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Background During transitions of care, including hospital discharge, patients are at risk of drug-related problems (DRPs). Aim To investigate the impact of pharmacist-led services, specifically medication reconciliation at admission and/or interprofessional ward rounds on the number of DRPs at discharge. Method In this retrospective, single-center cohort study, we analyzed routinely collected data of patients discharged from internal medicine wards of a regional Swiss hospital that filled their discharge prescriptions in the hospital’s community pharmacy between June 2016 and May 2019. Patients receiving one of the two or both pharmacist-led services (Study groups: Best Care = both services; MedRec = medication reconciliation at admission; Ward Round = interprofessional ward round), were compared to patients receiving standard care (Standard Care group). Standard care included medication history taken by a physician and regular ward rounds (physicians and nurses). At discharge, pharmacists reviewed discharge prescriptions filled at the hospital’s community pharmacy and documented all DRPs. Multivariable Poisson regression analyzed the independent effects of medication reconciliation and interprofessional ward rounds as single or combined service on the frequency of DRPs. Results Overall, 4545 patients with 6072 hospital stays were included in the analysis (Best Care n = 72 hospital stays, MedRec n = 232, Ward Round n = 1262, and Standard Care n = 4506). In 1352 stays (22.3%) one or more DRPs were detected at hospital discharge. The combination of the two pharmacist-led services was associated with statistically significantly less DRPs compared to standard care (relative risk: 0.33; 95% confidence interval: 0.16, 0.65). Pharmacist-led medication reconciliation alone showed a trend towards fewer DRPs (relative risk: 0.75; 95% confidence interval: 0.54, 1.03). Conclusion Our results support the implementation of pharmacist-led medication reconciliation at admission in combination with interprofessional ward rounds to reduce the number of DRPs at hospital discharge.

Background Hospital stays are often associated with medication changes, which may lead to drug-related problems (DRPs). Medication reconciliation and medication reviews are strategies to detect and resolve DRPs. Methods A descriptive cohort study was conducted using DRPs collected during routine pharmacist-led medication reconciliation and medication reviews in the hospital's community pharmacy at discharge (Zug Cantonal Hospital, Switzerland). In a simulation experiment, we retrospectively analysed the detection and resolution possibilities of these DRPs and their dependency on different information sources. Results Overall, 6,087 prescriptions were filled in the hospital's community pharmacy (between June 2016 and May 2019). Among 1,352 prescriptions (with ≥ 1 documented DRP) a total of 1,876 DRPs were detected. The retrospective assessment showed that 1,115 DRPs could have been detected by performing simple medication reviews (based on the discharge prescription and the medication history), whereas in the remaining cases, additional clinical and/or patient-specific information would have been needed. In 944 (84.7 %) DRPs, which are detectable by simple medication reviews, the pharmacist would need to consult the prescriber for resolution. Conclusion The detection of DRPs is strongly influenced by the information available. These results support models with pre-discharge medication reconciliation and pharmacist-led medication review procedures enabling both comprehensive detection and facilitated resolution of DRPs.

Zusammenfassung. Die Sarkoidose ist eine seltene Ursache der Hyperkalzämie. Als häufigste Ursachen kommen ein primärer Hyperparathyreoidismus sowie ein malignes Tumorleiden in Frage. Weitere Ursachen können eine Vitamin-D-Intoxikation, sonstige granulomatöse Erkrankungen (Tuberkulose, Pilzinfektionen etc.) oder ein multiples Myelom sein. Aufgrund der breiten Differenzialdiagnose ist eine systematische Abklärung entscheidend, um die korrekte Diagnose zu stellen. Zur Therapie einer Hyperkalzämie erfolgt eine Volumensubstitution und anschliessende Gabe von Bisphosphonaten. Bei einer Sarkoidose als Ursache der Hyperkalzämie ist zudem eine systemische Steroidtherapie mit Prednisolon indiziert.

Zusammenfassung. Die eosinophile Granulomatose mit Polyangiitis (EGPA, ehemals Churg-Strauss-Syndrom) ist eine Krankheit mit vielen Gesichtern. Aufgrund der variablen Gefäss- und Organbeteiligung kann sich EPGA klinisch sehr unterschiedlich manifestieren. Wir berichten über einen 60-jährigen Patienten mit bekanntem Asthma bronchiale, Pansinusitis und neu einer ausgeprägten Bluteosinophilie sowie einer akuten, rasch progredienten Mononeuritis multiplex. Die Diagnose konnte schliesslich histologisch gesichert werden. Nach Beginn der Therapie kann der Patient wieder mit Gehilfen selbstständig gehen.

A Rare Cause of Hypercalcemia

Eine Frau stellte sich mit subfebrilen Temperaturen und allgemeinem Krankheitsgefuhl auf der Notfallstation vor. Sie sei vor zehn Tagen von einem unbekannten Insekt wahrend einer Safari im Osten Sudafrikas gestochen worden.

Une femme s´est presentee aux urgences avec des temperatures subfebriles et une sensation generale de maladie. Elle s´etait fait piquer par un insecte inconnu lors d´un safari dans l´est de l´Afrique du Sud il y a dix jours.

Mononeuritis Multiplex: A Diagnostic Challenge

Un patient âge de 46 ans, jusqu’alors en bonne sante, a ete adresse pour une echographie abdominale avec recherche d’une cholecystite aigue en raison de douleurs epigastriques «en vagues».

Die Zuweisung eines 46-jahrigen, bislang gesunden Patienten erfolgte aufgrund «wellenformiger» Oberbauchschmerzen zur Abdomensonographie mit der Fragestellung nach einer akuten Cholezystitis.

Unexplained iron-deficiency anemia is an important marker for colorectal cancer (CRC). Our objectives were as follows: (a) to assess whether the association between anemia and CRC can be detected on the 'Clinical Practice Research Datalink', (b) to evaluate the timing between laboratory changes and CRC detection, and (c) to analyze its association with survival. We conducted a case-control study on patients with an incident CRC diagnosis during 2008-2012 and a 1 : 1-matched control group. We compared anemia markers serum ferritin (SF), hemoglobin (Hb), mean corpuscular volume (MCV), and red blood cell count between cases and controls using conditional logistic regression. We assessed survival in CRC cases. SF values up to 20 ng/ml were associated with an odds ratio [OR (95% confidence interval)] of 10.66 (6.88-16.51) compared with SF values of 101-300 ng/ml when restricted to measurements up to 180 days before the CRC diagnosis. For measurements taken at 1 year or earlier before the diagnosis, the OR was 2.02 (1.57-2.61). For Hb values less than 9 g/dl compared with Hb values of 13.0-15.9 g/dl the corresponding ORs were 74.25 (34.69-158.91) and 2.19 (1.31-3.67), respectively. The corresponding ORs for MCV values up to 80 fl compared with MCV values of 86-95 fl were 13.94 (10.31-18.85) and 1.89 (1.51-2.36), respectively. Low levels of these markers were only weakly associated with survival. Hb, MCV, and SF levels substantially dropped only shortly before the CRC diagnosis. Although slightly more cases had anemia markers compared with controls at 1 year or earlier before the diagnosis, most cases still had normal values. The Clinical Practice Research Datalink is well-suited to detect associations between low Hb, MCV, and SF levels and CRC.

