Development of an Automated Capillary Immunoassay to Detect Prion Glycotypes in Creutzfeldt-Jakob Disease.

Creutzfeldt-Jakob disease (CJD) comprises a group of transmissible neurodegenerative diseases with vast phenotypic diversity. Sporadic CJD heterogeneity is predominantly influenced by the genotype at codon 129 of the prion-encoding gene and the molecular weight of PrPSc fragments after protease digestion, resulting in a classification of 6 subtypes of CJD (MM1, MM2, MV1, MV2, VV1, and VV2). The majority of cases with CJD can be distinguished using this classification system. However, a number of reported CJD cases are phenotypically unique from others within their same subtype, such as variably protease-sensitive prionopathies, or exist as a mixture of subtypes within the same patient. Western blotting of brain tissue, along with the genotyping of codon 129 of the prion-encoding gene, is considered the "gold standard" for the biochemical characterization of CJD. Western blotting requires a significant amount of prion protein for detection, is labor-intensive, and is also associated with high interassay variability. In addition to these limitations, a growing body of research suggests that unique subtypes of CJD are often undetected or misdiagnosed using standard diagnostic western blotting protocols. Consequently, we successfully optimized and developed a capillary-based western assay using the JESS Simple Western (ProteinSimple) to detect and characterize prion proteins from patients with CJD. We found that this novel assay consistently differentiated CJD type 1 and type 2 cases with a limit of detection 10 to 100× higher than traditional western blotting. Cases with CJD in which type 1 and type 2 coexist within the same brain region can be detected using type 1-specific and type 2-specific antibodies, and we found that there was remarkable specificity for the detection of cases with variably protease-sensitive prionopathy. The assay presented displays outstanding sensitivity, allowing for the preservation of valuable samples and enhancing current detection methods.

Case 309: Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy.

HISTORY: A 64-year-old man presented with a 6-month history of lightheadedness and intermittent balance and coordination difficulties. Two months before admission, symptoms became more substantial and persistent, with a worsening sense of disequilibrium and unsteady gait. He reported difficulties pronouncing words and mild word-finding difficulties. His wife noted a change in his cognition and memory over the same time. His medical history included well-controlled chronic obstructive pulmonary disease (COPD) secondary to a long history of smoking with associated unintentional 30-lb (13.6-kg) weight loss over the previous 3 years, for which chest CT scanning was performed, revealing no abnormality. On clinical examination, the patient was alert and oriented but had slurred speech. A positive Romberg sign was noted, finger-to-nose and hand rapid alternating movement tests revealed impairment on the right side, and his gait was ataxic. The motor examination revealed normal muscle tone, bulk, and power in the upper and lower extremities. Sensory testing results were normal. Initial MRI of the brain at admission revealed abnormal findings in the left supratentorial brain. Of note, this patient's presentation predated the COVID-19 pandemic. Cerebrospinal fluid (CSF) analysis revealed predominant pleocytosis (23 × 106/L; normal range, [0-5] × 106/L) (78% lymphocytes, 22% monocytes), elevated protein level (1.23 g/L; normal range, 0.19-0.64 g/L), oligoclonal bands (faint one or two), and a high immunoglobulin G (IgG) index (0.130 g/L; normal reference, ≤0.059 g/L). Despite extensive initial work-up for inflammatory, infectious, autoimmune, or neoplastic causes, a definitive diagnosis was not reached. Thus, repeat MRI of the brain was performed 2 weeks after admission.

Diagnostic Accuracy of Centrally Restricted Diffusion Sign in Cerebral Metastatic Disease: Differentiating Radiation Necrosis from Tumor Recurrence.

