Long-term Use Of Analgesics Research Articles

Study protocol for a randomized controlled trial of neurofeedback mindfulness in chronic migraines

Chronic migraine is a debilitating headache disorder that is associated with excessive analgesic use. As the long-term use of analgesics could cause additional headaches due to medication overuse, there is a need to probe efficient nonprophylactic alternatives and migraineurs’ long-term adherence to such possible treatments. This protocol investigates the integration of neurofeedback and mindfulness which are the two common nonpharmacological therapies for migraines. We offer the use of portable EEG headbands for easy home-based data collection and consistent data access from researchers. In order to evaluate the efficacy of this recommended intervention, this is a protocol for a randomized control trial with a waitlisted group and an intervention group consisting of a daily attention task. The protocol presents important criteria which should be checked for consistency in longitudinal data collection from adults with chronic migraine.

Prevalence of chronic pain or analgesic use in children and young people and its long-term impact on substance misuse, mental illness, and prescription opioid use: a retrospective longitudinal cohort study

Epidemiological studies suggest chronic and recurrent pain affects around a quarter of children, while 8% report intense and frequent pain. The long-term implications of chronic pain in childhood are uncertain. Using electronic health records (EHRs) we used both disease codes and medicines prescription records to investigate the scale of chronic pain and long-term analgesic use in children and young people (CYP), and if chronic pain and/or use of analgesic medicines at an early age is associated with substance misuse, use of prescription opioids, and poor mental health in adulthood. We conducted a cohort study using data from IQVIA Medical Research Data UK. We identified individuals aged 2-24 with exposure to either a diagnostic code indicating chronic pain (diagnosis-exposed), repeat prescription for medicines commonly used to treat pain (prescription-exposed), or both. Follow-up began at 25, and the unexposed population acted as comparators. We calculated hazard ratios (HR) for mental health and substance misuse outcomes, and rate ratios (RR) for opioid prescriptions in adulthood. Additionally, we investigated which diagnoses, if any, were over-represented in the prescription-exposed subgroup. The cohort constituted 853,625 individuals; 146,431 had one or more of the exposures of interest (diagnosis-exposed=115,101, prescription-exposed=20,298, both-exposed=11,032), leaving 707,194 as comparators. Median age at index exposure was 18.7 years (IQR 14.7-22.3). On average during follow-up, the pooled exposed group had, respectively, a 31% and 17% higher risk of adverse mental health and substance misuse outcomes (adjusted HR [95% CI] of 1.31 [1.29-1.32] and 1.17 [1.11-1.24]). Exposed individuals also received prescription opioids at double the rate of unexposed individuals on average during follow-up (adjusted RR 2.01 [95% CI 1.95-2.10]). Outcomes varied between exposure subgroups, with prescription- and both-exposure tending to have worse outcomes. Unlike these two subgroups, in the diagnosis-exposed subgroup we did not detect a greater risk of substance misuse. Chronic pain in CYP is associated with increased prescription opioid use and adverse mental health outcomes in adulthood, as is repeat prescription for analgesic medicines, but only the latter is also associated with substance misuse in adulthood. It is essential to avoid the harms of under-treating pain in CYP while giving due consideration to the risks posed by analgesic medicines. Early recognition of chronic pain in CYP and utilising non-pharmacological management options may help minimise overprescribing, and long-term reliance on dependence-forming-drugs. AL is an NIHR funded academic clinical fellow, and was supported by funding from UCLH Charities while carrying out this work. RS and DS are part of the Advanced Pain Discovery Platform and were supported by a UKRI and Versus Arthritis grant (MR/W002566/1) as part of the Consortium Against Pain Inequality. AW was supported by the Wellcome Trust (220558/Z/20/Z).

The hidden impact of neuropathic pain after surgical fixation of wrist, hip, and ankle fractures: A cross-sectional retrospective study evaluating its prevalence and risk factors

