Background The exact risk of developing QTc-prolongation when using a combination of QTc-prolonging drugs is still unknown, making it difficult to interpret these QT drug-drug interactions (QT-DDIs... Show moreBackground The exact risk of developing QTc-prolongation when using a combination of QTc-prolonging drugs is still unknown, making it difficult to interpret these QT drug-drug interactions (QT-DDIs). A tool to identify high-risk patients is needed to support healthcare providers in handling automatically generated alerts in clinical practice. The main aim of this study was to develop and validate a tool to assess the risk of QT-DDIs in clinical practice. Methods A model was developed based on risk factors associated with QTc-prolongation determined in a prospective study on QT-DDIs in a university medical center inthe Netherlands. The main outcome measure was QTc-prolongation defined as a QTc interval > 450 ms for males and > 470 ms for females. Risk points were assigned to risk factors based on their odds ratios. Additional risk factors were added based on a literature review. The ability of the model to predict QTc-prolongation was validated in an independent dataset obtained from a general teaching hospital against QTc-prolongation as measured by an ECG as the gold standard. Sensitivities, specificities, false omission rates, accuracy and Youden's index were calculated. Results The model included age, gender, cardiac comorbidities, hypertension, diabetes mellitus, renal function, potassium levels, loop diuretics, and QTc-prolonging drugs as risk factors. Application of the model to the independent dataset resulted in an area under the ROC-curve of 0.54 (95% CI 0.51-0.56) when QTc-prolongation was defined as > 450/470 ms, and 0.59 (0.54-0.63) when QTc-prolongation was defined as > 500 ms. A cut-off value of 6 led to a sensitivity of 76.6 and 83.9% and a specificity of 28.5 and 27.5% respectively. Conclusions A clinical decision support tool with fair performance characteristics was developed. Optimization of this tool may aid in assessing the risk associated with QT-DDIs. Show less
In this thesis several aspects on the diagnosing and management of patients with acute abdominal pain are investigated. 1; The efficacy and safety of standard outpatient re-evaluation for patients... Show moreIn this thesis several aspects on the diagnosing and management of patients with acute abdominal pain are investigated. 1; The efficacy and safety of standard outpatient re-evaluation for patients not admitted to the hospital after emergency department evaluation for acute abdominal pain. 2; The use of a diagnostic strategy for patients clinically suspected to have appendicitis incorporating non-invasive modalities such as clinical evaluation, routine ultrasound and clinical re-evaluation, and a minimal use of complementary CT or laparoscopy. 3; The possibility to clinically differentiate between children with acute appendicitis and those with acute mesenteric lymphadenitis. 4; The value of secondary signs during the ultrasonographic evaluation of children with suspected appendicitis. 5; The impact of radiological imaging on diagnostic accuracy and clinical decision making for patients with acute colonic diverticulitis. 6; A systematic review on laparoscopic peritoneal lavage for patients with peritonitis due to perforated colonic diverticulitis. Show less
Joling, K.J.; Marwijk, H.W.J. van; Piek, E.; Horst, H.E. van der; Penninx, B.W.; Verhaak, P.; Hout, H.P.J. van 2011