Purpose: The centrally restricted diffusion sign of diffusion-weighted imaging (DWI) is associated with radiation necrosis (RN) in treated gliomas. Our goal was to evaluate its diagnostic accuracy to distinguish RN from tumor recurrence (TR) in treated brain metastases. Methods: Retrospective study of consecutive patients with brain metastases who developed a newly centrally necrotic lesion after radiotherapy (RT). One reader placed regions of interest (ROI) in the enhancing solid lesion and the non-enhancing central necrosis on the apparent diffusion coefficient (ADC) map. Two readers qualitatively assessed the presence of the centrally restricted diffusion sign. The final diagnosis was made by histopathology (n = 39) or imaging follow-up (n = 2). Differences between groups were assessed by Fisher's exact or Mann-Whitney U tests. Diagnostic accuracy and inter-reader agreement were evaluated using receiver operating characteristic (ROC) curve analysis and kappa scores. Results: Forty-one lesions (32 predominant RN; 9 predominant TR) were analyzed. An ADC value ≤ 1220 × 10-6 mm2/s (sensitivity 74%, specificity 89%, area under the curve [AUC] .85 [95% confidence interval {CI}, .70-.94] P < .0001) from the necrosis and an ADC necrosis/enhancement ratio ≤1.37 (sensitivity 74%, specificity 89%, AUC .82 [95% CI, .67-.93] P < .0001) provided the highest performance for RN diagnosis. The qualitative centrally restricted diffusion sign had a sensitivity of 69% (95% CI, .50-.83), specificity of 77% (95% CI, .40-.96), and a moderate (k = .49) inter-reader agreement for RN diagnosis. Conclusions: Radiation necrosis is associated with lower ADC values in the central necrosis than TR. A moderate interobserver agreement might limit the qualitative assessment of the centrally restricted diffusion sign.

Case 309.

HISTORY: A 64-year-old man presented with a 6-month history of lightheadedness, intermittent balance, and coordination difficulties. Two months before admission, symptoms became more substantial and persistent, with a worsening sense of disequilibrium and unsteady gait. He reported difficulties pronouncing words and mild word-finding difficulties. His wife noted a change in his cognition and memory over the same time. His medical history included well-controlled chronic obstructive pulmonary disease (COPD) secondary to a long history of smoking with associated unintentional 30-lb (13.6-kg) weight loss over the previous 3 years, for which chest CT scanning was performed, revealing no abnormality. On clinical examination, the patient was alert and oriented but had slurred speech. A positive Romberg sign was noted, finger-to-nose and hand rapid alternating movement tests revealed impairment on the right side, and his gait was ataxic. The motor examination revealed normal muscle tone, bulk, and power in the upper and lower extremities. Sensory testing results were normal. Initial MRI of the brain at admission revealed abnormal findings in the left supratentorial brain (Figs 1-3). Of note, this patient's presentation predated the COVID-19 pandemic. Cerebrospinal fluid analysis revealed predominant pleocytosis (23 × 106/L; normal range, [0-5] × 106/L) (78% lymphocytes, 22% monocytes), elevated protein level (1.23 g/L; normal range, 0.19-0.64 g/L), oligoclonal bands (faint one or two), and a high immunoglobulin G index (0.130 g/L; normal reference, ≤0.059 g/L). Despite extensive initial work-up for inflammatory, infectious, autoimmune, or neoplastic causes, a definitive diagnosis was not reached. Thus, repeat MRI of the brain was performed 2 weeks after admission (Fig 4).

Embryonal Tumor With Multilayered Rosettes of the Parietooccipital Region: A Case Report.

Embryonal tumor with multilayered rosettes is a rare and highly malignant early childhood brain tumor. We report a case of embryonal tumor with multilayered rosettes in the parietooccipital region of a 2-year-old girl. Histopathology of the tumor demonstrated amplification of the 19q13.42 locus and strong positivity for LIN28A. Treatment was multimodal and included 3 surgical resections, adjuvant chemotherapy with autologous stem cell rescue, and focal radiotherapy. The use of the agents vorinostat and isotretinoin, and the addition of focal radiation have not been extensively described in this patient population, but may attribute to our patient's sustained remission at 2.5-years follow-up.

The predictive values of a deliberative and a paternalistic attitude towards two situations of moral conflict: A study among Dutch nurse practitioners and physician assistants.

