Non-pharmacological Factors Research Articles

Intracellular regeneration of adrenocorticocytes in response to the prophylactic application of low-intensity electromagnetic radiation under the conditions of radiation (an experimental study)

Adaptation of the organism to the action of certain damaging factors, including radiation, is closely related to the state of the hypothalamic-pituitary-adrenal system. The important role in its activities is played by adrenocorticocytes (ACC) - the cells of the fascicular zone of the adrenal cortex. The disturbance of the structure and function of these cells can significantly impair and limit the development of the adaptive reactions in the body. One of the most promising ways to prevent the post-radiation changes in adrenocorticocytes consists of the application of the non-pharmacological therapeutic factors, such as low-intensity electromagnetic radiation (EMR) of ultra high frequency ( UHF) and the low-frequency (LF) magnetic field (MF) of low intensity (LI) after the exposition of the cells to the action of radiation. The objective of the present study was to identify the ultrastructural regenerative - adaptive changes in ACC of the fascicular zone of the adrenal gland in response to the primary preventive action of ultra high frequency EMR, microwave oven, and low-intensity MF after the exposition of the cells to the action of radiation. The investigations were carried using the outbred male rats (180-200 gr body weight). The experimental animals were allocated to four groups two of which had been preliminarily treated by the application of ultra high frequency EMR and low-intensity MF and were thereafter exposed to radiation. The animals of the third group were exposed to radiation alone without the treatment with the therapeutic physical factors and served as controls whereas the animals of the fourth group underwent no treatment whatever and were regarded as intact. Transmission electron microscopy was used to count light and dark adrenocorticocytes of the fascicular zone. The morphometric analysis of mitochondria included the determination of their number, the average and the total area per standard cell area, and the number of cristae per average area of mitochondria). In addition, the analysis of the lipid content and protein-synthesizing organelles was performed. The study has demonstrated that the primary prophylactic application of ultra high frequency EMR and the low-frequency MF caused stimulation of the cellular and intracellular regenerative-adaptive reactions and increased the resistance of the ultrastructure of ACC in the fascicular zone of the adrenal glands to the action of radiation. These changes were most pronounced in response to the application of ultra high frequency EMR. The resulting structural-adaptive rearrangements of the organelles (the enlargement of mitochondria with the simultaneous increase in the number of cristae, hyperplasia of ribosomes and smooth endoplasmic reticulum, preservation of membranes) were largely due to antioxidative and membrane-stabilizing effects of low-intensity electromagnetic radiation of ultra high frequency and were directly related to the formation of the mechanisms of ACC radioprotection. The Increased regenerative-adaptive potential of these cells prevented the development of the dystrophic processes and protected the adrenocorticocytes from aggressive radiation. The results of the present study suggests the necessity of the further studies on the action of the non-pharmacological therapeutic factors, especially low-intensity electromagnetic radiation (EMR) of ultra high frequency and the low-frequency magnetic field of low intensity as the tools for the prevention of post-radiation changes in the adrenocorticocytes of the fascicular zone of the adrenal cortex exposed to the action of radiation.

Using Placebo Beverages in Group Alcohol Studies.

Placebo beverage conditions remain a key element in the methodological toolkit for alcohol researchers interested in evaluating pharmacological and nonpharmacological factors influencing the effects of alcohol consumption. While interest in experimentally examining alcohol in social context is on the rise, there has been little research examining the effectiveness of placebo manipulations in group settings, when just 1 suspicious participant could potentially jeopardize the effect of the placebo on group members. Moreover, research has rarely considered the association between individual difference factors (e.g., gender) and placebo manipulation effectiveness. The present study, using an uncommonly large sample of placebo-consuming participants, was well suited to investigate fundamental questions regarding placebo efficacy that have not been assessed previously. Specifically, we aimed to examine placebo efficacy and general processes of placebo functioning in a group context. We also assessed potential associations between a variety of individual difference factors and placebo response. A total of 240 participants (50% male) consumed placebo beverages during a triadic drinking period (across 80 three-person groups). Participants reported their subjective intoxication, stimulation, and sedation 8minutes following drink consumption and estimated the alcohol content of their drink at the end of the study. Participants consuming placebo beverages in groups were nearly universal in reporting that they had consumed alcohol (>99%) and had experienced an increase in feelings of intoxication [t(239)=22.03, p<0.001] and stimulation [t(239)=5.53, p<0.001], levels that were similar to those observed in prior studies conducted with participants drinking placebos in isolation. Further, participants' placebo responses were independent of their 2 group members and were largely unaffected by a variety of individual difference factors. Placebo response generally operated independently of group-member influences, suggesting that researchers can successfully conduct placebo beverage studies utilizing group drinking designs.

