Hypertension Management Using Mobile Technology and Home Blood Pressure Monitoring: Results of a Randomized Trial in Two Low/Middle-Income Countries

Abstract Objective: Hypertension and other noncommunicable diseases represent a growing threat to low/middle-income countries (LMICs). Mobile health technologies may improve noncommunicable disease outcomes, but LMICs lack resources to provide these services. We evaluated the efficacy of a cloud computing model using automated self-management calls plus home blood pressure (BP) monitoring as a strategy for improving systolic BPs (SBPs) and other outcomes of hypertensive patients in two LMICs. Subjects and Methods: This was a randomized trial with a 6-week follow-up. Participants with high SBPs (≥140?mm Hg if nondiabetic and ≥130?mm Hg if diabetic) were enrolled from clinics in Honduras and Mexico. Intervention patients received weekly automated monitoring and behavior change telephone calls sent from a server in the United States, plus a home BP monitor. At baseline, control patients received BP results, hypertension information, and usual healthcare. The primary outcome, SBP, was examined for all patients in addition to a preplanned subgroup with low literacy or high hypertension information needs. Secondary outcomes included perceived health status and medication-related problems. Results: Of the 200 patients recruited, 181 (90%) completed follow-up, and 117 of 181 had low literacy or high hypertension information needs. The median annual income was $2,900 USD, and average educational attainment was 6.5 years. At follow-up intervention patients' SBPs decreased 4.2?mm Hg relative to controls (95% confidence interval ?9.1, 0.7; p=0.09). In the subgroup with high information needs, intervention patients' average SBPs decreased 8.8?mm Hg (?14.2, ?3.4, p=0.002). Compared with controls, intervention patients at follow-up reported fewer depressive symptoms (p=0.004), fewer medication problems (p<0.0001), better general health (p<0.0001), and greater satisfaction with care (p≤0.004). Conclusions: Automated telephone care management plus home BP monitors can improve outcomes for hypertensive patients in LMICs. A cloud computing model within regional telecommunication centers could make these services available in areas with limited infrastructure for patient-focused informatics support.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98494/1/tmj%2E2011%2E0271.pd

Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome

Objective The aim of this study was to evaluate the impact of fecal donor-unrelated donor mix (FMT-FURM) transplantation as first-line therapy for C. difficile infection (CDI) in intestinal microbiome. Methods We designed an open, two-arm pilot study with oral vancomycin (250mg every 6 h for 10–14 days) or FMT-FURM as treatments for the first CDI episode in hospitalized adult patients in Hospital Universitario “Dr. Jose Eleuterio Gonzalez”. Patients were randomized by a closed envelope method in a 1: 1 ratio to either oral vancomycin or FMT-FURM. CDI resolution was considered when there was a reduction on the Bristol scale of at least 2 points, a reduction of at least 50% in the number of bowel movements, absence of fever, and resolution of abdominal pain (at least two criteria). From each patient, a fecal sample was obtained at days 0, 3, and 7 after treatment. Specimens were cultured to isolate C. difficile, and isolates were characterized by PCR. Susceptibility testing of isolates was performed using the agar dilution method. Fecal samples and FMT-FURM were analyzed by 16S rRNA sequencing. Results We included 19 patients; 10 in the vancomycin arm and 9 in the FMT-FURM arm. However, one of the patients in the vancomycin arm and two patients in the FMT-FURM arm were eliminated. Symptoms resolved in 8/9 patients (88.9%) in the vancomycin group, while symptoms resolved in 4/7 patients (57.1%) after the first FMT-FURM dose (P = 0.26) and in 5/7 patients (71.4%) after the second dose (P = 0.55). During the study, no adverse effects attributable to FMT-FURM were observed in patients. Twelve isolates were recovered, most isolates carried tcdB, tcdA, cdtA, and cdtB, with an 18-bp deletion in tcdC. All isolates were resistant to ciprofloxacin and moxifloxacin but susceptible to metronidazole, linezolid, fidaxomicin, and tetracycline. In the FMT-FURM group, the bacterial composition was dominated by Firmicutes, Bacteroidetes, and Proteobacteria at all-time points and the microbiota were remarkably stable over time. The vancomycin group showed a very different pattern of the microbial composition when comparing to the FMT-FURM group over time. Conclusion The results of this preliminary study showed that FMT-FURM for initial CDI is associated with specific bacterial communities that do not resemble the donors’ sample.Peer reviewedFinal Published versio

A prospective study of symptoms, function, and medication use during acute illness in nursing home residents: design, rationale and cohort description