/ Summary We performed a retrospective observational study to evaluate mortality after Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN). In a cross-sectional study of 434 patients hospitalized with SJS/TEN in England between 1995 and 2013 (Hospital Episode Statistics Admitted Patient Care Data), 7.4% died during the index hospitalization (5.0% of patients with SJS and 23.2% with TEN). In a second analysis, we followed a validated cohort of 477 SJS/TEN patients from the UK-based Clinical Practice Research Datalink and 1908 matched comparator patients (1995-2013) over 5 years until death or until another censoring reason occurred. In total, 23 (4.8%) of SJS/TEN patients died within 90 days after the first recorded diagnosis and 36 (7.6%) died between day 91 and the end of follow-up. We observed a HR for death of 4.86 (95% CI 2.65-8.91) during the first 90 days after SJS/TEN, which attenuated to a HR of 0.80 (95% CI 0.55-1.16) between day 91 and the end of follow up. Results were not meaningfully different within sub-groups of sex, age and body mass index. In summary, 7.4% of patients hospitalized with SJS/TEN died during the index hospitalization. Long-term mortality up to five years was not increased compared to patients without SJS/TEN.

Long-term use of proton pump inhibitors (PPIs) has been associated with an increased risk of Alzheimer’s disease (AD) in observational studies. The role of exposure duration, and whether this applies to other dementia subtypes, has not been explored in these studies. The aim was to study the association between long-term use of PPIs (or of histamine-2 receptor antagonists [H2RAs], as a negative control) and the risk of developing AD or vascular dementia (VaD). We conducted a case–control analysis on the UK-based Clinical Practice Research Datalink (CPRD). We identified 41,029 patients aged ≥ 65 years with newly diagnosed AD or VaD between 1998 and 2015 and matched them 1:1 to dementia-free controls on age, sex, calendar time, general practice, and number of years of recorded history. We applied conditional logistic regression analyses to calculate adjusted odds ratios (aORs), with 95% confidence intervals (CIs), of developing AD or VaD in relation to previous use of PPIs or H2RAs, categorized by exposure duration. As compared to non-use, long-term PPI use (≥ 100 prescriptions) was not associated with an increased risk of developing AD (aOR 0.88, 95% CI 0.80–0.97) or VaD (aOR 1.18, 95% CI 1.04–1.33). Neither was long-term use of H2RAs (≥ 20 prescriptions) associated with an increased risk of developing AD (aOR 0.94, 95% CI 0.87–1.02) or VaD (aOR 0.99, 95% CI 0.89–1.10). In this large, case-control analysis, we did not find any evidence for an increased risk of either AD or VaD related to PPI or H2RA use.

Zusammenfassung. Die Arzneimitteltherapie bei niereninsuffizienten Patienten verlangt neben der Erfassung der Nierenfunktion Kenntnisse über die Prinzipien der Dosisanpassung und der Eigenschaften der einzusetzenden Substanzen. Durch die Nierenkrankheit wird neben der renalen auch die hepatische Elimination beeinflusst. Das Aufkommen direkt wirksamer oraler Antikoagulantien hat die Gerinnungshemmung in vielerlei Hinsicht vereinfacht, eine Indikationserweiterung auf ein dialysepflichtiges Patientengut wird von zukünftigem Interesse sein. GLP-1-Agonisten und SGLT-2-Inhibitoren sind neuere Therapieoptionen zur Behandlung eines Diabetes mellitus Typ 2. Die blutzuckersenkende Wirkung von SGLT-2-Inhibitoren lässt mit abnehmender Nierenfunktion nach, positive Wirkungen auf kardiovaskuläre Ereignisse scheinen aber auch bei fortgeschrittener Niereninsuffizienz erhalten. Die Cyclooxygenase-Hemmung durch NSAR beeinflusst Hämodynamik und tubuläre Funktion der Niere. Klinisch signifikante NSAR-induzierte renale Nebenwirkungen sind vor allem im Falle einer Begleitmedikation mit RAAS-Hemmern und Diuretika möglich.

SummaryObjective Older antiepileptic drugs (AEDs) are known to cause Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). However, evidence for newer AED is sparse. We quantified risks of SJS/TEN in association with use of all AEDs in the United Kingdom. Methods In a matched case-control study of 480 previously validated SJS/TEN cases (1995–2013) we used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs), and calculated absolute risks of SJS/TEN within separate cohorts of new users of 28 AEDs. We assessed causality between drugs and SJS/TEN in each exposed case, using an adapted version of the algorithm of drug causality for epidermal necrolysis (ALDEN) score. Results We observed a strong association between SJS/TEN and new use of carbamazepine (OR 92.57, 95% CI 19.89–∞), phenytoin (OR 49.96, 95% CI 10.13–∞), and lamotrigine (OR 26.90, 95% CI 4.88–∞), where causality, according to the ALDEN score, was very probable or probable for most exposed cases. Absolute risks for SJS/TEN were highest for phenytoin (45.86 cases/100,000 exposed), lamotrigine (44.17 cases/100,000 exposed), and carbamazepine (20.38 cases/100,000 exposed). Despite increased ORs for valproate (40,941 exposed), gabapentin (116,037 exposed), pregabalin (59,967 exposed), and clobazam (4,300 exposed), ALDEN suggested no causal association. There were no observed cases of SJS/TEN among new users of levetiracetam (n = 96,77), clonazepam (n = 18,075), or topiramate (n = 11,307). Significance The results of our study are consistent with those of previous studies of SJS/TEN, which found increased risks of SJS/TEN in new use of carbamazepine, phenytoin, and lamotrigine. Despite frequent use, no ALDEN-score confirmed cases were observed in new users of valproate, gabapentin, pregabalin, levetiracetam, topiramate, or clonazepam.

Zusammenfassung. Wir berichten über einen 52-jährigen Patienten, der sich mit Fieber, starken Muskelschmerzen, Ikterus, akuter Niereninsuffizienz, Anämie und Thrombozytopenie vorstellte. Aufgrund der Anamnese sowie der typischen Klinik konnte eine Leptospirose klinisch vermutet und mittels PCR diagnostiziert werden.

