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Poor research reporting is a major contributing factor to low study reproducibility, financial and animal waste. The ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines were developed to improve reporting quality and many journals support these guidelines. The influence of this support is unknown. We hypothesized that papers published in journals supporting the ARRIVE guidelines would show improved reporting compared with those in non-supporting journals. In a retrospective, observational cohort study, papers from 5 ARRIVE supporting (SUPP) and 2 non-supporting (nonSUPP) journals, published before (2009) and 5 years after (2015) the ARRIVE guidelines, were selected. Adherence to the ARRIVE checklist of 20 items was independently evaluated by two reviewers and items assessed as fully, partially or not reported. Mean percentages of items reported were compared between journal types and years with an unequal variance t-test. Individual items and sub-items were compared with a chi-square test. From an initial cohort of 956, 236 papers were included: 120 from 2009 (SUPP; n = 52, nonSUPP; n = 68), 116 from 2015 (SUPP; n = 61, nonSUPP; n = 55). The percentage of fully reported items was similar between journal types in 2009 (SUPP: 55.3 ± 11.5% [SD]; nonSUPP: 51.8 ± 9.0%; p = 0.07, 95% CI of mean difference -0.3–7.3%) and 2015 (SUPP: 60.5 ± 11.2%; nonSUPP; 60.2 ± 10.0%; p = 0.89, 95%CI -3.6–4.2%). The small increase in fully reported items between years was similar for both journal types (p = 0.09, 95% CI -0.5–4.3%). No paper fully reported 100% of items on the ARRIVE checklist and measures associated with bias were poorly reported. These results suggest that journal support for the ARRIVE guidelines has not resulted in a meaningful improvement in reporting quality, contributing to ongoing waste in animal research. [ABSTRACT FROM AUTHOR]

Objective: Hand osteoarthritis poses a significant health challenge globally due to its increasing prevalence and the substantial burden on individuals and the society. In current clinical practice, treatment options for hand osteoarthritis encompass a range of approaches, including biological agents, antimetabolic drugs, neuromuscular blockers, anti-inflammatory drugs, hormone medications, pain relievers, new synergistic drugs, and other medications. Despite the diverse array of treatments, determining the optimal regimen remains elusive. This study seeks to conduct a network meta-analysis to assess the effectiveness and safety of various drug intervention measures in the treatment of hand osteoarthritis. The findings aim to provide evidence-based support for the clinical management of hand osteoarthritis. Methods: We performed a comprehensive search across PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials was conducted until September 15th, 2022, to identify relevant randomized controlled trials. After meticulous screening and data extraction, the Cochrane Handbook's risk of bias assessment tool was applied to evaluate study quality. Data synthesis was carried out using Stata 15.1 software. Results: 21 studies with data for 3965 patients were meta-analyzed, involving 20 distinct Western medicine agents. GCSB-5, a specific herbal complex that mainly regulate pain in hand osteoarthritis, showed the greatest reduction in pain [WMD = -13.00, 95% CI (-26.69, 0.69)]. CRx-102, s specific medication characterized by its significant effect for relieving joint stiffness symptoms, remarkably mitigated stiffness [WMD = -7.50, 95% CI (-8.90, -6.10)]. Chondroitin sulfate displayed the highest incidence of adverse events [RR = 0.26, 95% CI (0.06, 1.22)]. No substantial variation in functional index for hand osteoarthritis score improvement was identified between distinct agents and placebo. Conclusions: In summary, GCSB-5 and CRx-102 exhibit efficacy in alleviating pain and stiffness in HOA, respectively. However, cautious interpretation of the results is advised. Tailored treatment decisions based on individual contexts are imperative. [ABSTRACT FROM AUTHOR]

Pain and inflammation are unpleasant experiences that usually occur as a result of tissue damage. Despite the number of existing analgesic drugs, side effects limit their use, stimulating the search for new therapeutic agents. In this sense, five hydrazone derivatives (H1, H2, H3, H4, and H5), with general structure R1R2C = NNR3R4, were synthesized with molecular modification strategies. In this paper, we describe the ability of hydrazone derivatives to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In both experimental models, the hydrazone with the greatest potency (H5) significantly (p < 0.05) reduced nociceptive behavior. Additionally, methods of acute and chronic inflammation induced by different chemicals (carrageenan and histamine) were performed to evaluate the anti-inflammatory effect of H5. Moreover, molecular docking analysis revealed that H5 can block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. H5 also changes locomotor activity. In summary, H5 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug., Competing Interests: The authors have declared that no competing interests exist.

Background: Sickle cell disease (SCD) induces chronic haemolytic anaemia and intermittent vaso-occlusion that results in tissue ischaemia causing acute, severe pain episodes that can lead to frequent hospitalizations. These consequences can have repercussions on family, social, school and/or professional life. Here, we present some of the results of the PHEDRE study (Pharmacodépendance Et DREpanocytose-drug dependence and sickle-cell disease), which is the largest study of patients with SCD in France. This paper intends to describe characteristics of the French SCD population. We also aimed to assess the impact of the disease on the lives of patients using objective and subjective variables., Methods: The PHEDRE study was a national multicentric observational study. Adults, adolescents and children with a confirmed SCD diagnosis were included in the study by their referring doctor. Then, they were interviewed by phone about their socioeconomic status, about the impact of the disease on their lives and about their analgesic and psychoactive drug use., Results: The study population consisted of 872 patients (28% were minors). Seventy-two percent of adults were active, and all minors were in school. Many patients presented criteria of severe SCD. Seventy-five percent were homozygous SS, 15% were double heterozygotes SC and 8% were heterozygotes Sβthal, 87% received specific treatment, 58% were hospitalized at least once for vaso-occlusive crisis in the past 12 months, and the number of analgesic drugs taken averaged 3.8. Seventy-five percent of patients reported academic or professional consequences related to their SCD, and 52% reported social consequences., Conclusions: The impact of SCD on patients' lives can be significant, nevertheless their social integration seems to be maintained. We highlighted respect of recommendations regarding analgesic treatments and only a few patients used tobacco, alcohol or cannabis., Trial Registration: Clinical Trials, NCT02580565; https://clinicaltrials.gov/ Registered 16 October 2015., Competing Interests: The authors have declared that no competing interests exist.

Background: There is an uncertainty regarding how to optimally prevent and/or reduce pain after dental treatment on children and adolescents., Aim: To conduct a systematic review (SR) and health technology assessment (HTA) of oral analgesics administered after dental treatment to prevent postoperative pain in children and adolescents aged 3-19 years., Design: A PICO-protocol was constructed and registered in PROSPERO (CRD42017075589). Searches were conducted in PubMed, Cochrane, Scopus, Cinahl, and EMBASE, November 2018. The researchers (reading in pairs) assessed identified studies independently, according to the defined inclusion and exclusion criteria, following the PRISMA-statement., Results: 3,963 scientific papers were identified, whereof 216 read in full text. None met the inclusion criteria, leading to an empty SR. Ethical issues were identified related to the recognized knowledge gap in terms of challenges to conduct studies that are well-designed from methodological as well as ethical perspectives., Conclusions: There is no scientific support for the use or rejection of oral analgesics administered after dental treatment in order to prevent or reduce postoperative pain in children and adolescents. Thus, no guidelines can be formulated on this issue based solely on scientific evidence. Well-designed studies on how to prevent pain from developing after dental treatment in children and adolescents is urgently needed., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs), weak and strong opioids are commonly used among elderly persons. The aim of this study was to describe the demographic and clinical characteristics of elderly analgesic users and to measure the frequency of analgesic use, including the frequency of potentially inappropriate analgesic use., Methods: The Arianna database was used to carry out this study. This database contains prescription data with associated indication of use for 1,076,486 inhabitants registered with their general practitioners (GPs) in the Caserta Local Health Unit (Caserta district, Campania region in Italy). A cohort of persons aged ≥65 years old with >1 year of database history having at least one analgesic drug (NSAIDs, strong or weak opioids) between 2010 and 2014 were identified. The date of the first analgesic prescription in the study period was considered the index date (ID)., Results: From a source population of 1,076,486 persons, 116,486 elderly persons were identified. Of these, 94,820 elderly persons received at least one analgesic drug: 36.6% were incident NSAID users (N = 36,629), while 13.2% were incident weak opioid users (N = 12,485) and 8.1% were incident strong opioid users (N = 7,658). In terms of inappropriate analgesic use, 9.2% (N = 10,763) of all elderly users were prescribed ketorolac/indomethacin inappropriately, since these drugs should not be prescribed to elderly persons. Furthermore, at least half all elderly persons with chronic kidney disease or congestive heart failure were prescribed NSAIDs, while these drugs should be avoided., Conclusion: Analgesics are commonly used inappropriately among elderly persons, suggesting that prescribing practice in the catchment area may yet be improved., Competing Interests: YI, JS, FG, EM, AS, MT, DUT, GB and GT have no conflict of interest related to the study. GT has attended advisory boards on topics not related to this paper in the last 10 years, organized by Sandoz, Hospira, Sanofi, Biogen, Ibsen, Shire, and is consultant for Otsuka. He is the principal investigator of observational studies funded by several pharmaceutical companies (e.g. Amgen, AstraZeneca, Daiichi Sankyo, IBSA) to University of Messina as well as scientific coordinator of the Master program “Pharmacovigilance, pharmacoepidemiology and pharmacoeconomics: real-world data evaluations” at University of Messina which is partly funded by several pharmaceutical companies.

