Search

Background: Accessing sexual and reproductive health (SRH) services in rural Australia presents complex challenges that negatively impact women's health and exacerbate health inequities across the life course. This systematic review synthesises evidence on the barriers and facilitators to women's access to SRH services in rural Australia, considering both supply and demand dimensions., Methods: We systematically searched peer-reviewed literature published between 2013 and 2023. Search terms were derived from three major topics: (1) women living in rural Australia; (2) spatial or aspatial access to SRH services; and (3) barriers or facilitators. We adopted the "best fit" approach to framework synthesis using the patient-centred access to healthcare model., Results: Database searches retrieved 1,024 unique records, with 50 studies meeting the inclusion criteria. Most studies analysed access to primary care services (n = 29; 58%), followed by hospital services (n = 14; 28%), health promotion and prevention (n = 5; 10%), and specialist care (n = 2; 4%). The type of care accessed was mostly maternity care (n = 21; 42%), followed by abortion services (n = 11; 22%), screening and testing (n = 8; 16%), other women's health services (n = 6; 12%), and family planning (n = 4; 8%). There were numerous barriers and facilitators in access from supply and demand dimensions. Supply barriers included fragmented healthcare pathways, negative provider attitudes, limited availability of services and providers, and high costs. Demand barriers encompassed limited awareness, travel challenges, and financial burdens. Supply facilitators included health system improvements, inclusive practices, enhanced local services, and patient-centred care. Demand facilitators involved knowledge and awareness, care preferences, and telehealth accessibility., Conclusion: This review highlights the urgent need for targeted interventions to address SRH service access disparities in rural Australia. Understanding the barriers and facilitators women face in accessing SRH services within the rural context is necessary to develop comprehensive healthcare policies and interventions informed by a nuanced understanding of rural women's diverse needs., (© 2024. The Author(s).)

Consensus guidelines exist for genotype-guided fluoropyrimidine dosing based on variation in the gene dihydropyrimidine dehydrogenase (DPYD). However, these guidelines have not been widely implemented in North America and most studies of pretreatment DPYD screening have been conducted in Europe. Given regional differences in treatment practices and rates of adverse events (AEs), we investigated the impact of pretreatment DPYD genotyping on AEs in a Canadian context. Patients referred for DPYD genotyping prior to fluoropyrimidine treatment were enrolled from December 2013 through November 2019 and followed until completion of fluoropyrimidine treatment. Patients were genotyped for DPYD c.1905+1G>A, c.2846A>T, c.1679T>G, and c.1236G>A. Genotype-guided dosing recommendations were informed by Clinical Pharmacogenetics Implementation Consortium guidelines. The primary outcome was the proportion of patients who experienced a severe fluoropyrimidine-related AE (grade ≥3, Common Terminology Criteria for Adverse Events version 5.0). Secondary outcomes included early severe AEs, severe AEs by toxicity category, discontinuation of fluoropyrimidine treatment due to AEs, and fluoropyrimidine-related death. Among 1394 patients, mean (SD) age was 64 (12) years, 764 (54.8%) were men, and 47 (3.4%) were DPYD variant carriers treated with dose reduction. Eleven variant carriers (23%) and 418 (31.0%) noncarriers experienced a severe fluoropyrimidine-related AE (p = 0.265). Six carriers (15%) and 284 noncarriers (21.1%) experienced early severe fluoropyrimidine-related AEs (p = 0.167). DPYD variant carriers treated with genotype-guided dosing did not experience an increased risk for severe AEs. Our data support a role for DPYD genotyping in the use of fluoropyrimidines in North America., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

This is a 2-center, retrospective study which aimed to evaluate the effect of baseline corticosteroid use on immunotherapy efficacy in patients with advanced melanoma. We included all patients with advanced unresectable and metastatic melanoma on single-agent programmed cell death protein 1 (PD-1) inhibitors at the Cancer Centre of Southeastern Ontario and London Regional Cancer Program. We defined baseline corticosteroid use as prednisone-equivalent of ≥10 mg within 30 days of immunotherapy initiation. Our study had 166 patients in total, and 25 were taking corticosteroids at the initiation of the PD-1 inhibitor. Baseline prednisone-equivalent ≥10 mg did not have effect on median overall survival (hazard ratio=1.590, 95% confidence interval: 0.773-3.270, P=0.208). However, a higher dose of baseline prednisone-equivalent ≥50 mg was independently associated with poor median overall survival (hazard ratio=2.313, 95% confidence interval: 1.103-4.830, P=0.026) when compared with baseline prednisone-equivalent 0-49 mg, even when controlled for confounders including baseline Eastern Cooperative Oncology Group ≥2 and baseline brain metastasis. Consideration should be made to decrease the use of unnecessary steroids as much as possible before initiation of PD-1 inhibitor treatment., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Female patients with breast cancer frequently develop arthralgia when treated with aromatase inhibitors (AI). Although the mechanism of AI-induced arthralgia is unknown, potential biomarkers have been identified. The purpose of this study was to investigate the clinical and genetic predictors of AI-induced arthralgia in a prospective cohort of patients with estrogen receptor-positive breast cancer., Methods: One hundred and ninety-six patients were enrolled at initiation of AI therapy with either letrozole or anastrozole. Patients completed two validated self-report questionnaires assessing pain, stiffness, and physical function at baseline, and repeated the questionnaires at two and at six months after the initiation of treatment with an AI. Germline DNA of all patients was genotyped for seven single-nucleotide polymorphisms (SNPs) previously identified by genetic screens and genome-wide association studies as associated with AI-induced arthralgia., Results: More than 50% of the study group experienced arthralgia symptoms. Genetic analysis revealed that four SNPs, in CYP19A1 (rs4775936) and ESR1 (rs9322336, rs2234693, rs9340799), were associated with the development of arthralgia (adjusted P = 0.016, 0.018, 0.017, 0.047). High body mass index (BMI) was also associated with the development of arthralgia symptoms (adjusted P = 0.001). Patients prescribed letrozole were significantly more likely to develop arthralgia than patients on anastrozole (P = 0.018), and also more likely to discontinue AI therapy due to arthralgia. The CYP19A1 (rs4775936) SNP was significantly associated with discontinuation of therapy due to intolerable arthralgia., Conclusions: Our results suggested that BMI and AI drug (letrozole versus anastrozole) were clinical predictors of arthralgia, while genetic variants rs4775936, rs9322336, rs2234693, and rs9340799 were genetic predictors of AI-induced arthralgia. Significantly, rs4775936 was also a predictor of discontinuation of therapy.