Pharmacotherapy in patients with reduced kidney function Abstract. Pharmacotherapy in patients with chronic kidney disease (CKD) requires careful assessment of renal function and a profound knowledge of dose adaption principles and pharmacological characteristics of the drugs used. Of importance, non-renal clearance is also affected by impaired kidney function. Direct acting anticoagulants play an increasingly important role in daily clinical practice also in patients with impaired kidney function. Limited data suggest possible use even in end stage renal disease. GLP-1-agonists and SGLT-2-inhibitors are new treatment modalities for type 2 diabetes mellitus. The efficacy of glucose lowering by SGLT-2-inhibitors steadily declines with impaired kidney function; however, positive effects on cardiovascular outcomes seem to be preserved in advanced CKD. NSAIDs affect renal hemodynamics as well as tubular function. Severe renal side effects may be observed especially when used in combination with RAAS-inhibitors and diuretics.Zusammenfassung. Die Arzneimitteltherapie bei niereninsuffizienten Patienten verlangt neben der Erfassung der Nierenfunktion Kenntnisse über die Prinzipien der Dosisanpassung und der Eigenschaften der einzusetzenden Substanzen. Durch die Nierenkrankheit wird neben der renalen auch die hepatische Elimination beeinflusst. Das Aufkommen direkt wirksamer oraler Antikoagulantien hat die Gerinnungshemmung in vielerlei Hinsicht vereinfacht, eine Indikationserweiterung auf ein dialysepflichtiges Patientengut wird von zukünftigem Interesse sein. GLP-1-Agonisten und SGLT-2-Inhibitoren sind neuere Therapieoptionen zur Behandlung eines Diabetes mellitus Typ 2. Die blutzuckersenkende Wirkung von SGLT-2-Inhibitoren lässt mit abnehmender Nierenfunktion nach, positive Wirkungen auf kardiovaskuläre Ereignisse scheinen aber auch bei fortgeschrittener Niereninsuffizienz erhalten. Die Cyclooxygenase-Hemmung durch NSAR beeinflusst Hämodynamik und tubuläre Funktion der Niere. Klinisch signifikante NSAR-induzierte renale Nebenwirkungen sind vor allem im Falle einer Begleitmedikation mit RAAS-Hemmern und Diuretika möglich.

Purpose To evaluate the validity of recorded diagnoses of Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in the Clinical Practice Research Datalink (CPRD). Methods We identified patients with a diagnosis of SJS or TEN between 1995 and 2013 in the CPRD. We reviewed information from patient records, free text, and hospital episode statistics (HES) data, and excluded patients with no indication of a secondary care referral. Remaining patients were classified as probable, possible, or unlikely cases of SJS/TEN by two specialised clinicians or based on pre-defined classification criteria. We quantified positive predictive values (PPV) for all SJS/TEN patients and for patients categorised as ‘probable/possible’ cases of SJS/TEN, based on a representative subsample of 118 patients for whom we had unequivocal information (original discharge letters or HES data). Results We identified 1324 patients with a diagnosis of SJS/TEN, among whom 638 had a secondary care referral recorded. Of those, 565 were classified as probable or possible cases after expert review. We calculated a PPV of 0.79 (95% CI, 0.71–0.86) for all SJS/TEN patients with a recorded secondary care referral, and a PPV of 0.87 (95% CI, 0.81–0.93) for probable/possible cases. After excluding 14 false positive patients, our study population consisted of 551 SJS/TEN patients. Conclusions Diagnoses of SJS/TEN are recorded with moderate diagnostic accuracy in the CPRD, which was substantially improved by additional expert review of all available information. We established a large population-based SJS/TEN study population of high diagnostic validity from the CPRD. Copyright © 2016 John Wiley & Sons, Ltd.

Antidepressant use has been associated with an increased risk of seizures. Evidence on the association between antidepressant use at therapeutic doses and seizures mainly comes from clinical trials that were not designed to investigate this potential relationship. The objective of this study was to assess the risk of first-time seizures in association with exposure to antidepressants in patients with depressive disorders. We conducted a retrospective follow-up study with a nested case–control analysis between 1998 and 2012, using data from the UK-based Clinical Practice Research Datalink (CPRD). We estimated crude incidence rates with 95 % confidence intervals (CIs) of seizures in depressed patients who used selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), ‘other antidepressants’, no antidepressants, or who had used antidepressants in the past. To adjust for potential confounding, we estimated odds ratios of antidepressant drug use among cases with seizures and matched controls in a nested case–control analysis. Of 151,005 depressed patients, 619 had an incident seizure during follow-up. Incidence rates per 10,000 person-years were 12.44 (95 % CI 10.67–14.21) in SSRI users, 15.44 (95 % CI 8.99–21.89) in SNRI users, 8.33 (95 % CI 4.68–11.98) in TCA users, 9.33 (95 % CI 6.19–12.46) in non-users of antidepressants, and 5.05 (95 % CI 4.49–5.62) in past users of antidepressants. In the case–control analysis, relative risk estimates for seizures were increased in current users of SSRIs (adjusted odds ratio 1.98, 95 % CI 1.48–2.66) and SNRIs (adjusted odds ratio 1.99, 95 % CI 1.20–3.29), but not TCAs (adjusted odds ratio 0.99, 95 % CI 0.63–1.53), compared with non-users. Current use of SSRIs or SNRIs was associated with a twofold increased risk of first-time seizures compared with non-use, while current use of TCAs (mostly low dose) was not associated with seizures. Treatment initiation in SSRI and SNRI users was associated with a higher risk of seizures than longer-term treatment.

OBJECTIVE This study aims to assess the odds of developing incident gout in association with the use of postmenopausal estrogen-progestogen therapy, according to type, timing, duration, and route of administration of estrogen-progestogen therapy. METHODS We conducted a retrospective population-based case-control analysis using the United Kingdom-based Clinical Practice Research Datalink. We identified women (aged 45 y or older) who had a first-time diagnosis of gout recorded between 1990 and 2010. We matched one female control with each case on age, general practice, calendar time, and years of active history in the database. We used multivariate conditional logistic regression to calculate odds ratios (ORs) with 95% CIs (adjusted for confounders). RESULTS The adjusted OR for gout with current use of oral formulations of opposed estrogens (estrogen-progestogen) was 0.69 (95% CI, 0.56-0.86) compared with never use. Current use was associated with a decreased OR for gout in women without renal failure (adjusted OR, 0.71; 95% CI, 0.57-0.87) and hypertension (adjusted OR, 0.62; 95% CI, 0.44-0.87) compared with never use. Tibolone was associated with a decreased OR for gout (adjusted OR, 0.77; 95% CI, 0.63-0.95) compared with never use. Estrogens alone did not alter the OR for gout. CONCLUSIONS Current use of oral opposed estrogens, but not unopposed estrogens, is associated with a decreased OR for incident gout in women without renal failure and is more pronounced in women with hypertension. Use of tibolone is associated with a decreased OR for incident gout. The decreased OR for gout may be related to the progestogen component rather than the estrogen component.

