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Benzodiazepine dosing schedule was not associated with risk of death from drug overdose.Conclusions Among veterans receiving opioid analgesics, receipt of benzodiazepines was associated with an increased risk of death from drug overdose in a dose response fashion.IntroductionDeaths from drug overdose, particularly involving opioid analgesics, have increased steadily over the past two decades and are now one of the leading causes of mortality from injury in the United States.1 Of the deaths from overdose related to pharmaceuticals, which constituted 58% of total deaths from drug overdose in 2010, 75% involved opioid analgesics.2 Thirty percent of overdose deaths related to opioid analgesics involved benzodiazepines, drugs commonly prescribed concurrently for patients who receive opioid analgesics.3 4 5 Although the toxicity of benzodiazepines used in isolation is generally considered mild in young and middle aged adults, the risks from oversedation are believed to be magnified when they are combined with other substances with sedating properties, such as opioids.6 7 Also, receipt of benzodiazepines could be a marker of the presence of a severe anxiety disorder, which carries its own risk for death from intentional and unintentional overdose.8 9Trends in deaths from overdose have been connected to patterns of opioid prescribing, an increasingly common treatment for pain.10 On a population level, increasing rates of opioid prescribing have been linked to an increased rate of death from overdose11; on an individual level, the risk of death from overdose is higher among those receiving higher doses of opioids.12 13 One study generated the hypothesis that receipt of benzodiazepines might be associated with increased risk of death from overdose in patients receiving opioid analgesics.13 To our knowledge, no large nationwide study has focused on death from drug overdose and receipt of benzodiazepines and their prescribing patterns, such as the daily benzodiazepine dose, the type of benzodiazepine prescribed, or the dosing schedule of the prescription, among those receiving opioids for pain.We investigated the relation between the receipt of concurrent benzodiazepines and opioid analgesics and death from drug overdose in patients receiving prescription opioids for the treatment of acute or chronic pain and pain associated with cancer. Quantification of the magnitude of risk associated with these patterns might help to identify individuals at particularly high risk for death from drug overdose and could potentially inform risk reduction approaches in this population. We hypothesized that receipt of concurrent benzodiazepines and opioid analgesics would be associated with death from drug overdose and that this association would be dose dependent and vary by type of benzodiazepine and dosing schedule.
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Low back pain has been the leading cause of years lost to disability over the past several decades,1 with a lifetime prevalence that ranges between 50% and 90%.2 3 The economic cost is estimated to exceed $100bn a year in the United States (67bn, 93bn), over half of which can be attributed to lost productivity.3 4 Efforts to deal with the worldwide burden posed by low back pain have become an international priority.The classification of back pain is perhaps the most important distinction for clinicians to make as it influences investigation and treatment decisions at all levels of care.5 Since the development of validated instruments to categorize low back pain,6 7 studies have determined that the proportion of chronic cases that are predominantly neuropathic (that is, sciatica, radicular pain from a herniated disc, or neurogenic claudication from spinal stenosis) ranges between 17% and 55%,7 8 9 10 11 with one review finding a median prevalence rate of 41%.12 Whereas the presence of neuropathic symptoms portends a more negative prognosis for acute episodes,13 lumbosacral radicular pain might be more responsive to procedural interventions than non specific back pain.12 14Epidural steroid injections are the most commonly performed procedure for pain relief in the world,15 being more commonly used and more effective for radicular pain than mechanical spine pain.12 16 Although mixed, most controlled studies have also found pharmacotherapy with gabapentinoids can be effective for lumbosacral radicular pain.17 18 19 20 21Numerous controlled trials have been performed to evaluate epidural steroid injections and drug treatment in people with low back pain, with review articles generally reporting modest effects.12 22 Yet for clinicians, the more relevant question is not whether a real treatment is better than a sham treatment, but which treatment is more effective.23Several small randomized open label studies have looked at epidural steroid injections compared with drug treatment. One study showed superiority for a single epidural steroid injection at one month but not later follow up compared with tramadol and a muscle relaxant.24 A second study showed that a single caudal epidural steroid injection provided better pain relief than non steroidal anti inflammatory drugs through three months.25 Neither study evaluated first line adjuvant treatments (such as gabapentin) as a comparison group. A more recent three armed multicenter study was performed in 169 patients with cervical radiculopathy.
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