A multifaceted strategy using mobile technology to assist rural primary healthcare doctors and frontline health workers in cardiovascular disease risk management: protocol for the SMARTHealth India cluster randomised controlled trial

Background

Blood Pressure related disease affected 118 million people in India in the year 2000; this figure will double by 2025. Around one in four adults in rural India have hypertension, and of those, only a minority are accessing appropriate care. Health systems in India face substantial challenges to meet these gaps in care, and innovative solutions are needed.

Methods

We hypothesise that a multifaceted intervention involving capacity strengthening of primary healthcare doctors and non-physician healthcare workers through use of a mobile device-based clinical decision support system will result in improved blood pressure control for individuals at high risk of a cardiovascular disease event when compared with usual healthcare. This intervention will be implemented as a stepped wedge, cluster randomised controlled trial in 18 primary health centres and 54 villages in rural Andhra Pradesh involving adults aged ≥40 years at high cardiovascular disease event risk (approximately 15,000 people). Cardiovascular disease event risk will be calculated based on World Health Organisation/International Society of Hypertension’s region-specific risk charts. Cluster randomisation will occur at the level of the primary health centres. Outcome analyses will be conducted blinded to intervention allocation.

Expected outcomes

The primary study outcome is the difference in the proportion of people meeting guideline-recommended blood pressure targets in the intervention period vs. the control period. Secondary outcomes include mean reduction in blood pressure levels; change in other cardiovascular disease risk factors, including body mass index, current smoking, reported healthy eating habits, and reported physical activity levels; self-reported use of blood pressure and other cardiovascular medicines; quality of life (using the EQ-5D); and cardiovascular disease events (using hospitalisation data). Trial outcomes will be accompanied by detailed process and economic evaluations.

Significance

The findings are likely to inform policy on a scalable strategy to overcome entrenched inequities in access to effective healthcare for under-served populations in low and middle income country settings.

Trial registration

Clinical Trial Registry India CTRI/2013/06/003753.

     

Genetic evidence for the phylogenetic relationship between Na-Dene and Yeniseian speakers

Ruhlen's hypothesis, based on linguistic evidence, for a common phylogenetic origin of Na-Dene and Yeniseian speakers is tested using genetic data. Gene frequency data for the Kets, the only surviving Yeniseian speakers, were collected during a field study in 1993. Data for several Na-Dene groups, as well as other New World and Siberian populations, were compiled from the literature. These data were analyzed using R-matrix, principal components analysis, and Mantel tests. In a comparison of 10 New World and Siberian populations using eight alleles, 55.8% of the variation was accounted for by the first principal component, and 22.1% of the variation was subsumed by the second principal component. Contrary to Ruhlen's interpretation of the linguistic data, analysis of the genetic data shows that the Na-Dene cluster with other Native American populations, while the Kets genetically resemble the surrounding Siberian groups. This conclusion is further supported by correlations that are higher when the Kets are considered unrelated to Na-Dene speakers, and an insignificant partial correlation between genes and language when geography is held constant, indicating that spatial patterning accounts for most of the variation present in these populations.     

Task Shifting for Non-Communicable Disease Management in Low and Middle Income Countries – A Systematic Review

Background

One potential solution to limited healthcare access in low and middle income countries (LMIC) is task-shifting- the training of non-physician healthcare workers (NPHWs) to perform tasks traditionally undertaken by physicians. The aim of this paper is to conduct a systematic review of studies involving task-shifting for the management of non-communicable disease (NCD) in LMIC.

Methods

A search strategy with the following terms “task-shifting”, “non-physician healthcare workers”, “community healthcare worker”, “hypertension”, “diabetes”, “cardiovascular disease”, “mental health”, “depression”, “chronic obstructive pulmonary disease”, “respiratory disease”, “cancer” was conducted using Medline via Pubmed and the Cochrane library. Two reviewers independently reviewed the databases and extracted the data.