Stevens–Johnson syndrome and toxic epidermal necrolysis have been associated with the use of various drugs, but evidence is scarce. We studied the association between new use of outpatient drugs other than anti-epileptic drugs and antibiotics and Stevens–Johnson syndrome and toxic epidermal necrolysis. We conducted a matched (1:4) case–control analysis in 480 previously validated Stevens–Johnson syndrome/toxic epidermal necrolysis cases (1995–2013). We calculated odds ratios with 95% confidence intervals for Stevens–Johnson syndrome/toxic epidermal necrolysis in new users of drugs compared to non-users. For cases of Stevens–Johnson syndrome/toxic epidermal necrolysis diagnosed ≤ 84 days after the first use of a drug, we assessed causality between drug exposure and Stevens–Johnson syndrome/toxic epidermal necrolysis using ALDEN (algorithm of drug causality in epidermal necrolysis). We calculated absolute risks by dividing the number of Stevens–Johnson syndrome/toxic epidermal necrolysis cases ≤ 84 days after new drug exposure by the total number of new users of the drug. There was an association between Stevens–Johnson syndrome/toxic epidermal necrolysis and the use of allopurinol (odds ratio 24.51, 95% confidence interval 2.94–204.04) and cyclooxygenase-2 inhibitors (odds ratio 24.19, 95% confidence interval 2.91–200.92). Proton pump inhibitors, fluoxetine, mirtazapine, and 5-aminosalicylates (sulfasalazine, mesalamine) were also associated with an increased risk of Stevens–Johnson syndrome/toxic epidermal necrolysis, though with lower odds ratios. ALDEN score application suggests a likely causality for these associations. Absolute risks of Stevens–Johnson syndrome/toxic epidermal necrolysis were 6.0/100,000 new users for allopurinol, and 1.9–4.3/100,000 new users for cyclooxygenase-2 inhibitors and 5-aminosalicylates, and 0.2–1.6/100,000 new users for proton pump inhibitors, fluoxetine, and mirtazapine. We found no association between Stevens–Johnson syndrome/toxic epidermal necrolysis and oxicams, benzodiazepines, citalopram, sertraline, paroxetine, venlafaxine, and phosphodiesterase-5 inhibitors despite > 100,000 new users. In this observational study, we observed likely causal associations between Stevens–Johnson syndrome/toxic epidermal necrolysis and use of allopurinol, cyclooxygenase-2 inhibitors, and 5-aminosalicylates, and potential associations for proton pump inhibitors, fluoxetine, and mirtazapine.

PURPOSE Metformin use has been associated with decreased cancer risks, though data on esophageal cancer are scarce. We explored the relation between use of metformin or other anti-diabetic drugs and the risk of esophageal cancer. METHODS We conducted a case-control analysis in the UK-based general practice research database (GPRD, now clinical practice research datalink, CPRD). Cases were individuals with an incident diagnosis of esophageal cancer between 1994 and 2010 at age 40-89 years. Ten controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD prior to the index date. Various potential confounders including diabetes mellitus, gastro-esophageal reflux, and use of proton-pump inhibitors were evaluated in univariate models, and the final results were adjusted for BMI and smoking. Results are presented as odds ratios (ORs) with 95 % confidence intervals (CI). RESULTS Long-term use (≥30 prescriptions) of metformin was not associated with a materially altered risk of esophageal cancer (adj. OR 1.23, 95 % CI 0.92-1.65), nor was long-term use of sulfonylureas (adj. OR 0.93, 95 % CI 0.70-1.23), insulin (adj. OR 0.87, 95 % CI 0.60-1.25), or of thiazolidinediones (adj. OR 0.71, 95 % CI 0.37-1.36). CONCLUSION In our population-based study, use of metformin was not associated with an altered risk of esophageal cancer.

To investigate the association between antipsychotic drug use and the development of first-time seizures in patients with schizophrenia, affective disorders, or dementia. We used data from the UK-based Clinical Practice Research Datalink database to conduct a follow-up study with a nested case–control analysis between 1998 and 2013. We identified patients with schizophrenia, affective disorders, or dementia, and estimated incidence rates of seizures among users of four antipsychotic drug subclasses, defined according to existing hypotheses on their seizure-inducing potential (1, olanzapine or quetiapine; 2, amisulpride, aripiprazole, risperidone, or sulpiride; 3, low-to-medium potency first-generation antipsychotic drugs [chlorpromazine, zuclopenthixol, flupenthixol, pericyazine, promazine, thioridazine]; 4, medium-to-high potency first-generation antipsychotic drugs [haloperidol, prochlorperazine, trifluoperazine]), and among those who did not use antipsychotic drugs. To adjust for confounding, we estimated odds ratios for seizures separately among patients with affective disorders or dementia, stratified by antipsychotic drug use and timing of use. In the total cohort of 60,121 patients (who had schizophrenia, affective disorders, or dementia), the incidence rate of seizures per 10,000 person-years was 32.6 (95 % confidence interval [CI] 22.6–42.6) in users of olanzapine or quetiapine, 24.1 (95 % CI 13.2–34.9) in users of amisulpride, aripiprazole, risperidone, or sulpiride, 49.4 (95 % CI 27.7–71.0) in users of low-to-medium potency antipsychotic drugs, 59.1 (95 % CI 40.1–78.2) in users of medium-to-high potency antipsychotic drugs, and 11.7 (95 % CI 10.0–13.4) in non-users of antipsychotic drugs. Patients with dementia had significantly higher incidence rates of first-time seizures compared with patients with affective disorders, irrespective of antipsychotic drug use. In patients with affective disorders, current use of medium-to-high potency first-generation antipsychotic drugs was associated with an increased risk of seizures (adjusted odds ratio 2.51 [95 % CI 1.51–4.18]) compared with non-use, while use of other antipsychotic drugs was not associated with seizures. In patients with dementia, current use of olanzapine or quetiapine (adjusted odds ratio 2.37 [95 % CI 1.35–4.15]), low-to-medium potency first-generation antipsychotic drugs (adjusted odds ratio 3.08 [95 % CI 1.34–7.08]), and medium-to-high potency first-generation antipsychotic drugs (adjusted odds ratio 2.24 [95 % CI 1.05–4.81]) was associated with an increased risk of seizures compared with non-use, but current use of amisulpride, aripiprazole, risperidone, or sulpiride (adjusted odds ratio 0.92 [95 % CI 0.48–1.75]) was not. Use of antipsychotic drugs in patients with schizophrenia could not be investigated because of small numbers. Current use of medium-to-high potency first-generation antipsychotic drugs was associated with a 2.5-fold increased risk of seizures compared with non-use of antipsychotic drugs in patients with affective disorders. In these patients, current use of all other antipsychotic drug subclasses was not associated with seizures. In patients with dementia, current and past use of all antipsychotic drug subclasses, except amisulpride, aripiprazole, risperidone, or sulpiride, was associated with an increased risk of seizures.