Background: Low-dose aspirin has been shown to reduce the incidence of cancer, but its role in the treatment of cancer is uncertain. Objectives: We conducted a systematic search of the scientific literature on aspirin taken by patients following a diagnosis of cancer, together with appropriate meta-analyses. Methods: Searches were completed in Medline and Embase in December 2015 using a pre-defined search strategy. References and abstracts of all the selected papers were scanned and expert colleagues were contacted for additional studies. Two reviewers applied pre-determined eligibility criteria (cross-sectional, cohort and controlled studies, and aspirin taken after a diagnosis of cancer), assessed study quality and extracted data on cancer cause-specific deaths, overall mortality and incidence of metastases. Random effects meta-analyses and planned sub-group analyses were completed separately for observational and experimental studies. Heterogeneity and publication bias were assessed in sensitivity analyses and appropriate omissions made. Papers were examined for any reference to bleeding and authors of the papers were contacted and questioned. Results: Five reports of randomised trials were identified, together with forty two observational studies: sixteen on colorectal cancer, ten on breast and ten on prostate cancer mortality. Pooling of eleven observational reports of the effect of aspirin on cause-specific mortality from colon cancer, after the omission of one report identified on the basis of sensitivity analyses, gave a hazard ratio (HR) of 0.76 (95% CI 0.66, 0.88) with reduced heterogeneity (P = 0.04). The cause specific mortality in five reports of patients with breast cancer showed significant heterogeneity (P<0.0005) but the omission of one outlying study reduced heterogeneity (P = 0.19) and led to an HR = 0.87 (95% CI 0.69, 1.09). Heterogeneity between nine studies of prostate cancer was significant, but again, the omission of one study led to acceptable homogeneity (P = 0.26) and an overall HR = 0.89 (95% CI 0.79–0.99). Six single studies of other cancers suggested reductions in cause specific mortality by aspirin, and in five the effect is statistically significant. There were no significant differences between the pooled HRs for the three main cancers and after the omission of three reports already identified in sensitivity analyses heterogeneity was removed and revealed an overall HR of 0.83 (95% CI 0.76–0.90). A mutation of PIK3CA was present in about 20% of patients, and appeared to explain most of the reduction in colon cancer mortality by aspirin. Data were not adequate to examine the importance of this or any other marker in the effect of aspirin in the other cancers. On bleeding attributable to aspirin two reports stated that there had been no side effect or bleeding attributable to aspirin. Authors on the other reports were written to and 21 replied stating that no data on bleeding were available. Conclusions and Implications: The study highlights the need for randomised trials of aspirin treatment in a variety of cancers. While these are awaited there is an urgent need for evidence from observational studies of aspirin and the less common cancers, and for more evidence of the relevance of possible bio-markers of the aspirin effect on a wide variety of cancers. In the meantime it is urged that patients in whom a cancer is diagnosed should be given details of this research, together with its limitations, to enable each to make an informed decision as to whether or not to take low-dose aspirin. Systematic Review Protocol Number: CRD42015014145 [ABSTRACT FROM AUTHOR]

Pain and inflammation are complex clinical conditions that are present in a wide variety of disorders. Most drugs used to treat pain and inflammation have potential side effects, which makes it necessary to search for new sources of bioactive molecules. In this paper, we describe the ability of LASSBio-1586, an N-acylhydrazone derivative, to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In these experimental models, LASSBio-1586 significantly (p<0.05) reduced nociceptive behavior. Several methods of acute and chronic inflammation induced by different chemical (carrageenan, histamine, croton oil, arachidonic acid) and physical (cotton pellet) agents were used to evaluate the anti-inflammatory effect of LASSBio-1586. LASSBio-1586 exhibited potent anti-inflammatory activity in all tests (p<0.05). Study of the mechanism of action demonstrated the possible involvement of the nitrergic, serotonergic and histamine signaling pathways. In addition, a molecular docking study was performed, indicating that LASSBio-1586 is able to block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. In summary, LASSBio-1586 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Opioids are one of the most important and effective drug classes in pain medicine with a key role in most medical fields. The increase of opioid prescription over time has led to higher numbers of prescription opioid misuse, abuse and opioid-related deaths in most developed OECD (Organisation for Economic Co-operation and Development) countries around the world. Whilst reliable data on the prevalence of opioid treatment is accessible for many countries, data on Germany specifically is still scarce. Considering Germany being the largest country in the European Union, the lack of evidence-based strategies from long-term studies is crucial. The aim of this work is to review and summarise relevant published literature on the prevalence of opioid prescription in Germany to adequately inform health policy strategies. Methods: A systematic review of the epidemiology of opioid prescription in Germany was conducted, searching PubMed and Web of Science. Eligibility criteria were defined prior to conducting the search. Literature concerning Germany, published in English and German was included and the search was replicated by three independent researchers. Two levels of screening were employed. Disagreement was resolved by face-to-face discussion, leading to a consensus judgement. Results: Our electronic search yielded 735 articles. Reviewing titles and abstracts yielded 19 relevant articles. Three authors examined each article’s full text more closely and determined that twelve papers should be included. Of the twelve identified studies—with publication dates ranging from 1985 to 2016—six were retrospective cross-sectional studies and six were retrospective repeated-measures cross-sectional studies. Sample sizes ranged from 92,842 to ≈ 11,000,000 participants. Data sources of included studies showed vast heterogeneity. The reviewed literature suggested an increase in the number of patients with opioid prescriptions and defined daily doses of opioids per recipient in Germany over time. The majority of opioid prescriptions was used for patients with non-cancer pain. Opioid use was more common in older people, women and in the north of Germany. Fentanyl was shown to be the most prescribed strong opioid in outpatient settings in Germany, despite not being the first-line choice for chronic pain conditions. All data published before 2000—but none of the more recent studies—suggested an insufficient treatment of pain using opioids. There were no signs for a current opioid epidemic in Germany. Conclusions: Despite some limitations of the review and the heterogeneity of studies, it can be stated that the number of opioid prescriptions overall as well as the number of people receiving opioid treatment have increased over time. Most prescriptions were found to be for strong opioids and patients with non-cancer pain. Even though patterns of opioid prescription follow trends observed in other developed countries, there are no signs of an opioid epidemic in Germany. Therefore, this review could currently not find a need for urgent health policy interventions regarding opioid prescription practices. However, critical gaps in the literature remain and more research is needed to make more reliable judgements. [ABSTRACT FROM AUTHOR]

Background: This study reports on physicians’ experiences with chronic pain management. For over a decade prescription opioids have been a primary treatment for chronic pain in North America. However, the current opioid epidemic has complicated long-standing practices for chronic pain management which historically involved prescribing pain medication. Caring for patients with chronic pain occurs within a context in which a growing proportion of patients suffer from chronic rather than acute conditions alongside rising social inequities. Methods: Our team undertook an ethnographic approach known as institutional ethnography in the province of Ontario, Canada in order to explore the social organization of chronic pain management from the standpoint of primary care physicians. This paper reports on a subset of this study data, specifically interviews with 19 primary care clinicians and 8 nurses supplemented by 40 hours of observations. The clinicians in our sample were largely primary care physicians and nurses working in urban, rural and Northern settings. Findings: In their reflections on providing care for patients with chronic pain, many providers describe being most challenged by the work involved in helping patients who also struggled with poverty, mental health and addiction. These frustrations were often complicated by concerns that they could lose their license for inappropriate prescribing, thus shifting their work from providing treatment and care to policing their patients for malingering and opioid abuse. Interpretation: Our findings show that care providers find the treatment of patients with chronic pain–especially those patients also experiencing poverty–to be challenging at best, and at worst frustrating and overwhelming. In many instances, their narratives suggested experiences of depersonalization, loss of job satisfaction and emotional exhaustion in relation to providing care for these patients, key dimensions of burnout. In essence, the work that they performed in relation to their patients’ social rather than medical needs seems to contribute to these experiences. Their experiences were further exacerbated by the fact that restricting and reducing opioid dosing in patients with chronic pain has become a major focus of care provision. [ABSTRACT FROM AUTHOR]

Opioids are widely used for treating different types of pains, but overuse and abuse of prescription opioids have led to opioid epidemic in the United States. Besides analgesic effects, chronic use of opioid can also cause tolerance, dependence, and even addiction. Effective treatment of opioid addiction remains a big challenge today. Studies on addictive effects of opioids focus on striatum, a main component in the brain responsible for drug dependence and addiction. Some transcription regulators have been associated with opioid addiction, but relationship between analgesic effects of opioids and dependence behaviors mediated by them at the molecular level has not been thoroughly investigated. In this paper, we developed a new computational strategy that identifies novel targets and potential therapeutic molecular compounds for opioid dependence and addiction. We employed several statistical and machine learning techniques and identified differentially expressed genes over time which were associated with dependence-related behaviors after exposure to either morphine or heroin, as well as potential transcription regulators that regulate these genes, using time course gene expression data from mouse striatum. Moreover, our findings revealed that some of these dependence-associated genes and transcription regulators are known to play key roles in opioid-mediated analgesia and tolerance, suggesting that an intricate relationship between opioid-induce pain-related pathways and dependence may develop at an early stage during opioid exposure. Finally, we determined small compounds that can potentially target the dependence-associated genes and transcription regulators. These compounds may facilitate development of effective therapy for opioid dependence and addiction. We also built a database () for all opioid-induced dependence-associated genes and transcription regulators that we discovered, as well as the small compounds that target those genes and transcription regulators. [ABSTRACT FROM AUTHOR]

Background: Motor cortex stimulation (MCS) was introduced as a last-resort treatment for chronic neuropathic pain. Over the years, MCS has been used for the treatment of various pain syndromes but long-term follow-up is unknown. Methods: This paper reports the results of MCS from 2005 until 2012 with a 3-year follow-up. Patients who suffered from chronic neuropathic pain treated with MCS were studied. The analgesic effect was determined as successful by decrease in pain-intensity on the visual analog scale (VAS) of at least 40%. The modifications in drug regimens were monitored with use of the medication quantification scale (MQS). Stimulation parameters and complications were also noted. Interference of pain with quality of life (QoL), the Quality of Life Index (QLI), was determined with use of a specific subset of questions from the MPQ-DLV score. Results: Eighteen patients were included. Mean pre-operative VAS changed from 89.4 ± 11.2 to 53.1 ± 25.0 after three years of follow-up (P < 0.0001). A successful outcome was achieved in seven responders (38.9%). All patients in the responder group suffered from pain caused by a central lesion. With regard to all the patients with central pain lesions (n = 10) and peripheral lesions (n = 8), a significant difference in response to MCS was noticed (P = 0.002). MQS scores and QLI-scores diminished during the follow-up period (P = 0.210 and P = 0.007, respectively). Conclusion: MCS seems a promising therapeutic option for patients with refractory pain syndromes of central origin. [ABSTRACT FROM AUTHOR]