BackgroundDysesthesia, electrical and burning sensations, in addition to allodynia are frequent symptoms of neuropathic pain. Despite the high frequency, scientific data on the development of neuropathic pain after surgery for fracture fixation are scarce. The goal of the present study was to determine the prevalence, risk factors, and evaluate potential associations among neuropathic pain, pain intensity, sociodemographic, and clinical variables after wrist, hip, and ankle fracture fixation. MethodsA cross-sectional retrospective study involving a cohort of 166 patients who underwent surgery for distal radius, proximal femur, malleolar fracture fixation was performed. Neuropathic pain was assessed one year after fracture fixation using the Doleur Neuropathique Questionnaire (DN4). ResultsThe incidence of neuropathic pain in our sample was 49 (29.5%). Predictors for the development of neuropathic pain included patients with a high body mass index (BMI), female gender, diabetes mellitus, long-term use of analgesics (especially using pain-modulating medication), patients who presented some fracture-related complication during the course of the treatment, who had limitations for daily activity, and who were away from work due to chronic pain. ConclusionIn our study, neuropathic pain after wrist, hip, and ankle fracture fixation was prevalent and associated with higher BMI values and amount of medication, in addition to higher proportions of female sex, absence from work, DM, limitation for daily activities, postoperative complications, and use of pain modulating medications.

Chronic pain following elective surgery under general anesthesia in older adults.

The purpose of this study was to investigate the association between age and chronic postsurgical pain (CPSP) in patients who underwent elective surgery under general anesthesia, with a focus on long-term postsurgical analgesic use. To our knowledge, no previous study has examined this relationship in detail between older and younger patients. We conducted a propensity score-matched (PSM) study to compare the rates of long-term (3 or 6months) postoperative analgesic use between older adult (≥ 65years) and younger (< 65years) patients. Multivariate logistic regression was used to assess the use of analgesics as a surrogate indicator of CPSP. The PSM analysis included 62,784 surgical patients (31,392 in each group). Three months after surgery, the rates of analgesic use were significantly higher in the older age group (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.41-1.49) as well as for opioid use specifically (aOR, 1.34; 95% CI, 1.29-1.39). Six months after surgery, the rates of analgesic use remained higher in the older age group (aOR, 1.52; 95% CI, 1.47-1.58), and similarly for opioid use specifically (aOR, 1.42; 95% CI, 1.36-1.48). Our findings suggest that older adults have higher rates of long-term analgesic use for CPSP after elective surgery under general anesthesia. This study highlights the importance of addressing CPSP in older adult patients and considering age-related factors when managing postoperative pain.

Clinical characteristics and long-term outcomes following pancreatic injury – An international multicenter cohort study

BackgroundTrauma to the pancreas is rare but associated with significant morbidity. Currently available management guidelines are based on low-quality evidence and data on long-term outcomes is lacking. This study aimed to evaluate clinical characteristics and patient-reported long-term outcomes for pancreatic injury. MethodsA retrospective cohort study evaluating treatment for pancreatic injury in 11 centers across 5 European nations over >10 years was performed. Data relating to pancreatic injury and treatment were collected from hospital records. Patients reported quality of life (QoL), changes to employment and new or ongoing therapy due to index injury. ResultsIn all, 165 patients were included. The majority were male (70.9%), median age was 27 years (range: 6–93) and mechanism of injury predominantly blunt (87.9%). A quarter of cases were treated conservatively; higher injury severity score (ISS) and American Association for the Surgery of Trauma (AAST) pancreatic injury scores increased the likelihood for surgical, endoscopic and/or radiologic intervention. Isolated, blunt pancreatic injury was associated with younger age and pancreatic duct involvement; this cohort appeared to benefit from non-operative management. In the long term (median follow-up 93; range 8–214 months), exocrine and endocrine pancreatic insufficiency were reported by 9.3% of respondents. Long-term analgesic use also affected 9.3% of respondents, with many reported quality of life problems (QoL) potentially attributable to side-effects of opiate therapy. Overall, impaired QoL correlated with higher ISS scores, surgical therapy and opioid analgesia on discharge. ConclusionsPancreatic trauma is rare but can lead to substantial short- and long-term morbidity. Near complete recovery of QoL indicators and pancreatic function can occur despite significant injury, especially in isolated, blunt pancreatic injury managed conservatively and when early weaning off opiate analgesia is achieved.

Sarcopenia is associated with an increase in long-term use of analgesics after elective surgery under general anesthesia

PurposeTo elucidate the association of presurgical sarcopenia and long-term non-opioid analgesic and opioid use after elective surgery under general anesthesia.MethodsWe conducted this population-based propensity score matched to investigate the effects...

