Pain expectations in neuropathic pain: Is it best to be optimistic?

BACKGROUND: Pain expectancy may be an important variable that has been found to influence the effectiveness of treatments for pain. Much of the literature supports a self-fulfilment perspective where expectations for pain relief predict the actual pain experienced. However, in conditions such as neuropathic pain (NeP) where pain relief is difficult to attain, expectations for pain relief could be unrealistic. The objective of this study was to investigate the relationship between realistic/unrealistic expectations and 6-month, post-treatment outcomes. METHODS: We performed a retrospective analysis of a large cohort of patients with NeP (n = 789) attending tertiary care centres to determine the association between unrealistic (both positive and negative) and realistic expectations with outcomes after multidisciplinary treatment. An expectation variable with three categories was calculated: realistic expectations were those whose expected reduction in pain was similar to the observed mean group reduction in pain, while optimistic and pessimistic expectations were those who over- or under-estimated the expected response to treatment, respectively. The association between baseline realistic/unrealistic expectations and 6-month pain-related disability, catastrophizing and psychological distress was assessed. RESULTS: Univariable analyses suggested that realistic expectations were associated with lower levels of disability, catastrophizing and psychological distress, compared to unrealistic expectations. However, after adjustment for baseline symptom severity, multivariable analysis revealed that patients with optimistic expectations had lower levels of disability, than those with realistic expectations. Those with pessimistic expectations had higher levels of catastrophizing and psychological distress at follow-up. CONCLUSIONS: These findings are largely congruent with the self-fulfilment perspective to expectations. SIGNIFICANCE: This study defined realistic pain expectations with patient data. Examining the relationship between expectations between pain and disability in a large cohort of patients with neuropathic pain.

The Predictive Link between Matrix and Metastasis.

Cancer spread (metastasis) is responsible for 90% of cancer-related fatalities. Informing patient treatment to prevent metastasis, or kill all cancer cells in a patient's body before it becomes metastatic is extremely powerful. However, aggressive treatment for all non-metastatic patients is detrimental, both for quality of life concerns, and the risk of kidney or liver-related toxicity. Knowing when and where a patient has metastatic risk could revolutionize patient treatment and care. In this review, we attempt to summarize the key work of engineers and quantitative biologists in developing strategies and model systems to predict metastasis, with a particular focus on cell interactions with the extracellular matrix (ECM), as a tool to predict metastatic risk and tropism.

Distress in patients with bleeding disorders: a single institutional cross-sectional study.

INTRODUCTION: Distress may affect a patient's ability to cope with and manage disease. AIM: To report distress prevalence in adult patients with bleeding disorders and determine whether specific clinical and health characteristics, including disease severity and employment status, are associated with distress. METHODS: Patients who visited a Haemophilia Treatment Centre (HTC) between January 1st, 2012 through February 28th, 2014 and who completed a distress screen, pain screen and questionnaire were evaluated cross sectionally. Distress was measured by the National Comprehensive Cancer Network Distress Management Tool, which allowed patients to rate recent distress on a 0-10 point scale. A rating of five or more was categorized as high distress. Pain was measured by the Brief Pain Inventory Short Form, which asked patients to rate pain types on 0-10 point scales. Patients reported employment and other demographic and behavioural information on the questionnaire. Primary diagnosis, age, HIV and HCV status were abstracted from medical records. Adjusted logistic regression was used to identify distress associations. RESULTS: High distress prevalence among 152 patients with bleeding disorders was 31.6%. Unemployment, disability, greater depressive symptoms and higher pain were associated with high distress in multivariable models. Bleeding disorder diagnosis, race/ethnicity, HIV/HCV status and on-demand treatment regimen were not associated with high distress. CONCLUSION: Distress among patients with congenital bleeding disorders followed at a comprehensive HTC was high and similar to that reported among patients with cancer. Future research should determine whether distress impacts clinical outcomes in patients with bleeding disorders as demonstrated in other chronic disorders.

Cannabinoids for the Treatment of Chronic Non-Cancer Pain: An Updated Systematic Review of Randomized Controlled Trials.

