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Background and aims Codeine is the most commonly used opioid in the world, and is available over the counter (OTC) in many countries, including Australia. Several countries are reconsidering codeine's OTC status due to concerns over addiction and misuse, with serious morbidity and mortality being reported. Australia's Therapeutic Goods Administration restricted codeine containing analgesics to 'Pharmacist Only' in 2010, and has recently been considering further up-scheduling to make codeine 'Prescription Only'. This paper estimated Australian trends of codeine misuse over the past 12 years, and examined whether trends changed following previous rescheduling efforts in 2010. Design A retrospective review of calls regarding codeine misuse made to the New South Wales Poisons Information Centre (NSWPIC, Australia's largest poisons centre), 2004-15. Joinpoint software was used to quantify the average annual change in calls, and whether there was a significant change in trend at any time, including following rescheduling. Setting Australia. Participants Four hundred patients about whom a call was made to the NSWPIC. Measures Calls per year, patient age, gender, tablets taken per day, formulation used, symptom disposition. Findings The NSWPIC database contained 400 cases of codeine combination analgesic misuse from 2004 to 2015. Joinpoint analysis showed that the frequency of cases increased significantly from 2004 to 2015, with an average annual percentage change (AAPC) of 19.5% [95% confidence interval (CI) = 13.8-25.5% P < 0.0001] for paracetamol/codeine and 17.9% (95% CI = 7.9-28.9%, P < 0.01) for ibuprofen/codeine. No significant change in trend was seen at any time, including following 2010 rescheduling. The median age of patients was 34 and 27 years for paracetamol/codeine and ibuprofen/codeine cases, respectively. Gender distribution was approximately equal. Clinical features reported were consistent with codeine, paracetamol and ibuprofen toxicity. Conclusions Misuse of codeine combination products appears to be increasing in Australia. Limited rescheduling in 2010 failed to curb this increase. [ABSTRACT FROM AUTHOR]

Objective This paper presents the final analysis of once-daily darunavir/ritonavir ( DRV/r) vs. lopinavir/ritonavir ( LPV/r) in treatment-naïve HIV-1-infected adults. Methods ARTEMIS ( AntiRetroviral Therapy with TMC114 ExaMined In naïve Subjects; NCT00258557) was a randomized, open-label, phase- III, 192-week trial. Patients were stratified by baseline HIV-1 RNA and CD4 count, and randomized to once-daily DRV/r 800/100 mg or LPV/r 800/200 mg total daily dose (either once or twice daily) plus tenofovir/emtricitabine. Results Of 689 randomized patients receiving treatment ( DRV/r: 343; LPV/r: 346), 85 and 114 patients in the DRV/r and LPV/r arms, respectively, had discontinued by week 192. Noninferiority was shown in the primary endpoint of virological response ( HIV-1 RNA < 50 copies/ mL) [ DRV/r: 68.8%; LPV/r: 57.2%; P < 0.001; intent to treat ( ITT)/time to loss of virological response; estimated difference in response 11.6% (95% confidence interval 4.4-18.8%)]. Statistical superiority in virological response of DRV/r over LPV/r was demonstrated for the primary endpoint ( P = 0.002) and for the ITT non-virological-failure-censored analysis (87.4% vs. 80.8%, respectively; P = 0.040). No protease inhibitor ( PI) primary mutations developed and only low levels of nucleoside reverse transcriptase inhibitor ( NRTI) resistance developed in virological failures in both groups. Significantly fewer discontinuations because of adverse events were observed with DRV/r (4.7%) than with LPV/r (12.7%; P = 0.005). Grade 2-4 treatment-related diarrhoea was significantly less frequent with DRV/r than with LPV/r (5.0% vs. 11.3%, respectively; P = 0.003). DRV/r was associated with smaller median increases in total cholesterol and triglyceride levels than LPV/r. Changes in low- and high-density lipoprotein cholesterol were similar between groups. Similar increases in aspartate aminotransferase and alanine aminotransferase for DRV/r and LPV/r were observed. Conclusion Over 192 weeks, once-daily DRV/r was noninferior and statistically superior in virological response to LPV/r, with a more favourable gastrointestinal profile, demonstrating its suitability for long-term use in treatment-naïve patients. [ABSTRACT FROM AUTHOR]