Complete and long-term rescue of lesioned adult motoneurons by lentiviral-mediated expression of glial cell line-derived neurotrophic factor in the facial nucleus.

To date, delivery of neurotrophic factors has only allowed to transiently protect axotomized facial motoneurons against cell death. In the present report, long-term protection of these neurons was evaluated by continuously expressing the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) within the facial nucleus using a lentiviral vector system. The viral vector was injected unilaterally into the facial nucleus of 4-month-old Balb/C mice. In contrast to axotomy in other adult rodents, facial nerve lesion in these animals leads to a progressive and sustained loss and/or atrophy of >50% of the motoneurons. This model thus represents an attractive model to evaluate potential protective effects of neurotrophic factors for adult-onset motoneuron diseases, such as amyotrophic lateral sclerosis. One month after unilateral lentiviral vector injection, the facial nerve was sectioned, and the animals were killed 3 months later. Viral delivery of the GDNF gene led to long-term expression and extensive diffusion of GDNF within the brainstem. In addition, axotomized motoneurons were completely protected against cell death, because 95% of the motoneurons were present as demonstrated by both Nissl staining and choline acetyltransferase immunoreactivity. Furthermore, GDNF prevented lesion-induced neuronal atrophy and maintained proximal motoneuron axons, despite the absence of target cell reinnervation. This is the first evidence that viral-mediated delivery of GDNF close to the motoneuron cell bodies of the facial nucleus of adult mice can lead to complete and long-term protection against lesion-induced cell death

GDNF reduces drug-induced rotational behavior after medial forebrain bundle transection by a mechanism not involving striatal dopamine

Parkinson's disease (PD) is characterized by the progressive loss of the substantia nigra (SN) dopaminergic neurons projecting to the striatum. Neurotrophic factors may have the potential to prevent or slow down the degenerative process occurring in PD. To that end, we examined whether low amounts of glial cell line-derived neurotrophic factor (GDNF) continuously released from polymer-encapsulated genetically engineered cells are able to prevent the loss of tyrosine hydroxylase immunoreactivity (TH-IR) in SN neurons and ameliorate the amphetamine-induced rotational asymmetry in rats that have been subjected to a unilateral medial forebrain bundle (MFB) axotomy. Baby hamster kidney (BHK) cells transfected with the cDNA for GDNF were encapsulated in a polymer fiber and implanted unilaterally at a location lateral to the MFB and rostral to the SN. ELISA assays before implantation show that the capsules release approximately 5 ng of GDNF/capsule per day. One week later, the MFB was axotomized unilaterally ipsilateral to the capsule placement. Seven days later, the animals were tested for amphetamine-induced rotational asymmetry and killed. The striatum was excised and analyzed either for catecholamine content or TH-IR, while the SN was immunostained for the presence of TH-IR. GDNF did not prevent the loss of dopamine in the striatum. However, GDNF significantly rescued TH-IR neurons in the SN pars compacta. Furthermore, GDNF also significantly reduced the number of turns per minute ipsilateral to the lesion under the influence of amphetamine. Improvement of rotational behavior in the absence of dopaminergic striatal reinnervation may reflect neuronal plasticity in the SN, as suggested by the dendritic sprouting observed in animals receiving GDNF. These results illustrate that the continuous release of low levels of GDNF close to the SN is capable of protecting the nigral dopaminergic neurons from an axotomy-induced lesion and significantly improving pharmacological rotational behavior by a mechanism other than dopaminergic striatal reinnervation

Workforce participation among international medical graduates in the National Health Service of England: a retrospective longitudinal study