<p>Abstract</p> <p>Background</p> <p>Nursing home residents are at high risk for developing acute illnesses. Compared with community dwelling adults, nursing home residents are often more frail, prone to multiple medical problems and symptoms, and are at higher risk for adverse outcomes from acute illnesses. In addition, because of polypharmacy and the high burden of chronic disease, nursing home residents are particularly vulnerable to disruptions in transitions of care such as medication interruptions in the setting of acute illness. In order to better estimate the effect of acute illness on nursing home residents, we have initiated a prospective cohort which will allow us to observe patterns of acute illnesses and the consequence of acute illnesses, including symptoms and function, among nursing home residents. We also aim to examine the patterns of medication interruption, and identify patient, provider and environmental factors that influence continuity of medication prescribing at different points of care transition.</p> <p>Methods</p> <p>This is a prospective cohort of nursing home residents residing in two nursing homes in a metropolitan area. Baseline characteristics including age, gender, race, and comorbid conditions are recorded. Participants are followed longitudinally for a planned period of 3 years. We record acute illness incidence and characteristics, and measure symptoms including depression, pain, withdrawal symptoms, and function using standardized scales.</p> <p>Results</p> <p>76 nursing home residents have been followed for a median of 666 days to date. At baseline, mean age of residents was 74.4 (± 11.9); 32% were female; 59% were white. The most common chronic conditions were dementia (41%), depression (38%), congestive heart failure (25%) and chronic obstructive lung disease (27%). Mean pain score was 4.7 (± 3.6) on a scale of 0 to 10; Geriatric Depression Scale (GDS-15) score was 5.2 (± 4.4). During follow up, 138 acute illness episodes were identified, for an incidence of 1.5 (SD 2.0) episodes per resident per year; 74% were managed in the nursing home and 26% managed in the acute care setting.</p> <p>Conclusion</p> <p>In this report, we describe the conceptual model and methods of designing a longitudinal cohort to measure acute illness patterns and symptoms among nursing home residents, and describe the characteristics of our cohort at baseline. In our planned analysis, we will further estimate the effect of the use and interruption of medications on withdrawal and relapse symptoms and illness outcomes.</p

Analysis of changes in the association of income and the utilization of curative health services in Mexico between 2000 and 2006

<p>Abstract</p> <p>Background</p> <p>A common characteristic of health systems in most developing countries is unequal access to health services. As a result, members of the poorest population groups often do not receive formal attention for health services, because they cannot afford it. In 2001 in Mexico, to address income-related differences in the use of health services, the government launched a major healthcare reform, which includes a health insurance program called <it>Seguro Popular</it>, aimed at improving healthcare access among poor, uninsured residents. This paper analyzes the before and after changes in the demand for curative ambulatory health services focusing on the association of income-related characteristics and the utilization of formal healthcare providers vs. no healthcare service utilization.</p> <p>Methods</p> <p>By using two nationally representative health surveys (ENSA-2000 and ENSANUT-2006), we modeled an individual's decision when experiencing an illness to use services provided by the (1) Ministry of Health (MoH), (2) social security, (3) private entities, or (4) to not use formal services (no healthcare service utilization).</p> <p>Results</p> <p>Poorer individuals were more likely in 2006 than in 2000 to respond to an illness by using formal healthcare providers. Trends in provider selection differed, however. The probability of using public services from the MoH increased among the poorest population, while the findings indicated an increase in utilization of private health services among members of low- and middle-income groups. No significant change was seen among formal workers -covered by social security services-, regardless of socioeconomic status.</p> <p>Conclusions</p> <p>Overall, for 2006 the Mexican population appears less differentiated in using healthcare across economic groups than in 2000. This may be related, in part, to the implementation of <it>Seguro Popular</it>, which seems to be stimulating healthcare demand among the poorest and previously uninsured segment of the population. Still, public health authorities need to address the remaining income-related healthcare utilization differences, the differences in quality between public and private health services, and the general perception that MoH facilities offer inferior services.</p

Hypothermia for encephalopathy in low and middle-income countries (HELIX): Study protocol for a randomised controlled trial

BACKGROUND: Therapeutic hypothermia reduces death and disability after moderate or severe neonatal encephalopathy in high-income countries and is used as standard therapy in these settings. However, the safety and efficacy of cooling therapy in low- and middle-income countries (LMICs), where 99% of the disease burden occurs, remains unclear. We will examine whether whole body cooling reduces death or neurodisability at 18-22 months after neonatal encephalopathy, in LMICs. METHODS: We will randomly allocate 408 term or near-term babies (aged ≤ 6 h) with moderate or severe neonatal encephalopathy admitted to public sector neonatal units in LMIC countries (India, Bangladesh or Sri Lanka), to either usual care alone or whole-body cooling with usual care. Babies allocated to the cooling arm will have core body temperature maintained at 33.5 °C using a servo-controlled cooling device for 72 h, followed by re-warming at 0.5 °C per hour. All babies will have detailed infection screening at the time of recruitment and 3 Telsa cerebral magnetic resonance imaging and spectroscopy at 1-2 weeks after birth. Our primary endpoint is death or moderate or severe disability at the age of 18 months. DISCUSSION: Upon completion, HELIX will be the largest cooling trial in neonatal encephalopathy and will provide a definitive answer regarding the safety and efficacy of cooling therapy for neonatal encephalopathy in LMICs. The trial will also provide important data about the influence of co-existent perinatal infection on the efficacy of hypothermic neuroprotection. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02387385. Registered on 27 February 2015