Previous observational studies have associated benzodiazepine use with an increased risk of dementia. However, limitations in the study methods leave questions unanswered regarding the interpretation of the findings. A case–control analysis was conducted using data from the UK-based Clinical Practice Research Datalink (CPRD). A total of 26,459 patients aged ≥65 years with newly diagnosed Alzheimer’s disease (AD) or vascular dementia (VaD) between 1998 and 2013 were identified and matched 1:1 to dementia-free controls on age, sex, calendar time, general practice, and number of years of recorded history. Adjusted odds ratios (aORs) were calculated with 95 % confidence intervals (CIs) of developing AD or VaD in relation to previous benzodiazepine use, stratified by duration and benzodiazepine type. The aOR (95 % CI) of developing AD for those who started benzodiazepines

More than 95% of the body carnitine is located in skeletal muscle, where it is essential for energy metabolism. Vegetarians ingest less carnitine and carnitine precursors and have lower plasma carnitine concentrations than omnivores. Principle aims of the current study were to assess the plasma and skeletal muscle carnitine content and physical performance of male vegetarians and matched omnivores under basal conditions and after L-carnitine supplementation.Sixteen vegetarians and eight omnivores participated in this interventional study with oral supplementation of 2 g L-carnitine for 12 weeks. Before carnitine supplementation, vegetarians had a 10% lower plasma carnitine concentration, but maintained skeletal muscle carnitine stores compared to omnivores. Skeletal muscle phosphocreatine, ATP, glycogen and lactate contents were also not different from omnivores. Maximal oxygen uptake (VO2max) and workload (P max) per bodyweight (bicycle spiroergometry) were not significantly different between vegetarians and omnivores. Sub-maximal exercise (75% VO2max for 1 h) revealed no significant differences between vegetarians and omnivores (respiratory exchange ratio, blood lactate and muscle metabolites). Supplementation with L-carnitine significantly increased the total plasma carnitine concentration (24% in omnivores, 31% in vegetarians) and the muscle carnitine content in vegetarians (13%). Despite this increase, P max and VO2max as well as muscle phosphocreatine, lactate and glycogen were not significantly affected by carnitine administration.Vegetarians have lower plasma carnitine concentrations, but maintained muscle carnitine stores compared to omnivores. Oral L-carnitine supplementation normalizes the plasma carnitine stores and slightly increases the skeletal muscle carnitine content in vegetarians, but without affecting muscle function and energy metabolism.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening mucocutaneous adverse drug reactions. Sulphonamide antibiotics are commonly accepted as one of the primary causes of SJS/TEN. This notion is based on results from two hospital-based case-control studies that identified the combined antibiotic cotrimoxazole (sulfamethoxazole and trimethoprim) as the cause of several SJS/TEN cases. Associations were also reported for penicillins, quinolones, cephalosporins, macrolides, tetracyclines, and metronidazole. Using data from the UK-based Clinical Practice Research Datalink, we conducted a 1:4-matched case-control study including 480 previously validated SJS/TEN cases (1995-2013) to quantify the association between SJS/TEN and antibiotics. We further quantified absolute risks of SJS/TEN within separate cohorts of antibiotic users and assessed causality in each exposed case using an adapted version of the algorithm of drug causality in epidermal necrolysis (ALDEN). We observed a strong association between SJS/TEN and trimethoprim alone (odds ratio=9.44, 95% CI 3.83-23.25; absolute risk: 0.98 cases/100’000 users), which suggests that the previously reported association between cotrimoxazole and SJS/TEN is at least partly attributable to the non-sulphonamide antibiotic trimethoprim, which is frequently prescribed as a single agent in the UK. Our study further corroborates previously reported associations between SJS/TEN and use of penicillins, quinolones, cephalosporins, and macrolides.

Saskia G Bruderer,1,2 Christoph R Meier,1–3 Susan S Jick,3 Michael Bodmer1,4 1Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, 2Hospital Pharmacy, University Hospital Basel, Basel, Switzerland; 3Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Lexington, MA, USA; 4Division of General Internal Medicine, Zug Community Hospital, Baar, Switzerland Context: Thyroid hormones influence kidney function and thereby might alter serum urate levels, a major risk factor for gouty arthritis.Objective: To assess the risk of developing incident gout in association with hypothyroidism or hyperthyroidism.Design: Retrospective population-based case–control analysis.Setting: UK-based Clinical Practice Research Datalink, a primary care research database.Patients: We identified adult patients with a diagnosis of incident gout between 1990 and 2014. We matched one control to each gout case in terms of age, sex, general practice, calendar time, and years of active history in the database.Main outcome measure: We used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for developing gout in association with hypo- or hyperthyroidism and adjusted for potential confounders.Results: The study population encompassed 68,159 incident gout cases, of whom 78.8% were male, and the same number of matched controls. There was no increased risk of gout in patients with hypothyroidism: adjusted OR of gout of 1.12 (95% CI 1.05–1.20) compared with no hypothyroidism. Current short-term treatment of thyroid hormone replacement therapy was associated with an adjusted OR of gout of 1.54 (95% CI 1.24–1.92), compared with no treatment. Neither hyperthyroidism nor current treatment with thyroid suppression therapy was associated with gout (adjusted OR, 1.08 [95% CI 0.95–1.22] and 0.82 [95% CI 0.57–1.17], respectively).Conclusion: This large observational study does not provide evidence that hypothyroidism or hyperthyroidism, irrespective of treatment, is associated with a clinically relevant increased risk of developing incident gout. There may be an exception among patients with newly diagnosed and treated hypothyroidism. Keywords: hypothyroidism, hyperthyroidism, Clinical Practice Research Datalink, epidemiology

Metformin use has been associated previously with a decreased risk of cancer, but its association with renal cell carcinoma has not yet been investigated in observational studies. We aimed to explore the association between the use of metformin and other antidiabetic drugs and the risk of renal cell carcinoma (RCC). We carried out a case-control analysis in the UK-based Clinical Practice Research Datalink. We included individuals with an incident RCC between January 1995 and December 2013 younger than the age of 90 years. Six controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the Clinical Practice Research Datalink before the index date. We included BMI, smoking, alcohol consumption, hypertension, and diabetes mellitus as potential confounders in a multivariate model using conditional logistic regression to calculate odds ratios with 95% confidence intervals, and we carried out a sensitivity analysis restricted only to diabetic cases and controls. Long-term use of metformin was not associated with an altered relative risk of RCC (≥30 prescriptions, adjusted odds ratio 1.18, 95% confidence interval 0.88-1.58), nor was use of other antidiabetic drugs. Results in the sensitivity analysis including only diabetic cases and controls were largely the same. Use of metformin or other antidiabetic drugs was not associated with a materially altered risk of RCC. Further studies are warranted.

2,5-Dimethoxy-4(n)-propylphenethylamine (2C-P) is a synthetic phenethylamine derivative belonging to the large family of the so-called 2C drugs. These compounds can differ significantly in receptor affinity, potency and duration of action, and an important structural difference is the ligand in the 4 position of the phenyl ring, such as propyl in 2C-P or bromine in 2,5-dimethoxy-4-bromophenethylamine (2C-B). The 2C drugs are known for their hallucinogenic properties. We present a case of a 19-year-old male admitted to the emergency department with severe hallucinations, mydriasis, tachycardia, agitation and confusion following the use of a substance sold as 2C-B. By using liquid chromatography-mass spectrometry, the more potent substance 2C-P was detected and quantified. On the basis of two blood sample concentrations, the estimated elimination half-life was 19 h. This case report illustrates and discusses the differences in potency and duration of action of 2C drugs.