Background: Recently, the need for rapid wound-healing has significantly increased because of the increasing number of patients who are diagnosed with diabetes and obesity. These conditions have contributed to a surge in the number of patients with chronic wounds worldwide. Furthermore, many cost-effective wound-healing technologies have been developed in order to keep up with the increased demand. In this paper, we performed a quantitative study of the trends associated with wound-healing technologies using patent data. Methodology: We analyzed the trends considering four different groups of patent applicants: firms, universities, research institutes, and individuals using a structural topic model. In addition, we analyzed the knowledge flow between patent applicants using citation analysis, and confirmed the role of applicants in the knowledge-flow network using k-means clustering. As a result, the primary wound-healing technology patents applied for by the four groups varied considerably, and we classified the roles of patent applicants were found in the knowledge-flow network. Conclusions: Our results showed the organizations that are leading each area of wound-healing technology. Furthermore, from the results, we identified specific institutions that are efficient for spreading knowledge related to wound-healing technology based on the patents. This information can contribute to the planning of investment strategies and technology policies related to wound-healing. [ABSTRACT FROM AUTHOR]

Objectives: To systematically review the literature comparing the efficacy and safety of dexmedetomidine and midazolam when used for procedural sedation. Materials and Methods: We searched MEDLINE, EMBASE and COCHRANE for clinical trials comparing dexmedetomidine and midazolam for procedural sedation up to June 20, 2016. Inclusion criteria: clinical trial, human subjects, adult subjects (≥18 years), article written in English, German, French or Dutch, use of study medication for conscious sedation and at least one group receiving dexmedetomidine and one group receiving midazolam. Exclusion criteria: patients in intensive care, pediatric subjects and per protocol use of additional sedative medication other than rescue medication. Outcome measures for efficacy comparison were patient and clinician satisfaction scores and pain scores; outcome measures for safety comparison were hypotension, hypoxia, and circulatory and respiratory complications. Results: We identified 89 papers, of which 12 satisfied the inclusion and exclusion criteria; 883 patients were included in these studies. Dexmedetomidine was associated with higher patient and operator satisfaction than midazolam. Patients receiving dexmedetomidine experienced less pain and had lower analgesic requirements. Respiratory and hemodynamic safety were similar. Conclusions: Dexmedetomidine is a promising alternative to midazolam for use in procedural sedation. Dexmedetomidine provides more comfort during the procedure for the patient and clinician. If carefully titrated, the safety profiles are similar. [ABSTRACT FROM AUTHOR]

Usage and reporting of analgesia in animal models of spinal cord injury (SCI) have been sparse and requires proper attention. The majority of experimental SCI research uses rats as an animal model. This study aimed to probe into the effects of some commonly used regimens with NSAIDs and opioids on well-being of the rats as well as on the functional outcome of the model. This eight-week study used forty-two female Wistar rats (Crl: WI), randomly and equally divided into 6 treatment groups, viz. I) tramadol (5mg/kg) and buprenorphine (0.05mg/kg); II) carprofen (5mg/kg) and buprenorphine (0.05mg/kg); III) carprofen (5mg/kg); IV) meloxicam (1mg/kg) and buprenorphine (0.05mg/kg); V) meloxicam (1mg/kg); and VI) no analgesia (0.5 ml sterile saline). Buprenorphine was administered twice daily whereas other treatments were given once daily for five days post-operatively. Injections were given subcutaneously. All animals underwent dental burr-assisted laminectomy at the T10-T11 vertebra level. A custom-built calibrated spring-loaded 200 kilodynes force deliverer was used to induce severe SCI. Weekly body weight scores, Rat Grimace Scale (RGS), and dark-phase home cage activity were used as markers for well-being. Weekly Basso Beattie and Bresnahan (BBB) scores served as markers for functionality together with Novel Object Recognition test (NOR) at week 8 and terminal histopathology using area of vacuolisation and live neuronal count from the ventral horns of spinal cord. It was concluded that the usage of analgesia improved animal wellbeing while having no effects on the functional aspects of the animal model in comparison to the animals that received no analgesics. [ABSTRACT FROM AUTHOR]

Background: Therapeutic hypothermia (TH) is a widely practiced neuroprotective strategy for neonates with hypoxic-ischemic encephalopathy. Induced hypothermia is associated with shivering, cold pain, agitation, and distress. Objective: This scoping review determines the breadth of research undertaken for pain and stress management in neonates undergoing hypothermia therapy, the pharmacokinetics of analgesic and sedative medications during hypothermia and the effect of such medication on short- and long-term neurological outcomes. Methods: We searched the following online databases namely, (i) MEDLINE, (ii) Web of Science, (iii) Cochrane Library, (iv) Scopus, (v) CINAHL, and (vi) EMBASE to identify published original articles between January 2005 and December 2022. We included only English full-text articles on neonates treated with TH and reported the sedation/analgesia strategy used. We excluded articles that reported TH on transport or extracorporeal membrane oxygenation, did not report the intervention strategies for sedation/analgesia, and reported hypoxic-ischemic encephalopathy in which hypothermia was not applied. Results: The eligible publications (n = 97) included cohort studies (n = 72), non-randomized experimental studies (n = 2), pharmacokinetic studies (n = 4), dose escalation feasibility trial (n = 1), cross-sectional surveys (n = 5), and randomized control trials (n = 13). Neonatal Pain, Agitation, and Sedation Scale (NPASS) is the most frequently used pain assessment tool in this cohort. The most frequently used pharmacological agents are opioids (Morphine, Fentanyl), benzodiazepine (Midazolam) and Alpha2 agonists (Dexmedetomidine). The proportion of neonates receiving routine sedation-analgesia during TH is center-specific and varies from 40–100% worldwide. TH alters most drugs' metabolic rate and clearance, except for Midazolam. Dexmedetomidine has additional benefits of thermal tolerance, neuroprotection, faster recovery, and less likelihood of seizures. There is a wide inter-individual variability in serum drug levels due to the impact of temperature, end-organ dysfunction, postnatal age, and body weight on drug metabolism. Conclusions: No multidimensional pain scale has been tested for reliability and construct validity in hypothermic encephalopathic neonates. There is an increasing trend towards using routine sedation/analgesia during TH worldwide. Wide variability in the type of medication used, administration (bolus versus infusion), and dose ranges used emphasizes the urgent need for standardized practice recommendations and guidelines. There is insufficient data on the long-term neurological outcomes of exposure to these medications, adjusted for underlying brain injury and severity of encephalopathy. Future studies will need to develop framework tools to enable precise control of sedation/analgesia drug exposure customized to individual patient needs. [ABSTRACT FROM AUTHOR]

Several uncorroborated, false, or misinterpreted conceptions have for years been widely distributed in academic publications, thus becoming scientific myths. How can such misconceptions persist and proliferate within the inimical environment of academic criticism? Examining 613 articles we demonstrate that the reception of three myth-exposing publications is skewed by an ‘affirmative citation bias’: The vast majority of articles citing the critical article will affirm the idea criticized. 468 affirmed the myth, 105 were neutral, while 40 took a negative stance. Once misconceptions proliferate wide and long enough, criticizing them not only becomes increasingly difficult, efforts may even contribute to the continued spreading of the myths. [ABSTRACT FROM AUTHOR]

There are many defined risk factors for wound healing. Comorbidities and their treatment are identified to be one of them. The aim of this study is to verify whether there are significant differences in wound healing between patients with and without systemic diseases, who underwent hallux valgus correction with Scarf osteotomy. A total of 155 consecutive patients were included into this prospective study. All of the patients underwent Scarf osteotomy for hallux valgus correction. In 60,6% of patients comorbidities were present, most often hypertension (57 patients, 36,8%), hypothyroidism (19 patients 12,3%) and diabetes (7 patients, 4,5%) occurred. Most of the patients were women (96,1%). During the study complication rate was noted. Patients underwent follow-up: 1,2, 3, 6 and 12 weeks and 6 months after the surgery. Preoperatively and during the last visit treatment results were assessed with AOFAS HMI scale. Scar assessment was performed by independent observer with VAS followed by patient scar assessment with VSS. In 30 patients complications were noted (19,4%). Surgical site infection was found in 6 patients (3,9%). In 13 patients (8,4%) partial wound dehiscence occurred, in 5 of them (3,2%) additional skin closure (Steri-Strips) was applied. Treatment results assessed with AOFAS HMI scale were good and very good in both healthy and comorbidity group, and the results improved significantly after surgical procedure. Scar assessment with VAS was on the average 1,5 pts. Average result in VSS was 2 pts. Results in both scales were rated as very good. No statistically significant differences were found in both healthy and comorbidity group in scar assessment. Based on the results of the study authors believe there are no significant differences between patients with and without comorbidities in aspects like: complication rate, surgery result and scar assessment as long as foot surgery is concerned. [ABSTRACT FROM AUTHOR]

