed with logistic regression. Mean age and tumor size were 60 ± 13years and 5.4 ± 3.8cm. Characteristics were similar between institutions except for patient age and race (both p < 0.001) and lesion laterality and histology (both p = 0.04). The PPV of ccLS increased with each increment in ccLS (ccLS1 5% [3/55], ccLS2 6% [3/47], ccLS3 35% [20/57], ccLS4 78% [85/109], ccLS5 93% [173/186]). Pooled analysis for ccRCC diagnosis revealed sensitivity 91% (258/284), PPV 87% (258/295) for ccLS ≥ 4, and specificity 56% (96/170), NPV 94% (96/102) for ccLS ≤ 2. Diagnostic performance was similar between institutions. We confirm the optimal diagnostic performance of mpMRI to identify ccRCC in all clinical stages. High PPV and NPV of ccLS can help inform clinical management decision-making. • The positive predictive value of the clear cell likelihood score (ccLS) for detecting clear cell renal cell carcinoma was 5% (ccLS1), 6% (ccLS2), 35% (ccLS3), 78% (ccLS4), and 93% (ccLS5). Sensitivity of ccLS ≥ 4 and specificity of ccLS ≤ 2 were 91% and 56%, respectively. • When controlling for confounding variables, ccLS is an independent risk factor for identifying clear cell renal cell carcinoma. • Utilization of the ccLS can help guide clinical care, including the decision for renal mass biopsy, reducing the morbidity and risk to patients.

A Novel Ten-Gene Signature Predicting Prognosis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has a dismal long-term outcome. We aimed to construct a multi-gene model for prognosis prediction to inform HCC management. The cancer-specific differentially expressed genes (DEGs) were identified using RNA-seq data of paired tumor and normal tissue. A prognostic signature was built by LASSO regression analysis. Gene set enrichment analysis (GSEA) was performed to further understand the underlying molecular mechanisms. A 10-gene signature was constructed to stratify the TCGA and ICGC cohorts into high- and low-risk groups where prognosis was significantly worse in the high-risk group across cohorts (P < 0.001 for all). The 10-gene signature outperformed all previously reported models for both C-index and the AUCs for 1-, 3-, 5-year survival prediction (C-index, 0.84 vs 0.67 to 0.73; AUCs for 1-, 3- and 5-year OS, 0.84 vs 0.68 to 0.79, 0.81 to 0.68 to 0.80, and 0.85 vs 0.67 to 0.78, respectively). Multivariate Cox regression analysis revealed risk group and tumor stage to be independent predictors of survival in HCC. A nomogram incorporating tumor stage and signature-based risk group showed better performance for 1- and 3-year survival than for 5-year survival. GSEA revealed enrichment of pathways related to cell cycle regulation among high-risk samples and metabolic processes in the low-risk group. Our 10-gene model is robust for prognosis prediction and may help inform clinical management of HCC.

Neurological Involvement in COVID-19 and Potential Mechanisms: A Review.

As the current understanding of COVID-19 continues to evolve, a synthesis of the literature on the neurological impact of this novel virus may help inform clinical management and highlight potentially important avenues of investigation. Additionally, understanding the potential mechanisms of neurologic injury may guide efforts to better detect and ameliorate these complications. In this review, we synthesize a range of clinical observations and initial case series describing potential neurologic manifestations of COVID-19 and place these observations in the context of coronavirus neuro-pathophysiology as it may relate to SARS-CoV-2 infection. Reported nervous system manifestations range from anosmia and ageusia, to cerebral hemorrhage and infarction. While the volume of COVID-19-related case studies continues to grow, previous work examining related viruses suggests potential mechanisms through which the novel coronavirus may impact the CNS and result in neurological complications. Namely, animal studies examining the SARS-CoV have implicated the angiotensin-converting-enzyme-2 receptor as a mediator of coronavirus-related neuronal damage and have shown that SARS-CoV can infect cerebrovascular endothelium and brain parenchyma, the latter predominantly in the medial temporal lobe, resulting in apoptosis and necrosis. Human postmortem brain studies indicate that human coronavirus variants and SARS-CoV can infect neurons and glia, implying SARS-CoV-2 may have similar neurovirulence. Additionally, studies have demonstrated an increase in cytokine serum levels as a result of SARS-CoV infection, consistent with the notion that cytokine overproduction and toxicity may be a relevant potential mechanism of neurologic injury, paralleling a known pathway of pulmonary injury. We also discuss evidence that suggests that SARS-CoV-2 may be a vasculotropic and neurotropic virus. Early reports suggest COVID-19 may be associated with severe neurologic complications, and several plausible mechanisms exist to account for these observations. A heightened awareness of the potential for neurologic involvement and further investigation into the relevant pathophysiology will be necessary to understand and ultimately mitigate SARS-CoV-2-associated neurologic injury.