BACKGROUND: In this study, we examined the predictive values of a moral deliberate and paternalistic attitude on the propensity of yielding to pressure. In these hypothesised positive and negative relationships, we further sought to ascertain whether moral disengagement plays a pivotal role when individuals deviate from ethical standards, rules and regulations when yielding to pressure. AIM(S): This study's primary aim was to assess the predictive value of a moral deliberative and paternalistic attitude for yielding to pressure when physician assistants (PAs) and nurse practitioners (NPs) face moral conflicts. METHOD: This validation study was cross-sectional and based on a convenience sample of Dutch PAs and NPs. The MSQ-DELIB and MSQ-PATER scales indicate a moral deliberate or paternalistic attitude. These scales were assumed to have a predictive value towards the degree of yielding to pressure by PAs and NPs. Yielding to pressure was measured by two vignettes in which respondents faced a moral conflict (vignette 1: prescribing unindicated antibiotics and vignette 2: discharging a difficult patient from the hospital). RESULTS: Only moral deliberation was a significant predictor of yielding to pressure. That is, we found a positive effect in vignette 1 (in which the pressure came from the patient). In contrast, we found a negative relationship in vignette 2 (in which pressure went from the working environment). Paternalism did not affect yielding to pressure in either vignette. CONCLUSION: This study suggests that PAs and NPs having a moral deliberative attitude makes them receptive to pressure exerted by patients to break moral standards. On the other hand, they are more resilient against doing so when this pressure comes from different sources than the patient. Further research is needed to find more conclusive evidence for this differential effect.

Qualitative Assessment of Advanced MRI in Post-Treatment High Grade Gliomas Follow Up: Do We Agree?

PURPOSE: MRI is commonly used in follow up of high grade glioma. Our purpose is to assess the interrater agreement on the increasingly used visual qualitative assessment of various conventional and advanced MR techniques in the setting of treated high grade glioma in comparison to the well established quantitative measurements. METHODS: We prospectively enrolled HGG patients who underwent reresection of a new enhancing lesion on post-treatment 3T MR examination including DWI, DCE and DSC sequences. Two neuroradiologists objectively assessed the diffusion and perfusion maps by placing ROI on representative post-processed maps. They subjectively assessed the post-contrast, perfusion and diffusion sequences. Interrater agreement and concordance correlation coefficient were calculated. RESULTS: Twenty-eight lesions were included. The interrater agreement on the qualitative assessment was good for k-trans (k = 0.73), moderate for Vp (k = 0.52), fair for AUC and Ve maps (k = 0.37 and 0.21), fair for corrected CBV (k = 0.39) and poor for the enhancement pattern and presence of diffusion restriction (k = 0.02 and 0.07). The concordance between the quantitative measurements was substantial for AUC and Vp (ρc = 0.98 and 0.97), moderate for k-trans and corrected CBV (ρc = 0.94) and poor for Ve and ADC (ρc = 0.86 and 0.24). CONCLUSION: While the quantitative measurements of DSC and DCE perfusion maps show satisfactory inter-rater agreement, the qualitative assessment has lower interobserver agreement and should not be relied upon solely in the interpretation. Similarly, the suboptimal inter-rater agreement on the interpretation of enhancement pattern and diffusion restriction potentially limits their usefulness in differentiating glioma recurrence from treatment related changes.

Preoperative Determination of Isocitrate Dehydrogenase Mutation in Gliomas Using Spectral Editing MRS: A Prospective Study.

