Personal mobile device-based pocket echocardiograph—The diagnostic value and clinical utility

PurposeA microUSB ultrasound probe, which can be connected to a personal mobile device constitutes a new class of diagnostic pocket-size imaging devices (PSID). The aim of this study was to assess the feasibility and diagnostic value of brief transthoracic echocardiographic examination (bTTE) performed with the use of such equipment.Material and methodsThe study population comprised 87 consecutive patients (58 men, mean age 61 ± 16 years), 53 of whom were admitted to intensive cardiac care unit and 34 patients, who were referred for transthoracic echocardiography from outpatient clinic. All patients underwent bTTE performed by cardiologist with the use of personal mobile device-based PSID. Within 18 h of bTTE all subjects underwent a standard TTE (sTTE) using a full sized echocardiograph by expert echocardiographer.ResultsIn all patients, PSID imaging provided sufficient diagnostic image quality. Echocardiographic measurements were completed for both bTTE and sTTE in 98% of patients. The linear measurements obtained during bTTE showed good to excellent correlation with sTTE results (r = 0.65–0.98; p < 0.001). The agreement in detection of various pathologies between the bTTE and sTTE examination was very good (k = 0.62–0.97; p < 0.01).ConclusionPersonal mobile device-based PSID allows for performing bTTE. The diagnostic value of such PSID in basic assessment of cardiac morphology and function as compared to standard echocardiography is very good.     

Comparison of Human Primary with Human iPS Cell-Derived Dopaminergic Neuron Grafts in the Rat Model for Parkinson’s Disease

Neuronal degeneration within the substantia nigra and the loss of the dopaminergic nigro-striatal pathway are the major hallmarks of Parkinson’s disease (PD). Grafts of foetal ventral mesencephalic (VM) dopaminergic (DA) neurons into the striatum have been shown to be able to restore striatal dopamine levels and to improve overall PD symptoms. However, human foetus-derived cell grafts are not feasible for clinical application. Autologous induced pluripotent stem cell (iPS cell)-derived DA neurons are emerging as an unprecedented alternative. In this review, we summarize and compare the efficacy of human iPS cell-derived DA neuron grafts to restore normal behaviour in a rat model for PD with that of human foetal primary DA neurons. The differences we observed in the efficacy to restore normal function between the 2 types of DA neuron grafts could be ascribed to intrinsic properties of the iPS cell-derived DA neurons that critically affected survival and proper neurite extension in the striatum after implantation.     

Parents’ perceptions of personal utility of exome sequencing results

PurposeClinical genome or exome sequencing (GS/ES) provides a diagnosis for many individuals with suspected genetic disorders, but also yields negative or uncertain results for the majority. This study examines how parents of a child with an undiagnosed condition attribute personal utility to all types of ES results.MethodsReturn of 31 exome sequencing results was observed during clinic sessions, followed by semistructured interviews with parents one month later. Observations and interviews were recorded and transcribed. Data display matrices were used for content analysis and systematic comparisons of parents’ perceptions of utility.ResultsES results could not provide all the answers to parents’ questions, especially in cases of clinically uninformative results, but parents nonetheless attributed utility to the knowledge gained. Parents across all results categories used the genomic information to rule out possible causes, end or postpone the diagnostic odyssey, and shift focus to treatment and management of symptoms.ConclusionThis study suggests that parents value even uninformative ES results while expressing hope for future discoveries. As pediatric genetics moves toward GS/ES as a first-tier test, how parents perceive the personal utility of negative or uncertain results is an important topic for genetic counseling and further research.     

