Building policy-making capacity in the Ministry of Health: the Kazakhstan experience.

BACKGROUND: Recent economic growth in Kazakhstan has been accompanied by slower improvements in population health and this has renewed impetus for health system reform. Strengthening strategic planning and policy-making capacity in the Ministry of Health has been identified as an important priority, particularly as the Ministry of Health is leading the health system reform process. CASE DESCRIPTION: The intervention was informed by the United Nations Development Programme (UNDP) framework for capacity building which views capacity building as an ongoing process embedded in local institutions and practices. In response to local needs extra elements were included in the framework to tailor the capacity building programme according to the existing policy and budget cycles and respective competence requirements, and link it with transparent career development structures of the Ministry of Health. This aspect of the programme was informed by the institutional capability assessment model used by the United Kingdom National Health Service (NHS) which was adapted to examine the specific organizational and individual competences of the Ministry of Health in Kazakhstan. DISCUSSION AND EVALUATION: There were clear successes in building capacity for policy making and strategic planning within the Ministry of Health in Kazakhstan, including better planned, more timely and in-depth responses to policy assignments. Embedding career development as a part of this process was more challenging. This case study highlights the importance of strong political will and high level support for capacity building in ensuring the sustainability of programmes. It also shows that capacity-building programmes need to ensure full engagement with all local stakeholders, or where this is not possible, programmes need to be targeted narrowly to those stakeholders who will benefit most, for the greatest impact to be achieved. In sum, high quality tailor-made capacity development programmes should be based on thorough needs assessment of individual and organizational competences in a specific institutional setting. CONCLUSIONS: The experience showed that complementary approaches to human resource development worked effectively in the context of organizations and systems, where an enabling environment was present, and country ownership and political will was complemented by strong technical assistance to design and deliver high quality tailor-made capacity building initiatives.

Health and health systems in the Commonwealth of Independent States.

The countries of the Commonwealth of Independent States differ substantially in their post-Soviet economic development but face many of the same challenges to health and health systems. Life expectancies dropped steeply in the 1990s, and several countries have yet to recover the levels noted before the dissolution of the Soviet Union. Cardiovascular disease is a much bigger killer in the Commonwealth of Independent States than in western Europe because of hazardous alcohol consumption and high smoking rates in men, the breakdown of social safety nets, rising social inequality, and inadequate health services. These former Soviet countries have embarked on reforms to their health systems, often aiming to strengthen primary care, scale back hospital capacities, reform mechanisms for paying providers and pooling funds, and address the overall shortage of public funding for health. However, major challenges remain, such as frequent private out-of-pocket payments for health care and underdeveloped systems for improvement of quality of care.

Denmark: Health System Review.

This analysis of the Danish health system reviews recent developments in organization and governance, health financing, health care provision, health reforms and health system performance. Population health in Denmark is good and improving, with life expectancy above the European Union (EU) average but is, however, lagging behind the other Nordic countries. Denmark has a universal and tax-financed health system, providing coverage for a comprehensive package of health services. Notable exclusions to the benefits package include outpatient prescription drugs and adult dental care, which require co-payment and are the main causes of out-of-pocket spending. The hospital sector has been transformed during the past 15 years through a process of consolidating hospitals and the centralization of medical specialties. However, in recent years, there has been a move towards decentralization to increase the volume and quality of care provided outside hospitals in primary and local care settings. The Danish health care system is, to a very high degree, based on digital solutions that health care providers, citizens and institutions all use. Ensuring the availability of health care in all parts of Denmark is increasingly seen as a priority issue. Ensuring sufficient health workers, especially nurses, poses a significant challenge to the Danish health system's sustainability and resilience. While a comprehensive package of policies has been put in place to increase the number of nurses being trained and retain those already working in the system, such measures need time to work. Addressing staffing shortages requires long-term action. Profound changes in working practices and working environments will be required to ensure the sustainability of the health workforce and, by extension, the health system into the future.

The economic burden of chronic disease care faced by households in Ukraine: a cross-sectional matching study of angina patients.