Strength Training as an Adjunct to the Maintenance of Muscle Mass in Patients with Head and Neck Cancer

Head and neck cancer (HNC) is one of the most common types of the disease, particularly among men, and is characterized by a high incidence of death. Among the non-pharmacological factors that help in survival and improving quality of life is physical exercise, especially strength training. The purpose of this short communication was to briefly review the literature and present a training proposal for oncology patients with HNC. Evidence is provided that physical exercise, mainly short-term strength (HIIT [High-Intensity Interval Training]) and aerobic training, contributes to increased expectation and quality of life in cancer survivors. After reviewing the current state of literature, we conclude that strength training, by providing maintenance of muscle mass, improves the autonomy and quality of life of oncology patients with HNC.

Impulse control disorders in Parkinson's disease patients with RLS: a cross sectional-study

BackgroundAlthough dopamine replacement therapy is the main risk factor for the occurrence of Impulse Control Disorders (ICDs) in Parkinson's disease (PD), non-pharmacological risk factors for have also been identified in that population and sleep disorders could be part of them. Our objective is to determine whether Restless Legs Syndrome (RLS), that has been associated with more impulsive choices in general population regardless of dopaminergic therapy, could be associated with a specific psycho-behavioral profile and ICDs in PD. MethodsEighty consecutive PD patients were screened for the presence of RLS in a cross-sectional study. Sleep features were evaluated during one video-polysomnography. The frequency of ICDs, according to standard criteria, together with a broad range of psycho-behavioral features using the Ardouin Scale of Behavior in PD, were compared in patients with RLS (PD-RLS, n = 30) versus without RLS (PD-nRLS, n = 50). ResultsPD patients with RLS reported significantly more ICDs than those without RLS (50% versus 26%, p = 0.03), especially compulsive eating disorders, and a different psycho-behavioral profile with more hyperdopaminergic behaviors. There was no between group difference for total and dopamine agonists levodopa equivalent doses. However, age and durations of both disease and dopaminergic treatment were greater in the RLS group. Multivariate and propensity score analyses controlling for age, gender, total sleep time, disease severity, dose and duration of treatment, anxiety and depression showed that RLS was an independent predictor of ICDs in PD (OR = 5.91 [1.63; 22.1] and OR = 2.89 [1.63; 6.67] respectively). ConclusionRLS per se could be a risk factor for impulsive behaviors in PD.

Hypertensive patients’ adherence to pharmacological and non-pharmacological treatment methods, in Turkey

Background: The present study was aimed at determining hypertensive patients’ adherence to pharmacological and non-pharmacological treatment methods and factors affecting their adherence. Methods: This cross-sectional study was conducted with 418 patients aged 18 and over who met the inclusion criteria. Adherence to pharmacological and some non-pharmacological treatment methods is the dependent variable of the study. Data were collected using the personal information form, Morisky medication adherence scale. In the analysis, descriptive statistics, the chi square test, and logistic regression analysis were used. The significance level was accepted as p&lt;0.05. Results: The rate of adherence to the pharmacological treatment was 78.2%. The rates of adherence to smoking cessation, diet and physical activity were 49.0%, 55.7% and 20.6% respectively. Age, employment status and perceived health status were associated with the adherence to smoking cessation; perceived income, resort to complementary alternative treatment methods and having regular controls (check-ups) were related to the adherence to the diet, and gender and perceived economic status were related to the adherence to physical activities (p&lt;0.05). Conclusions: While approximately four out of five patients complied with the pharmacological treatment, rates of adherence to non-pharmacological treatment methods were low. Multidisciplinary intervention programs should be planned in order to regularly monitor patients at family health centers, to assess their adherence to treatment modalities and to promote adherence.

