Budget impact analysis of the adoption of new hypertension guidelines in Colombia

Background

Hypertension represents a high burden of disease in different healthcare systems. Recent guideline published in 2017 by the American Heart Association and the American College of Cardiology has generated a debate between clinicians and policymakers due to the lowering of diagnosis threshold and the subsequent increase of the prevalence and healthcare costs. No empirical research exists addressing the question about the pressure on healthcare costs generated by new standards. This study aims to quantify the impact on the hypertension diagnosis and treatment costs for healthcare system using the new hypertension guideline.

Methods

We conducted a budget impact analysis from a Colombianhealthcare payer’s perspective with a 3-year time horizon (2018–2020), in which we estimated the difference in total medical care costs between previous hypertension cut-off points (140/90 mmHg) and new guideline cut-off points (130/80 mmHg).

Results

Our results show that the impact of the adoption of the new hypertension guideline would represent a decrease close to 22% in total annual high blood pressure costs in Colombia. This reduction is mainly driven by a lower number of cardiovascular complications. It is worth noting that these results should be taken with caution due to local available data.

Conclusions

A high-middle income country such as Colombia should carry out an exhaustive revision of the recommendations of the new hypertension guideline, due to its high probability of saving medical treatment costs for the healthcare system.

     

Lessons Learned From a Feasibility Study Delivered in 2 WIC Sites to Promote Physical Activity Among Pregnant Latinas

Objective

To assess the feasibility, including demand for and acceptability of a physical activity (PA) intervention among pregnant Latinas recruited at the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

Sloths host Anhanga virus‐related phleboviruses across large distances in time and space

Sloths are genetically and physiologically divergent mammals. Phleboviruses are major arthropod‐borne viruses (arboviruses) causing disease in humans and other animals globally. Sloths host arboviruses, but virus detections are scarce. A phlebovirus termed Anhanga virus (ANHV) was isolated from a Brazilian Linnaeus's two‐toed sloth (Choloepus didactylus) in 1962. Here, we investigated the presence of phleboviruses in sera sampled in 2014 from 74 Hoffmann's two‐toed (Choloepus hoffmanni, n = 65) and three‐toed (Bradypus variegatus, n = 9) sloths in Costa Rica by broadly reactive RT‐PCR. A clinically healthy adult Hoffmann's two‐toed sloth was infected with a phlebovirus. Viral load in this animal was high at 8.5 × 10⁷ RNA copies/ml. The full coding sequence of the virus was determined by deep sequencing. Phylogenetic analyses and sequence distance comparisons revealed that the new sloth virus, likely representing a new phlebovirus species, provisionally named Penshurt virus (PEHV), was most closely related to ANHV, with amino acid identities of 93.1%, 84.6%, 94.7% and 89.0% in the translated L, M, N and NSs genes, respectively. Significantly more non‐synonymous mutations relative to ANHV occurred in the M gene encoding the viral glycoproteins and in the NSs gene encoding a putative interferon antagonist compared to L and N genes. This was compatible with viral adaptation to different sloth species and with micro‐evolutionary processes associated with immune evasion during the genealogy of sloth‐associated phleboviruses. However, gene‐wide mean dN/dS ratios were low at 0.02–0.15 and no sites showed significant evidence for positive selection, pointing to comparable selection pressures within sloth‐associated viruses and genetically related phleboviruses infecting hosts other than sloths. The detection of a new phlebovirus closely‐related to ANHV, in sloths from Costa Rica fifty years after and more than 3,000 km away from the isolation of ANHV confirmed the host associations of ANHV‐related phleboviruses with the two extant species of two‐toed sloths.     