Painkillers among people aged 20-30 according to questionnaires

Aim. Painkillers are one of the most widespread drugs on the pharmaceutical market, individual analgesics belong to the OTC (over-the-counter drug) group, which are also available outside pharmacies. The universality and wide availability of painkillers posea real problem of medication errors. The aim of the study was to examine the attitude of people aged 20-30 to taking painkillers and to examine the level of knowledge of the respondents about them.Method. The study involved 70 people aged 20-30 who voluntarily fi lled in an original electronic questionnaire, which included the attitude of people of this age to taking medications and questions assessing their knowledge about the medications they take. It included questions about the type of drugs taken, frequency, intensity of pain at which the respondents took analgesics and knowledge about possible adverse effects in the case of long-term use of analgesics or their overdose. The most numerous age group were people aged 20-30, they constituted 55.7% of the respondents. People aged 24-27 accounted for 24.3%, while 20% were people aged 28-30. Most respondents showed that their current place of residence is a city with over 500,000 inhabitants. Most of the respondents had secondary education and it amounted to 51.4%.Results and conclusion. As many as 85.7% of people take painkillers. 35.7% of the respondents take medication once a month, while 34.3% take medication less frequently than once a month. 60.9% of people know the effects of chronic overuse of painkillers, butas many as 39.1% of respondents have a knowledge defi cit in this regard. The study found that 89.9% of people aged 20-30 know how to safely use painkillers, only 10.1% do not know in this regard. Most people in this age group use drugs when the intensity of pain is 4, which means that the most numerous group of people takes drugs when the intensity of pain is very high. This indicates that drugs are not taken without necessity, which results in their chronic non-use, as a result of which the risk of side effectscaused by overuse of painkillers is minimised. The study showed that 35.7% take painkillers once a month and 34.3% less than oncea month. Mostly women take medication once a month, this could possibly be associated with menstrual pain. The survey shows that 60.9% of people know the effects of chronic overuse of painkillers. It follows that most of the respondents know the consequences ofoverusing painkillers, but a large proportion of people in this age group show a defi cit of knowledge about what is dangerous to their health, therefore it is necessary to educate people aged 20-30 years in this regard.Cognitive value. The conducted research shows the attitude of young people toward painkillers. The cognitive value is the selection of a specifi c research group which from an early age, has the possibility to observe easy and wide access to analgesics.

Epidural caudal steroid injection in low backache and lumbar radiculopathy at tertiary care centre

Most of the lumbosacral radiculopathies are caused by irritation of spinal nerve roots associated with lower back and leg pain. Most common causes for spinal root irritation are intervertebral disc herniation and spinal canal stenosis, other causes include spondylolisthesis, spondylosis, thickening of ligamentum flavum, scoliosis etc. Lumbar radiculopathy frequently treated by epidural corticosteroid injections. Common route for administering epidural steroid injections are interlaminar, transforaminal and caudal. But there are concerns due to rare major neurologic complications after this treatment. Therefore this literature focuses on caudal route of epidural steroid injections. To know the benefits of caudal epidural steroid injection in lumbar radiculopathy and low backache by analyzing clinical and functional outcome.Out of 35 patients, in 28 patients (80%) low backache and radiating pain subsided after 3 days. But 7 patients (20%) get partial relief or having persistent complaints after 3 days, administered 2epidural steroid injection after a month. After one month 32 patients (91%) do not complain of pain but 3 patients (9%) tend to have some back pain which eventually improved on two to three months of regular physiotherapy and postural correction exercises.Caudal epidural steroid injections are safe, quick and effective. It can be performed on OPD basis, has considerably fewer side effects than surgery. Therefore injections can help to increase function while avoiding surgery and long term use of analgesics.

Chronic pain after breast surgery: incidence, associated factors, and impact on quality of life, an observational prospective study

