Rejected

The purpose of this study was to compare the immediate effect of spinal manipulation (SMa) and spinal mobilization (SMo) on muscular responses, spinal stiffness, and segmental spinal pressure evoked pain in a population of participants with chronic middle back pain (MBP).

Storage of trametinib tablets outside of 2-8°C protected from moisture may lead to loss of dimethyl sulfoxide (DMSO) and adversely impact trametinib bioavailability. In this open-label, phase 1, single-dose, randomized, 2-treatment, 2-period crossover study in healthy volunteers, bioavailability of a single 2-mg tablet of trametinib containing 9% DMSO (test formulation), corresponding to the lowest DMSO content in the tablet after storage at 25°C for 36 months, was evaluated vs bioavailability of a 2-mg tablet containing 11% DMSO (reference formulation). Sixty-five percent of subjects (n = 39/65) were men, and mean (standard deviation) age was 45.6 (11.17) years. Time to reach maximum plasma concentration occurred at 1.5 hours after dosing. The geometric mean ratio (90%CI) comparing 2-mg trametinib containing 9% DMSO with 2-mg trametinib containing 11% DMSO for area under the concentration-time curve from time 0 to the last measurable plasma concentration sampling time was 0.890 (0.848-0.935), suggesting the 2 formulations have similar bioavailability. The majority of adverse events were mild, with 1 subject experiencing 1 grade 3 headache. These results indicated that storage of trametinib at room temperatures ≤25°C during the overall shelf life of 36 months would not negatively impact trametinib bioavailability.

The purpose of this study was to determine whether baseline self-efficacy, fear of pain with movement (kinesiophobia), or change in either were associated with clinically important improvement in disability among older adults with chronic low back pain after 12 weeks of chiropractic spinal manipulation (CSM) and exercise.

Anxiety is an adaptive emotional response to potentially threatening or dangerous situations; moderated by the sympathetic nervous system. Dental anxiety is common and presents before, during or after dental treatment. The physiological response includes an increase in heart rate, blood pressure, respiratory rate, and cardiac output. Consequently, extensive distress leads to avoidance of dental treatment and multiple failed appointments, impacting both oral and general health. Dental anxiety can generate a variety of negative consequences for both the dentist and the patient. Evidence-based strategies are essential for mitigating and relieving anxiety in the dental clinic. Psychotherapeutic behavioural strategies can modify the patient's experience through a minimally invasive approach with nil or negligible side effects, depending on patient characteristics, anxiety level and clinical situations. These therapies involve muscle relaxation, guided imagery, physiological monitoring, utilising biofeedback, hypnosis, acupuncture, distraction and desensitisation. Pharmacological intervention utilises either relative analgesia (nitrous oxide), conscious intravenous sedation or oral sedation, which can have undesirable side effects, risks and contraindications. These modalities increase the cost and availability of dental treatment. © 2022 Australian Dental Association.

Individuals who experience burns are at higher risk of developing posttraumatic stress disorder and chronic pain. A synergistic relationship exists between posttraumatic stress disorder and chronic pain. We sought to evaluate the role of individual posttraumatic stress disorder symptom clusters as predictors of pain interference. We hypothesized that the hyperarousal and emotional numbing symptom clusters would be predictive of pain interference, even when accounting for the other two posttraumatic stress disorder symptom clusters, pain intensity, and other covariates. Multivariate linear regression analyses were completed using data from the Burn Model System National Database. A total of 439 adult participants had complete responses on self-report measures assessing posttraumatic stress disorder symptoms, pain intensity, and pain interference at 6-month after discharge and were included in analyses. Results indicate hyperarousal (B = .10, p = .03) and emotional numbing (B = .13, p = .01) posttraumatic stress disorder symptom clusters were each significantly associated with pain interference, even when accounting for pain intensity (B = .64, p < .001). Results highlight the importance of the emotional numbing and hyperarousal posttraumatic stress disorder symptom clusters in explaining pain interference. Findings suggest that when posttraumatic stress disorder symptoms or chronic pain are present, screening for and treating either condition may be warranted to reduce pain interference. Further, psychological interventions that target emotional numbing and hyperarousal posttraumatic stress disorder symptoms may be fruitful for promoting better coping with chronic pain and reducing pain interference.

