Interplay Between Thyroid Hormone Status and Pulmonary Hypertension in Graves’ Disease: Relevance of the Assessment in Thyrotoxic and Euthyroid Patients

BackgroundGraves’ disease (GD) is the most common cause of hyperthyroidism and can cause cardiac changes, such as pulmonary hypertension.MethodsThis is a prospective study in which we obtained demographic, clinical, laboratory data and characteristics of the GD, in addition to investigating cardiorespiratory function, focusing on the detection of pulmonary hypertension. Patients were separated into two groups: thyrotoxicosis and euthyroidism. Ninety patients with GD of both sexes, over 18 years of age, were included. The cardiorespiratory assessment included an echocardiographic evaluation, a questionnaire of specific symptoms, spirometry and a six-minute walk test.ResultsThe hyperthyroid group included 42 patients (47.73%) and the euthyroid group 46 patients (52.27%); 78 were women (86.67%). The prevalence of pulmonary hypertension between the hyperthyroidism (48.57%) and the euthyroidism (29.41%) groups was not different. Free thyroxine levels (FT4) (OR 1.266), higher left atrium volume (OR 1.113) and right ventricle diameter were associated with pulmonary hypertension. A direct correlation between FT4 with forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), as also an inverse correlation between initial oxygen saturation (SpO2) with diagnostic time and drop SpO2 with the ratio between the diastolic velocity E of the mitral flow and the diastolic velocity of the mitral ring (E/e’) were observed in the euthyroid group. An inverse correlation between FT4 levels with walked distance as % of predicted value, and a direct correlation between E/e’ ratio and walked distance as % of predicted value were observed in the hyperthyroid group.ConclusionWe emphasize the importance of a cardiorespiratory reassessment in GD, even after a long-term control of the thyrotoxic state, as we demonstrate that about 30% of these patients remain with PH and are subject to specific treatment.

Neurological Disorder Detection of Brain Abnormal Activities Using a New Enhanced Computer-aided Model

In the field of neurodevelopmental disorders, Autism Spectrum Disorders (ASD) are recognized as one of the dramatically increased etiologically and clinically heterogeneous diseases. Although, increasing the number of children who have difficulties in communication or suffer from sudden malfunction of the brain, the current diagnostic approaches for those kind of disease are time-consuming and are mainly based on clinical interviews. In this paper, a new enhanced diagnostic model is introduced addressing many of the challenges which threats the analysis of Electroencephalography (EEG) signals. A preprocessing stage is proposed to choose the key segment of EEG channel and remove the artifacts in the EEG signals to enhance their quality. The proposed model uses a set of discriminative features based on discrete wavelet transform (DWT) such as skewness, standard division, shannon entropy and relative wave energy. Also, extracting cross correction between brain regions to detect abnormal connectivity and synchronization. Two EEG datasets are used to verify the accuracy of the proposed model. The fusion of two EEG dataset helps in building a more generalized mode to diagnose epilepsy and ASD. In the fused dataset, the combination of the mentioned features and Random Forest have produced a very promising diagnosis result with minimum diagnostic time, with an average accuracy equals to 96.78%. The proposed model obtained better classification accuracy compared to the existing methods.

Anopheles drivers of persisting malaria transmission in Guna Yala, Panamá: an operational investigation