Efficacy of intralesional recombinant human epidermal growth factor in diabetic foot ulcers in Mexican patients: A randomized double‐blinded controlled trial

The healing process in diabetic foot ulcer (DFU) is hindered by factors such as chronic inflammation, defects in fibroblast function, poor angiogenesis, and lack of cell migration. Recombinant human epidermal growth factor (rhEGF) has been shown to enhance extracellular matrix formation, cellular proliferation, and angiogenesis. Therefore, intralesional application of rhEGF in DFU could accelerate wound healing. Our objective was to determine the efficacy and safety of rhEGF in patients with DFU. A randomized, double‐blinded, placebo‐controlled study was conducted comparing a thrice‐per‐week intralesional application of rhEGF (75 μg) or placebo in patients with DFU for 8 weeks. The number of completely healed ulcers, size, and wound bed characteristics were evaluated to determine the efficacy of rhEGF. Adverse events were recorded and analyzed to establish its safety. A total of 34 patients were recruited for the study. After three dropouts, we were able to follow and analyze 16 patients in the placebo group and 15 patients in the rhEGF study to the end of the trial. Baseline testing showed that both groups were similar. Compared to the placebo group, more ulcers achieved complete healing in the rhEGF group (rhEGF, n = 4; placebo, n = 0; p = 0.033); ulcers in the rhEGF group decreased in area size (12.5 cm2 [rhEGF] vs. 5.2 cm2 [placebo]; p = 0.049); and more epithelial islands in the wound bed were present (28% vs. 3%; p = 0.025). Mild transitory dizziness was the only side effect that was more frequently noted in the rhEGF group. Our results showed that in patients with DFU who received standard care, intralesional rhEGF application resulted in complete healing in more patients, promoted the epithelialization of the wound bed, and significantly reduced the area of the DFU treated. Therefore, rhEGF resulted in better outcomes for patients suffering from DFU.     

Choice for response alternatives differing in reinforcement frequency in dopamine D2 receptor mutant and Swiss-Webster mice

Rationale

A previous study showed that dopamine (DA) D₂ receptors (D₂Rs) are involved in the reinforcing effectiveness of food, but the specific involvement of DA D₂Rs in choice among food reinforcers remains unclear.

Objectives

The current study used genetic and pharmacological approaches to assess the role of D₂Rs in choice among food-reinforcement frequencies using the generalized matching law (GML), which specifies that logged response and time allocation ratios vary linearly with logged reinforcer ratios.

Methods

Congenic D₂R knockout (KO) and wild-type (WT) mice were exposed to concurrent variable-interval schedules of reinforcement with scheduled relative-reinforcement rates from 4:1 to 1:4. Effects of the D₂R antagonist (?)-eticlopride (0.1–1.0 mg/kg) were assessed in Swiss-Webster mice.

Results

Response and time allocation ratios were related to obtained reinforcement ratios as predicted by the GML. GML fits accounted for ≥92 % of the variance in allocation ratios and did not differ in D₂R KO and WT mice. Similarly, there were no significant effects of (?)-eticlopride dose on GML fits, despite effects on overall response rates.

Conclusions

The current results demonstrate that neither deletion nor acute blockade of D₂Rs affects choice among response alternatives varying in food-reinforcement frequencies. Because previously published results suggest a role of D₂Rs in choice between response alternatives differing in reinforcer magnitude and delay or magnitude and probability, the current findings suggest that D₂Rs play a role in choice only among certain parameters of reinforcement. Furthermore, these findings suggest parameters of reinforcement may only be fungible in a complex manner.     

The genomics of ecological flexibility,large brains,and long lives in capuchin monkeys revealed with fecalFACS

Ecological flexibility, extended lifespans, and large brains have long intrigued evolutionary biologists, and comparative genomics offers an efficient and effective tool for generating new insights into the evolution of such traits. Studies of capuchin monkeys are particularly well situated to shed light on the selective pressures and genetic underpinnings of local adaptation to diverse habitats, longevity, and brain development. Distributed widely across Central and South America, they are inventive and extractive foragers, known for their sensorimotor intelligence. Capuchins have among the largest relative brain size of any monkey and a lifespan that exceeds 50 y, despite their small (3 to 5 kg) body size. We assemble and annotate a de novo reference genome for Cebus imitator. Through high-depth sequencing of DNA derived from blood, various tissues, and feces via fluorescence-activated cell sorting (fecalFACS) to isolate monkey epithelial cells, we compared genomes of capuchin populations from tropical dry forests and lowland rainforests and identified population divergence in genes involved in water balance, kidney function, and metabolism. Through a comparative genomics approach spanning a wide diversity of mammals, we identified genes under positive selection associated with longevity and brain development. Additionally, we provide a technological advancement in the use of noninvasive genomics for studies of free-ranging mammals. Our intra- and interspecific comparative study of capuchin genomics provides insights into processes underlying local adaptation to diverse and physiologically challenging environments, as well as the molecular basis of brain evolution and longevity.

