Establishment of a Maternal Newborn Health Registry in the Belgaum District of Karnataka,India

Background

Pregnancy-related vital registration is important to inform policy to reduce maternal, fetal and newborn mortality, yet few systems for capturing accurate data are available in low-middle income countries where the majority of the mortality occurs. Furthermore, methods to effectively implement high-quality registration systems have not been described. The goal of creating the registry described in this paper was to inform public health policy makers about pregnancy outcomes in our district so that appropriate interventions to improve these outcomes could be undertaken and to position the district to be a leader in pregnancy-related public health research.

Methods

We created a prospective maternal and newborn health registry in Belgaum, Karnataka State, India. To initiate this registry, we worked with the Ministry of Health to first establish estimated birth rates and define the catchment areas of the clusters, working within the existing health system and primary health centers. We also undertook household surveys to identify women likely to become pregnant. We then implemented monitoring measures to ensure high quality and completeness of the maternal newborn health registry. All pregnant women in the catchment area were identified, consented and enrolled during pregnancy, with follow-up visits to ascertain pregnancy outcomes and mother/infant status at 42-days postpartum.

Results

From 2008 through 2014, we demonstrated continued improvements in both the coverage for enrollment and accuracy of reporting pregnancy outcomes within the defined catchment area in Belgaum, India. Nearly 100% of women enrolled had follow-up at birth and 99% had 42-day follow-up. Furthermore, we facilitated earlier enrollment of women during pregnancy while achieving more timely follow-up and decreased time of reporting from the date of the pregnancy event.

Conclusions

We created a pregnancy-related registry which includes demographic data, risk factors, and outcomes allowing for high rates of ascertainment and follow-up while working within the existing health system. Understanding the elements of the system used to create the registry is important to improve the quality of the results. Tracking of pregnancies and their outcomes is an important step toward reducing maternal and perinatal mortality.

     

X-linked chronic granulomatous disease: correction of NADPH oxidase defect by retrovirus-mediated expression of gp91-phox

Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting from the inability of an individual's phagocytes to produce superoxide anions because of defective NADPH oxidase. The disease may be treated by bone marrow transplantation and as such is a candidate for somatic gene therapy. Two thirds of patients have defects in an X- linked gene (X-CGD) encoding gp91-phox, the large subunit of the membrane cytochrome b-245 component of NADPH oxidase. Epstein-Barr virus-transformed B-cell lines from patients with CGD provide a model system for the disease. We have used retrovirus-mediated expression of gp91-phox to reconstitute functionally NADPH oxidase activity in B-cell lines from three unrelated patients with X-CGD. The protein is glycosylated and membrane associated, and the reconstituted oxidase is appropriately activated via protein kinase C. The kinetics of superoxide production by such reconstituted cells is similar to that of normal B-cell lines. These data show the potential of gene therapy for this disease.     

A phase II study of continuous infusion recombinant human granulocyte- macrophage colony-stimulating factor as an adjunct to autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma in first remission

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) clearly hastens myeloid recovery in patients with relapsed hematologic malignancies undergoing autologous bone marrow transplantation (ABMT). In efforts to further improve neutrophil engraftment and shorten hospital stay in ABMT patients, rhGM-CSF was administered by a potentially more potent route (continuous infusion) to non-Hodgkin's lymphoma (NHL) patients with better BM reserve (first remission). Time to myeloid engraftment was compared with that of NHL patients treated in first remission at our institution on a similar ABMT protocol but without growth factor support (controls). Median neutrophil engraftment (absolute neutrophil count, 500 cells/microL) in first remission patients treated with rhGM-CSF was 14 days, compared with 22 days in controls (P = .0001). Hospital stays were also significantly reduced for rhGM-CSF patients (P = .0003). Platelet engraftment did not differ between the two groups. Persistent fever and generalized serositis were the primary toxicities. rhGM-CSF, delivered by this route, was efficacious but more toxic than 2-hour rhGM-CSF infusions previously reported by other investigators. Future alterations in both dose and schedule may retain comparable efficacy yet diminish toxicity.     

