Non-pharmacological Factors Research Articles

Vitamin K in patients with familial hypercholesterolemia

Rationale: In patients with familial hypercholesterolemia (FH), different methods of health improvement are discussed – including non-pharmacological factors such as diet. Vitamin K could impact cardiovascular disease progress. Therefore, the aim of the study was to determine whether there is a deficiency of vitamin K in the serum in patients with familial hypercholesterolemia and to assess the vitamin K intake.

The impact of Mediterranean diet on coronary plaque vulnerability, microvascular function, inflammation and microbiome after an acute coronary syndrome: study protocol for the MEDIMACS randomized, controlled, mechanistic clinical trial

BackgroundPrimary prevention trials have demonstrated that the traditional Mediterranean diet is associated with a reduction in cardiovascular mortality and morbidity. However, this benefit has not been proven for secondary prevention after an acute coronary syndrome (ACS). We hypothesized that a high-intensity Mediterranean diet intervention after an ACS decreases the vulnerability of atherosclerotic plaques by complex interactions between anti-inflammatory effects, microbiota changes and modulation of gene expression.MethodsThe MEDIMACS project is an academically funded, prospective, randomized, controlled and mechanistic clinical trial designed to address the effects of an active randomized intervention with the Mediterranean diet on atherosclerotic plaque vulnerability, coronary endothelial dysfunction and other mechanistic endpoints. One hundred patients with ACS are randomized 1:1 to a monitored high-intensity Mediterranean diet intervention or to a standard-of-care arm. Adherence to diet is assessed in both arms using food frequency questionnaires and biomarkers of compliance. The primary endpoint is the change (from baseline to 12 months) in the thickness of the fibrous cap of a non-significant atherosclerotic plaque in a non-culprit vessel, as assessed by repeated optical coherence tomography intracoronary imaging. Indices of coronary vascular physiology and changes in gastrointestinal microbiota, immunological status and protein and metabolite profiles will be evaluated as secondary endpoints.DiscussionThe results of this trial will address the key effects of dietary habits on atherosclerotic risk and will provide initial data on the complex interplay of immunological, microbiome-, proteome- and metabolome-related mechanisms by which non-pharmacological factors may impact the progression of coronary atherosclerosis after an ACS.Trial registrationClinicalTrials.govNCT03842319. Registered on 13 May 2019

Quality of life in neuropathic pain: a literature review

Introduction: Neuropathic pain may develop after injury to the central nervous system, peripheral or both, when deleterious changes occur along the nociceptive modulatory pathways of the central nervous system. Proper management requires an interdisciplinary approach, as it can impact quality of life. Objectives: This review of the literature aims to assess the impact of pharmacological and non-pharmacological factors in the quality of life of patients with chronic neuropathic pain. Methodology: A systematized virtual search was carried out in PubMed®, collected articles between January 2010 and May 2020 using the terms “neuropathic pain”, “treatment”, “human” and “systematic review” using the filters of “systematic reviews ”E“ published in the last 10 years ”. All articles were formed by two independent reviewers and tabulated in a spreadsheet using Microsoft Excel® software. Results: Non-pharmacological interventions were addressed by most articles. Some articles addressed pharmacological interventions, with painful diabetic peripheral neuropathy being the main etiology. The most used quality of life measurement tools were: Medical Outcomes Study 36 (SF-36); EuroQol-5 Dimension (EQ-5D) and Beck Depression Inventory Score (BDI). Conclusion: The scarcity of high-quality studies that measure quality of life through validated tools is an obstacle to credible analysis of the impact of interventions on the life of chronic pain patients, however, in a preliminary way, cognitive behavioral therapy and the use of Spray THC/CBD oromucous has the potential to have a beneficial impact on quality of life.

