Evelina Chapman

The epidemic of chronic kidney disease in Central America

Immediate and coordinated action is needed to address the epidemic of chronic kidney disease sweeping across Central America. The disorder, known as CKDnT, is not related to traditional causes such as hypertension and diabetes, and mainly aff ects young male agricultural workers, the highest mortality being in El Salvador and Nicaragua (fi gure). However, CKDnT also aff ects women and non-agricultural workers living in farming communities. Mortality estimates from the Pan American Health Organization (PAHO) show that chronic kidney disease coded as N18 in WHO’s International Classifi cation of Diseases revision 10—a proxy for CKDnT—in men younger than 60 years has been responsible for thousands of deaths in the past decade in Central America. CKDnT is characterised by a tubulointerstitial nephropathy with low-grade proteinuria, which has a long subclinical period that tends to progress to end-stage renal disease in a short period of time. The scarcity of coverage and access to health services might contribute to the clinical course and high mortality rates of CKDnT. Health authorities, for example in El Salvador, responded to this poor coverage by increasing access to health services; however, the large number of patients and absence of adequate infrastructure and trained personnel led to overloaded hospitals. Similar epidemiological and clinical patterns of CKDnT have been reported in other countries, such as Sri Lanka. Causes of the CKDnT epidemic are not clear, although a consensus exists among researchers on its multifactorial character and relation to social, environmental, and economic determinants. Most commonly postulated causes include exposure to pesticides, heat stress with recurrent dehydration, and an excessive intake of high-sugar drinks. Exposure to heavy metals, use of non-steroidal anti-infl ammatory drugs and alcohol, and infectious diseases have similarly been postulated as causes for the CKDnT epidemic. Research to identify determinants of the epidemic is necessary, but the moral duty to address an epidemic cannot be postponed until its causes are identifi ed. A coordinated response from the public health sector and other related sectors is urgently needed. In addition to health services required to treat aff ected people, public health bodies need to consider environmental and occupational health measures. The two main hypotheses for the high incidence and excess mortality—ie, the use of pesticides and heat stress along with dehydration—are strongly related to the absence of a regulatory system to control agrochemical use and the poor compliance with rules and standards to protect the labour force’s health. Almost all Central American countries are signatories to the Stockholm Convention on Persistent Organic Pollutants and the Rotterdam Convention on Prior Informed Consent. Compliance, however, is far from

Chronic Kidney Disease Epidemic in Central America: Urgent Public Health Action Is Needed amid Causal Uncertainty

