Handling the desire to die- evaluation of an elective course for medical students.

BACKGROUND: The desire to die can occur in palliative care patients with a prevalence of up to 22%. Not every desire to die is accompanied by a pressure to act, but usually by a burden that can arise from various factors. To address this burden appropriately, health care workers should be trained. Based on an evaluated course on handling the desire to die, an elective course for medical students was developed and evaluated. In order to identify the impact of the elective course's content, a comparison of attitudes towards assisted dying with two other participant groups was conducted. Therefore, three questions from the evaluation of the elective course were used. METHOD: Online evaluation of the elective and questions addressing attitude were assessed using a five-point Likert scale. The specific outcome-based assessment was determined using the Comparative Self-Assessment Gain. The main participant group (group 1) were students who took the elective. The additional survey on attitudes towards assisted dying included undergraduate medical students who had taken compulsory palliative care courses (group 2) and physicians who had taken an introductory course in intensive care or emergency medicine (group 3). RESULTS: Group 1 (n = 13, response rate rr = 86.7%) was very satisfied with the blended learning format (100%) and the course itself (100%). They were able to deepen their knowledge (81.0%) and train skills (71.2%) through the course. In the additional surveys, there were 37 students in group 2 (rr = 66.1%) and 258 physicians in group 3 (rr = 73.6%). Willingness to assist with or accompany the various options for assisted dying varied according to the type of assistance. Among the participants, it can be summarised that the highest willingness was shown by the students of group 2 followed by the physicians of group 3 and the students of group 1. CONCLUSIONS: A course on handling the desire to die of palliative patients can deepen knowledge and train communication skills and thus support self-confidence. Dealing with the background of the desire to die, knowledge about assisted dying, but also one's own attitudes and responsibilities can influence the attitude towards assisted dying.

Structural and functional characterization of an egg-laying hormone signaling system in a lophotrochozoan - The pacific oyster (Crassostrea gigas).

The egg-laying hormones (ELHs) of gastropod mollusks were characterized more than forty years ago. Yet, they have remained little explored in other mollusks. To gain insights into the functionality of the ELH signaling system in a bivalve mollusk - the oyster Crassostrea gigas, this study investigates the processing of its ELH precursor (Cragi-ELH) by mass spectrometry. Some of the ELH mature peptides identified in this study were subsequently investigated by nuclear magnetic resonance and shown to adopt an extended alpha-helix structure in a micellar medium mimicking the plasma membrane. To further characterize the ELH signaling system in C. gigas, a G protein-coupled receptor phylogenetically related to ecdysozoan diuretic hormone DH44 and corticotropin-releasing hormone (CRH) receptors named Cragi-ELHR was also characterized functionally and shown to be specifically activated by the two predicted mature ELH peptides and their N-terminal fragments. Both Cragi-ELH and Cragi-ELHR encoding genes were mostly expressed in the visceral ganglia (VG). Cragi-ELH expression was significantly increased in the VG of both fully mature male and female oysters at the spawning stage. When the oysters were submitted to a nutritional or hyposaline stress, no change in the expression of the ligand or receptor genes was recorded, except for Cragi-ELHR only during a mild acclimation episode to brackish water. These results suggest a role of Cragi-ELH signaling in the regulation of reproduction but not in mediating the stress response in our experimental conditions.

Physical Activity Is Associated with Slower Cognitive Decline in Older Adults with Type 2 Diabetes.

BACKGROUND: Physical activity is associated with slower cognitive decline in old age. Type 2 diabetes (T2d) is a risk factor for dementia and cognitive decline. Physical activity protects against several T2d complications. Yet, little is known about the contribution of physical activity to cognitive health among the elderly with T2d. OBJECTIVES: To examine the association between physical activity and cognitive decline in older adults with T2d. DESIGN: This is a prospective longitudinal study using data from the Israel Diabetes and Cognitive Decline (IDCD) study. SETTING: ICDC study (N=1,213), is a population-based cohort of adults over the age of 65, diagnosed with type 2 diabetes, who were cognitively normal at baseline and followed up every 18 months. PARTICIPANTS: Participants with at least one follow-up assessment who were in the same physical activity group consistently and had complete demographic data. MEASUREMENTS: Physical activity was measured using Minnesota Leisure Time Activity Questionnaire, cognitive functioning was measured using a broad neuropsychological assessment measuring Executive Functioning, Attention/Working Memory, Semantic Categorization and Episodic Memory. RESULTS: Participants were classified into physical activity groups based on self-reported physical activity at baseline and all follow ups: "active" - participation in recreational physical activity (n=286); "non-active"- the only physical activity was walking from place to place (n=93) and "sedentary" (n=19). Linear mixed effects models were applied to adjust for key demographic and cardiovascular risk factors. Participants were 72.4 (SD 4.6) years old, had 13.3 (SD 3.6) years of education, and 163 (41%) were female. In the fully adjusted model, compared to the non-active group the active group had significantly slower rate of decline in Global Cognition (p=0.005), Executive Functioning (p=.014), and Attention/Working Memory (p=.01). There were no significant group differences for Semantic Categorization (p=.17) and Episodic Memory (p=.88). CONCLUSIONS: Among initially cognitively normal and independent older adults with T2d, a physically active lifestyle was associated with a slower rate of cognitive decline. Future research should examine whether promoting physical activity may prevent or delay onset of dementia in this high-risk population.

