Factors influencing clinical trial participation of women with fibromyalgia across the United States: a cross-sectional survey.

Although fibromyalgia is a widespread chronic pain condition where 90 percent of patients are women, they are underrepresented in Randomized Clinical Trials (RCTs). We aim to describe the willingness to participate, assess different factors, and explore the impact of sociodemographic and clinical characteristics on perceived barriers to trial participation. This is a cross-sectional survey targeting women with fibromyalgia. Univariate and multivariate logistic regression were performed. Of the 436 women with fibromyalgia, 56 percent were very likely to participate in RCTs. Minorities expressed less interest than non-minorities, while higher pain scores, previous participation, and younger patients reported a higher interest. Barriers significantly associated with a reduced willingness were: the participant's perception (side effects, distance, potential negative impact), the center (reputation), the trial protocol (number of visits, placebo), and trial awareness by their physician. In a multivariate analysis, older age, low education, lower income, and higher pain scores were associated with perceived barriers to RCT participation. Despite the high interest to participate, factors such as side effects, the center's distance, number of visits, placebo treatments, and the institution's reputation must be considered in clinical trials for women with fibromyalgia.

Enhanced peri-operative care to improve outcomes for high-risk surgical patients in Brazil: a single-centre before-and-after cohort study.

Mortality and morbidity for high-risk surgical patients are often high, especially in low-resource settings. Enhanced peri-operative care has the potential to reduce preventable deaths but must be designed to meet local needs. This before-and-after cohort study aimed to assess the effectiveness of a postoperative 48-hour enhanced care pathway for high-risk surgical patients ('high-risk surgical bundle') who did not meet the criteria for elective admission to intensive care. The pathway comprised of six elements: risk identification and communication; adoption of a high-risk post-anaesthesia care unit discharge checklist; prompt nursing admission to ward; intensification of vital signs monitoring; troponin measurement; and prompt access to medical support if required. The primary outcome was in-hospital mortality. Data describing 1189 patients from two groups, before and after implementation of the pathway, were compared. The usual care group comprised a retrospective cohort of high-risk surgical patients between September 2015 and December 2016. The intervention group prospectively included high-risk surgical patients from February 2019 to March 2020. Unadjusted mortality rate was 10.5% (78/746) for the usual care and 6.3% (28/443) for the intervention group. After adjustment, the intervention effect remained significant (RR 0.46 (95%CI 0.30-0.72). The high-risk surgical bundle group received more rapid response team calls (24% vs. 12.6%; RR 0.63 [95%CI 0.49-0.80]) and surgical re-interventions (18.9 vs. 7.5%; RR 0.41 [95%CI 0.30-0.59]). These data suggest that a clinical pathway based on enhanced surveillance for high-risk surgical patients in a resource-constrained setting could reduce in-hospital mortality.

Transcranial direct current stimulation (tDCS) prevents chronic stress-induced hyperalgesia in rats.

BACKGROUND: Chronic stress (CS) is associated with a decrease in pain threshold caused by the changes in neural pain circuits. It can be associated to glucocorticoid imbalance with alterations in neural circuitry. Inhibition of stress-induced pain-related neural changes by using techniques that safely induce neuroplasticity such as transcranial direct current stimulation (tDCS) may prevent hyperalgesia triggered by CS. OBJECTIVE: This study aimed to verify the effect of tDCS performed prior to CS exposure on nociceptive response. METHODS: Thirty-two rats were distributed in the following groups: control; stress; sham-tDCS + stress; and tDCS + stress. Bicephalic active tDCS was performed for 8 consecutive days before the CS exposure. The pain threshold was evaluated using a hot plate and tail flick latency (TFL) tests. RESULTS: The tDCS exposure increased the pain threshold on stressed rats. CONCLUSION: The data obtained indicate that the treatment with bicephalic active tDCS before chronic stress exposure prevents stress-induced hyperalgesia.

Development, psychometric evaluation and validation of a brief measure of emotional preoperative stress (B-MEPS) to predict moderate to intense postoperative acute pain.