Contextual Determinants of Childhood Injury: A Systematic Review of Studies With Multilevel Analytic Methods

Background. The definition of injury that underpins the contemporary approach to injury prevention is an etiological definition relating to bodily damage arising from transfer of energy to tissues of the body beyond the limits compatible with physiological function. Causal factors proximal to the energy transfer are nested within a more complex set of contextual determinants. For effective injury control, understanding of these determinants is critical.Objectives. The primary aims of this study were to describe the area-level determinants that have been included in multilevel analyses of childhood injury and to quantify the relationships between these area-level exposures and injury outcomes.Search methods. We conducted a systematic review of peer-reviewed, English-language literature published in scientific journals between January 1997 and July 2014, reporting studies that employed multilevel analyses to quantify the eco-epidemiological causation of physical unintentional injuries to children aged 16 years and younger. We conducted and reported the review in accordance with the PRISMA guidelines.Selection criteria. We included etiological studies of causal risk factors for unintentional traumatic injuries to children aged 0 to 16 years. Methodological inclusion criteria were as follows:

• Epidemiological studies quantifying the relationship between risk factors (at various levels) and injury occurrence in the individual;
• Studies that recognized individual exposure and at least 1 higher level of exposure with units at lower levels or microunits (e.g., individuals) nested within units at higher levels or macrounits (e.g., areas or neighborhoods);
• Injury outcomes (dependent variable) examined at the individual level; and
• Central analytic techniques belonging to the following categories: multilevel models, hierarchical models, random effects models, random coefficient models, covariance components models, variance components models, and mixed models.

We combined criteria from the checklist described by the Cochrane Effective Practice and Organization of Care Review Group with factors in the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement, and we used several quality assessment items from other injury-related systematic reviews to create a quality assessment checklist for this review.Data collection and analysis. Two authors independently extracted data and selected analysis features for the included studies by using preformatted tables. They extracted information as reported in the articles. We determined statistical significance of estimates and effects by using the conventional threshold, P < .05. Any differences in the information extracted were resolved by discussion between authors and by specifically rereading and rechecking the facts as reported in the relevant articles. We tabulated results from the final multilevel model(s) in each of the included articles with key aspects summarized in text. Interpretations of the results and identification of key issues raised by the collated material are reported in the Discussion section of this article.Main results. We identified 11 967 articles from the electronic search with only 14 being included in the review after a detailed screening and selection process. Nine of the 14 studies identified significant fixed effects at both the area and individual levels. The area-level variables most consistently associated with child injury rates related to poverty, education, employment, and access to services. There was some evidence that injury rates were lower in areas scoring well on area-level summary measures of neighborhood safety. There was marked variation in the methods used and in the mapping of measured variables onto the conceptual model of ecological causation.Author conclusions. These results help establish the scope for the public policy approach to injury prevention. More consistent reporting of multilevel study results would aid future interpretation and translation of such findings.PLAIN-LANGUAGE SUMMARY: Injury remains the leading cause of childhood deaths in many parts of the world. Part of the variation in child injury rates between populations can be explained by the different social and physical environments within which children live. We reviewed the current state of knowledge in this area.We examined 14 qualifying research articles relevant to the area of interest. Results of the review show that features of the social and physical environments most consistently associated with child injury rates involve neighborhood safety, poverty, levels of education, and access to services. Because there have been so few research projects conducted on this topic, and because of the wide variation in the methods used, existing knowledge does not offer a strong basis for explaining how the environments in which children live influence their risk of injury.Public policy offers great potential (e.g., through allocation of public resources, activities of social institutions, design of public spaces) to facilitate solutions to the problem of injury. Although the evidence provided by this review is somewhat limited in scope, what it does provide is critically important for the development of future research and future public policy initiatives.The definition of injury that underpins the contemporary approach to injury prevention is an etiological definition relating to bodily damage arising from transfer of energy to tissues of the body beyond the limits compatible with physiological function.1,2 Causal factors proximal to the energy transfer are nested within a more complex set of contextual determinants.3 For effective injury control, understanding of these contexts is critical.4The most common characterization of the context in which energy transfer occurs has been in terms of the social determinants of health literature.5 A systematic review of all articles published between 1960 and 2002 that quantified the role of socioeconomic determinants of injury identified 10 studies with data analyzed only at the individual level, 5 that used area-level analysis, and only 1 study that employed multilevel statistics.6 Overall, authors reported a strong, inverse association between socioeconomic status and unintentional injuries, but noted varied patterns depending on injury cause, setting, population, and level of analyses.6 There was also a general consensus among authors that the mixed results across the published literature may have been because the role of context as a determinant of injury was more nuanced than could be detected by the coarse measurements and methods used, and that the field needed to develop further in terms of measurement, conceptualization of cause, and analytic sophistication if it were to adequately describe the complex causal pathways.Since 2002, several qualitative efforts have been made to apply and adapt the developing concepts of ecological public health to the specific issue of injury causation.7–10 In 2010, Pickett et al. noted that the field of injury control research was starting to benefit from a recent application of the multilevel concept of injury causation, stated a priori, to guide more innovative etiological modeling.11 However, to date there remain few accounts in the literature of quantitative studies whose primary aim has been to elucidate ecological causation by using appropriate multilevel statistics. To the authors’ knowledge, there have been no published studies that have delineated the relevant multilevel causal factors for a given injury type and then developed, implemented, and evaluated a whole-of-population injury prevention program based on this eco-epidemiological framework.Interest in the need to understand the context within which injury occurs has been heightened by developments in the public policy approach to injury prevention. Public policy has long been an important tool for injury prevention practitioners, as the logical final step in the progression from knowledge to practice (e.g., the mandated use of child car seats and bike helmets to ensure widespread uptake). More recently, injury prevention practitioners have formally explored policy frameworks and approaches, such as Kingdon’s streams approach,12 that focus on the public domain, and on how and why policy issues rise and fall from the government agenda.13 In their explanation of road safety as a social issue, Johnson et al.14 discuss the role of public constituency, committed societal leadership, safety climate, an appropriate infrastructure, cooperation and coordination among all stakeholders, and a long-term perspective as critical elements of societal intervention to eliminate serious injury and death from road transport. In epidemiological terms, these social institutions are the area-level factors in a multilevel causal model of road crash injury that when optimized by practitioner action become components of the overall preventive intervention.Activities of social institutions, allocation of public resources, and design of public spaces are specified by public policy. Policy has a more direct influence on area-level than on individual-level factors. Thus, understanding the relationship between these area-level factors, the downstream individual-level behaviors, and the risk of child injury may be helpful in maximizing the effectiveness of child injury interventions at the population level.As the basis for encouraging further the development of an ecological approach to injury prevention, we have undertaken a systematic review to identify, collate, and synthesize the current quantitative evidence from studies that have used formal multilevel statistical methods to examine the causation of childhood injury. The primary aims of this study were to describe the multilevel determinants of childhood injury represented in the included studies and to quantify the relationships between these multilevel level exposures and injury outcomes.     