The 52nd Directing Council of the Pan American Health Organization (PAHO), in response to a call for action of the Minister of Health of El Salvador, recognized chronic kidney disease from nontraditional causes (CKDnT) affecting agricultural communities in Central America as a serious public health problem that requires urgent, effective, and concerted multisectoral action [1]. Most Central American countries do not have surveillance systems capable of detecting chronic kidney disease (CKD). However, many reports [2]–[4] and data from PAHO show the epidemiological magnitude of the disease. A proxy for CKDnT mortality, the age standardized mortality rate due to chronic kidney disease—coded as N18 (CKD-N18) by the 2010 International Classification of Diseases—is notably higher for men and women in Nicaragua and El Salvador compared to other countries in the region and has been since at least 2000 (http://www.paho.org/hq/index.php?option=com_content&view=article&id=9402). CKD-N18 data also show disproportionate mortality from the disease in males compared to females (Figure 1). Mortality due to CKD in El Salvador and Nicaragua exhibited a pattern of excess mortality in young adults (Figure 2), which is consistent with many other clinical and epidemiological reports [2]–[4]. Figure 1 Chronic kidney disease (N18; International Classification of Diseases, tenth revision [ICD-10]) age-standardized mortality rate, selected countries, 2000–2009. Figure 2 Chronic kidney disease (N18, ICD-10) age-specific mortality rate, selected countries, around 2008. CKDnT has been largely reported in some clustered farming communities traditionally burdened by socioeconomic disadvantages from northern Nicaragua [2], the Pacific coast of El Salvador [3], and other countries such as Costa Rica, Guatemala, Honduras, and the south of Mexico [4]. The disease affects mostly young adult male agricultural workers, e.g., sugarcane cutters. CKDnT has also been described in agricultural workers in Sri Lanka and India [5]–[6]. Studies reveal that patients affected by CKDnT show a clinical and pathologic pattern of a tubule-interstitial disease [7]–[8], which seems to progress to end-stage renal disease in a relatively short time. This clinical pattern explains at least in part the high burden imposed on the affected countries for the delivery of health services. For example, a 50% increase in hospitalizations for CKD from 2005 to 2012 was reported in El Salvador, making CKD the leading cause of death in El Salvadors main hospital [1]. CKDnT is a chronic and multifactorial condition that has been neglected for quite some time. The causes of this epidemic have not been elucidated yet. Several potential etiological factors have been considered [7]. Given the diseases higher prevalence in agricultural communities and its clinical and epidemiological characteristics, which are similar to CKDnT in Sri Lanka [5], it is reasonable to draw attention to two interdependent factors: the misuse of agrochemicals and the working conditions of the labor force. The misuse of pesticides has been widespread in Central America for a long time [9]. This region imported 33 million kg of active ingredient per year with an increase of 33% during 2000–2004. From a total of 403 pesticides (13 of which constitute 77% of the total pesticides that were imported), 22% were highly/extremely acutely toxic, 33% were moderately/severely irritating or sensitizing, and 30% had multiple chronic toxicities. Out of 41 banned or highly regulated pesticides as per international treaties, 16 were imported to Central America, four of which are among the 13 most imported pesticides [10]. Although the specific mechanisms to explain the nephrotoxicity of some pesticides are still under investigation, the nephrotoxicity of several of them is already known [11], [12]. Harsh working conditions, especially regular exposure to very hot temperatures and extreme physical effort, lead to heat stress and dehydration. Along with exposure to pesticides, these seem to play an important role in the occurrence of the disease, particularly among sugarcane cutters [13]. The weakness of regulatory systems [10], along with the agriculture dependency of local economies [14] and cultural agricultural practices [9], contribute to poor compliance with international safety and health standards for the use of agrochemicals and for occupational hygiene. Many questions related to these potential causative agents remain unanswered. For example, why is there such an important difference in the distribution of CKD between countries? Are there differences in the agricultural practices and work processes in areas with the same climatic characteristics and devoted to the same type of plantations (e.g., sugarcane)? Which types of agrochemicals have been used in the affected areas? How do we explain cases in nonsugarcane cutters, as well as in women? Other hypothesized causal agents merit further investigation. Nonsteroidal anti-inflammatory drugs, alcohol, and sugary beverage consumption have been associated with the disease [7], but their role remains controversial in current scientific evidence. The potential role of heavy metals and contamination of fertilizer has not been investigated in depth in the region and deserves more research. It has been argued that infectious diseases such as leptospirosis and dengue, which are prevalent in the region, could also play a role in the CKDnT epidemic [7]. However, these hypothesis have not been supported by evidence. Indeed, the human transmission of the West Nile virus, which has been associated with CKD [15], has not been documented in Central America until now. A CKDnT regional research agenda is imperative not only to drive efforts to determine the epidemics causative agents but also to bridge the gap between research and public health interventions. However, much-needed research must not delay action to address CKDnT. The resolution on CKDnT in Central America approved by PAHOs Directing Council [1] commits to coordinated and evidence-informed action to implement public policies, programs, and regulatory mechanisms to improve the social, environmental, occupational, and economic conditions of the affected communities and to strengthen surveillance and CKD-relevant health services. The resolution of PAHO [1] also highlighted the relevance of multisectorial actions outside of the health sector—for instance, agriculture, trade, environment, occupational safety, affected communities, academia, and civil society, among others—to coordinate efforts, mobilize resources, prioritize the sustainability of actions to promote evidence-based public policies, and to reach the high level of commitment to reduce environmental risk factors to mitigate, on an urgent basis, the health, social, and economic consequences of this disease. An effective and urgent response to address and ultimately stop the epidemic is a moral duty not only for Central America but for the whole Pan American community.

Litigios por derecho a la salud en tres países de América Latina: revisión sistemática de la literatura

