Participation in medical research as a resource‐seeking strategy in socio‐economically vulnerable communities: call for research and action

The freedom to consent to participate in medical research is a complex subject, particularly in socio‐economically vulnerable communities, where numerous factors may limit the efficacy of the informed consent process. Informal consultation among members of the Switching the Poles Clinical Research Network coming from various sub‐Saharan African countries, that is Burkina Faso, The Gambia, Rwanda, Ethiopia, the Democratic Republic of Congo (DRC) and Benin, seems to support the hypothesis that in socio‐economical vulnerable communities with inadequate access to health care, the decision to participate in research is often taken irrespectively of the contents of the informed consent interview, and it is largely driven by the opportunity to access free or better quality care and other indirect benefits. Populations' vulnerability due to poverty and/or social exclusion should obviously not lead to exclusion from medical research, which is most often crucially needed to address their health problems. Nonetheless, to reduce the possibility of exploitation, there is the need to further investigate the complex links between socio‐economical vulnerability, access to health care and individual freedom to decide on participation in medical research. This needs bringing together clinical researchers, social scientists and bioethicists in transdisciplinary collaborative research efforts that require the collective input from researchers, research sponsors and funders.     

Access to maternal and perinatal health services: lessons from successful and less successful examples of improving access to safe delivery and care of the newborn

The huge majority of the annual 6.3 million perinatal deaths and half a million maternal deaths take place in developing countries and are avoidable. However, most of the interventions aiming at reducing perinatal and maternal deaths need a health care system offering appropriate antenatal care and quality delivery care, including basic and comprehensive emergency obstetric care facilities. To promote the uptake of quality care, there are two possible approaches: influencing the demand and/or the supply of care. Five lessons emerged from experiences. First, it is difficult to obtain robust evidence of the effects of a particular intervention in a context, where they are always associated with other interventions. Second, the interventions tend to have relatively modest short‐term impacts, when they address only part of the health system. Third, the long‐term effects of an intervention on the whole health system are uncertain. Fourth, because newborn health is intimately linked with maternal health, it is of paramount importance to organise the continuum of care between mother and newborn. Finally, the transfer of experiences is delicate, and an intervention package that has proved to have a positive effect in one setting may have very different effects in other settings.     

Perioperative nutrition management as an important component of surgical capacity in low‐ and middle‐income countries

Needs for surgical care are growing in low‐ and middle‐income countries. Existing surgical care capacity indicators, focusing on the availability of equipment, personnel, and operation and anaesthetic skills, are not intended to evaluate perioperative nutrition management, which influences surgical outcomes. In this narrative review, we describe the prevalence of malnutrition and its clinical consequences among surgical patients in low‐ and middle‐income countries, suggest potential measures to improve nutrition management and discuss the necessity of considering nutrition management as a component of surgical care capacity.     

Quality of life assessment in HIV clinical research in resource‐limited settings: better late than never

Comprehensive and sustained optimal care for patients infected with HIV can now be achieved in resource‐constrained settings, thanks to the sustainability of programs providing antiretroviral therapy (ART). But the primary goals of HIV virological suppression and improved survival need to be accompanied by a substantial improvement in patient’s experience with HIV care and treatment. An assessment of both patients’ quality of life and perceived toxicity and symptoms should now be systematically integrated into HIV clinical research in resource‐constrained countries. This will allow treatment strategies aimed at optimizing the durability of response to ART in these settings to be properly evaluated and compared.     