INTRODUCTION: Non-communicable diseases (NCDs) are the leading cause of death and disability worldwide, and their prevalence in lower- and middle-income countries (LMIC) is on the rise. The burden of chronic health expenditure born by patient households in these countries may be very high, particularly where out-of-pocket payments for health care are common. One such country where out-of-pocket payments are especially high is Ukraine. The financial impact of NCDs on households in this country has not been researched. METHODS: We set out to explore the burden of NCD care in Ukraine with a study of angina patients. Using data from the Ukraine World Health Survey of 2003 we employed the novel Coarsened Exact Matching approach to estimate the difference in out-of-pocket payment (OPP) for health care between households with a stable angina pectoris (a chronic form of IHD) patient and those without. The likelihood of engaging in catastrophic spending and using various distress financing mechanisms (e.g., sale of assets, borrowing) among angina households compared with non-angina households was also explored. RESULTS: Among angina patient households (n = 203), OPP occupied an average of 32% of household effective income. After matching, angina households experienced significantly higher monthly per capita OPP for health care (B = $2.84) and medicines (B = $2.94), but were not at significantly higher odds of engaging in catastrophic spending. Odds of engaging in 'sale of assets' (OR = 2.71) and 'borrowing' (OR = 1.68) to finance OPP were significantly higher among angina households. CONCLUSIONS: The cost of chronic care in Ukraine places a burden on individual patient households. Households of angina patients are more likely to engage in distress financing to cover the cost of treatment, and a high proportion of patients do not acquire prescribed medicines because they cannot afford them. This warrants further research on the burden of NCD care in other LMIC, especially where OPP for health care is common. Health policies aimed at reducing OPP for health care, and especially medicines, would lessen the high health and financial burden of chronic care. Further research is also needed on the long-term impact of borrowing or sale of assets to finance OPP on patient households.

Analysing compliance of cigarette packaging with the FCTC and national legislation in eight former Soviet countries.

AIM: To analyse compliance of cigarette packets with the Framework Convention on Tobacco Control (FCTC) and national legislation and the policy actions that are required in eight former Soviet Union countries. METHODS: We obtained cigarette packets of each of the 10 most smoked cigarette brands in Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Moldova, Russia and Ukraine. The packets were then analysed using a standardised data collection instrument. The analysis included the placing, size and content of health warning labels and deceptive labels (eg, 'Lights'). Findings were assessed for compliance with the FCTC and national legislation. RESULTS: Health warnings were on all packets from all countries and met the FCTC minimum recommendations on size and position except Azerbaijan and Georgia. All countries used a variety of warnings except Azerbaijan. No country had pictorial health warnings, despite them being mandatory in Georgia and Moldova. All of the countries had deceptive labels despite being banned in all countries except Russia and Azerbaijan where still no such legislation exists. CONCLUSIONS: Despite progress in the use of health warning messages, gaps still remain-particularly with the use of deceptive labels. Stronger surveillance and enforcement mechanisms are required to improve compliance with the FCTC and national legislation.

Changing patterns of fruit and vegetable intake in countries of the former Soviet Union.

OBJECTIVE: To assess how the frequency of low fruit and vegetable consumption has changed in countries of the former Soviet Union (FSU) between 2001 and 2010 and to identify factors associated with low consumption. DESIGN: Cross-sectional surveys. A standard questionnaire was administered at both time points to examine fruit and vegetable consumption frequency. Logistic regression analysis was used to examine the relationship between demographic, socio-economic and health behavioural variables and low fruit and vegetable consumption in 2010. SETTING: Nationally representative population samples from Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia and Ukraine. SUBJECTS: Adults aged 18 years and older. RESULTS: Between 2001 and 2010 notable changes occurred in fruit and vegetable consumption in many countries resulting in a slight overall deterioration in diet. By 2010 in six countries about 40% of the population was eating fruit once weekly or less often, while for vegetables the corresponding figure was in excess of 20% in every country except Azerbaijan. A worse socio-economic situation, negative health behaviours (smoking and alcohol consumption) and rural residence were all associated with low levels of fruit and vegetable consumption. CONCLUSIONS: International dietary guidelines emphasise the importance of fruit and vegetable consumption. The scale of inadequate consumption of these food groups among much of the population in many FSU countries and its link to socio-economic disadvantage are deeply worrying. This highlights the urgent need for a greater focus to be placed on population nutrition policies to avoid nutrition-related diseases in the FSU countries.