Non-alcoholic fatty liver disease: Update on treatment options and translational implications of sleep disruption

Non-alcoholic fatty liver disease (NAFLD) is a condition that is associated with cirrhosis and hepatocellular carcinoma, and is increasing in prevalence worldwide. Sleep disruptions are commonly seen in NAFLD, and the disease process is associated with sleep disorders, including obstructive sleep apnea, circadian rhythm disorders, and insufficient sleep. The intermittent hypoxia seen in obstructive sleep apnea may contribute to fibrotic changes in the liver. A major component of this linkage may be related to gut microbiome changes. One notable change is increase in Bacteroidetes/Firmicutes ratio, and decrease in flora that ferment fiber into anti-inflammatory short-chain fatty acids. Several therapeutic options exist for NAFLD that target both sleep and NAFLD, including non-pharmacological factors, such as lifestyle modification (mainly diet and exercise). Pharmacological options include melatonin, Vitamin E, thiazolidinediones, and fecal microbiota transplantation. Core tip The pathogenesis of non-alcoholic fatty liver disease is closely tied to sleep and circadian rhythm abnormalities, through shared inflammatory pathways and altered metabolism. This review explores the pathogenesis of NAFLD in the context of sleep and circadian abnormalities. The associated inflammatory response is linked to changes in gut-microbiome interactions that contribute to the disease process. Understanding of this linkage has implications for various therapies for disease mitigation.

The Effect of Psychotropic Medications and Their Combinations on the QTc Interval Among Jordanian Outpatients: A Cross-Sectional Study.

To investigate the effect of psychotropic drugs and their combinations on the QTc interval as well as the prevalence of long QTc (LQTc) among ambulatory patients with psychiatric illness in Jordan. A cross-sectional study that included patients treated in an outpatient psychiatric clinic was conducted. The QTc duration was calculated using a combined QT correction (Bazett's formula for heart rate 60-100 and the Framingham formula for extremes of HR). Among 307 patients, about 60% received multiple psychotropic drugs. The LQTc frequency was 1.2%. QTc interval prolongation was observed in patients receiving selective serotonin reuptake inhibitors (SSRIs) (P = .011), tricyclic antidepressants (TCAs) (P = .033), citalopram (P = .044), or psychotropic polytherapy (P = .005). The addition of SSRIs to second-generation antipsychotics (SGAs) also lengthened the QTc interval (P = .029). There was a correlation between the number of psychotropic medications and the QTc length (P = .018). All patients with LQTc carried at least one risk factor for it other than the use of psychotropic medication(s), 3 of 4 patients had a combination therapy, all patients were prescribed SSRIs, and 2 of them had comorbid conditions. There is a high prevalence of psychotropic drugs polytherapy, and it is clearly associated with LQTc. Citalopram, SSRIs, and TCAs prolong QTc interval. It is recommended to assess non-pharmacological factors for LQTc and, if necessary, to obtain an electrocardiogram before starting patients on psychotropic drugs known to prolong the QTc interval.

Delirium – are we doing enough prevention and basic management in acute settings?

AimsTo identify the prevalence of delirium and/or dementia on complex medicine wards.To assess the use non-pharmacological prevention and management options in these patients.BackgroundDelirium, a common hospital syndrome, is often multi-factorial. So, the management needs not only treating a reversible cause but also minimising the factors that could increase the risk of developing delirium, or worsen its course.The Scottish-Intercollegiate-Guidelines-Network (SIGN) and National-Institute-for-Health-and-Care-Excellence (NICE) guidelines outline non-pharmacological factors to reduce the risk of developing delirium, and for its management once established.These factors include orientation, ensuring patients have their glasses and hearing aids, promoting sleep hygiene, maintaining optimal hydration and nutrition, early mobilisation, appropriate lighting and providing cognitively stimulating activities.MethodSIGN, NICE and local guidelines were used to develop a checklist of core non-pharmacological factors that minimise the risk of developing delirium and help in its management. Adherence to recommendations from these guidelines was thus evaluated in 4 Complex Medical Units of The John-Radcliffe Hospital (Oxford University Hospitals NHS Foundation Trust), cross sectionally. The data were collected by interviewing nursing staff on the wards, assessing the ward environment, reviewing nursing charts and electronic patient records.ResultThere were 57 patients aged >65 years across all four wards, with average percentages of delirium and dementia patients being 46% and 34%, respectively. Nurses were unsure about their patients having hearing or visual aids in 41% and 29%, respectively. On all four wards there was no clear signage, no digital clock, no calendar, and earplugs were not offered. Overall, the use of non-pharmacological recommendations was sub-optimal across a number of items. After a month, when the notes were reviewed, it was found that 18 out of those 57 patients had passed away (32%) and the average length of stay for delirium/dementia patients was way more than the other patients during that admission.ConclusionWe found high rates of delirium and dementia and a lack of consistent use of recommended non-pharmacological strategies for their management. Better adherence to these could help shorten length of stay and improve patient outcomes.Recommendations for patients with/at risk of delirium: –Bedside board for each patient with the name of the ward/hospital, picture of the named nurse.–Ensuring visible clock/calendar.–Non-pharmacological delirium management checklist to be added to the daily nursing notes.Emphasis on visual/hearing aids and daily reorientation. –Appropriate lighting in the bays.–Offer earplugs if not sleeping at night.

