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IntroductionPostoperative delirium (POD) is a common and serious adverse event of surgery in older people. Because of its great impact on patients' safety and quality of life, identification of modifiable risk factors could be useful. Although preoperative medication intake is assumed to be an important modifiable risk factor, the impact of anticholinergic drugs on the occurrence of POD seems underestimated in elective surgery. The aim of this study was to investigate the association between preoperative anticholinergic burden and POD. We hypothesized that a high preoperative anticholinergic burden is an independent, potentially modifiable predisposing and precipitating factor of POD in older people. MethodsBetween November 2017 and April 2019, 1,470 patients of 70 years and older undergoing elective orthopedic, general, cardiac, or vascular surgery were recruited in the randomized, prospective, multicenter PAWEL trial. Anticholinergic burden of a sub-cohort of 899 patients, who did not receive a multimodal intervention for preventing POD, was assessed by two different tools at hospital admission: The established Anticholinergic Risk Scale (ARS) and the recently developed Anticholinergic Burden Score (ABS). POD was detected by confusion assessment method (CAM) and a validated post discharge medical record review. Logistic regression analyses were performed to evaluate the association between anticholinergic burden and POD. ResultsPOD was observed in 210 of 899 patients (23.4%). Both ARS and ABS were independently associated with POD. The association persisted after adjustment for relevant confounding factors such as age, sex, comorbidities, preoperative cognitive and physical status, number of prescribed drugs, surgery time, type of surgery and anesthesia, usage of heart-lung-machine, and treatment in intensive care unit. If a patient was taking one of the 56 drugs listed in the ABS, risk for POD was 2.7-fold higher (OR = 2.74, 95% CI = 1.55-4.94) and 1.5-fold higher per additional point on the ARS (OR = 1.54, 95% CI = 1.15-2.02). ConclusionPreoperative anticholinergic drug exposure measured by ARS or ABS was independently associated with POD in older patients undergoing elective surgery. Therefore, identification, discontinuation or substitution of anticholinergic medication prior to surgery may be a promising approach to reduce the risk of POD in older patients.
BACKGROUND: Addiction is supposedly characterized by a shift from goal-directed to habitual decision making, thus facilitating automatic drug intake. The two-step task allows distinguishing between these mechanisms by computationally modeling goal-directed and habitual behavior as model-based and model-free control. In addicted patients, decision making may also strongly depend upon drug-associated expectations. Therefore, we investigated model-based versus model-free decision making and its neural correlates as well as alcohol expectancies in alcohol-dependent patients and healthy controls and assessed treatment outcome in patients. METHODS: Ninety detoxified, medication-free, alcohol-dependent patients and 96 age-and gender-matched control subjects underwent functional magnetic resonance imaging during the two-step task. Alcohol expectancies were measured with the Alcohol Expectancy Questionnaire. Over a follow-up period of 48 weeks, 37 patients remained abstinent and 53 patients relapsed as indicated by the Alcohol Timeline Followback method. RESULTS: Patients who relapsed displayed reduced medial prefrontal cortex activation during model-based decision making. Furthermore, high alcohol expectancies were associated with low model-based control in relapsers, while the opposite was observed in abstainers and healthy control subjects. However, reduced model-based control per se was not associated with subsequent relapse. CONCLUSIONS: These findings suggest that poor treatment outcome in alcohol dependence does not simply result from a shift from model-based to model-free control but is instead dependent on the interaction between high drug expectancies and low model-based decision making. Reduced model-based medial prefrontal cortex signatures in those who relapse point to a neural correlate of relapse risk. These observations suggest that therapeutic interventions should target subjective alcohol expectancies.
Objective: To estimate the prevalence and the type of antidepressant medication prescribed by German psychiatrists to patients with depression and cardiovascular diseases (CVD). Methods: This study was a retrospective database analysis in Germany using the Disease Analyzer Database (IMS Health, Germany). The study population included 2,288 CVD patients between 40 and 90 years of age from 175 psychiatric practices. The observation period was between 2004 and 2013. Follow-up lasted up to 12 months and ended in April 2015. Also included were 2,288 non-CVD controls matched (1 : 1) to CVD cases on the basis of age, gender, health insurance coverage, depression severity, and diagnosing physician. Results: Mean age was 68.6 years. 46.2% of patients were men, and 5.9% had private health insurance coverage. Mild, moderate, or severe depression was present in 18.7%, 60.7%, and 20.6% of patients, respectively. Most patients had treatment within a year, many of them immediately after depression diagnosis. Patients with moderate and severe depression were more likely to receive treatment than patients with mild depression. There was no difference between CVD and non-CVD in the proportion of patients treated. Nonetheless, CVD patients received selective serotonin reuptake inhibitors / serotonin-noradrenaline reuptake inhibitors (SSRIs/SNRIs) significantly more frequently. Conversely, patients without CVD were more often treated with TCA. Conclusion: There was no association between CVD and the initiation of depression treatment. Furthermore, CVD patients received SSRIs/SNRIs more frequently.