An updated systematic review of randomized controlled trials examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to PRISMA guidelines for systematic reviews reporting on health care outcomes. Eleven trials published since our last review met inclusion criteria. The quality of the trials was excellent. Seven of the trials demonstrated a significant analgesic effect. Several trials also demonstrated improvement in secondary outcomes (e.g., sleep, muscle stiffness and spasticity). Adverse effects most frequently reported such as fatigue and dizziness were mild to moderate in severity and generally well tolerated. This review adds further support that currently available cannabinoids are safe, modestly effective analgesics that provide a reasonable therapeutic option in the management of chronic non-cancer pain.

Effect of microwaves on the migration of lithium and silicon from lithium disilicate (Li2O-2SiO2) glass.

Lithium disilicate (Li2O-2SiO2) glass was immersed in a static solution of deionized water and heated by a microwave or by conventional means for various times. The resulting Li+ and Si migration was compared by solution analysis and the corroded glass surfaces were compared by Fourier transform infrared reflection spectroscopy and scanning electron microscopy. Results show no substantial differences in migration or glass corrosion under the test conditions using 7.00 GHz microwave radiation, but leave open the possibility of very slightly altered kinetics using 5.86 GHz radiation. More testing at 2.45 GHz is suggested.

Preclinical science regarding cannabinoids as analgesics: an overview.

Modern pharmacology of cannabinoids began in 1964 with the isolation and partial synthesis of delta-9-tetrahydrocannabinol, the main psycho-active agent in herbal cannabis. Since then, potent antinociceptive and antihyperalgesic effects of cannabinoid agonists in animal models of acute and chronic pain; the presence of cannabinoid receptors in pain-processing areas of the brain, spinal cord and periphery; and evidence supporting endogenous modulation of pain systems by cannabinoids has provided support that cannabinoids exhibit significant potential as analgesics. The present article presents an overview of the preclinical science.

Guidelines for the use of cannabinoid compounds in chronic pain.

OBJECTIVE: To provide clinicians with guidelines for the use of cannabinoid compounds in the treatment of chronic pain. METHODS: Publications indexed from 1990 to 2005 in the National Library of Medicine Index Medicus were searched through PubMed. A consensus concerning these guidelines was achieved by the authors through review and discussion. RESULTS: There are few clinical trials, case reports or case series concerning the use of cannabinoid compounds in the treatment of chronic pain. There are no randomized clinical trials examining the use of herbal cannabis in the treatment of chronic pain. CONCLUSIONS: A practical approach to the treatment of chronic pain with cannabinoid compounds is presented. Specific suggestions about the off-label dosing of nabilone (Cesamet, Valeant Canada limitee/Limited) and dronabinol (Marinol, Solvay Pharma Inc, Canada) in the treatment of chronic pain are provided.

Patterns of cannabis use among patients with multiple sclerosis.

To estimate the patterns and prevalence of cannabis use among patients with multiple sclerosis (MS), 220 patients were surveyed in Halifax, Nova Scotia. Seventy-two subjects (36%) reported ever having used cannabis for any purpose; 29 respondents (14%) reported continuing use of cannabis for symptom treatment. Medical cannabis use was associated with male gender, tobacco use, and recreational cannabis use. The symptoms reported by medical cannabis users to be most effectively relieved were stress, sleep, mood, stiffness/spasm, and pain.

A pilot study examining topical amitriptyline, ketamine, and a combination of both in the treatment of neuropathic pain.

OBJECTIVE: The involvement of ongoing peripheral activity in the generation of nociceptive input in neuropathic pain suggests that topical drug delivery may be useful as a treatment strategy. This is a pilot study providing initial information regarding the use of novel topical preparations containing amitriptyline (AMI), ketamine (KET), and a combination of both in the treatment of neuropathic pain. METHODS: The study design included a 2 day randomized, double blind, placebo controlled, 4 way cross-over trial of all treatments, followed by an open label treatment phase using the combination cream for 7 days. Twenty volunteers with chronic neuropathic pain were randomly assigned to treatment order and applied 5 mls of each topical treatment (1% AMI, 0.5% KET, combination AMI 1%/KET 0.5%, and placebo) for 2 days. Measures of pain at the end of each block included the short form McGill Pain Questionnaire (MPQ) and visual analog scales (VAS) for present pain intensity and pain relief. Eleven subjects who judged subjective improvement from any treatment in the initial trial entered the open-label trial and used the combination cream for 7 days. Pain levels were recorded daily using the same measures. Blood levels for amitriptyline and ketamine were performed at 7 days to determine whether systemic absorption had occurred. RESULTS: There was no statistically significant difference from placebo after 2 days for any treatment during the double blind component of the trial. In the 11 subjects who used the combination cream, there was a statistically significant effect, with subjects reporting significantly greater analgesia by days 3 to 7 according to measures of pain and pain relief. Blood levels revealed that there was no significant systemic absorption of amitriptyline or ketamine. Only 2 subjects experienced side effects; these were minor and did not lead to discontinuation of the cream. CONCLUSION: This pilot study demonstrated a lack of effect for all treatments in the 2 day double blind placebo controlled trial, followed by analgesia in an open label trial in a subgroup of subjects who chose to use the combination cream for 7 days. Blood analysis revealed no significant systemic absorption of either agent after 7 days of treatment, and creams were well tolerated. A larger scale randomized trial over a longer interval is warranted to examine further effects observed in the open label trial.

