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Introduction:Opioid addiction is a rising public health crisis. We evaluated if a New York State-mandated online opioid awareness course impacted our urology opioid prescription practices f...

Thiowurtzine, a hexaazaisowurtzitane derivate, is a novel original non-opioid analgesic. In this article, an HPLC–UV method has been developed for rapid detection and quantification of API and related substances contained in thiowurtzine capsules. Six thiowurtzine impurities were separated successfully from each other by isocratic elution using a Luna 5u PFP (2) (150 mm × 4.6 mm, 5 µm) column with 30 µL injection volumes at a wavelength of 254 nm. Commercially unavailable impurities were formed by degradation of thiowurtzine and preliminarily identified by high-resolution LC–MS. This method proved to be robust, linear, repeatable, sensitive, selective and handy.

Aim. In the second half of the 20th and the beginning of the 21st century, there were significant changes in the hemp growing that affected the improvement of morphological, biological and economic properties, by providing the opportunity, on the example of new varieties, to declare the creation of a new subset of sown hemp in which the main achievements of breeders and seedlings were accumulated. Methods. With the creation of the Institute of Bast Crops, scientific breeding has begun, based on improved and developed new breeding methods that include several significant steps as increasing of the yield of created monoecious form, as the elimination of their narcotic properties. Results. For the first time in the world, non-drug hemp that can produce high yields of straw, fiber and seeds while maintaining immunity to damage to pests and diseases were created. Conclusions. Responding to the doubts of tax of collectors and botanists about the classification of the hemp family, we share the opinion of the first scientists and our teachers that include Cannabis sativa L. and Cannabis indica L. to one species of Cannabis sativa L., combining all kinds and varieties. The elimination of a number of high-yielding varieties of non-drug monoecious hemp, which became the result of long-term breeding, testifies the creation of a new variety of Cannabis sativa L. convar non-narcotic Vyrovets, emphasizing the leadership and executive role of Professor V. Vyrovets during a long selection process. Keywords: hemp, genus, variety, geographical types, selection, productivity, elimination of narcotic.

No abstract available.

The opioid crisis continues to be a public health concern. Traditionally, an opioid-centric approach treats postoperative pain. The following PICOT question guided this project: Will initiating a multimodal analgesic virtual reality quality improvement program (I) compared to current practice (C) decrease opioid requirements (O) in robotic hysterectomy patients (P) during the postoperative period (T)? Several articles promote non-opioid analgesia and non-pharmacological interventions, such as multimodal analgesia and virtual reality (VR) for pain management. This project reviewed pre- and post-implementation data after implementing new evidence-based multimodal analgesia and VR protocols. The project captured a total of 64 patients in the pre-implementation group. A total of 22 patients received both multimodal analgesia and VR in the post-implementation group. There was no statistically significant difference in total opioid consumption converted as morphine milligram equivalents (MME) between the pre-implementation and post-implementation groups. However, there was a statistically significant difference in multimodal analgesia administered in Pre-op between the pre-implementation and post-implementation groups. In conclusion, the execution of the multimodal analgesic VR program allowed for nursing adoption of novel evidence-based practices (EBP) and promoted the use of non-opioid and non-pharmacological interventions. Although the combination of multimodal analgesia and VR did not reduce opioid consumption, the practice of incorporating multimodal analgesia as a standard workflow improved.

Aims To evaluate the risk of hepatotoxicity due to unintentional paracetamol misuse in patients with acute dental pain. Methods A prospective multicenter observational survey was performed in patients consulting, without appointment, the odontology departments of three main French hospitals in the Lorraine region over a 3-month period. Patients were asked to fill out a medical questionnaire while seated in the waiting room. Those who completed the questionnaire, had dental pain, and took paracetamol were included in the DAntaLor study. Misuse was defined as a daily dose of more than 4 g of paracetamol per day. The risk of hepatotoxicity was considered high if the supposed ingested dose was above the threshold of 150 mg.kg-1.24h-1, 125 mg.kg-1.24h-1, or 100 mg.kg1.24h-1 over periods of 24, 48, and 72 hours, respectively. Hepatotoxicity was suspected in the presence of clinical symptoms. Results Of the 1,810 patients consulting the odontology departments, 741 were included in the study. Painkillers were used in 74.4% of the cases, and paracetamol was taken by 81.7%. Paracetamol was self-medicated in 85.5% of the patients and misused by 6.0%. Clinical symptoms were observed in 1.6% of the patients with no paracetamol misuse. For patients consuming more than 4 g per day and experiencing mild unspecific clinical symptoms of hepatotoxicity, the suspected ingested dose category was below one of the three previously defined thresholds for 11.8% and was above for 40.0%. Conclusion Patients with dental pain are at risk of paracetamol overdose and hepatotoxicity.

