Update of the WHO global air quality guidelines: Systematic reviews - An introduction.

This paper aims to serve as an introduction to the Special Issue in Environment International entitled "Update of the WHO Global Air Quality Guidelines: Systematic Reviews". The article has two main objectives. One is to provide the context to this Special Issue, related to (a) policy context, overall exposure to air pollution, and burden of disease attributable to air pollution, and the other is to describe (b) the WHO guideline development process, with special emphasis on the systematic reviews. In particular, this paper presents the systematic reviews and other supporting evidence that was used and discussed during the process and summarizes important methodological information about the approaches taken to conduct the systematic reviews. These approaches include the definition of population, exposure, comparator, outcomes and study design (PECOS) questions, the assessment of the risk of bias in individual studies and the assessment of the overall certainty of the evidence. In summary, the new WHO global air quality guidelines are informed by the best available scientific evidence covering a vast number of research papers published until September 2018, and appraised by experts and stakeholders in the field of air quality. However, research gaps remain and, therefore, further research is warranted.

The role of burden of disease assessment in tracking progress towards achieving WHO global air quality guidelines.

OBJECTIVES: More than 90% of the global population live in areas exceeding the PM2.5 air quality guidelines (AQGs). We provide an overview of the ambient PM2.5-related burden of disease (BoD) studies along with scenario analysis in the framework of the WHO AQG update on the estimated reduction in the BoD if AQGs were achieved globally. METHODS: We reviewed the literature for large-scale studies for the BoD attributed to ambient PM2.5. Moreover, we used the latest WHO statistics to calculate the BoD at current levels and the scenarios of aligning with interim targets and AQG levels. RESULTS: The most recent BoD studies (2010 onwards) share a similar methodology, but there are differences in the input data which affect the estimates for attributable deaths (2.9-8.9 million deaths annually). Moreover, we found that if AQGs were achieved, the estimated BoD would be reduced by up to 50% in total deaths worldwide. CONCLUSIONS: Understanding the BoD across countries, especially in those that do not align with the AQGs, is essential in order to inform actions to reduce air pollution globally.

HTA and decision-making processes in Central, Eastern and South Eastern Europe: Results from a survey.

OBJECTIVE: To gain knowledge and insights on health technology assessment (HTA) and decision-making processes in Central, Eastern and South Eastern Europe (CESEE) countries. METHODS: A cross-sectional study was performed. Based on the literature, a questionnaire was developed in a multi-stage process. The questionnaire was arranged according to 5 broad domains: (i) introduction/country settings; (ii) use of HTA in the country; (iii) decision-making process; (iv) implementation of decisions; and (v) HTA and decision-making: future challenges. Potential survey respondents were identified through literature review-with a total of 118 contacts from the 24 CESEE countries. From March to July 2014, the survey was administered via e-mail. RESULTS: A total of 22 questionnaires were received generating an 18.6% response rate, including 4 responses indicating that their institutions had no involvement in HTA. Most of the CESEE countries have entities under government mandates with advisory functions and different responsibilities for decision-making, but mainly in charge of the reimbursement and pricing of medicines. Other areas where discrepancies across countries were found include criteria for selecting technologies to be assessed, stakeholder involvement, evidence requirements, use of economic evaluation, and timeliness of HTA. CONCLUSIONS: A number of CESEE countries have created formal decision-making processes for which HTA is used. However, there is a high level of heterogeneity related to the degree of development of HTA structures, and the methods and processes followed. Further studies focusing on the countries from which information is scarcer and on the HTA of health technologies other than medicines are warranted. CLASSIFICATION: Reviews/comparative analyses.

Adoption of trastuzumab for breast cancer in four emerging countries in the use of health technology assessment: a case study.