Osteoporosis: fracture epidemiology update 2016.

The purpose of this review is to provide an update on osteoporosis epidemiology. The focus is on fractures because fractures are the most important clinical consequence of osteoporosis. Studies published over the past 18 months are identified and reviewed. Finally, the clinical impact of these new findings is discussed. Important research in 2015-2016 include analyses of screening and rescreening in younger women and older men, risk factors for hip fractures in older men, obesity and weight loss/gain, and risk of fracture. Several dietary factors, including adherence to a Mediterranean diet and a diet rich in protein, fruits, and vegetables and maintenance of physical function with increasing age represent modifiable nonpharmacologic risk factors that improve bone health. Sarcopenia may have a more important role in fracture in men than women. Important biomarkers for fracture include low 25-hydroxyvitamin D and hemoglobin A1c. Updated literature on fracture epidemiology have identified important risk factors for fracture.

Constructing drug effects: A history of set and setting

Set and setting is a term which refers to the psychological, social, and cultural parameters which shape the response to psychedelic drugs. The concept is considered fundamental to psychedelic research and has also been used to describe nonpharmacological factors which shape the effects of other agents such as alcohol, heroin, amphetamines, or cocaine. This paper reviews the history and evolution of the concept of set and setting from the 19th-century Parisian Club des Hashischins, through to 1950s psychotomimetic research on nondrug determinants of psychopharmacology, the use of extra-drug techniques by psychedelic therapists of the 1950s, and the invention of the concept of set and setting by Leary. Later developments and expansions on the concept of set and setting are discussed, and the term of collective set and setting is suggested as a theoretical tool to describe the social forces which shape individual set and setting situations. The concept of set and setting, it is argued, is crucial not only for psychedelic research but also for advancing drug research and developing more effective drug policy.

Sedative effect of Clozapine is a function of 5-HT2A and environmental novelty

Antipsychotic drugs are the mainstay in the treatment of schizophrenia and bipolar disorder. However, antipsychotics often exhibit sedation or activity suppression among many other side effects, and the factors that influence them remain poorly understood. We now show, using a 5-HT2A knockout (Htr2a−/−) mouse, that environmental circumstances can affect suppression of activity induced by the atypical antipsychotic- Clozapine. We observed that Htr2a−/− mice were more resistant to Clozapine-induced suppression of activity (CISA) and this behaviour was dependent on the environment being ‘novel’. In their ‘home’ environment, at identical doses the mice exhibited CISA. Interestingly, the effect of genotype and environmental novelty on CISA could not be extended to the other antipsychotics that were tested, i.e. Haloperidol and Risperidone. Haloperidol-induced activity suppression was independent of context and genotype. Whereas context affected Risperidone-induced activity suppression only in the Htr2a+/+ mice. Furthermore, we observed that caffeine, a stimulant, elicited resistance to CISA similar to that seen in the ‘novel’ context. Our study establishes a previously unknown interaction between the environmental context, 5-HT2A and CISA and emphasises the role of non-pharmacological factors such as environment on the effects of the drug, which seem antipsychotic-specific. Our findings should advance the understanding of the side effects of individual antipsychotics and the role of environment to overcome side effects such as sedation.