OBJECTIVE: Identify and evaluate studies that analyzed characteristics of right-to-health litigation in Brazil, Colombia, and Costa Rica. METHODS: Studies were evaluated that analyzed characteristics of right-to-health litigation identified through a search of PubMed, LILACS, Cochrane Library, and Scirus (April 2012). Two reviewers evaluated the studies. Variables collected were, among others, grounds for litigation, proportion of lawsuits for benefits covered by the health system, and lawsuits on high-cost technologies. RESULTS: Thirty studies were identified (Brazil 19, Colombia 10, and Costa Rica 1). Judgments were frequently in favor of plaintiffs: Colombia (75%-87%), Costa Rica (89.7%), and Brazil (70%-100%). In Colombia, lawsuits were filed for benefits included in the Compulsory Health Plan (range: 41%-69.9%). In Brazil there was considerable variation in the amount of lawsuits between the Exceptional Circumstance Drug Dispensing Program (13%-31%) and basic medicines in the Unified Health System (approximately 50%). Lawsuits on drugs varied as a percentage of all lawsuits (Colombia 11.9%-35.6%, Costa Rica 30.2%, and Brazil 49.6%). A study in Brazil found a statistically significant difference when comparing lawsuits on exceptional drugs versus all other drugs, by social class; and in another study, according to lawsuits from municipalities with better socioeconomic indicators. A concentration of lawsuits on drug prescribing by a limited group of physicians was reported. Prescribing was not always supported by scientific evidence. Another study found that in half of the cases, the cost of legal proceedings was higher than the cost of the services being claimed. CONCLUSIONS: There are similarities in the grounds, nature, and impact of litigation in the context of the countries studied. The studies included show weaknesses of health systems to ensure access to different services as well as in the introduction of new health technologies.

What are the best methodologies for rapid reviews of the research evidence for evidence-informed decision making in health policy and practice: a rapid review

BackgroundRapid reviews have the potential to overcome a key barrier to the use of research evidence in decision making, namely that of the lack of timely and relevant research. This rapid review of systematic reviews and primary studies sought to answer the question: What are the best methodologies to enable a rapid review of research evidence for evidence-informed decision making in health policy and practice?MethodsThis rapid review utilised systematic review methods and was conducted according to a pre-defined protocol including clear inclusion criteria (PROSPERO registration: CRD42015015998). A comprehensive search strategy was used, including published and grey literature, written in English, French, Portuguese or Spanish, from 2004 onwards. Eleven databases and two websites were searched. Two review authors independently applied the eligibility criteria. Data extraction was done by one reviewer and checked by a second. The methodological quality of included studies was assessed independently by two reviewers. A narrative summary of the results is presented.ResultsFive systematic reviews and one randomised controlled trial (RCT) that investigated methodologies for rapid reviews met the inclusion criteria. None of the systematic reviews were of sufficient quality to allow firm conclusions to be made. Thus, the findings need to be treated with caution. There is no agreed definition of rapid reviews in the literature and no agreed methodology for conducting rapid reviews. While a wide range of ‘shortcuts’ are used to make rapid reviews faster than a full systematic review, the included studies found little empirical evidence of their impact on the conclusions of either rapid or systematic reviews. There is some evidence from the included RCT (that had a low risk of bias) that rapid reviews may improve clarity and accessibility of research evidence for decision makers.ConclusionsGreater care needs to be taken in improving the transparency of the methods used in rapid review products. There is no evidence available to suggest that rapid reviews should not be done or that they are misleading in any way. We offer an improved definition of rapid reviews to guide future research as well as clearer guidance for policy and practice.

Risk of bias of randomized trials over time.

OBJECTIVES To determine the variation in the risk of bias (RoB) of randomized controlled trials (RCTs) in time. STUDY DESIGN AND SETTING We reviewed all included RCTs from systematic reviews (SRs) published in the issue 12 (2012) of the Cochrane Databases of Systematic Reviews. We extracted the RoB authors evaluation per domain and other RCT characteristics. Multivariate logistic regression was used to evaluate association between the presence of a low RoB according to RoB domains and other characteristics. RESULTS We included 1,732 RCTs from 97 SRs. The rates of RCTs judged as having low and high RoB significantly increased over time, whereas the rates of unclear RoB decreased for several domains. Increased rates of low RoB were consistent when considering the type of intervention (drugs vs. others), sample size, and country income level. Multivariate logistic regression shows that RCTs published between 2006 and 2012, compared with those published before 1990, were more likely to be considered at low RoB for sequence generation (odds ratio [OR] = 3.96; 95% confidence interval [CI]: 2.29, 6.87), allocation concealment (OR = 3.56; 95% CI: 1.96, 6.46), incomplete outcome data (objective outcomes; OR = 1.89; 95% CI: 1.13, 3.15), and selective reporting (OR = 4.14; 95% CI: 2.35, 7.29) domains. CONCLUSION RCTs have improved reporting during the last decades decreasing the uncertainty for the RoB assessment.

Designing a rapid response program to support evidence-informed decision-making in the Americas region: using the best available evidence and case studies.

