Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer were updated and published online in 2023, and adapted, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with early breast cancer. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with breast cancer representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and KSMO. The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with early breast cancer across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling, as well as the age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.

Identifying prognostic biomarkers for palbociclib add-on therapy in fulvestrant-resistant breast cancer using cell-free DNA sequencing.

BACKGROUND: The FUTURE trial (UMIN000029294) demonstrated the safety and efficacy of adding palbociclib after fulvestrant resistance in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced and metastatic breast cancer (ABC/MBC). In this planned sub-study, cancer panel sequencing of cell-free DNA (cfDNA) was utilized to explore prognostic and predictive biomarkers for further palbociclib treatment following fulvestrant resistance. MATERIALS AND METHODS: Herein, 149 cfDNA samples from 65 patients with fulvestrant-resistant disease were analysed at the time of palbociclib addition after fulvestrant resistance (baseline), on day 15 of cycle 1, and at the end of treatment using the assay for identifying diverse mutations in 34 cancer-related genes. RESULTS: During the course of treatment, mutations in ESR1, PIK3CA, FOXA1, RUNX1, TBX3, and TP53 were the most common genomic alterations observed. Analysis of genomic mutations revealed that before fulvestrant introduction, baseline PIK3CA mutations were marginally lower in metastatic aromatase inhibitor (AI)-treated patients compared to adjuvant AI-treated patients (P = 0.063). Baseline PIK3CA mutations were associated with poorer progression-free survival [hazard ratio: 1.62, P = 0.04]. Comparative analysis between baseline and early-changing gene mutations identified poor prognostic factors including early-changing MAP3K1 mutations (hazard ratio: 4.66, P = 0.04), baseline AR mutations (hazard ratio: 3.53, P = 0.04), and baseline PIK3CA mutations (hazard ratio: 3.41, P = 0.02). Notably, the relationship between ESR1 mutations and mutations in PIK3CA, MAP3K1, and TP53 weakened as treatment progressed. Instead, PIK3CA mutations became correlated with TP53 and FOXA1 mutations. CONCLUSIONS: Cancer panel testing for cfDNA identified prognostic and predictive biomarkers for palbociclib add-on therapy after acquiring fulvestrant resistance in patients with HR+/HER2- ABC/MBC.

Large-scale prospective genome-wide association study of oxaliplatin in stage II/III colon cancer and neuropathy.

BACKGROUND: The severity of oxaliplatin (L-OHP)-induced peripheral sensory neuropathy (PSN) exhibits substantial interpatient variability, and some patients suffer from long-term, persisting PSN. To identify single-nucleotide polymorphisms (SNPs) predicting L-OHP-induced PSN using a genome-wide association study (GWAS) approach. PATIENTS AND METHODS: A large prospective GWAS including 1379 patients with stage II/III colon cancer who received L-OHP-based adjuvant chemotherapy (mFOLFOX6/CAPOX) under the phase II (JOIN/JFMC41) or the phase III (ACHIVE/JFMC47) trial. Firstly, GWAS comparison of worst grade PSN (grade 0/1 versus 2/3) was carried out. Next, to minimize the impact of ambiguity in PSN grading, extreme PSN phenotypes were selected and analyzed by GWAS. SNPs that could predict time to recovery from PSN were also evaluated. In addition, SNPs associated with L-OHP-induced allergic reactions (AR) and time to disease recurrence were explored. RESULTS: No SNPs exceeded the genome-wide significance (P < 5.0 × 10-8) in either GWAS comparison of worst grade PSN, extreme PSN phenotypes, or time to recovery from PSN. An association study focusing on AR or time to disease recurrence also failed to reveal any significant SNPs. CONCLUSION: Our results highlight the challenges of utilizing SNPs for predicting susceptibility to L-OHP-induced PSN in daily clinical practice.

Hydration influences on the phase heterogeneity of segmented copolymers.