The induced micellar-extraction preconcentration of mefenamic acid, naproxen, and indomethacin on Triton X-100 phases in the presence of salicylic and benzoic acids is studied. The optimal conditions for the preconcentration of analgetics are found: the pH of the solutions and the concentration of analytes. The maximum extraction of analgetics is observed at pH < pKa of the analyte and modifier. An increase in the recovery of analgetics with a decrease in their concentration in the initial solution is shown. A procedure for the determination of non-narcotic analgetics by HPLC with preliminary micellar-extraction concentration on Triton X-100 induced phases is developed. The procedure was used to analyze an urine sample with additives.

Evaluate efficacy and safety of an investigational, twice daily sustained-release (SR) paracetamol formulation in subjects with knee or hip osteoarthritis (OA).In this multicenter, double-blind, parallel study (NCT02311881), subjects with hip or knee OA were randomly assigned to SR paracetamol 2 × 1000 mg BID, extended-release (ER) paracetamol 2 × 665 mg TID or placebo for 12 weeks. Primary endpoint was mean change from baseline through 12 weeks in WOMAC Osteoarthritis Index pain. Secondary efficacy endpoints included other WOMAC categories, Global Patient Assessment of Osteoarthritis (GPAOA), Patient Global Assessment of Response to Therapy (PGART) and responder rate.A total of 676 subjects were included in the analysis population (mITT). Mean change from baseline in WOMAC pain subscale was not significantly greater with SR paracetamol BID versus placebo (LS mean [SE]: -28.25 [1.697] vs. -25.74 [1.713]; p = .163). Reduction in WOMAC physical function and stiffness subscales with SR paracetamol BID was not significantly greater than with placebo (p = .089 and .054, respectively). Significant improvement over placebo was observed for GPAOA (p = .043), PGART (p = .012), and proportion of high-improvement responders (p = .015). Safety and tolerability were consistent with the known profile of paracetamol.Improvement in WOMAC pain, physical function and stiffness subscales from treatment with SR paracetamol BID versus placebo in subjects with knee or hip OA was not significant. SR paracetamol BID demonstrated significant improvements in GPAOA, PGART, and high-responder rate. High placebo response may have contributed to lack of statistical separation on some outcomes. All interventions were generally well tolerated.

Acetaminophen, an analgesic and antipyretic available over-the-counter and used in over 600 medicines, is one of the most consumed drugs in the USA. Recent research has suggested that acetaminophen’s effects extend to the blunting of negative as well as positive affect. Because affect is a determinant of risk perception and risk taking, we tested the hypothesis that acute acetaminophen consumption (1000 mg) could influence these important judgments and decisions. In three double-blind, placebo-controlled studies, healthy young adults completed a laboratory measure of risk taking (Balloon Analog Risk Task) and in Studies 1 and 2 completed self-report measures of risk perception. Across all studies (total n = 545), acetaminophen increased risk-taking behavior. On the more affectively stimulating risk perception measure used in Study 2, acetaminophen reduced self-reported perceived risk and this reduction statistically mediated increased risk-taking behavior. These results indicate that acetaminophen can increase risk taking, which may be due to reductions in risk perceptions, particularly those that are highly affect laden.

Summary The objective of this review was to evaluate the efficacy of non-narcotic analgesics including non-steroidal anti-inflammatory drugs (NSAIDs) and/or paracetamol in the treatment of post-operative endodontic pain. Additionally, we aimed to examine the possible association of study covariates on the pain scores using meta-regression analysis. An electronic search was performed in 2016. After data extraction and quality assessment of the included studies (n = 27, representing 2188 patients), meta-analysis was performed using a random-effect inverse variance method. Meta-regression analysis was conducted to examine the associations between effect sizes and study-level covariates (P

