Metformin in patients with type 2 diabetes and kidney disease:a systematic review

IMPORTANCE: Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. OBJECTIVE: To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. EVIDENCE ACQUISITION: In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining tometformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014.We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. RESULTS: Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety ofmetformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus-use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use. CONCLUSIONS AND RELEVANCE: Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function.

Safety of antidiabetes medications:an update

Adverse iatrogenic effects of especial relevance for antidiabetes medications include hypoglycemic episodes, major adverse cardiovascular (CV) events, cancer, bone fractures, pancreatic effects, genital/urinary tract infections, and weight gain. Here, recent clinical studies addressing safety profiles of antidiabetes medications are reviewed. On balance, new prospective and population-based studies continue to indicate that the benefits of improved glucose control outweigh the risks associated with antidiabetes medications in most patients with type 2 diabetes.

Pregnancy complications in hyperemesis-affected pregnancy:a large hospital database study

Objective: Vomiting in pregnancy is a common condition affecting 80% of pregnant women. Hyperemesis is at one end of the spectrum, seen in 0.5–2% of the pregnant population. Known factors such as nulliparity, younger age and high body mass indexare associated with an increased risk of this condition in the first trimester. Late pregnancy complications attributable to hyperemesis, the pathogenesis of which is poorly understood, have not been studied in large population-based studies in the United Kingdom. The objective of this study was to determine a plausible association between hyperemesis and pregnancy complications,such as pregnancy-related hypertension, gestational diabetes and liver problems in pregnancy, and the rates of elective (ElCS) and emergency caesarean section (EmCS). Methods: Using a database based on ICD-10 classification, anonymised data of admissions to a large multi-ethnic hospital in Manchester, UK between 2000 and 2012 were examined.Notwithstanding the obvious limitations with hospital database-based research, this large volume of datasets allows powerful studies of disease trends and complications.Results Between 2000 and 2012, 156 507 women aged 45 or under were admitted to hospital. Of these, 1111 women were coded for hyperemesis (0.4%). A greater proportion of women with hyperemesis than without hyperemesis were coded forhypertensive disorders in pregnancy such as pregnancy-induced hypertension, pre-eclampsia and eclampsia (2.7% vs 1.5%;P=0.001). The proportion of gestational diabetes and liver disorders in pregnancy was similar for both groups (diabetes:0.5% vs. 0.4%; P=0.945, liver disorders: 0.2% vs. 0.1%;P=0.662). Hyperemesis patients had a higher proportion of elective and emergency caesarean sections compared with the non-hyperemesis group (ElCS: 3.3% vs. 2%; P=0.002, EmCS: 5% vs.3%; P=0.00). Conclusions: There was a higher rate of emergency and elective caesarean section in women with hyperemesis, which could reflect the higher prevalence of pregnancy-related hypertensive disorders(but not diabetes or liver disorders) in this group. The factors contributing to the higher prevalence of hypertensive disorders arenot known, but these findings lead us to question whether there is a similar pathogenesis in the development of both the conditions and hence whether further study in this area is warranted.

Causes of Childhood Blindness in North Ghana: Results From a School for the Blind in Wa, Upper West Region

Background: Because most developing countries lack sufficient resources and infrastructure to conduct population-based studies on childhood blindness, it can be difficult to obtain epidemiologically reliable data available for planning public health strategies to effectively address the major determinants of childhood blindness. The major etiologies of blindness can differ regionally and intra-regionally. The objective of this retrospective study was to determine (1) the major causes of childhood blindness (BL) and severe visual impairment (SVI) in students who attend Wa Methodist School for the Blind in Upper West Region, North Ghana, and (2) any potential temporal trends in the causes of blindness for this region.

Methods: In this retrospective study, demographic data and clinical information from an eye screening at Wa Methodist School for the Blind were coded according to the World Health Organization/Prevention of Blindness standardized reporting methodology. Causes of BL and SVI were categorized anatomically and etiologically. We determined the major causes of BL/SVI over time using information provided about the age at onset of visual loss for each student.

Results: The major anatomical causes of BL/SVI among the 190 students screened were corneal opacity and phthisis bulbi (n=28, 15%), optic atrophy (n=23, 13%), glaucoma (n=18, 9%), microphthalmos (n=18, 9%), and cataract (n=18, 9%). Within the first year of life, students became blind mainly due to whole globe causes (n=23, 26%), cataract (n=15, 17%), and optic atrophy (n=11, 13%). Those who became blind after age one year had whole globe causes (n=26, 26%), corneal opacity (n=24, 24%), and optic atrophy (n=13, 13%).