Background Though most of Panamá is free from malaria, localized foci of transmission persist, including in the Guna Yala region. Government-led entomological surveillance using an entomological surveillance planning tool (ESPT) sought to answer programmatically-relevant questions that would enhance the understanding of both local entomological drivers of transmission and gaps in protection that result in persisting malaria transmission to guide local vector control decision-making. Methods The ESPT was used to design a sampling plan centered around the collection of minimum essential indicators to investigate the relevance of LLINs and IRS in the communities of Permé and Puerto Obaldía, Guna Yala, as well as to pinpoint any remaining spaces and times where humans are exposed to Anopheles bites (gaps in protection). Adult Anopheles were collected at three time points via human landing catches (HLCs), CDC Light Traps (LT), and pyrethrum spray catches (PSCs) during the rainy and dry seasons. Mosquitoes were identified to species via molecular methods. Insecticide susceptibility testing of the main vector species to fenitrothion was conducted. Results In total, 7537 adult Anopheles were collected from both sites. Of the 493 specimens molecularly confirmed to species, two thirds (n = 340) were identified as Nyssorhynchus albimanus, followed by Anopheles aquasalis. Overall Anopheles human biting rates (HBRs) were higher outdoors than indoors, and were higher in Permé than in Puerto Obaldía: nightly outdoor HBR ranged from 2.71 bites per person per night (bpn) (Puerto Obaldía), to 221.00 bpn (Permé), whereas indoor nightly HBR ranged from 0.70 bpn (Puerto Obaldía) to 81.90 bpn (Permé). Generally, peak biting occurred during the early evening. The CDC LT trap yields were significantly lower than that of HLCs and this collection method was dropped after the first collection. Pyrethrum spray catches resulted in only three indoor resting Anopheles collected. Insecticide resistance (IR) of Ny. albimanus to fenitrothion was confirmed, with only 65.5% mortality at the diagnostic time. Conclusion The early evening exophagic behaviour of Anopheles vectors, the absence of indoor resting behaviours, and the presence of resistance to the primary intervention insecticide demonstrate limitations of the current malaria strategy, including indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs), and point to both gaps in protection and to the drivers of persisting malaria transmission in Guna Yala. These findings highlight the need for continued and directed entomological surveillance, based on programmatic questions, that generates entomological evidence to inform an adaptive malaria elimination strategy.

NeoSeq: a new method of genomic sequencing for newborn screening

Objective To explore the clinical application of NeoSeq in newborn screening. Methods Based on the results obtained from traditional newborn screening (NBS) with tandem mass spectrometry (TMS), three cohorts were recruited into the present study: 36 true positive cases (TPC), 60 false-positive cases (FPC), and 100 negative cases. The dried blood spots of the infants were analyzed with NeoSeq, which is based on multiplex PCR amplicon sequencing. Results Overall, the sensitivity of NeoSeq was 55.6% (20/36) in the detection of TPC. NeoSeq detected disease-related genes in 20 of 36 TPC infants, while it could not identify these genes in eight children. Five cases (3.1%) with disease risk were additionally found in the FPC and NC cohorts. There was a significant difference in the diagnostic time between the two methods—10 days for NeoSeq vs. 43 days for traditional NBS. Conclusions NeoSeq is an economic genomic screening test for newborn screening. It can detect most inborn errors of metabolism, reduce the rate of false positive results, shorten the porting cycles, and reduce the screening cost. However, it is still necessary to further optimize the panel design and add more clinically relevant genomic variants to increase its sensitivity.

Exome first approach to reduce diagnostic costs and time – retrospective analysis of 111 individuals with rare neurodevelopmental disorders

This single-center study aims to determine the time, diagnostic procedure, and cost saving potential of early exome sequencing in a cohort of 111 individuals with genetically confirmed neurodevelopmental disorders. We retrospectively collected data regarding diagnostic time points and procedures from the individuals’ medical histories and developed criteria for classifying diagnostic procedures in terms of requirement, followed by a cost allocation. All genetic variants were re-evaluated according to ACMG recommendations and considering the individuals’ phenotype. Individuals who developed first symptoms of their underlying genetic disorder when Next Generation Sequencing (NGS) diagnostics were already available received a diagnosis significantly faster than individuals with first symptoms before this cutoff. The largest amount of potentially dispensable diagnostics was found in genetic, metabolic, and cranial magnetic resonance imaging examinations. Out of 407 performed genetic examinations, 296 (72.7%) were classified as potentially dispensable. The same applied to 36 (27.9%) of 129 cranial magnetic resonance imaging and 111 (31.8%) of 349 metabolic examinations. Dispensable genetic examinations accounted 302,947.07€ (90.2%) of the total 335,837.49€ in potentially savable costs in this cohort. The remaining 32,890.42€ (9.8%) are related to non-required metabolic and cranial magnetic resonance imaging diagnostics. On average, the total potentially savable costs in our study amount to €3,025.56 per individual. Cost savings by first tier exome sequencing lie primarily in genetic, metabolic, and cMRI testing in this German cohort, underscoring the utility of performing exome sequencing at the beginning of the diagnostic pathway and the potential for saving diagnostic costs and time.

Abrogation of survival disparity between insured and uninsured individuals after the USPSTF's 2012 prostate-specific antigen-based prostate cancer screening recommendation.