Non-steroidal anti-inflammatory drugs are associated with a dose and duration-dependent coronary risk. There is little information concerning analgesic-dose ibuprofen, among the most widely used drugs worldwide.Our objective was to measure the risks of acute coronary syndrome (ACS) after dispensing of ibuprofen, versus paracetamol.Propensity score 1:2-matched cohorts of ibuprofen or paracetamol treatment episodes (TEs) in Echantillon Généraliste de Bénéficiaires (EGB), the 1/97 sample of Système National des Données de Santé (SNDS), the French nationwide claims database, from 2009 to 2014, were compared. Outcomes were hospital admissions for ACS during the 3 months after the dispensing of ibuprofen or paracetamol. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated overall and stratified on low-dose aspirin dispensing.A total of 315,269 ibuprofen TEs in 168,400 persons were matched to 630,457 paracetamol TEs in 395,952 patients. Event rates were 50-100 times higher in low-dose aspirin users (27 vs 0.28 per 1000 patient years). Overall there was no difference in risk of ACS at 3 months (HR 0.94, 95% CI 0.74-1.20) despite a transient increase in the first 2 weeks in ibuprofen users (HR 1.70, 95% CI 1.11-2.59). In the stratified analysis, this short-term risk was only found in aspirin users (5% of population, HR 1.84, 95% CI 1.24-3.24), but not in non-aspirin users (HR 1.09, 95% CI 0.40-2.94).There was no evidence for an increased risk of ACS in patients dispensed ibuprofen compared to paracetamol.

The group of synthetic low-molecular peptides exhibiting profound analgesic activity was developed by modifying the salmon calcitonin molecule fragment sCT16-21, which retains the previously reported analgesic activity of the full-sized molecule. The mechanism of analgesic action of these synthetic oligopeptides has been investigated and their analgesic effect was compared with analgesic activity of ketorolac tromethamine, one of the strongest non-steroidal anti-inflammatory drug painkiller. It was demonstrated that the analgesic effect of the developed synthetic oligopeptides was associated with the specific binding of the clathrin heavy chain. It is postulated that inhibition of clathrin-mediated endocytosis of pain receptors in the postsynaptic vesicular cycle causes is more efficient analgesia than inhibition of those receptors on plasma membranes that may allow to replace opioid and non-steroidal anti-inflammatory drug’s analgesics with a much less toxic low-molecular synthetic peptides with non-narcotic type of analgesia.

To the editorWe were interested to read the article by Hendrickson on acetylcysteine (NAC) dosing following large overdoses of paracetamol [1]. We wish to make the following observations.Ingesting ...

Critically ill patients commonly experience pain, and the provision of analgesia is an essential component of intensive care unit (ICU) care. Opioids are the mainstay of pain management in the ICU but are limited by their adverse effects, risk of addiction and abuse, and recent drug shortages of injectable formulations. A multimodal analgesia approach, utilizing nonopioid analgesics as adjuncts to opioid therapy, is recommended since they may modulate the pain response and reduce opioid requirements by acting on multiple pain mediators. Nonopioid analgesics discussed in detail in this article are acetaminophen, α-2 receptor agonists, gabapentinoids, ketamine, lidocaine, and nonsteroidal anti-inflammatory drugs. This literature review describes the clinical pharmacology, supportive ICU and relevant non-ICU data, and practical considerations associated with the administration of nonopioid analgesics in critically ill adult patients.

Acupuncture has been used for centuries by practitioners around the world for treatment of a variety of conditions. Even so, limited studies have evaluated the patient population that utilizes acupuncture. We aimed to explore the associations between patient characteristics and utilization of acupuncture services, as well as treatment outcomes. We conducted an exploratory retrospective study of adult patients in a large, eastern Wisconsin medical system that either (1) received acupuncture referral and treatment, (2) received acupuncture referral only, or (3) received treatment only, during 1/2005 - 6/2016. Basic descriptive statistics were performed. Chi-square tests were used to analyze the categorical variables, and t-tests were used to analyze the continuous variables. Among the 1,161 patients identified, 1,057 were seen for a pain related diagnosis of which 93.4% (987) were referred to acupuncture services. The majority of referrals for pain were ordered by primary care (40.5%) and orthopedic (37.3%) physicians. Those who were referred and attended a visit for pain (375; 35.5%) in comparison to those referred only were more likely to be older (57.0 vs 51.9 years; p=

Utilization of hemp stalks (Cannabis sativa L.) for energy purposes is a promising field of its application, so long as it is possible to use for fuel both whole stalk and waste products after its processing (awnchaff). Hemp stalk has a high calorific value, which is slightly inferior to coal, but exceed those for soft wood and peat. Despite intensive breeding works aimed at reducing tetrahydrocannabinol content, it became possible to keep the primary value of the crop that is an ability to form a good yield of stalks and fibre. As a result of many years of breeding work obtained were non-narcotic monoecious hemp varieties Hliana, Hlukhivskiy 46, Hlukhivski 51 with fibre content 30.0 to 38.9%. Of these, the most promising for the fibre production is variety Hlukhivski 51. By fibre yield, this variety exceeds standard one by 1.5 t/ha.

