Prevalence and Incidence Trends for Diagnosed Prescription Opioid Use Disorders in the United Kingdom.

INTRODUCTION: The prevalence of prescription opioid use disorders in the US has increased markedly in parallel with increases in opioid prescribing. Whilst an increase in opioid prescribing has also occurred in the UK, it remains unknown if there have been concurrent increases in opioid use disorders. The aim of this study was to examine national trends in the prevalence and incidence of physician-diagnosed opioid use disorders in the UK. METHODS: In a retrospective electronic health care database analysis using data from the UK Clinical Practice Research Datalink (CPRD), we identified persons receiving a first opioid prescription between January 1, 2008 and December 31, 2012. Persons with an opioid use disorder were identified by Read codes assigned by patients' physicians within 6 months following an opioid prescription. We calculated prevalence and incidence rates by dividing the analysis population by the total number of patients exposed (prevalence) or the total patient-years of exposure (incidence) using the 'exact' Clopper-Pearson Binomial method. RESULTS: Our analysis included 714,699 person-years of prescription opioid exposure. The 5-year period prevalence of opioid use disorders was 4.61 (95% CI 4.28-4.96) per 10,000 individuals, or 0.05%. The incidence rate of opioid use disorders was of 6.51 (95% CI 5.93-7.13) patients per 10,000 patient-years exposed. When examined by study year, there was no clear suggestion of a changing trend over time. When stratified by opioid drug, trends in the incidence rate during the study were either stable (i.e., codeine and tramadol), increasing (i.e., morphine) or decreasing (i.e., dihydrocodeine). CONCLUSIONS: Our study demonstrates that despite the marked increase in overall opioid prescribing in the UK in the past decade, there has not been an increase in the incidence of physician-diagnosed opioid use disorders.

The unique role of transdermal buprenorphine in the global chronic pain epidemic.

Pain is a global epidemic, exacerbated by barriers to access of opioid analgesics. Regulations about opioids attempt to protect public health from the risks of harmful use of opioids, diversion, and dependence. Transdermal buprenorphine is an effective opioid analgesic agent with unique properties that may make it particularly well suited for more widespread use. It is a versatile analgesic product with demonstrated safety and effectiveness in cancer and noncancer pain populations. Its pharmacological properties make it a first-line opioid analgesic for geriatric patients and patients with renal dysfunction; no dosing adjustments need to be made. The 7-day transdermal delivery system is convenient for patients and promotes compliance. A low dose of buprenorphine can provide effective and well-tolerated pain relief. Although buprenorphine has been associated with certain opioid-related adverse effects, such as dizziness and nausea, it is associated with a lower rate of constipation than many other opioid analgesics. The potential for nonmedical use of buprenorphine is relatively low compared with other opioid agents. Buprenorphine has a relatively low likeability for nonmedical use and the transdermal matrix patch renders the substance particularly difficult to extract for illicit purposes.

Utilization characteristics and treatment persistence in patients prescribed low-dose buprenorphine patches in primary care in the United Kingdom: a retrospective cohort study.