Do primary and secondary care doctors have a different experience and perception of cross-level clinical coordination? Results of a cross-sectional study in the Catalan National Health System (Spain)

BackgroundClinical coordination across care levels is a priority for health systems around the world, especially for those based on primary health care. The aim of this study is to analyse the degree of clinical information and clinical management coordination across healthcare levels in the Catalan national health system experienced by primary (PC) and secondary care (SC) doctors and explore the associated factors.MethodsCross-sectional study based on an online survey using the self-administered questionnaire COORDENA-CAT. Data collection: October–December 2017. Study population: PC and SC (acute and long term) doctors of the Catalan national health system. Participation rate was 21%, with a sample of 3308 doctors. Outcome variables: cross-level clinical information coordination, clinical management coordination, and perception of cross-level coordination within the area. Explanatory variables: socio-demographic, employment characteristics, attitude towards job, type of area (according to type of hospital and management), interactional factors, organizational factors and knowledge of existing coordination mechanisms. Stratification variable: level of care. Descriptive and multivariate analysis by logistic regression.ResultsThe degree of clinical coordination experienced across levels of care was high for both PC and SC doctors, although PC doctors experienced greater exchange and use of information and SC doctors experienced greater consistency of care. However, only 32.13% of PC and 35.72% of SC doctors found that patient care was coordinated across care levels within their area. In both levels of care, knowing the doctors of the other level, working in an area where the same entity manages SC and majority of PC, and holding joint clinical case conferences were factors positively associated with perceiving high levels of clinical coordination. Other associated factors were specific to the care level, such as being informed of a patient’s discharge from hospital for PC doctors, or trusting in the clinical skills of the other care level for SC doctors.ConclusionsInteractional and organizational factors are positively associated with perceiving high levels of clinical coordination. Introducing policies to enhance such factors can foster clinical coordination between different health care levels. The COORDENA questionnaire allows us to identify fields for improvement in clinical coordination.

Quantitative assessment of renal allograft pathologic changes: comparisons of mono-exponential and bi-exponential models using diffusion-weighted imaging.

Diffusion-weighted imaging (DWI) can noninvasively assess renal allograft pathologic changes that provide useful information for clinical management and prognostication. However, it is still unknown whether the bi-exponential model analysis of DWI signals is superior to that of the mono-exponential model. Pathologic and DWI data from a total of 47 allografts were prospectively collected and analyzed. Kidney transplant interstitial fibrosis was quantified digitally. The severity of acute and chronic pathologic changes was semi-quantified by calculating the acute composite scores (ACS) and chronic composite score (CCS). Mono-exponential total apparent diffusion coefficient (ADCT), and the bi-exponential parameters of true diffusion (D) and perfusion fraction (fp) were acquired. The diagnostic performances of both mono-exponential and bi-exponential parameters were assessed and compared by calculating the area under the curve (AUC) from receiver-operating characteristic (ROC) curve analysis. ADCT, D, and fp were all significantly correlated with interstitial fibrosis, ACS, and CCS. Cortical fp discriminated mild from moderate and severe ACS with the largest AUC of 0.89 [95% confidence interval (CI), 0.77-0.96]. Noticeably, only cortical fp could differentiate severe ACS from mild-to-moderate ACS (P<0.001) with an AUC of 0.80 (95% CI, 0.65-0.90) and a sensitivity of 100% (95% CI, 66.4-100%). Strikingly, the joint use of D and fp in either the cortex or the medulla could achieve a sensitivity of 100% for identifying either mild or severe interstitial fibrosis. Meanwhile, the serial use of cortical D and cortical fp showed the largest specificity for identifying both mild [88.9% (95% CI, 70.8-97.6%)] and severe [84.4% (95% CI, 67.2-94.7%)] interstitial fibrosis. For identifying mild CCS, the AUC of medullary ADCT (0.90, 95% CI, 0.78-0.97) was similar to that of cortical D (0.81, 95% CI, 0.67-0.91) and fp (0.86, 95% CI, 0.73-0.94), but statistically larger than that of medullary D (P=0.005) and fp (P=0.01). Furthermore, the parallel use of cortical D and cortical fp could increase the sensitivity to 95.0% (95% CI, 75.1-99.9%), whereas serial use of medullary D and medullary fp could increase the specificity to 100% (95% CI, 87.2-100%). The AUCs for differentiating severe from mild and moderate CCS were statistically insignificant among all parameters in the cortex and medulla (P≥0.15). Cortical fp was superior to the ADCT for identifying both mild and severe acute pathologic changes. Nevertheless, ADCT was equal to or better than single D or fp for evaluating chronic pathologic changes. Thus, both monoexponential and bi-exponential analysis of DWI images are complementary for evaluating kidney allograft pathologic changes, and the combined use of D and fp can increase the sensitivity and specificity for discriminating allograft pathologic changes severity.

