key: cord-0009443-v752wtut
authors: Guo, Yan; Huang, Yangmu
title: Realising equity in maternal health: China's successes and challenges
date: 2018-12-13
journal: Lancet
DOI: 10.1016/s0140-6736(18)32464-4
sha: f8bc73ebd1689f8a80a1ad624b8889d64ba11ef8
doc_id: 9443
cord_uid: v752wtut

nan

China has made remarkable progress in maternal and child health since the 1990s. Mortality among children younger than 5 years dropped from 54·1 deaths per 1000 livebirths in 1990 to 12·5 per 1000 livebirths in 2015, 1 meeting the Millennium Development Goal (MDG) 4 well ahead of schedule. Additionally, the maternal mortality ratio declined from 111·0 deaths per 100 000 livebirths in 1990 to 21·8 per 100 000 livebirths in 2015, 1 achieving MDG 5 on target. China has also met the target for reducing the number of maternal deaths in Sustainable Development Goal (SDG) 3, but the challenge of improving equity remains.

In The Lancet, Juan Liang and colleagues 2 report an analysis of maternal mortality ratios down to the county level in China. They used data from China's national Annual Report System on Maternal and Child Health to analyse the progress made in achieving MDG 5 and the level and trends of maternal mortality ratios across China from 1996 to 2015, including inequalities. Overall, maternal mortality ratios declined substantially and rapidly, from 108·7 per 100 000 livebirths in 1996 to 21·8 per 100 000 livebirths in 2015, making the annualised rate 8·5%. As expected, substantial heterogeneity was found at the reported randomised clinical trial in a dedicated peripheral T-cell lymphoma population performed to date, and is therefore a substantial addition to the existing evidence base for this rare non-Hodgkin lymphoma subtype.

Nevertheless, an urgent unmet need remains to improve upfront therapy for the remaining patients with CD30-negative peripheral T-cell lymphoma, for whom outcomes remain suboptimal with CHOP and CHOP-like therapies. As our knowledge of the disease biology improves, the heterogeneity of the molecular and genetic landscape in peripheral T-cell lymphoma is becoming increasingly apparent. Further optimisation of therapy in peripheral T-cell lymphoma is therefore likely to be achieved through incorporation of rational targeted therapies in biomarker-selected populations, as in the ECHELON-2 trial. 14 To this end, the importance of international collaboration in clinical studies will be key to further improving outcomes in this rare disease entity. county level. However, at the provincial level, trends in inequality varied, showing much smaller inequalities within provinces than between provinces. This disparity illustrates the substantial geo graphical inequity of maternal health in China. The Chinese Government has taken a series of actions to eliminate disparities in maternal health. For example, the programme Reducing Maternal Mortality and Eliminating Neonatal Tetanus, which was launched in 2000, was mainly targeted at rural areas, especially poverty-stricken areas. After years of effort, the urbanrural disparity of maternal mortality ratios in China has been greatly narrowed. In 2000, the maternal mortality ratio was 29·3 deaths per 100 000 livebirths in urban areas and 69·6 per 100 000 livebirths in rural areas, giving an urban-to-rural ratio of 1:2·37. By contrast, in 2015, the maternal mortality ratio had declined to 19·8 per 100 000 livebirths in urban areas and 20·8 per 100 000 livebirths in rural areas, reducing the urbanto-rural ratio to 1:1·05. 3 Because of socioeconomic imbalance between regions, however, health inequity is still substantial in China. 4 As noted by Liang and colleagues, 2 191 counties had maternal mortality ratios greater than the target in SDG 3. Most of these counties were in poor rural areas in western China. If as well as maternal mortality ratios, the rate of decline in these ratios in the western regions is taken into account, the gap has been gradually shrinking. From 1990 to 2015, the total maternal mortality ratio in China declined by 4·42 times, while that in Tibet declined by 7·12 times, catching up with the national average maternal mortality ratio. 5 Since the start of the 21st century, China has taken targeted measures to help people lift themselves out of poverty, improving women's status and education equity, which will all contribute to the improvement of maternal health. 1 China's health reforms since the severe acute respiratory syndromes epidemic have greatly strengthened the health system in the western regions. However, improvements were mainly made in health financing and improving infrastructure, and development of the health workforce has lagged behind. 6 In 2016, the total number of health-care institutions was similar in the eastern (0·35 million) and western (0·31 million) regions, but the health workforce, especially the number of health technicians, was much higher in the eastern region (3·7 million) than in the western region (2·2 million). Due to the shortage of health-care workers, there is a gap in the quality of health between the two regions. 7 This is a challenge for China on the way to achieving universal health coverage.