We elucidate the influences of hydration on the morphological heterogeneity of the class of hard-soft segmented copolymers by experimenting on three model members selected from this group. For influences on phase segmentation, we quantify the degree of phase separation, segment boundary diffusiveness and extent of interphase mixing. Qualitative variations induced by hydration in hydrogen bonding within the phases are also mapped. An inverse relationship between the degree of segmentation and inherent water miscibility of the polymer backbones is observed, that is, high miscibility reducing the degree of segmentation, whereas poor miscibility increasing it. We then quantify hydration induced variations in the size, volume fraction and interaction pair potentials of individual hard segments. The influences on hard segment assemblies are assessed by quantifying their size, volume fraction, interaction pair potential and intrasegment adhesion. This quantification reveals a complex interplay between the volume expansion of individual hard segments and simultaneous swelling and disassembly of their assemblies. Finally, we integrate the segmentation parameters with observed alterations in hydrogen bonding and the inherent polarizability of segments to present a mechanism that reasonably describes the hydrated state morphology. Besides revealing the influences of hydration on the morphological heterogeneity of this class of polymers, our insights give strategies for new synthesis methods for water contact applications and aids in predicting their hydration induced thermomechanical property alterations.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with early breast cancer: a KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS.

In view of the planned new edition of the most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of primary breast cancer published in 2015, it was decided at the ESMO Asia Meeting in November 2018, by both the ESMO and the Korean Society of Medical Oncology (KSMO), to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the latest ESMO 2019 guidelines to take into account the ethnic and geographical differences associated with the treatment of early breast cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with early breast cancer representing the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO) Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices, and the drug availability and reimbursement situations, in the individual participating Asian countries.

Associations Between Acute Conflict and Maternal Care Usage in Egypt: An Uncontrolled Before-and-After Study Using Demographic and Health Survey Data.

BACKGROUND: United Nations' (UN) data indicate that conflict-affected low- and middle-income countries (LMICs) contribute considerably to global maternal deaths. Maternal care usage patterns during conflict have not been rigorously quantitatively examined for policy insights. This study analysed associations between acute conflict and maternal services usage and quality in Egypt using reliable secondary data (as conflict-affected settings generally lack reliable primary data). METHODS: An uncontrolled before-and-after study used data from the 2014 Egypt Demographic and Health Survey (EDHS). The 'pre-conflict sample' included births occurring from January 2009 to January 2011. The 'peri-conflict sample' included births from February 2011 to December 2012. The hierarchical nature of demographic and household survey (DHS) data was addressed using multi-level modelling (MLM). RESULTS: In total, 2569 pre-conflict and 4641 peri-conflict births were reported. After adjusting for socioeconomic variables, conflict did not significantly affect antenatal service usage. Compared to the pre-conflict period, periconflict births had slightly lower odds of delivery in public institutions (odds ratio [OR]: 0.987; 95% CI: 0.975-0.998; P<.05), institutional postnatal care (OR: 0.995; 95% CI: 0.98-1.00; P=.05), and at least 24 hours post-delivery stay (OR: 0.921; 95% CI: 0.906-0.935; P<.01). Peri-conflict births had relatively higher odds of doctor-assisted deliveries (OR: 1.021; 95% CI: 1.004-1.035; P<.05), institutional deliveries (OR: 1.022; 95% CI: 1.00-1.04; P<.05), private institutional deliveries (OR: 1.035; 95% CI: 1.017-1.05; P<.001), and doctor-assisted postnatal care (OR: 1.015; 95% CI: 1.003-1.027; P<.05). Sensitivity analysis did not change results significantly. CONCLUSION: Maternal care showed limited associations with the acute conflict, generally reflecting pre-conflict usage patterns. Further qualitative and quantitative research could identify the effects of larger conflicts on maternal careseeking and usage, and inform approaches to building health system resilience.

FTIR characterization of the setting reaction of biodentine™.