Background: Mixtures ('cocktails') of various analgesics are more effective in controlling post-operative pain because of potential synergetic effects. Few studies have investigated such effects in large combinations of analgesics and no studies have determined the probabilities of effectiveness. Methods: We used one-hot encoding of the categorical variables reported pain levels and the administered cocktails (from a total of eight analgesics) and then applied an unsupervised neural network and then the unsupervised DBSCAN algorithm to detect clusters of cocktails. We used Bayesian statistics to classify the effectiveness of these cocktails. Results: Of the 61 different cocktails administered to 750 patients, we found that four combinations of three to four analgesics were by far the most effective. All these cocktails contained Metamizole and Paracetamol; three contained Hydromorphone and two contained Diclofenac and one Diclofenac-Orphenadrine. The ML probability that these cocktails decreased pain levels ranged from 0.965 to 0.981. Choice of a most effective cocktail involves choosing the optimum in a 4-dimensional parameter space: maximum probability of efficacy, confidence interval about maximum probability, fraction of patients with increase in pain levels, relative number of patients with successful pain level decrease. Conclusions: We observed that administering one analgesic or at most two is not effective. We found no statistical indicators that interactions between analgesics in the most effective cocktails decreased their effectiveness. Pairs of most effective cocktails differed by the addition of only one analgesic (Diclofenac-Orphenadrine for one pair and Hydromorphone for the other). We conclude that the listed cocktails are to be recommended. [ABSTRACT FROM AUTHOR]

Scientists who perform major survival surgery on laboratory animals face a dual welfare and methodological challenge: how to choose surgical anesthetics and post-operative analgesics that will best control animal suffering, knowing that both pain and the drugs that manage pain can all affect research outcomes. Scientists who publish full descriptions of animal procedures allow critical and systematic reviews of data, demonstrate their adherence to animal welfare norms, and guide other scientists on how to conduct their own studies in the field. We investigated what information on animal pain management a reasonably diligent scientist might find in planning for a successful experiment. To explore how scientists in a range of fields describe their management of this ethical and methodological concern, we scored 400 scientific articles that included major animal survival surgeries as part of their experimental methods, for the completeness of information on anesthesia and analgesia. The 400 articles (250 accepted for publication pre-2011, and 150 in 2014–15, along with 174 articles they reference) included thoracotomies, craniotomies, gonadectomies, organ transplants, peripheral nerve injuries, spinal laminectomies and orthopedic procedures in dogs, primates, swine, mice, rats and other rodents. We scored articles for Publication Completeness (PC), which was any mention of use of anesthetics or analgesics; Analgesia Use (AU) which was any use of post-surgical analgesics, and Analgesia Completeness (a composite score comprising intra-operative analgesia, extended post-surgical analgesia, and use of multimodal analgesia). 338 of 400 articles were PC. 98 of these 338 were AU, with some mention of analgesia, while 240 of 338 mentioned anesthesia only but not post-surgical analgesia. Journals’ caliber, as measured by their 2013 Impact Factor, had no effect on PC or AU. We found no effect of whether a journal instructs authors to consult the ARRIVE publishing guidelines published in 2010 on PC or AC for the 150 mouse and rat articles in our 2014–15 dataset. None of the 302 articles that were silent about analgesic use included an explicit statement that analgesics were withheld, or a discussion of how pain management or untreated pain might affect results. We conclude that current scientific literature cannot be trusted to present full detail on use of animal anesthetics and analgesics. We report that publication guidelines focus more on other potential sources of bias in experimental results, under-appreciate the potential for pain and pain drugs to skew data, and thus mostly treat pain management as solely an animal welfare concern, in the jurisdiction of animal care and use committees. At the same time, animal welfare regulations do not include guidance on publishing animal data, even though publication is an integral part of the cycle of research and can affect the welfare of animals in studies building on published work, leaving it to journals and authors to voluntarily decide what details of animal use to publish. We suggest that journals, scientists and animal welfare regulators should revise current guidelines and regulations, on treatment of pain and on transparent reporting of treatment of pain, to improve this dual welfare and data-quality deficiency. [ABSTRACT FROM AUTHOR]

Background: Polypharmacy is potentially harmful and under-researched amongst the fastest growing subpopulation, the very old (aged ≥85). We aimed to characterise polypharmacy using data from the Newcastle 85+ Study—a prospective cohort of people born in 1921 who turned 85 in 2006 (n = 845). Methods: The prevalence of polypharmacy at baseline (mean age 85.5) was examined using cut-points of 0, 1, 2–4, 5–9 and ≥10 medicines—so-called 'no polypharmacy', 'monotherapy', 'minor polypharmacy', 'polypharmacy' and 'hyperpolypharmacy.' Cross-tabulations and upset plots identified the most frequently prescribed medicines and medication combinations within these categories. Mixed-effects models assessed whether gender and socioeconomic position were associated with prescribing changes over time (mean age 85.5–90.5). Participant characteristics were examined through descriptive statistics. Results: Complex multimorbidity (44.4%, 344/775) was widespread but hyperpolypharmacy was not (16.0%, 135/845). The median medication count was six (interquartile range 4–8). Preventative medicines were common to all polypharmacy categories, and prescribing regimens were diverse. Nitrates and oral anticoagulants were more frequently prescribed for men, whereas bisphosphonates, non-opioid analgesics and antidepressants were more common in women. Cardiovascular medicines, including loop diuretics, tended to be more frequently prescribed for socioeconomically disadvantaged people (<25th centile Index of Multiple Deprivation (IMD)), despite no difference in the prevalence of cardiovascular disease (p = 0.56) and diabetes (p = 0.92) by IMD. Conclusion: Considering their complex medical conditions, prescribing is relatively conservative amongst 85-year-olds living in North East England. Prescribing shows significant gender and selected socioeconomic differences. More support for managing preventative medicines, of uncertain benefit, might be helpful in this population. [ABSTRACT FROM AUTHOR]

An effective and pain-free killing method is required to achieve the goal of euthanasia, a "good death". Overdose of sodium pentobarbital (PB) by intraperitoneal (IP) injection is a widely accepted technique in laboratory rats, but questions remain regarding pain associated with administration. As PB rapidly causes sedation and loss of consciousness, most studies have relied on indirect evidence of pain. The objective of this study was to assess pain associated with IP PB using an appropriate vehicle control. Adult male and female Sprague Dawley (SD) and female Wistar rats (N = 84) were block randomised by sex and strain to receive one of three treatments: 1) 800 mg/kg PB (pH 11), 2) saline or 3) vehicle controls (pH 11 or 12.5). Behavior (Rat Grimace Scale (RGS), writhing, back arching) was evaluated at baseline, before loss of righting reflex (LORR, PB group), and at 80s, 151s and 10 min post-injection (PI; saline and vehicle control groups). In the PB group, mean time to LORR was 78 ± 7.9 seconds. In the vehicle control groups, RGS scores were increased at 151s PI (SD: p = 0.0002, 95%CI 0.73 to 0.20) from baseline, as was relative frequency of writhing (SD: p < 0.0001; Wistar; p = 0.0004). RGS scores remained elevated 10 mins PI (SD: p = 0.0005, 95%CI 0.71 to 0.18; Wistar: p = 0.0234, 95%CI 0.91 to 0.07) but the relative frequency of writhing did not (p > 0.999). The RGS scores and the relative frequency of writhing remained low in the PB and saline groups (p > 0.05). These results show that, vehicle controls for IP PB result in signs associated with pain, pain may not be experienced following IP PB when LORR occurs quickly, and that the effects of PB limit behavioral pain assessments. [ABSTRACT FROM AUTHOR]

Recent research shows that preschool children born to opioid-dependent mothers are at increased risk for cognitive, psychomotor, attention, and social-emotional adjustment problems. But very little is known about their school-age functioning, particularly their educational achievement. This analysis examined the educational outcomes of a regional cohort of 100 prenatally methadone-exposed children who were prospectively studied from birth to age 9.5 years alongside a comparison group of 110 randomly identified non-exposed children born between 2003 and 2008. At age 9.5, as part of a comprehensive neurodevelopmental evaluation, children's teachers rated their achievement across the school curriculum, and children completed the Woodcock Johnson-III Tests of Achievement (WJ-III). Detailed information about the birth mother's social background, pregnancy substance use, and mental health was also collected during pregnancy/at term. Infant clinical data were collected after birth. Methadone-exposed children performed less well than non-exposed children across seven school curriculum areas rated by teachers (ps ≤.001), performed less well than non-exposed children on all reading and mathematics subtests of the WJ-III, and had higher rates of any educational delay on the WJ-III (57% vs. 15%), OR = 7.47 (3.71–15.02). Results were similar when children with severe intellectual impairment were excluded. After adjusting for confounding factors, methadone-exposed children had increased odds of educational delay, but this was only marginally significant (OR = 3.62, [1.01–13.01], p = .049). Maternal educational attainment level (OR = 0.69, [0.50–0.89], p = .006), and maternal benzodiazepine use during pregnancy (OR = 2.70 [1.03–7.12], p = .044) were also associated with later educational risk. Findings suggest that children born to opioid-dependent women enrolled in methadone maintenance are at high risk of educational delay by age 9.5 years. Children's academic difficulties appeared to reflect the effects of both adverse prenatal exposures and postnatal social risk. [ABSTRACT FROM AUTHOR]

Opioid prescriptions for chronic pain and subsequent opioid-related complications have risen dramatically in the US. Recent data suggest that medical marijuana laws have been associated with lower state-level opioid overdose mortality. In a national survey, we examined the prevalence of substitution of marijuana for opioids among US adults taking opioids for pain.Using GfK’s KnowledgePanel, we conducted an Internet-based survey of a nationally representative sample of 16,280 adults in 2017 about individual perceptions and use of marijuana. We developed questions designed to assess the extent and reasons for substitution of marijuana for opioids. We examined opioid substitution among respondents with a history of ever using marijuana who used opioids in the past 12 months. There were 9,003 respondents, corresponding to a 55.3% response rate. The mean age was 48 years. Among the 5% (n = 486) who reported ever using marijuana and using opioids in the past year, 43% used opioids daily, and 23% reported current (past 30 day) marijuana use. Forty-one percent reported a decrease or cessation of opioid use due to marijuana use; 46% reported no change in opioid use; and 8% reported an increase in opioid use. We found that a substantial number of US adults reported that they substituted marijuana for opioids. [ABSTRACT FROM AUTHOR]