Prevalence and factors associated with the use of alternative (folk) medicine practitioners in 8 countries of the former Soviet Union.

BACKGROUND: Research suggests that since the collapse of the Soviet Union there has been a sharp growth in the use of complementary and alternative medicine (CAM) in some former Soviet countries. However, as yet, comparatively little is known about the use of CAM in the countries throughout this region. Against this background, the aim of the current study was to determine the prevalence of using alternative (folk) medicine practitioners in eight countries of the former Soviet Union (fSU) and to examine factors associated with their use. METHODS: Data were obtained from the Living Conditions, Lifestyles and Health (LLH) survey undertaken in eight former Soviet countries (Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia and Ukraine) in 2001. In this nationally representative cross-sectional survey, 18428 respondents were asked about how they treated 10 symptoms, with options including the use of alternative (folk) medicine practitioners. Multivariate logistic regression analysis was used to determine the factors associated with the treatment of differing symptoms by such practitioners in these countries. RESULTS: The prevalence of using an alternative (folk) medicine practitioner for symptom treatment varied widely between countries, ranging from 3.5% in Armenia to 25.0% in Kyrgyzstan. For nearly every symptom, respondents living in rural locations were more likely to use an alternative (folk) medicine practitioner than urban residents. Greater wealth was also associated with using these practitioners, while distrust of doctors played a role in the treatment of some symptoms. CONCLUSIONS: The widespread use of alternative (folk) medicine practitioners in some fSU countries and the growth of this form of health care provision in the post-Soviet period in conditions of variable licensing and regulation, highlights the urgent need for more research on this phenomenon and its potential effects on population health in the countries in this region.

Elimination of a Postoperative Brace Does Not Increase Complications Following Hip Arthroscopy.

Background The practice of routine postoperative bracing to limit abduction and internal rotation, along with weight-bearing restrictions after hip arthroscopy (HA), varies significantly among surgeons. It is unclear whether the use of a postoperative brace improves short-term outcomes in patients undergoing HA. The purpose of this study was to determine the differences in patient outcomes before and after eliminating routine usage of a postoperative brace. Methods A retrospective review was conducted of 176 adult patients undergoing HA by a single, high-volume surgeon. The no-brace protocol was implemented in October 2020. The patients were divided into two groups: pre-implementation (January-October 2020) and post-implementation (October 2020-April 2021). Twenty-three patients that used a brace during the post-implementation period were excluded. All patients had weight-bearing restrictions with crutches for three weeks postoperatively. The primary endpoint was any complication in the first six weeks postoperatively. Results There were no significant differences in demographics between groups, although the body mass index in the brace group was higher (28.1 vs. 26.4 kg/m2, p = 0.066) and the rate of additional procedures performed was higher in the brace group (55.2% vs. 40.1%, p = 0.056). There was no significant difference in postoperative outcomes between groups when looking at 90-day emergency department visits (1.7% vs. 0%, p = 0.548), complications at two (1.7% vs. 1.7%, p = 1.000) and six weeks (0% vs. 1.7%, p = 0.341) postoperatively, all complications in the first six weeks (1.7% vs. 1.7%, p = 1.000), and continued pain at six weeks (10.3% vs. 16.7%, p = 0.238). Conclusion The brace and no-brace groups were similar demographically. Patients undergoing HA with no brace and crutches experienced no significant differences in pain or complications in comparison to those receiving a traditional bracing protocol. Routine use of a postoperative brace may not be necessary in this population.

Childhood deaths from injuries: trends and inequalities in Europe.