BackgroundChronic pain after breast surgery (CPBS) has a disabling impact on postoperative health status. Mainly because of the lack of a clear definition, inconsistency does exist in the literature concerning both the actual incidence and the risk factors associated to CPBS. The aim of this prospective, observational study is to describe the incidence of and risk factors for CPBS, according to the definition provided by the IASP taskforce. The impact of CPBS on patients’ function and quality of life is also described.MethodsWomen aged 18+ undergoing oncological or reconstructive breast surgery from Jan until Apr 2018 at the Breast Unit of Careggi Hospital (Florence, Italy) were prospectively observed. Postoperative pain was measured at 0 h, 3 h, 6 h, 12 h, 24 h, 48 h, and 3 months (CPBS) after surgery. Preoperative, intraoperative, and postoperative factors were compared in CPBS and No-CPBS groups through multivariate logistic regression analysis.ResultsAmong the 307 patients considered in this study, the incidence of CPBS was 28% [95% CI 23.1–33.4%]. Results from the logistic regression analysis suggest that axillary surgery (OR [95% CI], 2.99 [1.13–7.87], p = 0.03), preoperative use of pain medications (OR [95% CI], 2.04 [1.20–3.46], p = 0.01), and higher dynamic NRS values at 6 h postoperatively (OR [95% CI], 1.28 [1.05–1.55], p = 0.01) were all independent predictors for CPBS.ConclusionsChronic pain after breast surgery is a frequent complication. In our cohort, long-term use of analgesics for pre-existing chronic pain, axillary surgery, and higher dynamic NRS values at 6 h postoperatively were all factors associated with increased risk of developing CPBS. The possibility to early detect persistent pain, particularly in those patients at high risk for CPBS, might help physicians to more effectively prevent pain chronicisation.Trial registrationClinicalTrials.gov registration NCT04309929.

Screening of novel 2-4methylphenylimino-3-carboxamide substituted thiophene compound for peripheral analgesic activity

Background: Pain is an unpleasant sensation that can range from mild, localized discomfort to agony. The mechanism of pain perception involves dedicated subsets of peripheral and central neurons. For management of pain, currently, available treatment regimens are opioid analgesics and NSAIDs which are easily available over the counter drugs. Long term use of analgesics can lead to significant impact on human renal system, cardiovascular system and analgesic abuse etc. So, there is a need for novel, safe and cost effective analgesic compound. Hence a study on 2-4methylphenylimino-3-carboxamide substituted thiophene compound, a novel thiophene compound has been carried out in different experimental animal models.Methods: Two methods were used to evaluate the peripheral analgesic activity of 2-4methylphenylimino-3-carboxamide substituted thiophene compound. First method was Acetic acid induced writhing and compared to standard drug aspirin. Second method was late phase of formalin induced paw licking in mice and compared to a standard drug, aspirin.Results: With Acetic acid induced writhing, 40mg/kg dose of 2-4methylphenylimino-3-carboxamide substituted thiophene compound has shown maximum Pain Inhibition Percentage (PIP) of 78 % compared to 91% by Aspirin. Whereas with late phase of Formalin test, 40mg/kg dose of 2-4methylphenylimino-3-carboxamide substituted thiophene compound has shown maximum PIP of 58% in late phase compared to 86% by aspirin. The results were statistically significant with p&lt;0.05.Conclusions: It can be concluded that 2-4methylphenylimino-3-carboxamide substituted thiophene compound found to have moderate peripheral analgesic activity as evident in acetic acid induced writhing and late phase of formalin tests.

Screening of novel 2-4 methylphenylimino-3-carboxamide substituted thiophene compound for central analgesic activity

Background: Pain is an unpleasant sensation that can range from mild, localized discomfort to agony. The mechanism of pain perception involves dedicated subsets of peripheral and central neurons. For management of pain, currently, available treatment regimens are opioid analgesics and NSAIDs which are easily available over the counter drugs. Long term use of analgesics can lead to significant impact on human renal system, cardiovascular system and analgesic abuse etc. So, there is a need for novel, safe and cost-effective analgesic compound. Hence a study on 2-4 methylphenylimino-3-carboxamide substituted thiophene compound, a novel thiophene compound has been carried out in different experimental animal models.Methods: Two methods were used to evaluate the central analgesic activity of 2-4 methylphenylimino-3-carboxamide substituted thiophene compound. First method was Eddy’s hot plate method and compared to standard central analgesic, morphine. Second method was early phase of formalin induced paw licking in mice and compared to a standard drug, aspirin.Results: With eddy’s hot plate method, 40mg/kg dose of 2-4 methylphenylimino-3-carboxamide substituted thiophene compound has shown maximum pain inhibition percentage (PIP) of 45% at 60 min compared to 125% by morphine. Whereas with early phase of formalin test, 40 mg/kg dose of 2-4 methylphenylimino-3-carboxamide substituted thiophene compound has shown maximum PIP of 44% in early phase compared to 60% by aspirin. The results were statistically significant with p&lt;0.05.Conclusions: It can be concluded that 2-4 methylphenylimino-3-carboxamide substituted thiophene compound found to have minimal central analgesic activity as evident in eddy’s hot plate and early phase of formalin tests.