A multicenter cross-sectional study was designed to assess the quality of treatment of 1190 patients with chronic pain at the time of referral to a specialized pain unit. A total of 119 physicians from 77 pain units throughout Spain collected 23 indicators of the quality of care from 10 consecutive clinical records of chronic pain patients (5 men, 5 women). Degenerative spinal diseases (38.6%) and lumbosciatic pain (29.8%) were the most common etiologies. At the time of referral to the pain unit, 9.8% of patients were not receiving any analgesic treatment. Treatment was modified in 88.1% of the patients by adding adjuvant drugs, adding opioids or increasing the doses of analgesic medications, and using analgesic techniques. Women had higher percentages of osteoarthritis, headache and fibromyalgia as the cause of pain, longer duration of pain and severe pain intensity, and a higher proportion of changes in the diagnosis of the underlying condition with which they had been referred to the pain unit. Improvements should be made in the patient management and referral protocols not only in the clinics prior to patient referral to the pain unit, but also in the pain units themselves.

Liver disease is a leading cause of mortality worldwide, resulting in 1.3 million deaths annually. The vast majority of liver disease is caused by metabolic disease (i.e., NASH) and alcohol-induced hepatitis, and to a lesser extent by acute and chronic viral infection. Furthermore, multiple insults to the liver is becoming common due to the prevalence of metabolic and alcohol-related liver diseases. Despite this rising prevalence of liver disease, there are few treatment options: there are treatments for viral hepatitis C and there is vaccination for hepatitis B. Aside from the management of metabolic syndrome, no direct liver therapy has shown clinical efficacy for metabolic liver disease, there is very little for acute alcohol-induced liver disease, and liver transplantation remains the only effective treatment for late-stage liver disease. Traditional pharmacologic interventions have failed to appreciably impact the pathophysiology of alcohol-related liver disease or end-stage liver disease. The difficulties associated with developing liver-specific therapies result from three factors that are common to late-stage liver disease arising from any cause: hepatocyte injury, inflammation, and aberrant tissue healing. Hepatocyte injury results in tissue damage with inflammation, which sensitizes the liver to additional hepatocyte injury and stimulates hepatic stellate cells and aberrant tissue healing responses. In the setting of chronic liver insults, there is progressive scarring, the loss of hepatocyte function, and hemodynamic dysregulation. Regenerative strategies using hepatocyte-like cells that are manufactured from mesenchymal stromal cells may be able to correct this pathophysiology through multiple mechanisms of action. Preclinical studies support their effectiveness and recent clinical studies suggest that cell replacement therapy can be safe and effective in patients with liver disease for whom there is no other option.

Hybrid lesions of intralobar sequestration (ILS) associated with congenital pulmonary airway malformation (CPAM) is rare and could be undetected by prenatal ultrasound. Some of the cases are discovered incidentally or following lung infection in late childhood or adulthood.

The purpose of this study was to describe the diagnoses and chiropractic services performed by doctors of chiropractic operating within 3 military treatment facilities for patients with low back pain (LBP).

Microglial activation plays an important role in the onset and progression of neuropathic pain by producing a variety of pro-inflammatory cytokines that interact with neurons to enhance neuronal hyperexcitability. Corydalis decumbens (Thunb.) pers., a traditional Chinese medicine has been used to treat mild cancer pain, dementia and to remit cerebral ischemia in clinics. Phenylphthalide isoquinolines are the major type of metabolites of C. decumbens and one of the derivatives, Corydecumine G (Cor G) has been shown to inhibit neuronal excitability. The present study aims to investigate the analgesic efficacy of Cor G in neuropathic pain rat model, the effects of Cor G on microglia activation and the possible mechanisms.