Comparison of tranexamic acid plasma concentrations when administered via intraosseous and intravenous routes

Introduction

There is a lack of information regarding intraosseous (IO) administration of tranexamic acid (TXA). Our hypothesis was that a single bolus IO injection of TXA will have a similar pharmacokinetic profile to TXA administered at the same dose IV.

Participation in decision‐making about medication: A qualitative analysis of medication adherence

Rates of relapse in BD are high with medication nonadherence identified as an important contributor to relapse. Psychopharmacology remains a key component to the treatment of BD; therefore, increased understanding of medication use and ways to promote greater adherence is essential. The aim of the study was to identify how participants with BD experience taking prescribed medication. Participants had BD I or BD II, were users of specialist mental health services, aged 18–64 years, euthymic, mildly hypomanic or depressed, and on any combination of medication. Exclusion criteria were minimal. A semistructured interview was completed exploring patients’ views of BD and factors influencing adherence based on the Subjective Experience of Medication Interview. An inductive thematic analysis was used to identify themes. The study participants (n = 36) had predominantly bipolar I (78%) and were female (69%), and of New Zealand European ethnicity (67%) with 14% Maori. The mean age was 41 years (SD: 12.0). Findings from the thematic analysis generated three themes: Learning about the clinical meaning of having BD, Understanding how to use medication, and Understanding what works for me. The qualitative nature of our study limits the generalizability of our findings to a broader population of individuals with BD. The participants developed confidence in being in charge of their BD through a process of learning about BD and medication and understanding what this meant for them. The findings support greater emphasis on collaborative approaches that recognize the expertise of the individual with BD and the clinician.     

山莨菪碱不同方式给药对亚低温治疗大鼠脑缺血的影响

目的：探讨不同途径用山莨菪碱对亚低温治疗大鼠脑缺血再灌注损伤的影响。方法：利用前脑缺血动物模型,观察缺血再灌注后海马神经元的病理改变及一氧化氮（ＮＯ）、一氧化氮合成酶（ＮＯＳ）的变化。结果：大鼠海马中央区（ＣＡ１区）存活神经元计数：亚低温大剂量山莨菪碱颈动脉灌注组＞亚低温组,亚低温大剂量山莨菪碱静脉用药组＞常温组。ＮＯＳ活性则表现为亚低温大剂量山莨菪碱颈动脉灌注组＜亚低温组,亚低温大剂量山莨菪碱静脉用药组和亚低温小剂量山莨菪碱颈动脉灌注组＜常温组。而且亚低温及亚低温复合用山莨菪碱均能显著抑制ＮＯ值的升高,减轻大量ＮＯ生成所导致的细胞毒性作用。结论：亚低温,大剂量山莨菪碱颈动脉灌注可以提高亚低温治疗效果（优于静脉滴注法）,能够减轻海马迟发性神经元损伤;并抑制ＮＯＳ活性,减少ＮＯ的生成。这可能是颈动脉灌注大剂量山莨菪碱治疗效果的作用机制之一     

Insular cortex lesion diminishes neuropathic and inflammatory pain‐like behaviours

Injury to the insular cortex in humans produces a lack of appropriate response to pain. Also, there is controversial evidence on the lateralization of pain modulation. The aim of this study was to test the effect of insular cortex lesions in three models of pain in the rat. An ipsilateral, contralateral or bilateral radiofrequency lesion of the rostral agranular insular cortex (RAIC) was performed 48 h prior to acute, inflammatory or neuropathic pain models in all the experimental groups. Acute pain was tested with paw withdrawal latency (PWL) after thermal stimulation. Inflammation was induced with carrageenan injected in the paw and PWL was tested 1 h and 24 h afterwards. Neuropathic pain was tested after ligature of the sciatic nerve by measuring mechanical nociceptive response after stimulation with the von Frey filaments. Another model of neuropathy consisted of thermo stimulation followed by right sciatic neurectomy prior to the recording of autotomy behaviour. Acute pain was not modified by the RAIC lesion. All the RAIC lesion groups showed diminished pain‐related behaviours in inflammatory (increased PWL) and neuropathic models (diminished mechanical nociceptive response and autotomy score). The lesion of the RAIC produces a significant decrease in pain‐related behaviours, regardless of the side of the lesion. This is a clear evidence that the RAIC plays an important role in the modulation of both inflammatory and neuropathic—but not acute—pain.     