<p>Abstract</p> <p>Background</p> <p>Balancing medical workforce supply with demand requires good information about factors affecting retention. Overseas qualified doctors comprise 30% of the National Health Service (NHS) workforce in England yet little is known about the impact of country of qualification on length of stay. We aimed to address this need.</p> <p>Methods</p> <p>Using NHS annual census data, we calculated the duration of 'episodes of work' for doctors entering the workforce between 1992 and 2003. Survival analysis was used to examine variations in retention by country of qualification. The extent to which differences in retention could be explained by differences in doctors' age, sex and medical specialty was examined by logistic regression.</p> <p>Results</p> <p>Countries supplying doctors to the NHS could be divided into those with better or worse long-term retention than domestically trained doctors. Countries in the former category were generally located in the Middle East, non-European Economic Area Europe, Northern Africa and Asia, and tended to be poorer with fewer doctors per head of population, but stronger economic growth. A doctor's age and medical specialty, but not sex, influenced patterns of retention.</p> <p>Conclusion</p> <p>Adjusting workforce participation by country of qualification can improve estimates of the number of medical school places needed to balance supply with demand. Developing countries undergoing strong economic growth are likely to be the most important suppliers of long stay medical migrants.</p

Internship workplace preferences of final-year medical students at Zagreb University Medical School, Croatia: all roads lead to Zagreb

BACKGROUND: Human resources management in health often encounters problems related to workforce geographical distribution. The aim of this study was to investigate the internship workplace preferences of final-year medical students and the reasons associated with their choices. METHOD: A total of 204 out of 240 final-year medical students at Zagreb University Medical School, Croatia, were surveyed a few months before graduation. We collected data on each student's background, workplace preference, academic performance and emigration preferences. Logistic regression was used to analyse the factors underlying internship workplace preference, classified into two categories: Zagreb versus other areas. RESULTS: Only 39 respondents (19.1%) wanted to obtain internships outside Zagreb, the Croatian capital. Gender and age were not significantly associated with internship workplace preference. A single predictor variable significantly contributed to the logistic regression model: students who believed they would not get the desired specialty more often chose Zagreb as a preferred internship workplace (odds ratio 0.32, 95% CI 0.12–0.86). CONCLUSION: A strong preference for Zagreb as an internship workplace was recorded. Uncertainty about getting the desired specialty was associated with choosing Zagreb as a workplace, possibly due to more extensive and diverse job opportunities

Uses of population census data for monitoring geographical imbalance in the health workforce: snapshots from three developing countries

BACKGROUND: Imbalance in the distribution of human resources for health (HRH), eventually leading to inequities in health services delivery and population health outcomes, is an issue of social and political concern in many countries. However, the empirical evidence to support decision-making is often fragmented, and many standard data sources that can potentially produce statistics relevant to the issue remain underused, especially in developing countries. This study investigated the uses of demographic census data for monitoring geographical imbalance in the health workforce for three developing countries, as a basis for formulation of evidence-based health policy options. METHODS: Population-based indicators of geographical variations among HRH were extracted from census microdata samples for Kenya, Mexico and Viet Nam. Health workforce statistics were matched against international standards of occupational classification to control for cross-national comparability. Summary measures of inequality were calculated to monitor the distribution of health workers across spatial units and by occupational group. RESULTS: Strong inequalities were found in the geographical distribution of the health workforce in all three countries, with the highest densities of HRH tending to be found in the capital areas. Cross-national differences were found in the magnitude of distributional inequality according to occupational group, with health professionals most susceptible to inequitable distribution in Kenya and Viet Nam but less so in Mexico compared to their associate professional counterparts. Some discrepancies were suggested between mappings of occupational information from the raw data with the international system, especially for nursing and midwifery specializations. CONCLUSIONS: The problem of geographical imbalance among HRH across countries in the developing world holds important implications at the local, national and international levels, in terms of constraints for the effective deployment, management and retention of HRH, and ultimately for the equitable delivery of health services. A number of advantages were revealed of using census data in health research, notably the potential for producing detailed statistics on health workforce characteristics at the sub-national level. However, lack of consistency in the compilation and processing of occupational information over time and across countries continues to hamper comparative analyses for HRH policy monitoring and evaluation

A technical framework for costing health workforce retention schemes in remote and rural areas