OBJECTIVE: To provide insight of the setting reactions of Biodentine™, a hydraulic calcium silicate cement, based upon observations using Fourier Transform Infra-Red (FTIR) spectroscopy. METHODS: FTIR spectra of components before and during the setting reaction were taken using the attenuated total reflectance (ATR) technique. Measurements over wavelengths 600-4000cm-1 were taken at regular intervals for two days. RESULTS: FTIR spectrum of Biodentine™ powder revealed a number of peaks from 650 to 1100cm-1 and a plateau from 1400 to 1500cm-1, indicative of SiO and CO3-bonding, while the mixing fluid exhibited water peaks. Results following mixing displayed three distinct regimes; (i) incubation phase, during the first 35min, when minimal change occurred, (ii) rapid transitory stage, between 35 and 90min, when major changes occurred, and (iii) slow sustained reaction stage for remaining 45h. Incubation appears to be associated with the presence of CO3-peaks. The transition region indicates formation of CaOH and Jennite OH-peaks, anticipated intermediate reaction phases. At 90min, the end of second stage, CaOH and Jennite are replaced by a dominant Portlandite (Ca(OH)2)-peak and minor presence of Tobermorite, another anticipated intermediate phase, and water reduction. During the following 45h Portlandite and Tobermorite decline while the water peak increases. SIGNIFICANCE: FTIR can be used to follow the chemical reactions in dental cements and provides insight into the relatively slow setting reactions of hydraulic calcium silicate cements.

Maternal and neonatal service usage and determinants in fragile and conflict-affected situations: a systematic review of Asia and the Middle-East.

BACKGROUND: Fragile and conflict-affected situations (FCS) in Asia and the Middle-East contribute significantly to global maternal and neonatal deaths. This systematic review explored maternal and neonatal health (MNH) services usage and determinants in FCS in Asia and the Middle-East to inform policy on health service provision in these challenging settings. METHODS: This systematic review was conducted using a standardised protocol. Pubmed, Embase, Web of Science, and selected development agency websites were searched for studies meeting inclusion criteria. Studies were assessed for methodological quality using an adapted evaluation tool. Qualitative and quantitative data were synthesized and pooled odds ratios generated for meta-analysis of service-usage determinants. RESULTS: Of 18 eligible peer-reviewed studies, eight were from Nepal, four from Afghanistan, and two each from Iraq, Yemen, and the Palestinian Territories. Fragile situations provide limited evidence on emergency obstetric care, postnatal care, and newborn services. Usage of MNH services was low in all FCS, irrespective of economic growth level. Demand-side determinants of service-usage were transportation, female education, autonomy, health awareness, and ability-to-pay. Supply-side determinants included service availability and quality, existence of community health-workers, costs, and informal payments in health facilities. Evidence is particularly sparse on MNH in acute crises, and remains limited in fragile situations generally. CONCLUSIONS: Findings emphasize that poor MNH status in FCS is a leading contributor to the burden of maternal and neonatal ill-health in Asia and the Middle-East. Essential services for skilled birth attendance and emergency obstetric, newborn, and postnatal care require improvement in FCS. FCS require additional resources and policy attention to address the barriers to appropriate MNH care. Authors discuss the 'targeted policy approach for vulnerable groups' as a means of addressing MNH service usage inequities.

Outcomes of fulvestrant therapy among japanese women with advanced breast cancer: a retrospective multicenter cohort study (JBCRG-C06; Safari).