Adolescent chronic pain‐related functioning: Concordance and discordance of mother‐proxy and self‐report ratings

Accurate assessment of adolescent chronic pain is critical to guiding treatment decisions. Given the multifaceted role of the parents in their children's lives, parents, and patients often each provide reports of adolescents’ pain‐related functioning. In order to make sense of these data, clinicians should be aware of patterns of discordance in perspectives. In this study, we aimed to examine concordance and discordance in adolescents’ self‐report and mothers’ proxy‐report of adolescents’ chronic pain‐related functioning. Results suggested that although there were high correlations between the raters, there were also significant discordance with mothers rating their adolescents as having greater disability in social functioning, depression, and pain‐specific anxiety. Analyses suggested that high pain and being older predicted greater concordance in ratings. Findings suggest that mothers and adolescents tended to have greater concordance for more observable and shared disability (e.g., physical disability, family functioning) and greater discordance for internal experiences (e.g., pain‐specific anxiety, depression). Awareness of these patterns of concordance and discordance should help clinicians in interpreting mothers’ proxy‐reports and adolescents’ self‐reports of chronic pain‐related functioning.     

Vector‐mediated release of GABA attenuates pain‐related behaviors and reduces NaV1.7 in DRG neurons

Pain is a common and debilitating accompaniment of neuropathy that occurs as a complication of diabetes. In the current study, we examined the effect of continuous release of gamma amino butyric acid (GABA), achieved by gene transfer of glutamic acid decarboxylase (GAD67) to dorsal root ganglia (DRG) in vivo using a non‐replicating herpes simplex virus (HSV)‐based vector (vG) in a rat model of painful diabetic neuropathy (PDN). Subcutaneous inoculation of vG reduced mechanical hyperalgesia, thermal hyperalgesia and cold allodynia in rats with PDN. Continuous release of GABA from vector transduced cells in vivo prevented the increase in the voltage‐gated sodium channel isoform 1.7 (Na_V1.7) protein that is characteristic of PDN. In vitro, infection of primary DRG neurons with vG prevented the increase in Na_V1.7 resulting from exposure to hyperglycemia. The effect of vector‐mediated GABA on Na_V1.7 levels in vitro was blocked by phaclofen but not by bicuculline, a GABA_B receptor effect that was blocked by pertussis toxin‐(PTX) interference with Gα(_i/o) function. Taken in conjunction with our previous observation that continuous activation of delta opioid receptors by vector‐mediated release of enkephalin also prevents the increase in Na_V1.7 in DRG exposed to hyperglycemia in vitro or in vivo, the observations in this report suggest a novel common mechanism through which activation of G protein coupled receptors (GPCR) in DRG neurons regulate the phenotype of the primary afferent.     

Comparative effectiveness of different stimulation modes in relieving pain. Part I. A pilot study.

In this pilot study, to assess the optimal stimulation parameters, 3 different forms of transcutaneous electrical nerve stimulation were performed in 27 patients. Conventional continuous stimulation with a constant frequency of 70 Hz, burst stimulation (90 msec trains of pulses with an internal frequency of 100 Hz repeated at 2 Hz, each train consisting of 10 pulses), and frequency-modulated stimulation (continuous pulses changed from 90 Hz to 55 Hz over 90 msec) were randomly delivered to the patients for half an hour in 3 separate sessions. The patients were blind to the modes of stimulation. This pilot study demonstrated that patients preferred modulated stimulation modes such as frequency modulation and burst rather than conventional constant mode.     

Reference values of mechanical and thermal pain tests in a pain‐free population

Quantitative sensory tests are widely used in human research to evaluate the effect of analgesics and explore altered pain mechanisms, such as central sensitization. In order to apply these tests in clinical practice, knowledge of reference values is essential. The aim of this study was to determine the reference values of pain thresholds for mechanical and thermal stimuli, as well as withdrawal time for the cold pressor test in 300 pain‐free subjects. Pain detection and pain tolerance thresholds to pressure, heat and cold were determined at three body sites: (1) lower back, (2) suprascapular region and (3) second toe (for pressure) or the lateral aspect of the leg (for heat and cold). The influences of gender, age, height, weight, body‐mass index (BMI), body side of testing, depression, anxiety, catastrophizing and parameters of Short‐Form 36 (SF‐36) were analyzed by multiple regressions. Quantile regressions were performed to define the 5th, 10th and 25th percentiles as reference values for pain hypersensitivity and the 75th, 90th and 95th percentiles as reference values for pain hyposensitivity. Gender, age and/or the interaction of age with gender were the only variables that consistently affected the pain measures. Women were more pain sensitive than men. However, the influence of gender decreased with increasing age. In conclusion, normative values of parameters related to pressure, heat and cold pain stimuli were determined. Reference values have to be stratified by body region, gender and age. The determination of these reference values will now allow the clinical application of the tests for detecting abnormal pain reactions in individual patients.