To assess incidence rates (IRs) of and identify risk factors for incident severe hypoglycaemia in patients with type 2 diabetes newly treated with antidiabetic drugs.; Using the UK-based General Practice Research Database, we performed a retrospective cohort study between 1994 and 2011 and a nested case-control analysis. Ten controls from the population at risk were matched to each case with a recorded severe hypoglycaemia during follow-up on general practice, years of history in the database and calendar time. Using multivariate conditional logistic regression analyses, we adjusted for potential confounders.; Of 130,761 patients with newly treated type 2 diabetes (mean age 61.7 ± 13.0 years), 690 (0.5%) had an incident episode of severe hypoglycaemia recorded [estimated IR 11.97 (95% confidence interval, CI, 11.11-12.90) per 10,000 person-years (PYs)]. The IR was markedly higher in insulin users [49.64 (95% CI, 44.08-55.89) per 10,000 PYs] than in patients not using insulin [8.03 (95% CI, 7.30-8.84) per 10,000 PYs]. Based on results of the nested case-control analysis increasing age [≥ 75 vs. 20-59 years; adjusted odds ratio (OR), 2.27; 95% CI, 1.65-3.12], cognitive impairment/dementia (adjusted OR, 2.00; 95% CI, 1.37-2.91), renal failure (adjusted OR, 1.34; 95% CI, 1.04-1.71), current use of sulphonylureas (adjusted OR, 4.45; 95% CI, 3.53-5.60) and current insulin use (adjusted OR, 11.83; 95% CI, 9.00-15.54) were all associated with an increased risk of severe hypoglycaemia.; Severe hypoglycaemia was recorded in 12 cases per 10,000 PYs. Risk factors for severe hypoglycaemia included increasing age, renal failure, cognitive impairment/dementia, and current use of insulin or sulphonylureas.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening mucocutaneous diseases. SJS/TEN mostly manifest as a reaction to new drug use, but little is known about their incidence and epidemiology. We conducted a large observational study on the epidemiology of SJS/TEN using data from the UK-based Clinical Practice Research Datalink. Among 551 validated SJS/TEN patients, we calculated an incidence rate of 5.76 SJS/TEN cases per million person-years between 1995 and 2013, which was consistent throughout the study period and was highest in patients aged 1-10 years and 80 years or older. Within a 1:4 matched case-control analysis, black and Asian patients were at a 2-fold risk of SJS/TEN when compared with white patients. Among patients with epilepsy and gout, odds ratios for SJS/TEN were significantly increased only in the presence of recent new drug treatment with antiepileptics or allopurinol, respectively. We observed statistically significant associations between SJS/TEN and pre-existing depression, lupus erythematosus, recent pneumonia, chronic kidney disease, and active cancer, but confounding by drug use needs to be followed up. This large and longitudinal observational study on the epidemiology of SJS/TEN contributes to the understanding of this still underinvestigated severe skin disease in a European and largely white study population.

Objective: Use of diuretics has been associated with an increased risk of gout. Data for different types of diuretics are scarce. This study investigated the association between use of loop diuretics, thiazide or thiazide-like diuretics, and potassium sparing agents and the risk of developing incident gout. Methods: We conducted a retrospective population-based case-control analysis using the General Practice Research Database (GPRD) from the United Kingdom. We identified case patients with incident gout between 1995 and 2010. We matched one control patient to each case patient on age, sex, general practice, calendar time, and years of active history in the database, used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs), and adjusted for potential confounders. Results: We identified 91,530 incident cases of gout and the same number of matched controls. Compared to past-use of the respective drug class, adjusted ORs for current use of loop diuretics, thiazide diuretics, thiazide-like diuretics, and potassium sparing diuretics were 2.64 (95% CI 2.47-2.83), 1.70 (95% CI 1.62-1.79), 2.30 (95% CI 1.95-2.70), and 1.06 (95% CI 0.91-1.23), respectively. Combined use of loop diuretics and thiazide diuretics was associated with the highest relative risk estimates of gout (adj. OR 4.65, 95% CI 3.51-6.16). Current use of calcium channel blockers or losartan slightly attenuated the risk of gout in users of various diuretics. Conclusion: Use of loop, thiazide, and thiazide-like diuretics, but not use of potassium-sparing agents, was associated with an increased risk of incident gout. © 2013 American College of Rheumatology.

Drogenscreeningtests mittels Immunoassay werden im klinischen Alltag immer wieder durchgeführt. Diese Tests detektieren je nach Hersteller die nachzuweisenden Substanzen sehr unterschiedlich. So können positive Messergebnisse auch durch Medikamente hervorgerufen werden, die nicht zur untersuchten Substanzklasse gehören. Andererseits kann es zu falsch negativen Resultaten kommen, wenn ein Patient eine Substanz eingenommen hat, die vom Antikörper im eingesetzten Test nicht erkannt wird. Deshalb müssen unplausible Resultate hinterfragt werden. Chromatographische Bestätigungs- und Screeningmethoden sind in der Durchführung und Interpretation aufwendiger und werden nur von wenigen Laboratorien angeboten. Ihre Spezifität ist aber sehr gut und eine Vielzahl verschiedener Substanzen können nachgewiesen werden, abhängig von der verwendeten Massenspektrenbibliothek. Liegt aufgrund der klinischen Beurteilung ein möglicher Vergiftungsfall vor, können Drogenscreeningtests von Nutzen sein, eine eingenommen Substanz- oder Substanzgruppe nachzuweisen, das klinische Bild kann jedoch durch Resultate dieser qualitativen Tests in der Regel nicht erklärt werden. Zudem konnte bis jetzt nicht gezeigt werden, dass durch diese Tests die Triage, Behandlung, Diagnostik oder die weitere Therapie vergifteter Patienten in klinisch relevanter Weise beeinflusst werden kann. Die quantitative Bestimmung von Einzelsubstanzen im Blut erlaubt zum Beispiel bei der Einnahme von Paracetamol oder Methanol eine Abschätzung der Prognose und hilft, die Indikation spezifischer Therapien zu stellen. Neue Designerdrogen können mit den klassischen Drogenscreeningtests nicht detektiert werden und müssen mittels chromatographischer Methoden identifiziert werden.

