Serum concentrations of antidepressants, antipsychotics, and antiepileptics over the bariatric surgery procedure.

PURPOSE: As a substantial proportion of bariatric surgery patients use psychotropic/antiepileptic drugs, we investigated the impact of this procedure on serum concentrations. METHODS: In a naturalistic, longitudinal, prospective case series, we compared dose-adjusted trough concentrations of antidepressants, antipsychotics, or antiepileptics in consecutive patients before and after bariatric surgery. Adherence to treatment over 2 weeks preceding each sampling was considered. RESULTS: In all, 85 participants were included (86% female, median age 45 years, median body mass index 42 kg/m2). They were being treated with 18 different psychotropic/antiepileptic drugs (7 substances: 6-17 individuals, 11 substances: 1-4 individuals) and contributed 237 samples over a median of 379 days after surgery. For four out of seven substances with pre-/post-surgery samples available from six or more individuals, the dose-adjusted concentration was reduced (sertraline: 51%, mirtazapine: 41%, duloxetine: 35%, citalopram: 19%). For sertraline and mirtazapine, the low-calorie-diet before surgery entirely explained this reduction. A consistent finding, irrespective of drug, was the association between the mean ratio of the post-/pre-diet dose-adjusted concentration and the lipophilicity of the drug (logD; correlation coefficient: -0.69, P = 0.0005), the low-calorie diet often affecting serum concentration more than the surgery itself. CONCLUSIONS: Serum concentrations of psychotropic/antiepileptic drugs vary after bariatric surgery and can be hard to predict in individual patients, suggesting that therapeutic drug monitoring is of value. Conversely, effects of the pre-surgery, low-calorie diet appear generalizable, with decreased concentrations of highly lipophilic drugs and increased concentrations of highly hydrophilic drugs. Interaction effects (surgery/dose/concentration) were not evident but cannot be excluded.

Developing professional confidence in the art of prescribing-a randomized controlled study on structured collegial discussions during internship.

PURPOSE: To evaluate whether an educational intervention based on collegial discussions on patient cases could increase interns' professional confidence in prescribing. METHODS: In a randomized controlled study at Sahlgrenska University Hospital, Gothenburg, Sweden, 69 interns (median age: 29 years, 54% female) were allocated to an intervention or control group. The intervention consisted of two 3-h seminars based on collegial discussions of patient cases focused on performing medication reviews. This included reconciling the drug treatment and ascertaining that it is reasonable given the patient's current health status, as well as tips on practical handling of the medical records system and integrated decision support. Self-assessed confidence in performing medication reviews was evaluated with questionnaires distributed at baseline and at 6-month follow-up. RESULTS: Fifty-seven (83%) interns completed the questionnaires. Although the opposite was found at baseline, intervention interns, in comparison with controls, at follow-up, were more confident in performing medication reviews (4.3 ± 0.9 vs. 3.6 ± 1.3, P = 0.034; 1 = completely disagree to 5 = completely agree). At follow-up, the intervention participants had increased their confidence in prescribing to a greater extent compared with the control participants, including performing medication reviews as well as taking responsibility for the medication list at discharge: + 1.5/+ 1 vs ± 0 on the 5-point agreement scale (all P ≤ 0.01). Among other positive outcomes, the intervention increased the interns' awareness of adverse effects as a potential cause of symptoms and their confidence in withdrawing a medication. CONCLUSION: Structured collegial discussions on pharmacotherapy, even of a relatively short duration, can increase junior physicians' professional confidence in prescribing medicines.

Medication reviews for nursing home residents to reduce mortality and hospitalization: systematic review and meta-analysis.