Expert Opinion on the Extensive Use of Prescription Crystalline Glucosamine Sulfate in the Multimodal Treatment of Osteoarthritis in Ukraine, Kazakhstan, Uzbekistan, and Armenia.

Objective:The present work was led by a multidisciplinary panel of experts and proposes an extensive review on the use of prescription crystalline glucosamine sulfate (pCGS) in the multimodal treatment of osteoarthritis (OA) applicable in Ukraine and other Commonwealth of Independent States (CIS) countries.Methods:A panel of rheumatologists, orthopedic surgeons, and field experts from Ukraine and CIS regions discussed the management of OA. Literature was systematically searched using Medline, EMBASE, CIHNAL, and Cochrane Library databases. The 2-day meeting critically reviewed the available literature, treatment algorithms, pharmacoeconomic aspects, and real-world instances to form a multimodal approach based both on real-life clinical practice and systematic literature research for the management of OA in Ukraine and CIS countries.Expert Opinion:pCGS plays a pivotal role in the stepwise approach to OA treatment. If it is necessary (step 1), the combined use of pCGS with paracetamol and topical nonsteroidal anti-inflammatory drugs (NSAIDs) has been recommended. If symptoms persist, oral NSAIDs and intra-articular (IA) hyaluronic acid or corticosteroids are added to the therapy (step 2) of pCGS in the patients. In case of insufficient relief and severe OA (step 3), pCGS along with oral NSAIDs, IA corticosteroids, and duloxetine have been recommended. Patient stratification with regular monitoring and careful alterations in treatment were advocated.Conclusions:This expert opinion article recommends a modified approach to the existing guidelines incorporating pCGS in treatment modality of OA in Ukraine and CIS countries. Extensive use of pCGS targets early symptomatic relief in OA while limiting the adverse effects due to long-term use of analgesics and NSAIDs.

A comparison of axillary thoracotomy versus video-assisted thoracoscopic surgery in the surgical treatment of primary spontaneous pneumothorax.

This study aims to compare the results of video-assisted thoracoscopic surgery and axillary thoracotomy in the surgical treatment of primary spontaneous pneumothorax. Between January 2009 and December 2015, a total of 199 patients (178 males, 21 females; mean age 21.3±7.1 years; range 13 to 35 years) with primary spontaneous pneumothorax who were operated at Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital, Department of Thoracic Surgery and Kadikoy and Kozyatagi Acibadem hospitals were retrospectively analyzed. Of these patients, 48 underwent axillary thoracotomy, wedge resection, apical pleurectomy, and tissue adhesives, while 151 were administered videoassisted thoracoscopic surgery, wedge resection, apical pleurectomy, and tissue adhesives. Both groups were compared in terms of age, gender, the amount of long-term analgesic use, duration of surgery, length of hospitalization, recurrence, complication, and mortality rates. The patients were followed for one year. No mortality was observed in any patient. There was no significant difference in the age and gender distributions of the patients, postoperative length of hospital stay, recurrence rates, and complication rates according to the type of operation. However, the duration of operation was longer in the videoassisted thoracoscopic surgery patients. Video-assisted thoracoscopic surgery is associated with less pain and higher patient satisfaction and allows returning to daily activities in a shorter time period. Based on our study results, we suggest that video-assisted thoracoscopic surgery is more suitable, compared to axillary thoracotomy, owing to its advantages, such as being less invasive and providing a better angle of view.

Effects of analgesics on olfactory function and the perception of intranasal trigeminal stimuli.

There is some evidence suggesting that analgesics have an impact on human chemosensory function, especially opioids and cannabinoids are known to interfere with olfactory function. However, largely unknown is the effect of a long-term use of analgesics on the intranasal trigeminal system so far. Here, we investigated olfactory function and the perception of intranasal trigeminal stimuli in pain patients with long-term use of analgesics compared to age-matched healthy controls. For this purpose, a psychophysical approach was chosen to measure these sensory functions in 100 chronic pain patients and 95 controls. Olfactory testing was performed using the 'Sniffin' Sticks' test kit, which involves tests for odour threshold, odour discrimination and odour identification. Further, participants were asked to rate the intensity of trigeminal stimuli by using a visual analogue scale. We observed that the chronic use of pain medication was associated with significantly reduced perception of intranasal trigeminal stimuli and olfactory function compared to age-matched controls without intake of analgesics. Results indicate that non-opioid and opioid drugs, or a combination of both did not differ in their effects on chemosensory function. Further, after eliminating the effect of a co-existing depression and the use of co-analgesics, the negative influence of analgesics on olfactory function and trigeminal perception was still evident. The observed effect might be mediated due to interaction with opioid receptors in trigeminal ganglia and nuclei or due to trigeminal/olfactory interaction. As a practical consequence, patients should be made aware of a possible impairment of their olfactory and trigeminal function under long-term analgesic treatment. WHAT DOES THIS STUDY ADD?: We observed that the chronic use of pain medication was associated with significantly reduced olfactory function and perception of intranasal trigeminal stimuli compared to age-matched controls without intake of analgesics. Non-opioid and opioid drugs did not differ in their effects on chemosensory function.