Findings

Our search generated 7176 articles of which 22 were included in the review. Seven studies were randomised controlled trials and 15 were observational studies. Tasks performed by NPHWs included screening for NCDs and providing primary health care. The majority of studies showed improved health outcomes when compared with usual healthcare, including reductions in blood pressure, increased uptake of medications and lower depression scores. Factors such as training of NPHWs, provision of algorithms and protocols for screening, treatment and drug titration were the main enablers of the task-shifting intervention. The main barriers identified were restrictions on prescribing medications and availability of medicines. Only two studies described cost-effective analyses, both of which demonstrated that task-shifting was cost-effective.

Conclusions

Task-shifting from physicians to NPHWs, if accompanied by health system re-structuring is a potentially effective and affordable strategy for improving access to healthcare for NCDs. Since the majority of study designs reviewed were of inadequate quality, future research methods should include robust evaluations of such strategies.     

Genetic structure of native circumpolar populations based on autosomal,mitochondrial, and Y chromosome DNA markers

This study investigates the genetic structure of the present‐day inhabitants of Beringia in order to answer questions concerning their origins and evolution. According to recent studies, the ancestors of Native Americans paused for a time in Beringia, during which they differentiated genetically from other Asians before peopling the New World. Furthermore, the Koryaks of Kamchatka share a “ubiquitous” allele (D9S1120) with Native Americans, indicating they may have descended from the same ancestral Beringian population that gave rise to the New World founders. Our results show that a genetic barrier exists between Kamchatkans (Koryaks and Even) and Bering Island inhabitants (Aleuts, mixed Aleuts, and Russians), based on Analysis of Molecular Variance (AMOVA) and structure analysis of nine autosomal short tandem repeats (STRs). This is supported by mitochondrial DNA evidence, but not by analysis of Y chromosome markers, as recent non‐native male admixture into the region appears to have partially obscured ancient population relationships. Our study indicates that while Aleuts are descended from the original New World founders, the Koryaks are unlikely to represent a Beringian remnant of the ancestral population that gave rise to Native Americans. They are instead, like the Even, more recent arrivals to Kamchatka from interior Siberia, and the “ubiquitous” allele in Koryaks may result from recent gene flow from Chukotka. Genbank accession numbers for mtDNA sequences: GQ922935‐GQ922973. Am J Phys Anthropol 143:62–74, 2010. © 2010 Wiley‐Liss, Inc.     

Surname distributions and their association with Y-chromosome markers in the Aleutian Islands

We examine surname distribution, origin, and association with Y-chromosome haplogroups in native communities from the Aleutian archipelago. The underlying hypothesis is that surnames and Y-chromosome haplogroups should be associated because both are paternally inherited markers. We used Lasker's coefficient of relationship through isonymy (R(ib) ) to identify the distribution of 143 surnames in the Aleutian Islands. The geographic distribution of surnames was explored both through frequency distribution and through the use of Mantel tests. Multidimensional scaling, chi-square, and Mantel tests were used to examine the relationship between surname and Y-chromosome markers. Overall, we observed that the distribution of surnames in the Aleutian archipelago is culturally driven rather than being one of paternal inheritance. Surnames follow a gradient from east to west, with high frequencies of Russian surnames found in western Aleut communities and high levels of non-Russian surnames found in eastern Aleut communities. A nonsignificant correlation (r = -0.0132; P = 0.436) was found between distance matrices based on haplogroups of the nonrecombining portion of the Y chromosome and surnames, although an association was found between non-Russian surnames and the predominantly non-Russian haplogroups (R1b, I1a, and I).     

Epidemiology of sudden cardiac death in rural South India - insights from the andhra pradesh rural health initiative

Background

Sudden cardiac death (SCD) is a common initial presentation of coronary artery disease (CAD). Despite the growing epidemic of CAD in India, the epidemiology of SCD is largely unknown.

Objective

The objective of the study was to define the prevalence and determinants of sudden cardiac deaths in rural South India.