Conclusion: At the Wa Methodist School for the Blind, the major anatomical causes of BL/SVI were corneal opacity and phthisis bulbi. About half of all students became blind within the first year of life, and were disproportionately affected by cataract and retinal causes in comparison to the other students who became blind after age one year. While research in blind schools has a number of implicit disadvantages and limitations, considering the temporal trends and other epidemiological factors of blindness may increase the usefulness and/or implications of the data that come from blind school studies in order to improve screening methods for newborns in hospitals and primary care centers, and to help tailor preventative and treatment programs to reduce avoidable childhood blindness in neonates and schoolchildren.

A Rare Loss-of-Function Variant in Scavenger Receptor Class B Type I (SCARB1) Raises HDL Cholesterol and Increases Risk of Coronary Disease

Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL)
cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a
lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI
knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased
atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains
unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328
individuals with extremely high plasma HDL-C levels, we identified a homozygote for a lossof-function
variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene
encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and
abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells
derived from induced pluripotent stem cells from the homozygous subject, and in mice.
Large population-based studies revealed that subjects who are heterozygous carriers of
the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have
a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is
statistically significant).

NOD2 mutations and colorectal cancer - Where do we stand?

Due to the overwhelming burden of colorectal cancer (CRC), great effort has been placed on identifying genetic mutations that contribute to disease development and progression. One of the most studied polymorphisms that could potentially increase susceptibility to CRC involves the nucleotide-binding and oligomerization-domain containing 2 (NOD2) gene. There is growing evidence that the biological activity of NOD2 is far greater than previously thought and a link with intestinal microbiota and mucosal immunity is increasingly sought after. In fact, microbial composition may be an important contributor not only to inflammatory bowel diseases (IBD) but also to CRC. Recent studies have showed that deficient NOD2 function confers a communicable risk of colitis and CRC. Despite the evidence from experimental models, population-based studies that tried to link certain NOD2 polymorphisms and an increase in CRC risk have been described as conflicting. Significant geographic discrepancies in the frequency of such polymorphisms and different interpretations of the results may have limited the conclusions of those studies. Since being first associated to IBD and CRC, our understanding of the role of this gene has come a long way, and it is tempting to postulate that it may contribute to identify individuals with susceptible genetic background that may benefit from early CRC screening programs or in predicting response to current therapeutic tools. The aim of this review is to clarify the status quo of NOD2 mutations as genetic risk factors to chronic inflammation and ultimately to CRC. The use of NOD2 as a predictor of certain phenotypic characteristics of the disease will be analyzed as well.

The use of motivational interviews by nurses to promote health behaviors in adolescents: a scoping review protocol

