Reduced gastrointestinal-related hospitalisation costs following rescheduling of over-the-counter codeine-containing compound analgesics in Australia: results of a single hospital audit in South Australia.

BACKGROUND: Codeine-containing compound analgesics (CCCAs) are associated with dependence and, when taken in excess, significant risks of harm. A previous audit showed significant costs related to admissions for gastrointestinal (GI) complications of CCCA. Based on this and other evidence of harm, the Australian Therapeutic Goods Administration changed CCCAs to prescription only in 2018. AIMS: We aimed to identify the costs associated with codeine-related GI complications and whether the schedule change in 2018 led to a reduced clinical and financial strain on the health care system. METHODS: We conducted an audit of GI admissions and associated costs of CCCAs at a tertiary teaching hospital in Adelaide between 2016 and 2020. Patients were grouped by 2-year time periods before (group 1) and following (group 2) schedule change. Costs for the index presentation were multiplied for subsequent presentations. Costs and outcomes were compared for groups (standard statistics; P value < 0.05 significant.) RESULTS: Three hundred forty patients (group 1, n = 164; group 2, n = 119) were identified, with the majority of these admitted due to nonsteroidal anti-inflammatory drugs (NSAIDs) only. For CCCAs (NSAID-containing), the same patients were admitted repeatedly with a reduction from 31 to eight admissions (P = 0.005), following rescheduling. The total cost of CCCA admissions was reduced from AU$ 561 691 for group 1 to AU$ 261 764 for group 2 (P < 0.001). CONCLUSIONS: Australian rescheduling of CCCAs in 2018 resulted in a reduction in hospital admissions and costs related to GI complications. The cost savings, even in a single hospital department, were substantial.

Improved Survival of Hepatocellular Carcinoma Patients Diagnosed with a Dedicated Screening Programme-a Propensity Score Adjusted Analysis.

AIM: To assess the overall survival (OS) in those with hepatocellular carcinoma (HCC) diagnosed within a programmatic, centrally co-ordinated, regional screening programme. METHODS: A retrospective cohort analysis of consecutive HCC patients diagnosed between 2004 and 2013. Patients were followed up till death or end of study period (30 April 2015). A dedicated screening programme was commenced in 2009 to screen high-risk patients for HCC. Primary objective is to compare the OS between HCC patients diagnosed within the screening group versus those diagnosed outside this group. Other objectives were to compare tumour stage at diagnosis and the proportion having curative treatments in the two groups. Propensity score adjustments were performed to assess the survival benefit. RESULTS: HCC was diagnosed in 130 subjects during the study period (82.3% males, median [IQR] age 62 [± 19] years and median [IQR] follow-up of 11.3 (± 23.5) months). Ninety-six patients (73.8%) died during the follow-up, and the median (95%CI) OS was 15.7 (9.7-21.8) months. HCC diagnosed within the screening programme had a better OS compared to those diagnosed outside this programme (26.8 vs 11.5 months, p = 0.01). Further, those diagnosed within the programme had an earlier stage HCC ([58.3% vs 23.6%], Ó¼2 = 11.3, p = 0.001), and a significant proportion were treated with curative intent ([62.5% vs 31.1%], Ó¼2 = 8.3, p = 0.004). Propensity score adjustment showed a 58% reduction in mortality for HCC diagnosed within the screening programme (HR [95%CI] 0.42 [0.20-0.89], p = 0.02). CONCLUSION: A programmatic, regional HCC screening programme improved the OS and detected tumours at an earlier stage enabling more patients to have curative therapies.

Involvement of the NO-cGMP-K(ATP) channel pathway in the mesenteric lymphatic pump dysfunction observed in the guinea pig model of TNBS-induced ileitis.

Mesenteric lymphatic vessels actively transport lymph, immune cells, fat, and other macromolecules from the intestine via a rhythmical contraction-relaxation process called lymphatic pumping. We have previously demonstrated that mesenteric lymphatic pumping was compromised in the guinea pig model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced ileitis, corroborating clinical and experimental observations of a dilated and/or obstructed phenotype of these vessels in inflammatory bowel disease. Many mediators released during the inflammatory process have been shown to alter lymphatic contractile activity. Among them, nitric oxide (NO), an inflammatory mediator abundantly released during intestinal inflammation, decreases the frequency of lymphatic contractions through activation of ATP-sensitive potassium (K(ATP)) channels. The objective of this study was to investigate the role of NO and K(ATP) channels in the lymphatic dysfunction observed in the guinea pig model of TNBS-induced ileitis. Using quantitative real-time PCR, we demonstrated that expression of Kir6.1, SUR2B, and inducible NO synthase (iNOS) mRNAs was significantly upregulated in TNBS-treated animals. Pharmacological studies performed on isolated, luminally perfused mesenteric lymphatic vessels showed that the K(ATP) channels blocker glibenclamide, the selective iNOS inhibitor 1400W, and the guanylyl cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) significantly improved lymphatic pumping in quiescent lymphatic vessels from TNBS-treated animals. Membrane potential measurement with intracellular microelectrodes revealed that vessels from TNBS-treated animals were hyperpolarized compared with their sham counterpart and that the hyperpolarization was significantly attenuated in the presence of glibenclamide and ODQ. Our findings suggest that NO and K(ATP) play a major role in the lymphatic contractile dysfunction that occurred as a consequence of the intestinal inflammation caused by TNBS.

Mechanisms of VIP-induced inhibition of the lymphatic vessel pump.

Lymphatic vessels serve as a route by which interstitial fluid, protein and other macromolecules are returned to the blood circulation and immune cells and antigens gain access to lymph nodes. Lymph flow is an active process promoted by rhythmical contraction-relaxation events occurring in the collecting lymphatic vessels. This lymphatic pumping is an intrinsic property of the lymphatic muscles in the vessel wall and consequent to action potentials. Compromised lymphatic pumping may affect lymph and immune cell transport, an action which could be particularly detrimental during inflammation. Importantly, many inflammatory mediators alter lymphatic pumping. Vasoactive intestinal peptide (VIP) is a neuro- and immuno-modulator thought to be released by nerve terminals and immune cells in close proximity to lymphatic vessels. We demonstrated the presence of the peptide in lymphatic vessels and in the lymph and examined the effects of VIP on mesenteric collecting lymphatic vessels of the guinea pig using pharmacological bioassays, intracellular microelectrode electrophysiology, immunofluorescence and quantitative real-time PCR. We showed that VIP alters lymphatic pumping by decreasing the frequency of lymphatic contractions and hyperpolarizing the lymphatic muscle membrane potential in a concentration-dependent manner. Our data further suggest that these effects are mainly mediated by stimulation of the VIP receptor VPAC2 located on the lymphatic muscle and the downstream involvement of protein kinase A (PKA) and ATP-sensitive K⁺ (KATP) channels. Inhibition of lymphatic pumping by VIP may compromise lymph drainage, oedema resolution and immune cell trafficking to the draining lymph nodes.