Pathophysiologic studies in human rabies

Six patients with proved rabies were studied with a combination of clinical, physiologic and pathologic technics. Three were given a type of intensive care but died with evidence of respiratory failure. Although circulatory failure did not develop in any of the six patients, three had supraventricular arrhythmias: interstitial myocarditis was found in one of these and rabies virus was isolated from the myocardium of another.Inspiratory muscle spasm was the dominant clinical feature In all cases. This occurred as part of the hydrophobic response and followed stimulation of the upper respiratory tract and skin. Hydrophobia may represent an exaggerated respiratory tract irritant reflex with associated arousal. Later in the course of the disease, various patterns of periodic and ataxic breathing were observed.Widespread brain stem encephalitis was discovered at autopsy, with particular involvement of the neighborhood of the nucleus ambiguous in two of the three patients examined. In one patient cerebral metabolism was grossly abnormal, with greatly reduced cerebral oxygen consumption suggesting irreversible brain damage. Respiratory and circulatory disturbances may well be immediate causes of death in patients with rabies, but the present studies reemphasize the severity of the encephalitis which remains the ultimate barrier to survival.In the developing countries in which rabies is still a major problem and in which the cost precludes intensive care, the clinical management of rabies can aim only to reduce suffering by heavy, sedation.     

Trends in health worker performance after implementing the Integrated Management of Childhood Illness strategy in Benin

Objective Training health workers to use Integrated Management of Childhood Illness (IMCI) guidelines can improve care for ill children in outpatient settings in developing countries. However, even after IMCI training, important performance gaps exist. One potential reason is that the effect of training can rapidly wane. Our aim was to determine if the performance of IMCI‐trained health workers deteriorated over 3 years. Methods We studied two departments in Benin. First, we performed a record review of 32 IMCI‐trained health workers during the first year of IMCI implementation (2001–2002). Second, we analysed data from cross‐sectional health facility surveys from 2001 to 2004 that represented the entire study area. Primary outcomes were the proportion of children under 5 years old with potentially life‐threatening illnesses who received either recommended or adequate treatment, and among all children, an index of overall guideline adherence. Secondary outcomes reflected the treatment of individual diseases. Outcomes were calculated monthly, and time trends were evaluated with regression modelling. Results The record review included 9393 consultations, and the surveys included 411 consultations performed by 105 health workers. For both data sources, performance trends were essentially flat for nearly all outcomes. Absolute levels of performance revealed substantial performance gaps. Conclusions We found no evidence that performance declined over 3 years after IMCI training. However, important performance gaps found immediately after IMCI training persisted and should be addressed.     

Research needs for an improved primary care response to chronic non‐communicable diseases in Africa

With non‐communicable diseases (NCDs) projected to become leading causes of morbidity and mortality in developing countries, research is needed to improve the primary care response, especially in sub‐Saharan Africa. This region has a particularly high double burden of communicable diseases and NCDs and the least resources for an effective response. There is a lack of good quality epidemiological data from diverse settings on chronic NCD burden in sub‐Saharan Africa, and the approach to primary care of people with chronic NCDs is currently often unstructured. The main primary care research needs are therefore firstly, epidemiological research to document the burden of chronic NCDs, and secondly, health system research to deliver the structured, programmatic, public health approach that has been proposed for the primary care of people with chronic NCDs. Documentation of the burden and trends of chronic NCDs and associated risk factors in different settings and different population groups is needed to enable health system planning for an improved primary care response. Key research issues in implementing the programmatic framework for an improved primary care response are how to (i) integrate screening and prevention within health delivery; (ii) validate the use of standard diagnostic protocols for NCD case‐finding among patients presenting to the local health facilities; (iii) improve the procurement and provision of standardised treatment and (iv) develop and implement a data collection system for standardised monitoring and evaluation of patient outcomes. Important research considerations include the following: selection of research sites and the particular NCDs targeted; research methodology; local research capacity; research collaborations; ethical issues; translating research findings into policy and practice and funding. Meeting the research needs for an improved health system response is crucial to deliver effective, affordable and equitable care for the millions of people with chronic NCDs in developing countries in Africa.     

