Establishing community advisory boards for clinical trial research in Malawi: Engendering ethical conduct in research

In this article I deal with extending the ethical principles of research to include communities through the establishment of Community Advisory Boards  (CABs). The aim of the project on which this article is based demonstrates the need for protecting communities that participate in research in order to stimulate ethical conduct in research in Malawi. In the article, I provide an overview on the role and functions of CABs. I discuss the establishment of CABs in Malawi and present descriptions of the processes and challenges involved. I conclude by sharing experiences of some of the key lessons learnt from the establishment of CABs

The patient-provider relationship and antenatal care uptake at two referral hospitals in Malawi: A qualitative study

Background In post-stroke patients, impairment of quality of life (QOL) has been associated with functional impairment, age, anxiety, depression, and fatigue. Good social support, higher education, and better socioeconomic status are associated with better QOL among stroke survivors. In Africa, studies from Nigeria and Tanzania have reported on post-stroke QOL.Background Approximately 90% of Malawian women attend antenatal care at least once during their pregnancies; however, most mothers first present during months five and six and do not adhere to the World Health Organization’s recommended four visits. The objective of this study was to explore the role the patient-provider relationship has on antenatal care uptake.Methods A qualitative study, consisting of interviews with 20 urban pregnant mothers and eight health workers, was conducted from September to December 2014. Two large tertiary care hospitals in the Central and Southern regions of Malawi were selected as study sites.Results Several factors influenced antenatal care attendance. Significant barriers reported included the patient-provider relationship, clinic wait times, family and friend support, distance from home to the clinic, transportation, cost, and number of visits. The patient-provider relationship appears to have a large impact on antenatal clinic participation. Mothers indicated that health workers often mistreat or demean them during visits. Additionally, health workers revealed that, due to staff shortages, patients often do notreceive the care they deserve.Conclusions The results of this study suggest that, in addition to other factors, healthcare provider attitudes influence antenatal clinic attendance. Improving the patient-provider relationship may increase antenatal clinic attendance and decrease pregnancy complications during pregnancy. Professional development opportunities and quality improvement programmes are would help improve patient care and health outcomes while the continued staff shortages in the country are addressed

Prevention and management of malaria during pregnancy: findings from qualitative studies in Ghana and Malawi

BACKGROUND: In endemic regions of sub-Saharan Africa, malaria during pregnancy (MiP) is a major preventable cause of maternal and infant morbidity and mortality. Current recommended MiP prevention and control includes intermittent preventive treatment (IPTp), distribution of insecticide-treated bed nets (ITNs) and appropriate case management. This article explores the social and cultural context to the uptake of these interventions at four sites across Africa. METHODS: A comparative qualitative study was conducted at four sites in three countries: Ghana, Malawi and Kenya. Individual and group interviews were conducted with pregnant women, their relatives, opinion leaders, other community members and health providers. Observations, which focused on behaviours linked to MiP prevention and treatment, were also undertaken at health facilities and in local communities. RESULTS: ITNs were generally recognized as important for malaria prevention. However, their availability and use differed across the sites. In Malawi and Kenya, ITNs were sought-after items, but there were complaints about availability. In central Ghana, women saved ITNs until the birth of the child and they were used seasonally in northern Ghana. In Kenya and central Ghana, pregnant women did not associate IPTp with malaria, whereas, in Malawi and northern Ghana, IPTp was linked to malaria, but not always with prevention. Although IPTp adherence was common at all sites, whether delivered with directly observed treatment or not, a few women did not comply with IPTp often citing previous side effects. Although generally viewed as positive, experiences of malaria testing varied across the four sites: treatment was sometimes administered in spite of a negative diagnosis in Ghana (observed) and Malawi (reported). Despite generally following the advice of healthcare staff, particularly in Kenya, personal experience, and the availability and accessibility of medication – including anti-malarials – influenced MiP treatment. CONCLUSION: Although ITNs were valued as malaria prevention, health messages could address issues that reduce their use during pregnancy in particular contexts. The impact of previous side effects on adherence to IPTp and anti-malarial treatment regimens during pregnancy also requires attention. Overtreatment of MiP highlights the need to monitor the implementation of MiP case management guidelines