Assessing Adverse Health Effects of Long-Term Exposure to Low Levels of Ambient Air Pollution: Implementation of Causal Inference Methods.

This report provides a final summary of the principal findings and key conclusions of a study supported by an HEI grant aimed at "Assessing Adverse Health Effects of Long-Term Exposure to Low Levels of Ambient Air Pollution." It is the second and final report on this topic. The study was designed to advance four critical areas of inquiry and methods development. First, it focused on predicting short- and long-term exposures to ambient fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) at high spatial resolution (1 km × 1 km) for the continental United States over the period 2000-2016 and linking these predictions to health data. Second, it developed new causal inference methods for estimating exposure-response (ER) curves (ERCs) and adjusting for measured confounders. Third, it applied these methods to claims data from Medicare and Medicaid beneficiaries to estimate health effects associated with short- and long-term exposure to low levels of ambient air pollution. Finally, it developed pipelines for reproducible research, including approaches for data sharing, record linkage, and statistical software. Our HEI-funded work has supported an extensive portfolio of analyses and the development of statistical methods that can be used to robustly understand the health effects of short- and long-term exposure to low levels of ambient air pollution. Our Phase 1 report (Dominici et al. 2019) provided a high-level overview of our statistical methods, data analysis, and key findings, grouped into the following five areas: (1) exposure prediction, (2) epidemiological studies of ambient exposures to air pollution at low levels, (3) sensitivity analysis, (4) methodological contributions in causal inference, and (5) an open access research data platform. The current, final report includes a comprehensive overview of the entire research project.Considering our (1) massive study population, (2) numerous sensitivity analyses, and (3) transparent assessment of covariate balance indicating the quality of causal inference for simulating randomized experiments, we conclude that conditionally on the required assumptions for causal inference, our results collectively indicate that long-term PM2.5 exposure is likely to be causally related to mortality. This conclusion assumes that the causal inference assumptions hold and, more specifically, that we accounted adequately for confounding bias. We explored various modeling approaches, conducted extensive sensitivity analyses, and found that our results were robust across approaches and models. This work relied on publicly available data, and we have provided code that allows for reproducibility of our analyses.Our work provides comprehensive evidence of associations between exposures to PM2.5, NO2, and O3 and various health outcomes. In the current report, we report more specific results on the causal link between long-term exposure to PM2.5 and mortality, even at PM2.5 levels below or equal to 12 µg/m3, and mortality among Medicare beneficiaries (ages 65 and older). This work relies on newly developed causal inference methods for continuous exposure.For the period 2000-2016, we found that all statistical approaches led to consistent results: a 10-µg/m3 decrease in PM2.5 led to a statistically significant decrease in mortality rate ranging between 6% and 7% (= 1 - 1/hazard ratio [HR]) (HR estimates 1.06 [95% CI, 1.05 to 1.08] to 1.08 [95% CI, 1.07 to 1.09]). The estimated HRs were larger when studying the cohort of Medicare beneficiaries that were always exposed to PM2.5 levels lower than 12 µg/m3 (1.23 [95% CI, 1.18 to 1.28] to 1.37 [95% CI, 1.34 to 1.40]).Comparing the results from multiple and single pollutant models, we found that adjusting for the other two pollutants slightly attenuated the causal effects of PM2.5 and slightly elevated the causal effects of NO2 exposure on all-cause mortality. The results for O3 remained almost unchanged.We found evidence of a harmful causal relationship between mortality and long-term PM2.5 exposures adjusted for NO2 and O3 across the range of annual averages between 2.77 and 17.16 µg/m3 (included >98% of observations) in the entire cohort of Medicare beneficiaries across the continental United States from 2000 to 2016. Our results are consistent with recent epidemiological studies reporting a strong association between long-term exposure to PM2.5 and adverse health outcomes at low exposure levels. Importantly, the curve was almost linear at exposure levels lower than the current national standards, indicating aggravated harmful effects at exposure levels even below these standards.There is, in general, a harmful causal impact of long-term NO2 exposures to mortality adjusted for PM2.5 and O3 across the range of annual averages between 3.4 and 80 ppb (included >98% of observations). Yet within low levels (annual mean ≤53 ppb) below the current national standards, the causal impacts of NO2 exposures on all-cause mortality are nonlinear with statistical uncertainty.The ERCs of long-term O3 exposures on all-cause mortality adjusted for PM2.5 and NO2 are almost flat below 45 ppb, which shows no statistically significant effect. Yet we observed an increased hazard when the O3 exposures were higher than 45 ppb, and the HR was approximately 1.10 when comparing Medicare beneficiaries with annual mean O3 exposures of 50 ppb versus those with 30 ppb.institutions, including those that support the Health Effects Institute; therefore, it may not reflect the views or policies of these parties, and no endorsement by them should be inferred.A list of abbreviations and other terms appears at the end of this volume.

