Use of selective serotonin reuptake inhibitors and risk of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Selective serotonin reuptake inhibitors (SSRI) decrease platelet-function, which suggests that SSRI use may increase the risk of post-surgical bleeding. Few studies have investigated this potential association.</p> <p>Methods</p> <p>We conducted a population-based study of the risk of re-operation due to post-surgical bleeding within two weeks of primary surgery among Danish women with primary breast cancer. Patients were categorised according to their use of SSRI: never users, current users (SSRI prescription within 30 days of initial breast cancer surgery), and former users (SSRI prescription more than 30 days before initial breast cancer surgery). We calculated the risk of re-operation due to post-surgical bleeding within 14 days of initial surgery, and the relative risk (RR) of re-operation comparing SSRI users with never users of SSRI adjusting for potential confounders.</p> <p>Results</p> <p>389 of 14,464 women (2.7%) were re-operated. 1592 (11%) had a history of SSRI use. Risk of re-operation was 2.6% among never users, 7.0% among current SSRI users, and 2.7% among former users. Current users thus had an increased risk of re-operation due to post-operative bleeding (adjusted relative risk = 2.3; 95% confidence interval (CI) = 1.4, 3.9) compared with never users. There was no increased risk of re-operation associated with former use of SSRI (RR = 0.93, 95% CI = 0.66, 1.3).</p> <p>Conclusions</p> <p>Current use of SSRI is associated with an increased risk of re-operation due to bleeding after surgery for breast cancer.</p

Effect of apomorphine on cognitive performance and sensorimotor gating in humans

Contains fulltext : 88792.pdf (publisher's version ) (Closed access)INTRODUCTION: Dysfunction of brain dopamine systems is involved in various neuropsychiatric disorders. Challenge studies with dopamine receptor agonists have been performed to assess dopamine receptor functioning, classically using the release of growth hormone (GH) from the hindbrain as primary outcome measure. The objective of the current study was to assess dopamine receptor functioning at the forebrain level. METHODS: Fifteen healthy male volunteers received apomorphine sublingually (2 mg), subcutaneously (0.005 mg/kg), and placebo in a balanced, double-blind, cross-over design. Outcome measures were plasma GH levels, performance on an AX continuous performance test, and prepulse inhibition of the acoustic startle. The relation between central outcome measures and apomorphine levels observed in plasma and calculated in the brain was modeled using a two-compartmental pharmacokinetic-pharmacodynamic analysis. RESULTS: After administration of apomorphine, plasma GH increased and performance on the AX continuous performance test deteriorated, particularly in participants with low baseline performance. Apomorphine disrupted prepulse inhibition (PPI) on high-intensity (85 dB) prepulse trials and improved PPI on low intensity (75 dB) prepulse trials, particularly in participants with low baseline PPI. High cognitive performance at baseline was associated with reduced baseline sensorimotor gating. Neurophysiological measures correlated best with calculated brain apomorphine levels after subcutaneous administration. CONCLUSION: The apomorphine challenge test appears a useful tool to assess dopamine receptor functioning at the forebrain level. Modulation of the effect of apomorphine by baseline performance levels may be explained by an inverted U-shape relation between prefrontal dopamine functioning and cognitive performance, and mesolimbic dopamine functioning and sensorimotor gating. Future apomorphine challenge tests preferentially use multiple outcome measures, after subcutaneous administration of apomorphine.1 januari 201

Dopaminergic drugs and the risk of hip or femur fracture: a population-based case–control study

SUMMARY: The effect of dopaminergic medication on the risk of hip/femur fractures is not clear. Our results showed a nearly twofold increased risk of hip/femur fractures in current dopaminergic drug users. Concomitant use of antidepressants further increased this risk. Fracture risk assessment may be warranted in elderly users of dopaminergic drugs. INTRODUCTION: Dopaminergic drugs, often used in the treatment of Parkinson's disease, have several pharmacological effects that may increase or decrease the risk of falling and fractures. Thus, the effect of dopaminergic medication on the risk of hip/femur fractures is not clear. The objective of the study was to examine the effect of dopaminergic medication and concomitant use of psychotropics on the risk of hip/femur fractures taking into account the timing of dopaminergic drug use. METHODS: A population-based case-control study in the PHARMO database was conducted for the period 1991 to 2002. Cases were patients aged 18 years and older with a first hip or femur fracture and matched to four control patients by year of birth, sex and geographical region. RESULTS: The study population included 6,763 cases and 26,341 controls. Current use of dopaminergic drugs (1-30 days before the index date) was associated with an increased risk of hip/femur fractures compared to never use (OR(adj) 1.76, 95% CI = 1.39-2.22), but this excess risk rapidly dropped to baseline levels when treatment had been discontinued >1 year ago. Concomitant use of antidepressants among current dopaminergic drug users further increased the risk of hip/femur fractures (OR(adj) 3.51, 95% CI = 2.10-5.87) while there was no additional risk with concomitant use of other psychotropics. CONCLUSIONS: Although the observed association between dopaminergic drugs and fracture risk may not be entirely causal, due to absence of information on the (severity of the) underlying disease, fracture risk assessment may be warranted in elderly users of dopaminergic drugs