BACKGROUND: In 1998, a UNICEF report quantified the large East-West gap in Europe in child mortality from external causes (injuries and violence). In the past decade, much has changed in central and eastern Europe, economically, politically and socially. This study updates the earlier analysis, tracking changes in deaths from external causes in the different parts of Europe. METHODS: The WHO mortality database was used to examine mortality from external causes for children aged 1-14 years between 1993 and 2008, by country, European subregion and cause. RESULTS: Deaths from external causes have fallen in all of Europe since 1993. However, a clear east-west divide persists, with higher death rates in the former Soviet countries, especially the Commonwealth of Independent States (CIS). Trends in specific causes also vary geographically; the greatest overall declines have been in transport-related deaths, drowning, poisoning and 'other' external causes. Transport, drowning and 'other' remain the commonest external causes of death in childhood. CONCLUSION: Child injury mortality rates have fallen across Europe. In the former Soviet countries, this is likely to reflect improvements in living conditions since transition. Yet, large geographical inequalities remain, highlighting the need for enhanced measures to prevent injuries, particularly in the CIS countries and the Baltic states. However, except in a few countries, there is still little research on the nature of the problem or the effectiveness of potential interventions. Child deaths from injuries are avoidable and measures to reduce them would have a significant impact upon the overall burden of child mortality in Europe.

What have European countries done to prevent the spread of COVID-19? Lessons from the COVID-19 Health system response monitor.

Although some European countries imposed measures that successfully slowed the transmission of Covid-19 during the first year of the pandemic, others struggled, either because they acted slowly or implemented measures ineffectively. In this paper we consider the European experience with public health measures designed to prevent transmission of COVID-19. Based on literature and country responses described in the COVID-19 Health System Response Monitor from March 2020 to December 2020, we consider some critical aspects of public health policy responses. These include the importance of public health capacity that can scale up surveillance and outbreak control, including effective testing and contract tracing, of clear messaging based on an understanding of human behaviour, policies that address the undesirable consequences of necessary measures, such as support for those isolating or unable to earn, and the ability to implement at pace and scale a major vaccine rollout. We conclude that for countries to be successful at preventing COVID-19 transmission, there is a need for a clear strategy with explicit goals and a whole systems approach to implementation.

Using Targets to Reduce Waiting Times for Elective Care: What Can We Learn from the Russian Experience?

This article explores the potential for maximum waiting times targets to improve access to healthcare in a country with limited financial resources. The study combines policy analysis, off-the-record communications, face-to-face interviews, public opinion surveys and open access patient complaints to create a rich picture of how waiting time targets are monitored and implemented in theory and practice. The study found that most waiting time targets in the Russian Federation are unrealistically low, while institutional and operational arrangements for their implementation have not been built in most regions. Estimates of actual waiting times are fragmented and unreliable. The lack of meaningful regulation and monitoring encourages opportunistic behavior among health providers to meet the targets while there is growing uncertainty among patients. Maximum waiting times targets alone are insufficient to reduce excessive waiting times. Successful implementation relies on robust data systems and standardized measurements for waiting times as well as meaningful regulation and monitoring.

Disability and loneliness in nine countries of the former Soviet Union.

BACKGROUND: People with disabilities (PWD) often face structural and other barriers to community involvement and may therefore be at risk of loneliness. Yet, so far, this issue has received little attention. OBJECTIVE: This cross-sectional study aimed to examine the association between disability and loneliness in nine countries of the former Soviet Union (FSU). METHODS: Data were analyzed from 18000 respondents aged ≥18 that came from the Health in Times of Transition (HITT) survey that was undertaken in Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia and Ukraine in 2010/11. Respondents reported on whether they had a disability (no/yes) and its severity. A single-item question was used to assess loneliness. Logistic regression analysis was used to examine the associations. RESULTS: Across the countries, 6.8% of respondents reported being disabled. In a fully adjusted combined country analysis, disability was associated with higher odds for loneliness (odds ratio: 1.30, 95% confidence interval: 1.06-1.60). In an analysis restricted to PWD, individuals in the most severe disability category (Group 1) had over two times higher odds for loneliness when compared to those in the least severe disability category (Group 3). CONCLUSIONS: Disability is associated with higher odds for reporting loneliness in the FSU countries and this association is especially strong among those who are more severely disabled. An increased focus on the relationship between disability and loneliness is now warranted given the increasing recognition of loneliness as a serious public health problem that is associated with a number of detrimental outcomes.