BackgroundThe objective of this work was to inform the design of a rapid response program to support evidence-informed decision-making in health policy and practice for the Americas region. Specifically, we focus on the following: (1) What are the best methodological approaches for rapid reviews of the research evidence? (2) What other strategies are needed to facilitate evidence-informed decision-making in health policy and practice? and (3) How best to operationalize a rapid response program?MethodsThe evidence used to inform the design of a rapid response program included (i) two rapid reviews of methodological approaches for rapid reviews of the research evidence and strategies to facilitate evidence-informed decision-making, (ii) supplementary literature in relation to the “shortcuts” that could be considered to reduce the time needed to complete rapid reviews, (iii) four case studies, and (iv) supplementary literature to identify additional operational issues for the design of the program.ResultsThere is no agreed definition of rapid reviews in the literature and no agreed methodology for conducting them. Better reporting of rapid review methods is needed. The literature found in relation to shortcuts will be helpful in choosing shortcuts that maximize timeliness while minimizing the impact on quality. Evidence for other strategies that can be used concurrently to facilitate the uptake of research evidence, including evidence drawn from rapid reviews, is presented. Operational issues that need to be considered in designing a rapid response program include the implications of a “user-pays” model, the importance of recruiting staff with the right mix of skills and qualifications, and ensuring that the impact of the model on research use in decision-making is formally evaluated.ConclusionsWhen designing a new rapid response program, greater attention needs to be given to specifying the rapid review methods and reporting these in sufficient detail to allow a quality assessment. It will also be important to engage in other strategies to facilitate the uptake of the rapid reviews and to evaluate the chosen model in order to make refinements and add to the evidence base for evidence-informed decision-making.

Effectiveness of interventions to prevent motorcycle injuries: systematic review of the literature.

Globally, 49% of deaths from traffic crashes occur among vulnerable road users, including pedestrians, bicyclists, and motorcyclists. Approximately, a quarter of those killed are motorcyclists. The authors carried out a systematic review of the literature to evaluate the effectiveness of interventions to prevent motorcycle crashes and the associated morbidity and mortality. The studies included in this review provide evidence for the effectiveness of helmet use, protective clothing, training, and penalties for alcohol consumption and speeding in preventing injury and death to motorcyclists. The use of helmets is effective, especially if it is universally required by law for drivers and passengers. Training to obtain a license also has positive effects but not when it is totally voluntary. There is limited but consistent evidence that strengthening laws for penalties related to alcohol consumption or speeding has an impact on risk. Traffic calming interventions could help reduce crashes in urban areas. In jurisdictions where there is limited regulation or adherence to effective measures, such as the use of helmets, efforts should be directed primarily at expanding such practices. In other areas, efforts can focus on approaches based on alternative effective measures or on more innovative interventions adapted to local conditions.

Prioritization of strategies to approach the judicialization of health in Latin America and the Caribbean

ABSTRACT OBJECTIVE To describe strategies that contribute to the comprehensive approach to the judicialization of health in countries of Latin America and the Caribbean. METHODS A search was structured to identify articles presenting strategies to approach the judicialization of health. A survey was designed, which included actors of the health system and judiciary sector. We prioritized the strategies qualified by more than the 50.0% of the participants as “very relevant”. Strategies were categorized according to: governance, provision of services, human resources, information systems, financing, and medical products. RESULTS We included 64 studies, which identified 50 strategies, related to the sub-functions and components of health systems. Of the 165 people who answered the survey, 80.0% were aged 35-64 years. The distribution of men and women was homogeneous. Half of the respondents were from Colombia (20.0%), Uruguay (16.9%), and Argentina (12.7%). We prioritized strategies that addressed aspects of generation of useful scientific evidence for decision making according to the health needs of the population, empowerment for the society, and creating spaces for discussion of measures of inclusion or exclusion of health technologies. The executive and judiciary decision makers prioritized questions that dealt with strategies that would ensure accountability. CONCLUSIONS The results of this study contribute to the identification of effective strategies to approach the phenomenon of judicialization of health, guaranteeing the right to health.MÉTODOS: Se estructuró una búsqueda para identificar artículos que presentaran estrategias para el abordaje de la judicialización en salud. Se diseñó una encuesta, en donde se incluyeron actores del sistema de salud y del sector judicial. Se priorizaron las estrategias calificadas por más del 50,0% de los participantes como “muy relevantes”. Se categorizaron las estrategias según: gobernanza, prestación de servicios, recursos humanos, sistemas de información, financiación y productos médicos.