PURPOSE: This retrospective study evaluated the effect of clinical background and treatment line on time to treatment failure (TTF) in advanced/metastatic breast cancer (AMBC) patients receiving F500 in Japan (UMIN 000015168). METHODS: Patients who commenced F500 treatment were registered at 16 sites in Japan. Correlations between baseline clinicopathological factors, treatment line, and TTF were investigated by Kaplan-Meier analysis. TTF data were analyzed using univariate analysis and multivariate analysis with a Cox proportional hazards model. RESULTS: Data for 1072 patients were available; 1031 patients (96.2%) were evaluable for efficacy. F500 was administered as first-line treatment in 2.0%, second-line in 22.7%, third-line in 26.7%, and ≥fourth-line in 48.6% patients. Median TTF was 5.4 months. Multivariate analysis found that earlier F500 use (first and second vs. third vs. ≥fourth line; hazard ratio (HR) = 0.80, 95% confidence interval (CI) 0.74-0.86; P < 0.001), longer period from AMBC diagnosis to F500 use (≥3 vs. <3 years; HR 0.60, 95% CI 0.51-0.70; P < 0.001), and no prior palliative chemotherapy administered for unresectable or metastatic breast cancer (no vs. yes; HR 0.69, 95% CI 0.60-0.80; P < 0.001) were associated with significantly longer TTF. Among 691 patients, where information on histologic/nuclear grade was available, a low grade was also associated with a longer TTF, but this finding was not maintained among patients with recurrent breast cancer (N = 558). Among women with recurrent breast cancer, a longer DFI between a patient's initial breast cancer diagnosis and their recurrence was associated with a longer TTF on F500 therapy. CONCLUSIONS: Our study showed that treatment period of F500 was longer when used in earlier-line treatment. For patients on F500, TTF was also longer for patients who had not received prior palliative chemotherapy and for those who had a longer period from their AMBC diagnosis to F500 use.

A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC).

BACKGROUNDS: Preventing distant recurrence and achieving local control are important challenges in rectal cancer treatment, and use of adjuvant chemotherapy has been studied. However, no phase III study comparing adjuvant chemotherapy regimens for rectal cancer has demonstrated superiority of a specific regimen. We therefore conducted a phase III study to evaluate the superiority of S-1 to tegafur-uracil (UFT), a standard adjuvant chemotherapy regimen for curatively resected stage II/III rectal cancer in Japan, in the adjuvant setting for rectal cancer. PATIENTS AND METHODS: The ACTS-RC trial was an open-label, randomized, phase III superiority trial conducted at 222 sites in Japan. Patients aged 20-80 with stage II/III rectal cancer undergoing curative surgery without preoperative therapy were randomly assigned to receive UFT (500-600 mg/day on days 1-5, followed by 2 days rest) or S-1 (80-120 mg/day on days 1-28, followed by 14 days rest) for 1 year. The primary end point was relapse-free survival (RFS), and the secondary end points were overall survival and adverse events. RESULTS: In total, 961 patients were enrolled from April 2006 to March 2009. The primary analysis was conducted in 480 assigned to receive UFT and 479 assigned to receive S-1. Five-year RFS was 61.7% [95% confidence interval (CI) 57.1% to 65.9%] for UFT and 66.4% (95% CI 61.9% to 70.5%) for S-1 [P = 0.0165, hazard ratio (HR): 0.77, 95% CI 0.63-0.96]. Five-year survival was 80.2% (95% CI 76.3% to 83.5%) for UFT and 82.0% (95% CI 78.3% to 85.2%) for S-1. The main grade 3 or higher adverse events were increased alanine aminotransferase and diarrhea (each 2.3%) in the UFT arm and anorexia, diarrhea (each 2.6%), and fatigue (2.1%) in the S-1 arm. CONCLUSION: One-year S-1 treatment is superior to UFT with respect to RFS and has therefore become a standard adjuvant chemotherapy regimen for stage II/III rectal cancer following curative resection.

Large-scale prospective pharmacogenomics study of oxaliplatin-induced neuropathy in colon cancer patients enrolled in the JFMC41-1001-C2 (JOIN Trial).