Unraveling the functional attributes of the language connectome: crucial subnetworks, flexibility and variability.

Language processing is a highly integrative function, intertwining linguistic operations (processing the language code intentionally used for communication) and extra-linguistic processes (e.g., attention monitoring, predictive inference, long-term memory). This synergetic cognitive architecture requires a distributed and specialized neural substrate. Brain systems have mainly been examined at rest. However, task-related functional connectivity provides additional and valuable information about how information is processed when various cognitive states are involved. We gathered thirteen language fMRI tasks in a unique database of one hundred and fifty neurotypical adults (InLang [Interactive networks of Language] database), providing the opportunity to assess language features across a wide range of linguistic processes. Using this database, we applied network theory as a computational tool to model the task-related functional connectome of language (LANG atlas). The organization of this data-driven neurocognitive atlas of language was examined at multiple levels, uncovering its major components (or crucial subnetworks), and its anatomical and functional correlates. In addition, we estimated its reconfiguration as a function of linguistic demand (flexibility) or several factors such as age or gender (variability). We observed that several discrete networks could be specifically shaped to promote key functional features of language: coding-decoding (Net1), control-executive (Net2), abstract-knowledge (Net3), and sensorimotor (Net4) functions. The architecture of these systems and the functional connectivity of the pivotal brain regions varied according to the nature of the linguistic process, gender, or age. By accounting for the multifaceted nature of language and modulating factors, this study can contribute to enriching and refining existing neurocognitive models of language. The LANG atlas can also be considered a reference for comparative or clinical studies involving various patients and conditions.

Display and perception of risk: Analysis of decision support system display and its impact on perceived clinical risk of sepsis-induced health deterioration.

Despite acknowledging the value of clinical decision support systems (CDSS) in identifying risk for sepsis-induced health deterioration in-hospitalized patients, the relationship between display features, decision maker characteristics, and recognition of risk by the clinical decision maker remains an understudied, yet promising, area. The objective of this study is to explore the relationship between CDSS display design and perceived clinical risk of in-hospital mortality associated with sepsis. The study utilized data collected through in-person experimental sessions with 91 physicians from the general medical and surgical floors who were recruited across 12 teaching hospitals within the United States. Results of descriptive and statistical analyses provided evidence supporting the impact of display configuration and clinical case severity on perceived risk associated with in-hospital mortality. Specifically, findings showed that a high level of information (represented by the Predisposition, Infection, Response and Organ dysfunction (PIRO) score) and Figure display (as opposed to Text or baseline) increased awareness to recognizing the risk for in-hospital mortality of hospitalized sepsis patients. A CDSS display that synthesizes the optimal features associated with information level and design elements has the potential to enhance the quantification and communication of clinical risk in complex health conditions beyond sepsis.

Communication in the face of death and dying - how does the encounter with death influence the patient management competence of medical students? An outcome-evaluation.