<p>Abstract</p> <p>Background</p> <p>Increasing the availability of health workers in remote and rural areas through improved health workforce recruitment and retention is crucial to population health. However, information about the costs of such policy interventions often appears incomplete, fragmented or missing, despite its importance for the sound selection, planning, implementation and evaluation of these policies. This lack of a systematic approach to costing poses a serious challenge for strong health policy decisions.</p> <p>Methods</p> <p>This paper proposes a framework for carrying out a costing analysis of interventions to increase the availability of health workers in rural and remote areas with the aim to help policy decision makers. It also underlines the importance of identifying key sources of financing and of assessing financial sustainability.</p> <p>The paper reviews the evidence on costing interventions to improve health workforce recruitment and retention in remote and rural areas, provides guidance to undertake a costing evaluation of such interventions and investigates the role and importance of costing to inform the broader assessment of how to improve health workforce planning and management.</p> <p>Results</p> <p>We show that while the debate on the effectiveness of policies and strategies to improve health workforce retention is gaining impetus and attention, there is still a significant lack of knowledge and evidence about the associated costs. To address the concerns stemming from this situation, key elements of a framework to undertake a cost analysis are proposed and discussed.</p> <p>Conclusions</p> <p>These key elements should help policy makers gain insight into the costs of policy interventions, to clearly identify and understand their financing sources and mechanisms, and to ensure their sustainability.</p

Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

Developing evidence-based ethical policies on the migration of health workers: conceptual and practical challenges

It is estimated that in 2000 almost 175 million people, or 2.9% of the world's population, were living outside their country of birth, compared to 100 million, or 1.8% of the total population, in 1995. As the global labour market strengthens, it is increasingly highly skilled professionals who are migrating. Medical practitioners and nurses represent a small proportion of highly skilled workers who migrate, but the loss of health human resources for developing countries can mean that the capacity of the health system to deliver health care equitably is compromised. However, data to support claims on both the extent and the impact of migration in developing countries is patchy and often anecdotal, based on limited databases with highly inconsistent categories of education and skills. The aim of this paper is to examine some key issues related to the international migration of health workers in order to better understand its impact and to find entry points to developing policy options with which migration can be managed. The paper is divided into six sections. In the first, the different types of migration are reviewed. Some global trends are depicted in the second section. Scarcity of data on health worker migration is one major challenge and this is addressed in section three, which reviews and discusses different data sources. The consequences of health worker migration and the financial flows associated with it are presented in section four and five, respectively. To illustrate the main issues addressed in the previous sections, a case study based mainly on the United Kingdom is presented in section six. This section includes a discussion on policies and ends by addressing the policy options from a broader perspective

Monitoring and evaluation of human resources for health: an international perspective

BACKGROUND: Despite the undoubted importance of human resources to the functions of health systems, there is little consistency between countries in how human resource strategies are monitored and evaluated. This paper presents an integrated approach for developing an evidence base on human resources for health (HRH) to support decision-making, drawing on a framework for health systems performance assessment. METHODS: Conceptual and methodological issues for selecting indicators for HRH monitoring and evaluation are discussed, and a range of primary and secondary data sources that might be used to generate indicators are reviewed. Descriptive analyses are conducted drawing primarily on one type of source, namely routinely reported data on the numbers of health personnel and medical schools as covered by national reporting systems and compiled by the World Health Organization. Regression techniques are used to triangulate a given HRH indicator calculated from different data sources across multiple countries. RESULTS: Major variations in the supply of health personnel and training opportunities are found to occur by region. However, certain discrepancies are also observed in measuring the same indicator from different sources, possibly related to the occupational classification or to the sources' representation. CONCLUSION: Evidence-based information is needed to better understand trends in HRH. Although a range of sources exist that can potentially be used for HRH assessment, the information that can be derived from many of these individual sources precludes refined analysis. A variety of data sources and analytical approaches, each with its own strengths and limitations, is required to reflect the complexity of HRH issues. In order to enhance cross-national comparability, data collection efforts should be processed through the use of internationally standardized classifications (in particular, for occupation, industry and education) at the greatest level of detail possible