77 Background: In 2012, the U.S. Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA)-based screening for prostate cancer. Studies have found that insured patients with prostate cancer have better outcomes than uninsured patients. We examined the recommendation’s effects on survival disparities based on insurance status as well as socioeconomic quintile, marital status, and housing (urban/rural). Methods: Using the SEER18 database, we examined prostate cancer-specific survival (PCSS) based on diagnostic time period and one of four factors: insurance status, socioeconomic quintile, marital status, and housing (urban/rural). The SEER-designated socioeconomic quintile was based on variables including median household income and education index. Patients were designated as belonging to the pre-USPSTF era if diagnosed in 2010-2012 or post-USPSTF era if diagnosed in 2014-2016. Disparities were measured with the Cox proportional hazards model. Results: We identified 282,994 patients diagnosed with prostate cancer. During the pre-USPSTF era, uninsured patients experienced worse PCSS compared to insured patients (adjusted HR 1.29, 95% CI 1.06-1.58, p = 0.01). This survival disparity narrowed during the post-USPSTF era as a result of decreased PCSS among insured patients combined with unchanged PCSS among uninsured patients. Moreover, the survival disparity was no longer observed during the post-USPSTF era (aHR 0.91, 95% CI 0.61-1.38, p = 0.67). The survival disparity based on socioeconomic quintile also narrowed but remained significant. In contrast, the survival disparity based on marital status widened, while housing status was not associated with survival disparities in either era. Conclusions: From the pre- to the post-USPSTF era, insured patients with prostate cancer observed a significant decrease in survival that made their survival outcomes similar to that of uninsured patients. Although the underlying reasons are not clear, the USPSTF’s 2012 PSA screening recommendation may have hindered insured patients from being regularly screened for prostate cancer and selectively led to worse outcomes for insured patients without improving the survival of uninsured patients.[Table: see text]

Forum ophthalmicum – how to take control over accumulation of diagnostic data from macular OCT with benefit for both doctor and patient?

Wet age-related macular degeneration (wet AMD) is a disease which requires regular diagnostic tests such as macular optical coherent tomography which is extremely important both in diagnosis and disease monitoring. With constant aging of the population, we are dealing with an increasing incidence rate of AMD, which makes it even more important to have a tool allowing for quick and precise analysis of anatomical changes in macular region, particularly in the current complicated epidemiological situation when diagnostic time should be used most efficiently to plan the follow-up treatment. Forum® software allows for the precise analysis of many tests performed in a single patient and combining it with treatment effectiveness assessment which substantially accelerates the diagnostics.

Global Rural and Remote Patients with Rheumatoid Arthritis

Introduction: Rural and remote patients with rheumatoid arthritis (RA) are at risk for inequities in health outcomes based on differences in physical environments and healthcare access potential compared to urban populations. The aim of this systematic review was to synthesize epidemiology, clinical outcomes and health service use reported for global populations with RA residing in rural/remote locations. Methods: Medline, EMBASE, Healthstar, CINAHL and Cochrane were searched from inception to June 2019 using librarian-developed search terms for RA and rural/remote populations. Peer-reviewed published manuscripts were included if they reported on any of an epidemiology, clinical or health service use outcomes. Results: 54 articles were included for data synthesis, representing studies from all continents. In 11 studies where there was an appropriate urban population comparator, rural/remote populations were not at increased risk for RA, 1 study reported increased and 5 studies reported decreased prevalence in rural/remote populations. Clinical characteristics of rural/remote populations in studies with an appropriate urban comparator showed no significant differences in disease activity measures or disability, but with 1 study reporting worse physical function and health-related quality of life in rural/remote populations. Studies reporting on health service use provided evidence that rural/remote residence impacts diagnostic time, ongoing follow-up, access to RA-care related practitioners and services, and with variation in medication access and use. Conclusion: This synthesis highlights that RA epidemiology and clinical outcomes are not necessarily different between rural/remote and urban populations, however rural/remote patients face greater barriers to care which increases the risk for inequities in outcomes. From a public health perspective, we need leadership to implement structures and policies to support better outcomes in rural and remote populations. Access to health services is a recognized determinant of health, which presents the opportunity for actionable strategies and approaches to resolve inequities in care delivery.