Adolescents - defined as young people between 10 and 19 years of age1 - are, in general, a relatively healthy segment of the population.2 However, the developmental changes that take place during adolescence may affect their subsequent risk for diseases and for a variety of health-related behaviors. In fact, early onset of preventable health problems (e.g. obesity, malnutrition, STDs) and the engagement in health risk behaviors (e.g., sedentary life style, excessive alcohol consumption, unprotected sex) during adolescence, are likely to put them at greater risk for physical and mental health problems at a later stage in life. Moreover, health related problems and health risk behaviors may disrupt adolescents' physical and cognitive development and therefore may affect their ability to think and act in relation to decisions about their health in the future.1 In summary, health-related behaviors in adolescence, apart from their influence on the continuum of "health-disease", they also have the potential to influence future behaviors. In fact, several studies have shown that past behaviors are good predictors of future behaviors .3,4 Thus, promoting healthy practices during adolescence and taking measures to better protect young people from health risks are essential for the prevention of health problems in adulthood.5 According to the World Health Organization, the main problems affecting young people include mental health problems (such as behavioral disorders, eating disorders, suicide, anxiety or depression), the use of substances (illegal substances, alcohol and tobacco), interpersonal violence, nutrition (a proper nutrition consists of healthy eating habits and physical exercise), unintentional injuries (which are a leading cause of death and disability among young people, with road traffic injuries accounting for about 700 deaths per day), sexual and reproductive health (for example, risky sexual behaviors, early pregnancy and childbirth) and HIV (resulting from sexual transmission and drug injection).5,6 On the other hand, the number of children and youth with chronic health conditions has increased dramatically in the past four decades7 as larger numbers of chronically ill children survive beyond the age of 10.8 Despite the lack of data on adolescents' health making it difficult to determine the prevalence of chronic illnesses in this age group9, it is known that one in ten adolescents suffers from a chronic condition worldwide.10 In fact, national population based studies from Western countries show that 20-30% of teenagers have a chronic illness, defined as one that lasts longer than six months.8 The most prevalent chronic illness among adolescents is asthma and the one with the highest incidence is diabetes mellitus, particularly type II.9 Traditionally, healthcare professionals have been mainly investing in health education activities, through the transmission of knowledge with a view to creating habits, customs and behaviors, and promoting healthy lifestyles. However, empowering people does not only consist of giving them the right information11 , i.e. good information is not enough to cause people to make changes.12 The motivation or desire to change unhealthy behaviors and habits depends on many factors, namely intrinsic motivation, control over personal decisions, self-confidence and perception of effectiveness, personal ambivalence, and individualized assistance.12 Many professionals assume that supplying knowledge is sufficient for behavioral changes; however, even very good advice often fails to generate behavioral change. After all, people continue to engage in unhealthy behaviors despite clearly knowing what they should do and how to change. "What is lacking is the motivation to apply that knowledge".13, p.1233 In fact, behavioral change is a complex phenomenon with multiple determinants that also includes motivational variables. It is associated with ambivalent processes expressed in the dilemma between keeping the current status and moving on to new ways of acting. For example, telling adolescents that if they keep on engaging in a certain behavior, they are increasing the risk of developing a long-term condition such as cardiovascular disease, stroke or diabetes is rarely enough to trigger the desired behavioral change; people are more likely to change when they believe that the change is really effective and that they are able to implement it.12 Therefore, it is essential to provide specific training for "healthcare professionals to master motivational techniques, avoid confrontation with the users, and facilitate behavioral changes".14 In this context, motivating patients to make behavioral changes is also an important nursing task where change in lifestyle is a major element of patients' treatment and preventive interventions.15 One of the nurse's goals is to help improve a patient's health or help them to manage existing health conditions. Once nurses are in a position where they have to focus on accomplishing tasks and telling patients what needs to be accomplished16, the role of the nurse is expanding even more into the use of motivational strategies.17 MI is bringing nurses back to therapeutic communication and moving them closer to successful health promotion and disease management, by promoting behavior change and empowering their patients. As the nursing profession evolves, MI is seen as a challenge and the basis of nurse's interactions with individuals, families and communities.16, 17 In the same way, MI may be taken as an essential tool in the provision of nursing care to adolescents, being itself a workspace with possible therapeutic effects regarding problems, clarification of doubts, and development of skills.18 In fact, MI may be particularly applicable in work with adolescents because of their specific developmental stage. Adolescents attempt to establish their own autonomy and identity while struggling with social interactions and moral issues, which leads to ambivalence.19 Consistent with the developmental challenges during adolescence, "MI explicitly honors autonomy, people's right and irrevocable ability to decide about their own behavior"20 while allowing the person to explore possibilities for change of risky or maladaptive behaviours.19 MI can be defined as a directive, client-centred counselling style for eliciting behavior change by helping clients to explore and resolve ambivalence. It is most centrally defined not by technique but by its spirit as a facilitative style of interpersonal relationship.21 It is a set of strategies and techniques widely used in clinical practice based on the transtheoretical model of change. The Stages of Change model describes five stages of readiness—precontemplation, contemplation, preparation, action, and maintenance—and provides a framework for understanding behavior change.22 The MI has been widely tested and applied in different areas, such as modification of addictive behaviors, interventions with offenders in the context of justice, eating disorders, promotion of therapeutic adherence among chronic patients, promotion of learning in school settings or intervention with adolescents at risk.18,23 In general, clinical practice has been adopting the perspective of motivation as something relatively immutable, i.e., the adolescent is either motivated for change/treatment and, in these conditions, the professional's role is to help him/her, or the adolescent is not motivated and then change/treatment is not feasible. Alternatively the theoretical model underlying the MI technique postulates that the individual's adherence to change/treatment depends on his/her motivation, which can change throughout the therapeutic intervention. As several studies found positive results for effects of MI24-26 and its use by health professionals is encouraged23,27 nurses may play an important role in patients' process of change. As nurses have a crucial role in clinical contexts, they can facilitate the process of ending risk behaviors and/or adopting positive health behaviors through some motivational techniques, namely with adolescents. A considerable number of systematic reviews about MI already exist pointing to some benefits of its use in the treatment of a broad range of behavioral problems and diseases.13,28,29 Some of the current reviews focus on examining the effectiveness of MI for adolescents with diverse health risks/problems 30-32. However, to date there are no reviews that present and assess the evidence for the use of nurse-led MI in adolescents. Therefore, we have little knowledge of what works for whom (which adolescent subpopulation) under what circumstances (in which setting, for what problem) in relation to motivational interviewing by nurses. There is a clear need for scoping or mapping the use of MI by nurses with adolescents to identify evidence gaps and to inform opportunities for future development in nursing practice. On the other hand, information regarding nurse-led implemented and evaluated interventions, techniques and/or strategies used, contexts of application and adolescents subpopulation groups is dispersed in the literature33-36 which impedes the formulation of precise questions about the effectiveness of those interventions conducted by nurses and therefore the realization of a systematic review. In other words, it is known that different kind of motivational interventions have been implemented in different contexts by nurses, however does not exist a map about all the motivational techniques and/or strategies used. Furthermore the literature does not clarify which is the role of nurses at cross professional motivational intervention implemented programs and finally the outcomes and evaluation of interventions are unclear. Thus, the practical implication of this mapping will be clarifying all these aspects. Without this clarification is not possible to proceed to the realization of a systematic review about the effectiveness of the use of motivational interviews by nurses to promote health behaviors in adolescents, in a particular context and/or health risk behavior; or regarding the effectiveness of certain technique and/or strategy of MI. Consequently, there are important questions about the nature of the evidence in this area that need to be answered before formulating a precise question of effectiveness. This scoping review aims to respond to these questions. An initial search of the JBI Database of Systematic Reviews & Implementation Reports, Cochrane Database of Systematic Reviews, , Database of promoting health effectiveness reviews (DoPHER), The Campbell Library, Medline and CINAHL, has revealed that currently there is no Scoping Review (published or in progress) on the subject. In this context, this scoping review will examine and map the published and unpublished research around the use of MI by nurses implemented and evaluated to promote health behaviors in adolescents; to establish its current extent, range and nature and identify its feasibility, outcomes and gaps in the evidence defining research priorities in this field. This scoping review will be informed by the JBI methodology37 that suggests a five stage methodological framework for conducting scoping reviews which includes: identifying the research question, searching for relevant studies, selecting studies, charting data, collating, summarizing and reporting the results.