Large brains, long lifespans, extended juvenescence, tool use, and problem solving are hallmark characteristics of great apes, and are of enduring interest in studies of human evolution (1–4). Similar suites of traits have arisen in other lineages, including some cetaceans, corvids and, independently, in another radiation of primates, the capuchin monkeys. Like great apes, they have diverse diets, consume and seek out high-energy resources, engage in complex extractive foraging techniques (5, 6) to consume difficult-to-access invertebrates and nuts (6), and have an extended lifespan, presently recorded up to 54 y in captivity (7, 8). While they do not show evidence of some traits linked with large brain size in humans (e.g., human-like social networks and cultural and technological transmission from older to younger groupmates), their propensity for tool use and their ecological flexibility may have contributed to their convergence with the great apes (9), offering opportunities for understanding the evolution of key traits via the comparative method (10–12). Similar approaches have revealed positive selection on genes related to brain size and long lives in great apes and other mammals (13, 14), but our understanding of the genetic underpinnings of these traits remains far from complete.Capuchins also offer excellent opportunities to study local adaptation to challenging seasonal biomes. They occupy diverse habitats, including rainforests and, in the northern extent of their range, tropical dry forests. Particular challenges of the tropical dry forest are staying hydrated during the seasonally prominent droughts, high temperatures in the absence of foliage, and coping metabolically with periods of fruit dearth (Fig. 1). The long-term study of white-faced capuchins (Cebus imitator) occupying these seasonal forests has demonstrated that high infant mortality rates accompany periods of intense drought, illustrating the strength of this selective pressure (15). Furthermore, the seasonally low abundance of fruit is associated with muscular wasting and low circulating levels of urinary creatinine among these capuchins (16). Additionally, the sensory challenges of food search in dry versus humid biomes are also distinct. Odor detection and propagation is affected by temperature and humidity (17), and color vision is hypothesized to be adaptive in the search for ripe fruits and young reddish leaves against a background of thick, mature foliage (18), which is absent for long stretches in dry deciduous forests. The behavioral plasticity of capuchins is widely acknowledged as a source of their ability to adapt to these dramatically different habitats (19–21). However, physiological processes, including water balance and metabolic adaptations to low caloric intake, and sensory adaptations to food search, are also anticipated to be targets of natural selection, as seen in other mammals (22–24). Understanding population-level differences between primates inhabiting different biomes, contextualized by their demographic history, genomic diversity, and historical patterns of migration, will generate new insights.Open in a separate windowFig. 1.SSR during wet (Left) and dry (Center) seasons. (Right) Map of sampling locations in Costa Rica. The two northern sites, SSR and Cañas, have tropical dry-forest biomes, whereas the two southern sites, Quepos and Manuel Antonio, are tropical wet forests. Photos courtesy of A.D.M. Drawing of white-faced capuchin monkey by Alejandra Tejada-Martinez; map courtesy of Eric Gaba–Wikimedia Commons user: Sting.Unfortunately, high-quality biological specimens from wild capuchins are not readily available. As is the case with most of the world’s primates, many of which are rare or threatened (25), this has limited the scope of questions about their biology that can be answered. Although recent advances in noninvasive genomics have allowed for the sequencing of partial genomes by enriching the proportion of endogenous DNA in feces (26–29), it has not yet been feasible to sequence whole genomes from noninvasive samples at high coverage; this has limited the extent to which noninvasive samples can be used to generate genomic resources for nonmodel organisms, such as capuchins.Toward identifying the genetic underpinnings of local adaptation to seasonally harsh environments, large brains, and long lifespans, we assembled and annotated a reference genome of C. imitator (SI Appendix, Table S1). Additionally, we sequenced the genomes of individuals inhabiting two distinct environments in Costa Rica: Lowland evergreen rainforest (southern population) and lowland tropical dry forest (northern population). We conducted high-coverage resequencing (10× to 47×) for 10 of these individuals, and sequenced an additional 13 at low-coverage (0.1× to 4.4×). Importantly, to facilitate the population-wide analyses without the need for potentially harmful invasive sampling of wild primates, we developed a method for minimally biased, whole-genome sequencing of fecal DNA using fluorescence-activated cell sorting (fecalFACS) that we used to generate both high- and low-coverage genomes (Fig. 2). With these genomes, we assess the genetic underpinnings of capuchin-specific biology and adaptation in a comparative framework. First, we scanned the high-coverage genomes (six from the northern dry forest and four from the southern rainforest) for regions exhibiting population specific divergence to assess the extent of local adaptation to dry forest and rainforest environments. We examine how genes related to water balance, metabolism, muscular wasting, and chemosensation have diverged between populations. Second, we conduct an analysis of positive selection on the white-faced capuchin genome through codon-based models of evolution and enrichment tests focusing on genes that may underlie brain development and lifespan. Third, we identify the population structure, genomic diversity, and demographic history of the species using a mixture of traditional and noninvasive fecalFACS genomes (n = 23).Open in a separate windowFig. 2.Mapping percentages of sequencing reads from RNAlater preserved fecal DNA libraries prepared with FACS for (A) all samples (box-plot elements: center line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range; points, outliers), and (B) individual libraries. (C) Increase in mapping rate for RNAlater preserved samples. (D) Relationship between mapped read duplication and number of cells with LOESS smoothing. The duplication rate decreases sharply once a threshold of about 1,000 cells is reached.     