Device Matters: Looking Beyond the Drug

Prof Helen Reddel opened the symposium by discussing the need to examine the modifiable nonpharmacological factors in the treatment of asthma and chronic obstructive pulmonary disease (COPD) that can be addressed to improve clinical outcomes. Dr Kai-Michael Beeh set the scene and discussed the need to review patient behaviour and drug delivery mechanisms to improve outcomes for patients with asthma and COPD. Dr John Haughney then discussed how patient preferences for inhalers can impact real-world outcomes. Prof Sinthia Bosnic-Anticevich outlined the challenges in learning and maintaining correct inhaler technique, while Prof Henry Chrystyn highlighted how inhaler design can help minimise the impact of inhaler errors on clinical outcomes. Prof Helen Reddel closed the session by bridging the gap between guidelines and clinical care, describing ways to incorporate regular checking and training of inhaler skills into a range of settings. The meeting objectives were to look beyond drugs to the role of devices in optimising asthma and COPD management, to understand the impact of inhaler technique on treatment efficacy, to review how patient perspectives about their inhaler can impact on clinical outcomes, and to discuss how to implement current clinical guidelines on inhaler technique in day-to-day clinical care.

Antipsychotic-induced sensitization and tolerance: Behavioral characteristics, developmental impacts, and neurobiological mechanisms.

Antipsychotic sensitization and tolerance refer to the increased and decreased drug effects due to past drug use, respectively. Both effects reflect the long-term impacts of antipsychotic treatment on the brain and result from the brain’s adaptive response to the foreign property of the drug. In this review, clinical evidence of the behavioral aspect of antipsychotic sensitization and tolerance is selectively reviewed, followed by an overview of preclinical literature that examines these behavioral characteristics and the related pharmacological and nonpharmacological factors. Next, recent work on the developmental impacts of adolescent antipsychotic sensitization and tolerance is presented and recent research that delineates the neurobiological mechanisms of antipsychotic sensitization and tolerance is summarized. A theoretical framework based on “drug learning and memory” principles is proposed to account for the phenomena of antipsychotic sensitization and tolerance. It is maintained that antipsychotic sensitization and tolerance follow basic principles of learning or acquisition (“induction”) and memory (“expression”). The induction and expression of both effects reflect the consequences of associative and nonassociative processing and are strongly influenced by various pharmacological, environmental, and behavioral factors. Drug-induced neuroplasticity, such as functional changes of striatal dopamine D2 and prefrontal serotonin (5-HT)2A receptors and their mediated signaling pathways, in principle, is responsible for antipsychotic sensitization and tolerance. Understanding the behavioral characteristics and neurobiological underpinnings of antipsychotic sensitization and tolerance has greatly enhanced our understanding of mechanisms of antipsychotic action, and may have important implications for future drug discovery and clinical practice.

Time to Analgesia Onset and Pharmacokinetics After Separate and Combined Administration of Liposome Bupivacaine and Bupivacaine HCl: Considerations for Clinicians

Background: Liposome bupivacaine is a prolonged-release bupivacaine formulation indicated for single-dose administration into the surgical site to produce postsurgical analgesia.Methods:An overview of time to onset of analgesia observed with liposome bupivacaine in human studies is provided, as well as a summary of data from pharmacokinetic studies including those that assessed pharmacokinetics after separate versus coadministration of liposome bupivacaine and bupivacaine HCl.Results:Data from multiple studies show that local administration of liposome bupivacaine is associated with rapid onset and effective analgesia after surgery. However, the efficacy profile observed in controlled settings may not replicate the profile observed in clinical practice; time to onset may be impacted by nonpharmacologic factors, such as amount of drug given, location and relative vascularity, and variances in surgical techniques. Some clinicians coadminister or admix bupivacaine HCl and liposome bupivacaine based on the supposition that adjuvant use will result in more rapid onset of efficacy. To date, no clinical studies have been conducted comparing pain-related outcomes following coadministration versus liposome bupivacaine alone. Preclinical pharmacokinetic studies have assessed the potential impact of combined use, which resulted in predictable, additive systemic exposure without compromising the prolonged-release profile of liposome bupivacaine, and without signs of toxicity.Conclusion:Based on available data and approved package insert, in the setting of wound infiltration, clinicians have the flexibility to administer liposome bupivacaine alone, coadminister separately with bupivacaine HCl, or admix with bupivacaine HCl prior to injection, providing the bupivacaine HCl dose does not exceed 50% of the liposome bupivacaine dose.