Exploration on the Construction of Intensive Care Clinical Information Management System

This study introduces the feasibility study experience of intensive care clinical information management system in order to provide reference for the construction of intensive care clinical information management system in other hospitals. Four kinds of mainstream intensive care clinical information management system software were used to evaluate the implementation effect of each software such as equipment integration, information integration and application function module, so as to explore the construction scheme of intensive care clinical information management system. The optimized construction scheme and comprehensive feasibility study report of intensive care clinical information management system were formed, which provided an objective basis for the final scheme design, demonstration, procurement and decision-making of the hospital. The trial and feasibility study of intensive care clinical information management system contribute to optimize the construction scheme.

Polypharmacy in HIV: recent insights and future directions.

Update findings regarding polypharmacy among people with HIV (PWH) and consider what research is most needed. Among PWH, polypharmacy is common, occurs in middle age, and is predominantly driven by nonantiretroviral (ARV) medications. Many studies have demonstrated strong associations between polypharmacy and receipt of potentially inappropriate medications (PIMS), but few have considered actual adverse events. Falls, delirium, pneumonia, hospitalization, and mortality are associated with polypharmacy among PWH and risks remain after adjustment for severity of illness. Polypharmacy is a growing problem and mechanisms of injury likely include potentially inappropriate medications, total drug burden, known pairwise drug interactions, higher level drug interactions, drug--gene interactions, and drug--substance use interactions (alcohol, extra-medical prescription medication, and drug use). Before we can effectively design interventions, we need to use observational data to gain a better understanding of the modifiable mechanisms of injury. As sicker individuals take more medications, analyses must account for severity of illness. As self-report of substance use may be inaccurate, direct biomarkers, such as phosphatidylethanol (PEth) for alcohol are needed. Large samples including electronic health records, genetics, accurate measures of substance use, and state of the art statistical and artificial intelligence techniques are needed to advance our understanding and inform clinical management of polypharmacy in PWH.

Design and practice of drug clinical trial information management system

Design and practice of drug clinical trial information management system

Exploring perceptions on medical app use in clinical communication among Austrian physicians: Results of a validation study.

Physicians increasingly use medical applications to facilitate clinical information management. The respective effect on clinical communication and quality of healthcare provision has not been studied in the Austrian context so far. Thus, the current cross-sectional online study analyzed prevalent medical applications use and views on clinical communication competence in everyday medical practice among Austrian physicians (n = 151) and validated the survey tool. More than half of the participants used medical applications in daily clinical practice. The top three benefits of medical applications use were higher quality of healthcare, location-independent health service access, and higher efficiency in healthcare resource allocation. Moreover, study participants felt that communication competence acquired during medical studies inadequately prepared them for daily clinical practices. Medical applications use certainly affects the therapeutic alliance between patients and physician. This study supports the importance of initiating an open, constructive discussion among healthcare stakeholders and developing according to evidence-based guidelines.