Recently, the United States Food and Drug Administration approved a new oral dosage preparation of amlodipine besylate (AML) and celecoxib (CEL) for the management of hypertension and osteoarthritis. However, no simultaneous estimation procedures for these two analytes have been described. Hence, two simple, accurate, and precise ultraviolet spectroscopic procedures that manipulated the ratio spectra were established for concurrent quantification of AML and CEL using ethanol as a solvent. The first method involves determining the peak-to-trough amplitude difference of the ratio spectra of AML and CEL. The second method involves determining the peak amplitude of the ratio first derivative (Δλ 4 nm) spectra of AML and CEL at 334.2 nm and 254.2 nm, correspondingly. Both methods showed linearity in the range of 1–6 μg mL-1 for AML and 5–40 μg mL-1 for CEL with an excellent correlation coefficient (<0.999). The proposed procedures were validated by following the International Conference on Harmonization guidelines for accuracy, precision, selectivity, recovery, and stability studies. It is evident from the low %RSD and %RE that both analytical procedures were found to be accurate and precise, respectively. The percent recovery of AML and CEL from the formulation was found to be 99.79% and 99.34% using the ratio-difference method and 100.13% and 99.70% using the ratio first-derivative method, with a low percent relative standard deviation. Further, the proposed techniques permit concurrent quantification of AML and CEL in different concentration ratios without interference from each other; hence, these techniques can be adopted for regular quality-control studies. [ABSTRACT FROM AUTHOR]

Syzygium cumini (S. cumini) is an evergreen tropical plant that is well recognized for its therapeutic potential of common diseases. In this study, the therapeutic potential and biomedical application of S. cumini are assessed in vitro and in vivo to find its effectiveness for different complications. The methanolic crude extract of S. cumini leaves were screened for total phenolic and flavonoid content. In vitro, the DPPH scavenging assay, XTT assay, prothrombin and activated partial thromboplastin time were used to assess antioxidant, cytoprotective and thrombolytic activity of the S. cumini extract, respectively. The anti-inflammatory potential and the analgesic activity of the S. cumini extract were analyzed in rabbits by the Carrageenan induced paw edema method and the writhing method, respectively. Phytochemical analysis showed the presence of considerable amounts of total phenolic (369.75 ± 17.9 mg GAE/g) and flavonoid (75.8 ± 5.3 mgRE/g) content in the S. cumini extract. The DPPH assay demonstrated a higher antioxidant potential (IC-50 value of 133 μg/ml), which was comparable to the IC-50 of ascorbic acid (122.4 μg/ml). Moreover, the S. cumini extract showed a dose dependent cytoprotective effect against H2O2 treated bone marrow mesenchymal stem cells (BM-MSCs). S. cumini also possesses significant anticoagulant activity with a prothrombin time of 28.3 ± 1.8 seconds vs 15.8 ± 0.2 seconds of control, p<0.05. The leaf extract also demonstrated an analgesic effect in rabbits as indicated by the decrease in writhing (12.2 ± 1.7 control vs. 3.7 ± 0.6 treated) and anti-inflammatory activity in rabbits paw with a protection against inflammation of 64.1 ± 2.4%. Our findings suggest that the methanolic extract of S. cumini leaves has antioxidant, cytoprotective, anticoagulant, analgesic and anti-inflammatory properties, and therefore, can be applied for treating cardiovascular diseases and cancers. [ABSTRACT FROM AUTHOR]

Background: In light of the opioid epidemic in the United States, there is growing concern about the use of opioids in Sweden as it may lead to misuse and overuse and, in turn, severe public health problems. However, little is known about the distribution of opioid use across different demographic and socioeconomic dimensions in the Swedish general population. Therefore, we applied an intersectional Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA), to obtain an improved mapping of the risk heterogeneity of and socioeconomic inequalities in opioid prescription receipt. Methods and findings: Using data from 6,846,106 residents in Sweden aged 18 and above, we constructed 72 intersectional strata from combinations of gender, age, income, cohabitation status, and presence or absence of psychological distress. We modelled the absolute risk (AR) of opioid prescription receipt in a series of multilevel logistic regression models distinguishing between additive and interaction effects. By means of the Variance Partitioning Coefficient (VPC) and the area under the receiver operating characteristic curve (AUC), we quantified the discriminatory accuracy (DA) of the intersectional strata for discerning those who received opioid prescriptions from those who did not. The AR of opioid prescription receipt ranged from 2.77% (95% CI 2.69–2.86) among low-income men aged 18–34, living alone, without psychological distress, to 28.25% (95% CI 27.95–28.56) among medium-income women aged 65 and older, living alone, with psychological distress. In a model that conflated both additive and interaction effects, the intersectional strata had a fair DA for discerning opioid users from non-users (VPC = 13.2%, AUC = 0.68). However, in the model that decomposed total effects into additive and interaction effects, the VPC was very low (0.42%) indicating the existence of small interaction effects for a number of the intersectional strata. Conclusions: The intersectional MAIHDA approach aligns with the aims of precision public health, through improving the evidence base for health policy by increasing understanding of both health inequalities and individual heterogeneity. This approach is particularly relevant for socioeconomically conditioned outcomes such as opioid prescription receipt. We have identified intersections of social position within the Swedish population at greater risk for opioid prescription receipt. [ABSTRACT FROM AUTHOR]

Background: Inappropriate utilization of prescription opioids and benzodiazepines is a public health problem. This study examined and compared user-types and trends in dispensing of these medicines, and identified associated factors related to the duration of dispensing in Australia. Methods: A random 10% sample of unit-record data of opioids and benzodiazepines dispensed nationally during 2013–2016 was analyzed. Users were categorized into four types: single-quarter (i.e., three months), medium-episodic (dispensed 2–6 quarters), long-episodic (dispensed 7–11 quarters), chronic (dispensed 12–16 quarters). Dispensing quantity was computed in defined daily dose (DDD). Generalized multilevel ordinal models were developed to examine the factors associated with the duration of dispensing. Results: There were similarities in terms of trends of dispensing of opioids and benzodiazepines in Australia. Overall, more people were dispensed opioids than benzodiazepines. Around 52% of opioids users and 46% of benzodiazepines users were dispensed these medicines for a single quarter. However, chronic users were dispensed 60% of opioids and 50% of benzodiazepines in DDD/1000 people/day, respectively. On average, 16.6 DDD/1000 people/day of opioids and 14.2 DDD/1000 people/day of benzodiazepines were dispensed in Australia during the study period. Tasmania was dispensed the highest quantity (in DDD/1000 people/day) of these medicines, followed by South Australia and Queensland. Women compared to men, and clients of age-group 20–44, 45–64 and 65+ compared to age-group 0–19, were significantly more likely to have dispensed opioids/benzodiazepine for a relatively long duration. Clients with a history of dispensing of one of these two medicines were significantly more likely to have dispensed the other for a relatively long period. Conclusions: There were similarities in patterns of dispensing of opioids and benzodiazepines in terms of user characteristics and structural variables. Consistent use of real-time drug monitoring program and tailored intervention are recommended. [ABSTRACT FROM AUTHOR]

Background: Injection drug use-associated endocarditis (IDUaIE) incidence in Ontario has recently been associated with hydromorphone prescribing rates. Staphylococcus aureus causes the majority of cases of IDUaIE in Ontario and across North America. Hydromorphone controlled-release (Hydromorphone-CR) requires a complex technique for injection and therefore provides multiple opportunities for contamination. Hydromorphone-CR contains several excipients, which could enhance staphylococcal survival and increase risk of contaminating the injectate. Methods: Used injection drug preparation equipment (cookers/filters) was collected from persons who inject drugs (PWID), rinsed with water, and plated on Mannitol salt agar. Bacterial isolates from bacteremic PWID were used to assess the survival of S. aureus and Streptococcus pyogenes on cookers/filters with Hydromorphone-CR, hydromorphone immediate-release (Hydromorphone-IR) or oxycodone controlled-release (Oxycodone-CR). The solutions spiked with S. aureus were heated and the remaining viable bacteria enumerated. Results: S. aureus was detected in 12/87 (14%, 95%CI 8–23%) cookers/filters samples used for injection of Hydromorphone-CR. Hydromorphone-CR was the only opioid associated with greater survival of methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) on cookers/filters when compared to sterile water vehicle control. There was a ~2 log reduction in the number of S. aureus that survived when cookers/filters were heated. Conclusion: 14% of all cookers/filters used in the preparation of Hydromorphone-CR were contaminated with S. aureus. Hydromorphone-CR prolongs the survival of MRSA and MSSA in cookers/filters. Heating cookers/filters may be a harm-reduction strategy. [ABSTRACT FROM AUTHOR]