Selective Serotonin Reuptake Inhibitors and Gastrointestinal Bleeding: A Case-Control Study

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been associated with upper gastrointestinal (GI) bleeding. Given their worldwide use, even small risks account for a large number of cases. This study has been conducted with carefully collected information to further investigate the relationship between SSRIs and upper GI bleeding. METHODS: We conducted a case-control study in hospitals in Spain and in Italy. Cases were patients aged ≥18 years with a primary diagnosis of acute upper GI bleeding diagnosed by endoscopy; three controls were matched by sex, age, date of admission (within 3 months) and hospital among patients who were admitted for elective surgery for non-painful disorders. Exposures to SSRIs, other antidepressants and other drugs were defined as any use of these drugs in the 7 days before the day on which upper gastrointestinal bleeding started (index day). RESULTS: 581 cases of upper GI bleeding and 1358 controls were considered eligible for the study; no differences in age or sex distribution were observed between cases and controls after matching. Overall, 4.0% of the cases and 3.3% of controls used an SSRI antidepressant in the week before the index day. No significant risk of upper GI bleeding was encountered for SSRI antidepressants (adjusted odds ratio, 1.06, 95% CI, 0.57-1.96) or for whichever other grouping of antidepressants. CONCLUSIONS: The results of this case-control study showed no significant increase in upper GI bleeding with SSRIs and provide good evidence that the magnitude of any increase in risk is not greater than 2

Het effect van geïnhaleerde glycopyrroniumbromide op ernstige speekselvloed en kwijlen bij patienten met de ziekte van Parkinson

OBJECTIVE: To investigate the safety and tolerability of glycopyrronium inhalation powder using different dosing regimens and to determine the decrease of drooling in patients with Parkinson's disease. DESIGN: We conducted a 5-week safety study. METHODS: Following a baseline week, each participant used glycopyrronium inhalations during four weeks, with weekly changing dosing regimes. The safety and tolerability was determined by monitoring side effects and the experience of participants. The decrease in drooling was determined by comparing the mean sialorrhea scores obtained every week. An interim analysis was performed after including seven participants. RESULTS: Side effects occurred in 71.4% of participants, which led to discontinuation of the study in three out of seven participants. The most common side effects were coughing and headache. Side effects that caused discontinuation were a swollen tongue, dry mouth, and gastro-enteritis. No unknown side effects of glycopyrronium led to discontinuation. Four participants experienced improvement in sialorrhea and three participants continued inhalation treatment after completion of the study. Two participants mentioned an instant effect after inhalation of glycopyrronium. CONCLUSION: Despite the reported side effects and the fact that we performed an interim analysis, we believe that glycopyrronium inhalations could be considered after failing of oral therapy

Stabiliteit van meropenem in een draagbare medicatiecassette omgeven door koelelementen

Stability of meropenem infusions in a portable medication cassette stored in a bag enclosed by cooling elementsBackground: Meropenem is a parenteral P-lactamase resistant broad spectrum carbapenem antibiotic. After dissolution, it is relatively unstable. Therefore, in the outpatient setting, it cannot be stored nor given as prolonged (continuous) infusion at room temperature.Objective: The aim of this study was to investigate the chemical stability of meropenem solutions in a medication cassette packed in a bag enclosed by cooling elements (changed every 12 hours), stored at room temperature for 24 hours.Design and methods: Meropenem was reconstituted and diluted with cold 0.9% sodium chloride (4.3 °C) to obtain solutions with concentrations of 12 mg/mL (n = 3) and 24 mg/mL (n = 3) in portable 250 mL CADD medication cassettes. Cassettes were individually enclosed by two frozen cooling elements and stored at room temperature for 24 hours. Cooling elements were changed every 12 hours. Samples were taken at t = 0 followed by a sample every 3 hours during 24 hours. Samples were analysed using a validated stability indicating high performance liquid chromatography with diode array detection method. Solutions retaining &gt; 90% of the initial concentration were considered stable.Results: All tested samples showed a meropenem concentration &gt; 90% of the initial concentration. No degradation products were found.Conclusion: The results demonstrate that meropenem continuous infusion can be used in outpatient setting when above-mentioned conditions are met.</p

The association between concomitant use of serotonergic antidepressants and lithium-induced polyuria. A multicenter medical chart review study