AIM: To describe processes for the adoption of trastuzumab in four countries in the use of health technology assessment (HTA): Poland, Albania, Brazil and Colombia. MATERIALS & METHODS: Mixed methods were used for collection and triangulation of data. Data were examined following a conceptual framework connecting HTA process steps and key principles. RESULTS: Trastuzumab was generally assessed following well-structured HTA processes. Nonetheless, areas of improvement were detected in terms of transparency and inclusiveness, as well as in methods used. The extent to which different criteria influenced decisions was unclear. CONCLUSION: This study covers an area in which information may not always be available, and sets the example for emerging countries interested in HTA. Further studies to gain a better understanding on decision-making across settings are warranted.

A cost-utility analysis of alternative drug regimens for newly diagnosed severe lupus nephritis patients in Thailand.

OBJECTIVE: The aim of this study was to assess the value of four drug regimens for newly diagnosed severe LN from a societal perspective. METHODS: A model-based cost-utility analysis was devised to measure lifetime costs and health outcomes. Current treatment options consisting of different combinations of i.v. CYC, AZA and MMF were compared with a baseline regimen of i.v. CYC in both the induction and maintenance phases. Resource use and costs were derived from medical records reviews and databases. Event rates were elicited from randomized controlled trials. Relative treatment effects were obtained from meta-analyses. Health utilities were obtained from a real cohort of patients to estimate the outcome of quality-adjusted life years. RESULTS: It was found that a treatment regimen that combined i.v. CYC in the induction phase with AZA in the maintenance phase was cost saving compared with the baseline regimen. Treatment with i.v. CYC in the induction phase and MMF in the maintenance phase and treatment with MMF in the induction phase and a reduced dose of the same in the maintenance phase turned out to be a negatively dominated regimen. CONCLUSION: In the Thai context, the combination of i.v. CYC for the induction phase followed by AZA for the maintenance phase should be considered as the first-line therapy for newly diagnosed severe LN, as it seems to be the most cost-saving regimen.

Efficiency or equity: value judgments in coverage decisions in Thailand.

PURPOSE: The purpose of this paper is to analyse the roles of social values in the reform of coverage decisions for Thailand's Universal Health Coverage (UC) plan in 2009 and 2010. DESIGN/METHODOLOGY/APPROACH: Qualitative techniques, including document review and personal communication, were employed for data collection and triangulation. All relevant data and information regarding the reform and three case study interventions were interpreted and analysed according to the thematic elements in the conceptual framework. FINDINGS: Social values determined changes in the UC plan in two steps: the development of coverage decision guidelines and the introduction of such guidelines in benefit package formulation. The former was guided by process values, while the latter was shaped by different content ideals of stakeholders and policymakers. Analysis of the three interventions suggests that in allocating its resources to subsidise particular services, the UC authority took into account not only cost-effectiveness, but also budget impacts, equity and solidarity. These social values competed with each other and, in many instances, the prioritisation of benefit candidates was not led solely by evidence, but also by value judgments, even though transparency was recognised as an ultimate goal of reform. RESEARCH LIMITATIONS/IMPLICATIONS: The study findings indicate room for improvement and for future research--the current conceptual framework is inadequate to capture all the crucial elements which influence health prioritisation, as well as their interactions with social values. ORIGINALITY/VALUE: The paper fills a gap in literature as it enhances understanding of the effects of social value judgments in real-life health prioritisation.

Systematic review of economic evaluations of preparedness strategies and interventions against influenza pandemics.

BACKGROUND: Although public health guidelines have implications for resource allocation, these issues were not explicitly considered in previous WHO pandemic preparedness and response guidance. In order to ensure a thorough and informed revision of this guidance following the H1N1 2009 pandemic, a systematic review of published and unpublished economic evaluations of preparedness strategies and interventions against influenza pandemics was conducted. METHODS: The search was performed in September 2011 using 10 electronic databases, 2 internet search engines, reference list screening, cited reference searching, and direct communication with relevant authors. Full and partial economic evaluations considering both costs and outcomes were included. Conversely, reviews, editorials, and studies on economic impact or complications were excluded. Studies were selected by 2 independent reviewers. RESULTS: 44 studies were included. Although most complied with the cost effectiveness guidelines, the quality of evidence was limited. However, the data sources used were of higher quality in economic evaluations conducted after the 2009 H1N1 pandemic. Vaccination and drug regimens were varied. Pharmaceutical plus non-pharmaceutical interventions are relatively cost effective in comparison to vaccines and/or antivirals alone. Pharmaceutical interventions vary from cost saving to high cost effectiveness ratios. According to ceiling thresholds (Gross National Income per capita), the reduction of non-essential contacts and the use of pharmaceutical prophylaxis plus the closure of schools are amongst the cost effective strategies for all countries. However, quarantine for household contacts is not cost effective even for low and middle income countries. CONCLUSION: The available evidence is generally inconclusive regarding the cost effectiveness of preparedness strategies and interventions against influenza pandemics. Studies on their effectiveness and cost effectiveness should be readily implemented in forthcoming events that also involve the developing world. Guidelines for assessing the impact of disease and interventions should be drawn up to facilitate these studies.