Linking women who test HIV‐positive in pregnancy‐related services to long‐term HIV care and treatment services: a systematic review

Objectives To quantify attrition between women testing HIV‐positive in pregnancy‐related services and accessing long‐term HIV care and treatment services in low‐ or middle‐income countries and to explore the reasons underlying client drop‐out by synthesising current literature on this topic. Methods A systematic search in Medline, EMBASE, Global Health and the International Bibliography of the Social Sciences of literature published 2000–2010. Only studies meeting pre‐defined quality criteria were included. Results Of 2543 articles retrieved, 20 met the inclusion criteria. Sixteen (80%) drew on data from sub‐Saharan Africa. The pathway between testing HIV‐positive in pregnancy‐related services and accessing long‐term HIV‐related services is complex, and attrition was usually high. There was a failure to initiate highly active antiretroviral therapy (HAART) among 38–88% of known‐eligible women. Providing ‘family‐focused care’, and integrating CD4 testing and HAART provision into prevention of mother‐to‐child HIV transmission services appear promising for increasing women’s uptake of HIV‐related services. Individual‐level factors that need to be addressed include financial constraints and fear of stigma. Conclusions Too few women negotiate the many steps between testing HIV‐positive in pregnancy‐related services and accessing HIV‐related services for themselves. Recent efforts to stem patient drop‐out, such as the MTCT‐Plus Initiative, hold promise. Addressing barriers and enabling factors both within health facilities and at the levels of the individual woman, her family and society will be essential to improve the uptake of services.     

Substandard emergency obstetric care – a confidential enquiry into maternal deaths at a regional hospital in Tanzania

Objective (i) To identify clinical causes of maternal deaths at a regional hospital in Tanzania and through confidential enquiry (CE) assess major substandard care and make a comparison to the findings of the internal maternal deaths audits (MDAs); (ii) to describe hospital staff reflections on causes of substandard care. Methods A CE into maternal deaths was conducted based on information available from written sources supplemented with participatory observations and interviews with staff. The compiled information was summarized and presented anonymously for external expert review to assess for major substandard care. Hospital based maternal deaths between 2006 and 2008 (35 months) were included. Of 68 registered maternal deaths sufficient information for reviewing was retrieved for 62 cases (91%). As a supplement, in‐depth interviews with staff about the underlying causes of substandard care were performed. Results The causes of death were infection (40%), abortion (25%), eclampsia (13%), post‐partum haemorrhage (12%), obstructed labour (6%) and others (4%). The median time available for hospital staff to manage the fatal complication was 47 h. The CE identified major substandard care in 46 (74%) of the 62 cases reviewed. During the same time period MDA identified substandard care in 18 cases. Staff perceived poor organization of work and lack of training as important causes for substandard care. Local MDA was considered useful although time‐consuming and sometimes threatening, and staff dedication to the process was questioned. Conclusion Quality assurance of emergency obstetric care might be strengthened by supplementing internal MDA with external CE.     

Seroepidemiology: an underused tool for designing and monitoring vaccination programmes in low‐ and middle‐income countries

Seroepidemiology, the use of data on the prevalence of bio‐markers of infection or vaccination, is a potentially powerful tool to understand the epidemiology of infection before vaccination and to monitor the effectiveness of vaccination programmes. Global and national burden of disease estimates for hepatitis B and rubella are based almost exclusively on serological data. Seroepidemiology has helped in the design of measles, poliomyelitis and rubella elimination programmes, by informing estimates of the required population immunity thresholds for elimination. It contributes to monitoring of these programmes by identifying population immunity gaps and evaluating the effectiveness of vaccination campaigns. Seroepidemiological data have also helped to identify contributing factors to resurgences of diphtheria, Haemophilus Influenzae type B and pertussis. When there is no confounding by antibodies induced by natural infection (as is the case for tetanus and hepatitis B vaccines), seroprevalence data provide a composite picture of vaccination coverage and effectiveness, although they cannot reliably indicate the number of doses of vaccine received. Despite these potential uses, technological, time and cost constraints have limited the widespread application of this tool in low‐income countries. The use of venous blood samples makes it difficult to obtain high participation rates in surveys, but the performance of assays based on less invasive samples such as dried blood spots or oral fluid has varied greatly. Waning antibody levels after vaccination may mean that seroprevalence underestimates immunity. This, together with variation in assay sensitivity and specificity and the common need to take account of antibody induced by natural infection, means that relatively sophisticated statistical analysis of data is required. Nonetheless, advances in assays on minimally invasive samples may enhance the feasibility of including serology in large survey programmes in low‐income countries. In this paper, we review the potential uses of seroepidemiology to improve vaccination policymaking and programme monitoring and discuss what is needed to broaden the use of this tool in low‐ and middle‐income countries.     