Local illness concepts and their relevance for the prevention and control of malaria during pregnancy in Ghana, Kenya and Malawi: findings from a comparative qualitative study

BACKGROUND: In sub-Saharan Africa, the burden of morbidity and mortality linked to malaria during pregnancy (MiP) is significant and compounded by its unclear symptoms and links with other health problems during pregnancy. Mindful of the biomedical and social complexity of MiP, this article explores and compares local understandings of MiP and their links with other pregnancy-related health problems. METHODS: A comparative qualitative study was undertaken at four sites in three countries: Ghana, Malawi and Kenya. Individual and group interviews were conducted with pregnant women, their relatives, opinion leaders, other community members and health providers. MiP-related behaviours were also observed at health facilities and in local communities. RESULTS: Across the four sites, local malaria concepts overlapped with biomedically defined malaria. In terms of symptoms, at-risk groups, outcomes and aetiology of malaria during pregnancy, this overlap was however both site-specific and partial. Moreover, the local malaria concepts were not monolithic and their descriptions varied amongst respondents. The symptoms of pregnancy and malaria also overlapped but, for respondents, symptom severity was the distinguishing factor. Malaria was generally, though not universally, perceived as serious for pregnant women. Miscarriage was the most widely known outcome, and links with anaemia, low birth weight and congenital malaria were mentioned. Nonetheless, amongst many potential causes of miscarriage, malaria was not recognized as the most important, but rather interacted with other pregnancy-related problems. CONCLUSIONS: Given the overlap of common pregnancy problems with the symptoms of malaria, and the limited association of malaria with its main outcomes, a comprehensive antenatal care programme is the most appropriate strategy for the provision of health education, prevention and treatment for MiP. Variations in locally shared understandings of MiP must however be taken into account when designing and promoting MiP intervention strategies

The use of technology enhanced learning in health research capacity development: lessons from a cross country research partnership.

BACKGROUND: With the recognition of the need for research capacity strengthening for advancing health and development, this research capacity article explores the use of technology enhanced learning in the delivery of a collaborative postgraduate blended Master's degree in Malawi. Two research questions are addressed: (i) Can technology enhanced learning be used to develop health research capacity?, and: (ii) How can learning content be designed that is transferrable across different contexts? METHODS: An explanatory sequential mixed methods design was adopted for the evaluation of technology enhanced learning in the Masters programme. A number of online surveys were administered, student participation in online activities monitored and an independent evaluation of the programme conducted. RESULTS: Remote collaboration and engagement are paramount in the design of a blended learning programme and support was needed for selecting the most appropriate technical tools. Internet access proved problematic despite developing the content around low bandwidth availability and training was required for students and teachers/trainers on the tools used. Varying degrees of engagement with the tools used was recorded, and the support of a learning technologist was needed to navigate through challenges faced. CONCLUSION: Capacity can be built in health research through blended learning programmes. In relation to transferability, the support required institutionally for technology enhanced learning needs to be conceptualised differently from support for face-to-face teaching. Additionally, differences in pedagogical approaches and styles between institutions, as well as existing social norms and values around communication, need to be embedded in the content development if the material is to be used beyond the pilot resource-intensive phase of a project

Influence of Inhaled Amiloride on Lung Fluid Clearance in Response to Normobaric Hypoxia in Healthy Individuals.