A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats

Ayahuasca is a plant concoction containing N,N-dimethyltryptamine (DMT) and certain β-carboline alkaloids from South America. Previous research in naturalistic settings has suggested that ingestion of ayahuasca can improve mental health and well-being; however, these studies were not placebo controlled and did not control for the possibility of expectation bias. This naturalistic observational study was designed to assess whether mental health changes were produced by ayahuasca or by set and setting. Assessments were made pre- and post-ayahuasca sessions in 30 experienced participants of ayahuasca retreats hosted in the Netherlands, Spain, and Germany. Participants consumed ayahuasca (N = 14) or placebo (N = 16). Analysis revealed a main effect of time on symptoms of depression, anxiety, and stress. Compared to baseline, symptoms reduced in both groups after the ceremony, independent of treatment. There was a main treatment × time interaction on implicit emotional empathy, indicating that ayahuasca increased emotional empathy to negative stimuli. The current findings suggest that improvements in mental health of participants of ayahuasca ceremonies can be driven by non-pharmacological factors that constitute a placebo response but also by pharmacological factors that are related to the use of ayahuasca. These findings stress the importance of placebo-controlled designs in psychedelic research and the need to further explore the contribution of non-pharmacological factors to the psychedelic experience.

Associations between fatigue impact and lifestyle factors in people with multiple sclerosis – The Danish MS hospitals rehabilitation study

Background: The lack of medical treatment options to reduce fatigue in patients with multiple sclerosis (MS) emphasize the importance of identifying potential non-pharmacological modifiable factors, as this may help advance current treatment strategies. The aim of this study was to identify potential modifiable lifestyle factors as well as patient- and disease-related characteristics, that are associated with fatigue in a large sample of clinically well-characterized patients with MS.Methods: This study was a secondary analysis of a pragmatic randomized controlled trial of inpatient multidisciplinary rehabilitation in Denmark. MS patients aged 18 to 65 years and with a disease severity score ≤ 7.5 according to the Expanded Disability Status Scale participated. Data on patient- and disease-related characteristics, fatigue impact (Modified Fatigue Impact Scale (MFIS)), and on lifestyle factors (tobacco smoking, alcohol intake, and physical activity), were collected at baseline.A linear mixed model was used to compare MFIS total, physical, cognitive, and psychosocial scores across subgroups of selected characteristics. Regression analyses were used to examine associations between lifestyle factors and MFIS total, physical, cognitive, and psychosocial scores.Results: In the sample of 417 MS patients, median age was 51 years, 69% were female, median time since diagnosis was 8 years, with 41% having relapsing remitting MS.Higher MFIS total scores were observed in MS patients with shorter time since diagnosis, being a tobacco smoker, and not undertaking regular physical activity. Somewhat similar findings were observed for MFIS subscores (physical, cognitive, psychosocial), especially MFIS physical scores.In the multivariate analyses, physical activity was significantly associated with fatigue impact on total, physical and psychosocial functioning. Tobacco smoking was significantly associated with fatigue impact on psychosocial functioning. Alcohol intake was not associated with fatigue impact. None of the lifestyle factors were associated with fatigue impact on cognitive functioning. In the adjusted models time since diagnosis was significantly associated with fatigue impact on total, physical and cognitive functioning, as was disease severity with fatigue impact on physical and cognitive functioning.Conclusion: Physical activity showed the most pronounced associations with fatigue impact on physical and psychosocial functioning, while the impact on cognitive functioning showed a trend. Tobacco smoking contributed significantly to impact on psychosocial functioning, while alcohol intake did not contribute to fatigue impact. Introducing or supporting maintenance of physical activity/exercise and cessation of tobacco smoking seems to be a useful approach for rehabilitation services to help patients with MS manage fatigue.

Dosing Psychedelics and MDMA.