A review of training opportunities for ultrasonography in low and middle income countries

Objective To review the current training opportunities for ultrasound use for health workers practising in low‐ and middle‐income countries (LMICs). Methods A PubMed search using terms ultrasound, sonography, echocardiography, developing country/countries, developing world, low resource settings, low income country/countries, training and education was conducted. Articles from 2000 to 2011 that included data on ultrasonography training were eligible for inclusion. Results This review shows that most ultrasound scans are performed by generalist and obstetric physicians and even non‐medical personnel with little to no formal training in ultrasonography. The spectrum of ultrasonography training described spanned from no formal training to formal certification and residency programmes. All courses included some component of didactics and hands‐on training. Follow‐up of trainee skills ranged from none, to telemedicine case review, to formal re‐evaluations and intensive refresher courses. Ultrasonographic training in LMICs often does not meet the WHO criteria such as the number of scans under supervision and length of training programme recommended by WHO. Nevertheless, some programmes manage to have excellent outcomes with regard to diagnostic accuracy and retention of knowledge by trained personnel. Conclusion Regulation and quality control of training in ultrasound skills for those working in LMICs can be improved. Research on effective training and follow‐up should be encouraged.     

Implications of the global increase of diabetes for tuberculosis control and patient care

Objectives To review the current knowledge about tuberculosis (TB) and diabetes, assessing the implication of the global increase of diabetes for TB control and patient care. Methods Systematic literature review. Results Using public databases, it can be estimated that 12.6% (95% CI 9.2–17.3%) of new TB cases in the 10 countries with the highest TB burden will be attributable to TB in 2030, a relative increase of 25.5% compared to 2010. Diabetes is associated with a higher age and body weight among patients with TB, but probably not with a specific clinical presentation of TB. Rifampicin hampers glycemic control by increasing the metabolism of most oral antidiabetic drugs, while diabetes patients may have lower concentrations of anti‐TB drugs. This might be one factor contributing to higher TB treatment failure rates. Conclusions The global epidemic of diabetes has implications for control and treatment of TB. Prospective studies are needed to improve prevention, early detection and treatment of concomitant diabetes and TB, especially in developing countries.     

‘I never thought that this baby would survive; I thought that it would die any time’: perceptions and care for preterm babies in eastern Uganda

Objective To explore the current care for and perceptions about preterm babies among community members in eastern Uganda. Methods A neonatal midwife observed care of preterm babies in one general hospital and 15 health centres using a checklist and a field diary. In‐depth interviews were conducted with 11 community health workers (CHWs) and also with 10 mothers, six fathers and three grandmothers of preterm babies. Three focus group discussions were conducted with midwives and women and men in the community. Content analysis of data was performed. Results Community members mentioned many features which may correctly be used to identify preterm babies. Care practices for preterm babies at health facilities and community level were inadequate and potentially harmful. Health facilities lacked capacity for care of preterm babies in terms of protocols, health workers’ skills, basic equipment, drugs and other supplies. However, community members and CHWs stated that they accepted the introduction of preterm care practices such as skin‐to‐skin and kangaroo mother care. Conclusion In this setting, care for preterm babies is inadequate at both health facility and community level. However, acceptance of the recommended newborn care practices indicated by the community is a window of opportunity for introducing programmes for preterm babies. In doing so, consideration needs to be given to the care provided at health facilities as well as to the gaps in community care that are largely influenced by beliefs, perceptions and lack of awareness.     