Background: New mothers often need support to establish and maintain breastfeeding, and rural women may find it difficult to access breastfeeding resources locally. There are many smartphone applications for breastfeeding mothers; however, very few have been developed by health professionals. We evaluated a smartphone application, Breastfeeding Solutions, developed by U.S. IBCLC Nancy Mohrbacher. Research aims: The aims were (a) to explore usability of the application among rural Australian breastfeeding women and (b) to describe participants' infant feeding outcomes compared with the general population., Methods: A prospective longitudinal self-report survey design was used. Data were collected via online questionnaires at baseline and at 3 and 6 months from a convenience sample of new mothers. The setting was southwest Victoria, Australia, from 2016 to 2017. Descriptive statistics were used to answer research aims., Results: Of the initial 46 participants who received the app, 63% ( n = 29) completed surveys at 3 and 6 months. Usability was assessed at 3 months: 93.5% of participants (29 of 31) rated the application favorably, whereas 96.8% (30 of 31) found the application helpful and 87.1% (27 of 31) would recommend it to other mothers. At the 6-month survey, 79% of participants ( n = 23) were breastfeeding; 10% ( n = 3) had stopped breastfeeding during the first 3 months. The local breastfeeding rate at 6 months was approximately 50% according to routinely collected data; however, we cannot infer that the application was responsible for the difference., Conclusion: The smartphone application was acceptable to breastfeeding women in an Australian rural setting. Further evaluation using a user-centered design could improve rural postpartum women's access to reliable, evidence-based information.

Purpose: The aromatase inhibitor (AI) letrozole is a first-line drug in the adjuvant treatment of breast cancer in postmenopausal women. Adherence to AI therapy, including letrozole, remains problematic due to the development of debilitating AI-induced arthralgia. Letrozole is metabolized in the liver by CYP2A6. It remains unknown if plasma letrozole levels or CYP2A6 genetic variation is associated with the development of arthralgia., Methods: We enrolled 126 female breast cancer patients initiated on letrozole therapy and prospectively collected blood samples at baseline and two follow-up time points to determine letrozole plasma concentrations and CYP2A6 genotype. At each visit, participants completed two validated questionnaires to assess the severity of arthralgia symptoms., Results: More than half (55%) of patients experienced a significant increase in their arthralgia symptoms after initiation of treatment. The clinical variables of body mass index (P = 0.0003) and age (P = 0.0430) were negatively and positively associated with plasma letrozole concentrations, respectively. CYP2A6 genotype was significantly associated with letrozole levels (P < 0.0001), and increased plasma letrozole levels were observed in patients with CYP2A6 reduced-function genotypes. Plasma levels of letrozole and CYP2A6 genotype were not significantly associated with a change in pain score from baseline., Conclusions: CYP2A6 genotype was a significant predictor of letrozole plasma levels, but was not associated with the development of arthralgia.

Recently protein kinases have emerged as some of the most promising drug targets; and therefore, pharmaceutical strategies have been developed to inhibit kinases in the treatment of a variety of diseases. CK2 is a serine/threonine-protein kinase that has been implicated in a number of cellular processes, including maintenance of cell viability, protection of cells from apoptosis, and tumorigenesis. Elevated CK2 activity has been established in a number of cancers where it was shown to promote tumorigenesis via the regulation of the activity of various oncogenes and tumor suppressor proteins. Consequently the development of CK2 inhibitors has been ongoing in preclinical studies, resulting in the generation of a number of CK2-directed compounds. In the present study, an unbiased evaluation of CK2 inhibitors 4,5,6,7-tetrabromo-1H-benzotriazole (TBB), 4,5,6,7-tetrabromo-1H-benzimidazole (TBBz), and 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) was carried out to elucidate the mechanism of action as well as inhibitor specificity of these compounds. Utilizing a chemoproteomics approach in conjunction with inhibitor-resistant mutant studies, CK2alpha and CK2alpha' were identified as bona fide targets of TBB, TBBz, and DMAT in cells. However, inhibitor-specific cellular effects were observed indicating that the structurally related compounds had unique biological properties, suggesting differences in inhibitor specificity. Rescue experiments utilizing inhibitor-resistant CK2 mutants were unable to rescue the apoptosis associated with TBBz and DMAT treatment, suggesting the inhibitors had off-target effects. Exploitation of an unbiased chemoproteomics approach revealed a number of putative off-target inhibitor interactions, including the discovery of a novel TBBz and DMAT (but not TBB) target, the detoxification enzyme quinone reductase 2 (QR2). The results described in the present study provide insight into the molecular mechanism of action of the inhibitors as well as drug specificity that will assist in the development of more specific next generation CK2 inhibitors.