BACKGROUND: The edited magnetic resonance spectroscopy (MRS) technique has not yet been formally evaluated for the in vivo detection of 2-hydroxyglutarate (2-HG) in patients with gliomas of various grades. PURPOSE: To evaluate the diagnostic accuracy of edited MRS in the preoperative identification of the isocitrate dehydrogenase (IDH) mutation status in patients with gliomas. STUDY TYPE: Prospective. POPULATION: Fifty-eight subjects (31 glioblastomas, 27 grade II and III gliomas). FIELD STRENGTH/SEQUENCE: Mescher-Garwood (MEGA)-PRESS and routine clinical brain tumor MR sequences were used at 3T. ASSESSMENT: Data were analyzed using an advanced method for accurate, robust, and efficient spectral fitting (AMARES) from jMRUI software. The amplitudes of the 2-HG, N-acetyl-aspartate (NAA), choline (Cho), and creatine/phosphocreatine (Cr) resonances were calculated with their associated Cramer-Rao lower bound (CRLB). The IDH1 R132H mutation status was assessed by immunohistochemistry for all patients. Patients with grades II and III gliomas with negative immunohistochemistry underwent DNA sequencing to further interrogate IDH mutation status. STATISTICAL TEST: The differences in 2-HG amplitudes, 2-HG/NAA, 2-HG/Cho, and 2-HG/Cr between IDH-mutant and IDH-wildtype gliomas were assessed using Mann-Whitney U-tests. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic accuracy of each parameter. RESULTS: The 2-HG amplitudes, 2-HG/NAA, and 2-HG/Cho were higher for IDH-mutant gliomas than IDH-wildtype gliomas (P < 0.007). Using a CRLB threshold <30%, a 2-HG cutoff greater than 0 had a sensitivity of 80% (95% confidence interval [CI]: 52-96%) and a specificity of 81% (95% CI: 54-96%) in identifying IDH-mutant gliomas. In the subset of patients with grades II and III gliomas, the sensitivity was 80% (95% CI: 52-96%) and specificity was 100% (95% CI: 40-100%). Among 2-HG ratios, the highest AUC for the identification of IDH mutant status was achieved using the 2-HG/NAA (AUC = 0.8, 95% CI 0.67-.89). DATA CONCLUSION: Preoperative edited MRS appears to be able to help identify IDH-mutant gliomas with high specificity. Level of Evidence 1 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:416-426.

Prospective Study Demonstrates Utility of EP-QuIC in Creutzfeldt-Jakob Disease Diagnoses.

Prospectively acquired Canadian cerebrospinal fluid samples were used to assess the performance characteristics of three ante-mortem tests commonly used to support diagnoses of Creutzfeldt-Jakob disease. The utility of the end-point quaking-induced conversion assay as a test for Creutzfeldt-Jakob disease diagnoses was compared to that of immunoassays designed to detect increased amounts of the surrogate markers 14-3-3γ and hTau. The positive predictive values of the end-point quaking-induced conversion, 14-3-3γ, and hTau tests conducted at the Prion Diseases Section of the Public Health Agency of Canada were 96%, 68%, and 66%, respectively.

A novel Gerstmann-Sträussler-Scheinker disease mutation defines a precursor for amyloidogenic 8 kDa PrP fragments and reveals N-terminal structural changes shared by other GSS alleles.

To explore pathogenesis in a young Gerstmann-Sträussler-Scheinker Disease (GSS) patient, the corresponding mutation, an eight-residue duplication in the hydrophobic region (HR), was inserted into the wild type mouse PrP gene. Transgenic (Tg) mouse lines expressing this mutation (Tg.HRdup) developed spontaneous neurologic syndromes and brain extracts hastened disease in low-expressor Tg.HRdup mice, suggesting de novo formation of prions. While Tg.HRdup mice exhibited spongiform change, PrP aggregates and the anticipated GSS hallmark of a proteinase K (PK)-resistant 8 kDa fragment deriving from the center of PrP, the LGGLGGYV insertion also imparted alterations in PrP's unstructured N-terminus, resulting in a 16 kDa species following thermolysin exposure. This species comprises a plausible precursor to the 8 kDa PK-resistant fragment and its detection in adolescent Tg.HRdup mice suggests that an early start to accumulation could account for early disease of the index case. A 16 kDa thermolysin-resistant signature was also found in GSS patients with P102L, A117V, H187R and F198S alleles and has coordinates similar to GSS stop codon mutations. Our data suggest a novel shared pathway of GSS pathogenesis that is fundamentally distinct from that producing structural alterations in the C-terminus of PrP, as observed in other prion diseases such as Creutzfeldt-Jakob Disease and scrapie.