BACKGROUND: Preoperative stress might influence postoperative pain, thereby, it is desirable to assess it more precisely. Thus, we developed and evaluated the psychometric properties of a brief measure of emotional preoperative stress (B-MEPS) index using Item Response Category Characteristic Curves. We validated and assessed whether the B-MEPS can predict moderate to intense acute postoperative pain (MIAPP). METHODS: We included 863 adult patients who underwent elective surgeries (ASA I-III physical status). The B-MEPS was constructed based on items selected from instruments to assess anxiety, depression, future self-perception and minor psychiatric disorders. We identified 24 items with greatest discriminant power to identify patients who should undergo surgery to treat cancer with MIAPP. The reliability was maximized using the Cronbach's alpha indices. Fifteen items remained, which were adjusted by the Generalized Partial Credit Model. The convergent validity was assessed correlating the B-MEPS index with the pain catastrophizing (n = 100). Finally, the B-MEPS was applied in a prospective cohort of patients who underwent an abdominal hysterectomy (n = 150). RESULTS: The Cronbach's alpha for selected items was 0.83. The correlation coefficient between B-MEPS index and catastrophizing was r = 0.37 (P < 0.01). A hierarchical regression model evidenced that the B-MEPS index was a factor independent to predict MIAPP after an abdominal hysterectomy [odds ratio (OR)=1.20, confidence interval (CI) 95% 1.05-1.43). CONCLUSIONS: The B-MEPS index presents satisfactory psychometric evaluations based on its internal consistency, convergent, and discriminant validity. The B-MEPS is a propensity index to MIAPP, which might help the clinician to decide on the best therapeutic approaches for acute postoperative pain.

Repeated transcranial direct current stimulation reduces food craving in Wistar rats.

It has been suggested that food craving-an intense desire to consume a specific food (particularly foods high in sugar and fat)-can lead to obesity. This behavior has also been associated with abuse of other substances, such as drugs. Both drugs and food cause dependence by acting on brain circuitry involved in reward, motivation, and decision-making processes. The dorsolateral prefrontal cortex (DLPFC) can be activated following evocation and is implicated in alterations in food behavior and craving. Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique capable of modulates brain activity significantly, has emerged as a promising treatment to inhibit craving. This technique is considered safe and inexpensive; however, there is scant research using animal models. Such studies could help elucidate the behavioral and molecular mechanisms of eating disorders, including food craving. The aim of our study was to evaluate palatable food consumption in rats receiving tDCS treatment (anode right/cathode left). Eighteen adult male Wistar rats were randomized by weight and divided into three groups (n = 6/group): control, with no stimulation; sham, receiving daily 30 s tDCS (500 µA) sessions for 8 consecutive days; and tDCS, receiving daily 20 min tDCS (500 µA) sessions for 8 consecutive days. All rats were evaluated for locomotor activity and anxiety-like behavior. A palatable food consumption test was performed at baseline and on treatment completion (24 h after the last tDCS session) under fasting and feeding conditions and showed that tDCS decreased food craving, thus corroborating human studies. This result confirms the important role of the prefrontal cortex in food behavior, which can be modulated by noninvasive brain stimulation.

Chronic stress associated with hypercaloric diet changes the hippocampal BDNF levels in male Wistar rats.

Chronic stress, whether associated with obesity or not, leads to different neuroendocrine and psychological changes. Obesity or being overweight has become one of the most serious worldwide public health problems. Additionally, it is related to a substantial increase in daily energy intake, which results in substituting nutritionally adequate meals for snacks. This metabolic disorder can lead to morbidity, mortality, and reduced quality of life. On the other hand, brain-derived neurotrophic factor (BDNF) is widely expressed in all brain regions, particularly in the hypothalamus, where it has important effects on neuroprotection, synaptic plasticity, mammalian food intake-behavior, and energy metabolism. BDNF is involved in many activities modulated by the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, this study aims to evaluate the effect of obesity associated with chronic stress on the BDNF central levels of rats. Obesity was controlled by analyzing the animals' caloric intake and changes in body weight. As a stress parameter, we analyzed the relative adrenal gland weight. We found that exposure to chronic restraint stress during 12 weeks increases the adrenal gland weight, decreases the BDNF levels in the hippocampus and is associated with a decrease in the calorie and sucrose intake, characterizing anhedonia. These effects can be related stress, a phenomenon that induces depression-like behavior. On the other hand, the rats that received the hypercaloric diet had an increase in calorie intake and became obese, which was associated with a decrease in hypothalamus BDNF levels.

Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel.

The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. We therefore convened a group of research and clinician experts on tDCS to review the research and clinical use of tDCS. In this report, we review the regulatory status of tDCS, and we summarize the results according to research, off-label and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan and United States. Research use, off label treatment and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials.