NOD2 mutations and colorectal cancer - Where do we stand?

Due to the overwhelming burden of colorectal cancer (CRC), great effort has been placed on identifying genetic mutations that contribute to disease development and progression. One of the most studied polymorphisms that could potentially increase susceptibility to CRC involves the nucleotide-binding and oligomerization-domain containing 2 (NOD2) gene. There is growing evidence that the biological activity of NOD2 is far greater than previously thought and a link with intestinal microbiota and mucosal immunity is increasingly sought after. In fact, microbial composition may be an important contributor not only to inflammatory bowel diseases (IBD) but also to CRC. Recent studies have showed that deficient NOD2 function confers a communicable risk of colitis and CRC. Despite the evidence from experimental models, population-based studies that tried to link certain NOD2 polymorphisms and an increase in CRC risk have been described as conflicting. Significant geographic discrepancies in the frequency of such polymorphisms and different interpretations of the results may have limited the conclusions of those studies. Since being first associated to IBD and CRC, our understanding of the role of this gene has come a long way, and it is tempting to postulate that it may contribute to identify individuals with susceptible genetic background that may benefit from early CRC screening programs or in predicting response to current therapeutic tools. The aim of this review is to clarify the status quo of NOD2 mutations as genetic risk factors to chronic inflammation and ultimately to CRC. The use of NOD2 as a predictor of certain phenotypic characteristics of the disease will be analyzed as well.

A century of trends in adult human height

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.

Faeces as a source of DNA for molecular studies in a threatened population of great bustards

With recent advances in molecular biology, it is now possible to use the trace amounts of DNA in faeces to non-invasively sample endangered species for genetic studies. A highly vulnerable population of approximately 100 great bustards (Otis tarda) exists in Morocco necessitating the use of non-invasive protocols to study their genetic structure. Here we report a reliable silica-based method to extract DNA from great bustard faeces. We found that successful extraction and amplification correlated strongly with faeces freshness and composition. We could not extract amplifiable DNA from 30% of our samples as they were dry or contained insect material. However 100% of our fresh faecal samples containing no obvious insect material worked, allowing us to assess the levels of genetic variation among 25 individuals using a 542 bp control region sequence. We were able to extract DNA from four out of five other avian species, demonstrating that faeces represents a suitable source of DNA for population genetics studies in a broad range of species.