BACKGROUND: Peripheral sensory neuropathy (PSN) is a dose-limiting toxicity of oxaliplatin-based chemotherapy. Several genetic markers have been shown to predict oxaliplatin-induced PSN; however, results remain to be validated in a large-scale and prospective pharmacogenomics study. PATIENTS AND METHODS: Among 882 patients enrolled in the JFMC41-1001-C2 (JOIN trial), which was designed to investigate the tolerability of adjuvant-modified FOLFOX6 (mFOLFOX6) in Japanese Patients with stage II or III colon cancers undergoing curative resection, 465 patients were eligible for this pharmacogenomics analysis. Twelve single-nucleotide polymorphisms (SNPs) were selected based on published data. The effect of each genotype on time to PSN onset was evaluated in all patients (n = 465) using the Cox proportional hazard model. For the association analysis between severity of PSN and 12 SNP markers, 84 patients who failed to complete 12 cycles of mFOLFOX6 from grade 0/1 PSN group were excluded because the termination of the protocol treatment had been caused by reasons other than PSN. RESULTS: Comparison of grade 0/1 PSN with grade 2/3 PSN or grade 3 PSN showed no significant associations with any of the 12 SNP markers after adjustment for total dose of oxaliplatin. Time-to-onset analysis also failed to reveal any significant differences. CONCLUSIONS: Our large-scale and prospective pharmacogenomics study of Japanese patients receiving protocol treatment of adjuvant mFOLFOX6 could not verify a role for any of the 12 SNP markers reported as being significantly associated with PSN. Considering the OR observed in this study (range: 0.76-1.89), further evaluation of these 12 SNP markers in the context of L-OHP-induced PSN is unlikely to be clinically informative.

Effect of pay for performance to improve quality of maternal and child care in low- and middle-income countries: a systematic review.

BACKGROUND: Pay for Performance (P4P) mechanisms to health facilities and providers are currently being tested in several low- and middle-income countries (LMIC) to improve maternal and child health (MCH). This paper reviews the existing evidence on the effect of P4P program on quality of MCH care in LMICs. METHODS: A systematic review of literature was conducted according to a registered protocol. MEDLINE, Web of Science, and Embase were searched using the key words maternal care, quality of care, ante natal care, emergency obstetric and neonatal care (EmONC) and child care. Of 4535 records retrieved, only eight papers met the inclusion criteria. Primary outcome of interest was quality of MCH disaggregated into structural quality, process quality and outcomes. Risk of bias across studies was assessed through a customized quality checklist. RESULTS AND DISCUSSION: There were four controlled before after intervention studies, three cluster randomized controlled trials and one case control with post-intervention comparison of P4P programs for MCH care in Burundi, Democratic Republic of Congo, Egypt, the Philippines, and Rwanda. There is some evidence of positive effect of P4P only on process quality of MCH. The effect of P4P on delivery, EmONC, post natal care and under-five child care were not evaluated in these studies. There is weak evidence for P4P's positive effect on maternal and neonatal health outcomes and out-of-pocket expenses. P4P program had a few negative effects on structural quality. CONCLUSION: P4P is effective to improve process quality of ante natal care. However, further research is needed to understand P4P's impact on MCH and their causal pathways in LMICs. TRIAL REGISTRATION: PROSPERO registration number CRD42014013077 .

Solvent transport through hard-soft segmented polymer nanocomposites.

We conducted transport studies of a common solvent (toluene) in its condensed state, through a model hard-soft segmented polyurethane-clay nanocomposite. The solvent diffusivity is observed to be non-monotonic in a functional relationship with a filler volume fraction. In stark contrast, both classical tortuous path theory based geometric calculations and free volume measurements suggest the normally expected monotonic decrease in diffusivity with increase in clay volume fraction. Large deviations between experimentally observed diffusivity coefficients and those theoretically estimated from geometric theory are also observed. However, the equilibrium swelling of a nanocomposite as indicated by the solubility coefficient did not change. To gain an insight into the solvent interaction behavior, we conducted a pre- and post swollen segmented phase analysis of pure polymers and nanocomposites. We find that in a nanocomposite, the solvent has to interact with a filler altered hard-soft segmented morphology. In the altered phase separated morphology, the spatial distribution of thermodynamically segmented hard blocks in the continuous soft matrix becomes a strong function of filler concentration. Upon solvent interaction, this spatial distribution gets reoriented due to sorption and de-clustering. The results indicate strong non-barrier influences of nanoscale fillers dispersed in phase segmented block co-polymers, affecting solvent diffusivity through them. Based on pre- and post swollen morphological observations, we postulate a possible mechanism for the non-monotonic behaviour of solvent transport for hard-soft segmented co-polymers, in which the thermodynamic phase separation is influenced by the filler.