Pain-autonomic interaction after work-induced sleep restriction.

BACKGROUND AND PURPOSE: Poor sleep is commonly associated with alterations in pain perception. However, there is a lack of studies that address work-associated sleep restriction (SR) and changes in non-nociceptive perception and autonomic responses after work-induced SR. METHODS: This study was performed with 19 medical students after a normal-sleep night (NS phase) and after a night shift at the local emergency room (SR phase). We performed clinical assessment, quantitative sensory testing for electrical and temperature sensation, RR interval analysis, and recorded sudomotor skin responses (SSRs). RESULTS: The total mean duration of sleep was 436 ± 18 min in the NS group and 120 ± 28 min in the SR group (P<0.001). The anxiety scores were higher following the SR phase compared with those after the NS phase (P<0.01). After SR, there was a decrease in heat-pain threshold, but neither warm nor electrical thresholds were affected. Following SR, subjects showed higher SSR amplitudes and an increased number of double responses at an interstimulus interval of 2 s. We also observed a moderate inverse correlation between heat-pain thresholds and SSR amplitude (r= -0.46; P<0.01). However, there was no correlation between anxiety scores and SSR parameters. CONCLUSIONS: The effects of SR in the context of work stress on pain are specific and appear unrelated to general changes in sensory perception. Hyperalgesia was associated with abnormal autonomic responses, but not with increased anxiety, which suggests an association between the nociceptive and autonomic nervous systems that is independent of the emotional state.

Neonatal morphine administration leads to changes in hippocampal BDNF levels and antioxidant enzyme activity in the adult life of rats.

It is know that repeated exposure to opiates impairs spatial learning and memory and that the hippocampus has important neuromodulatory effects after drug exposure and withdrawal symptoms. Thus, the aim of this investigation was to assess hippocampal levels of BDNF, oxidative stress markers associated with cell viability, and TNF-α in the short, medium and long term after repeated morphine treatment in early life. Newborn male Wistar rats received subcutaneous injections of morphine (morphine group) or saline (control group), 5 µg in the mid-scapular area, starting on postnatal day 8 (P8), once daily for 7 days, and neurochemical parameters were assessed in the hippocampus on postnatal days 16 (P16), 30 (P30), and 60 (P60). For the first time, we observed that morphine treatment in early life modulates BDNF levels in the medium and long term and also modulates superoxide dismutase activity in the long term. In addition, it was observed effect of treatment and age in TNF-α levels, and no effects in lactate dehydrogenase levels, or cell viability. These findings show that repeated morphine treatment in the neonatal period can lead to long-lasting neurochemical changes in the hippocampus of male rats, and indicate the importance of cellular and intracellular adaptations in the hippocampus after early-life opioid exposure to tolerance, withdrawal and addiction.

Cafeteria diet-induced obesity plus chronic stress alter serum leptin levels.

Obesity is a disease that has become a serious public health issue worldwide, and chronic stressors, which are a problem for modern society, cause neuroendocrine changes with alterations in food intake. Obesity and chronic stress are associated with the development of cardiovascular diseases and metabolic disorders. In this study, a rat model was used to evaluate the effects of a hypercaloric diet plus chronic restraint stress on the serum leptin and lipids levels and on the weight of specific adipose tissue (mesenteric, MAT; subcutaneous, SAT and visceral, VAT). Wistar rats were divided into the following 4 groups: standard chow (C), hypercaloric diet (HD), stress plus standard chow (S), and stress plus hypercaloric diet (SHD). The animals in the stress groups were subjected to chronic stress (placed inside a 25 cm × 7 cm plastic tube for 1h per day, 5 days per week for 6 weeks). The following parameters were evaluated: the weight of the liver, adrenal glands and specific adipose tissue; the delta weight; the Lee index; and the serum levels of leptin, corticosterone, glucose, total cholesterol, and triglycerides. The hypercaloric diet induced obesity in rats, increasing the Lee index, weight, leptin, triglycerides, and cholesterol levels. The stress decreased weight gain even in animals fed a hypercaloric diet but did not prevent a significant increase in the Lee index. However, an interaction between the independent factors (hypercaloric diet and stress) was observed, which is demonstrated by the increased serum leptin levels in the animals exposed to both protocols.

Obesity and shift work: chronobiological aspects.

