Electrolytes variability and clinical outcomes, in-hospital mortality and acute kidney injury

Serum electrolytes are essential for basic life functioning. They play an important role in maintaining electrical neutrality in cells, generating and conducting action potentials in the nerves and muscles, cooperating to enzymatic functions. Electrolytes come from diet and serum concentrations are strictly regulated by the kidney, the main human organ deputed to control human hydro-electrolyte homeostasis. These electrolytes can have an imbalance, leading to either high or low levels. Disorders of sodium (Na+ ) and potassium (K+ ) are the most common electrolytes derangements observed in hospitalized population. High or low electrolytes levels disrupt normal bodily functions and can lead to even life-threatening complications. Medical literature has clearly demonstrated the association of Na+ and K+ disorders with poor prognosis of hospitalized patient. Recent scientific research reveals, however, that even little electrolyte changes might have a significant influence on patient survival. Furthermore, electrolytes fluctuations in a theoretical normal range should also warn medical attention. Given that the kidney is the primary organ engaged in electrolyte and water balance, the link between renal dysfunction and electrolyte abnormalities is unsurprising. Even though these disorders are generally considered to be a consequence of renal damage or simple bystanders, recent scientific evidence are now suggesting that electrolytes imbalance might precede kidney injury. The aim of my dissertation will focus on the studies conducted during the three years of my PhD program. Herein I am going to analyse the strong association between Na+ and K+ derangements and in-hospital clinical outcomes with particular attention on electrolytes variability or fluctuations even in the normal ranges and its relationship with in-hospital mortality and acute kidney injury

Association between borderline dysnatremia and mortality insight into a new data mining approach

Abstract Background Even small variations of serum sodium concentration may be associated with mortality. Our objective was to confirm the impact of borderline dysnatremia for patients admitted to hospital on in-hospital mortality using real life care data from our electronic health record (EHR) and a phenome-wide association analysis (PheWAS). Methods Retrospective observational study based on patient data admitted to Hôpital Européen George Pompidou, between 01/01/2008 and 31/06/2014; including 45,834 patients with serum sodium determinations on admission. We analyzed the association between dysnatremia and in-hospital mortality, using a multivariate logistic regression model to adjust for classical potential confounders. We performed a PheWAS to identify new potential confounders. Results Hyponatremia and hypernatremia were recorded for 12.0% and 1.0% of hospital stays, respectively. Adjusted odds ratios (ORa) for severe, moderate and borderline hyponatremia were 3.44 (95% CI, 2.41–4.86), 2.48 (95% CI, 1.96–3.13) and 1.98 (95% CI, 1.73–2.28), respectively. ORa for severe, moderate and borderline hypernatremia were 4.07 (95% CI, 2.92–5.62), 4.42 (95% CI, 2.04–9.20) and 3.72 (95% CI, 1.53–8.45), respectively. Borderline hyponatremia (ORa = 1.57 95% CI, 1.35–1.81) and borderline hypernatremia (ORa = 3.47 95% CI, 2.43–4.90) were still associated with in-hospital mortality after adjustment for classical and new confounding factors identified through the PheWAS analysis. Conclusion Borderline dysnatremia on admission are independently associated with a higher risk of in-hospital mortality. By using medical data automatically collected in EHR and a new data mining approach, we identified new potential confounding factors that were highly associated with both mortality and dysnatremia

Additional file 3: of Association between borderline dysnatremia and mortality insight into a new data mining approach

Manhattan Plots Representing the –Log(p-value) of the Association Tests Between ICD-10 Billing Codes, Borderline Hyponatremia, Borderline Hypernatremia and Mortality (DOCX 85 kb

Additional file 4: of Association between borderline dysnatremia and mortality insight into a new data mining approach

Association between Dysnatremia and In-Hospital mortality. Comparison of the different regression models (DOCX 27 kb

Additional file 2: of Association between borderline dysnatremia and mortality insight into a new data mining approach

Unadjusted and Adjusted Risk of In-Hospital Mortality for Each Patients Subgroup According to Their Serum Sodium Concentration at Hospital Admission (DOCX 87 kb

Additional file 1: of Association between borderline dysnatremia and mortality insight into a new data mining approach

SQL code extraction from the HEGP-CDW and R Code for the PheWAS analysis (DOCX 69 kb

Improving the evaluation and treatment of neuroendocrine disorders

The aim of this thesis was to improve the diagnosis and treatment of neuroendocrine disorders. In addition, it shows further possibilities to achieve this goal in the long term

Improving the evaluation and treatment of neuroendocrine disorders

The aim of this thesis was to improve the diagnosis and treatment of neuroendocrine disorders. In addition, it shows further possibilities to achieve this goal in the long term