Association Between Neighborhood Disadvantage and Hypertension Prevalence,Awareness, Treatment,and Control in Older Adults: Results From the University of Alabama at Birmingham Study of Aging

Objectives. We evaluated the effect of neighborhood disadvantage (ND) on older adults’ prevalence, awareness, treatment, and control of hypertension.Methods. Data were from the University of Alabama at Birmingham Study of Aging, an observational study of 1000 community-dwelling Black and White Alabamians aged 65 years and older, in 1999 to 2001. We assessed hypertension prevalence, awareness, treatment, and control with blood pressure measurements and self-report data. We assessed ND with US Census data corresponding with participants’ census tracts, created tertiles of ND, and fit models with generalized estimating equations via a logit link function with a binomial distribution. Adjusted models included variables assessing personal advantage and disadvantage, place-based factors, sociodemographics, comorbidities, and health behaviors.Results. Living in mid-ND (adjusted odds ratio [AOR] = 1.6; 95% confidence interval [CI] = 1.2, 2.1) and high-ND tertiles (AOR = 1.8; 95% CI = 1.3, 2.3) was associated with higher hypertension prevalence, and living in high-ND tertiles was associated with lower odds of controlled hypertension (AOR = 0.6; 95% CI = 0.4, 0.6). In adjusted models, ND was not associated with hypertension awareness or treatment.Conclusions. These findings show that neighborhood environmental factors matter for hypertension outcomes and suggest the importance of ND for hypertension management in older adults.The characteristics of the geographic spaces or neighborhoods where people live influence their health throughout the life course.1–9 The mechanisms whereby neighborhood characteristics affect individuals’ health include psychosocial and material resources in those geographic spaces. Specifically, neighborhoods have the potential to be a source of social capital, providing support to persons in need; to have physical capital, offering parks and recreation resources for physical activity; and to have human capital, generating economic output. Any of these resources can contribute to the overall well-being of individuals living there.10 Alternatively, stress caused by high crime, low social support, limited economic resources, or a lack of material resources such as health services6 may ultimately negatively affect the health of individuals living in a neighborhood. Furthermore, limited community-based assistance programs, as well as limited access to healthful foods or adequate shopping opportunities and recreational facilities11 in disadvantaged neighborhoods may also have adverse effects on health. The daily stress of living in such disadvantaged neighborhoods may place a high burden on individuals’ physiological systems, a burden which is sometimes called allostatic load.12,13These risks and benefits of neighborhood contexts may accrue over a long period of time and may affect people either right away or for many years in the future14 and lead to conditions such as hypertension. In fact, neighborhood-level psychosocial and material deprivations are particularly problematic for individuals’ cardiovascular health and for management of cardiovascular risk factors. In 2004, Diez Roux et al.15 demonstrated an association between negative environments and both cardiovascular and noncardiovascular mortality. Other researchers have found similar effects, including Mujahid et al.16 who showed that walkability, access to healthy food, greater safety, and greater social cohesion were associated with a lower likelihood of hypertension.Although these findings are useful for gaining insights into the general population, work is needed to assess the effects of neighborhood characteristics on specific, unique subpopulations. To that end, there has been a growing interest in the effects of neighborhood context on older adults because of their potentially greater sensitivity (than the general population) to the effects of their neighborhood contexts on health.8,17–22 This is particularly important, as Lawton and Simon purported in the environmental docility hypothesis,23 because, as persons age and become more ill, losing control of their ability to perform activities of daily living, they may become more sensitive to characteristics of their environments, including the neighborhoods where they live. Specifically, then, older adults’ inability to navigate through disadvantaged neighborhoods may put them at higher risk for hypertension because of more concentrated exposure to psychosocial stressors. In addition, deprivation of health services including access to physicians and pharmacies in disadvantaged neighborhoods may cause adverse outcomes. Finally, older adults’ negative perception of their neighborhood environment may have a negative impact on their likelihood of being mobile and active, even when, in reality, theirs is not an unsafe or disadvantaged neighborhood.Although there is a burgeoning literature on the relationship between neighborhood characteristics and cardiovascular outcomes and a growing interest in neighborhood effects on older adults, no work known to these authors has examined neighborhood effects on hypertension specifically among older adults. Therefore, we aimed to assess if an association exists between neighborhood disadvantage (ND), measured by a validated ND index (NDI),24 and hypertension prevalence, awareness, treatment, and control in a cohort of community-dwelling older adults.     

The in vivo effects of combination antiretroviral drug therapy on peripheral blood CD34+ cell colony-forming units from HIV type 1-infected patients

This study investigated the effects of a combination antiretroviral drug regimen (indinavir and two nucleoside analogs or ritonavir and saquinavir) on the levels of CD34+ colony-forming units (CFU-Cs) in the peripheral blood of HIV-1+ patients. Ten patients who were receiving combination antiretroviral drug therapy were studied and their peripheral blood CD34+ CFU-Cs were measured prior to, 1 month after, and 4 to 6 months after the commencement of therapy. The levels of CD4+ T cells increased significantly in these patients (paired t test, p = 0.0027) and plasma viral load became undetectable in all but one patient studied. Measurements of the CFU-Cs showed that their levels tended to increase on the commencement of therapy, and these levels became significantly higher than baseline by 4-6 months (paired t test, p = 0.0293). Analysis of the different colony phenotype demonstrated that the main contributor to this increase consisted of burst-forming unit erythroid (BFU-E) cells. These data also demonstrated that there was an inverse correlation between the rise in CFU-Cs at 4-6 months compared with CD4+ cell, CD8+ cell, and neutrophil counts, and hemoglobin concentration, at baseline. The demonstrated increase in the levels of CD34+ CFU-Cs suggests that HIV-1 may have an inhibitory effect on these cells in vivo, and that this inhibition may be abrogated by suppression of viral replication.     

Infection of chimpanzees with the Uganda I/CDC strain of Plasmodium malariae

Nine splenectomized chimpanzees were infected with the Uganda I/CDC strain of Plasmodium malariae. Two had no history of previous malarial infection, whereas 6 had been infected with P. vivax and 1 with P. vivax and P. ovale. The animals with no previous infection had maximum parasitemias of 8,740 and 10,800/mm3. The other animals had maximum parasite counts of 930-75,700/mm3. Anopheles freeborni, An. stephensi, An. dirus, An. maculatus, An. quadrimaculatus, An. culicifacies, An. arabiensis, and An. gambiae were readily infected by feeding through membranes on heparinized blood from these animals.