Leveraging community-based financing for women's nonmaternal health care: experiences of rural Indian women.

Given the increasing need for mainstreaming household financing for women's nonmaternal health care and evidences on community-based financing's contribution to women's health care in general, this study explored their scope for nonmaternal health care in Orissa. A qualitative assessment conducted focus group discussions with rural women who met the eligibility criteria. Community-based financing provided financial access and risk protection for women's nonmaternal health care during the previous 1 year, though not adequately. Schemes covering outpatient care (or mild illnesses) provided relatively more financial access. The major determinants of their restricted financial access were limited sum assured, noncomprehensive coverage of services, exclusion of elderly women, and the lower priority households gave to nonmaternal health care. Community-based financing requires relevant structural changes along with demand-side behavioral modifications to ensure optimal attention to women's nonmaternal health care.

Health sector demand-side financial incentives in low- and middle-income countries: a systematic review on demand- and supply-side effects.

Demand-side financial incentive (DSF) is an emerging strategy to improve health seeking behavior and health status in many low- and middle-income countries. This narrative synthesis assessed the demand- and supply-side effects of DSF. Forty one electronic data bases were searched to screen relevant experimental and quasi-experimental study designs. Out of the 64 selected papers, 28 were eligible for this review and they described 19 DSF initiatives across Asia, Africa and Latin America. There were three categories of initiatives, namely long-run multi-sectoral programs or LMPs (governmental); long-run health-exclusive programs (governmental); and short-run health-exclusive initiatives (both governmental and non-governmental). Irrespective of the nature of incentives and initiatives, all DSF programs could achieve their expected behavioral outcomes on healthcare seeking and utilization substantially. However, there existed a few negative and perverse outcomes on health seeking behavior and DSF's impact on continuous health seeking choices (e.g. bed net use and routine adult health check-ups) was mixed. Their effects on maternal health status, diarrhea, malaria and out-of-pocket expenditure were under-explored; while chronic non-communicable diseases were not directly covered by any DSF programs. DSF could reduce HIV prevalence and child deaths, and enhance nutritional and growth status of children. The direction and magnitude of their effects on health status was elastic to the evaluation design employed. On health system benefits, despite prioritizing on vulnerable groups, DSF's substantial effect on the poorest of the poor was mixed compared to that on the relatively richer groups. Though DSF initiatives intended to improve service delivery status, many could not optimally do so, especially to meet the additionally generated demand for care. Causal pathways of DSF's effects should be explored in-depth for mid-course corrections and cross-country learning on their design, implementation and evaluation. More policy-specific analyses on LMPs are needed to assess how 'multi-sectoral' approaches can be cost-effective and sustainable in the long run compared to 'health exclusive' incentives.

What makes Health Demand-Side Financing Schemes Work in Low-and Middle-Income Countries? A Realist Review.

This realist review explored causal pathways of the possible consumer effects of health sector demand-side financial (DSF) incentives, their contextual factors and mechanisms in low-and-middle-income countries. We searched six electronic data bases and identified 659 abstracts with different evaluation designs. Based on methodological rigor and content relevance, only 24 studies published up to April 2013 were selected for the final review. A conceptual framework consisting of various program theories on potential context-mechanism-outcome (C-M-O) configuration of DSF initiative was designed, tested and adapted during the review. Synthesized results were presented as a C-M-O configuration for each of the consumer -side effect. DSF was effective to improve health seeking behaviour considerably and health status to some extent. The causal pathway of DSF's functioning and effectiveness was not linear. Key demand-side contextual factors which affected DSF's consumer-side effects were background characteristics of the beneficiaries including their socio-cultural beliefs, motivations, and level of health awareness. At the supply-side, service availability status and provider incentives were contextual determinants. The mechanisms which enabled the interaction of contextual influence were consumer and provider accountability and consumer trust on providers. In order to enhance DSF programs' effectiveness, their design and implementation should carefully consider the potential contextual elements that may influence the causal pathways. Significance for public healthThis article focuses on a rare topic i.e. Realist Review, which is an emerging concept to explore causal factors behind every intervention that make it effective or ineffective. This manuscript is a first attempt on a Realist Review of health sector demand-side financing (DSF) in a number of low-and middle-income countries. DSF is a widely employed health promotion strategy in many countries to improve health seeking behaviour. However, the existing evidence explores only its effectiveness and not the determinants of its effectiveness. It is also essential to understand the causal pathways of DSF's effectiveness, i.e. what are the factors affecting its effectiveness. This Realist Review attempts to explore the causal pathways of effectiveness of many prominent DSF initiatives in the world. The study findings have policy implications and will be widely referred to in future.