Timing and magnitude of surface uplift are key to understanding the impact of crustal deformation and topographic growth on atmospheric circulation, environmental conditions, and surface processes. Uplift of the East African Plateau is linked to mantle processes, but paleoaltimetry data are too scarce to constrain plateau evolution and subsequent vertical motions associated with rifting. Here, we assess the paleotopographic implications of a beaked whale fossil (Ziphiidae) from the Turkana region of Kenya found 740 km inland from the present-day coastline of the Indian Ocean at an elevation of 620 m. The specimen is similar to 17 My old and represents the oldest derived beaked whale known, consistent with molecular estimates of the emergence of modern straptoothed whales (Mesoplodon). The whale traveled from the Indian Ocean inland along an eastward-directed drainage system controlled by the Cretaceous Anza Graben and was stranded slightly above sea level. Surface uplift from near sea level coincides with paleoclimatic change from a humid environment to highly variable and much drier conditions, which altered biotic communities and drove evolution in east Africa, including that of primates.
In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.
Objective: Demographic changes are increasing the pressure to improve therapeutic strategies against cognitive decline in Alzheimer disease (AD) and mild cognitive impairment (MCI). Besides drug treatment, physical activity seems to be a promising intervention target as epidemiological and clinical studies suggest beneficial effects of exercise training on cognition. Using comparable inclusion and exclusion criteria, we analyzed the efficacy of drug therapy (cholinesterase inhibitors, memantine, and Ginkgo biloba) and exercise interventions for improving cognition in AD and MCI populations. Methods: We searched The Cochrane Library, EBSCO, OVID, Web of Science, and U.S Food and Drug Administration data from inception through October 30, 2013. Randomized controlled trials in which at least one treatment arm consisted of an exercise or a pharmacological intervention for AD or MCI patients, and which had either a non-exposed control condition or a control condition that received another intervention. Treatment discontinuation rates and Standardized Mean Change score using Raw score standardization (SMCR) of cognitive performance were calculated. Results: Discontinuation rates varied substantially and ranged between 0% and 49% with a median of 18%. Significantly increased discontinuation rates were found for galantamine and rivastigmine as compared to placebo in AD studies. Drug treatments resulted in a small pooled effect on cognition (SMCR: 0.23, 95% CI: 0.20 to 0.25) in AD studies (N = 45, 18,434 patients) and no effect in any of the MCI studies (N = 5, 3,693 patients; SMCR: 0.03, 95% CI: 0.00 to 0.005). Exercise interventions had a moderate to strong pooled effect size (SMCR: 0.83, 95% CI: 0.59 to 1.07) in AD studies (N = 4, 119 patients), and a small effect size (SMCR: 0.20, 95% CI: 0.11 to 0.28) in MCI (N = 6, 443 patients). Conclusions: Drug treatments have a small but significant impact on cognitive functioning in AD and exercise has the potential to improve cognition in AD and MCI. Head-to-head trials with sufficient statistical power are necessary to directly compare efficacy, safety, and acceptability. Combining these two approaches might further increase the efficacy of each individual intervention. Identifier: PROSPERO (2013:CRD42013003910).
Continuous treatment with antidementia drugs in Germany 2003-2013: a retrospective database analysis
(2015)
Background: Continuous treatment is an important indicator of medication adherence in dementia. However, long-term studies in larger clinical settings are lacking, and little is known about moderating effects of patient and service characteristics.
Methods: Data from 12,910 outpatients with dementia (mean age 79.2 years; SD = 7.6 years) treated between January 2003 and December 2013 in Germany were included. Continuous treatment was analysed using Kaplan-Meier curves and log-rank tests. In addition, multivariate Cox regression models were fitted with continuous treatment as dependent variable and the predictors antidementia agent, age, gender, medical comorbidities, physician specialty, and health insurance status.
Results: After one year of follow-up, nearly 60% of patients continued drug treatment. Donezepil (HR: 0.88; 95% CI: 0.82-0.95) and memantine (HR: 0.85; 0.79-0.91) patients were less likely to be discontinued treatment as compared to rivastigmine users. Patients were less likely to be discontinued if they were treated by specialist physicians as compared to general practitioners (HR: 0.44; 0.41-0.48). Younger male patients and patients who had private health insurance had a lower discontinuation risk. Regarding comorbidity, patients were more likely to be continuously treated with the index substance if a diagnosis of heart failure or hypertension had been diagnosed at baseline.
Conclusions: Our results imply that besides type of antidementia agent, involvement of a specialist in the complex process of prescribing antidementia drugs can provide meaningful benefits to patients, in terms of more disease-specific and continuous treatment.