Liang and colleagues provide the first estimates of the progress of maternal mortality ratios and MDG 5 and SDG 3 at the county level in China. However, a question worth exploring is whether it is appropriate to calculate and compare maternal mortality ratios by county. The population differences between provinces in China are large, and between counties are even greater. The largest county in China has a population of 2·44 million, while the smallest has a population of less than 10 000. The number of livebirths in the small counties can be less than 200 per year. 8 Many of the small counties are located in the western regions. Thus, the maternal mortality in these counties can be very unstable from year to year, which should be considered when drawing conclusions from Liang and colleagues' research.

High-dose melphalan with autologous stem cell transplantation (ASCT) has improved survival of patients with multiple myeloma considerably; 1-3 how ever, most patients eventually relapse. Among strategies to improve outcomes after ASCT is the use of maintenance therapy to sustain disease response and delay relapse.

Thalidomide was the first novel agent evaluated as maintenance therapy. Although post-transplant thalidomide improves progression-free survival (PFS) and overall survival, 4 prolonged use is limited by peripheral neuropathy, the main cause of treatment discontinuation. 5 Lenalidomide-a more potent and less toxic second-generation immunomodulatory drug-is the only agent approved for post-transplant maintenance on the basis of improved PFS with lenalidomide versus placebo or observation. [6] [7] [8] [9] Moreover, lenalidomide maintenance also prolongs overall survival, reducing risk of death by approximately 25%. 9,10 Prolonged use of lenalidomide, however, is associated with increased risk of cytopenias, diarrhoea, thromboembolic events, and secondary primary malignancies. 10 Furthermore, efficacy in patients with high-risk cytogenetics remains a matter of debate, with a meta-analysis 10 of three randomised phase 3 trials showing no survival benefit in this patient subset. By contrast, the Myeloma XI study 9 showed improved overall survival irrespective of cytogenetic risk, but lenalidomide maintenance did not completely abrogate the inferior outcomes associated with adverse cytogenetic abnormalities. 9 Importantly, the use of the proteasome inhibitor bortezomib for induction and as post-transplant maintenance improves outcomes of patients with newly diagnosed multiple myeloma, especially those with high-risk features such as del(17p). 11 Longterm bortezomib therapy, however, is limited by neurotoxicity and the inconvenience of subcutaneous administration. Thus, the development of the oral proteasome inhibitor ixazomib represents an important advance.

In The Lancet, Meletios Dimopoulos and colleagues 12 report the results of a randomised phase 3 study TOURMALINE-MM3, in which 656 newly diagnosed adults with multiple myeloma, treated with standard-of-care induction therapy followed by high-dose melphalan and who had received single ASCT within 12 months of diagnosis, were randomly assigned to receive once-weekly ixazomib or placebo on days 1, 8, and 15 of a 4-week cycle for 26 cycles or until progression. Ixazomib maintenance improved depth of response when compared to the placebo group. At a median follow-up of 31 months (IQR 27·3-35·7), ixazomib improved PFS (median PFS 26·5 months [95% CI 23·69-33·81] vs 21·3 months [17·97-24·67]; hazard ratio 0·72, 95% CI 0·58-0·89; p=0·0023), representing a 28% reduction in risk of death or progression. The PFS benefit of ixazomib main tenance was observed irrespective of cytogenetic risk or minimal residual disease status at study entry. Importantly, ixazomib maintenance was well tolerated, with few occurrences of peripheral neuropathy (affecting 73 [19%] of 394 patients in the ixazomib group and 39 [15%] of 259 patients in the placebo group) and without increased risk of thromboembolic events or secondary primary malignancies. Although thrombocytopenia and gastrointestinal adverse events were more common with ixazomib, these

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