Effect of ethnicity and rurality on treatment delays in patients with colorectal cancer in Northland, New Zealand.

BACKGROUND: Ethnic and rural disparities in medical treatment and outcomes have been demonstrated across a range of conditions, including colorectal cancer. Timely treatment and investigation of symptoms in patients with suspicion of cancer is likely to improve outcomes and patient experience. Achieving equity in timeliness of care is important in achieving the goal of equitable cancer outcomes outlined in the New Zealand cancer action plan. The aim of this study was to compare treatment times in patients with colorectal cancer, between Maori and non-Maori patients as well as urban and rural patients in Northland, New Zealand. METHODS: All adult patients diagnosed with colorectal adenocarcinoma from 2011 to 2016 were identified using hospital coding. Further information on the primary cohort was then obtained using the hospitals electronic results system, CONCERTO. The primary outcomes of interest were differences in delays to treatment between Maori and non-Maori as well as Urban versus rural residence. Secondary outcomes of interest included rate of emergency admission and treatment by curative intent in different groups. RESULTS: A total of 511 patients formed the primary cohort; 12% were Maori and were on average 6 years younger than non-Maori. Maori had a 6% higher emergency admission rate and a 5% higher rate of palliative treatment intent. No significant difference in treatment delay times was seen between different ethnicities or different domiciles. CONCLUSION: Ethnicity and rurality were not shown to affect treatment delays. Further research in this area is needed to help attain equitable outcomes for patients with colorectal cancer in New Zealand.

Pathological complete response rates with pertuzumab-based neoadjuvant chemotherapy in breast cancer: A single-center experience.

BACKGROUND: Pertuzumab-based neoadjuvant chemotherapy (NAC) has demonstrated successful pathologic complete response (pCR) rates when administered to patients with human epidermal growth factor receptor 2 (HER2)-positive, locally advanced breast cancer and has become standard of care. This study aimed to identify pCR rates in patients receiving a variety of pertuzumab-based NAC regimens. The effect of the addition of an anthracycline and impact of anthracycline and taxane sequencing on pCR was also assessed. METHODS: A retrospective, single-center review was conducted on patients with operable, human epidermal growth factor receptor 2 (HER2)-positive breast cancer that received one of five pertuzumab-containing NAC regimens followed by definitive surgery. RESULTS: Ninety-six patients were included in the analysis; overall, pCR was attained in 49 patients (51%). Of the 61 patients who received an anthracycline-containing NAC regimen, 30 (49%) attained a pCR. Of the 35 patients who received the non-anthracycline NAC regimen, 19 (54%) attained a pCR; difference in pCR was not statistically significant (p = 0.63). Anthracycline/taxane sequence analysis showed that of the patients attaining pCR with an anthracycline-containing NAC, 77% of patients received the taxane portion upfront (p = 0.17). Relative dose intensity of the anthracycline portion was similar irrespective of treatment sequence. However, relative dose intensity of the taxane portion was decreased with upfront anthracycline administration. CONCLUSION: These findings support current recommendations of adding pertuzumab to established regimens for treatment of locally advanced, HER2-positive, early stage breast cancer. The benefit of adding an anthracycline in the neoadjuvant setting remains unclear. Patients treated with the taxane portion of NAC upfront appeared to have a higher rate of pCR and better relative dose intensity than patients who received the anthracycline portion upfront, but differences were not statistically significant. These findings should be verified in a prospective clinical trial.

Tocilizumab as first-line therapy for steroid-refractory acute graft-versus-host-disease: analysis of a single-center experience.

Acute graft-versus-host-disease (aGVHD) is a complication after allogeneic stem cell transplant. After the failure of treatment with high dose corticosteroids, steroid-refractory aGVHD (SR aGVHD) is associated with high rates of mortality. Tocilizumab has evidence of activity in SR aGVHD. For patients ineligible for trials, the OSU James Comprehensive Cancer Center has been utilizing tocilizumab as first-line therapy for SR aGVHD. We retrospectively report on 15 patients who received tocilizumab. aGVHD grading and responses were based on consensus criteria. Median age at transplant was 49 years. Median time to tocilizumab administration was 9 days (range, 3-16). Six patients had complete responses (40%) with a resolution of aGVHD. From the last contact, median overall survival for responders was not yet reached vs. 31 days for non-responders (p = .0002). Patients with skin and/or GI aGVHD demonstrated the greatest benefit. Patients with liver aGVHD did not respond. Future studies are needed to evaluate tocilizumab prior to steroid failure.

Efficacy of Palbociclib Combinations in Hormone Receptor-Positive Metastatic Breast Cancer Patients After Prior Everolimus Treatment.

PURPOSE: Outcome data on hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2) nonamplified (HER2-) metastatic breast cancer (MBC) treated with palbociclib after treatment with everolimus are lacking. The PALOMA-3 trial, showing benefit of palbociclib plus fulvestrant compared to fulvestrant alone in HR+HER2- MBC after progression while receiving endocrine therapy excluded women previously treated with everolimus. The objective of this study was to examine outcomes of HR+HER2- MBC with prior exposure to everolimus while receiving palbociclib-based therapy. PATIENTS AND METHODS: A retrospective, single-institute review was conducted of HR+HER2- MBC from January 2014 to November 2016 in patients treated with palbociclib after prior treatment with everolimus. Progression-free survival (PFS) was defined as the time from initiation of palbociclib to the date of progression as determined by the treating physician based on radiologic, biochemical, and/or clinical criteria. Response rates were determined on the basis of available radiologic data. Objective response rate (ORR) was defined as the rate of any complete or partial responses; clinical benefit rate (CBR) was the rate of complete response, partial response, or stable disease for at least 24 weeks. RESULTS: Twenty-three patients with a mean (range) age of 68 (42-81) years were identified. Kaplan-Meier estimate showed median PFS of 2.9 months (95% confidence interval, 2.1-4.2); ORR was 0 of 23 and CBR was 4 (17.4%) of 23. In the PALOMA-3 trial, median PFS, ORR, and CBR of palbociclib cohort were 9.5 months (95% confidence interval, 9.2-11.0), 19%, and 67%, respectively. CONCLUSION: There is a limited clinical activity of palbociclib combinations after progression with everolimus combination therapy. Further studies are necessary to confirm these findings.