Long term use of analgesics and risk of osteoarthritis progressions and knee replacement: propensity score matched cohort analysis of data from the Osteoarthritis Initiative

To determine the association between the long-term use of analgesics and progression of osteoarthritis (OA) as evidenced by up to 3-years follow-up worsening of radiographic Kellgren-Lawrence (KL) grade and incidence of knee replacement (KR). Using nearest neighbor matching of the propensity scores with caliper in the Osteoarthritis Initiative (OAI) cohort, 173 index (Analgesic+) and 173 referent (Analgesic-) subjects were included. Analgesic+ and- subjects had analgesics in all and none of their visits, respectively. Analgesic+ and- subjects were balanced in their demographics, baseline, first, second and third year body mass index (BMI), Western Ontario and McMaster (WOMAC) total score, Physical and Mental health summary scales (SF-12), Physical Activity Scale for the Elderly (PASE) and Charleston Comorbidity Scale. Analgesic+ and- subjects were also matched for baseline radiographic KL grade. Interval increase in the KL grade and incidence of KR were defined as the outcome. Included subjects had average 6.5 years of follow-up. By the third year, 44 subjects had an interval increase in the KL grade; 29 in Analgesic+ and 15 among Analgesic- subjects (P=0.024). By the eighth-year, 41 subjects had their first KR; 29 in Analgesic+ and 12 among Analgesic- subjects (P=0.005). Hazard Ratio (HR) of OA progression and KR for Analgesic+ subjects was 1.91 (1.02-3.57) and 2.57 (1.31-5.04), respectively. Long-term use of analgesics may be associated with radiographic progression of knee OA and increased risk of future KR.

Prescription pain medications and chronic headache in Denmark: implications for preventing medication overuse.

The aim of the present paper is to study which prescription pain medications are most commonly dispensed to people with chronic headache (CH), particularly those with medication-overuse headache (MOH). This cross-sectional study analysed prescription pain medications dispensed within 1 year to 68,518 respondents of a national health survey. Participants with headache ≥ 15 days per month for 3 months were classified as having CH. Those with CH and over-the-counter analgesic use ≥ 15 days per month or purchase of ≥ 20 or ≥ 30 defined daily doses (DDDs) of prescription pain medication per month (depending on the drug) were classified as having MOH. Associations between CH and other chronic pain conditions were analysed by logistic regression. Among those with CH (adjusted prevalence 3.3%, CI 3.2-3.5%), pain medications most commonly dispensed were paracetamol, tramadol, ibuprofen and codeine. CH was associated with osteoarthritis, back pain, and rheumatoid arthritis. Among those with MOH, 32.4% were dispensed an opioid at least once within 1 year. Only 5.1% of people with CH were dispensed triptans. High prevalence of opioid use among people with CH may be due to inappropriate headache treatment or development of MOH among those treated for other pain conditions. While there were cases of triptan overuse, triptans remain underutilized among those with CH, suggesting that migraine may be under-recognized and inappropriately treated, leading to overuse of other medications. Education of physicians on appropriate headache management is essential for MOH prevention. There is a need to increase universal awareness about MOH as an adverse effect of long-term analgesic use.