Review of granulocyte colony-stimulating factors in the treatment of established febrile neutropenia.

PURPOSE: To assess the value of granulocyte colony-stimulating factors (G-CSF) in promoting recovery from established episodes of febrile neutropenia (FN) after chemotherapy in cancer patients. METHOD: The literature was searched using the MEDLINE, EMBASE, BIOSIS, and IPA databases. Reference lists from the retrieved papers and hand searches of relevant journals complemented the search. Eleven randomized controlled trials were selected for review. RESULT: G-CSF use in established FN appears to be limited to a small reduction in neutropenia duration, length of hospitalization, and duration of antibiotic use. Overall, there are no significant reductions in time to neutrophil recovery and fever resolution. The cost analyses performed do not show significant cost savings. CONCLUSION: Granulocyte colony-stimulating factors (G-CSF) are biological agents typically used for prevention of febrile neutropenia (FN) or as adjunctive treatment with antibiotics of established FN. Most clinical guidelines discourage the general use of G-CSF for adjunctive treatment of ongoing neutropenic fever; however, its use in special situations, such as high-risk for infectious complications or adverse prognostic factors, is advised. G-CSF should be reserved for high-risk cancer patients, in accordance with the results of this review. This recommendation needs to be taken with caution in view of the disparities and methodological flaws found among trials. It is necessary to design further trials appropriately, well-powered and focused on high-risk patients. Moreover, it is necessary to perform an appropriate economic evaluation for this setting.

Granulocyte colony-stimulating factor use in a large British hospital: comparison with published experience / Uso de factor estimulante de colonias de granulocitos en un gran hospital británico: comparación con la experiencia publicada

Granulocyte colony-stimulating factors (G-CSF) are high-cost agents recommended as prophylaxis of febrile neutropenia or as adjunctive treatment of severe neutropenic sepsis. Their use in high-risk situations such as acute myeloid leukaemia, acute lymphocytic leukaemia, myelodysplastic syndrome and stem cell transplantation is also indicated. Objective: This audit assessed the use of G-CSF within the Oncology and Haematology Service Delivery Unit at Guy's and St. Thomas' hospital (London, United Kingdom). Methods: Patients who received G-CSF in April-May 2008 were identified retrospectively from the pharmacy labelling system, and chemotherapy front sheets, clinic letters and transplantation protocols were reviewed. Patients on lenograstim, in clinical trials or under non-approved chemotherapy protocols were excluded. Results: A total of 104 G-CSF treatments were assessed. The most commonly treated malignancy was breast cancer (41.3%), with docetaxel 100 mg/m2 (34.6%) being the most frequent chemotherapy regimen. The chemotherapy intent was curative in 66.3 % of cases. Pegfilgrastim was used in 73.1 % of cases and primary prophylaxis was the most common indication (54.8%). Stem cell transplantation was the first indication to meet the audit criterion (93.3%), followed by primary prophylaxis (89.5%). There was a considerable non-adherence for secondary prophylaxis (6.7%). Conclusion: The overall level of compliance with the audit criteria was 72.1%. The results for primary and secondary prophylaxis would have been different if FEC100 (fluorouracil, epirubicin, cyclophosphamide) and docetaxel 100 mg/m2 had been considered a single chemotherapy regimen. Also, the lack of access to medical notes may have affected the reliability of the results for «therapeutic» use (AU)