BACKGROUND INFORMATION: As part of an elective course, the Interdisciplinary Centre for Palliative Medicine at Duesseldorf University Hospital offers medical students the opportunity to personally meet and talk to a seriously ill patient on one or more occasions. The future physicians are provided with an opportunity to broaden their professional competence, i.e. their knowledge and skills in patient-centred communication at the end of life, and enhance their personal competence, for example in how to professionally handle their own emotions. A topical e-learning module helps the students to prepare for the meetings, and writing a reflection paper forms the basis for the concluding reflection seminar. OBJECTIVES: The study's objective is a global and outcome-based evaluation of the elective blended-learning course that provides real-world patient interaction. The outcome-based evaluation or outcome assessment aims to objectively evaluate changes identified in knowledge, skills and attitude among the participants of the elective-course. Furthermore, the evaluation aims to answer the question of whether changes especially in attitude (social skills and self-competence) should be expected after the students have met with severely ill or dying patients. METHOD: On two questionnaires specifically developed for this survey the students were able to provide a global rating of the elective course and describe their learning gains in palliative care. The students' learning gains were measured by means of 14 items reflecting the specific educational objectives of the offered elective course. Using the German school grading system as a rating scale, the students assessed their learning progress by retrospectively evaluating their skills before and after completion of the elective course (Comparative Self-Assessment, CSA). RESULTS: In the time from April 2018 till March 2020, 62 students participated in the evaluation. Overall, learning progress among students could be observed across all areas of competence, and in 50% of all retrospective self-assessment items the learning gains were ≥ 50%. The highest learning gain (63.6%) was observed in the students' ability to meet a severely ill patient without fear. The lowest learning gain was observed when students had to confront and accept their own mortality. CONCLUSIONS: The offered elective course supports students in achieving social and self-competence development goals. According to the obtained results, contact with real-world patients helps mould the students' attitude.

National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany - study protocol of a mixed-methods project.

BACKGROUND: In the SARS-CoV-2 pandemic, general and specialist Palliative Care (PC) plays an essential role in health care, contributing to symptom control, psycho-social support, and providing support in complex decision making. Numbers of COVID-19 related deaths have recently increased demanding more palliative care input. Also, the pandemic impacts on palliative care for non-COVID-19 patients. Strategies on the care for seriously ill and dying people in pandemic times are lacking. Therefore, the program 'Palliative care in Pandemics' (PallPan) aims to develop and consent a national pandemic plan for the care of seriously ill and dying adults and their informal carers in pandemics including (a) guidance for generalist and specialist palliative care of patients with and without SARS-CoV-2 infections on the micro, meso and macro level, (b) collection and development of information material for an online platform, and (c) identification of variables and research questions on palliative care in pandemics for the national pandemic cohort network (NAPKON). METHODS: Mixed-methods project including ten work packages conducting (online) surveys and qualitative interviews to explore and describe i) experiences and burden of patients (with/without SARS-CoV-2 infection) and their relatives, ii) experiences, challenges and potential solutions of health care professionals, stakeholders and decision makers during the SARS-CoV-2 pandemic. The work package results inform the development of a consensus-based guidance. In addition, best practice examples and relevant literature will be collected and variables for data collection identified. DISCUSSION: For a future "pandemic preparedness" national and international recommendations and concepts for the care of severely ill and dying people are necessary considering both generalist and specialist palliative care in the home care and inpatient setting.

[PARPACT: Paramedic Palliative Care Test : Validation of a questionnaire to assess palliative care knowledge and self-efficacy expectations of paramedics]. / PARPACT ­ Paramedic Palliative Care Test : Validierung eines Tests für palliatives Wissen und Selbstwirksamkeitserwartung bei Mitarbeiter*innen im Rettungswesen.

BACKGROUND: Given the large number of palliative patients cared for by the emergency services, education and training in palliative care topics are playing an increasingly important role. To support decision-making in an emergency setting a palliative or emergency card has been introduced in many cities. OBJECTIVES: To assess the success of educational interventions and the effect of the palliative or emergency card, a questionnaire was developed and validated to determine palliative knowledge and palliative self-efficacy expectations in the emergency services. MATERIALS AND METHODS: A Delphi process was applied for development and content validation. Factor analysis was used for construct validation. Criterion validity was assessed with the help of 22 nurses specially trained in palliative care. Reliability was determined using Cronbach's alpha as a measure of internal consistency. RESULTS: In all, 291 of 750 paramedics participated in the voluntary survey. After completion of the Delphi process, there was consensus that the important topics of pain, dyspnea, sedation, end-of-life care, euthanasia, and legal aspects were covered in the questionnaire. Factor analysis was in favor of a six-factor solution. Criterion validation revealed a significant difference in palliative knowledge between palliative care nurses (MRang 289.73) and paramedics (MRang 146.97, U = 281.000, r = 0.40, p < 0.001). Cronbach's alpha was 0.70 for the knowledge questions and 0.82 for the palliative care self-efficacy expectancy subscale. CONCLUSIONS: The Paramedic Palliative Care Test (PARPACT) is a validated measurement tool for testing educational interventions in paramedicine.

[General palliative care during the pandemic]. / Allgemeine Palliativversorgung in Pandemiezeiten.