Prospective comparative diagnostic accuracy evaluation of dynamic contrast-enhanced (DCE) vs. dynamic susceptibility contrast (DSC) MR perfusion in differentiating tumor recurrence from radiation necrosis in treated high-grade gliomas.

BACKGROUND: The appearance of a new enhancing lesion after surgery and chemoradiation for high-grade glioma (HGG) presents a common diagnostic dilemma. Histopathological analysis remains the reference standard in this situation. PURPOSE: To prospectively compare the diagnostic accuracy of dynamic contrast-enhanced (DCE) vs. dynamic susceptibility contrast (DSC) in differentiating tumor recurrence (TR) from radiation necrosis (RN). STUDY TYPE: Prospective diagnostic accuracy study. POPULATION: In all, 98 consecutive treated HGG patients with new enhancing lesion. We excluded 32 patients due to inadequate follow-up or technical limitation. FIELD STRENGTH/SEQUENCE: 3 T DCE and DSC MR. ASSESSMENT: Histogram and hot-spot analysis of cerebral blood volume (CBV), corrected CBV, Ktrans , area under the curve (AUC), and plasma volume (Vp). The reference standard of TR and/or RN was determined by histopathology in 43 surgically resected lesions or by clinical/imaging follow-up in the rest. STATISTICAL TESTS: Mann-Whitney U-tests, receiver operating characteristic (ROC) curve, and logistic regression analysis. RESULTS: A total of 68 lesions were included. There were 37 TR, 28 RN, and three lesions with equal proportions of TR and RN. TR had significantly higher CBV, corrected CBV, CBV ratio, corrected CBV ratio, AUC ratio, and Vp ratio (P < 0.05) than RN on hot-spot analysis. CBV had the highest diagnostic accuracy (AUROC 0.71). On histogram analysis, TR had higher CBV and corrected CBV maximal value compared with RN (P = 0.006, AUROC = 0.70). Only CBV on hot-spot analysis remained significant after correction for multiple comparison, with no significant improvement in diagnostic accuracy when using a combination of parameters (AUROC 0.71 vs. 0.76, P = 0.24). DATA CONCLUSION: DSC-derived CBV is the most accurate perfusion parameter in differentiating TR and RN. DSC and DCE-derived parameters reflecting the blood volume in an enhancing lesion are more accurate than the DCE-derived parameter Ktrans . Clinical practice may be best guided by blood volume measurements, rather than permeability assessment for differentiation of TR from RN. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2019;50:573-582.

Moral reasoning explained by personality traits and moral disengagement: A study among Dutch nurse practitioners and physician assistants.

AIM: To explore the direct and indirect effect of the personality meta-traits 'Stability' and 'Plasticity' on moral reasoning among nurse practitioners (NPs) and physician assistants (PAs). BACKGROUND: Moral reasoning is influenced by being prone to moral disengagement and personality traits. Moral disengagement is observed among professionals in many fields, including healthcare providers. Moral disengagement is known to be provoked by environmental stressors and influenced by certain personality traits. DESIGN: A cross-sectional approach was used including self-report questionnaires. METHODS: A convenience sample of Dutch NPs (N = 67) and PAs (N = 88) was surveyed via online questionnaires between January and March 2015, using (a) the Defining Issues Test; (b) the BIG five inventory; and (c) the Moral Disengagement Scale. Structural equation modelling (SEM) was employed for estimating the construct validity of two meta-traits of personality and to test unidirectional influences on moral reasoning. RESULTS: Only the Stability trait was a direct predictor of moral reasoning whereas both Stability and Plasticity were precursors of moral disengagement. Both personality meta-traits had statistically significant indirect effects on moral reasoning through a low level of moral disengagement. The influence of both personality traits on the level of moral reasoning was increased by strong self-censure on entering into morally disengaged interactions. CONCLUSION: The personality meta-trait 'Stability' is an indicator of moral reasoning and is explained by a lower propensity to morally disengage among highly stable people. Although the meta-trait Plasticity exerts an indirect effect through moral disengagement on moral reasoning, it is not a direct indicator of moral reasoning.