Without awareness of what I am

Introduction Fifty-year-old male. As a summary note that has a history of psychotic disorder from 25 years to coincide with the theological studies and your income as a priest. It has continued since then reviews and consultations in psychiatry, with two previous hospitalizations in private hospitals. It was stable with low doses of risperidone. Apparently, it makes a routine life linked to the activities of the church. Two months ago, he began to be irritable, suspicious, with discussions and problems at work, coinciding with the abandonment of treatment. Since the death of her mother a year ago has presented worsening. Objectives It presents the case of a patient who has no awareness of illness. Methods Psychopathological examination: conscious, oriented, scarcely manageable. Psychomotor restlessness. Expansive while maintaining distances, dysphoric and irritable. Verbiage. Ideas prejudice family-centered. There appears to be perceptual disturbances. Sleep-wake rhythms preserved. Results Treatment was initiated with injectable paliperidone administered dose of 150mg and 100mg, with 12mg of oral paliperidone with good response progressively. At high partial remission of symptoms, it is factual. Conclusions The lack of awareness of the disease is non-pharmacological factors that can make it difficult to comply with neuroleptic treatment. These patients do not calibrate well how important that medication has on the evolution of his illness. Therefore, the therapeutic substance of such failure worsens the quality of life of patients and their families, as well as the prognosis of their disease presenting increasingly severe relapses.

An observational study of clozapine-induced sedation and its pharmacological management

IntroductionClozapine is the only drug approved for resistant schizophrenia, but remains underused because of its side effects. Sedation is common, but its management is unclear.ObjectivesTo analyze factors associated with clozapine-induced sedation and the efficacy of common treatment strategies.AimsTo determine clozapine-induced sedation factors and possible therapeutic strategies.MethodsUsing two years’ electronic records of a community cohort of resistant schizophrenia spectrum disorder cases on clozapine, we performed three analyses: a cross-sectional analysis of which factors were associated with number of hours slept (objective proxy of sedation), and two prospective analyses: which factors were associated with changes in hours slept, and the efficacy of the main pharmacological strategies for improving sedation.ResultsOne hundred and thirty-three patients were included; 64.7% slept at least 9 hours/daily. Among monotherapy patients (n = 30), only norclozapine levels (r = .367, P = .033) correlated with sleeping hours. Multiple regression analyses confirmed the findings (r = .865, P &lt; .00001). Using the cohort prospectively assessed (n = 107), 42 patients decreased the number of hours slept between two consecutive appointments. Decreasing clozapine (40%) or augmenting with aripiprazole (36%) were the most common factors. In the efficacy analysis, these two strategies were recommended to 22 (20.6%) and 23 (21.5%) subjects, respectively. The majority (81.8% and 73.9%) did not report differences in the hours slept.ConclusionsSedationis common and involves pharmacological and non-pharmacological factors. The only correlation was a weak correlation between norclozapine plasma levels and total sleeping hours. Reducing clozapine and aripiprazole augmentation were the most successful strategies to ameliorate sedation, although both strategies were effective only in a limited numbers of subjects.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Predictors of Response to Cholinesterase Inhibitors Treatment of Alzheimer's Disease: Date Mining from the TREDEM Registry.

The pharmacological treatment of Alzheimer's disease (AD) is based largely on cholinesterase inhibitors (ChEI). To investigate whether or not some non-pharmacological and contextual factors measured prior to starting treatment such as past occupation, lifestyles, marital status, degree of autonomy and cognitive impairment, living alone or with others, and the degree of brain atrophy are associated with a better response to ChEI treatment. Eighty-four AD and six AD with cerebrovascular disease (AD + CVD) outpatients of Treviso Dementia (TREDEM) Registry, with an average cholinesterase inhibitors treatment length of four years, were considered. The outpatients had undergone a complete evaluation and some non-pharmacological and contextual factors were collected. We defined responder a patient with a delta score T0 - T1 equal or inferior to 2.0 points per year of MMSE and a non-responder a patient with a delta score T0 - T1 superior to 2.0 points per year. In order to identify hidden relationships between variables related to response and non-response, we use a special kind of artificial neural network called Auto-CM, able to create a semantic connectivity map of the variables considered in the study. A higher cognitive profile, a previous intellectual occupation, healthier lifestyles, being married and not living alone, a higher degree of autonomy, and lower degree of brain atrophy at baseline resulted in affecting the response to long-term ChEI therapy. Non-pharmacological and contextual factors appear to influence the effectiveness of treatment with ChEI in the long term.