Classic psychedelics, including psilocybin, lysergic acid diethylamide (LSD), dimethyltryptamine, and mescaline, and entactogens/empathogens, especially 3,4-methylenedioxymethamphetamine, have received renewed attention in psychiatric research and may be developed into medications for such indications as anxiety, depression, cluster headache, and posttraumatic stress disorder, among others. However, identifying proper doses is crucial. Controlled study data on dosing using well-characterized pharmaceutical formulations of the substances are scarce. The dose equivalence of different substances, dose-response effects, and subjective effects of different doses are of great interest and practically important for their clinical use in psychotherapy. Furthermore, the so-called microdosing of psychedelics has recently gained popularity, and the first placebo-controlled studies of LSD have been published. This chapter discusses different aspects of psychedelic dosing, including pharmaceutical aspects, definitions and characteristics of different doses, including microdoses, aspects of personalized dosing, and non-pharmacological factors, that can influence the response to psychedelics.

Longitudinal Modeling of Non-Pharmacological Factors Related to Frequency, Severity and Duration in Both Migraine and Tension-Type Headaches

Background: Frequency, severity, and duration of attacks are some major parameters in headache management, affected by some other factors. Ignoring these factors in headache-related studies can lead to incorrect results. We aimed to model both socio-demographic characteristics and headache-associated symptoms related to frequency, severity and duration of headache attacks. Study design: A longitudinal panel study. Methods: Overall, 275 migraines or tension Type Headache (TTH) patients were visited at three different times in 2012 in Isfahan, Iran. On the first visit socio-demographic characteristics and headache symptoms of the patients were asked. In all of the visits, headache frequency, severity and attack duration were recorded. Results: Frequency of headaches was influenced by headache type, age, job status, working hours, residency, disease duration, laterality, and type of pain onset. In terms of intensity, headaches were more severe in patients with migraine-type; those suffering from longer headache history; and those who suffered from vomiting, photophobia, and phonophobia. On the other hand patients with migraine, married people, women and patients suffering from vomiting experienced longer headache attacks. Conclusion: Headache type (migraine/TTH), age, job status, residency, years of headache, laterality, type of onset, nausea, vomiting, photophobia, and phonophobia were the factors to be considered in the studies that would apply frequency, severity, and duration of headache attacks in order to evaluate headache management.

Influenza A (H1N1)pdm09 outbreak of unknown source in a Ghanaian senior high school

BackgroundInfluenza is an acute viral respiratory tract infection caused by influenza virus and transmitted from person to person. Though usually seasonal in temperate climates, influenza occurs throughout the year in the tropics with outbreaks occurring at irregular intervals. On February 6, 2018, a number of students from a Senior High School (SHS) in Accra reported to a district hospital with cough, fever and other respiratory symptoms. An influenza-like illness (ILI) outbreak was suspected. We investigated to determine the magnitude and source of the outbreak and implement control and preventive measures.MethodsWe interviewed health workers, staff and students of the school as well as case-patients and reviewed health records to collect data on demographic characteristics, signs and symptoms, date of illness onset and outcome. We defined ILI case as “any person in the SHS with fever (measured axillary temperature of ≥ 37.5 °C or history of fever) and cough with or without sore throat or runny nose from January 21 to February 26, 2018”. We conducted active case search to identify more cases and took oropharyngeal samples for laboratory testing. We performed descriptive and inferential analysis by calculating attack rate ratios (ARR) and their exact 95% confidence intervals (CI).ResultsOf the 3160 students, 104 case-patients were recorded from January 25, 2018 to February 13, 2018 (overall attack rate of 3.3%). Mean age of case-patients was 16.1 (±2.3) years with males constituting 71.2% (74/104). Sex specific attack rates were 5.6% (74/1331) and 1.6% (30/1829) for males and females respectively. Compared to females, males were 3.4 times as likely to be ill [ARR =3.4, 95%CI = (2.23–5.15)]. Nine oropharyngeal samples from 17 suspected case-patients tested positive for influenza A (H1N1)pdm09.ConclusionOutbreak of influenza A (H1N1)pdm09 occurred in a SHS in Accra from January to February, 2018. Even though source of the outbreak could not be determined, prompt case management and health education on hand and personal hygiene as non-pharmacological factors probably contributed to the outbreak control. The outbreak ended with a scheduled mid-term break. This underscores the need for more evidence on the effect of school closure in influenza outbreak control.