Alcohol, drugs, and road traffic crashes in India: a systematic review.

OBJECTIVE: India reported the highest number of road traffic crashes, related injuries, and deaths among all countries in the world, with 105,725 road traffic fatalities and 452,922 nonfatal road traffic injuries in 2007. In this report we present a systematic review of available literature on the use of psychoactive substances (alcohol and drugs) among road users, particularly those involved in road traffic crashes (RTCs). METHODS: MEDLINE, EMBASE, Ind Medica, and several other databases were searched for reports published between 1980 and 2011 that present data on the prevalence or extent of substance use among road users in India. RESULTS: Among the 23 studies eligible for the review, alcohol was reported by all, but only 2 mentioned the use of drugs. Most of the studies were hospital based, included injured or killed road users, and belonged to southern parts of India. Seven studies did not report any method for detecting alcohol use, whereas 7 used analytical testing, 7 used self-reporting, and 2 used observation. Utilizing the various means of verification, the studies reported that 2 to 33 percent of injured and 6 to 48 percent of killed RTC victims had consumed alcohol or drugs; only 2 mentioned drugs without specifying which types. Most studies did not distinguish between drivers, passengers, bicyclists, and pedestrians, and none investigated alcohol or drug use among those responsible for the accident. CONCLUSION: A significant proportion of injured or killed road users in India had used alcohol before the accident. However, the existing studies cannot be used to estimate the risk of accident involvement among drunk drivers. There is a need for more rigorous research and capacity building on substance use vis-à-vis road traffic crashes.

Addressing maternal healthcare through demand side financial incentives: experience of Janani Suraksha Yojana program in India.

BACKGROUND: Demand side financing (DSF) is a widely employed strategy to enhance utilization of healthcare. The impact of DSF on health care seeking in general and that of maternal care in particular is already known. Yet, its effect on financial access to care, out-of-pocket spending (OOPS) and provider motivations is not considerably established. Without such evidence, DSFs may not be recommendable to build up any sustainable healthcare delivery approach. This study explores the above aspects on India's Janani Suraksha Yojana (JSY) program. METHODS: This study employed design and was conducted in three districts of Orissa, selected through a three-stage stratified sampling. The quantitative method was used to review the Health Management Information System (HMIS). The qualitative methods included focus groups discussions with beneficiaries (n = 19) and community intermediaries (n = 9), and interviews (n = 7) with Ministry of Health officials. HMIS data enabled to review maternal healthcare utilization. Group discussions and interviews explored the perceived impact of JSY on in-facility delivery, OOPS, healthcare costs, quality of care and performance motivation of community health workers. RESULTS: The number of institutional deliveries, ante-and post-natal care visits increased after the introduction of JSY with an annual net growth of 18.1%, 3.6% and 5% respectively. The financial incentive provided partial financial risk-protection as it could cover only 25.5% of the maternal healthcare cost of the beneficiaries in rural areas and 14.3% in urban areas. The incentive induced fresh out-of-pocket spending for some mothers and it could not address maternal care requirements comprehensively. An activity-based community worker model was encouraging to augment maternal healthcare consumption. However, the existing level of financial incentives and systemic support were inadequate to motivate the volunteers optimally on their performance. CONCLUSION: Demand side financial incentive could enhance financial access to maternal healthcare. However, it did not adequately protect households from financial risks. An effective integration of JSY with similar social protection or financial risk-protection measures may protect mothers substantially from potential out-of-pocket spending. Further, this integrated approach may help upholding more awareness on maternal health rights and entitlements. It can also address maternal health beyond 'maternal healthcare' and ensure sustainability through pooled financial and non-financial resources.