Does Pukawakawa (the regional-rural programme at the University of Auckland) influence workforce choice?

AIMS: Relative shortages of rural doctors persist. In 2008 the University of Auckland medical programme introduced a Year 5 regional and rural immersion programme, Pukawakawa, based in Northland, New Zealand (NZ). This study evaluates the early workforce outcomes of graduates of this programme. METHODS: During 2013 we surveyed Auckland medical graduates who were in the 2008-2011 Pukawakawa cohorts. Questions were asked regarding recent and current place of work, future intentions for place of work, and career preference with reasons why. Qualitative analysis was undertaken to analyse free text responses about experiences of Pukawakawa on this choice. RESULTS: Of the 72 Pukawakawa participants, 45 completed the survey, for a response rate of 63%. In 2013, 62% were working in rural or regional areas, with 31% in the Northland DHB. The great majority intend to work rurally or regionally, with 35.6% intending to return to Northland DHB. Of the respondents, 68% listed general practice in their top three future career intentions. CONCLUSIONS: In the early postgraduate years, medical graduates who participated in Pukawakawa are very likely to be working in rural and regional areas. These graduates also show an intention to work in general practice and rural medicine.

A clozapine conundrum: clozapine toxicity in an acute medical illness.

OBJECTIVE: The following report presents a case in which significant clozapine toxicity was demonstrated in a patient on established therapy, in the absence of identifiable risk factors. Through this case report, the authors aim to highlight the potential for clozapine toxicity to occur unexpectedly in times of acute medical illness, and the need to remain vigilant in such situations. METHODS: Case report and review of the relevant literature. RESULTS: We describe a case of a 62 year old man whom developed life-threatening clozapine toxicity in the context of a severe lower respiratory infection. Following investigation to exclude the usual causes of toxicity, it was surmised that impaired CYP1A2 function, secondary to the acute inflammatory process, had led to a toxic level of the drug. CONCLUSIONS: Given the possibility that serum clozapine levels may significantly rise in acute illness, the team recommends measurement of clozapine levels in these situations, in combination with the usual full blood count investigation. Such a practice should be considered in the local monitoring protocol, to avoid incidence of potentially toxic outcomes.

Long-acting reversible contraception: a review in special populations.

Almost half of the pregnancies in the United States are unintended. Currently available contraceptive methods are highly efficacious, but the most commonly used methods rely on patients for appropriate use. There has been a push to advocate for long-acting reversible contraceptives (LARCs) as first-line methods because they are placed by medical professionals and are the most effective form of reversible contraception available. There are four LARCs currently available in the United States: the Copper T intrauterine device, two forms of the levonorgestrel intrauterine system, and the etonogestrel subdermal implant. Once inserted, they can be left in place for 3-10 years, depending on the device. Some of these devices have been available for a number of years, but their use is limited in the United States due to controversies and misconceptions. A MEDLINE search from 1990-2012 was conducted to identify articles describing the use of LARCs in populations with limited data, including postpartum women, adolescents and nulliparous women, and women with sexually transmitted infections, including human immunodeficiency virus (HIV). Health care provider safety concerns surrounding intrauterine device (IUD) expulsions and infection are issues for use in adolescents and nulliparous women. Concern regarding IUD expulsion in the postpartum population questions the benefit of immediate versus delayed insertion, and the progestin effect in the levonorgestrel IUD and etonogestrel implant is of theoretic concern for breastfeeding women. In women with HIV, concerns have been raised about increased viral shedding with the IUD and drug interactions with the progestin methods. Many misconceptions surrounding LARCs are unfounded, but individual risk factors may leave LARC users at risk of unintended pregnancy if not addressed properly.

Redox susceptibility of SOD1 mutants is associated with the differential response to CCS over-expression in vivo.

Over-expression of CCS in G93A SOD1 mice accelerates neurological disease and enhances mitochondrial pathology. We studied the effect of CCS over-expression in transgenic mice expressing G37R, G86R or L126Z SOD1 mutations in order to understand factors which influence mitochondrial dysfunction. Over-expression of CCS markedly decreased survival and produced mitochondrial vacuolation in G37R SOD1 mice but not in G86R or L126Z SOD1 mice. Moreover, CCS/G37R SOD1 spinal cord showed specific reductions in mitochondrial complex IV subunits consistent with an isolated COX deficiency, while no such reductions were detected in CCS/G86R or CCS/L126Z SOD1 mice. CCS over-expression increased the ratio of reduced to oxidized SOD1 monomers in the spinal cords of G37R SOD1 as well as G93A SOD1 mice, but did not influence the redox state of G86R or L126Z SOD1 monomers. The effects of CCS on disease are SOD1 mutation dependent and correlate with SOD1 redox susceptibility.