Sex steroid levels in corresponding cerebrospinal fluid and serum samples quantified by mass spectrometry in men.

Objective: Sex steroids exert important biological functions within the CNS, but the underlying mechanisms are poorly understood. The contribution of circulating sex steroids to the levels in CNS tissue and cerebrospinal fluid (CSF) has been sparsely investigated in human and with inconclusive results. This could partly be due to lack of sensitive validated assays. To address this, we validated a gas chromatography-tandem mass spectrometry (GC-MS/MS) assay for quantification of sex steroid hormones/precursors in CSF. Methods: GC-MS/MS quantification of dihydrotestosterone (DHT, CSF lower limit of quantification, 1.5 pg/mL), testosterone (4.9), estrone (E1, 0.88), estradiol (E2, 0.25), dehydroepiandrosterone (DHEA, 38.4), androstenedione (4D, 22.3), and progesterone (P, 4.2) in CSF, and corresponding serum samples from 47 men. Results: Analyses of CSF revealed that DHEA was the major sex steroid (73.5 ± 31.7 pg/mL) followed by 4D (61.4 ± 29.6 pg/mL) and testosterone (49.5 ± 18.9 pg/mL). The CSF levels of DHT, E2, and E1 were substantially lower, and P was in general not detectable in CSF. For all sex steroids except E2, strong associations between corresponding CSF and serum levels were observed. We propose that testosteronein CSF is derived from circulating testosterone, DHT in CSF is from local conversion from testosterone, while E2 in CSF is from local conversion from 4D in CNS. Conclusions: We describe the first thoroughly validated highly sensitive mass spectrometric assay for a broad sex steroid hormone panel suitable for human CSF. This assay constitutes a new tool for investigation of the role of sex steroid hormones in the human CNS. Significance statement: In this study, a fully validated highly sensitive mass spectrometric assay for sex steroids was applied to human CSF. The results were used to describe the relative contribution of peripheral circulating sex steroids together with locally transformation of sex steroids to the levels in CSF. The results are of importance to understand the biological processes of the human brain.

Impact of Pharmacist-Directed Medication Reconciliation in Reducing Medication Discrepancies: A Randomized Controlled Trial.

Background: In hospital surgical wards, patients are at higher risk for medication errors, in part because physicians may not consider themselves sufficiently trained to prescribe medications. Hence, collaborative teamwork involving the pharmacist is needed. Objectives: To assess the impact of medication reconciliation directed by pharmacists on decreasing medication discrepancies after discharge from the surgical ward. Methods: Patients admitted to the surgical unit at a tertiary teaching hospital in Amman, Jordan, between July 2017 and July 2018 were selected and randomly assigned to either the control or the intervention group. Upon admission, the number and kinds of unintentional medication discrepancies were determined for both groups. Medication reconciliation was then provided to patients in the intervention group. The number of unintentional discrepancies was re-evaluated upon discharge for both groups. To assess differences between the control and intervention groups, the χ2 or Fisher exact test was used for categorical variables and an independent-sample t test for continuous data. A paired t test was conducted to determine whether the number of medication discrepancies was reduced as a result of pharmacists' recommendations. Results: A total of 123 patients met the inclusion criteria, 61 in the intervention group and 62 in the control group. Discrepancies of omission and wrong dose constituted 41 (77%) of the 53 discrepancies in the intervention group and 25 (76%) of the 33 discrepancies in the control group. The number of unintentional discrepancies was significantly reduced from admission to discharge in both the intervention group (p = 0.002) and the control group (p = 0.007). Of 53 recommendations made by pharmacists, 20 (38%) were accepted by the treating physician, and all of these discrepancies were resolved. Conclusions: This study sheds light on the existence of unintentional medication discrepancies upon admission for surgical patients, which may expose the patients to potential harm upon discharge from hospital. Additional studies with a larger sample size are needed to gain further insights on pharmacists' role in implementing medication reconciliation for surgical patients.