AIMS: Medication reviews by a third party have been introduced as a method to improve drug treatment in older people. We assessed whether this intervention reduces mortality and hospitalization for nursing home residents. METHODS: Systematic literature searches were performed (from January 1990 to June 2012) in Medline, EMBASE, Cochrane Library, ProQuest Nursing & Allied Health Sources and Health Technology Assessment databases. We included randomized and nonrandomized controlled trials (RCTs and non-RCTs) of medication reviews compared with standard care or other types of medication reviews in nursing home residents. The outcome variables were mortality and hospitalization. Study quality was assessed systematically. We performed meta-analyses using random-effects models. RESULTS: Seven RCTs and five non-RCTs fulfilled the inclusion criteria. The mean age of included patients varied between 78 and 86 years. They were treated with a mean of 4-12 drugs. The study quality was assessed as high (n = 1), moderate (n = 4) or low (n = 7). Eight studies compared medication reviews with standard care. In six of them, pharmacists were involved in the intervention. Meta-analyses of RCTs revealed a risk ratio (RR) for mortality of 1.03 [medication reviews vs. standard care; five trials; 95% confidence interval (CI) 0.85-1.23]. The corresponding RR for hospitalization was 1.07 (two trials; 95% CI 0.61-1.87). CONCLUSIONS: Our findings indicate that medication reviews for nursing home residents do not reduce mortality or hospitalization. More research in the setting of controlled trials remains to be done in order to clarify how drug treatment can be optimized for these patients.

Association between genetic variation on chromosome 9p21 and aneurysmal subarachnoid haemorrhage.

BACKGROUND AND AIM: Genetic factors play a role in susceptibility to subarachnoid haemorrhage, but little is known about which genes are involved. Recently, genome wide association studies have identified the 9p21 region as a risk locus for intracranial aneurysms (IA). The aim of the present study was to examine the possible association between 9p21 and ruptured IA--that is, aneurysmal subarachnoid haemorrhage (aSAH)--in a Swedish population. There is one study showing an association between 9p21 and arterial stiffness, and arterial stiffness plays a role in the development of hypertension. Therefore, a second aim was to investigate whether a putative association is independent of hypertension. METHODS: The study comprised 183 patients presenting with aSAH to the Neurointensive Care Unit at Sahlgrenska University Hospital and 366 healthy, age and sex matched population based controls. As the causative functional variant in the region has not yet been identified, a 44 kbp region on 9p21 was tagged using HapMap. Six single nucleotide polymorphism (SNPs) were genotyped. RESULTS: Two SNPs, rs10757278 and rs1333045, showed significant associations with aSAH in univariate analyses. After adjustment for hypertension as well as for smoking, the association between aSAH and rs10757278 remained significant with an OR for aSAH of 1.42 (95% CI 1.08 to 1.87; p=0.01) for the uncommon G allele. CONCLUSIONS: These data confirm earlier results showing that 9p21 is a susceptibility locus for IA, and that this association is present in a Swedish sample restricted to ruptured IA. For the first time, it has been demonstrated that this association is independent of hypertension.

Association between factor XIII single nucleotide polymorphisms and aneurysmal subarachnoid hemorrhage.

OBJECT: Family studies have suggested a role of genetic factors in susceptibility to aneurysmal subarachnoid hemorrhage (aSAH), but the underlying genetic risk factors remain poorly defined. There is an activation of the fibrinolytic system in aSAH, and fibrinolytic markers may be useful in predicting outcome. The authors investigate associations between putative functional variants in genes of importance for fibrinolysis and aSAH and/or outcome following aSAH. METHODS: One hundred eighty-three patients presenting with aSAH at a neurointensive care unit were consecutively recruited. Two healthy controls per case, matched for age, sex, and geographic region, were randomly recruited. Outcome was assessed after 1 year according to the extended Glasgow Outcome Scale. Single nucleotide polymorphisms (SNPs) in the tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), and factor XIII (FXIII) genes were investigated. RESULTS: Participants carrying the FXIII 34Leu allele showed an increased risk of aSAH. When adjusting for smoking and hypertension, 2 haplotypes, differing on either the FXIII Val34Leu or the Pro564Leu position, showed an association to aSAH. No significant association was observed for the tPA -7351 C > T, PAI-1 -675 4G > 5G, or TAFI Ala147Thr SNPs. No specific SNP or haplotype was associated with outcome after aSAH, whereas a weak association was observed for a tPA/PAI-1 genotype combination. CONCLUSIONS: Polymorphisms in the FXIII gene showed association to aSAH. The finding of an increased risk of bleeding in FXIII 34Leu carriers is biologically plausible.