Introduction: Dysmenorrhea (period pain) is common and affects around three quarters of all young women under the age of 25. The majority of young women, for a variety of reasons, think of period pain as ‘normal’ and something to be managed or endured. This normalisation of pain often is reinforced by family and friends and results in young women using self-care strategies to manage their pain rather than seeking medical advice. This systematic review and meta-analysis examined observational studies reporting on the prevalence of different types of self-care, both pharmaceutical and non-pharmaceutical, self-rated effectiveness of self-care and the sources of information on menstruation in young women under 25 Methods: A search of Medline, PsychINFO, EMBASE and CINAHL in English was carried out from 1980 to December 2018. Studies that reported on menstrual self-care strategies in young women were included. Results: Nine hundred and forty-seven articles were screened. Twenty-four studies including 12,526 young women were eligible and included in the meta-analysis. Fifteen studies were from low, lower-middle or upper-middle-income countries (LMIC) and nine studies were from high income countries (HIC). Self-care was used by over half of all young women (55%, 95%CI 34.1–74.3) with both pharmaceutical (48%, 95%CI 40.0–57.0) and non-pharmaceutical (51.8%, 95%CI 31.3–71.7) options used. Paracetamol was the most common analgesic used (28.7%, 95%CI 19.6–39.9) but did not always provide sufficient pain relief in almost half of those using it. Contraceptive use was significantly higher (P<0.001) in HIC (22%) compared to LMIC (1%). Only 11% (95%CI 8.4–15.2) of young women reported seeing a medical doctor for their period pain. Conclusions: Self-care usage, both pharmaceutical and non-pharmaceutical, was common, but young women were not necessarily choosing the most effective options for pain management. High-quality information on self-care for period pain is urgently needed. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is an adverse event that carries significant morbidity. Given that interventions after AKI occurrence have poor performance, there is substantial interest in prediction of AKI prior to its diagnosis. However, integration of real-time prognostic modeling into the electronic health record (EHR) has been challenging, as complex models increase the risk of error and complicate deployment. Our goal in this study was to create an implementable predictive model to accurately predict AKI in hospitalized patients and could be easily integrated within an existing EHR system.Methods and Findings: We performed a retrospective analysis looking at data of 169,859 hospitalized adults admitted to one of three study hospitals in the United States (in New Haven and Bridgeport, Connecticut) from December 2012 to February 2016. Demographics, medical comorbidities, hospital procedures, medications, and laboratory data were used to develop a model to predict AKI within 24 hours of a given observation. Outcomes of AKI severity, requirement for renal replacement therapy, and mortality were also measured and predicted. Models were trained using discrete-time logistic regression in a subset of Hospital 1, internally validated in the remainder of Hospital 1, and externally validated in Hospital 2 and Hospital 3. Model performance was assessed via the area under the receiver-operator characteristic (ROC) curve (AUC). The training set cohort contained 60,701 patients, and the internal validation set contained 30,599 patients. External validation data sets contained 43,534 and 35,025 patients. Patients in the overall cohort were generally older (median age ranging from 61 to 68 across hospitals); 44%-49% were male, 16%-20% were black, and 23%-29% were admitted to surgical wards. In the training set and external validation set, 19.1% and 18.9% of patients, respectively, developed AKI. The full model, including all covariates, had good ability to predict imminent AKI for the validation set, sustained AKI, dialysis, and death with AUCs of 0.74 (95% CI 0.73-0.74), 0.77 (95% CI 0.76-0.78), 0.79 (95% CI 0.73-0.85), and 0.69 (95% CI 0.67-0.72), respectively. A simple model using only readily available, time-updated laboratory values had very similar predictive performance to the complete model. The main limitation of this study is that it is observational in nature; thus, we are unable to conclude a causal relationship between covariates and AKI and do not provide an optimal treatment strategy for those predicted to develop AKI.Conclusions: In this study, we observed that a simple model using readily available laboratory data could be developed to predict imminent AKI with good discrimination. This model may lend itself well to integration into the EHR without sacrificing the performance seen in more complex models. [ABSTRACT FROM AUTHOR]

There is a growing interest in the use of voluntarily displayed ongoing behaviours in laboratory animals to assess the pain experience. In rats, two behavioural pain scales, the Rat Grimace Scale (RGS, a facial expression scale) and a composite behaviour score (CBS, a behavioural ethogram reliant on postural changes), are both promising pain assessment methods. Both scales have been used to assess pain in a laparotomy model, however, they have never been compared directly and the knowledge of how different analgesics may affect these two scales is limited. This study aimed to provide a comparison to discriminate the temporal and analgesic response in a laparotomy model. Female Wistar (n = 26) and Sprague Dawley rats (n = 26) were block randomized to receive saline, meloxicam (2 mg/kg) or buprenorphine (0.05 mg/kg) 30 minutes before laparotomy. Rats were video-recorded before surgery (BL) and at 30, 150, 270, and 390 minutes post-operatively. Videos were assessed according to both scales by a trained, blinded observer. Both CBS and RGS scores increased significantly at all post surgical timepoints in the saline group. Both buprenorphine and meloxicam reduced CBS scores to baseline levels following laparotomy; however, RGS scores were only reduced following buprenorphine. RGS scores in the meloxicam group remained similar to scores of the saline group. These findings suggest that the CBS and RGS differ in their sensitivity to discriminating analgesic effects. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prevalence of depressive symptoms in rheumatoid arthritis (RA) patients using two previously validated questionnaires in a large patient sample, and to evaluate depressive symptoms in the context of clinical characteristics (e.g. remission of disease) and patient-reported impact of disease. Methods: In this cross-sectional study, the previously validated Patient Health Questionnaire (PHQ-9) and Beck-Depression Inventory II (BDI-II) were used to assess the extent of depressive symptoms in RA patients. Demographic background, RA disease activity score (DAS28), RA impact of disease (RAID) score, comorbidities, anti-rheumatic therapy and antidepressive treatment, were recorded. Cut-off values for depressive symptomatology were PHQ-9 ≥5 or BDI-II ≥14 for mild depressive symptoms or worse and PHQ-9 ≥ 10 or BDI-II ≥ 20 for moderate depressive symptoms or worse. Prevalence of depressive symptomatology was derived by frequency analysis while factors independently associated with depressive symptomatology were investigated by using multiple logistic regression analyses. Ethics committee approval was obtained, and all patients provided written informed consent before participation. Results: In 1004 RA-patients (75.1% female, mean±SD age: 61.0±12.9 years, mean disease duration: 12.2±9.9 years, DAS28 (ESR): 2.5±1.2), the prevalence of depressive symptoms was 55.4% (mild or worse) and 22.8% (moderate or worse). Characteristics independently associated with depressive symptomatology were: age <60 years (OR = 1.78), RAID score >2 (OR = 10.54) and presence of chronic pain (OR = 3.25). Of patients classified as having depressive symptoms, only 11.7% were receiving anti-depressive therapy. Conclusions: Mild and moderate depressive symptoms were common in RA patients according to validated tools. In routine clinical practice, screening for depression with corresponding follow-up procedures is as relevant as incorporating these results with patient-reported outcomes (e.g. symptom state), because the mere assessment of clinical disease activity does not sufficiently reflect the prevalence of depressive symptoms. Clinical trial registration number: This study is registered in the Deutsches Register Klinischer Studien () and ClinicalTrials.gov (). [ABSTRACT FROM AUTHOR]

Background: Sickle cell disease (SCD) is an inherited blood disorder associated with acute pain crisis and other complications that lead to frequent emergency department (ED) visits. To improve outcomes, the National Heart, Lung and Blood Institute (NHLBI) published recommendations for management of acute pain crisis. NHLBI also funded eight centers across the United States to participate in the Sickle Cell Disease Implementation Consortium. This six-year effort consists of two phases. Phase one involved conducting needs assessments of barriers and facilitators to SCD care. The aim of this study was to describe challenges and facilitators to caring for SCD from the perspective of ED providers in central North Carolina (NC). Methods and findings: We conducted a needs assessment survey with ED providers throughout NC. We also conducted focus groups and an interview with ED providers from three healthcare facilities in central NC. One hundred and eleven surveys (60.6% physicians, 26% registered nurses, 13.5% physician assistants) were completed and 13 providers participated in 3 focus groups and 1 interview. Slightly more than half (50. 4%) utilized individualized dosing protocols to treat sickle cell pain. Only 32.4% of the providers were aware of the NHLBI SCD recommendations. Barriers to care from the survey included: patient behavior (67.57%), the opioid epidemic (67.57%), overcrowding (64.86%), and concern about addiction (49.55%). Perceived barriers to care identified in the focus groups and interview included: high patient volumes, lack of SCD care protocols, poor communication among providers and stigma. Facilitators to care included: individualized pain plans, comfort prescribing opioids and electronic medical records. Conclusion: SCD care is influenced by many factors. Our results illuminate the need for increased use of the NHLBI SCD recommendations, individualized pain protocols, and use of electronic medical records and other care-interventions, specifically geared towards improving provider knowledge and mitigating provider bias. [ABSTRACT FROM AUTHOR]

Background: Intentional drug overdose is the most common method of self-harm. As psychiatric disorders are very common in self-harm patients, the medication used to treat these disorders can become the means for the self-harm act. The present study aimed at investigating an association between the use of prescribed medication (analgesics and antipyretics, anti-epileptics, antipsychotics, antidepressants and psychostimulants) as a method of self-harm and prescription rates of this medication in Flanders. We investigated the possible effect of gender, alcohol use during the self-harm act and a history of self-harm. Methods: Data from the multicenter study of self-harm in Flanders between 2008 and 2013 were used. The significance of differences in percentages was calculated by GEE and the strength by odds ratios (OR). Results: There was an increase in the odds of using antidepressants (0.8%) and antipsychotics (2%) among females when the rate of prescription increases. Analgesics and antipyretics (39.3/1,000) and antidepressants (124.9/1,000) were the most commonly prescribed drugs among females. Antidepressants (63.9/1,000) and antipsychotics (26.5/1,000) were the most commonly prescribed drugs among males. Antidepressants and analgesics and antipyretics were the most frequently used medications for self-harm. Analgesics and antipyretics during the self-harm act were more common among first-timers, while repeaters more commonly overdosed using antipsychotics and antidepressants. Conclusion: These findings suggest that the availability of medication via prescriptions plays an important role in the choice of the medication ingested during the self-harm act. Precautions are necessary when prescribing medication, including restrictions on the number of prescriptions and the return of unused medication to pharmacies after cessation of treatment. These issues should be a focus of attention in the education and training of physicians and pharmacists. [ABSTRACT FROM AUTHOR]