The medical rehabilitation of the children presenting with atopic dermatitis (a literature review)

Atopic dermatitis takes the predominant position in the structure of skin pathologies in the children of various age. Both the scientifically based forecasts and the data of numerous investigations give evidence not only of the significant increase in the number of patients presenting with this condition but also of the growing severity of this disease. Taken together, these facts account for the serious medico-social importance of the problems arising in connection with this pathology. The introduction of the eliminative actions, a hypoallergenic diet, local and systemic pharmacotherapeutic modalities do not always allow to prevent or arrest the inflammatory process and achieve the long-standing remission. The high frequency of undesirable reactions to the pharmacological products turns the attention of many clinicians to the application of the non-pharmacological factors and methods for the treatment of atopic dermatitis in the children. The main objectives of physical therapy in the case of atopic dermatitis include the normalization of the state of the central and vegetative nervous system, the achievement of hyposensitization, sedative, anti-toxic, and anti-inflammatory effects, as well as the application of the dissolving, trophic, and antipruritogenic agents, strengthening of the general health status of the children.

Phenomenology, Structure, and Dynamic of Psychedelic States.

Classic serotonergic hallucinogens or psychedelics produce an altered states of consciousness (ASC) that is characterized by profound alterations in sensory perception, mood, thought including the perception of reality, and the sense of self. Over the past years, there has been considerable progress in the search for invariant and common features of psychedelic states. In the first part of this review, we outline contemporary approaches to characterize the structure of ASCs by means of three primary etiology-independent dimensions including oceanic boundlessness, anxious ego-dissolution, and visionary restructuralization as well as by 11 lower-order factors, all of which can be reliably measured by the altered state of consciousness questionnaire (APZ-OAV). The second part sheds light on the dynamic nature of psychedelic experiences. Frequently, psychedelic subjects progress through different stages over time and levels of changes along a perception-hallucination continuum of increasing arousal and ego-dissolution. We then review in detail the acute effects of psychedelics on sensory perception, emotion, cognition, creativity, and time perception along with possible neural mechanisms underlying them. The next part of this review outlines the influence of non-pharmacological factors (predictors) on the acute psychedelic experience, such as demographics, genetics, personality, mood, and setting, and also discusses some long-term effects succeeding the acute experience. The last part presents some recent concepts and models attempting to understand different facets of psychedelic states of consciousness from a neuroscientific perspective.

Psychiatrists' Attitudes Toward Non-Pharmacologic Factors Within the Context of Antidepressant Pharmacotherapy.

Recent meta-analyses of antidepressant clinical trials have suggested that up to 82% of response can be attributed to non-medication-related factors. The present study examines psychiatrists' attitudes regarding non-pharmacologic factors within the context of antidepressant pharmacotherapy. A web-based, 20-question cross-sectional survey was distributed to 101 staff psychiatrists and 48 post-graduate trainees in psychiatry at an academic hospital in Boston, MA. Demographics, practice characteristics, beliefs about non-pharmacologic factors affecting prescribing practices, perceived response and remission rates, and opinions about the need for further investigations in the psychopharmacology process were assessed. Overall completion rate was 53%. The final sample included 79 responses. The medians for clinician-perceived response rates (54%) and remission rates (33%) were in agreement with published rates. The reported median of the what portion of clinical outcomes is believed to be due to placebo effects (26%) was numerically lower than suggested by literature. The contribution of the active ingredients of medications was perceived to be significantly higher than the contribution of patient characteristics and clinician characteristics. A longer time since graduation from medical school was significantly associated with higher belief in the effect of the active ingredients of antidepressant medications and with less perceived importance of placebo effects. These findings suggest a discrepancy between empirical evidence and psychiatrists' beliefs on the impact of placebo effects on clinical outcomes. Educating antidepressant prescribers about the evidence based on psychosocial mediators of placebo effects' contribution to outcome may represent a promising strategy for improving clinical outcomes.