Methods

Prospective mortality surveillance was conducted in 45 villages (180,162 subjects) in rural South India between January 2006 and October 2007. Trained multipurpose health workers sought to do verbal autopsies within 4 weeks of any death. Detailed questionnaires including comorbidities and circumstances surrounding death were recorded. SCD was adjudicated using the modified Hinkle-Thaler classification.

Results

A total of 1916 deaths occurred in the study population over the 22 month time period and verbal autopsy was obtained in 1827 (95%) subjects. Overall mean age of the deceased was 62 ± 20 years and 1007 (55%) were men. Cardiovascular and cerebrovascular diseases together accounted for 559 deaths (31%), followed by infectious disease (163 deaths, 9%), cancer (126 deaths, 7%) and suicide (93 deaths, 5%).Of the 1827 deaths, after excluding accidental deaths (89 deaths), 309 deaths (17%) met criteria for SCD. Cardiovascular disease was the underlying causes in the majority of the SCD events (231/309 (75%)). On multivariate analyses, previous MI/CAD (p < 0.001, OR 14.25), hypertension (p < 0.001, OR 1.84), and age groups between 40-60 yrs (p=0.029) were significantly associated with SCD.

Conclusion

Sudden cardiac death accounted for up to half of the cardiovascular deaths in rural Southern India. Traditional cardiovascular risk factors were strongly associated with SCD.     

Effects of the Endpoint Adjudication Process on the Results of a Randomised Controlled Trial: The ADVANCE Trial

Background

Endpoint adjudication committees (EPAC) are widely used in clinical trials. The aim of the present analysis is to assess the effects of the endpoint adjudication process on the main findings of the ADVANCE trial (Trial registration: ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00145925","term_id":"NCT00145925"}}NCT00145925).

Methods and Findings

The ADVANCE trial was a multicentre, 2×2 factorial randomised controlled trial of blood pressure lowering and intensive blood glucose control in 11140 patients with type 2 diabetes. Primary outcomes were major macrovascular (nonfatal myocardial infarction, nonfatal stroke and cardiovascular death) and microvascular (new or worsening nephropathy and retinopathy) events. Suspected primary outcomes were initially reported by the investigators at the 215 sites with subsequent adjudication by the EPAC. The EPAC also adjudicated upon potential events identified directly by ongoing screening of all reported events. Over a median follow-up of 5 years, the site investigators reported one or more primary outcomes among 2443 participants. After adjudication these events were confirmed for 2077 (85%) with 48 further events added through the EPAC-led database screening process. The estimated relative risk reductions (95% confidence intervals) in the primary outcome for the blood pressure lowering comparison were 8% (−1 to 15%) based on the investigator-reported events and 9% (0 to 17%) based on the EPAC-based events (P for homogeneity = 0.70). The corresponding findings for the glucose comparison were 8% (1 to 15%) and 10% (2% to 18%) (P for homogeneity = 0.60). The effect estimates were also highly comparable when studied separately for macrovascular events and microvascular events for both comparisons (all P for homogeneity>0.6).

Conclusions

The endpoint adjudication process had no discernible impact on the main findings in ADVANCE. These data highlight the need for careful consideration of the likely impact of an EPAC on the findings and conclusions of clinical trials prior to their establishment.     