Background: The evidence supporting the benefit of femoral nerve block (FNB) for positioning before spinal anesthesia (SA) in patients suffering from a femur fracture remains inconclusive. In the present study, the authors intended to determine the efficacy and safety of FNB versus an intravenous analgesic (IVA) for positioning before SA in patients with a femur fracture. Method: PubMed, EMBASE, Cochrane, and Scopus databases were searched up to January 2018. We included randomized controlled studies (RCTs) and observational studies that compared FNB versus IVA for the positioning of patients with femur fracture receiving SA. The primary outcome was pain scores during positioning within 30 min before SA. Secondary outcomes were the time for SA, additional analgesic requirements, anesthesiologist’s satisfaction with the quality of positioning for SA, participant acceptance, and hemodynamic changes. A random-effects model was used to synthesize the data. We registered the study at PROSPERO with an ID of CRD42018091450. Results: Ten studies with 584 patients were eligible for inclusion. FNB achieved significantly lower pain scores than IVA during positioning within 30 min before SA (pooled standardized mean deviation (SMD): -1.27, 95% confidence interval (CI): -1.84 to -0.70, p < 0.05). A subgroup analysis showed that the analgesic effect was larger in patients in the sitting position for SA than a non-sitting position (sitting position vs non-sitting: pooled SMD: -1.75 (p < 0.05) vs -0.61 (not significant). A multivariate regression showed that the analgesic effect was also associated with age and the total equivalent amount as lidocaine after adjusting for gender (age: coefficient 0.048, p < 0.05; total equivalent amount as lidocaine: coefficient 0.005, p < 0.05). Patients receiving FNB also had a significantly shorter time for SA, greater anesthesiologist satisfaction, and higher patient acceptance than patients receiving IVA. The use of local anesthetics did not produce significant clinical hemodynamic change. Conclusion: Compared to IVA, FNB was an effective and safe strategy for the positioning of femur fracture patients for a spinal block, particularly patients who received SA in the sitting position. [ABSTRACT FROM AUTHOR]

Smoking is a leading cause of preventable death. The effect of tobacco is even more contundent in people with mental illness and, in general, cigarette smoking addiction is influenced by genetic factors. The opioid system is involved in the mesolimbic reward system, which is of great importance in addictive behaviors, such as smoking and is influenced by genes such as the OPRM1. The aim of this study was to evaluate if selecting a comparison group that include light smokers versus people that never smoked impacts the results of genetic association studies. In addition, to evaluate the genetic association in different groups of smokers by analyzing independent covariates such as mental illness and clinical dental data. All subjects were participants of the Dental Registry and DNA Repository project. Genotyping was carried out using TaqMan chemistry for two markers in OPRM1 (rs553202 and rs7755635). Logistic regression analyses were performed as implemented in PLINK. The established value for alpha was 5%, and the Hardy-Weinberg equilibrium was evaluated by the chi-square test with one degree of freedom for each marker. 1,897 patients were included, which were allocated to eight distinct groups, according to the frequency and quantity of cigarettes smoked and mental illness status. There was no significant association between the two markers in OPRM1 and smoking. When mental illness and dental clinical data (tooth loss, dental caries, and periodontitis) were used as covariates, there were associations between heavy smoking and OPRM1, when non-smokers were used as comparison. We did not have diet or microbiome data to consider for these dental analyses and suggest that these kinds of data should be always incorporated in the future. Significant results were found only when the covariables mental illness and oral clinical data were added to the analysis. [ABSTRACT FROM AUTHOR]

Background: Postoperative pain remains a challenge in the developed world, but the consequences of inadequately treated postoperative pain are particularly severe in low- and middle-income countries. Since 2011, reports have drawn attention to the poor quality of postoperative pain management in Ethiopia; however, our multicenter qualitative study was the first to attempt to understand the factors that are barriers to and facilitators of quality pain managment in the country. To this aim, the study explored the perspectives of patients, healthcare professionals, and hospital officials. We expected that the results of this study would inform strategies to improve the provision of quality pain management in Ethiopia and perhaps even in other low- and middle-income countries. Methods: This study used a qualitative, descriptive approach in which nine healthcare professionals, nine patients, and six hospital officials (i.e. executives in a managerial or leadership position in administration, nursing, or education) participated in face-to-face, semi-structured interviews. Thematic data analysis was conducted, and patterns were explained with the help of a theoretical framework. Findings: The barriers identified ranged from healthcare professionals’ lack of empathy to a positive social appraisal of patients’ ability to cope with pain. They also included a lack of emphasis on pain and its management during early medical education, together with the absence of available resources. Enhancing the ability of healthcare professionals to create favorable rapport with patients and increasing the cultural competence of professionals are essential ingredients of future pain education interventions. Conclusions: Barriers to and facilitators of postoperative pain management do not exist independently but are reciprocally linked. This finding calls for holistic and inclusive interventions targeting healthcare professionals, patients, and hospital officials. The current situation is unlikely to improve if only healthcare professionals are educated about pain physiology, pharmacology, and management. Patients should also be educated, and the hospital environment should be modified to provide high-quality postoperative pain management. [ABSTRACT FROM AUTHOR]

Objective: This pilot study assessed the efficacy of a knee guard device, which used magnetophoresis to transdermally deliver Glucosamine, Chondroitin and Hyaluronic Acid in a cohort of individuals with prior knee injury. The aim was to determine if the change in physical function and pain with the knee guard device was equivalent to the change produced by an established topical NSAID formulation containing diclofenac sodium 1%. Methods: A randomized, controlled, equivalence trial evaluated outcomes following treatment with the knee guard device or NSAID formulation. The study recruited 114 male participants (aged 40–55 years). Participants were randomly allocated to wear the knee guard device or to use a NSAID gel daily for two weeks. The primary outcomes were the knee injury osteoarthritis function score (KOOS-F) and an aggregated function score (AFS). The lower extremity functional scale (LEFS), pain numerical rating scale (PNRS), global rating of change (GROC) and other KOOS scores were also evaluated. Results: Multiple linear regression analyses indicated that there were no significant differences between the interventions for changes in the primary outcomes of AFS and KOOS_F. The 95% confidence interval (-2.89 to 5.15) of the estimated treatment difference for KOOS-F was within the lower (-5.61) and upper (5.61) bounds of the 7% equivalence margin for that measure, The mean value for the AFS was within, but the 95% CI (-3.11 to 7.37) exceeded the 7% equivalence margin (-2.97 to 2.97) for that measure. There was a significant difference in PNRS, which favored the knee guard device. Conclusion: The knee guard device demonstrated equivalence for the KOOS-F measure but not the AFS measure of function over the two week trial period when compared to a widely available NSAID gel that has been shown to be superior to placebo. The knee guard produced a greater reduction in pain report (p = 0.002) than the NSAID gel. Users of the knee guard device experienced more skin irritation than participants using the NSAID gel. Further research is required to fully evaluate the therapeutic potential of this innovative treatment approach. [ABSTRACT FROM AUTHOR]

Current drug discovery procedures require fast and effective quantification of the pharmacological response evoked in living cells by agonist compounds. In the case of G-protein coupled receptors (GPCRs), the efficacy of a particular drug to initiate the endocytosis process is related to the formation of endocytic vesicles or endosomes and their subsequent internalisation within intracellular compartments that can be observed with high spatial and temporal resolution by fluorescence microscopy techniques. Recently, an algorithm has been proposed to evaluate the pharmacological response by estimating the number of endosomes per cell on time series of images. However, the algorithm was limited by the dependence on some manually set parameters and in some cases the quality of the image does not allow a reliable detection of the endosomes. Here we propose a simple, fast and automated image analysis method—the Δm algorithm- to quantify a pharmacological response with data obtained from fluorescence microscopy experiments. This algorithm does not require individual object detection and computes the relative increment of the third order moment in fluorescence microscopy images after filtering with the Laplacian of Gaussian function. It was tested on simulations demonstrating its ability to discriminate different experimental situations according to the number and the fluorescence signal intensity of the simulated endosomes. Finally and in order to validate this methodology with real data, the algorithm was applied to several time-course experiments based on the endocytosis of the mu opioid receptor (MOP) initiated by different agonist compounds. Each drug displayed a different Δm sigmoid time-response curve and statistically significant differences were observed among drugs in terms of efficacy and kinetic parameters. [ABSTRACT FROM AUTHOR]

Headache disorders are considered the second leading cause of years lived with disability worldwide, and 90% of people have a headache episode at least once a year, thus representing a relevant public health priority. As the pharmacist is often the first and only point of reference for people complaining of headache, we carried out a survey in a nationwide sample of Italian pharmacies, in order to describe the distribution of migraine or non-migraine type headaches and medicines overuse among people entering pharmacies seeking for self-medication; and to evaluate the association, in particular of migraine, with socio-demographic and clinical characteristics, and with the pathway of care followed by the patients. A 14-item questionnaire, including socio-demographic and clinical factors, was administered by trained pharmacists to subjects who entered a pharmacy requesting self-medication for a headache attack. The ID Migraine™ Screener was used to classify headache sufferers in four classes. From June 2016 to January 2017, 4424 people have been interviewed. The prevalence of definite migraines was 40%, significantly higher among women and less educated people. About half of all headache sufferers and a third of migraineurs do not consider their condition as a disease and are not cared by any doctor. Among people seeking self-medication in pharmacies for acute headache attacks, the rate of definite or probable migraine is high, and a large percentage of them is not correctly diagnosed and treated. The pharmacy can be a valuable observatory for the study of headaches, and the first important step to improve the quality of care delivered to these patients. [ABSTRACT FROM AUTHOR]