Primary care use and cardiovascular disease risk in Russian 40-69 year olds: a cross-sectional study.

BACKGROUND: The Russian Federation has very high cardiovascular disease (CVD) mortality rates compared with countries of similar economic development. This cross-sectional study compares the characteristics of CVD-free participants with and without recent primary care contact to ascertain their CVD risk and health status. METHODS: A total of 2774 participants aged 40-69 years with no self-reported CVD history were selected from a population-based study conducted in Arkhangelsk and Novosibirsk, Russian Federation, 2015-2018. A range of co-variates related to socio-demographics, health and health behaviours were included. Recent primary care contact was defined as seeing primary care doctor in the past year or having attended a general health check under the 2013 Dispansarisation programme. RESULTS: The proportion with no recent primary care contact was 32.3% (95% CI 29.7% to 35.0%) in males, 16.3% (95% CI 14.6% to 18.2%) in females, and 23.1% (95% CI 21.6% to 24.7%) overall. In gender-specific age-adjusted analyses, no recent contact was also associated with low education, smoking, very good to excellent self-rated health, no chest pain, CVD 10-year SCORE risk 5+%, absence of hypertension control, absence of hypertension awareness and absence of care-intensive conditions. Among those with no contact: 37% current smokers, 34% with 5+% 10-year CVD risk, 32% untreated hypertension, 20% non-anginal chest pain, 18% problem drinkers, 14% uncontrolled hypertension and 9% Grade 1-2 angina. The proportion without general health check attendance was 54.6%. CONCLUSION: Primary care and community interventions would be required to proactively reach sections of 40-69 year olds currently not in contact with primary care services to reduce their CVD risk through diagnosis, treatment, lifestyle recommendations and active follow-up.

Understanding the role of physicians within the managerial structure of Russian hospitals.

This article examines the role of physicians within the managerial structure of Russian hospitals. A comparative qualitative methodology with a structured assessment framework is used to conduct case studies that allow for international comparison. The research is exploratory in nature and comprises 63 individual interviews and 49 focus groups with key informants in 15 hospitals, complemented by document analysis. The material was collected between February and April 2017 in five different regions of the Russian Federation. The results reveal three major problems of hospital management in the Russian Federation. First, hospitals exhibit a leaky system of coordination with a lack of structures for horizontal exchange of information within the hospitals (meso-level). Second, at the macro-level, the governance system includes implementation gaps, lacking mechanisms for coordination between hospitals that may reinforce existing inequalities in service provision. Third, there is little evidence of a learning culture, and consequently, a risk that the same mistakes could be made repeatedly. We argue for a new approach to governing hospitals that can guide implementation of structures and processes that allow systematic and coherent coordination within and among Russian hospitals, based on modern approaches to accountability and organisational learning.

Georgia: Health System Review.

