Screening for Atrial Fibrillation in Sub-Saharan Africa: A Health Economic Evaluation to Assess the Feasibility in Nigeria.

Background: Cardiovascular disease reflects a major burden of non-communicable disease in Sub-Saharan Africa (SSA). Early detection and treatment of atrial fibrillation (AF), as a preventive measure against stroke, is currently not in the scope of the World Health Organization recommendation to reduce cardiovascular disease. Objective: We hypothesized that screening for AF would be an important approach to determine the true AF prevalence in the general population in African countries and to identify asymptomatic AF patients at risk for stroke to optimize prevention. Methods: A decision analytic model was developed to study the health-economic impact of AF screening in Nigeria over a life-time horizon. The patient population explored in the model was a population of newly detected AF cases that would be diagnosed with a one-time systematic screening for AF with a single lead ECG device in community health centres across Nigeria. Conclusions: The health gain per newly detected AF patient (N = 31,687) was 0.41 QALY at a cost of $5,205 per patient with 100% NOAC use, leading to an ICER of $12,587 per QALY gained. The intervention was cost-effective with a 99.9% warfarin use with an ICER of $1,363 per QALY gained. The total cost of a single screening session was $7.3 million for the total screened population in Nigeria or $1.60 per patient screened. Screening for AF to detect AF patients in need for stroke prevention can be a cost-effective intervention in the Sub-Saharan region, depending on type of anticoagulant used and drug costs.

Inappropriate non-vitamin K antagonist oral anticoagulants prescriptions: be cautious with dose reductions.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are prescribed to patients with atrial fibrillation (AF) to reduce the risk of stroke. Prescribing the correct dose warrants careful consideration of the prevailing dose criteria that differ per NOAC. Electronic systems are useful to intercept prescriptions that are incorrect based on simple 'primary' criteria, for example dosing frequency and drug-drug interactions with concomitant medication. However, these systems do not take into account patient characteristics such as age, renal function or weight, which are crucial elements to determine the NOAC dose. METHODS: Our goal was to determine the appropriateness of all prescriptions, as compared with the product labelling approved by the European Medicines Agency, to address common pitfalls in prescribing NOACs. AF patients with a first NOAC prescription between January 2012 and December 2016 were identified from our electronic hospital information system (Martini Hospital, Groningen, the Netherlands). RESULTS: The study included 3,231 AF patients who had started on an NOAC; 10.7% received an inappropriate dose and the appropriateness of the prescription could not be determined in 14.1%. Underdosing and overdosing occurred in 5.4% and 4.5% of all prescriptions, respectively. A reduced-dose NOAC was a predictor for incorrect prescribing (odds ratio: 2.70, 95% confidence interval: 2.13-3.41). Patient factors were identified that predicted incorrect prescriptions for dabigatran and apixaban. CONCLUSION: An incorrect prescription occurred more often in the reduced-dose NOAC group. Clinical parameters such as renal function are often unknown whilst these are essential to determine the right NOAC and dose.

Optimal antithrombotic treatment of patients with atrial fibrillation undergoing percutaneous coronary intervention: triple therapy is too much!

Patients with atrial fibrillation who undergo a coronary intervention are eligible for both anticoagulation and (dual) antiplatelet therapy ((D)APT). An optimal balance has to be found to reduce the thromboembolic risk (i.e. stroke, systemic embolism and myocardial infarction) and to minimise the increased risk of bleeding with concomitant use of an anticoagulant and (D)APT. Owing to a lack of evidence, the guideline recommendations are predominantly based on expert opinion. Current evidence indicates that the combination of a non-vitamin K oral anticoagulant (NOAC) and clopidogrel is safer than vitamin-K oral antagonists plus DAPT, which increases the risk of bleeding, without clear advantages in regard to efficacy. Concerning whether (N)OACs should be combined with single APT rather than DAPT, the findings of the WOEST, PIONEER AF-PCI and RE-DUAL PCI trials seem to favour a combination with clopidogrel only, thus omitting aspirin. Choosing the optimal treatment strategies for individual patients on NOACs and (D)APT will remain a challenge for clinicians, though triple therapy seems to be the less favourable option owing to the increased risk of bleeding.