BACKGROUND: The German healthcare system is facing unprecedented challenges due to the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Palliative care for critically ill patients and their families was also severely compromised, especially during the first wave of the pandemic, in both inpatient and outpatient settings. MATERIALS AND METHODS: The paper is based on our experience in routine inpatient palliative care and partial results of a study conducted as part of the collaborative project "National Strategy for Palliative Care in Pandemic Times (PallPan)". Based on our experience from the inpatient care of patients suffering from severe or life-limiting disease, best-practice examples for improving or maintaining care in the on-going pandemic are described. RESULTS: Restrictive visitor regulations, communication barriers and insufficient possibilities to accompany dying patients or their grieving relatives continue to pose major challenges in general and specialized inpatient palliative care. In order to maintain high-quality palliative care, it is necessary to create structures that enable targeted therapy discussions and end-of-life care in the presence of relatives. Therefore, innovative communication methods like video calls or individualized exceptions from visitor restrictions are needed. CONCLUSIONS: Adequate care for seriously ill and dying patients and their relatives must be guaranteed during the pandemic. Individual arrangements should be arranged and implemented. If available, earlier involvement of specialized palliative care teams can be beneficial.

Hypothalamic Pilomyxoid Astrocytoma in a Child with Lipodystrophy.

Pilomyxoid astrocytoma is a rare form of pediatric CNS malignancy first classified in 2007 by the World Health Organization. The tumors are similar to pilocytic astrocytomas, sharing both some imaging and histologic traits. However, pilomyxoid astrocytomas portend a more ominous prognosis, with more aggressive local tendencies and a greater proclivity for leptomeningeal spread. Although tissue sampling is ultimately required to differentiate pilocytic astrocytomas and pilomyxoid astrocytomas, some imaging features can be used to suggest a pilomyxoid astrocytoma, including homogeneous enhancement, leptomeningeal seeding, and lack of intratumoral cysts. In this article, a case of a hypothalamic pilomyxoid astrocytoma is described, in which the presenting disorder was profound generalized lipodystrophy. The aforementioned imaging characteristics of pilomyxoid astrocytomas are reviewed, as are the pathologic features of such tumors, including their angiocentric cellular arrangement and myxoid background.

[Palliative care in patients with left ventricular assist devices: systematic review]. / "Palliative care" bei Patienten mit Linksherzunterstützungssystem: systematische Übersichtsarbeit.

BACKGROUND: An increasing number of patients reach the final stage of heart failure with heart transplantation as the only curative treatment. Mechanical circulatory support, such as left ventricular assist devices (LVAD) are becoming increasingly more important at this stage of the disease. An LVAD improves the quality of life and prolongs the lifespan. The LVAD is used as a bridge to transplantation (BTT) for patients waiting for a donor heart or as a destination therapy (DT) with no transplantation intended; nevertheless, implantation is often associated with complications and the prognosis remains unfavorable in DT cases or after transition from BTT to DT. For patients the device may be a source of physical and psychological distress and can become a burden for families and caregivers. So far it remains unclear whether LVAD treatment is an indication for concurrent palliative care. OBJECTIVE: The aim of this study was to collect the current data on the influence of palliative care in LVAD patients and to identify possible formats of palliative care in clinical practice. MATERIAL AND METHODS: In May 2020, a systematic literature search was performed using the PICOS instrument in six different databases, i.e. PubMed, Cochrane library, Google scholar, Scopus, Web of Science and Journals@Ovid. We included quantitative and qualitative studies in English and German. Case reports, comments and pediatric studies were excluded. RESULTS: A total of 21 publications from an initial number of 491 were included in this review. The integration of palliative care in the context of LVAD implantation increased the number of advance directives and documented surrogate decision makers. Studies found a positive influence of palliative care on the conditions and place of death, family involvement and symptom and pain management. Involvement in the decision-making process may improve patient selection for LVAD treatment and helps patients to make the decision on informed consent. Various formats for the integration of palliative medical concepts into LVAD treatment are reported. It is not clear when palliative care involvement should start; however, most articles support an early and continuous integration in the LVAD process. We have aggregated possible topics for palliative care consultations from a number of publications. Mutual teaching of both LVAD and palliative care teams is recommended. Integration of a dedicated LVAD palliative care specialist as part of the LVAD team can support care for patients as well as clinicians. CONCLUSION: The role of palliative care in LVAD patients in clinical practice in the German-speaking area is not standardized. Early and continuous integration of palliative care into the course of LVAD treatment can improve the quality of care. Benefits for LVAD patients, caregivers and clinicians are described. For this purpose, recommendations as well as professional training for palliative care practitioners are useful. Further studies are needed to clarify the impact of palliative care in both DT and BTT patients.