AIM: To investigate the role of epithelial sodium channels (ENaC) on lung fluid clearance in response to normobaric hypoxia, 20 healthy subjects were exposed to 15 hours of hypoxia (fraction of inspired oxygen [FiO2] = 12.5%) on two randomized occasions: (1) inhaled amiloride (A) (1.5 mg/5 mL saline); and (2) inhaled saline placebo (P). Changes in lung fluid were assessed through chest computed tomography (CT) for lung tissue volume (TV), and the diffusion capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO) for pulmonary capillary blood volume (VC). Extravascular lung water (EVLW) was derived as TV-VC and changes in the CT attenuation distribution histograms were reviewed. RESULTS: Normobaric hypoxia caused (1) a reduction in EVLW (change from baseline for A vs. P, -8.5% ± 3.8% vs. -7.9% ± 5.2%, p  0.05), and (4) CT attenuation distribution became more negative, leftward skewed, and kurtotic (p < 0.05). CONCLUSION: Acute normobaric hypoxia caused a reduction in lung fluid that was unaffected by ENaC inhibition through inhaled amiloride. Although possible amiloride-sensitive ENaC may not be necessary to maintain lung fluid balance in response to hypoxia, it is more probable that normobaric hypoxia promotes lung fluid clearance rather than accumulation for the majority of healthy individuals. The observed reduction in interstitial lung fluid means alveolar fluid clearance may not have been challenged

Prevention and management of malaria during pregnancy: findings from a comparative qualitative study in Ghana, Kenya and Malawi

BACKGROUND: In endemic regions of sub-Saharan Africa, malaria during pregnancy (MiP) is a major preventable cause of maternal and infant morbidity and mortality. Current recommended MiP prevention and control includes intermittent preventive treatment (IPTp), distribution of insecticide-treated bed nets (ITNs) and appropriate case management. This article explores the social and cultural context to the uptake of these interventions at four sites across Africa. METHODS: A comparative qualitative study was conducted at four sites in three countries: Ghana, Malawi and Kenya. Individual and group interviews were conducted with pregnant women, their relatives, opinion leaders, other community members and health providers. Observations, which focused on behaviours linked to MiP prevention and treatment, were also undertaken at health facilities and in local communities. RESULTS: ITNs were generally recognized as important for malaria prevention. However, their availability and use differed across the sites. In Malawi and Kenya, ITNs were sought-after items, but there were complaints about availability. In central Ghana, women saved ITNs until the birth of the child and they were used seasonally in northern Ghana. In Kenya and central Ghana, pregnant women did not associate IPTp with malaria, whereas, in Malawi and northern Ghana, IPTp was linked to malaria, but not always with prevention. Although IPTp adherence was common at all sites, whether delivered with directly observed treatment or not, a few women did not comply with IPTp often citing previous side effects. Although generally viewed as positive, experiences of malaria testing varied across the four sites: treatment was sometimes administered in spite of a negative diagnosis in Ghana (observed) and Malawi (reported). Despite generally following the advice of healthcare staff, particularly in Kenya, personal experience, and the availability and accessibility of medication – including anti-malarials – influenced MiP treatment. CONCLUSION: Although ITNs were valued as malaria prevention, health messages could address issues that reduce their use during pregnancy in particular contexts. The impact of previous side effects on adherence to IPTp and anti-malarial treatment regimens during pregnancy also requires attention. Overtreatment of MiP highlights the need to monitor the implementation of MiP case management guidelines

Characterisation of time-dependent mechanical behaviour of trabecular bone and its constituents