This analysis of the Georgian health system reviews developments in its organization and governance, health financing, health care provision, health reforms and health system performance. Since 2012, political commitment to improving access to health care, to protecting the population from the financial risks of health care costs and to reducing inequalities has led to the introduction of reforms to provide universal health coverage. Considerable progress has been made. Over 90% of the resident population became entitled to a tightly defined package of state-funded benefits in 2013; previously, only 45% of the population had been eligible. The package of services has variable depth of coverage depending on the groups covered, with the lowest income groups enjoying the most comprehensive benefits. To finance the broader coverage, the government increased health spending significantly, although this remains low in international comparisons. Out-of-pocket (OOP) payments have fallen as public spending has increased. Nevertheless, current health expenditure (CHE) is still dominated by OOP payments (57% in 2015), two thirds of which are for outpatient pharmaceuticals. For this reason, in July 2017, the package of benefits was expanded for the most vulnerable households to cover essential medicines for four common chronic conditions. The system has retained extensive infrastructure with strong geographical coverage. Georgia also has a large number of doctors per capita, but an acute shortage of nurses. Incentives in the system for patients and providers favour emergency and inpatient care over primary care. There are also limited financial incentives to improve the quality of care and a lack of disincentives to inhibit poor quality care. Future reform plans focus on ensuring universal access to high-quality medical services, strengthening primary care and public health services, and increasing financial protection.

Direct demonstration of negative regulation of tumor growth and metastasis by host-inducible nitric oxide synthase.

Inducible nitric oxide synthase (NOS) II expression can be induced in the tumor bed, predominantly in host cells that infiltrate and surround a tumor. However, the impact of this physiological NOS II expression in host cells on tumor growth and metastasis remains unclear because of a lack of appropriate experimental approaches. In the present study, three NOS II-null (NOS II(-/-)) tumor cell lines, KX-dw1, KX-dw4, and KX-dw7, were established and verified using Southern, Northern, and Western blot analysis, and nitric oxide production assays. Cells from these lines were then s.c. and i.v. injected into NOS II(+/+) and NOS II(-/-) C57BL/6 mice. NOS II protein expression and enzyme activity were clearly detected in the tumors that formed in NOS II(+/+) mice but not in those that formed in NOS II(-/-) mice. Consistent with the absence of NOS II expression in the tumor stroma, KX-dw1, KX-dw4, and KX-dw7 cells grew much faster and produced many more experimental lung metastases in NOS II(-/-) mice than in NOS II(+/+) mice. Therefore, physiological expression of NOS II in host cells directly inhibits tumor growth and metastasis.

Persistent low adherence to hypertension treatment in Kyrgyzstan: How can we understand the role of drug affordability?

It is well known that cardiovascular diseases (CVD) are a growing cause of mortality and morbidity in low-and middle-income countries (LMIC). While hypertension (HTN), a leading risk factor for CVD, can be easily managed with widely available medicines, there is a huge gap in treatment for HTN in many LMIC. One such country is Kyrgyzstan, where HTN is a major public health concern and adherence to medication is low. The reasons for low adherence in Kyrgyzstan are not well understood, but some evidence suggests that HTN medicines may be unaffordable for low-income families, resulting in inequitable access to HTN treatment. With data from the 2010 Kyrgyzstan Integrated Household Survey, we estimate the prevalence and factors associated with adherence to HTN medication in Kyrgyzstan. We then investigate the hypothesis that affordability may be an important factor in adherence to HTN medication. Using the coarsened exact matching approach, we estimate the economic burden faced by households with at least one member with elevated blood pressure (EBP) in Kyrgyzstan and their risk of catastrophic spending on health care. We find that EBP households have significantly higher total expenditure on health, as well as on medicines, and are more likely to experience catastrophic health spending, suggesting that out-of-pocket expenditure for EBP may be prohibitively expensive for the poorest in Kyrgyzstan. Our findings also reveal a high prevalence of self-medication (i.e. purchasing and using medication without a doctor's prescription), and increased expenditure due to self-medication, among those with EBP. Our research suggests that affordability of HTN medicines may be an important factor in low adherence to treatment in Kyrgyzstan. Low affordability may be due partly to the prescription of medicines that are not reimbursable under the national drug benefit plan, but more research is needed to identify solutions to the affordability problem.

Introducing Diagnosis-Related Groups in Kazakhstan: Evolution, achievements, and challenges.

