Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Prophylactic influences of prebiotics on gut microbiome and immune response of heat-stressed broiler chickens

Abstract Climatic changes and elevated ambient temperature are significant environmental stressors with a negative impact on birds’ physiological, immunological, and behavioral status, increasing their susceptibility to stressors and immunosuppression and consequently increasing intestinal permeability (leaky gut). Prebiotics have been utilized to stop or diminish the harmful effects of stress in chickens. We aimed to evaluate the role of mannan-oligosaccharides, and beta-d-glucan prebiotics supplements in drinking water against experimentally induced heat stress (HS) on broiler chickens and study their impact on birds’ performance, gut microbiome, and immune response. A total of 120 1-day-old Ross broiler chicks were allocated into four groups (30 birds/group), and each group was subdivided into triplicates (10 birds each). The experimental groups were classified as follows; the 1st (G1) control birds, the 2nd (G2) birds exposed experimentally to HS, the 3rd (G3) birds administered prebiotics in drinking water without exposure to HS, and the 4th (G4) birds exposed to HS and administered prebiotics in drinking water. After each vaccination, blood samples and serum samples were collected to evaluate the birds’ immune status. Fecal samples were also collected for the molecular evaluation of the gut microbiome based on the genetic analyses and sequencing of 16S rRNA gene. The results showed that HS has reduced the birds’ performance and badly affected the birds’ immune response and gut microbiome. However, the addition of prebiotics to drinking water, with or without stress, enhanced the growth rate, maintained a normal gut microbiome, and improved immune parameters. Moreover, the usage of prebiotics improved the chicken gut microbiome and alleviated the negative effect of heat stress. Administering prebiotics significantly (p < 0.05) increased the relative abundance of beneficial bacteria and eradicated pathogenic ones in the birds’ gut microbiome. Prebiotics showed a positive effect on the gut microbiome and the immune status of chickens under HS in addition to their efficacy as a growth promoter

Effect of 25-hydroxyvitamin D on metabolic parameters and insulin resistance in patients with polycystic ovarian syndrome

Objectives: To investigate the correlation between the levels of 25-hydroxyvitamin D and insulin resistance in patients with polycystic ovarian syndrome (PCOS). Patients and methods: In 30 untreated PCOS patients and 15 control subjects, levels of 25-hydroxyvitamin D were measured. In addition, endocrine and metabolic variables were evaluated and a glucose tolerance test was performed to assess indices of insulin resistance. Results: Obese PCOS women (n = 15) had lower 25-hydroxyvitamin D levels than lean PCOS women (n = 15) and control subjects (8.9 ± 3.1 vs 26.5 ± 6.4 vs 79.2 ± 19.1 nmol/l respectively; P < 0.001). In the entire cohort, 25-hydroxyvitamin D levels were negatively correlated with body mass index (r = −0.390), fasting insulin (r = −0.707), HOMA-β (r = −0.705), and HOMA-IR (r = −0.635), and positively correlated with QUICKI (r = 0.723) (all P < 0.001). Conclusion: In PCOS women, low 25-hydroxyvitamin D levels are associated with obesity and insulin resistance

Neuroprotective Effect of Gold Nanoparticles and Alpha-Lipoic Acid Mixture against Radiation-Induced Brain Damage in Rats

The current study aims to evaluate the possible neuroprotective impact of gold nanoparticles (AuNPs) and an alpha-lipoic acid (ALA) mixture against brain damage in irradiated rats. AuNPs were synthesized and characterized using different techniques. Then, a preliminary investigation was carried out to determine the neuroprotective dose of AuNPs, where three single doses (500, 1000, and 1500 µg/kg) were orally administrated to male Wistar rats, one hour before being exposed to a single dose of 7Gy gamma radiation. One day following irradiation, the estimation of oxidative stress biomarkers (malondialdehyde, MDA; glutathione peroxidase, GPX), DNA fragmentation, and histopathological alterations were performed in brain cortical and hippocampal tissues in both normal and irradiated rats. The chosen neuroprotective dose of AuNPs (1000 µg/kg) was processed with ALA (100 mg/kg) to prepare the AuNPs-ALA mixture. The acute neuroprotective effect of AuNPs-ALA in irradiated rats was determined against valproic acid as a neuroprotective centrally acting reference drug. All drugs were orally administered one hour before the 7Gy-gamma irradiation. One day following irradiation, animals were sacrificed and exposed to examinations such as those of the preliminary experiment. Administration of AuNPs, ALA, and AuNPs-ALA mixture before irradiation significantly attenuated the radiation-induced oxidative stress through amelioration of MDA content and GPX activity along with alleviating DNA fragmentation and histopathological changes in both cortical and hippocampal tissues. Notably, the AuNPs-ALA mixture showed superior effect compared to that of AuNPs or ALA alone, as it mitigated oxidative stress, DNA damage, and histopathological injury collectively. Administration of AuNPs-ALA resulted in normalized MDA content, increased GPX activity, restored DNA content in the cortex and hippocampus besides only mild histopathological changes. The present data suggest that the AuNPs-ALA mixture may be considered a potential candidate for alleviating radiation-associated brain toxicity

Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression

ABSTRACTDuring solid tumor progression, the tumor microenvironment (TME) evolves into a highly immunosuppressive milieu. Key players in the immunosuppressive environment are regulatory myeloid cells, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), which are recruited and activated via tumor-secreted cytokines such as colony-stimulating factor 1 (CSF-1). Therefore, the depletion of tumor-secreted cytokines is a leading anticancer strategy. Here, we found that CSF-1 secretion by melanoma cells is decreased following treatment with Cannabis extracts. Cannabigerol (CBG) was identified as the bioactive cannabinoid responsible for the effects. Conditioned media from cells treated with pure CBG or the high-CBG extract reduced the expansion and macrophage transition of the monocytic-MDSC subpopulation. Treated MO-MDSCs also expressed lower levels of iNOS, leading to restored CD8+ T-cell activation. Tumor-bearing mice treated with CBG presented reduced tumor progression, lower TAM frequencies and reduced TAM/M1 ratio. A combination of CBG and αPD-L1 was more effective in reducing tumor progression, enhancing survival and increasing the infiltration of activated cytotoxic T-cells than each treatment separately. We show a novel mechanism for CBG in modulating the TME and enhancing immune checkpoint blockade therapy, underlining its promising therapeutic potential for the treatment of a variety of tumors with elevated CSF-1 expression

Phytochemicals as Micronutrients: What Is their Therapeutic Promise in the Management of Traumatic Brain Injury?

Traumatic brain injury (TBI) is one of the key causes of deaths and disabilities worldwide. TBI progresses in two phases. The primary phase of injury is the direct result of the physical damage caused by the external force applied to the brain while the secondary injury takes place minutes to days after the primary injury. The secondary phase of TBI is marked by a series of pathological events that start following the initial mechanical impact. The mechanisms underlying TBI pathogenesis in the secondary phase are intricate and include metabolic alterations, excitotoxicity, oxidative stress, and neuroinflammation, among others; all culminating in neuronal cell damage and death. Currently, there is no FDA-licensed drug that targets TBI. Hence, the search for novel therapeutic agents that can target one or more of the mechanisms underlying the pathology of the secondary phase of TBI is warranted. Such novel therapeutic agents are expected to ameliorate the adverse consequences of TBI. Over the years, evidence has accumulated regarding the role of phytochemicals as novel agents in the management of TBI. Phytochemicals are a class of micronutrients composed of herbal or plant secondary metabolites. Phytochemicals offer appropriate candidates for the treatment of TBI since their use can warrant the inhibition of the progression of the secondary injury and the activation of major neuroprotective signaling pathways following TBI. In this regards, phytochemicals have been acknowledged to cause a significant decrease in neuronal injury through different mechanisms including the activation of the Nrf2 transcription factor leading to activation of several antioxidant enzyme systems such as superoxide dismutase, inhibition of NADPH oxidases (NOX) enzymes, suppression of nuclear factor kappa B (NF-κB) activity and reduction of the release of inflammatory mediators, suppression of the NLRP3 inflammasome, stimulation of neurogenesis by activating neurotrophic factors (BDNF), among others. As such, the chapter aims to evaluate the neuroprotective effects of phytochemicals in TBI by reviewing the available literature. In this chapter, we introduce TBI and the mechanisms that underlie its pathology. Also, we overview the current conventional strategies that are being used to manage TBI. Then, we overview phytochemicals and explore their use in the management of diseases with a special focus on their use in the treatment of neurological diseases. Finally, we discuss the therapeutic potentials of phytochemicals in the management of TBI by focusing on six phytochemicals: ginseng, curcumin, coumarin, genistein, apocynin, and baicalein. We review the available literature on the use of these phytochemicals in the context of TBI. In addition, we document the recent studies aimed that discuss the in vitro and in vivo experimental evidence on the cellular and molecular mechanisms of neuroprotection by these phytochemicals. We conclude that all of the studied phytochemicals have shown experimental preclinical promise. But, well-designed and controlled clinical trials are urgently needed to demonstrate their safety and efficacy in order to realize their benefits in human TBI patients

Phytochemicals as Micronutrients: What Is their Therapeutic Promise in the Management of Alzheimer’s Disease?

Alzheimer’s disease (AD) is a debilitating neurodegenerative disease with devastating outcomes to patients and exhaustive burdens to healthcare systems. Alzheimer’s disease has always been the focus of extensive research since its discovery in the early 1900s; however, AD continues to wreak havoc among the elderly population. Unfortunately, until now AD is still without any defined treatment that can curb its otherwise insidious progression. In the wake of this crisis and in the absence of a restorative cure, alternative approaches to AD management have been sought. In this regard, phytochemicals—a class of micronutrients composed of herbal or plant secondary metabolites— have shown potential as novel agents in the management of several diseases including cancer, hyperlipidemia, cardiovascular diseases, hyperglycemia, and neurodegenerative disorders including AD. Phytochemicals therapeutic abilities can be attributed to their ability to protect against several AD pathologic events such as inflammation, oxidative stress, protein misfolding, aggregation, and several more. In this chapter, we overview AD and its progression to pathology. Next, we highlight the available conventional treatments currently used to mitigate symptoms of AD. Then, we expose phytochemicals and their known therapeutic potential in several diseases including neurodegenerative disorders. Lastly, we explore the available literature concerning the use of phytochemicals in the management of AD. Specifically, light is shed on the possible curative capacity of certain plant phytochemicals—namely those of Ginkgo biloba, Piper nigrum, Withania somnifera, Lavandula angustifolia, Olea europaea, Nigella sativa, Ficus carica, and Panax ginseng—in the management of AD. Mechanisms by which extracts of these plants exert their neuroprotective effects are discussed alongside other aspects pertaining to the efficacy, safety, and druggability of some of these phytochemicals. We conclude that phytochemicals have shown promise in the management of AD. However, clinical trials remain lacking in this area and extensive efforts need to be exerted to determine the safety, efficacy, and exact modes of action of phytochemicals in human AD patients

International Finance and Economics Review (InFER) - Issue no. 3 (June 2019)

InFER articles focus on economic theories and the capstone papers highlight data driven analyses that make inferences to business and policy decisions