Adaptive Sampling of Information in Perceptual Decision-Making

In many perceptual and cognitive decision-making problems, humans sample multiple noisy information sources serially, and integrate the sampled information to make an overall decision. We derive the optimal decision procedure for two-alternative choice tasks in which the different options are sampled one at a time, sources vary in the quality of the information they provide, and the available time is fixed. To maximize accuracy, the optimal observer allocates time to sampling different information sources in proportion to their noise levels. We tested human observers in a corresponding perceptual decision-making task. Observers compared the direction of two random dot motion patterns that were triggered only when fixated. Observers allocated more time to the noisier pattern, in a manner that correlated with their sensory uncertainty about the direction of the patterns. There were several differences between the optimal observer predictions and human behaviour. These differences point to a number of other factors, beyond the quality of the currently available sources of information, that influences the sampling strategy

Genome-Wide Identification of Transcriptional Start Sites in the Plant Pathogen Pseudomonas syringae pv. tomato str. DC3000

RNA-Seq has provided valuable insights into global gene expression in a wide variety of organisms. Using a modified RNA-Seq approach and Illumina's high-throughput sequencing technology, we globally identified 5′-ends of transcripts for the plant pathogen Pseudomonas syringae pv. tomato str. DC3000. A substantial fraction of 5′-ends obtained by this method were consistent with results obtained using global RNA-Seq and 5′RACE. As expected, many 5′-ends were positioned a short distance upstream of annotated genes. We also captured 5′-ends within intergenic regions, providing evidence for the expression of un-annotated genes and non-coding RNAs, and detected numerous examples of antisense transcription, suggesting additional levels of complexity in gene regulation in DC3000. Importantly, targeted searches for sequence patterns in the vicinity of 5′-ends revealed over 1200 putative promoters and other regulatory motifs, establishing a broad foundation for future investigations of regulation at the genomic and single gene levels

Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh

Background: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia. Methods: We did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18–22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02387385. Findings: We screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87–1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention. Interpretation: Therapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available. Funding: National Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation. Translations: For the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section

Information Routing Driven by Background Chatter in a Signaling Network

Living systems are capable of processing multiple sources of information simultaneously. This is true even at the cellular level, where not only coexisting signals stimulate the cell, but also the presence of fluctuating conditions is significant. When information is received by a cell signaling network via one specific input, the existence of other stimuli can provide a background activity –or chatter– that may affect signal transmission through the network and, therefore, the response of the cell. Here we study the modulation of information processing by chatter in the signaling network of a human cell, specifically, in a Boolean model of the signal transduction network of a fibroblast. We observe that the level of external chatter shapes the response of the system to information carrying signals in a nontrivial manner, modulates the activity levels of the network outputs, and effectively determines the paths of information flow. Our results show that the interactions and node dynamics, far from being random, confer versatility to the signaling network and allow transitions between different information-processing scenarios

Phylogenetic and Morphologic Analyses of a Coastal Fish Reveals a Marine Biogeographic Break of Terrestrial Origin in the Southern Caribbean

Marine allopatric speciation involves interplay between intrinsic organismal properties and extrinsic factors. However, the relative contribution of each depends on the taxon under study and its geographic context. Utilizing sea catfishes in the Cathorops mapale species group, this study tests the hypothesis that both reproductive strategies conferring limited dispersal opportunities and an apparent geomorphologic barrier in the Southern Caribbean have promoted speciation in this group from a little studied area of the world.Mitochondrial gene sequences were obtained from representatives of the Cathorops mapale species group across its distributional range from Colombia to Venezuela. Morphometric and meristic analyses were also done to assess morphologic variation. Along a approximately 2000 km transect, two major lineages, Cathorops sp. and C. mapale, were identified by levels of genetic differentiation, phylogenetic reconstructions, and morphological analyses. The lineages are separated by approximately 150 km at the Santa Marta Massif (SMM) in Colombia. The northward displacement of the SMM into the Caribbean in the early Pleistocene altered the geomorphology of the continental margin, ultimately disrupting the natural habitat of C. mapale. The estimated approximately 0.86 my divergence of the lineages from a common ancestor coincides with the timing of the SMM displacement at approximately 0.78 my.Results presented here support the hypothesis that organismal properties as well as extrinsic factors lead to diversification of the Cathorops mapale group along the northern coast of South America. While a lack of pelagic larval stages and ecological specialization are forces impacting this process, the identification of the SMM as contributing to allopatric speciation in marine organisms adds to the list of recognized barriers in the Caribbean. Comparative examination of additional Southern Caribbean taxa, particularly those with varying life history traits and dispersal capabilities, will determine the extent by which the SMM has influenced marine phylogeography in the region