Objective: To explore the risk of ischemic stroke, hemorrhagic stroke, or TIA in patients with Alzheimer disease (AD) or vascular dementia (VD). Methods: We conducted a follow-up study with a nested case-control analysis using the UK-based General Practice Research Database. We included patients aged 65 years and older with an incident diagnosis of AD or VD between 1998 and 2008 and a comparison group of dementia-free patients. We estimated incidence rates of ischemic stroke, hemorrhagic stroke, or TIA in patients with AD, VD, or without dementia, and we calculated odds ratios with 95% confidence intervals (CIs) of developing such an outcome in patients with AD or VD, stratified by use of antipsychotic drugs. Results: We followed 6,443 cases with AD, 2,302 with VD, and 9,984 dementia-free patients over time and identified 281 cases with incident ischemic stroke, 139 with hemorrhagic stroke, and 379 with TIA. The incidence rates of ischemic stroke for patients with AD, VD, or no dementia were 4.7/1,000 person-years (PYs) (95% CI 3.8–5.9), 12.8/1,000 PYs (95% CI 9.8–16.8), and 5.1/1,000 PYs (95% CI 4.3–5.9), respectively. Compared with dementia-free patients, the odds ratio of developing a TIA for patients with AD treated with atypical antipsychotic drugs was 4.5 (95% CI 2.1–9.2). Conclusions: Patients with VD, but not AD, have a markedly higher risk of developing an ischemic stroke than those without dementia. In patients with AD, but not VD, use of atypical antipsychotic drugs was associated with an increased risk of TIA.

AIMS: This study's objective is to assess the safety of non-therapeutic atomoxetine exposures reported to the US National Poison Database System (NPDS). METHODS: This is a retrospective database study of non-therapeutic single agent ingestions of atomoxetine in children and adults reported to the NPDS between 2002 and 2010. RESULTS: A total of 20 032 atomoxetine exposures were reported during the study period, and 12 370 of these were single agent exposures. The median age was 9 years (interquartile range 3, 14), and 7380 were male (59.7%). Of the single agent exposures, 8813 (71.2%) were acute exposures, 3315 (26.8%) were acute-on-chronic, and 166 (1.3%) were chronic. In 10 608 (85.8%) cases, exposure was unintentional, in 1079 (8.7%) suicide attempts, and in 629 (5.1%) cases abuse. Of these cases, 3633 (29.4 %) were managed at health-care facilities. Acute-on-chronic exposure was associated with an increased risk of a suicidal reason for exposure compared with acute ingestions (odds ratio 1.44, 95% confidence interval 1.26-1.65). Most common clinical effects were drowsiness or lethargy (709 cases; 5.7%), tachycardia (555; 4.5%), and nausea (388; 3.1%). Major toxicity was observed in 21 cases (seizures in nine (42.9%), tachycardia in eight (38.1%), coma in six (28.6%), and ventricular dysrhythmia in one case (4.8%)). CONCLUSIONS: Non-therapeutic atomoxetine exposures were largely safe, but seizures were rarely observed. Copyright © 2013 John Wiley & Sons, Ltd. Language: en

Purpose: Patients with Alzheimer's disease (AD) have an increased risk of developing seizures or epilepsy. Little is known about the role of risk factors and about the risk of developing seizures/epilepsy in patients with vascular dementia (VD). The aim of this study was to assess incidence rates (IRs) of seizures/epilepsy in patients with AD, VD, or without dementia, and to identify potential risk factors of seizures or epilepsy. Methods: We conducted a follow-up study with a nested case-control analysis using the United Kingdom-based General Practice Research Database (GPRD). We identified patients aged ≥65 years with an incident diagnosis of AD or VD between 1998 and 2008 and a matched comparison group of dementia-free patients. Conditional logistic regression was used to estimate the odds ratio (OR) with a 95% confidence interval (CI) of developing seizures/epilepsy in patients with AD or VD, stratified by age at onset and duration of dementia as well as by use of antidementia drugs. Key Findings: Among 7,086 cases with AD, 4,438 with VD, and 11,524 matched dementia-free patients, we identified 180 cases with an incident diagnosis of seizures/epilepsy. The IRs of epilepsy/seizures for patients with AD or VD were 5.6/1,000 person-years (py) (95% CI 4.6-6.9) and 7.5/1,000 py (95% CI 5.7-9.7), respectively, and 0.8/1,000 py (95% CI 0.6-1.1) in the dementia-free group. In the nested case-control analysis, patients with longer standing (≥3 years) AD had a slightly higher risk of developing seizures or epilepsy than those with a shorter disease duration, whereas in patients with VD the contrary was observed. Significance: Seizures or epilepsy were substantially more common in patients with AD and VD than in dementia-free patients. The role of disease duration as a risk factor for seizures/epilepsy seems to differ between AD and VD.

To evaluate the validity of recorded diagnoses of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in the Clinical Practice Research Datalink (CPRD).We identified patients with a diagnosis of SJS or TEN between 1995 and 2013 in the CPRD. We reviewed information from patient records, free text, and hospital episode statistics (HES) data, and excluded patients with no indication of a secondary care referral. Remaining patients were classified as probable, possible, or unlikely cases of SJS/TEN by two specialised clinicians or based on pre-defined classification criteria. We quantified positive predictive values (PPV) for all SJS/TEN patients and for patients categorised as 'probable/possible' cases of SJS/TEN, based on a representative subsample of 118 patients for whom we had unequivocal information (original discharge letters or HES data).We identified 1324 patients with a diagnosis of SJS/TEN, among whom 638 had a secondary care referral recorded. Of those, 565 were classified as probable or possible cases after expert review. We calculated a PPV of 0.79 (95% CI, 0.71-0.86) for all SJS/TEN patients with a recorded secondary care referral, and a PPV of 0.87 (95% CI, 0.81-0.93) for probable/possible cases. After excluding 14 false positive patients, our study population consisted of 551 SJS/TEN patients.Diagnoses of SJS/TEN are recorded with moderate diagnostic accuracy in the CPRD, which was substantially improved by additional expert review of all available information. We established a large population-based SJS/TEN study population of high diagnostic validity from the CPRD. Copyright © 2016 John WileySons, Ltd.

Background Metformin use has been linked to a decreased cancer risk. We explored the association between use of metformin or other antidiabetic drugs and the risk of lung cancer. Methods We assessed the association between metformin, and other antidiabetic drugs and lung cancer using a case–control analysis in the UK-based General Practice Research Database (GPRD). Cases were people with an incident diagnosis of lung cancer. Up to 6 controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD. The contribution of potential confounders including tuberculosis, chronic obstructive pulmonary disease (COPD), diabetes mellitus, and co-morbid conditions to diabetes was evaluated in univariate models, and final results were adjusted for BMI and smoking. Results Long-term use (≥40 prescriptions) of metformin was not associated with an altered risk of lung cancer (adj. OR 1.21, 95% CI 0.97–1.50. Long-term use of sulfonylureas was linked to a marginally decreased risk of lung cancer (adj. OR 0.74, 95% CI 0.60–0.90. This risk decrease was observed in men (adj. OR 0.64, 95% CI 0.50–0.83) but not in women (adj. OR 0.97, 95% CI 0.69–1.37) and this risk decrease was not statistically significant in an analysis restricted to diabetic patients only (adj. OR. 0.82, 95% CI 0.65–1.02). Long-term use of insulin was associated with a slightly increased risk of lung cancer (adj. OR 1.33, 95% CI 1.04–1.71); however, no consistent trend across duration strata was observed. Conclusion Metformin did not decrease the risk of lung cancer.