Predictors for total hospital and cardiology cost claims among patients with atrial fibrillation initiating dabigatran or acenocoumarol in The Netherlands.

AIMS: The prevalence of atrial fibrillation (AF) has increased over the past years due to aging of the population, and healthcare costs associated with AF reflect a significant financial burden. The aim of this study was to explore predictors for the real-world AF-related in-hospital costs in patients that recently initiated anticoagulation with acenocoumarol or dabigatran. METHODS: Predictors for claimed total hospital care costs and cardiology costs in AF patients were explored by using hospital financial claims data from propensity score matched patient groups in a large Dutch community hospital. This study analyzed the total dataset (n = 766) and carried out a secondary analysis for all matched pairs of anticoagulation naïve AF patients (n = 590) by ordinal regression. RESULTS: Dabigatran was a predictor for significantly lower cardiology and total hospital care costs (Odds Ratio [OR] = 0.43, 95% confidence interval (CI) = 0.33-0.57; and OR = 0.60, 95% CI = 0.46-0.79, respectively). Female gender was a predictor for lower total hospital care costs. Predictors for an increase in total hospital care costs were the occurrence of stroke or systemic embolism, major bleeding, and minor bleeding. The costs predictors were comparable when limiting the analysis to patients that were anticoagulation naïve. Age and CHA2DS2-VASc were not predictors for either cardiology or total hospital care costs in both analyses. CONCLUSION: Dabigatran treatment was as a predictor for lower cardiology costs and lower total hospital care costs in AF patients that initiated oral anticoagulation.

Synthesis of a fluorescent analog of polychlorinated biphenyls for use in a continuous flow immunosensor assay.

A synthetic scheme has been developed for the preparation of a dye-labeled analog of polychlorinated biphenyls. The reaction of 2,3,5-trichlorophenol with 3-bromopropylamine hydrobromide under basic conditions was used to introduce a free primary amine group into the parent compound by formation of a stable ether linkage. Reaction of this amine with the succinimidyl ester of a sulfoindocyanine dye resulted in amide bond formation to produce a fluorescently-labeled product. The dye conjugate was used to charge a column containing immobilized antibodies against polychlorinated biphenyls. Upon application of samples containing various concentrations of polychlorinated biphenyls, the fluorescent analog was displaced from the column in amounts proportional to the concentration of analyte. Concentrations of polychlorinated biphenyl as low as 1 ppm were measurable using this system.

An investigation of dental luting cement solubility as a function of the marginal gap.

The purpose of this study was to investigate the rate of type I zinc phosphate cement solubility as it relates to the degree of marginal opening. Standardized test samples were constructed that would simulate clinically relevant marginal gaps of 25, 50, 75, and 150 microns and their subsequent cement lines. The study was divided into two phases. Phase 1 evaluated the effects of simple diffusion on cement solubility in a static environment, whereas phase 2 investigated the effects of convective forces on cement dissolution in a dynamic environment. Both the phase 1 and phase 2 studies demonstrated no significant difference in the rate of cement dissolution for the 25-, 50-, and 75-micron test groups. The 150-micron test groups for both studies, however, demonstrated an increase in the rate of cement dissolution. The results of the phase 1 and phase 2 studies should not be compared because different methodologies were used.

Rates of protein synthesis--a review.

The rates of protein synthesis can be measured by a variety of methods including pulse labeling, massive precursor administration, Scornik method, continuous feeding of labeled precursor, infusion, and pellet implantation. Each technique has some advantages and disadvantages. Massive precursor administration and infusion are the most widely used. The advantage of massive precursor administration is its simplicity, however, the amino acid concentration used is much higher than physiological levels. Infusion, however, is much more complicated as a technique and requires complicated calculations. The synthesis rates can also be calculated from degradation curves. Some of the above techniques can be used both in vivo and in vitro, and also for different organs (Shahbazian et al. (1987), Int. J. Dev. Neurosci., 5: 39-42). The brain has rapid rates of protein synthesis both in vivo and in vitro, the latter being much lower for adults.