Development of polymorphic markers in the immune gene complex loci of cattle.

The addition of cattle health and immunity traits to genomic selection indices holds promise to increase individual animal longevity and productivity, and decrease economic losses from disease. However, highly variable genomic loci that contain multiple immune-related genes were poorly assembled in the first iterations of the cattle reference genome assembly and underrepresented during the development of most commercial genotyping platforms. As a consequence, there is a paucity of genetic markers within these loci that may track haplotypes related to disease susceptibility. By using hierarchical assembly of bacterial artificial chromosome inserts spanning 3 of these immune-related gene regions, we were able to assemble multiple full-length haplotypes of the major histocompatibility complex, the leukocyte receptor complex, and the natural killer cell complex. Using these new assemblies and the recently released ARS-UCD1.2 reference, we aligned whole-genome shotgun reads from 125 sequenced Holstein bulls to discover candidate variants for genetic marker development. We selected 124 SNPs, using heuristic and statistical models to develop a custom genotyping panel. In a proof-of-principle study, we used this custom panel to genotype 1,797 Holstein cows exposed to bovine tuberculosis (bTB) that were the subject of a previous GWAS study using the Illumina BovineHD array. Although we did not identify any significant association of bTB phenotypes with these new genetic markers, 2 markers exhibited substantial effects on bTB phenotypic prediction. The models and parameters trained in this study serve as a guide for future marker discovery surveys particularly in previously unassembled regions of the cattle genome.

Effect of Ventral vs Dorsal Spinal Surgery on Patient-Reported Physical Functioning in Patients With Cervical Spondylotic Myelopathy: A Randomized Clinical Trial.

Importance: Cervical spondylotic myelopathy is the most common cause of spinal cord dysfunction worldwide. It remains unknown whether a ventral or dorsal surgical approach provides the best results. Objective: To determine whether a ventral surgical approach compared with a dorsal surgical approach for treatment of cervical spondylotic myelopathy improves patient-reported physical functioning at 1 year. Design, Setting, and Participants: Randomized clinical trial of patients aged 45 to 80 years with multilevel cervical spondylotic myelopathy enrolled at 15 large North American hospitals from April 1, 2014, to March 30, 2018; final follow-up was April 15, 2020. Interventions: Patients were randomized to undergo ventral surgery (n = 63) or dorsal surgery (n = 100). Ventral surgery involved anterior cervical disk removal and instrumented fusion. Dorsal surgery involved laminectomy with instrumented fusion or open-door laminoplasty. Type of dorsal surgery (fusion or laminoplasty) was at surgeon's discretion. Main Outcomes and Measures: The primary outcome was 1-year change in the Short Form 36 physical component summary (SF-36 PCS) score (range, 0 [worst] to 100 [best]; minimum clinically important difference = 5). Secondary outcomes included 1-year change in modified Japanese Orthopaedic Association scale score, complications, work status, sagittal vertical axis, health resource utilization, and 1- and 2-year changes in the Neck Disability Index and the EuroQol 5 Dimensions score. Results: Among 163 patients who were randomized (mean age, 62 years; 80 [49%] women), 155 (95%) completed the trial at 1 year (80% at 2 years). All patients had surgery, but 5 patients did not receive their allocated surgery (ventral: n = 1; dorsal: n = 4). One-year SF-36 PCS mean improvement was not significantly different between ventral surgery (5.9 points) and dorsal surgery (6.2 points) (estimated mean difference, 0.3; 95% CI, -2.6 to 3.1; P = .86). Of 7 prespecified secondary outcomes, 6 showed no significant difference. Rates of complications in the ventral and dorsal surgery groups, respectively, were 48% vs 24% (difference, 24%; 95% CI, 8.7%-38.5%; P = .002) and included dysphagia (41% vs 0%), new neurological deficit (2% vs 9%), reoperations (6% vs 4%), and readmissions within 30 days (0% vs 7%). Conclusions and Relevance: Among patients with cervical spondylotic myelopathy undergoing cervical spinal surgery, a ventral surgical approach did not significantly improve patient-reported physical functioning at 1 year compared with outcomes after a dorsal surgical approach. Trial Registration: ClinicalTrials.gov Identifier: NCT02076113.