The present review has the objective of summarising chronobiological aspects of shift work and obesity. There was a systematic search in PubMed databases, using the following descriptors: shift work; obesity; biological clock. Shift work is extremely frequent in several services and industries, in order to systematise the needs for flexibility of the workforce, necessary to optimise productivity and business competitiveness. In developing countries, this population represents a considerable contingent workforce. Recently, studies showed that overweight and obesity are more prevalent in shift workers than day workers. In addition, the literature shows that shift workers seem to gain weight more often than those workers submitted to a usual work day. In conclusion, there is considerable epidemiological evidence that shift work is associated with increased risk for obesity, diabetes and CVD, perhaps as a result of physiological maladaptation to chronically sleeping and eating at abnormal circadian times. The impact of shift work on metabolism supports a possible pathway to the development of obesity and its co-morbities. The present review demonstrated the adverse cardiometabolic implications of circadian misalignment, as occurs chronically with shift workers.

Preoperative predictors of moderate to intense acute postoperative pain in patients undergoing abdominal surgery.

BACKGROUND: Pain is a sensory and emotional experience that is influenced by physiologic, sensory, affective, cognitive, socio-cultural, and behavioral factors. Consistent with the perspective to improve the postoperative pain control, the present study has the purpose of assessing the effect of presurgical clinical factors, psychological and demographic characteristics as predictors for reporting moderate to intense acute postoperative pain. METHODS: A prospective cohort study was performed with 346 inpatients undergoing abdominal elective surgery (ASA physical status I-III, age range 18-60 years). The measuring instruments were Pain Visual Analog Scale, the State-Trait Anxiety Inventory, and the Montgomery-Asberg Depression Rating Scale. Multivariate conditional regression modeling was used to determine independent predictors for moderate to intense acute postoperative pain. RESULTS: Moderate to intense acute postoperative pain was associated with status ASA III (odds ratio (OR) = 1.99), age (OR = 4.72), preoperative moderate to intense pain (OR = 2.96), chronic pain (OR = 1.75), high trait-anxiety and depressive mood moderate to intense (OR = 1.74 and OR = 2.00, respectively). Patients undergoing surgery to treat cancer presented lower risk for reporting moderate to intense pain OR = 0.39, as well as those that received the epidural analgesia and multimodal analgesia with systemic opioid (OR = 0.09 and OR = 0.16, respectively). CONCLUSIONS: The identification of predictive factors for intense acute postoperative pain may be useful for designing specific preventive interventions to relieve patient suffering. Especially because few of these variables are accessible for medical intervention, which would improve the clinical outcomes and quality of life of patients at risk of moderate to intense acute postoperative pain.

Effect of pre-operative anxiolysis on postoperative pain response in patients undergoing total abdominal hysterectomy.

In a double blind, placebo-controlled trial, we have assessed the effects of pre-operative anxiolysis on postoperative pain scores in 112 ASA I-II women, aged 18-65 years, scheduled to undergo total abdominal hysterectomy. Subjects were randomly allocated to receive either oral diazepam 10 mg (n=56) or placebo (n=56) pre-operatively. Postoperative anxiety, pain scores, analgesic consumption, and sedation were evaluated at several time points during the first 24 h following surgery. Postoperative pain scores were found to be significantly higher in the diazepam group. Trait and state anxiety showed a significant effect on pain scores, independent of the treatment group. No difference was found between the groups in morphine consumption, but there was a significant reduction in morphine consumption with time.

Sleep disturbances associated with minor psychiatric disorders in medical students.

We performed a cross-sectional study with 342 medical students (age range, 18-35 years) to identify, among a group of sleep disturbances, those which are related to minor psychiatric disorders in this population. The instruments employed for data collection were the self-reporting questionnaire (SRQ-20), the morningness/eveningness questionnaire, the Epworth sleepiness scale, and a general questionnaire regarding demographic characteristics, use of drugs, history of psychopathology, usual fall-asleep time, usual wake-up time, amount of sleep, arousal during the night, and insomnia. We used a logistic regression model to determine independent factors associated with minor psychiatry disorders. Daytime sleepiness [odds ratio (OR), 2.12; 95% CI, 1.21-3.71], arousal [OR, 4.54; 95% CI, 1.97-10.47], insomnia [OR 2.45; 95% CI, 1.32-4.56], and sleeping less than 7 hours per night [OR, 2.02; 95% CI, 1.11-3.67] were associated with minor psychiatric disorders. This group of variables determined a cumulative risk ratio of 5.47 [95% CI, 2.87-10.41] for the main outcome.