Biomarkers of osteoarthritis: translating information from in vitro culture systems to human patients

Biomarkers are anatomic, physiologic, biochemical, or molecular parameters that may be associated with the presence and severity of a specific disease. They are detectable by using a variety of methods, including physical examination, laboratory assays, and imaging and can be used as indicators of pharmacologic responses to therapeutic interventions. Despite the interest in biomarkers, there are currently no reliable, quantifiable and easily measured markers that provide an earlier diagnosis of arthritic diseases such as osteoarthritis (OA), especially during the asymptomatic and pre-radiographic stages of the disease. For example, many of the existing biomarkers of joint damage identify fragments of the extracellular matrix of cartilage (i.e. fragments of type II collagen, aggrecan and smaller proteoglycans). Identification of fragments of these molecules in urine or serum does not consistently correlate with radiographic changes and symptoms. Furthermore, biomarkers of type II collagen and aggrecan are not specific for the various stages of OA, and in some cases, may not even be specific for OA. Consequently, there are no reliable assays that can inform prognostic evaluations and monitor responses to therapeutic modalities. The lack of such biomarkers has also hampered the development of structure-modifying pharmacological agents for the treatment of OA. Current pharmacological management of this disease is dominated by analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), slow-acting symptomatic drugs and intra-articular injection of hyaluronic acid (viscosupplementation) or corticosteroids. Analgesics and NSAIDs are commonly administrated to all patients, irrespective of the stage of the disease. However, clinical trials have shown that only 20 to 60 percent of patients actually respond to treatment. This means that many patients will not benefit from the drugs that are administered. Also, long-term use of analgesics and NSAIDs is associated with adverse reactions and gastro-intestinal side effects. Therefore, identification of more sensitive biomarkers of pre-radiographic joint tissue turnover have the capacity to reflect disease relevant biological activity and provide useful diagnostic and therapeutic information, enabling a more rational, targeted and individualized approach to disease management. The recent proliferation of post-genomic technologies has resulted in rapid growth and progress in biomarker research. Current research on OA biomarkers focuses on identification of biomarkers in urine, serum and synovial fluid using approaches including proteomics, metabolomics, lipidomics, advanced imaging techniques, genomics, epigenomics and transcriptmoics and bioinformatics. This presentation will discuss how these technologies are currently being applied to identify early biomarkers of joint inflammation and tissue damage using 2-D and 3-D culture systems and translating the information for the benefit of human patients. There is considerable interest in developing “combination biomarkers” that include biochemical, immunologic, genetic and imaging data. It is anticipated that “combination biomarkers” will have the diagnostic and prognostic power to predict responses to pharmaceutical agents and non-pharmacological therapies and facilitate patient sub-classification/stratification strategies to increase homogeneity in study and treatment groups. However, the availability of tools and reagents is a major bottleneck in the biomarker pipeline, which has consequences for the development of disease-modifying osteoarthritis drugs (DMOADs).

Postoperative opioids

Postoperative opioids

Long-term Analgesic Use: Sometimes Less Is Not More—Reply

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Long-term Analgesic Use After Low-Risk Surgery

This study evaluated the risk of long-term analgesic use after low-risk surgery in older adults not previously prescribed analgesics. We conducted a retrospective cohort study using linked, population-based administrative data in Ontario, Canada, from April 1, 1997, through December 31, 2008. We identified Ontario residents 66 years and older who were dispensed an opioid within 7 days of a short-stay surgery (cataract surgery, laparoscopic cholecystectomy, transurethral resection of the prostate, or varicose vein stripping) and assessed the risk of long-term opioid use, defined as a prescription for an opioid within 60 days of the 1-year anniversary of the surgery. In a secondary analysis, we examined the risk of long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs). We used multivariate logistic regression to examine the association between postsurgical use of analgesics and long-term use. Among 391,139 opioid-naive patients undergoing short-stay surgery, opioids were newly prescribed to 27,636 patients (7.1%) within 7 days of being discharged from the hospital, and opioids were prescribed to 30,145 patients (7.7%) at 1 year from surgery. An increase in the use of oxycodone was found during this time (from 5.4% within 7 days to 15.9% at 1 year). In our primary analysis, patients receiving an opioid prescription within 7 days of surgery were 44% more likely to become long-term opioid users within 1 year compared with those who received no such prescription (adjusted odds ratio, 1.44; 95% CI, 1.39-1.50). In a secondary analysis, among 383,780 NSAID-naive patients undergoing short-stay surgery, NSAIDs were prescribed to 1169 patients (0.3%) within 7 days of discharge and to 30,080 patients (7.8%) at 1 year from surgery. Patients who began taking NSAIDs within 7 days of surgery were almost 4 times more likely to become long-term NSAID users compared with patients with no such prescription (adjusted odds ratio, 3.74; 95% CI, 3.27-4.28). Prescription of analgesics immediately after ambulatory surgery occurs frequently in older adults and is associated with long-term use.