PTH como predictor de hipocalcemia postiroidectomía total / PTH as a predictor of hypocalcemia after total thyroidectomy

Resumen Objetivo: Evaluar la asociación entre el valor de PTH medido a las 6 h posoperatorias de los pacientes sometidos a una tiroidectomía total, y la presentación de hipocalcemia en las primeras 24 h posoperatorias. Materiales y Método: Estudio analítico retrospectivo que utiliza una base de datos de 173 pacientes operados de tiroidectomía total entre enero de 2016 a diciembre de 2018 en el Hospital Militar de Santiago (HMS). Se revisaron datos demográficos y perioperatorios. Se utilizó curva ROC para evaluar la asociación entre PTH e hipocalcemia en nuestros pacientes. Resultados: 106 pacientes que cumplen criterios de inclusión. Promedio de PTH 30,5 (1,4-169), 58% presentó hipocalcemia, solo 17 pacientes fueron sintomáticos. PTH promedio en pacientes sintomáticos fue de 7,8 pg/ml. Curva ROC con área bajo la curva de 0,83 (0,75-0,92). Considerando valores útiles para la práctica clínica, una PTH menor a 6,3 (valor más bajo en nuestro laboratorio), tiene sensibilidad de 97%. El valor 18 de PTH (límite inferior del rango de normalidad del laboratorio) se obtiene 88,89% de sensibilidad con 66,07% de especificidad. Y con un valor de 47 pg/ml, se obtiene con un 91% de especificidad para predecir pacientes que no tendrían hipocalcemia. Conclusión: Con un valor de PTH disminuido bajo su valor normal, se puede decir que el riesgo de tener hipocalcemia es sobre el 80%, por lo que se debería iniciar tratamiento profiláctico y desistir del alta. En cambio, para definir un valor superior sobre el cual dar de alta precoz con seguridad, faltan más estudios.

Aim: To evaluate the association between PTH (parathormone) value measured at 6 hours postoperatively of patients submitted to total thyroidectomy, and the presentation of hypocalcemia in the first 24 hours. Materials and Method: Retrospective study of 173 patients with total thyroidectomy between January 2016 to December 2018 in HMS. Demographic and perioperative data were reviewed. The ROC curve was used to evaluate the association between PTH and hypocalcemia in our patients. Results: 106 patients meet inclusion criteria. Average of PTH 30.5 (1.4-169), 58% presented hypocalcemia, 17 patients were symptomatic. ROC curve with area under the curve of 0.83 (0.75-0.92) was obtained considering useful values for clinical practice, a PTH less than 6.3 (lowest value in our laboratory), has 97% sensitivity to predict hypocalcemia. If we use the value 18 we obtain 88.89% sensitivity with 66.07% specificity. And with a value of 47, it is obtained with 91% specificity to predict patients who would not have hypocalcemia Conclusion: With a PTH value decreased below its normal value, it can be said that the risk of having hypocalcemia is over 80%, so that prophylactic treatment should be initiated. To define a value on which to register early with security, more study is needed.

Identification of clinically useful predictive genetic variants in pachyonychia congenita.

BACKGROUND: Pachyonychia congenita (PC) refers to a group of autosomal dominant disorders caused by mutations in five keratin genes (KRT16,KRT6A,KRT17,KRT6B or KRT6C). Current disease classification is based on the gene harbouring disease-causing variants. AIMS: We harnessed the International Pachyonychia Congenita Research Registry (IPCRR) containing both clinical and molecular data on patients with PC worldwide, to identify genetic variants predicting disease severity. METHODS: We ascertained 815 individuals harbouring keratin mutations registered in the IPCRR. We looked for statistically significant associations between genetic variants and clinical manifestations in a subgroup of patients carrying mutations found in at least 10% of the cohort. Data were analysed using χ2 and Kruskal-Wallis tests. RESULTS: We identified five mutations occurring in at least 10% of the patients registered in the IPCRR. The KRT16 p.L132P mutation was significantly associated with younger age of onset, presence of palmar keratoderma oral leucokeratosis and a higher number of involved nails. By contrast, the KRT16 p.N125S and p.R127C mutations resulted in a milder phenotype featuring a decreased number of involved nails and older age of onset. Patients carrying the p.N125S mutation were less likely to develop palmar keratoderma while p.R127C was associated with an older age of palmoplantar keratoderma onset. Moreover, the KRT17 p.L99P mutation resulted in an increased number of involved fingernails and patients demonstrating 20-nail dystrophy, while the opposite findings were observed with KRT17 p.N92S mutation. CONCLUSIONS: We have identified novel and clinically useful genetic predictive variants in the largest cohort of patients with PC described to date.

[Cooperation between intensive care and palliative care : The status quo in German Comprehensive Cancer Centers]. / Zusammenarbeit von Intensivmedizin und Palliativmedizin : Eine Bestandsaufnahme an den deutschen onkologischen Spitzenzentren.