A case cluster of variant Creutzfeldt-Jakob disease linked to the Kingdom of Saudi Arabia.

As of mid-2016, 231 cases of variant Creutzfeldt-Jakob disease-the human form of a prion disease of cattle, bovine spongiform encephalopathy-have been reported from 12 countries. With few exceptions, the affected individuals had histories of extended residence in the UK or other Western European countries during the period (1980-96) of maximum global risk for human exposure to bovine spongiform encephalopathy. However, the possibility remains that other geographic foci of human infection exist, identification of which may help to foreshadow the future of the epidemic. We report results of a quantitative analysis of country-specific relative risks of infection for three individuals diagnosed with variant Creutzfeldt-Jakob disease in the USA and Canada. All were born and raised in Saudi Arabia, but had histories of residence and travel in other countries. To calculate country-specific relative probabilities of infection, we aligned each patient's life history with published estimates of probability distributions of incubation period and age at infection parameters from a UK cohort of 171 variant Creutzfeldt-Jakob disease cases. The distributions were then partitioned into probability density fractions according to time intervals of the patient's residence and travel history, and the density fractions were combined by country. This calculation was performed for incubation period alone, age at infection alone, and jointly for incubation and age at infection. Country-specific fractions were normalized either to the total density between the individual's dates of birth and symptom onset ('lifetime'), or to that between 1980 and 1996, for a total of six combinations of parameter and interval. The country-specific relative probability of infection for Saudi Arabia clearly ranked highest under each of the six combinations of parameter × interval for Patients 1 and 2, with values ranging from 0.572 to 0.998, respectively, for Patient 2 (age at infection × lifetime) and Patient 1 (joint incubation and age at infection × 1980-96). For Patient 3, relative probabilities for Saudi Arabia were not as distinct from those for other countries using the lifetime interval: 0.394, 0.360 and 0.378, respectively, for incubation period, age at infection and jointly for incubation and age at infection. However, for this patient Saudi Arabia clearly ranked highest within the 1980-96 period: 0.859, 0.871 and 0.865, respectively, for incubation period, age at infection and jointly for incubation and age at infection. These findings support the hypothesis that human infection with bovine spongiform encephalopathy occurred in Saudi Arabia.

Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia.

Amyotrophic lateral sclerosis (ALS) is a paralytic and usually fatal disorder caused by motor-neuron degeneration in the brain and spinal cord. Most cases of ALS are sporadic but about 5-10% are familial. Mutations in superoxide dismutase 1 (SOD1), TAR DNA-binding protein (TARDBP, also known as TDP43) and fused in sarcoma (FUS, also known as translocated in liposarcoma (TLS)) account for approximately 30% of classic familial ALS. Mutations in several other genes have also been reported as rare causes of ALS or ALS-like syndromes. The causes of the remaining cases of familial ALS and of the vast majority of sporadic ALS are unknown. Despite extensive studies of previously identified ALS-causing genes, the pathogenic mechanism underlying motor-neuron degeneration in ALS remains largely obscure. Dementia, usually of the frontotemporal lobar type, may occur in some ALS cases. It is unclear whether ALS and dementia share common aetiology and pathogenesis in ALS/dementia. Here we show that mutations in UBQLN2, which encodes the ubiquitin-like protein ubiquilin 2, cause dominantly inherited, chromosome-X-linked ALS and ALS/dementia. We describe novel ubiquilin 2 pathology in the spinal cords of ALS cases and in the brains of ALS/dementia cases with or without UBQLN2 mutations. Ubiquilin 2 is a member of the ubiquilin family, which regulates the degradation of ubiquitinated proteins. Functional analysis showed that mutations in UBQLN2 lead to an impairment of protein degradation. Therefore, our findings link abnormalities in ubiquilin 2 to defects in the protein degradation pathway, abnormal protein aggregation and neurodegeneration, indicating a common pathogenic mechanism that can be exploited for therapeutic intervention.

