Urban Rural Differences in Breast Cancer in New Zealand

Many rural communities have poor access to health services due to a combination of distance from specialist services and a relative shortage of general practitioners. Our aims were to compare the characteristics of urban and rural women with breast cancer in New Zealand, to assess breast cancer-specific and all-cause survival using the Kaplan–Meier method and Cox proportional hazards model, and to assess whether the impact of rurality is different for Māori and New Zealand (NZ) European women. We found that rural women tended to be older and were more likely to be Māori. Overall there were no differences between urban and rural women with regards their survival. Rural Māori tended to be older, more likely to be diagnosed with metastatic disease and less likely to be screen detected than urban Māori. Rural Māori women had inferior breast cancer-specific survival and all-cause survival at 10 years at 72.1% and 55.8% compared to 77.9% and 64.9% for urban Māori. The study shows that rather than being concerned that more needs to be done for rural women in general it is rural Māori women where we need to make extra efforts to ensure early stage at diagnosis and optimum treatment

The Profile of Non-Communicable Disease (NCD) research in the Middle East and North Africa (MENA) region: Analyzing the NCD burden, research outputs and international research collaboration.

OBJECTIVES: Despite the rising risk factor exposure and non-communicable disease (NCD) mortality across the Middle East and the North African (MENA) region, public health policy responses have been slow and appear discordant with the social, economic and political circumstances in each country. Good health policy and outcomes are intimately linked to a research-active culture, particularly in NCD. In this study we present the results of a comprehensive analysis of NCD research with particular a focus on cancer, diabetes and cardiovascular disease in 10 key countries that represent a spectrum across MENA between 1991 and 2018. METHODS: The study uses a well validated bibliometric approach to undertake a quantitative analysis of research output in the ten leading countries in biomedical research in the MENA region on the basis of articles and reviews in the Web of Science database. We used filters for each of the three NCDs and biomedical research to identify relevant papers in the WoS. The countries selected for the analyses were based on the volume of research outputs during the period of analysis and stability, included Egypt, Iran, Jordan, Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, Turkey and the United Arab Emirates. RESULTS: A total of 495,108 biomedical papers were found in 12,341 journals for the ten MENA countries (here we consider Turkey in the context of MENA). For all three NCDs, Turkey's output is consistently the highest. Iran has had considerable growth in research output to occupy second place across all three NCDs. It appears that, relative to their wealth (measured by GDP), some MENA countries, particularly Oman, Qatar, Kuwait and the United Arab Emirates, are substantially under-investing in biomedical research. In terms of investment on particular NCDs, we note the relatively greater commitment on cancer research compared with diabetes or cardiovascular disease in most MENA countries, despite cardiovascular disease causing the greatest health-related burden. When considering the citation impact of research outputs, there have been marked rises in citation scores in Qatar, Lebanon, United Arab Emirates and Oman. However, Turkey, which has the largest biomedical research output in the Middle East has the lowest citation scores overall. The level of intra-regional collaboration in NCD research is highly variable. Saudi Arabia and Egypt are the dominant research collaborators across the MENA region. However, Turkey and Iran, which are amongst the leading research-active countries in the area, show little evidence of collaboration. With respect to international collaboration, the United States and United Kingdom are the dominant research partners across the region followed by Germany and France. CONCLUSION: The increase in research activity in NCDs across the MENA region countries during the time period of analysis may signal both an increasing focus on NCDs which reflects general global trends, and greater investment in research in some countries. However, there are several risks to the sustainability of these improvements that have been identified in particular countries within the region. For example, a lack of suitably trained researchers, low political commitment and poor financial support, and minimal international collaboration which is essential for wider global impact

Methods of a national colorectal cancer cohort study: the PIPER Project

A national study looking at bowel cancer in New Zealand has previously been completed (the PIPER Project). The study included 5,610 patients and collected medical information about how each person was found to have bowel cancer and the treatment they received. This paper reports how the study was carried out. The information collected in the study will be used to look at the quality of care being provided to New Zealand patients with bowel cancer, and to find out if differences in care occur based on where people live, their ethnicity and their socioeconomic status

Ethnic disparities in breast cancer survival in New Zealand: which factors contribute?

Background: New Zealand has major ethnic disparities in breast cancer survival with Maori (indigenous people) and Pacific women (immigrants or descended from immigrants from Pacific Islands) faring much worse than other ethnic groups. This paper identified underlying factors and assessed their relative contribution to this risk differential. Methods: This study involved all women who were diagnosed with primary invasive breast cancer in two health regions, covering about 40% of the national population, between January 2000 and June 2014. Maori and Pacific patients were compared with other ethnic groups in terms of demographics, mode of diagnosis, disease factors and treatment factors. Cox regression modelling was performed with stepwise adjustments, and hazards of excess mortality from breast cancer for Maori and Pacific patients were assessed. Results: Of the 13,657 patients who were included in this analysis, 1281 (9.4%) were Maori, and 897 (6.6%) were Pacific women. Compared to other ethnic groups, they were younger, more likely to reside in deprived neighbourhoods and to have co-morbidities, and less likely to be diagnosed through screening and with early stage cancer, to be treated in a private care facility, to receive timely cancer treatment, and to receive breast conserving surgery. They had a higher risk of excess mortality from breast cancer (age and year of diagnosis adjusted hazard ratio: 1.76; 95% CI: 1.51-2.04 for Maori and 1.97; 95% CI: 1.67-2.32 for Pacific women), of which 75% and 99% respectively were explained by baseline differences. The most important contributor was late stage at diagnosis. Other contributors included neighbourhood deprivation, mode of diagnosis, type of health care facility where primary cancer treatment was undertaken and type of loco-regional therapy. Conclusions: Late diagnosis, deprivation and differential access to and quality of cancer care services were the key contributors to ethnic disparities in breast cancer survival in New Zealand. Our findings underscore the need for a greater equity focus along the breast cancer care pathway, with an emphasis on improving access to early diagnosis for Maori and Pacific women

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Common femoral artery injury secondary to bicycle handlebar trauma

AbstractBlunt trauma from bicycle handlebars is associated with well-described injuries of the abdominal viscera. These injuries result from the forceful compression of the relatively immobile abdominal organs between the handlebar end and the vertebral bodies. The common femoral artery is also immobile as it passes anterior to the superior pubic ramus, rendering this vessel susceptible to a similar mechanism of injury. We have treated two children who sustained thrombosis of the common femoral artery caused by bicycle handlebar trauma. The lack of familiarity with this uncommon mode of injury may contribute to delayed diagnosis and increased morbidity. We therefore wish to draw attention to this mechanism of injury. (J Vasc Surg 2002;35:589-91.