Trabecular bone is a porous composite material which consists of a mineral phase (mainly hydroxyapatite), organic phase (mostly type I collagen) and water assembled into a complex, hierarchical structure. In biomechanical modelling, its mechanical response to loads is generally assumed to be instantaneous, i.e. it is treated as a time-independent material. It is, however, recognised that the response of trabecular bone to loads is time-dependent. Study of this time-dependent behaviour is important in several contexts such as: to understand energy dissipation ability of bone; to understand the age-related non-traumatic fractures; to predict implant loosening due to cyclic loading; to understand progressive vertebral deformity; and for pre-clinical evaluation of total joint replacement. To investigate time-dependent behaviour, bovine trabecular bone samples were subjected to compressive loading, creep, unloading and recovery at multiple load levels (corresponding to apparent strain of 2,000-25,000 με). The results show that: the time-dependent behaviour of trabecular bone comprises of both recoverable and irrecoverable strains; the strain response is nonlinearly related to applied load levels; and the response is associated with bone volume fraction. It was found that bone with low porosity demonstrates elastic stiffening followed by elastic softening, while elastic softening is demonstrated by porous bone at relatively low loads. Linear, nonlinear viscoelastic and nonlinear viscoelastic-viscoplastic constitutive models were developed to predict trabecular bone’s time-dependent behaviour. Nonlinear viscoelastic constitutive model was found to predict the recovery behaviour well, while nonlinear viscoelastic-viscoplastic model predicts the full creep-recovery behaviour reasonably well. Depending on the requirements all these models can be used to incorporate time-dependent behaviour in finite element models. To evaluate the contribution of the key constituents of trabecular bone and its microstructure, tests were conducted on demineralised and deproteinised samples. Reversed cyclic loading experiments (tension to compression) were conducted on demineralised trabecular bone samples. It was found that demineralised bone exhibits asymmetric mechanical response - elastic stiffening in tension and softening in compression. This tension to compression transition was found to be smooth. Tensile multiple-load-creep-unload-recovery experiments on demineralised trabecular samples show irrecoverable strain (or residual strain) even at the low stress levels. Demineralised trabecular bone samples demonstrate elastic stiffening with increasing load levels in tension, and their time-dependent behaviour is nonlinear with respect to applied loads . Nonlinear viscoelastic constitutive model was developed which can predict its recovery behaviour well. Experiments on deproteinised samples showed that their modulus and strength are reasonably well related to bone volume fraction. The study considers an application of time-dependent behaviour of trabecular bone. Time-dependent properties are assigned to trabecular bone in a bone-screw system, in which the screw is subjected to cyclic loading. It is found that separation between bone and the screw at the interface can increase with increasing number of cycles which can accentuate loosening. The relative larger deformation occurs when this system to be loaded at the higher loading frequency. The deformation at the bone-screw interface is related to trabecular bone’s bone volume fraction; screws in a more porous bone are at a higher risk of loosening

Gene duplications and evolution of vertebrate voltage-gated sodium channels

Author Posting. © The Author(s), 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Molecular Evolution 63 (2006): 208-221, doi:10.1007/s00239-005-0287-9.Voltage-gated sodium channels underlie action potential generation in excitable tissue. To establish the evolutionary mechanisms that shaped the vertebrate sodium channel a-subunit (SCNA) gene family and their encoded Nav1 proteins, we identified all SCNA genes in several teleost species. Molecular cloning revealed that teleosts have eight SCNA genes, comparable to the number in another vertebrate lineage, mammals. Prior phylogenetic analyses had indicated that teleosts and tetrapods share four monophyletic groups of SCNA genes and that tandem duplications selectively expanded the number of genes in two of the four mammalian groups. However, the number of genes in each group varies between teleosts and tetrapods suggesting different evolutionary histories in the two vertebrate lineages. Our findings from phylogenetic analysis and chromosomal mapping of Danio rerio genes indicate that tandem duplications are an unlikely mechanism for generation of the extant teleost SCNA genes. Instead, analysis of other closely mapped genes in D. rerio supports the hypothesis that a whole genome duplication was involved in expansion of the SCNA gene family in teleosts. Interestingly, despite their different evolutionary histories, mRNA analyses demonstrated a conservation of expression patterns for SCNA orthologues in teleosts and tetrapods, suggesting functional conservation.The authors’ work was supported by NIH grants (NS 38937; AEN, ADT and ABR, NS 25513; HHZ and YL and NSF IBN 0236147; MCJ)

The Generation R Study: design and cohort update 2010

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. General follow-up rates until the age of 4 years exceed 75%. Data collection in mothers, fathers and preschool children included questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome wide association screen is available in the participating children. Regular detailed hands on assessment are performed from the age of 5 years onwards. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children