Inhalation efficacy of RFI-641 in an African green monkey model of RSV infection.

Human respiratory syncytial virus (RSV) is a major cause of acute upper and lower respiratory tract infections. RFI-641 is a novel RSV fusion inhibitor with potent in vitro activity. In vivo efficacy of RFI was determined in an African green monkey model of RSV infection involving prophylactic and therapeutic administration by inhalation exposure. Inhalation was with an RFI-641 nebulizer reservoir concentration of 15 mg/ml for 15 minutes (short exposure) or 2 hours (long exposure). Efficacy and RFI-641 exposure was determined by collection of throat swabs, nasal washes and bronchial alveolar lavage (BAL) on selected days. The short-exposure group (15 minutes) exhibited no effect on the nasal, throat or BAL samples. The throat and nasal samples for the long-exposure group failed to show a consistent reduction in viral titers. RFI-641 2 hours exposure-treated monkeys showed a statistically significantly log reduction for BAL samples of 0.73-1.34 PFU/ml (P-value 0.003) over all the sampling days. Analysis indicates that the long-exposure group titer was lower than the control titer on day 7 and when averaged across days. The results of this study demonstrate the ability of RFI-641 to reduce the viral load of RSV after inhalation exposure in the primate model of respiratory infection.

Antidepressants as analgesics: a review of randomized controlled trials.

This review provides an overview of 59 randomized placebo-controlled trials that examined the analgesic effect of antidepressants. To summarize, there is significant evidence that the tricyclic group of antidepressants is analgesic and that trazodone is not; the data regarding selective serotonin reuptake inhibitors are conflicting. To date, there are no randomized controlled trials examining the potential analgesic action of nefazodone or venlafaxine, but on the basis of initial clinical reports and its structural similarity to other analgesics, venlafaxine shows promise as an analgesic.

Subjective overachievement: individual differences in self-doubt and concern with performance.

We discuss the construct of doubt about one's competence and suggest that doubt can have myriad consequences (e.g., self-handicapping, defensive pessimism). We focus on the effect of self-doubt when it is combined with a concern with performance and assert that this combination leads to the phenomenon of subjective overachievement. In two studies, we present a new 17-item Subjective Overachievement Scale (SOS), which includes two independent subscales measuring individual differences in self-doubt and concern with performance. The first study, consisting of two large samples (Ns = 2,311 and 1,703), provides evidence that the scale has high internal consistency and a clear two-factor structure. Additionally, the subscales have adequate test-retest reliability (Ns = 67 and 115). A second study reveals that the SOS has good convergent and discriminant validity. Both subscales are unrelated to social desirability but exhibit the predicted patterns of associations with other related constructs. The Concern with Performance Subscale is correlated with achievement motivation, whereas the Self-Doubt Subscale is correlated with scales assessing negative affectivity (e.g., self-esteem, social anxiety) and other self-related strategies associated with concerns about one's competence (e.g., self-handicapping, defensive pessimism, impostor phenomenon). The SOS, which combines the two subscales, appears to tap a unique strategy that individuals may use to deal with doubts about their own competence.

The effects of prenatal drug exposure, term status, and caregiving on arousal and arousal modulation in 8-week-old infants.