Background: A previous Study aimed at revealing the prevalence and determinants Of lithium induced polyuria Suggested an increased risk of polyuria (urine volume >= 3L/24h) in those using serotonergic antidepressants next to lithium. Objective: The objective of our study was to re-evaluate this secondary finding in another study population. Methods: We performed a multicenter medical chart review study in patients using lithium in whom a 24-hour urine volume had been determined. Results: We included 116 patients, twelve (26 %) of the 46 patients with polyuria used serotonergic antidepressants compared to ten (14%) of the 70 patients without polyuria. We found an increased risk of polyuria in lithium users concurrently using serotonergic antidepressants (odds ratio 2.86; 95 % confidence interval 1.00-8.21), adjusted for age, gender, use of antiepileptics and thyreomimetics. Conclusion: Our results Confirm the previous secondary finding of an increased risk of polyuria in patients using serotonergic antidepressants next to lithium. Physicians should take this into account when evaluating polytiria in patients using lithium and when choosing an antidepressant in patients using lithium

Amoxicillin concentrations in relation to beta-lactamase activity in sputum during exacerbations of chronic obstructive pulmonary disease

Marjolein Brusse-Keizer,1 Paul VanderValk,2 Rogier W van der Zanden,3 Lars Nijdam,4 Job van der Palen,1,5 Ron Hendrix,6,7 Kris Movig4 1Medical School Twente, 2Department of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, 3Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht, 4Department of Clinical Pharmacy, Medisch Spectrum Twente, 5Department of Research Methodology, Measurement and Data Analysis, University of Twente, 6Regional Laboratory of Public Health, Enschede, 7Department of Medical Microbiology, University Medical Centre Groningen, and University of Groningen, Groningen, the Netherlands&nbsp;Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are often treated with antibiotics. Theoretically, to be maximally effective, the antibiotic concentration at sites of infection should exceed the minimum inhibitory concentration at which 90% of the growth of potential pathogens is inhibited (MIC90). A previous study showed that most hospitalized COPD patients had sputum amoxicillin concentrations&nbsp;&lt;MIC90 when treated with amoxicillin/clavulanic acid. Those with adequate sputum concentrations had better clinical outcomes. Low amoxicillin concentrations can be caused by beta-lactamase activity in the lungs. This study investigated whether patients with sputum amoxicillin concentrations&nbsp;&lt;MIC90 had higher beta-lactamase activity in sputum than patients with a concentration &ge;MIC90.Methods: In total, 23 patients hospitalized for acute exacerbations of COPD and treated with amoxicillin/clavulanic acid were included. Sputum and serum samples were collected at day 3 of treatment to determine beta-lactamase activity in sputum and amoxicillin concentrations in both sputum and serum.Results: We found no difference in beta-lactamase activity between patients with sputum amoxicillin concentrations&nbsp;&lt;MIC90 and &ge;MIC90 (P=0.79). Multivariate logistic regression analysis showed no significant relationship between beta-lactamase activity and sputum amoxicillin concentrations&nbsp;&lt;MIC90 or &ge;MIC90 (odds ratio 0.53; 95% confidence interval 0.23&ndash;1.2; P=0.13). Amoxicillin concentrations were&nbsp;&lt;MIC90 in 78% of sputum samples and in 30% of serum samples.Conclusion: In patients treated with amoxicillin/clavulanic acid for an acute exacerbation of COPD, sputum beta-lactamase activity did not differ between those with sputum amoxicillin concentrations&nbsp;&lt;MIC90 or &ge;MIC90. The finding that the majority of patients had sputum amoxicillin concentrations &lt;MIC90 suggests that current treatment with antibiotics for acute exacerbations of COPD should be optimized.Keywords: chronic obstructive pulmonary disease, exacerbation, amoxicillin, clavulanic acid, MIC90, concentration&nbsp

Relation between amoxicillin concentration in sputum of COPD patients and length of hospitalization

Amoxicillin is a widely used antibiotic in COPD. Little is known about the transfer of amoxicillin into sputum of COPD patients. The objective was to investigate the relationship between the concentration of amoxicillin in sputum in hospitalized COPD patients and length of hospitalization. To be effective against bacterial pathogens, the amoxicillin concentration in target tissues should be higher than the Minimal Inhibiting Concentration (MIC) of 2mg/l. Therefore, this was also used as the cut-off value for the amoxicillin concentration in sputum, as amarker for lung tissue concentration. Fifty-two COPD in-patients with an exacerbation, treated with amoxicillin clavulanic acid, were included in this cohort study. Of these patients 7 also had pneumonia. Patients were divided in patients with an amoxicillin sputum concentration >= 2mg/l and <2 mg/l. Furthermore, inflammation markers in sputum and serum and clinical parameters were obtained. Of the 33 patients with usable sputum, 11 had a concentration in sputum >= 2 mg/l. The mean length of hospitalization for patients with concentrations below the MIC90 to common respiratory pathogens was 11.0 days, while for patients with concentrations at or above the MIC90 this was 7.0 days (p = 0.005). COPD patients admitted for an acute exacerbation of COPD, with a sputum concentration of amoxicillin >= 2 mg/l had a markedly reduced length of hospitalization compared to patients with a concentration <2 mg/l. It is worthwhile testing whether individualized treatment based on sputum amoxicillin concentrations of patients during hospitalization for acute exacerbations can effectively reduce hospital stay