Mitochondrial DNA variation and the origins of the Aleuts

The mitochondrial DNA (mtDNA) variation in 179 Aleuts from five different islands (Atka, Unalaska, Umnak, St. Paul, and St. George) and Anchorage was analyzed to better understand the origins of Aleuts and their role in the peopling of the Americas. Mitochondrial DNA samples were characterized using polymerase chain reaction amplification, restriction fragment length polymorphism analysis, and direct sequencing of the first hypervariable segment (HVS-I) of the control region. This study showed that Aleut mtDNAs belonged to two of the four haplogroups (A and D) common among Native Americans. Haplogroup D occurred at a very high frequency in Aleuts, and this, along with their unique HVS-I sequences, distinguished them from Eskimos, Athapaskan Indians, and other northern Amerindian populations. While sharing several control region sequences (CIR11, CHU14, CIR60, and CIR61) with other circumarctic populations, Aleuts lacked haplogroup A mtDNAs having the 16265G mutation that are specific to Eskimo populations. R-matrix and median network analyses indicated that Aleuts were closest genetically to Chukotkan (Chukchi and Siberian Eskimos) rather than to Native American or Kamchatkan populations (Koryaks and Itel'men). Dating of the Beringian branch of haplogroup A (16192T) suggested that populations ancestral to the Aleuts, Eskimos, and Athapaskan Indians emerged approximately 13,120 years ago, while Aleut-specific A and D sublineages were dated at 6539 +/- 3511 and 6035 +/- 2885 years, respectively. Our findings support the archaeologically based hypothesis that ancestral Aleuts crossed the Bering Land Bridge or Beringian platform and entered the Aleutian Islands from the east, rather than island hopping from Kamchatka into the western Aleutians. Furthermore, the Aleut migration most likely represents a separate event from those responsible for peopling the remainder of the Americas, meaning that the New World was colonized through multiple migrations.     

How Much Does a Verbal Autopsy Based Mortality Surveillance System Cost in Rural India?

ObjectiveThis paper aims to determine the cost of establishing and sustaining a verbal-autopsy based mortality surveillance system in rural India.ResultsVerbal-autopsies were completed for 96.7% (5786) of all deaths (5895) recorded. The annual cost in year 1 was INR 1,133,491 (USD 24,943) and the total cost per death was INR 757 (USD 16.66). These costs included training of NPHWs and physician reviewers Rs 67,025 (USD 1474), data collection INR 248,400 (USD 5466), dual physician review for cause of death assignment INR 375,000 (USD 8252), and project management INR 341,724 (USD 7520). The average annual cost to run the system each year was INR 822,717 (USD18104) and the cost per death was INR 549 (USD 12) for the next 3 years. Costs were reduced by using single physician review and shortened re-training sessions. The annual cost of running a surveillance system was INR 900,410 (USD 19814).DiscussionThis study provides detailed empirical evidence of the costs involved in running a mortality surveillance site using verbal-autopsy.     

Anthropometric variation among Bering Sea natives

Recent research indicates that anthropometrics can be used to study microevolutionary forces acting on humans. We examine the use of morphological traits in reconstructing the population history of Aleuts and Eskimos of the Bering Sea. From 1979 to 1981, W. S. Laughlin measured a sample of St. Lawrence Island Eskimos and Pribilof Island Aleuts. These samples included adult participants from St. George and St. Paul in the Pribilof Islands and from Gambell and Savoonga on St. Lawrence Island. The Relethford-Blangero method was used to examine the phylogenetic relationship between Aleuts and Eskimos. Anthropometric measurements for Native North Americans (measured by Boas and a team of trained anthropometrists in 1890-1904) and Native Mesoamericans (compiled from the literature for 1898-1952) were used for comparison. A principal components analysis of means for measurements and a neighbor-joining tree were constructed using Euclidean distances. All these tests revealed the same strong relationship among the focus populations. The R matrix from the Relethford-Blangero method clusters Aleuts and Eskimos separately and accounts for 97.3% of the variation in the data. Phenotypic variation within the population is minimal and therefore minimum F(ST) values are low. Genetic distances were compared to a Euclidean distance matrix of anthropometric measurements using a Mantel test and gave a high but not significant correlation. Our results provide evidence of a close phylogenetic relationship between Aleut and Eskimo populations in the Bering Sea. However, it is apparent that history has affected the relationship among the populations. Despite previous findings of higher European admixture in Gambell (based on blood group markers) than in Savoonga, Savoonga has greater within-group variation in anthropometric measurements. Anthropometrics reveal a close relationship between Gambell and St. Paul as a result of European admixture. The St. George population was the most divergent of the populations, indicating that it diverged from the Eskimos and St. Paul because of the compounding effects of genetic drift and limited European gene flow. These findings are in agreement with previous anthropometric and genetic studies of the Aleut and Eskimo populations and support the utility of anthropometrics in inferring population history and structure.