Prenatal exposure to cocaine, as well as other drugs, has been linked with "dysregulation," usually defined as problems in arousal and/or behavioral regulation. This study was designed to describe the physiological basis of dysregulation as a function of prenatal cocaine/polydrug exposure and term status. Eight-week-old infants were selected because they are just developing the ability to modulate arousal. One hundred-eighteen infants (23 preterm control, 27 preterm drug-exposed, 29 full-term control, and 39 full-term drug-exposed) completed a protocol during which heart rate (HR) and respiratory rate (RR) were measured. Drug group differences were found in baseline, arousal (response to stress), and arousal modulation (recovery from stress). A hierarchical multiple regression analysis was conducted to determine the portion of variance attributable to postnatal caregiving environment, term status, and specific drug exposure. Term status accounted for significant variance in arousal (both RR and HR), and in arousal modulation (only RR). Prenatal exposure to cocaine contributed a significant amount of unique variance in HR arousal whereas tobacco contributed significantly to HR arousal modulation. Prenatal drug exposure and preterm status contributed differently to dysregulation as measured by physiological responses.

Attentional response at eight weeks in prenatally drug-exposed and preterm infants.

To evaluate the effect of prenatal polydrug exposure on infant attention, 105 8-week-old African-American infants were presented a series of stimuli and their heart rates (HRs) were recorded. Infants were identified postnatally based on mothers' substance use. Four groups were tested: 1) preterm drug-exposed infants (n = 25); 2) full-term, drug-exposed (n = 32); 3) preterm nonexposed (n = 22); and 4) full-term, nonexposed (n = 26). Preterm infants' ages were corrected. Infant's baseline HRs were recorded and then stimuli presented in the following order: auditory (rattle), visual (red ring), and social (examiner's face and voice). There were no HR differences at baseline or in auditory or visual conditions. However, significant differences (F(2, 103) = 6.54, p < 0.01) were seen in response to social stimuli. Drug-exposed infants showed an acceleratory HR indicating distress or arousal and control infants showed a deceleratory response indicating focused attention and there was an interaction due to greater HR response in preterms. Hierarchical regression indicated cocaine (R2 = 0.034, p < 0.05) but not other drug use and instability in parenting (R2 = 0.137, p < 0.001) accounted for the observed differences.

Use of the laryngeal mask airway in the ambulatory setting.

STUDY OBJECTIVE: To determine the utility of the laryngeal mask airway (LMA) in an ambulatory surgery practice. DESIGN: Prospective, longitudinal device (survival) study. SETTING: University-based ambulatory surgery center. PATIENTS: 1,831 ASA physical status I, II, and III outpatients undergoing superficial ambulatory surgery procedures. INTERVENTIONS: Twenty LMA devices were entered into service over a 2-year period and the number of uses, as well as the structural integrity, were assessed at the end of this study period. The serial number on each LMA device was used to track the number of times it was autoclaved, as well as the date that the device failed any of the standardized pre-use tests or was lost. MEASUREMENTS AND MAIN RESULTS: During the 2-year survey, 6,430 general anesthetics were administered at the ambulatory surgery center, with 1,831 (28%) using an LMA device for airway management. At the end of the study period, nine devices were still in use, three had been withdrawn for structural analysis by the manufacturer (after > 100 uses), three failed the pre-use test (after 38-82 uses), and five devices were lost (after 21-162 uses). The structural examination revealed that the tubes were 50% weaker; however, the cuffs, pilot balloons, and values were functioning normally. The median (range) number of uses was 92 (21-195). Thus, the 20 LMA devices evaluated tolerated an average of 92 autoclave cycles each over the 2-year observation period. CONCLUSIONS: To optimize the use of the LMA device in the ambulatory setting, it is necessary to increase awareness that it is a nondisposable piece of equipment and to adhere to the manufacturer's instructions for cleaning, sterilization, and insertion.

Role of antifungal drug resistance in the pathogenesis of recurrent vulvovaginal candidiasis.

The aetiology of recurrent vulvovaginal candidiasis (RVVC) caused by Candida albicans remains unclear. To adequately address the role of antifungal resistance as a potential mechanism for RVVC, a longitudinal susceptibility analysis of 177 C. albicans isolates collected from 50 C. albicans RVVC patients over a period of 3 months to 7 years was performed. Antifungals tested included clotrimazole, ketoconazole, miconazole, itraconazole and fluconazole. Results showed that all vaginal isolates were uniformly susceptible to all drugs tested and that successive isolates from individual patients did not show increased resistance to any drug despite long-term exposure to azoles. These results suggest that episodes of RVVC caused by C. albicans are rarely of ever attributable to azole antifungal resistance.