Case 232: Amyloid ß-related Angiitis.

History A 78-year-old woman presented to a community hospital after an unwitnessed fall at her nursing home. Initial head computed tomography (CT) performed in the emergency department showed vasogenic edema in the right temporal parietal region, which prompted her transfer to our institution for additional work-up. Further history taking revealed recurrent transient motor and sensory transient ischemic attack-like symptoms over the preceding weeks. She denied having a fever or night sweats. There was no history of infection, bleeding, immunodeficiency, intravenous drug use, alcohol or tobacco abuse, malignancy, or genetic disorders. Her medical history included memory impairment and a left posterior cerebral artery territory infarction. She was not known to have any systemic inflammatory disorder. Physical examination findings at presentation were noncontributory. She was not taking any anticoagulants or immunosuppressive medication. Pertinent hematologic laboratory investigations revealed a white blood cell count of 6.7 × 10(9), a C-reactive protein level of 29 mg/L (276.2 nmol/L) (normal value, <10 mg/L [95.2 nmol/L]), and an erythrocyte sedimentation rate of 35 mm per hour (normal value, 0-10 mm per hour). Shortly after this patient was admitted to our institution, she had a generalized tonic-clonic seizure. Magnetic resonance (MR) imaging of the brain was performed the next day.

Nurse practitioners' focus on health care in terms of cure and care: analysis of graduate theses using the International Classification of Functioning, Disability and Health.

AIM: To explore the focus of nurse practitioners on health care in terms of cure and care. BACKGROUND: Nurse practitioners are expected to act on the intersection of cure and care. However, in clinical practice and education, a clear model covering this area is lacking; therefore, it is unknown to what extent nurse practitioners are focused on this specific area. Graduate theses may reflect the focus of nurse practitioners. DESIGN: Sequential exploratory mixed method. METHODS: In total, 413 published abstracts of graduate theses of a Dutch Master of Advanced Nursing Practice (2000-2015) were analysed using the International Classification of Functioning, Disability and Health. Data source included aim, question and outcome of each thesis and graduates' characteristics. A qualitative deductive approach was used for the analyses. Theses were classified as focused on cure, care, or on the intersection of cure and care. RESULTS: A small majority of 53% (N = 219) of the graduate theses addressed patient's health status and could be classified in the International Classification of Functioning, Disability and Health. Of the classified theses, 48% were focused on cure, 39% on the intersection of cure and care and 13% on care. While the percentage of theses addressing health status increased significantly over the 15-year period, the percentage of theses focused on cure, care and on the intersection of cure and care remained the same. CONCLUSION: The graduate theses reflected that nurse practitioners are increasingly oriented towards patients' health status. However, their focus is predominantly on cure rather than on the intersection of cure and care.

Does language ambiguity in clinical practice justify the introduction of standard terminology? An integrative review.