Contexte: Dans les services chirurgicaux des hôpitaux, les patients sont exposés à un risque d'erreurs de médication plus élevé, en partie parce que les médecins ne se considèrent pas suffisamment formés pour prescrire des médicaments. Par conséquent, un travail d'équipe collaboratif impliquant le pharmacien est nécessaire. Objectifs: Évaluer l'impact du bilan comparatif des médicaments dirigé par les pharmaciens sur la diminution des écarts médicamenteux après la sortie du service de chirurgie. Méthodes: Les patients admis à l'unité chirurgicale d'un hôpital d'enseignement tertiaire à Amman, en Jordanie, entre juillet 2017 et juillet 2018 ont été sélectionnés et affectés au hasard au groupe témoin ou au groupe d'intervention. Lors de l'admission, le nombre et les types de divergences médicamenteuses non intentionnelles ont été définis pour les deux groupes. Le bilan comparatif des médicaments a ensuite été fourni aux patients du groupe d'intervention. Le nombre d'écarts non intentionnels a été réévalué à la sortie pour les deux groupes. Pour évaluer les différences entre le groupe témoin et le groupe d'intervention, le test χ2 ou le test exact de Fisher a été utilisé pour les variables catégorielles et un test t pour échantillon indépendant, pour les données continues. Un test t apparié a été effectué pour déterminer si le nombre d'écarts de médicaments a été réduit à la suite des recommandations des pharmaciens. Résultats: Au total, 123 patients répondaient aux critères d'inclusion : 61 dans le groupe d'intervention et 62 dans le groupe témoin. Les divergences d'omission et de mauvaise dose constituaient 41 (77 %) des 53 divergences dans le groupe d'intervention et 25 (76 %) des 33 divergences dans le groupe témoin. Le nombre d'écarts non intentionnels a été significativement réduit de l'admission à la sortie à la fois dans le groupe d'intervention (p = 0,002) et dans le groupe témoin (p = 0,007). Sur 53 recommandations émises par des pharmaciens, 20 (38 %) ont été acceptées par le médecin traitant et toutes ces divergences ont été résolues. Conclusions: Cette étude met en lumière l'existence d'écarts médicamenteux non intentionnels lors de l'admission des patients chirurgicaux, ce qui peut exposer les patients à des risques au moment de leur sortie de l'hôpital. D'autres études avec un échantillon plus important sont nécessaires pour mieux comprendre le rôle des pharmaciens dans la mise en œuvre du bilan comparatif des médicaments pour les patients chirurgicaux.

Patients with Alzheimer's Disease Have Increased Levels of Insulin-like Growth Factor-I in Serum but not in Cerebrospinal Fluid.

BACKGROUND: Insulin-like growth factor-I (IGF-I) is important for amyloid-ß (Aß) metabolism, and also interacts with the brain vasculature. In previous IGF-I studies, it has not been evaluated whether Alzheimer's disease (AD) patients had vascular comorbidities. OBJECTIVE AND METHODS: A cross-sectional study of 40 consecutive non-diabetic AD patients and 36 healthy controls. We measured IGF-I in serum and cerebrospinal fluid (CSF) and also serum insulin. Mixed forms of AD and vascular dementia were excluded. RESULTS: After adjustment for covariates including age, serum IGF-I level was higher in the AD group than in the controls, whereas CSF IGF-I and serum insulin were unchanged. Binary logistic regression confirmed that high serum IGF-I was associated with increased prevalence of AD [adjusted Odds Ratio (OR) = 1.83, 95% confidence interval (CI): 1.005-3.32 per standard deviation (SD) increase in serum IGF-I]. This association was more robust after exclusion of patients receiving treatment with acetylcholinesterase inhibitors or N-methyl D-aspartate (NMDA) receptor antagonists (OR = 2.23, 95 % CI: 1.10-4.48). In the total study population (n = 76) as well in the AD group (n = 40), serum IGF-I correlated negatively with CSF Aß1-42, and CSF IGF-I correlated positively with CSF/serum albumin ratio, CSF total tau, and CSF phosphorylated tau. CONCLUSION: In AD patients without major brain vascular comorbidities, serum but not CSF levels of IGF-I were increased after correction for covariates. This association was strengthened by exclusion of patients receiving medical treatment. Overall, the results support the notion of IGF-I resistance in mild AD dementia.