Los factores estimulantes de colonias de granulocitos (G-CSF) son agentes de alto coste recomendados en la profilaxis de la neutropenia febril o como tratamiento coadyuvante de sepsis neutropénica grave. También está indicado su uso en situaciones de alto riesgo, tales como leucemia aguda mieloide, leucemia linfocítica aguda, síndrome mielodisplásico y trasplante de células madre. Objetivo: Este audit evaluó el uso de G-CSF en la unidad de dispensación de los servicios de oncología y hematología del Hospital Guy y St. Thomas (Londres, Reino Unido). Métodos: Mediante el sistema de etiquetado de farmacia, se identificó retrospectivamente a los pacientes que recibieron G-CSF entre abril y mayo de 2008 y se revisaron las hojas de quimioterapia, las notas clínicas y los protocolos de trasplante. Se excluyó a los pacientes en lenogastrim, en ensayos clínicos o bajo protocolos de quimioterapia no aprobados. Resultados: Se evaluó un total de 104 tratamientos de G-CSF. La neoplasia más comúnmente tratada fue el cáncer de mama (41,3%), siendo el docetaxel 100 mg/m2 el régimen terapéutico más comúnmente utilizado (34,6%). El objetivo terapéutico fue curativo en el 66,3% de los casos. El pegfilgastrim se usó en el 73,1/ de los casos y la profilaxis primaria fue la indicación más frecuente (54,8%). El trasplante de células madre fue la primera indicación en cumplir los criterios del audit (93,3%), seguida de la profilaxis primaria (89,5%). Hubo un incumplimiento considerable en la profilaxis secundaria (6,7%). Conclusión: El nivel total de cumplimiento en el audit fue del 72,1%. Los resultados de profilaxis primaria y secundaria hubieran sido diferentes si el FEC100 (fluorouracilo, epirubicina, ciclofosfamida) y el docetaxel 100 m g/m2 se considerasen como régimen de quimioterapia único. Asimismo, la falta de acceso a las notas clínicas puede haber afectado a la fiabilidad de los resultados de objetivo terapéutico (AU)

Granulocyte colony-stimulating factor use in a large British hospital: comparison with published experience.

UNLABELLED: Granulocyte colony-stimulating factors (G-CSF) are high-cost agents recommended as prophylaxis of febrile neutropenia or as adjunctive treatment of severe neutropenic sepsis. Their use in high-risk situations such as acute myeloid leukaemia, acute lymphocytic leukaemia, myelodysplastic syndrome and stem cell transplantation is also indicated. OBJECTIVE: This audit assessed the use of G-CSF within the Oncology and Haematology Service Delivery Unit at Guy's and St. Thomas' hospital (London, United Kingdom). METHODS: Patients who received G-CSF in April-May 2008 were identified retrospectively from the pharmacy labelling system, and chemotherapy front sheets, clinic letters and transplantation protocols were reviewed. Patients on lenograstim, in clinical trials or under non-approved chemotherapy protocols were excluded. RESULTS: A total of 104 G-CSF treatments were assessed. The most commonly treated malignancy was breast cancer (41.3%), with docetaxel 100 mg/m (2) (34.6%) being the most frequent chemotherapy regimen. The chemotherapy intent was curative in 66.3 % of cases. Pegfilgrastim was used in 73.1 % of cases and primary prophylaxis was the most common indication (54.8%). Stem cell transplantation was the first indication to meet the audit criterion (93.3%), followed by primary prophylaxis (89.5%). There was a considerable nonadherence for secondary prophylaxis (6.7%). CONCLUSION: The overall level of compliance with the audit criteria was 72.1%. The results for primary and secondary prophylaxis would have been different if FEC100 (fluorouracil, epirubicin, cyclophosphamide) and docetaxel 100 mg/m (2) had been considered a single chemotherapy regimen. Also, the lack of access to medical notes may have affected the reliability of the results for 'therapeutic' use.