Patient Experience Contributing to Outcomes of Laryngeal Botulinum Toxin Injection

Laryngeal Botulinum Toxin injection (LBTX) in the adductor musculature is the current therapy for Adductor Spasmodic Dysphonia. This study explores nonbiological factors that can affect the patient experience during this procedure and their association with better or worse self-reported effectiveness. A 14 item survey was used to evaluate the patient experience in patients who had undergone LBTX in Mayo Clinic Jacksonville, Florida, during 2019. Information from the survey, previous medical history, and demographic data were collected, and a descriptive analysis was performed. Of the 36 patients who participated, the mean age was 65 years and a female predominance was found (66%). The average age at onset of symptoms was 57 years, and voice tremor was associated with 36.1% of patients. Preprocedure education was recognized as a factor affecting outcomes in 87% of patients; 11 patients reported that body position used during the injection could affect the results. Pain or stress experienced at the time of procedure was referred in one-third of patients as an influencing factor too. This study has shown that nonpharmacological factors such as education before the procedure, body position, pain, and stress sensation before LBTX may have a role in the botulinum toxin effect on Adductor Spasmodic Dysphonia patients. This study is the first to describe these variables qualitatively, and further studies may help to improve the patient experience and outcome of LBTX around the world.

Factors related to the adverse events of antiepileptic drugs

ObjectiveThe aim of the present study was to explore the factors related to the severity of the adverse effects of antiepileptic drugs (AEDs), experienced by patients with epilepsy. Materials and methodsA case study was conducted in adult patients with epilepsy and followed up at the Epilepsy Outpatients of the University Hospital of Ioannina in Northwest Greece.The Adverse Event Profile (AEP) questionnaire for AEDs adverse effects assessment, the Defense style questionnaire (DSQ-88) and the Patient Health Questionnaire (PHQ-9) for depression’ severity evaluation were used to estimate the severity of adverse effects, the defense style, and the depressive symptoms, respectively. ResultsSixty-three patients with epilepsy (M/F:28/35), with a mean age of 37.6 ± 13.41, were recruited in the study.The univariate analysis showed that both the Maladaptive style of defense and the PHQ-9 score were significantly associated with the AEP score.After multivariate regression analysis female gender, the load of AEDs, the PHQ-9 score, and the Adaptive defense style remained significant coefficients. ConclusionThere are also nonpharmacological factors that may contribute to the severity of the adverse effects of AEDs, experienced by the patients with epilepsy.

Non Pharmacological Factors in Containment of COVID-19 Virus in India: An Insight

The disease COVID-19 is caused by a novel Coronavirus SARS-CoV-2 from Wuhan, China The disease has become pandemic, spreading in more than 213 countries The first report on COVID-19 in India was recorded on 30th January, 2020 Other countries, i e , Russia, Spain, Brazil, UK, Italy, Turkey and Iran also recorded their first cases either on the same day or later India being the most populated country with 17 7% of the total population of the world, the number of cases recorded in India was 106,886 as of 20th May, 2020 However, in other countries, infection exceeded the number than India with their meager population Researchers throughout the world developed an interest to know the reasons in the containment of the disease in India The aim of this study is to provide an insight on the role of non-pharmacological factors in the containment of COVID-19 in India The perspectives on the role of the factors like air handling systems, mode of transport, nutritional facts and traditional medicine which are unique to India are highlighted The role of insects like cockroaches and housefly in spreading the virus and other body fluids of an infected person is also highlighted It concludes the importance of conducting the studies on the airborne spread of the virus, role of insects and body fluids of the infected subjects in spreading the disease It is recommended to conduct joint studies representing different geographical zones at the International level Bringing policies in the containment of SARS-CoV-2 virus as well as for other microbes in all countries is recommended

Characterization and prediction of acute and sustained response to psychedelic psilocybin in a mindfulness group retreat

Meditation and psychedelics have played key roles in humankind’s search for self-transcendence and personal change. However, neither their possible synergistic effects, nor related state and trait predictors have been experimentally studied. To elucidate these issues, we administered double-blind the model psychedelic drug psilocybin (315 μg/kg PO) or placebo to meditators (n = 39) during a 5-day mindfulness group retreat. Psilocybin increased meditation depth and incidence of positively experienced self-dissolution along the perception-hallucination continuum, without concomitant anxiety. Openness, optimism, and emotional reappraisal were predictors of the acute response. Compared with placebo, psilocybin enhanced post-intervention mindfulness and produced larger positive changes in psychosocial functioning at a 4-month follow-up, which were corroborated by external ratings, and associated with magnitude of acute self-dissolution experience. Meditation seems to enhance psilocybin’s positive effects while counteracting possible dysphoric responses. These findings highlight the interactions between non-pharmacological and pharmacological factors, and the role of emotion/attention regulation in shaping the experiential quality of psychedelic states, as well as the experience of selflessness as a modulator of behavior and attitudes. A better comprehension of mechanisms underlying most beneficial psychedelic experiences may guide therapeutic interventions across numerous mental conditions in the form of psychedelic-assisted applications.