Paracetamol overdose is one of the commonest pharmaceutical poisonings in the world. For nearly four decades, intravenous acetylcysteine regimens have been used to treat most patients successfully and prevent or mitigate hepatotoxicity. However, the rate of occurrence of adverse reactions to acetylcysteine is quite high, and there is a potential for these to be reduced. Recent studies show that distributing the loading-dose of acetylcysteine over the first few hours of treatment may decrease the incidence of adverse reactions. In addition, varying the duration of acetylcysteine administration may potentially benefit certain cohorts of poisoned patients, depending on their risk of developing hepatotoxicity.

Commentary on : da Costa BR, Reichenbach S, Keller N, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet 2017;390:e21–33. Treatment of osteoarthritis includes analgesics, exercise, lifestyle changes, weight loss and other adaptations. Analgesics are often recommended and used together with exercise therapy. Recent studies and reviews support the use of exercise therapy as the first choice of treatment for osteoarthritis, followed by non-steroidal anti-inflammatory drugs (NSAIDs) and other modalities.1–4 However, several NSAIDs are available, and the preferred NSAID and dose for osteoarthritis are different between the available studies and recommendations. This was a network meta-analysis of randomised controlled trials (RCTs) of different doses of NSAIDs or paracetamol …

I read with great interest the recent report by Hickman et al.[1][1] about oral versus i.v. acetaminophen. The authors performed a prospective randomized study of 486 patients undergoing orthopedic surgery and concluded that oral acetaminophen given preoperatively was equivalent to i.v.

Resume Introduction La ketamine est utilisee a doses subanesthesiques pour ses proprietes antinociceptives et d’epargne morphinique chez l’adulte. Chez l’enfant, elle ne produit pas d’effet d’epargne morphinique aux doses allant jusqu’a 0,5 mg/kg. Elle pourrait s’averer cependant efficace afin de reduire les risques lies a l’utilisation de morphine au cours d’une chirurgie a risque telle l’amygdalectomie. L’objectif de l’etude etait d’evaluer la consommation postoperatoire de morphine apres un bolus preoperatoire de 1 mg/kg de ketamine. Patients et methodes Il s’agit d’une etude retrospective, monocentrique, incluant deux groupes de 30 enfants operes dans notre institution. Trente patients etaient consecutivement operes juste avant l’ajout d’un bolus de ketamine de 1 mg/kg au cours de l’induction anesthesique et 30 patients apres la mise en place de cette pratique. Les donnees recueillies etaient : l’âge, le poids, le score ASA, les doses de sufentanil intra-operatoire, la douleur en SSPI, la consommation de morphine en SSPI, la presence de douleur a la realimentation, le score OPS a j1, la consommation de morphine a j1, la presence de nausees ou vomissements postoperatoires, les manifestations psychodysleptiques, l’alimentation a h6 sans douleur et les complications respiratoires ou hemorragiques postoperatoires. Resultats Les deux groupes de patients ne differaient pas en termes de donnees demographiques. On ne retrouve aucune difference de consommation de morphine et de score de douleur en salle de reveil ou au cours des premieres 24 heures postoperatoires, entre les deux groupes. Aucune difference dans les autres donnees n’etait retrouvee. Discussion Notre travail suggere que la ketamine administree a 1 mg/kg a l’induction de l’anesthesie n’a pas d’effet d’epargne morphinique dans le cadre de l’amygdalectomie chez l’enfant.