Risk factors for postoperative anxiety in adults.

We identified risk factors for postoperative anxiety and quantified their effect on 712 adults between 18 and 60 years of age (ASA I-III physical status) undergoing elective surgery under general anaesthesia, neural blockade or both. The measuring instruments were a structured questionnaire, a pain visual analogue scale, the McGill Pain Questionnaire, the State-Trait Anxiety Inventory, the Montgomery-Asberg Depression Rating Scale, a Self-Reporting Questionnaire-20, and a Self-Perception of Future Questionnaire. Multivariate conditional regression modelling taking into account the hierarchical relationship between risk factors revealed that postoperative anxiety was associated with ASA status III (OR = 1.48), history of smoking (1.62), moderate to intense postoperative pain (OR = 2.62) and high pain rating index (OR = 2.35), minor psychiatric disorders (OR = 1.87), pre-operative state-anxiety (OR = 2.65), and negative future perception (OR = 2.20). Neural block anaesthesia (OR = 0.72), systemic multimodal analgesia (OR = 0.62) and neuroaxial opioids with or without local anaesthesia (OR = 0.63) were found to be protective factors against postoperative anxiety.

Risk factors for preoperative anxiety in adults.

BACKGROUND: Patients who undergo surgery experience acute psychological distress in the preoperative period. The objective of this study was to identify and quantify the effect of risk factors for preoperative anxiety in adults. METHODS: A cross-sectional study was performed with 592 inpatients scheduled for elective surgery. Age ranged from 18 to 60 years (ASA physical status I-III). Demographic information was collected using a structured questionnaire. The measuring instruments were a visual analog scale, the State-Trait Anxiety Inventory; the Montgomery-Asberg Depression Rating Scale, the WHO Self-Reporting Questionnaire-20, and the future self-perception questionnaire. Multivariate conditional regression modeling was used to control confounding factors and to determine independent predictors of preoperative anxiety, taking into account the hierarchical relationship between risk factors. RESULTS: High preoperative anxiety was associated with history of cancer (odds ratio (OR)=2.26) and smoking (OR=7.47), psychiatric disorders (OR=5.93), negative future perception (OR= 2.30), moderate to intense depressive symptoms (3.22), high trait-anxiety (3.83), moderate to intense pain (2.12), medium surgery (OR=1.52), female gender (OR=2.0), ASA category III (OR=3.41), up to 12 years of education (OR=1.36), and more than 12 years of education (OR=1.68). Previous surgery (OR= 0.61) was associated with lower risk for preoperative state-anxiety. CONCLUSIONS: History of cancer and smoking, psychiatric disorders, negative future perception, moderate to intense depressive symptoms, high trait-anxiety, moderate to intense pain, medium surgery, female gender, ASA category III, up to 12 years of education and more than 12 years of education constituted independent risk factors for preoperative state-anxiety. Previous surgery reduced the risk for preoperative anxiety.

Risk factors for postoperative anxiety in children.

BACKGROUND: Anxiety is defined as a set of behavioural manifestations that can be divided into state- and trait-anxiety. State-anxiety is a transitory emotional condition that varies in intensity and fluctuates over time. Trait-anxiety is a personality trait which remains relatively stable over time. The objective of this study was to identify and quantify perioperative risk factors for immediate postoperative anxiety in children. METHODS: A prospective cohort study was performed with 90 schoolchildren, ages ranging from 7 to 13 years old, ASA physical status I-II, submitted to elective surgery. The measuring instruments were verbal scale of pain, visual analogue scale (VAS), Trait-State Anxiety Inventory for Children (STAIC), Trait-State Anxiety Inventory (STAI) for parents, and structured questionnaire. RESULTS: Patients not submitted to analgesic block and patients with moderate and intense pain presented an estimated risk 5- and 13-fold greater for high levels of postoperative state-anxiety, respectively. High levels of preoperative state-anxiety and administration of doses of midazolam less than 0.056 mg x kg(-1) constituted an estimated risk for postoperative state-anxiety of 3- and 4-fold, respectively. A positive history of previous surgery was associated with lower risk for postoperative anxiety. CONCLUSIONS: High levels of preoperative state-anxiety, administration of less than 0.056 mg x kg(-1) of midazolam, absence of analgesic block and presence of moderate and intense postoperative pain constituted risk factors for immediate postoperative state-anxiety in children. Previous surgery reduced the risk for postoperative anxiety.