Visual cortex of the dolphin: an image analysis study.

On cytoarchitectonic grounds we have identified two distinct types of cortical formations composing the lateral gyrus (visual cortex) of the dolphin and have termed these heterolaminar cortex and homolaminar cortex. The heterolaminar cortex occupies the medial and lateral banks of the entolateral sulcus whereas the homolaminar cortex occupies the remainder of the lateral gyrus both lateral and medial to the entolateral sulcus. Each of these cortices exhibits special cytoarchitectonic features, a major difference being that heterolaminar cortex contains an incipient layer IV whereas layer IV is clearly absent in homolaminar cortex. Quantitative imaging procedures reveal that there is greater laminar differentiation in heterolaminar than in homolaminar cortex. Golgi analysis of neuronal forms and dendritic architecture confirms this distinction between the two types of cortex composing the lateral gyrus. Computer-assisted morphometric methods have been applied to both types of cortex and indicate by a variety of parameters several quantitative differences in the cellular numbers, types, and organization in each type of cortex. Both types of cortex, homolaminar and heterolaminar, exhibit a markedly higher cellular density in the posterior sector of the lateral gyrus than in the anterior sector. We have also for the first time been able to identify a columnar type of organization of the cetacean visual cortex and have described two types of cytoarchitectonic columns, major and minor, in each of these types of cortex. Comparisons in organization of these basic columnar units between the bat, representing a prototypic brain, and the dolphin reveal many similarities but also major quantitative differences in type of organization between the visual cortices in these species. Marked differences are also seen between the cytoarchitectonic columnar organization of the visual cortices in the dolphin and columnar organization of striate cortex in the human brain, the number of columns per unit of cortex in the human being almost twice that seen in the dolphin brain. Some phylogenetic implications of these findings are discussed in relation to the so-called "initial" type of cortical organization reconstructed largely by retrospective inference.

Ultrastructure of the blood-brain barrier in the dolphin (Stenella coeruleoalba).

Light and electron microscopic methods were used for investigation of angioarchitectonics, glioarchitectonics and the structural basis of the blood-brain barrier in the dolphin Stenella coeruleoalba. It was shown that the cortical plate of the dolphin brain is extremely rich in capillaries and small arteries that are organized into a complicated net of continuous loops surrounding neuronal groups. The density of the capillary loops is related to the cytoarchitectural density of the cortex. It was also found that the neuronal microenvironment in the dolphin cortex is characterized by the presence of a large number of the astroglia-like cells that make a multi-layered investment surrounding capillaries and small arteries. These glial cells, unlike typical astrocytes of terrestrial mammals, have a large number of different organelles and their nuclei are similar to those of the oligocytes. The ultrastructure of the blood-brain barrier in the dolphin is characterized by the presence of extremely long tight junctions between endothelial cells and by specialized junctions between pericapillary astroglia-like cells. A belt of the glial end-feet interlocked with different types of junctions such as zonulae adherentes, maculae adherentes and gap junctions was found around all investigated capillaries. This system of specialized interendothelial and glio-glial junctions is tentatively hypothesized to be a feature of adaptation of the dolphin to the aquatic environment.

Conservative features of neocortical evolution in dolphin brain.

A Golgi survey of the convexity cortex in the brain of the dolphin, Tursiops truncatus, has revealed many cellular characteristics which may be indicative of conservative cortical evolution. These include a high degree of pyramidalization, and an accentuation of layer II. The presence of an accentuated layer II in convexity cortex is a protoneocortical characteristic found in more 'primitive' cortical arrangements. The growth ring concepts of cortical development outward in concentric waves from archicortical and paleocortical origins are discussed. In that context we have not been able to identify cores of hyperspecialization in the dolphin cortex corresponding to koniocortex and gigantopyramidal areas. This leads us to suggest that the cortex of the dolphin reflects a condition of the paralimbic-parinsular stage of evolutionary development. Thus, the dolphin brain may serve as a model of the theoretical mammalian archetype brain and its study may shed light on the organization of the brains of the initial ancestors of modern mammals.