AIMS AND OBJECTIVES: To research the use of ambiguous language in written information concerning patients' functioning and to identify problems resulting from the use of ambiguous language in clinical practice. BACKGROUND: Many projects that aimed to introduce standard terminology concerning patients' functioning in clinical practice are unsuccessful because standard terminology is rarely used in clinical practice. These projects mainly aim to improve communication by reducing ambiguous language. Considering their lack of success, the validity of the argument that language ambiguity is used in clinical practice is questioned. DESIGN: An integrative literature review. METHODS: A systematic search of the MEDLINE (1950-2012) and CINAHL (1982-2012) databases was undertaken, including empirical and theoretical literature. The selected studies were critically appraised using a data assessment and extraction form. RESULTS: Seventeen of 767 papers were included in the review and synthesis. The use of ambiguous language in written information concerning patients' functioning was demonstrated. Problems resulting from the use of ambiguous language in clinical practice were not identified. However, several potential problems were suggested, including hindered clinical decision-making and limited research opportunities. CONCLUSION: The results of this review demonstrated the use of ambiguous language concerning patients' functioning, but health professionals in clinical practice did not experience this issue as a problem. This finding might explain why many projects aimed at introducing standard terminology concerning functioning in clinical practice to solve problems caused by ambiguous language are often unsuccessful. Language ambiguity alone is not a valid argument to justify the introduction of standard terminology. RELEVANCE TO CLINICAL PRACTICE: The introduction of standard terminology concerning patients' functioning will only be successful when clinical practice requires the aggregation and reuse of data from electronic patient records for different purposes, including multidisciplinary decision-making and research.

The nursing profession: public image, self-concept and professional identity. A discussion paper.

AIM: To discuss the actual public image of nurses and other factors that influence the development of nurses' self-concept and professional identity. BACKGROUND: Nurses have become healthcare professionals in their own right who possess a great deal of knowledge. However, the public does not always value the skills and competences nurses have acquired through education and innovation. DESIGN: Discussion paper. DATA SOURCES: We identified 1216 relevant studies by searching MEDLINE, CINAHL and PsycINFO databases in the period 1997-2010. Finally, 18 studies met our inclusion criteria. DISCUSSION: The included studies show that the actual public image of nursing is diverse and incongruous. This image is partly self-created by nurses due to their invisibility and their lack of public discourse. Nurses derive their self-concept and professional identity from their public image, work environment, work values, education and traditional social and cultural values. IMPLICATIONS FOR NURSING: Nurses should work harder to communicate their professionalism to the public. Social media like the Internet and YouTube can be used to show the public what they really do. CONCLUSION: To improve their public image and to obtain a stronger position in healthcare organizations, nurses need to increase their visibility. This could be realized by ongoing education and a challenging work environment that encourages nurses to stand up for themselves. Furthermore, nurses should make better use of strategic positions, such as case manager, nurse educator or clinical nurse specialist and use their professionalism to show the public what their work really entails.

Functioning assessment vs. conventional medical assessment: a comparative study on health professionals' clinical decision-making and the fit with patient's own perspective of health.

AIMS AND OBJECTIVES: To compare a functioning assessment based on the International Classification of Functioning, Disability and Health (ICF) with a conventional medical assessment, in terms of their respective consequences for health professionals' clinical decision-making and the fit with patient's own perspective of health. BACKGROUND: In chronic diseases, pathogenic-oriented health care falls short in generating all the information required for determining healthcare provision to improve health. A broader, so-called salutogenic approach, by using the ICF, focusing on how to stay healthy, rather than on what causes diseases, seems more appropriate. DESIGN: A cross-sectional comparative study using data from a randomised controlled trial. METHODS: Data about patient problems and professional healthcare activities were collected from a total of 81 patients with severe multiple sclerosis who were randomly assigned to one of two groups: the ICF group, assessed with a functioning assessment (n = 43), and the medical group, assessed with a conventional medical assessment (n = 38). Data were analysed statistically using descriptive and inferential statistics. RESULTS: A functioning assessment resulted in the registration of significantly more patient problems in the health components 'participation' and 'environmental factors', as well as significantly more professional healthcare activities befitting these components. The ICF group had a significant positive correlation between registered problems by health professionals and patients' self-reported problems, whereas the medical group had several negative correlations. CONCLUSION: A functioning assessment resulted in a care plan that not only was broader and more complete but also reflected the patients' self-reported problems more closely than a medical assessment, without a loss of focus on medical problems. RELEVANCE TO CLINICAL PRACTICE: This study has shown that some health problems remain unnoticed by a medical assessment alone, which is especially important for the chronically ill. A functioning assessment provides a strong foundation for identifying all relevant information related to health.