Objective: To develop key performance indicators that evaluate the effectiveness of a prescription medication system. Methods: A modified RAND/UCLA appropriateness method was used to develop key performance indicators (KPIs) for a prescription medication system. A broad list of potential KPIs was compiled. A multidisciplinary group composed of 21 experts rated the potential KPIs. A face-to-face meeting was held following the first rating exercise to discuss each potential KPI individually. The expert panel undertook a final rating of KPIs. The final set of KPIs were those indicators where at least 80 percent of experts rated the indicator highly i.e. rating of ≥ 7 on a scale from 1 to 9. Results: 292 KPIs were identified from the published literature. After removing duplicates and combining similar indicators 71 KPIs were included. The final ranking resulted in six indicators being ranked 7 or higher by 80% of the respondents and an additional seven indicators being ranked 7 or higher by ≥70 but ≤80% of respondents. The six selected indicators include four specific disease areas, measure structural and process aspects of health service delivery, and assessed three of the domains of healthcare quality: efficiency, effectiveness, and safety. Conclusions: These indicators are recommended as a starting point to assess the current performance of prescription medication systems. Consideration should be given to developing indicators in additional disease areas as well as indicators that measure the domains of timeliness and patient–centeredness. Future work should focus on the feasibility of measuring these indicators. [ABSTRACT FROM AUTHOR]

Dexmedetomidine is an imidazole derivative, with high affinity for α2 adrenergic receptors, used for sedation, analgesia and adjuvant anaesthesia. In this study, an analytical method for the quantification of dexmedetomidine in dried blood spots was developed, validated and applied. The drug was extracted from dried blood spot by liquid extraction; the separation was carried out by ultra high-resolution liquid chromatography in reverse phase coupled to tandem mass spectrometry method. An X Select cyano 5 μm HSS column (2.1 X 150 mm, Waters) and a mobile phase composed of 0.1% formic acid: acetonitrile [50:50 v/v], were used. The test was linear over the concentration range of 50 to 2000 pg/mL. The coefficients of variation for the intra and interday trials were less than 15%. The drug was stable under the conditions tested. The method was successfully applied for the quantification of 6 patients, aged 0 to 2 years, with classification ASA I, who underwent ambulatory surgeries, receiving a dose of 1 μg/Kg dexmedetomidine IV. The drug concentrations in the different sampling times were in the range of 76 to 868 pg/mL. [ABSTRACT FROM AUTHOR]

Introduction: British Columbia (BC), Canada declared a public health emergency in April 2016 for opioid overdose. Comprehensive data was needed to identify risk factors, inform interventions, and evaluate response actions. We describe the development of an overdose cohort, including linkage strategy, case definitions, and data governance model, and present the resulting characteristics, including data linkage yields and case overlap among data sources. Methods: Overdose events from hospital admissions, physician visits, poison centre and ambulance calls, emergency department visits, and coroner’s data were grouped into episodes if records were present in multiple sources. A minimum of five years of universal health care records (all prescription dispensations, fee-for-service physician billings, emergency department visits and hospitalizations) were appended for each individual. A 20% random sample of BC residents and a 1:5 matched case-control set were generated. Consultation and prioritization ensured analysts worked to address questions to directly inform public health actions. Results: 10,456 individuals suffered 14,292 overdoses from January 1, 2015 to Nov 30, 2016. Only 28% of overdose events were found in more than one dataset with the unique contribution of cases highest from ambulance records (32%). Compared with fatal overdoses, non-fatal events more often involved females, younger individuals (20 to 29 years) and those 60 or older. In 78% of illegal drug deaths, there was no associated ambulance response. In the year prior to first recorded overdose, 60% of individuals had at least one ED visit, 31% at least one hospital admission, 80% at least one physician visit, and 87% had filled at least one prescription in a community pharmacy. Conclusion: While resource-intensive to establish, a linked cohort is useful for characterizing the full extent of the epidemic, defining sub-populations at risk, and patterns of contact with the health system. Overdose studies in other jurisdictions should consider the inclusion of multiple data sources. [ABSTRACT FROM AUTHOR]

Objective: Increasing evidence purports exercise as a first-line therapeutic for the treatment of nearly all forms of chronic pain. However, knowledge of efficacious dosing respective to treatment modality and pain condition is virtually absent in the literature. The purpose of this analysis was to calculate the extent to which exercise treatment shows dose-dependent effects similar to what is seen with pharmacological treatments. Methods: A recently published comprehensive review of exercise and physical activity for chronic pain in adults was identified in May 2017. This report reviewed different physical activity and exercise interventions and their effectiveness in reducing pain severity and found overall modest effects of exercise in the treatment of pain. We analyzed this existing data set, focusing specifically on the dose of exercise intervention in these studies. We re-analyzed data from 75 studies looking at benefits of time of exercising per week, frequency of exercise per week, duration of intervention (in weeks), and estimated intensity of exercise. Results: Analysis revealed a significant positive correlation with exercise duration and analgesic effect on neck pain. Multiple linear regression modeling of these data predicted that increasing the frequency of exercise sessions per week is most likely to have a positive effect on chronic pain patients. Discussion: Modest effects were observed with one significant correlation between duration and pain effect for neck pain. Overall, these results provide insufficient evidence to conclude the presence of a strong dose effect of exercise in pain, but our modeling data provide tes predictions that can be used to design future studies to explicitly test the question of dose in specific patient populations. [ABSTRACT FROM AUTHOR]

Introduction: Thai patients do not routinely receive patient information leaflets (PILs) with medicines, so awareness of safety issues is low. This study aimed: i) to develop Thai PILs for NSAIDs and subject these to user-testing, and ii) to assess the potential value of PILs from the patient perspective and effect on patient knowledge. Methods: Four PILs for NSAIDs were developed and subjected to multiple rounds of user-testing by the general public. Self-administered questionnaires were distributed to orthopaedic out-patients prescribed one of these NSAIDs, assessing knowledge before and after providing a PIL. The follow-up questionnaire also sought use of and views on the PILs using a visual analogue scale (VAS). Results: 1,240 baseline questionnaires were completed; only 13.5% of patients had good knowledge. 688 patients returned follow-up questionnaires (55.5%), of whom75% had good knowledge. In patients completing both questionnaires, mean knowledge score increased from 6.22±1.40 to 8.42±1.41 (p<0.001). Patients with high educational levels had high baseline scores (OR = 2.728) and showed greatest improvement in knowledge (OR = 5.628). 90% (625) of follow-up respondents indicated they read all information in the PILs. All also agreed that these PILs should distributed to all patients taking NSAIDs. The median VAS score for usefulness was 9.3 (IQR 8.6–10.0). Conclusions: User-testing of PILs was feasible in a Thai population and enabled the development of acceptable and desirable PILs. PILs could improve patients' knowledge about their medicine, particularly among those with higher educational level. User-tested PILS could meet the need for more written medicine information. [ABSTRACT FROM AUTHOR]

Background: An improved understanding of patients’ perceived needs for medical services for low back pain (LBP) will enable healthcare providers to better align service provision with patient expectations, thus improving patient and health care system outcomes. Thus, we aimed to identify the existing literature regarding patients’ perceived needs for medical services for LBP. Methods: A systematic scoping review was performed of publications identified from MEDLINE, EMBASE, CINAHL and PsycINFO (1990–2016). Descriptive data regarding each study, its design and methodology were extracted and risk of bias assessed. Aggregates of patients’ perceived needs for medical services for LBP were categorised. Results: 50 studies (35 qualitative, 14 quantitative and 1 mixed-methods study) from 1829 were relevant. Four areas of perceived need emerged: (1) Patients with LBP sought healthcare from medical practitioners to obtain a diagnosis, receive management options, sickness certification and legitimation for their LBP. However, there was dissatisfaction with the cursory and superficial approach of care. (2) Patients had concerns about pharmacotherapy, with few studies reporting on patients’ preferences for medications. (3) Of the few studies which examined the patients’ perceived need of invasive therapies, these found that patients avoided injections and surgeries (4) Patients desired spinal imaging for diagnostic purposes and legitimation of symptoms. Conclusions: Across many different patient populations with data obtained from a variety of study designs, common themes emerged which highlighted areas of patient dissatisfaction with the medical management of LBP, in particular, the superficial approach to care perceived by patients and concerns regarding pharmacotherapy. Patients perceive unmet needs from medical services, including the need to obtain a diagnosis, the desire for pain control and the preference for spinal imaging. These issues need to be considered in developing approaches for the management of LBP in order to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Limited real-world data are available regarding the comparative safety of non-vitamin K antagonist oral anticoagulants (NOACs). The objective of this retrospective claims observational cohort study was to compare the risk of bleeding among non-valvular atrial fibrillation (NVAF) patients prescribed apixaban, dabigatran, or rivaroxaban. NVAF patients aged ≥18 years with a 1-year baseline period were included if they were new initiators of NOACs or switched from warfarin to a NOAC. Cox proportional hazards modelling was used to estimate the adjusted hazard ratios of any bleeding, clinically relevant non-major (CRNM) bleeding, and major inpatient bleeding within 6 months of treatment initiation for rivaroxaban and dabigatran compared to apixaban. Among 60,227 eligible patients, 8,785 were prescribed apixaban, 20,963 dabigatran, and 30,529 rivaroxaban. Compared to dabigatran or rivaroxaban patients, apixaban patients were more likely to have greater proportions of baseline comorbidities and higher CHA2DS2-VASc and HAS-BLED scores. After adjusting for baseline clinical and demographic characteristics, patients prescribed rivaroxaban were more likely to experience any bleeding (HR: 1.35, 95% confidence interval [CI]: 1.26–1.45), CRNM bleeding (HR: 1.38, 95% CI: 1.27–1.49), and major inpatient bleeding (HR: 1.43, 95% CI: 1.17–1.74), compared to patients prescribed apixaban. Dabigatran patients had similar bleeding risks as apixaban patients. In conclusion, NVAF patients treated with rivaroxaban appeared to have an increased risk of any bleeding, CRNM bleeding, and major inpatient bleeding, compared to apixaban patients. There was no significant difference in any bleeding, CRNM bleeding, or inpatient major bleeding risks between patients treated with dabigatran and apixaban. [ABSTRACT FROM AUTHOR]