Phylogenetic relationships in Solanaceae and related species based on cpDNA sequence from plastid trnE-trnT region

Intergenic spacers of chloroplast DNA (cpDNA) are very useful in phylogenetic and population genetic studies of plant species, to study their potential integration in phylogenetic analysis. The non-coding trnE-trnT intergenic spacer of cpDNA was analyzed to assess the nucleotide sequence polymorphism of 16 Solanaceae species and to estimate its ability to contribute to the resolution of phylogenetic studies of this group. Multiple alignments of DNA sequences of trnE-trnT intergenic spacer made the identification of nucleotide variability in this region possible and the phylogeny was estimated by maximum parsimony and rooted with Convolvulaceae Ipomoea batalas, the most closely related family. Besides, this intergenic spacer was tested for the phylogenetic ability to differentiate taxonomic levels. For this purpose, species from four other families were analyzed and compared with Solanaceae species. Results confirmed polymorphism in the trnE-trnT region at different taxonomic levels.

Genetic population structure of the catadromous perciform: Macquaria novemaculeata (Percichthyidae)

Genetic population structure in the catadromous Australian bass Macquaria novemaculeata was investigated using samples from four locations spanning 600 km along the eastern Australian coastline. Both allozymes and mtDNA control region sequences were examined. Population subdivision estimates based on allozymes revealed low levels of population structuring (G(st)=0.043, P<0.05). However, mtDNA indicated moderate levels of geographic population structure (G(st)=0.146, P<0.01). Phylogenetic analysis of mtDNA control region sequences (mean sequence divergence 1.9%) indicated little phylogeographic structuring. Results suggested that genotypic variation within each river population, while bring affected primarily by genetic drift, was also prevented from more significant divergence by homogenizing levels of gene flow-synonymous with a one-dimensional stepping-stone model of population structure. The catadromous life history of Macquaria novemaculeata was considered to br influential on the pattern of population structure displayed. Results were compared to the few population genetic studies involving catadromous fishes, indicating that catadromy alone is unlikely to be a good predictor of population structure. A more comprehensive suite of biological characteristics than simple life-history traits must be considered fully to allow reliable predictive models of population structure to be formulated. (C) 1997 The Fisheries Society of the British Isles.

Validity of the self reporting questionnaire-20 in epidemiological studies with older adults

This study examined the validity of the self-reporting questionnaire (SRQ-20) in a population-based survey with older adults in Sao Paulo, Brazil. The study sample consisted of 2,008 individuals aged 65 years or more who were living in an economically disadvantaged area of the city. The geriatric mental state (GMS) was used as the gold standard for the assessment of common mental disorders (CMD). The optimal SRQ-20 threshold for case definition was 4/5 (sensitivity = 76.1%, specificity = 74.6%, area under ROC curve = 0.82). Women, older participants and those with lower income were more likely to be misclassified by the questionnaire. The inclusion of older persons with dementia or psychosis did not change the ability of the SRQ-20 to identify cases of CMD. The SRQ-20 may be a useful instrument to be used in large epidemiological studies in resource-poor settings for the identification of cases of depression and anxiety in later life. The performance of the SRQ-20 among older adults was similar to that observed with the adult population in Brazil.

Development and implementation of the population Fisher information matrix for the evaluation of population pharmacokinetic designs.

In population pharmacokinetic studies, the precision of parameter estimates is dependent on the population design. Methods based on the Fisher information matrix have been developed and extended to population studies to evaluate and optimize designs. In this paper we propose simple programming tools to evaluate population pharmacokinetic designs. This involved the development of an expression for the Fisher information matrix for nonlinear mixed-effects models, including estimation of the variance of the residual error. We implemented this expression as a generic function for two software applications: S-PLUS and MATLAB. The evaluation of population designs based on two pharmacokinetic examples from the literature is shown to illustrate the efficiency and the simplicity of this theoretic approach. Although no optimization method of the design is provided, these functions can be used to select and compare population designs among a large set of possible designs, avoiding a lot of simulations.

Difficulties encountered in a community-based study of acute respiratory infections in Uruguay

A cohort study on acute respiratory infections, involving 270 children observed by pediatricians in their homes every 10 days over a period of 32 months, gave the opportunity to experience logistic and methodological problems seldom described in the literature. The purpose of this article is to alert researchers as to the difficulties faced when performing community-based studies in developing countries. Although a carefully planned project was undertaken, problem areas included the establishment of the target population, population dynamics, field related problems, laboratory aspects and data management. It is hoped that other investigators may benefit from the extensive experience gained from our program in foreseeing and coping with the difficulties involved.