In 2012, Kazakhstan introduced Diagnosis-Related Groups (DRGs), as part of a package of reforms which sought to contain costs and to improve efficiency and transparency in the health system; but the main challenge was to design and implement a DRG system in just one year. In 2011-2012, Kazakhstan developed its own DRG system. Initially 180 DRGs were defined to group inpatient cases but this number was subsequently expanded to more than 400. Because of time limits, the cost weights had to be derived in the absence of existing standard hospital cost accounting systems, and a national patient data transfer system also needed developing. Most importantly, huge efforts were needed to develop a regulatory framework and build up DRG capabilities at a national level. The implementation of DRGs was facilitated by strong political will for their introduction as part of a coherent package of health reforms, and consolidated efforts to build capacity. DRGs are now the key payment mechanism for hospitals. However the reforms are not fully institutionalized: the DRG structure is continuously being refined in a context of data limitations, and the revision of cost weights is most affected by insufficient data and the lack of standardized reporting mechanisms. Capacity around DRG coding is also still being developed. Countries planning to introduce DRG systems should be aware of the challenges in moving too quickly to implement DRGs as the main hospital reimbursement mechanism.

Data for development in health: a case study and monitoring framework from Kazakhstan.

Healthcare reforms are often not coupled with a relevant and appropriate monitoring framework, leaving policymakers and the public without evidence about the implications of such reforms. Kazakhstan has embarked on a large-scale reform of its healthcare system in order to achieve Universal Health Coverage. The health-related 2020 Strategic Development Goals reflect this political ambition. In a case-study approach and on the basis of published and unpublished evidence as well as personal involvement and experience (A) the indicators in the 2020 Strategic Development Goals were assessed and (B) a 'data-mapping' exercise was conducted, where the WHO health system framework was used to describe the data available at present in Kazakhstan and comment on the different indicators regarding their usefulness for monitoring the current health-related 2020 Strategic Development Goals in Kazakhstan. It was concluded that the country's current monitoring framework needs further development to track the progress and outcomes of policy implementation. The application of a modified WHO/World Bank/Global Fund health system monitoring framework was suggested to examine the implications of recent health sector reforms. Lessons drawn from the Kazakhstan experience on tailoring the suggested framework, collecting the data, and using the generated intelligence in policy development and decision-making can serve as a useful example for other middle-income countries, potentially enabling them to fast-track developments in the health sector.

A novel model system for studying the double-edged roles of nitric oxide production in pancreatic cancer growth and metastasis.

In the present study, a model system for studying the role of nitric oxide (NO) in tumor growth and metastasis was reported. Incubation of Panc02 murine pancreatic adenocarcinoma cells in vitro with cytokines and interferon led to heterogeneous expression of NO synthase II (NOS II) protein. Clonal sublines expressing different levels of NOS II were then established using a limited dilution technique. After orthotopical implantation into the pancreas of syngeneic C57BL/6 mice, clones with a low level of NOS II expression produced tumors in pancreas, metastasized to the liver, and formed ascites, whereas those having a high level of NOS II expression did not. Liver-metastasis variants having low to high metastatic ability were also established using in vivo/in vitro passage. Compared with parental Panc02 cells exhibiting a high level of NOS II expression, these variants had a decreased level of NOS II expression. Furthermore, the heterogeneous Panc02 cells were injected intravenously into a large number of syngeneic mice. Variants that metastasized to the liver, lung, skin, peritoneum, ovary, and lymph nodes were established. All of the metastatic variants exhibited a lower level of NOS II expression than the parental Panc02 cell line did. However, the phenotypes of NOS II induction and metastatic ability were unstable. Multiple in vitro/in vivo selection led to stable low NOS II expression and high metastatic potential. Finally, to further confirm the role of NOS II expression derived from tumor cells in metastasis, poorly metastatic Panc02-H0 and highly metastatic Panc02-H7 cells were injected into the pancreas of syngeneic NOS II(-/-) mice, and groups of mice received i.p. injections of either phosphate-buffered saline or L-N(6)-(1-iminoethyl) lysine. Inhibition of NOS II activity in vivo significantly promoted distant liver metastasis. Collectively, these data show that NOS II expression is highly heterogeneous and dynamically regulated, which can directly influence tumor growth and metastasis.