Serum glial fibrillary acidic protein is related to focal brain injury and outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (aSAH) stands out from other subtypes of stroke because of the high early mortality and the risk of complications. Serum glial fibrillary acidic protein (s-GFAP) concentrations are increased after stroke. The aim of this study was to investigate whether s-GFAP could be used as a marker of brain damage and outcome after aSAH. METHODS: Serum samples were obtained on a regular basis from 116 adults during a 2-week period after aSAH and analyzed using an enzyme-linked immunosorbent assay. The World Federation of Neurological Surgeons scale was used for neurological evaluation. Outcome was assessed after 1 year and categorized according to the Extended Glasgow Outcome Scale. RESULTS: Increased s-GFAP levels were seen in 81 of the 116 patients. Maximum s-GFAP correlated with World Federation of Neurological Surgeons scale on arrival and on days 10 to 15 (r=0.37, P<0.001 and r=0.47, P<0.001, respectively). Furthermore, maximum s-GFAP levels were increased in the patient group with radiological signs of focal lesions acute or at 1 year, compared with the group without focal lesions (P<0.001 in both comparisons). Patients with secondary events (re-bleeding or ischemia) reached maximum levels later in the series and both maximum and final s-GFAP levels increased compared with the levels in patients without secondary events (P<0.001 in all 3 comparisons). Finally, maximum s-GFAP correlated with outcome (r=-0.48, P<0.001) and s-GFAP was an independent predictor of dichotomized outcome. CONCLUSIONS: s-GFAP provides information about brain injury severity and outcome after aSAH, which can be useful as a complement to clinical data.

Marked increase of beta-amyloid(1-42) and amyloid precursor protein in ventricular cerebrospinal fluid after severe traumatic brain injury.

Severe traumatic brain injury (TBI) may result in widespread damage to axons, termed diffuse axonal injury. Alzheimer's disease (AD) is characterised by synaptic and axonal degeneration together with senile plaques (SP). SP are mainly composed of aggregated beta-amyloid (Abeta), which are peptides derived from the amyloid precursor protein (APP). Apart from TBI in itself being considered a risk factor for AD, severe head injury seems to initiate a cascade of molecular events that are also associated with AD. We have therefore analysed the 42 amino acid forms of Abeta (Abeta1-42) and two soluble forms of APP (alpha-sAPP and ss-sAPP) in ventricular cerebrospinal fluid (VCSF) and Abeta(1-42) in plasma from 28 patients in a serial samples 0-11 days after TBI. The levels of alpha-sAPP, ss-sAPP and Abeta(1-42) were determined using ELISA assays. After TBI, there was a significant stepwise increase in VCSF-Abeta(1-42) up to 1173 % from day 0-1 to day 5-6 and in VCSF-beta-sAPP up to 2033 % increase from day 0-1 to day 7-11. There was also a slight but significant increase of VCSF-beta-sAPP from day 0-1 to day 5-6 and day 7-11. By contrast, the plasma- Abeta(1-42) level is unchanged after injury. The marked increase in VCSFAbeta(1-42) implies that increased Abeta expression may occur as a secondary phenomenon after TBI with axonal damage. The unchanged level of plasma-Abeta(1-42) in contrast to the marked increase in VCSF-Abeta(1-42) after severe TBI, supports the suggestion that plasma Abeta(1-42) does not reflect Abeta metabolism in the central nervous system (CNS).

Neuronal and astrocytic damage in systemic lupus erythematosus patients with central nervous system involvement.

OBJECTIVE: Symptoms originating from the central nervous system (CNS) frequently occur in patients with systemic lupus erythematosus (SLE). CNS involvement in lupus is associated with increased morbidity and mortality. Currently, reliable markers for activity in this condition are absent. The goal of this study was to determine the level of the light subunit of the neurofilament triplet protein (NFL) and that of glial fibrillary acidic protein (GFAP) in the cerebrospinal fluid of SLE patients with clinically verified CNS involvement and compare them with the levels in SLE patients without CNS involvement. METHODS: We assessed cerebrospinal fluid obtained from 99 patients with SLE and 99 age-matched controls for the presence of soluble molecules indicating neuronal destruction and astrogliosis-NFL and GFAP, respectively. Patients were evaluated clinically, with magnetic resonance imaging (MRI) of the brain, cerebrospinal fluid analyses, and neuropsychiatric tests. RESULTS: In the group of lupus patients with CNS involvement, intrathecal levels of NFL and GFAP were increased an average of 7-fold (P