Automated identification of patient subgroups: A case-study on mortality of COVID-19 patients admitted to the ICU.

BACKGROUND: - Subgroup discovery (SGD) is the automated splitting of the data into complex subgroups. Various SGD methods have been applied to the medical domain, but none have been extensively evaluated. We assess the numerical and clinical quality of SGD methods. METHOD: - We applied the improved Subgroup Set Discovery (SSD++), Patient Rule Induction Method (PRIM) and APRIORI - Subgroup Discovery (APRIORI-SD) algorithms to obtain patient subgroups on observational data of 14,548 COVID-19 patients admitted to 73 Dutch intensive care units. Hospital mortality was the clinical outcome. Numerical significance of the subgroups was assessed with information-theoretic measures. Clinical significance of the subgroups was assessed by comparing variable importance on population and subgroup levels and by expert evaluation. RESULTS: - The tested algorithms varied widely in the total number of discovered subgroups (5-62), the number of selected variables, and the predictive value of the subgroups. Qualitative assessment showed that the found subgroups make clinical sense. SSD++ found most subgroups (n = 62), which added predictive value and generally showed high potential for clinical use. APRIORI-SD and PRIM found fewer subgroups (n = 5 and 6), which did not add predictive value and were clinically less relevant. CONCLUSION: - Automated SGD methods find clinical subgroups that are relevant when assessed quantitatively (yield added predictive value) and qualitatively (intensivists consider the subgroups significant). Different methods yield different subgroups with varying degrees of predictive performance and clinical quality. External validation is needed to generalize the results to other populations and future research should explore which algorithm performs best in other settings.

The association between symptom severity and physical activity participation in people seeking care for acute low back pain.

PURPOSE: To investigate the association between symptom severity and physical activity participation in people with acute non-specific low back pain (LBP). METHODS: The sample included a total of 999 patients who presented to primary care with an acute episode of low back pain. Symptom severity, in terms of activity limitation and severity of pain; and physical activity participation before (habitual) and after pain onset were assessed using self-report questionnaires. All participants were interviewed within 14 days of pain onset. RESULTS: At interview most of the participants (87.5 %) reported having moderate to extreme activity limitation due to back pain. There was a significant decrease in physical activity participation after pain onset (mean difference: -176 min, 95 % CI 327-400; p < 0.0001) but no association between habitual or change in physical activity participation and symptom severity was observed (p > 0.21). CONCLUSION: Pain onset causes a significant and immediate decrease in physical activity participation, but this change does not seem to be associated with symptom severity.

[Persistent tachypnea in infants: possibly due to interstitial pneumonitis]. / Aanhoudende tachypneu bij een zuigeling: mogelijk interstitiële pneumonitis.

In three male infants aged 3, 4.5 and 11 months with tachypnea and feeding problems, the initial supplementary examination revealed no possible cause. The tissue obtained by open lung biopsy showed interstitial pneumonia/pneumonitis. The two youngest patients were treated with hydrochloroquine and prednisone; the youngest died at the age of 18 months. Both the infant who was maintained on hydrochloroquine and the one who did not receive treatment showed a normal respiratory frequency and growth during the following years. Tachypnea is less easily recognised in infants than in older patients. It may be the only early symptom of interstitial pneumonitis. A normal chest X-ray cannot exclude an incipient interstitial pneumonitis as the cause of the tachypnea. A high-resolution CT-scan of the lung parenchyma is necessary in order to detect the disease at an early stage. Histological examination of an open lung biopsy specimen is essential for the specific diagnosis, therapy and prognosis.

[Relative adrenocortical insufficiency with sepsis, diagnosed and treated with hydrocortisone supplementation]. / Relatieve bijnierschorsinsufficiëntie bij sepsis, gediagnosticeerd en behandeld door hydrocortisonsuppletie.

An 82-year-old woman was admitted to the ICU with septic shock and multiple organ failure. Despite the lack of a persistent septic focus she continued to be dependent on large doses of norepinephrine whilst receiving adequate antimicrobial therapy. After a trial treatment with hydrocortisone the norepinephrine infusion could be withdrawn within a few days and she made a full recovery. In the case of seriously ill patients the diagnosis 'relative adrenocortical insufficiency' is predominantly made on the basis of the clinical picture. The remarkable clinical response to the administration of hydrocortisone (400 mg in the first 24 h) confirmed the diagnosis. The dosage of vasopressors can be reduced remarkably quickly. The stimulatory test for adrenocorticotropin hormone (ACTH) has no added value as reference values for critically ill patients are not available and because the results do not predict the response to the treatment.

Nursing migration: global treasure hunt or disaster-in-the-making?

International nurse migration--moving from one country to another in the search of employment--is the focus of this article. The majority of member states of the World Health Organization report a shortage, maldistribution and misutilisation of nurses. International recruitment has been seen as a solution. The negative effects of international migration on the 'supplier' countries may be recognised today but are not effectively addressed. Nurse migration is motivated by the search for professional development, better quality of life and personal safety. Pay and learning opportunities continue to be the most frequently reported incentives for nurse migration, especially by nurses from less-developed countries. Career opportunities were considered key incentives for nurses emigrating from high-income countries. Language was reported to be a significant barrier. The positive global economic/social/professional development resulting from international migration needs to be weighed against a substantial 'brain and skills drain' experienced by supplier countries. The vulnerable status of migrant nurses is also of concern in certain cases. The focus on short-term solutions as opposed to resolving the problem of a worldwide shortage of nurses causes great concern. Recent initiatives attempt to curb or channel international recruitment. The delicate balance between recognising the right of individual nurses to migrate and a collective concern for the health of a nation's population must be achieved.