To quantify the effect of therapeutic doses of acetaminophen on serum alanine aminotransferase (ALT) levels in subjects who consumed ethanol.Systematic review of six randomized placebo-controlled trials, of which five were included in a meta-analysis.Subjects included in the meta-analysis were those who consumed ethanol and received acetaminophen in doses up to 4 g/day (551 subjects) or placebo (350 subjects).A comprehensive literature search of the MEDLINE, EMBASE, and International Pharmaceutical Abstracts databases and the Cochrane Central Register of Controlled Trials was performed to identify randomized, placebo-controlled trials that enrolled subjects who consumed ethanol, received acetaminophen in therapeutic doses up to 4 g/day, and had serum ALT level measurements. A total of 184 articles were identified; six articles met all criteria. Five of the six articles reported ALT levels on study day 4 for both groups of subjects who received acetaminophen or placebo. Thus, for the meta-analysis, we used the primary outcome of mean change in serum ALT level from baseline to day 4 in the acetaminophen groups compared with the placebo groups. We found that the difference in mean change from baseline ALT levels between the acetaminophen and placebo groups on day 4 was 0.0 U/L (95% confidence interval -0.2-0.1 U/L). There were no reports of liver dysfunction, liver failure, or death in any of the trials.In randomized, placebo-controlled trials of subjects who consumed ethanol, no elevation of ALT level on study day 4 was noted when subjects ingested up to 4 g/day of acetaminophen.

The objective of this study was to explore the association between use of metformin or other antidiabetic drugs, diabetes, and the risk of pancreatic cancer.; We conducted a case-control study using the UK-based General Practice Research Database (GPRD). Cases had a first-time diagnosis of pancreatic cancer, and six controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD before the index date. Results were further adjusted in multivariate logistic regression analyses for potential confounders such as body mass index, smoking, alcohol consumption, and diabetes duration.; In all, 2,763 case patients with a recorded diagnosis of pancreatic cancer were identified. Mean age ± s.d. was 69.5 ± 11.0 years. Long-term use (≥ 30 prescriptions) of metformin was not associated with a materially altered risk of pancreatic cancer (adjusted odds ratio (adj. OR): 0.87, 95% confidence interval (CI): 0.59-1.29), but there was a suggestion of effect modification by gender, as long-term use of metformin was linked to a decreased risk in women (adj. OR: 0.43, 95% CI: 0.23-0.80). Both use of sulfonylureas (≥ 30 prescriptions, adj. OR: 1.90, 95% CI: 1.32-2.74) and of insulin (≥ 40 prescriptions, adj. OR: 2.29, 95% CI: 1.34-3.92) were associated with an increased risk of pancreatic cancer.; Use of metformin was associated with a decreased risk of pancreatic cancer in women only, whereas use of sulfonylureas and of insulin was associated with an increased risk of pancreatic cancer.

To explore the risk of developing Alzheimer's disease (AD) in individuals with diabetes mellitus treated with metformin or other antidiabetic drugs.; Case-control study.; The United Kingdom-based General Practice Research Database (GPRD), a well-established primary care database.; Seven thousand eighty-six individuals aged 65 and older with an incident diagnosis of AD identified between 1998 and 2008 and the same number of matched controls without dementia. Matching criteria were age, sex, general practice, calendar time, and years of history in the database.; Comparison of previous use of metformin or other antidiabetic drugs between cases and controls and calculation of corresponding odds ratios (ORs) with 95% confidence intervals (CIs), using conditional logistic regression. Risk estimates were stratified according to duration of use and adjusted for potential confounders.; As compared with nonusers, long-term users of 60 or more metformin prescriptions were at greater risk of developing AD (adjusted OR (AOR) = 1.71, 95% CI = 1.12-2.60), but there was no consistent trend with increasing number of prescriptions. Long-term use of other antidiabetic drugs such as sulfonylureas (AOR = 1.01, 95% CI = 0.72-1.42), thiazolidinediones (AOR = 0.87, 95% CI = 0.31-2.40), or insulin (AOR = 1.01, 95% CI = 0.58-1.73) was not related to an altered risk of developing AD.; Long-term use of sulfonylureas, thiazolidinediones, or insulin was not associated with an altered risk of developing AD. There was a suggestion of a slightly higher risk of AD in long-term users of metformin.

The most important psychoactive constituent of Cannabis sativa L. is Δ 9 -tetrahydrocannabinol (THC). Cannabidiol (CBD), another important con- stituent,isabletomodulatethedistinctunwanted psychotropic effect of THC. In natural plant ex- tracts of C. sativa, large amounts of THC and CBD appear in the form of THCA‑A (THC-acid-A) and CBDA (cannabidiolic acid), which can be trans- formed to THC and CBD by heating. Previous re- ports of medicinal use of cannabis or cannabis preparations with higher CBD/THC ratios and use in its natural, unheated form have demonstrated that pharmacological effects were often accompa- nied with a lower rate of adverse effects. There- fore, in the present study, the pharmacokinetics and metabolic profiles of two different C. sativa extracts (heated and unheated) with a CBD/THC ratio > 1 were compared to synthetic THC (dro- nabinol) in a double-blind, randomized, single center, three-period cross-over study involving 9 healthy male volunteers. The pharmacoki- netics of the cannabinoids was highly variable. The metabolic pattern was significantly different after administration of the different forms: the heated extract showed a lower median THC plasma AUC24h than the unheated extract of 2.84 vs. 6.59 pmol h/mL, respectively. The later was slightly higher than that of dronabinol (4.58pmol h/mL). On the other hand, the median sum of the metabolites (THC, 11-OH‑THC, THC- COOH, CBN) plasma AUC24h was higher for the heated than for the unheated extract. The median CBD plasma AUC24h was almost 2-fold higher for the unheated than for the heated extract. These results indicate that use of unheated extracts may lead to a beneficial change in metabolic pat- tern and possibly better tolerability. " Cannabis sativa L. l " Cannabaceae l " tetrahydrocannabinol l " THC l " THC metabolites l " CBD l " pharmacokinetics

Methylphenidat (MPH) wird in der Behandlung des Aufmerksamkeits-Defizit und Hyperaktivität-Syndroms (ADHS) eingesetzt. Zusammen mit dem Anstieg der Anzahl Verschreibungen von MPH in den letzten Jahren hat auch der nichtmedizinische und damit missbräuchliche Gebrauch von MPH als Suchtmittel und als kognitiver Leistungsverstärker zugenommen. Systematisch erhobene Prävalenzdaten zum Missbrauch von MPH in der Schweiz sind aktuell jedoch nicht verfügbar. MPH wird auch in Kombination mit illegalen Drogen eingenommen. Auch ADHS-Patienten missbrauchen nicht selten verschriebenes MPH. Oraler und nasaler Missbrauch von MPH ist mit geringer bis moderater sympathomimetischer Toxizität assoziiert. Sowohl die intravenöse als auch die versehentliche intraarterielle Applikation von Tablettenfragmenten kann jedoch zu schwerwiegender Toxizität führen.