The impacts of actual and perceived nicotine administration on insula functional connectivity with the anterior cingulate cortex and nucleus accumbens

Background:Changes in resting state functional connectivity between the insula and dorsal anterior cingulate cortex as well as between the insula and nucleus accumbens have been linked to nicotine withdrawal and/or administration. However, because many of nicotine’s effects in humans appear to depend, at least in part, on the belief that nicotine has been administered, the relative contribution of nicotine’s pharmacological actions to such effects requires clarification.Aims:The purpose of this study was to examine the impacts of perceived and actual nicotine administration on neural responses.Methods:Twenty-six smokers were randomly assigned to receive either a nicotine inhaler (4 mg deliverable) or a nicotine-free inhaler across two sessions. Inhaler content instructions (told nicotine vs told nicotine-free) differed across sessions. Resting state functional connectivity between sub-regions of the insula and the dorsal anterior cingulate cortex and nucleus accumbens was measured using magnetic resonance imaging before and after inhaler administration.Results:Both actual and perceived nicotine administration independently altered resting state functional connectivity between the anterior insula and the dorsal anterior cingulate cortex, with actual administration being associated with decreased resting state functional connectivity, and perceived administration with increased resting state functional connectivity. Actual nicotine administration also contralaterally reduced resting state functional connectivity between the anterior insula and nucleus accumbens, while reductions in resting state functional connectivity between the mid-insula and right nucleus accumbens were observed when nicotine was administered unexpectedly. Changes in resting state functional connectivity associated with actual or perceived nicotine administration were unrelated to changes in subjective withdrawal and craving. Changes in withdrawal and craving were however independently associated with resting state functional connectivity between the nucleus accumbens and insula.Conclusions:Our findings highlight the importance of considering non-pharmacological factors when examining drug mechanisms of action.

Race as a component of set and setting: How experiences of race can influence psychedelic experiences

Background and aims Set and setting function both as a concept that guides research and practice with psychedelic drugs and as a meme aimed at reducing harm among psychedelic users. Referring to non-pharmacological factors that shape drug experiences, the concept of set and setting was popularized in the West during the mid-20th century. However, little theoretical development has occurred regarding what falls under the umbrella of set and setting since its conception. Methods By bridging set and setting theory with research from the fields of social psychology and sociology of medicine, this review calls attention to how race can contribute the set and setting for a psychedelic experience. Results I argue that psychosocial factors influencing racial differences in mental health also constitute meaningful differences in set. Furthermore, I suggest that the character of race relations in the United States provides a distinct cultural setting for racialized psychedelic users, both in therapeutic and naturalistic contexts. In turn, racial identification may contribute to the variation in framing and interpretation of psychedelic experiences. Conclusion These considerations have important implications beyond understanding non-pharmacological influences on psychedelic experiences, including developing protocols for clinical applications of psychedelics, educating future practitioners, and meeting the needs of diverse patient populations.

Non-pharmacological Considerations in Human Research of Nicotine and Tobacco Effects: A Review.

Growing research demonstrates that non-pharmacological factors systematically alter responses to acute nicotine, tobacco, and placebo administration. Indeed, varying beliefs about nicotine and/or tobacco administration and effects, differing perceptions about nicotine and/or tobacco use opportunities, and inconsistent motivation to quit smoking have been found to exert important influences on subjective, physiological, and behavioral responses. These variables are infrequently measured or manipulated in nicotine and tobacco research, which compromises the validity of study findings. Incorporating methodological strategies to better account for these non-pharmacological factors has the potential to improve the quality of addiction research and treatment.