Addressing women's non-maternal healthcare financing in developing countries: what can we learn from the experiences of rural Indian women?

BACKGROUND AND OBJECTIVES: This paper focuses on the inadequate attention on women's non-maternal healthcare in low- and middle-income countries. The study assessed the purchase of and financial access to non-maternal healthcare. It also scoped for mainstreaming household financial resources in this regard to suggest for alternatives. METHODS: A household survey through multi-stage stratified sampling in the state of Orissa interviewed rural women above 15 years who were neither pregnant nor had any pregnancy-related outcome six weeks preceding the survey. The questions explored on the processes, determinants and outcomes of health seeking for non-maternal ailments. The outcome measures were healthcare access, cost of care and financial access. The independent variables for bivariate and multivariate analyses were contextual factors, health seeking and financing pattern. RESULTS: The survey obtained a response rate of 98.64% and among 800 women, 43.8% had no schooling and 51% were above 60 years. Each woman reported at least one episode of non-maternal ailment; financial constraints prevented 68% from receiving timely and complete care. Distress coping measures (e.g. borrowings) dominated the financing source (67.9%) followed by community-based measures (32.1%). Only 6% had financial risk-protection; financial risk of not obtaining care doubled for women aged over 60 years (OR 2.00, 95% CI 0.84-4.80), seeking outpatient consultation (OR 2.01, 95% CI 0.89-4.81), facing unfavourable household response (OR 2.04, 95% CI 1.09-3.83), and lacking other financial alternatives (OR 2.13, 95% CI 1.11-4.07). When it comes to timely mobilization of funds and healthcare seeking, 90% (714) of the households preferred maternal care to non-maternal healthcare. CONCLUSION: The existing financing options enable sub-optimal purchase of women's non-maternal healthcare. Though dominant, household economy extends inadequate attention in this regard owing to its unfavourable approach towards non-maternal healthcare and limited financial capacity and support from other financial resources.

Challenges and opportunities for policy decisions to address health equity in developing health systems: case study of the policy processes in the Indian state of Orissa.

INTRODUCTION: Achieving health equity is a pertinent need of the developing health systems. Though policy process is crucial for planning and attaining health equity, the existing evidences on policy processes are scanty in this regard. This article explores the magnitude, determinants, challenges and prospects of 'health equity approach' in various health policy processes in the Indian State of Orissa - a setting comparable with many other developing health systems. METHODS: A case-study involving 'Walt-Gilson Policy Triangle' employed key-informant interviews and documentary reviews. Key informants (n = 34) were selected from the departments of Health and Family Welfare, Rural Development, and Women and Child Welfare, and civil societies. The documentary reviews involved various published and unpublished reports, policy pronouncements and articles on health equity in Orissa and similar settings. RESULTS: The 'health policy agenda' of Orissa was centered on 'health equity' envisaging affordable and equitable healthcare to all, integrated with public health interventions. However, the subsequent stages of policy process such as 'development, implementation and evaluation' experienced leakage in the equity approach. The impediment for a comprehensive approach towards health equity was the nexus among the national and state health priorities; role, agenda and capacity of actors involved; and existing constraints of the healthcare delivery system. CONCLUSION: The health equity approach of policy processes was incomprehensive, often inadequately coordinated, and largely ignored the right blend of socio-medical determinants. A multi-sectoral, unified and integrated approach is required with technical, financial and managerial resources from different actors for a comprehensive 'health equity approach'. If carefully geared, the ongoing health sector reforms centered on sector-wide approaches, decentralization, communitization and involvement of non-state actors can substantially control existing inequalities through an optimally packaged equitable policy. The stakeholders involved in the policy processes need to be given orientation on the concept of health equity and its linkage with socio-economic development.