Rabies

Human rabies is extremely rare and canine rabies is largely controlled in the United States. Wild animals are now responsible for most of the rabies prevention costs and postexposure treatments in the United States, either by direct exposure of humans or by exposure of domestic animals. Although the situation is similar in most other developed countries, canine rabies remains widespread and a substantial risk to persons traveling in developing countries, where millions of people are exposed and tens of thousands die of rabies each year. People living in the United States should be advised to avoid contact with wild animals and stray or ill-appearing domestic animals. Travelers to rabies enzootic countries can substantially reduce the risk of rabies exposures by avoiding all dogs as well as wild animals; those persons whose risk of exposure cannot be reduced should be educated about rabies and should receive preexposure vaccination.     

Osteoporosis among patients with type 1 and type 2 diabetes

Both diabetes and fractures are prevalent in adults. The relationship between diabetes and osteoporosis is complex and, although it has been investigated extensively, the subject remains controversial. While low bone mineral density (BMD) is consistently observed in type 1 diabetes, the relationship is less clear in type 2 diabetes, with some studies reporting modestly increased or unchanged BMD. Both type 1 and type 2 diabetes have been associated with a higher risk of fractures. Despite discrepancies between BMD and fracture rates, clinical trials uniformly support the fact that new bone formation and bone microarchitecture and, thus, bone quality, are altered in both types of diabetes. Although a causal association between diabetes and osteoporosis cannot be established on the basis of existing data, it is possible to conclude from many studies and from a better understanding of the physiopathology of diabetes that it can increase the risk of fractures through skeletal (decreased BMD and bone quality) and extraskeletal (increased risk of falls) factors. Even though osteoporosis screening or prophylactic treatment in all patients with type 1 and type 2 diabetes is not being recommended at present, such patient populations should be given general guidelines regarding calcium and vitamin D intakes, exercise and the avoidance of potential risk factors for osteoporosis. The extent of diagnostic and therapeutic interventions should be based on the individual's risk profile for fractures.     

Drug dispensing practices during implementation of artemisinin-based combination therapy at health facilities in rural Tanzania, 2002-2005

Objective To assess the degree to which policy changes to artemisinin‐based combination therapies (ACTs) as first‐line treatment for uncomplicated malaria translate into effective ACT delivery. Methods Prospective observational study of drug dispensing practices at baseline and during the 3 years following introduction of ACT with sulfadoxine–pyrimethamine (SP) plus artesunate (AS) in Rufiji District, compared with two neighbouring districts where SP monotherapy remained the first‐line treatment, was carried out. Demographic and dispensing data were collected from all patients at the dispensing units of selected facilities for 1 month per quarter, documenting a total of 271 953 patient encounters in the three districts. Results In Rufiji, the proportion of patients who received a clinical diagnosis of malaria increased from 47.6% to 57.0%. A majority (75.9%) of these received SP + AS during the intervention period. Of patients who received SP + AS, 94.6% received the correct dose of both. Among patients in Rufiji who received SP, 14.2% received SP monotherapy, and among patients who received AS, 0.3% received AS monotherapy. Conclusions The uptake of SP + AS in Rufiji was rapid and sustained. Although some SP monotherapy occurred, AS monotherapy was rare, and most received the correct dose of both drugs. These results suggest that implementation of an artemisinin combination therapy, accompanied by training, job aids and assistance in stock management, can rapidly increase access to effective antimalarial treatment.     

Management of multidrug-resistant tuberculosis and patients in retreatment.