Nicotine or expectancies? Using the balanced-placebo design to test immediate outcomes of vaping

IntroductionElectronic (e-)cigarette use has increased in popularity, especially among those attempting to quit smoking. Previous studies evaluating the therapeutic efficacy of e-cigarettes have suggested that non-pharmacologic factors, such as expectancies about nicotine effects, may influence the experienced effects of e-cigarettes. MethodThe independent and synergistic influences of drug and expectancies were parsed using a balanced-placebo design, whereby 128 participants (52 dual users) were provided an e-cigarette that either contained nicotine or non-nicotine solution, while told that it did or did not contain nicotine. We hypothesized main effects of nicotine content on physiological, objective outcomes (attention, appetite, aversion, respiratory tract sensations), and main effects of the instructions on more subjective, psychosocial outcomes (affect, reward, satisfaction). Sex was included as a moderator. ResultsResults showed that nicotine increased sustained attention, and more so among females. Nicotine delivery was associated with aversion among females, but not males. Among those who were both told and did not receive nicotine, higher enjoyment of respiratory tract sensations was reported. Nicotine with complementary instructions produced the highest reward ratings; additionally, nicotine was rewarding to males but not females. DiscussionFindings demonstrated that both nicotine content and non-pharmacologic factors impact acute outcome effects of e-cigarettes, with moderation by sex in some cases. Results are relevant to the interpretation of clinical trials of e-cigarettes and suggest a more nuanced view of reinforcement pathways.

КЛИНИЧЕСКИЕ ПРЕДИКТОРЫ НЕЭФФЕКТИВНОСТИ СТАРТОВОЙ МОНОТЕРАПИИ ЭПИЛЕПСИИ У ДЕТЕЙ

Actuality. Effectiveness of epilepsy treatment in children is determined by the possibility of achieving clinical remission at initial monotherapy. The spectrum of anticonvulsants recommended for initial treatment of epilepsy in children is relatively known, but the analysis of their prescription indicates the influence of other non-pharmacologic factors on the possibility of achieving adequate control over epileptic seizures. Objective of the study: to find the frequency of achieving clinical remission in children with epilepsy while taking initial anticonvulsant and to define a combination of independent clinical factors which determine ineffectiveness of initial anticonvulsant monotherapy. Material and methods. Using the method of target selection there was performed a cohort retrospective-prospective comparative study of 447 children with epilepsy aged from birth to 17 years old. The frequency of clinical remission at initial anticonvulsant therapy was analyzed; a comparative study of clinical parameters was made within the frames of mono-factor analysis in order to find significant differences with consideration of age of epilepsy onset and effectiveness of initial treatment. Results. The study found the influence of a child’s age at epilepsy debut on achieving clinical remission at initial monotherapy: the younger the child, the lower is the possibility of its acheving, pllat<0.001. The highest frequency of absence of remission was noted in children under 1 year (72.5%) and those aged 1-3 years (71.4%) in comparison to children of older age groups (33.0%-59.5%), pFisher<0.001.The factors which define the prognosis of initial treatment of epilepsy in children were determined: in case of chronic somatic comorbidity ineffectiveness of therapy was noted in 69.8% of cases (pFisher<0.001) and chances of remission absence raised by 2.5 times (ОR=2.480; S=0.201; 95% CI [1.672; 3.681]; in case of psychic comorbidity therapy was ineffective in 87.6% of cases (pFisher<0.001) with a 7-fold increase of chances of remission absence (ОR=7.06; S=0.283; 95% CI [4.054; 12.291]; in case of neurologic comorbidity monotherapy was ineffective in 76.3% of cases (pFisher<0.001) and chances of remission absence increased by 3.9 times (ОR=3.925; S=0.206; 95% CI [2.62; 5.88]. For the first time the combination of independent factors in patients with epilepsy was stated – age at disease onset less than 6 years, presence of neurologic disorders, focal or combined types of epilepsy, presence of chronic somatic comorbidity. The set of these factors validly defines prognosis of effectiveness of initial anticonvulsant therapy with precision of 78.5% (AUC = 0.785; 95% CI [0.742; 0.828]) (p<0.001) by the results of ROC-analysis and with precision of 72.5% by the results of logistic regression (0.725 with 95% CI [0.680; 0.765]), which proves the tactics of fast correction of anticonvulsant dosage, its change and using rational polytherapy at initial stage of epilepsy treatment in children. Conclusions. New data regarding prognosis of effectiveness of initial anticonvulsant momotherapy in children were received; they allow defining the possibility of achieving clinical remission at prescribing the first anticonvulsant with a probability of more than 70%.