Transesophageal Echocardiographic Diagnosis of Right-Sided Aortic Arch

We present the transesophageal echocardiographic findings in two adult patients with right-sided aortic arch: one without dissection and the other with traumatic aortic injury (dissection). In both patients, the branching pattern was the left common carotid artery and then the right common carotid artery, followed by the right and left subclavian arteries. The technique for the diagnosis of this anomaly and the identification of adjacent vascular structures using contrast echocardiography is described. Three-dimensional reconstruction of the aortic arch also was performed in both patients.     

Understanding Perinatal Death: A Systematic Analysis of New York City Fetal and Neonatal Death Vital Record Data and Implications for Improvement, 2007–2011

We aimed to compare demographic, medical, and cause-of-death information reported for third-trimester fetal and neonatal death vital records collected in New York City (NYC) before and after implementation of the revised fetal death certificate to identify: (1) the limitations of combining fetal and neonatal death records for the purpose of perinatal death prevention; and (2) improvement opportunities for fetal death vital records registration. Using Chi squared tests, we compared data completeness and cause-of-death information between third-trimester NYC fetal (n = 1,930) and neonatal deaths (n = 735) from 2007 to 2011. We also compared fetal death data before and after the 2011 implementation of the 2003 United States (US) Standard Report of Fetal Death and an electronic reporting system. Compared with neonatal deaths, fetal death data were generally less complete (P < 0.0001). Fetal death data much more frequently reported an ill-defined cause of death (67 vs. 5 %). Most ill-defined reported causes of fetal death (73 %) were attributed to stillbirth synonyms (e.g., “fetal demise”). Ill-defined causes of fetal death decreased from 68 to 61 % (P < 0.01) after 2011. Both data completeness and ill-defined causes of death varied widely by hospital. In NYC, fetal deaths lack demographic, medical, and cause-of-death information compared with neonatal deaths, with implications for research that uses combined perinatal mortality data sets. Electronic implementation of the US Standard Report of Fetal Death minimally improved cause-of-death information. Substantial variability by hospital suggests opportunities for improvement exist.     

What's the hold up? Factors contributing to delays in discharge of trauma patients after medical clearance

Background

One area of potential savings in healthcare spending is the identification of nonmedical delays in discharge. The purpose of this study was to identify factors associated with discharge delays.

Methods

All patients admitted to our trauma center over a 1-year period with a social work consult were retrospectively evaluated to identify delays in discharge after medical clearance.

Results

Over half of our patients experienced a delay in discharge. Age was not associated with delay in discharge. Higher injury severity score, intensive care unit admission, and hospital length of stay greater than 1 week were all associated with increased delays in discharge. Other factors such as disposition to a rehabilitation/nursing facility and mechanism of injury were also associated with a nonmedical delay.

Conclusions

We have identified nonmedical factors associated with delays in discharge. Strategies using these data could be used to improve discharge planning and may help decrease healthcare costs.