An observational study of clozapine induced sedation and its pharmacological management

Clozapine induced sedation is common but its management is unclear. We analyzed the factors associated with clozapine-induced sedation and the efficacy of common pharmacological strategies. We conducted a naturalistic observational study using two years electronic records of a cohort patients and three analyses: a cross sectional analysis of factors associated with total number of hours slept (as an objective proxy of sedation), and two prospective analyses of which factors were associated with changes in hours slept and the efficacy of two pharmacological strategies. 133 patients were included, of which 64.7% slept at least 9h daily. Among monotherapy patients (n=30), only norclozapine levels (r=.367, p=.03) correlated with hours slept.Using the prospective cohort (n=107), 42 patients decreased the number of hours slept, due to decreasing clozapine (40%) or augmenting with aripiprazole (36%). These two strategies were recommended to 22 (20.6%) and 23 (21.5%) subjects respectively but the majority (81.8% and 73.9%) did not reduce number of hours slept. Thus, pharmacological and non-pharmacological factors are involved in sedation.Norclozapine plasma levels correlated with total sleeping hours. Reducing clozapine and aripiprazole augmentation were associated to amelioration of sedation, although both strategies were effective only in a limited numbers of subjects.

Awake craniotomy: improving the patient's experience.

Awake craniotomy patients are exposed to various stressful stimuli while their attention and vigilance is important for the success of the surgery. We describe several recent findings on the perception of awake craniotomy patients and address nonpharmacological perioperative factors that enhance the experience of awake craniotomy patients. These factors could also be applicable to other surgical patients. Proper preoperative counseling gives higher patient satisfaction and should be individually tailored to the patient. Furthermore, there is a substantial proportion of patients who have significant pain or fear during an awake craniotomy procedure. There is a possibility that this could induce post-traumatic stress disorder or related symptoms. Preoperative preparation is of utmost importance in awake craniotomy patients, and a solid doctor-patient relationship is an important condition. Nonpharmacological intraoperative management should focus on reduction of fear and pain by adaptation of the environment and careful and well considered communication.

Pharmacological and non-pharmacological factors that regulate the acquisition of ketamine self-administration in rats

Recreational ketamine use may be modulated by factors such as ketamine infusion patterns, associated conditioned stimuli and spatial-temporal contexts. Our aim was to study the pharmacological and non-pharmacological factors that regulate the acquisition of ketamine use. In experiment 1, four groups of male rats were trained to self-administer ketamine during nine 1-h daily sessions, under four reinforcement schedules: i) pre-session ketamine priming (Priming-[KET]), ii) conditioned stimulus (CS) paired to the ketamine infusions ([KET + CS]), iii) neither priming nor CS ([KET]), iv) combination of both (Priming-[KET + CS]). In experiment 2, two groups of male rats were trained to self-administer ketamine during nine 1-h daily or weekly sessions, under the Priming-[KET + CS] schedule. Lever pressing was then extinguished by saline substitution for ketamine infusion. Afterwards, ketamine was made available again upon responding under the same schedule. The Priming-[KET + CS] schedule of reinforcement showed a significant increase in the number of ketamine reinforcements and a significant discrimination between active vs. inactive levers. The same schedule allowed the establishment of ketamine self-administration on a weekly basis. During the extinction phase, rate of responding significantly dropped in both weekly and daily groups although it was twofold longer in the former, which showed a lack of reacquisition. Both pre-session ketamine priming and a conditioned stimulus paired to the ketamine infusions are required for the acquisition of ketamine self-administration. The longer extinction and the lack of reacquisition in the weekly group could be due to changes in temporal context that might affect the conditioning process.