BACKGROUND: The 7-day, low-dose buprenorphine patch has been available in the United Kingdom since 2005 for the treatment of chronic nonmalignant pain that is unresponsive to nonopioid analgesics. Osteo-arthritis pain, a significant cause of pain and disability in the elderly, is a common reason for prescribing bu-prenorphine patches. OBJECTIVES: The goals of this study were to investigate utilization and treatment persistence in patients receiving low-dose buprenorphine patches and the expected patterns of treatment 12 months after the initiation of treatment. METHODS: This was a retrospective cohort study of patients who were prescribed low-dose buprenorphine patches in general practice in the United Kingdom. Patients in this cohort were matched by age, sex, and practice with comparator cohorts prescribed oral codeine, dihydrocodeine, or tramadol. Data on baseline characteristics, utilization, and adverse events were obtained from the General Practice Research Database, which contains computerized medical records from UK general practice. Treatment persistence was determined based on repeat prescribing within 90 days after the expected end of a prescription; rates of persistence were compared between the buprenorphine and comparator cohorts. Cox proportional hazards regression models were used to compare the incidence of typical opioid adverse effects (constipation, dizziness, and nausea and/or vomiting) between cohorts. RESULTS: The study cohort included 4968 patients who were prescribed low-dose buprenorphine patches. The majority of patients (64.2%) were aged >65 years, and the most frequently recorded indication for low-dose buprenorphine patches was osteoarthritis (48.7%). Most patients (76.1%) started treatment at the lowest patch strength (5 microg/h). The mean patch strength prescribed over time stabilized at 10 to 12 microg/h. Persistence with low-dose buprenorphine patches over 6 months was significantly higher than with codeine, dihydrocodeine, and tramadol (28.9%, 22.4%, 24.4%, and 23.8%, respectively; P < 0.01). Persistence over 12 months also was significantly higher with low-dose buprenorphine patches compared with the comparators (18.5%, 16.1%, 18.0%, and 17.6%; P < 0.01). After 12 months, the difference in persistence levels between cohorts was not statistically significant. In the Cox proportional hazards regression models, patients using buprenorphine patches had an increased incidence of constipation, dizziness, and nausea and vomiting compared with those who used the comparator opioids (P < 0.05). CONCLUSIONS: Significantly more patients receiving low-dose buprenorphine patches in this study persisted with treatment at 6 and 12 months compared with those receiving other opioid analgesics. Treatment with low-dose buprenorphine patches was most frequently initiated at the lowest patch strength and stabilized at a mean of 10 to 12 microg/h.

Pharmacokinetics of recombinant human growth hormone administered by cool.click 2, a new needle-free device, compared with subcutaneous administration using a conventional syringe and needle.

BACKGROUND: Growth hormone (GH) is used to treat growth hormone deficiency (GHD, adult and paediatric), short bowel syndrome in patients on a specialized diet, HIV-associated wasting and, in children, growth failure due to a number of disorders including Turner's syndrome and chronic renal failure, and in children born small for gestational age. Different brands and generic forms of recombinant human growth hormone (r-hGH) are approved for varying indications in different countries. New ways of administering GH are required because the use of a needle and syringe or a device where a patient still has to insert the needle manually into the skin on a daily basis can lead to low adherence and sub-optimal treatment outcomes. The objective of this study was to assess the relative bioavailability of r-hGH (Saizen, Merck Serono) administered by a new needle-free device, cool.click 2, and a standard needle and syringe. METHODS: The study was performed with 38 healthy volunteers who underwent pituitary somatotrope cell down-regulation using somatostatin, according to a randomized, two-period, two-sequence crossover design. Following subcutaneous administration of r-hGH using cool.click 2 or needle and syringe, pharmacokinetic parameters were analysed by non-compartmental methods. Bioequivalence was assessed based on log-transformed AUC and C(max) values. RESULTS: The 90% confidence intervals for test/reference mean ratio of the plasma pharmacokinetic variables Cmax and AUC(0-inf) were 103.7-118.3 and 97.1-110.0, respectively, which is within the accepted bioequivalence range of 80-125%. r-hGH administered by cool.click 2 is, therefore, bioequivalent to administration by needle and syringe with respect to the rate and extent of GH exposure. Treatment using cool.click 2 was found to be well tolerated. With cool.click 2 the tmax was less (3.0 hours) than for needle and syringe delivery (4.5 hours), p = 0.002 (Friedman test), although this is unlikely to have any clinical implications. CONCLUSION: These results demonstrate that cool.click 2 delivers subcutaneous r-hGH exposure that is bioequivalent to the conventional mode of injection. The new device has the additional advantage of being needle-free, and should help to increase patient adherence and achieve good therapeutic outcomes from r-hGH treatment.