BACKGROUND: For intensive care patients with limited life expectancy the integration of palliative care in intensive care may be beneficial. However, little is known about the extent of this interdisciplinary collaboration. OBJECTIVES: The support given by palliative medicine in German oncological centers and used by the intensive care units should be recorded. MATERIAL AND METHODS: A descriptive survey was conducted in all of the 16 Comprehensive Cancer Centers (CCC) funded by German Cancer Aid. The questionnaires were sent to the head of department of the CCCs' specialized palliative care teams. Data were collected for the year 2016. Quantitative data were analysed to establish frequencies, given as mean and median. A qualitative section asked for trigger factors, i.e., patient characteristics triggering a palliative care consultation. Evaluation was inductively carried out by content analysis according to Mayring. RESULTS: Data from 15 of the 16 CCCs (94%) were obtained between July and August 2017. In 2016, the median of intensive care patients with palliative care consultations was 33 (minimum 0, maximum 100). The median of nine patients were transferred from an intensive care unit to a palliative care unit (minimum 1, maximum 30). Multidisciplinary ward rounds by both intensive and palliative care staff were available in two CCCs on a regular basis. Two CCCs implemented screening tools to integrate specialized palliative care into intensive care. From 23 responses concerning triggers, three categories were established, i.e., "team's decision and attitude", "patient's condition" and "desires of patients and relatives". CONCLUSIONS: Palliative care is available in German CCCs. However, the degree of integration of specialized palliative care into intensive care units is low. Screening tools are available to identify patients with complex needs and to trigger a palliative care consultation. These tools, as well as joint ward rounds of intensive and palliative care staff, can improve the quality of patient centred care.

Hepatocellular carcinoma: epidemiology, screening, and assessment of hepatic reserve.

Hepatocellular carcinoma is a leading cause of cancer-related mortality worldwide. This review summarizes the epidemiology and causes of the disease, and the roles of screening and surveillance for early tumour detection. It also highlights the important role of assessment of hepatic reserve in consideration of appropriate staging and treatment.

TRIO Method for Detection of Beta-Lactams, Sulfonamides, and Tetracyclines in Raw Commingled Cows' Milk.

A qualitative 3 min one-step assay for detecting beta-lactam, sulfonamide, and tetracycline antibiotics was validated following milk screening test guidelines developed by FDA-CVM, AOAC-RI, and IDF. The validated 90% detection levels with 95% confidence were: penicillin G 2 part per billion (ppb); amoxicillin 4 ppb; ampicillin 9 ppb; ceftiofur plus metabolites 50 ppb; cloxacillin 9 ppb; cephapirin 15 ppb; sulfadimethoxine 8 ppb; sulfamethazine 9 ppb; chlortetracycline 34 ppb; oxytetracycline 53 ppb; and tetracycline 42 ppb. Detection levels were lower than U.S. and Canadian allowable limits for milk and were consistent with most European Maximum Residue Limits. Tests of raw commingled cows' milk indicated a low positive error rate of <0.3% with no interferences demonstrated by 1.08 MM/mL somatic cells, Gram-positive or Gram-negative bacteria < 300 K/mL, freeze/thawing, or non-targeted drugs. Detection of incurred residues were similar to, or more sensitive to, fortified samples. Some cross reactivity across drug families occurred in interference studies and therefore initial positive samples should be confirmed with drug family specific screening methods. The National Conference of Interstate Milk Shipments approval as a bulk tank/tanker screening test was completed in three stages for each drug family, including a tetracycline confirmation procedure to target U.S. tolerance levels. Detection and robustness were found to be appropriate for multiple countries' regulatory requirements for screening tests. The method development, validation, and approval was intended to diversify and increase the verification tools for the control of the major antibiotic drug families used in managing cows' health and welfare.

Heterogeneous ozone effects on the DNA methylome of bronchial cells observed in a crossover study.

We used a randomized crossover experiment to estimate the effects of ozone (vs. clean air) exposure on genome-wide DNA methylation of target bronchial epithelial cells, using 17 volunteers, each randomly exposed on two separated occasions to clean air or 0.3-ppm ozone for two hours. Twenty-four hours after exposure, participants underwent bronchoscopy to collect epithelial cells whose DNA methylation was measured using the Illumina 450 K platform. We performed global and regional tests examining the ozone versus clean air effect on the DNA methylome and calculated Fisher-exact p-values for a series of univariate tests. We found little evidence of an overall effect of ozone on the DNA methylome but some suggestive changes in PLSCR1, HCAR1, and LINC00336 DNA methylation after ozone exposure relative to clean air. We observed some participant-to-participant heterogeneity in ozone responses.