Retreatment of tuberculosis involves the management of entities as diverse as relapse, failure, treatment after default, and poor patient adherence to the previous treatment. The emergence of conditions for selection of resistance (failure and partial abandonment) is a matter of great concern. The development of a retreatment regimen for tuberculosis requires consideration of certain basic premises. The importance of a comprehensive and directed history of drugs taken in the past, and the limited reliability of susceptibility tests to many of these drugs, should be kept in mind. Taking this into account, and possessing a thorough knowledge of all anti-tuberculosis medications, it is possible to cure almost all patients with an appropriate retreatment regimen including a minimum of three or four drugs not previously used. Nonetheless, the treatment of these patients is so complex that it should only be carried out by experienced staff. Concern about treating tuberculosis patients with drug resistance varies greatly depending on the available resources. High-income countries should provide individual treatment regimens adapted to each patient; however, in other settings, restricted resources could justify the implementation of standardised therapeutic guidelines with second-line drugs in order to facilitate management and reduce costs.     

How to improve the validity of sexual behaviour reporting: systematic review of questionnaire delivery modes in developing countries

Objectives To systematically review comparative research from developing countries on the effects of questionnaire delivery mode. Methods We searched Medline, EMbase and PsychINFO and ISSTDR conference proceedings. Randomized control trials and quasi‐experimental studies were included if they compared two or more questionnaire delivery modes, were conducted in a developing country, reported on sexual behaviours and occurred after 1980. Results A total of 28 articles reporting on 26 studies met the inclusion criteria. Heterogeneity of reported trial outcomes between studies made it inappropriate to combine trial outcomes. Eighteen studies compared audio computer‐assisted survey instruments (ACASI) or its derivatives [personal digital assistant (PDA) or computer‐assisted personal interview (CAPI)] against another self‐administered questionnaires, face‐to‐face interviews or random response technique. Despite wide variation in geography and populations sampled, there was strong evidence that computer‐assisted interviews lowered item‐response rates and raised rates of reporting sensitive behaviours. ACASI also improved data entry quality. A wide range of sexual behaviours were reported including vaginal, oral, anal and/or forced sex, age of sexual debut, condom use at first and/or last sex. Validation of self‐reports using biomarkers was rare. Conclusions These data reaffirm that questionnaire delivery modes do affect self‐reported sexual behaviours and that use of ACASI can significantly reduce reporting bias. Its acceptability and feasibility in developing country settings should encourage researchers to consider its use when conducting sexual health research. Triangulation of self‐reported data using biomarkers is recommended. Standardizing sexual behaviour measures would allow for meta‐analysis.     

Cost‐effectiveness of educational outreach to primary care nurses to increase tuberculosis case detection and improve respiratory care: economic evaluation alongside a randomised trial

Objective To evaluate the cost‐effectiveness of an educational outreach intervention to improve primary respiratory care by South African nurses. Methods Cost‐effectiveness analysis alongside a pragmatic cluster randomised controlled trial, with individual patient data. The intervention, the Practical Approach to Lung Health in South Africa (PALSA), comprised educational outreach based on syndromic clinical practice guidelines for tuberculosis, asthma, chronic obstructive pulmonary disease, pneumonia and other respiratory diseases. The study included 1999 patients aged 15 or over with cough or difficult breathing, attending 40 primary care clinics staffed by nurses in the Free State province. They were interviewed at first presentation, and 1856 (93%) were interviewed 3 months later. Results The intervention increased the tuberculosis case detection rate by 2.2% and increased the proportion of patients appropriately managed (that is, diagnosed with tuberculosis or prescribed an inhaled corticosteroid for asthma or referred with indicators of severe disease) by 10%. It costs the health service $68 more for each extra patient diagnosed with tuberculosis and $15 more for every extra patient appropriately managed. Analyses were most sensitive to assumptions about how long training was effective for and to inclusion of household and tuberculosis treatment costs. Conclusion This educational outreach method was more effective and more costly than usual training in improving tuberculosis, asthma and urgent respiratory care. The extra cost of increasing tuberculosis case detection was comparable to current costs of passive case detection. The syndromic approach increased cost‐effectiveness by also improving care of other conditions. This educational intervention was sustainable, reaching thousands of health workers and hundreds of clinics since the trial.