Access to new cancer medicines in Australia: dispelling the myths and informing a public debate

Despite the high level of spending on cancer medicines in Australia, consumer organisations and the pharmaceutical industry often make claims of delayed or lack of access to new cancer medicines—claims that are frequently supported by prominent coverage in the Australian media. These claims, while morally and psychologically compelling, tend to ignore the complexity of medicines funding decisions. In this commentary we summarise the current situation regarding the registration and funding of cancer medicines in Australia, elucidate the main challenges associated with access to cancer medicines in the Australian context, and describe some of the steps that have been taken to address these challenges. Keywords: Cancer medicines, Funding, High prices, Consumer engagement, Transparency, Public debateNHMRC project grant, App 108067

Photoaffinity labeling of the azidoatrazine receptor site in reaction centers of Rhodopseudomonas sphaeroides

AbstractPhotoaffinity labeling of photosynthetic reaction centers of Rhodopseudomonas sphaeroides by the herbicide inhibitor, azido[14C]atrazine, occurs principally on the L-subunit. The specificity of labeling is greater at 77 than at 295 K. Kinetic studies of charge recombination in reaction centers indicate competition between azidoatrazine and ubiquinone-1 (Q-1) for binding to the reaction center. This competition occurs through the L-subunit binding site, as increasing concentrations of Q-1 decrease azido[14C]atrazine labeling of this site. It is proposed that the inhibitor binding site, predominantly on the L-subunit, and the secondary quinone binding site on the M-subunit, are adjacent so that there is partial overlap by one molecule of the domain occupied by the other

Influence of medication risks and benefits on treatment preferences in older patients with multimorbidity

Multimorbidity is associated with use of multiple medicines, increased risk of adverse events and treatment conflicts. This study aimed to examine how older patients with multimorbidity and clinicians balance the benefits and harms associated with a medication and in the presence of competing health outcomes. Interviews were conducted with 15 participants aged ≥65 years with 2 or more chronic conditions. Three clinical scenarios were presented to understand patient preference to take a medicine according to i) degree of benefit, ii) type of adverse event and impact on daily living and iii) influence of comorbid conditions as competing health outcomes. Semi-structured interviews were also conducted with participants (n=15) and clinicians (n=5) to understand patient preferences and treatment decisions, in the setting of multimorbidity. The median age of participants was 79 years, 55% had 5 or more conditions and 47% took 8 or more medicines daily. When the level of benefit of the medicine ranged from 14% to 70%, 80% of participants chose to take the medicine, but when adverse effects were present, this was reduced to 0-33% depending upon impact on daily activities. In the presence of competing health outcomes, 13%-26% of patients chose to take the medicine. Two-thirds of patients reported that their doctor respects and considers their preferences and discussed medication benefits and harms. Interviews with clinicians showed that their overall approach to treatment decision-making for older individuals with multimorbidity was based upon 2 main factors, the patients' prognosis and their preferences. The degree of benefit gained was not the driver of patients' preference to take a medicine; rather, this decision was influenced by type and severity of adverse effects. Inclusion of patient preferences in the setting of risks and benefits of medicines with consideration and prioritization of competing health outcomes may result in improved health outcomes for people with multimorbidity.Gillian E Caughey, Kirsty Tait, Agnes I Vitry, Sepehr Shaki

Cost driver analysis of statin expenditure on Australia’s pharmaceutical benefits scheme

The Australian Pharmaceutical Benefits Scheme (PBS) provides universal access to subsidised medicines. In 2013, statins as a class had the highest expenditure on the PBS. To assess the influence of policies and drivers affecting PBS statin utilisation and expenditure between 1992 and 2013. Analyses conducted from 1992 to 2013 and over three distinct time periods, including monthly expenditure/prescription, annual utilisation (calculated as Defined Daily Doses/1000 inhabitants/day) and statin strengths dispensed. The major driver of increased PBS expenditure for statins was increased volumes. After adjusting for inflation, the average PBS expenditure on statin prescriptions was the major negative driver. Other influential drivers included the increased use of newer statins and increased strength of statins dispensed. Whilst the inflation-adjusted reimbursed price of statins decreased, increased utilisation, including increased use of patented statins, increased total statin expenditure. Successful measures adopted by other countries could be applied to Australia to decrease total medicines expenditure

A dedicated haem lyase is required for the maturation of a novel bacterial cytochrome c with unconventional covalent haem binding

In bacterial c-type cytochromes, the haem cofactor is covalently attached via two cysteine residues organized in a haem c-binding motif. Here, a novel octa-haem c protein, MccA, is described that contains only seven conventional haem c-binding motifs (CXXCH), in addition to several single cysteine residues and a conserved CH signature. Mass spectrometric analysis of purified MccA from Wolinella succinogenes suggests that two of the single cysteine residues are actually part of an unprecedented CX15CH sequence involved in haem c binding. Spectroscopic characterization of MccA identified an unusual high-potential haem c with a red-shifted absorption maximum, not unlike that of certain eukaryotic cytochromes c that exceptionally bind haem via only one thioether bridge. A haem lyase gene was found to be specifically required for the maturation of MccA in W. succinogenes. Equivalent haem lyase-encoding genes belonging to either the bacterial cytochrome c biogenesis system I or II are present in the vicinity of every known mccA gene suggesting a dedicated cytochrome c maturation pathway. The results necessitate reconsideration of computer-based prediction of putative haem c-binding motifs in bacterial proteomes

Associations of advanced age with comorbidity, stage and primary subsite as contributors to mortality from colorectal cancer

PUBLISHED 06 April 2023Background: Although survival from colorectal cancer (CRC) has improved substantially in recent decades, people with advanced age still have a high likelihood of mortality from this disease. Nonetheless, few studies have investigated how cancer stage, subsite and comorbidities contribute collectively to poor prognosis of older people with CRC. Here, we decided to explore the association of age with mortality measures and how other variables influenced this association. Methods: Using linkage of several administrative datasets, we investigated the risk of death among CRC cases during 2003–2014. Different models were used to explore the association of age with mortality measures and how other variables influenced this association. Results: Our results indicated that people diagnosed at a young age and with lower comorbidity had a lower likelihood of all-cause and CRC-specific mortality. Aging had a greater association with mortality in early-stage CRC, and in rectal cancer, compared that seen with advanced-stage CRC and right colon cancer, respectively. Meanwhile, people with different levels of comorbidity were not significantly different in terms of their increased likelihood of mortality with advanced age. We also found that while most comorbidities were associated with all-cause mortality, only dementia [SHR = 1.43 (1.24–1.64)], Peptic ulcer disease [SHR = 1.12 (1.02–1.24)], kidney disease [SHR = 1.11 (1.04–1.20)] and liver disease [SHR = 1.65 (1.38–1.98)] were risk factors for CRC-specific mortality. Conclusion: This study showed that the positive association of advanced age with mortality in CRC depended on stage and subsite of the disease.We also found only a limited number of comorbidities to be associated with CRC-specific mortality. These novel findings implicate the need for more attention on factors that cause poor prognosis in older people.Kazzem Gheybi, Elizabeth Buckley, Agnes Vitry and David Rode