The purpose of this study is twofold: first, to describe the non-narcotic pathway (NNP) for the management of postoperative pain after robotic pyeloplasty (RP); second, to compare perioperative outcomes for children undergoing RP whose postoperative pain was managed with and without the NNP.A retrospective review was performed on 96 consecutive patients from October 2011 to December 2015 who underwent RP by three primary surgeons at a single pediatric institution. Children managed with an NNP received alternating doses of scheduled intravenous acetaminophen and ketorolac every 3 hours throughout the postoperative course. Perioperative outcomes were compared after grouping patients according to the type of postoperative pain management pathway. Continuous variables were compared using the Mann-Whitney U test, and categorical variables were compared using the two-tailed chi-squared test.A total of 49 (51.0%) patients were managed with the NNP, and 47 (49.0%) patients were managed without the NNP. A larger proportion of patients in the NNP did not receive postoperative narcotic medications (71.4% vs 25.5%; p 0.001). Patients in the NNP were administered less narcotics (median 0.000 mg vs 0.041 mg morphine equivalents/kg/day; p 0.001) and had a shorter length of stay (median 1.0 day vs 2.0 days; p 0.001). There was no significant difference in the proportion of patients with postoperative complications (p = 0.958) or surgical success (p = 0.958).An NNP following pediatric RP is a viable and effective analgesic regimen that is associated with less narcotic use. It may also facilitate a shorter hospital stay. The majority of patients managed with this pathway had adequate pain control without being subject to the potential adverse effects of narcotic medications.

In 2014, the US Food and Drug Administration limited the production of prescription acetaminophen-opioid combination products to 325 mg per dose unit. The goal of this mandate was to decrease the likelihood of unintentional acetaminophen hepatotoxicity. This study was designed to determine if this federal regulation has succeeded in reducing unintentional acetaminophen-induced hepatotoxicity from opioid combination products. Using data from the National Poison Data System (NPDS), we analyzed all calls to US Poison Control Centers in the years 2013 and 2015 for acetaminophen-opioid combination product exposures. We then excluded cases that were classified as intentional and those aged 12 years and younger. We used a primary endpoint of N-acetylcysteine administration; secondary endpoints included evidence of hepatotoxicity as aspartate aminotransferase elevation, opioid antagonist administration and severity of overall medical outcome. A total of 18,259 calls between the two yearlong periods met inclusion criteria. 5.16 and 5.01% of calls resulted in N-acetylcysteine administration in 2013 and 2015, respectively. 3.63 and 4.02% received naloxone in 2013 and 2015, respectively, and 0.9% in each year developed hepatotoxicity. Rates of N-acetylcysteine administration, naloxone administration, and hepatotoxicity did not differ significantly between 2013 and 2015. Severity of medical outcome was worse in 2015 as compared to 2013 with more cases being categorized as “major effect” and fewer cases being categorized as “no effect.” The Food and Drug Administration limitation on acetaminophen content per dose unit in opioid combination products did not reduce the occurrence of unintentional acetaminophen-induced hepatotoxicity or N-acetylcysteine administration as reported to NPDS.

Aim. To evaluate the effectiveness of pre-, intra- and postoperative intravenous administration of paracetamol in combined anesthesia in patients undergoing surgical interventions in the surgical oncology practice. Methods. Examined were 35 patients aged from 43 to 75 years, operated on under combined anesthesia. During the operation and after its completion an infusion of liquid paracetamol at a dose of 3.3 mg/h was performed. Cardiac monitoring was conducted, the content of cortisol in the blood and the Bispectral Index were determined. The pain indices measured by visual analogue and digital rating scales were determined in the postoperative period. The control group included 35 patients in whom anesthesia was performed without the use of paracetamol. Results. During the infusion of paracetamol an adequate level of analgesia was achieved without development of adverse reactions on the part of the vital systems. The use of paracetamol in the early postoperative period contributed to the reduction of pain on digital rating and visual analogue scales compared to the group with basic anesthesia. Conclusion. The use of liquid paracetamol is a promising and safe method of additional analgesia.

Self-emulsifying systems (SES) emulsify spontaneously to produce fine oil-in-water emulsion when introduced into aqueous phase. The self-emulsification process plays an important role during formation of emulsion. The objective of current work was to understand and explore the inner structuration of SES through controlled hydration and further to study the influence of additive on the same which ultimately governs performance of final formulation in terms of droplet size.Droplet size of final formulations containing structural analogues of ibuprofen was determined. Microstructural properties of intermediate hydrated regimes of SES were investigated using techniques such as small angle X-ray scattering, differential scanning calorimetry and rheology.The current work established inverse relationship between droplet size of the formulations containing structural analogues of ibuprofen and their Log P values. Microstructural analysis of intermediate hydrated regimes of the prepared samples showed formation of local lamellar structure. Structural analogues of ibuprofen significantly altered microstructure of lamellae which was well correlated with the droplet size of final formulations. In vitro drug release study showed increase in dissolution rate of lipophillic drugs when formulated as SES.The current work emphasizes the fact that tailor-made formulations can be prepared by controlling the properties of intermediate regimes.