Real-time imaging of the dynamics of secretory granules in growth cones.

Secretory granules containing a hybrid protein consisting of the regulated secretory protein tissue plasminogen activator and an enhanced form of green fluorescent protein were tracked at high spatial resolution in growth cones of differentiated PC12 cells. Tracking shows that granules, unlike synaptic vesicles, generally are mobile in growth cones. Quantitative analysis of trajectories generated by granules revealed two dominant modes of motion: diffusive and directed. Diffusive motion was observed primarily in central and peripheral parts of growth cones, where most granules diffused two to four orders of magnitude more slowly than comparably sized spheres in dilute solution. Directed motion was observed primarily in proximal parts of growth cones, where a subset of granules underwent rapid, directed motion at average speeds comparable to those observed for granules in neurites. This high-resolution view of the dynamics of secretory granules in growth cones provides insight into granule organization and release at nerve terminals. In particular, the mobility of granules suggests that granules, unlike synaptic vesicles, are not tethered stably to cytoskeletal structures in nerve terminals. Moreover, the slow diffusive nature of this mobility suggests that secretory responses involving centrally distributed granules in growth cones will occur slowly, on a time scale of minutes or longer.

Real-time imaging of the axonal transport of granules containing a tissue plasminogen activator/green fluorescent protein hybrid.

A hybrid protein, tPA/GFP, consisting of rat tissue plasminogen activator (tPA) and green fluorescent protein (GFP) was expressed in PC12 cells and used to study the distribution, secretory behavior, and dynamics of secretory granules containing tPA in living cells with a neuronal phenotype. High-resolution images demonstrate that tPA/GFP has a growth cone-biased distribution in differentiated cells and that tPA/GFP is transported in granules of the regulated secretory pathway that colocalize with granules containing secretogranin II. Time-lapse images of secretion reveal that secretagogues induce substantial loss of cellular tPA/GFP fluorescence, most importantly from growth cones. Time-lapse images of the axonal transport of granules containing tPA/GFP reveal a surprising complexity to granule dynamics. Some granules undergo canonical fast axonal transport; others move somewhat more slowly, especially in highly fluorescent neurites. Most strikingly, granules traffic bidirectionally along neurites to an extent that depends on granule accumulation, and individual granules can reverse their direction of motion. The retrograde component of this bidirectional transport may help to maintain cellular homeostasis by transporting excess tPA/GFP back toward the cell body. The results presented here provide a novel view of the axonal transport of secretory granules. In addition, the results suggest that tPA is targeted for regulated secretion from growth cones of differentiated cells, strategically positioning tPA to degrade extracellular barriers or to activate other barrier-degrading proteases during axonal elongation.

Marketing and nursing in a competitive environment.

Marketing can no longer be considered vulgar commercialism. Ethically applied, marketing is in fact one of the necessary building stones and development tools for the future development of nursing. In the new competitive environment being created in health sectors to improve efficiency and cost-effectiveness, the nursing profession must learn to use marketing techniques to survey the needs, identify gaps in services and develop products and services that will be relevant for today's empowered consumer.

Influence of indapamide and chlorthalidone on reperfusion-induced ventricular fibrillation in isolated guinea pig hearts.

The delayed rectifier potassium current (IK) is a major repolarizing current in guinea pig ventricular myocytes. Blockade of IK or other repolarizing currents is of increasing interest for development of antiarrhythmic drugs; however, these interventions may also be proarrhythmic. In the present study, we compared the potential antiarrhythmic properties of indapamide and chlorthalidone, two structurally related sulfonamide diuretics which differ in their ability to block the slow component of the delayed rectifier (IKs) in isolated, buffer-perfused guinea pig hearts. Hearts underwent 30-min global no-flow ischemia and 10-min reperfusion. Dose-response (10(-7)-10(-4) M) effects of indapamide or chlorthalidone on reperfusion-induced arrhythmias, coronary flow, and heart rate (HR) were evaluated in a randomized blinded fashion. There was no significant difference in the incidence of ventricular fibrillation (VF) for either compound as compared with untreated controls. However, VF duration was reduced to < 40 s in all hearts treated with indapamide 10(-4) M). Mean VF duration with indapamide 10(-4) M was 31 +/- 4 versus 70 +/- 40 s in controls (p < 0.05). Chlorthalidone did not protect against reperfusion-induced arrhythmias. HR was unchanged with either compound; coronary flow during the control perfusion period increased approximately 43% with indapamide 10(-4) M (p < 0.05 vs. all treatment groups). These results demonstrate that indapamide, but not chlorthalidone, confers significant protection against reperfusion-induced VF in this experimental preparation and suggest that selective block of IKs may be antiarrhythmic.

Professional and socioeconomic issues: separate but interdependent.

The common view is that professional issues should relate directly to nursing practice, socioeconomic issues to work conditions. But if nurses' associations are to deal effectively with nursing concerns, this distinction should not exist. Below, an explanation of why not.

Effect of alprazolam on ischemia and reperfusion-induced ventricular arrhythmias in the isolated perfused rat heart.

The effects of the triazolobenzodiazepine anxiolytic, alprazolam, on the incidence of ischemia- and reperfusion-induced ventricular arrhythmias was studied in the isolated buffer-perfused rat heart. Administration of alprazolam before and after myocardial ischemia resulted in a dosage-dependent reduction in the incidence and duration of reperfusion-induced ventricular fibrillation and was significant at a concentration of 1 X 10(-3) mol/l alprazolam. This cardioprotective effect was not extended to ischemia-induced ventricular dysrhythmias. In conclusion, our findings provide evidence that benzodiazepine drugs are able to provide a cardioprotective effect in the experimental setting of myocardial ischemia followed by coronary reperfusion.