The insular formations of the dolphin brain: quantitative cytoarchitectonic studies of the insular component of the limbic lobe.

The large insula of the bottlenose dolphin consists of radial gyri arising, in fanlike fashion, from the transverse insular gyrus, and is covered completely by the frontal, parietal, and temporal opercula . On cytoarchitectonic grounds, the dolphin insula is divided into anterior, middle, and posterior sectors that may be the equivalent of the three similar sectors present in the primate insula. Rostrocaudally, these sectors become increasingly more homogeneous and less laminated. Within each sector progressive differentiation occurs in the direction of the circular sulcus. A transitional cortex, the peripaleocortex in the transverse insular gyrus, is interposed between the prepiriform and the periamygdalar cortex and the proisocortex of the insula proper. This peripaleocortex consists of outer and inner cellular strata separated by a hypocellular lamina dissecans. The outer cell stratum is continuous with layers II and III of the insular proisocortex ; the more prominent inner stratum is continuous with proisocortical layers V and VI; the intervening lamina dissecans becomes partially filled, mostly with modified pyramidal cells of medium size that may constitute an incipient layer IV. A band of myelinated fibers corresponding to the external band of Baillarger is found within the lamina dissecans. The anterior insular sector is characterized by distinct lamination and a well-defined, ribbonlike layer Va. In the middle sector, the cortex is internodense and lamination is less clear. The posterior sector is even less laminated and tends to be externodense . Within each sector, lamination becomes clearer in the direction of the circular sulcus. Furthermore, the rostrocaudal architectonic changes suggest a possible transition from a motor-type to a sensory-type cortex. Beyond the insula, the architecture of the opercular cortices reflect, in turn, the influences of the insular sectors.

The limbic lobe of the dolphin brain: a quantitative cytoarchitectonic study.

In these cytoarchitectonic studies of the cortical limbic formations of the bottlenose dolphin and other whale brains we have carried out quantitative analyses of the entire limbic lobe, including all of its sectors: supracallosal, retrosplenial and temporal. The limbic lobe proper has been examined as well as transitional areas between the limbic lobe and the archicortical and paleocortical formations and the extralimbic neocortices, including the entorhinal area and presubiculum. Analyses include total cortical thickness, thickness of individual cortical layers, overall cortical cell densities and glia/neuron ratios, individual laminar counts and glia/neuron ratios and neuron size. Comparisons have been made between these parameters in the brains of the dolphin (Tursiops truncatus), beluga whale (Delphinapterus leucas) and humpback whale (Megaptera novaeangliae). Cortical neuron density values (cells per mm3) in these three species of whales and in the human brain have been compared with similar data given in the literature for elephant, fin whale (Balaenoptera physalus) and human brains. Our values reflect the inverse relationship between brain size and neuron density. Thus, the dolphin shows approximately 13,000 neurons/mm3 in its limbic cortex, compared to 12,000 in the beluga whale and 8,000 in the humpback whale. Further, the data provide the first quantitative accounts on a layer by layer basis of the limbic cortices in the whale brain. In the dolphin, the anterior limbic cortices have a much lower cell density than the posterior limbic area. However, in the humpback whale these two cortices have similar neuron densities. In the temporal region, the entorhinal area is well differentiated into many architectonic subdivisions in the dolphin though not to the extent described in the primate brains. Our findings in the three whale species are discussed in terms of their possible significance and provide quantitative data for future comparative studies with other mammalian species.

Reservoir hosts of human babesiosis on Nantucket Island.

The host range of Babesia microti was studied on Nantucket Island in order to identify the enzootic reservoir of this human pathogen. White-footed mice (Peromyscus leucopus) were more frequently parasitized than were other indigenous animals. Infection was ubiquitous in locations where deer were abundant. Mice were most frequently parasitemic during spring and summer and adults more frequently than juveniles. Parasitemia, which was rarely intense, was sustained for as long as 4 months. Mice lived as long as 10 months, and juveniles were most abundant during early summer. Prevalence of zoonotic infection, in certain locations, appeared to be inversely correlated with abundance of mice. B. microti was present solely in regions harboring deer.