HHV-8 DNA replication correlates with the clinical status in AIDS-related Kaposi’s sarcoma

BackgroundThe value of plasma levels of human herpesvirus 8 (HHV-8) DNA as a marker of clinical status in acquired immunodeficiency syndrome-related Kaposi’s sarcoma (AIDS-KS) remains to be elucidated.ObjectivesTo investigate the relationship between the plasma HHV-8 DNA viral load and the clinical status of AIDS-KS.Study DesignA total of 378 blood samples were obtained from 62 patients with AIDS-KS followed longitudinally. All patients received antiretroviral therapy (ART) or anti-neoplastic therapy. The patients were divided into four groups according to their clinical status: onset disease (OD), progressive disease (PD), stable or partial remission (S/PR) and complete remission (CR).ResultsPlasma HHV-8 DNAaemia was detected in all samples obtained from patients with OD or PD (100%); in contrast, HHV-8 DNAaemia was found only in a minority of patients with CR (8%) and was invariably undetectable in patients with stable CR. HHV-8 DNA detection in plasma was strongly associated with an unfavourable outcome (odds ratio = 231.9; p < 0.0001). Conversely, neither the HIV-1 viral load nor peripheral CD4⁺ T-cell counts were associated with the KS clinical status, though both parameters did affect HHV-8 DNAaemia levels (p < 0.0001). Multivariate analysis confirmed that HHV-8 DNAaemia was strongly and independently correlated with both clinical status (p < 0.05) and HIV-1 plasma viraemia (p = 0.027).ConclusionsThe strong association of plasma HHV-8 DNAaemia with onset or progressive disease is compatible with an active role of replicating virus in clinically active AIDS-KS. An accurate evaluation of the plasma HHV-8 load might be useful for monitoring AIDS-KS under antiretroviral or antineoplastic therapy.     

Human Immunoglobulin 10 % with Recombinant Human Hyaluronidase: Replacement Therapy in Patients with Primary Immunodeficiency Disorders

Human immunoglobulin is an established replacement therapy for patients with primary immunodeficiency disorders (PIDs). Recombinant human hyaluronidase (rHuPH20) is a spreading factor that temporarily digests hyaluronan in the skin interstitium enabling large volumes of fluid or drug solutions to be infused and absorbed subcutaneously. HyQvia^® (IGHy) is a new combination product whereby rHuPH20 is injected subcutaneously, followed by human immunoglobulin 10 % infused through the same needle. Thus, IGHy can be administered at a reduced frequency compared with non-facilitated subcutaneous injection of human immunoglobulin, and with a lower frequency of infusion reactions than with intravenous administration. Home-based administration of IGHy is also feasible for adequately trained patients. IGHy was compared with intravenous human immunoglobulin 10 % in a non-randomized, open-label, phase 3 study in patients aged ≥2 years with PIDs who were receiving human immunoglobulin replacement therapy (n = 87). In this study, trough IgG concentrations, acute serious bacterial infection rates (primary endpoint) and occurrences of adverse events during the IGHy treatment period were generally similar to those observed during an intravenous treatment period. IGHy was associated with a numerically lower rate of systemic adverse events and a numerically higher rate of localized adverse events than those observed with intravenous treatment. Compared with intravenous administration, IGHy was administered at a significantly higher maximum flow rate and at a similar frequency. Most patients preferred IGHy over intravenous administration. IGHy offers a new method for subcutaneous delivery of human immunoglobulin replacement therapy in patients with PIDs.     

Human induced pluripotent stem cells—from mechanisms to clinical applications

Human pluripotent stem cells hold great promise for basic research and regenerative medicine due to their inherent property to propagate infinitely, while maintaining the potential to differentiate into any given cell type of the human body. Since the first derivation in 1998, pluripotent human embryonic stem cells (ESCs) have been studied intensively, and although these cells provoke ethical and immune rejection concerns, translation of human ESC research into the clinics has been initiated. The generation of embryonic stem cell-like human induced pluripotent stem cells (iPSCs) from somatic cells by virus-mediated overexpression of distinct sets of reprogramming factors (OCT4, SOX2, KLF4, and c-MYC, or OCT4, SOX2, NANOG, and LIN28) in 2007 has opened up further opportunities in the field. While circumventing the major disputes associated with human ESCs, iPSCs offer the same advantages and, in addition, new perspectives for personalized medicine. This review summarizes technical advances toward the generation of potentially clinically relevant human iPSCs. We also highlight key molecular events underlying the process of cellular reprogramming and discuss inherent features of iPSCs, including genome instability and epigenetic memory. Furthermore, we will give an overview of particular envisaged human iPSC applications and point out which improvements are yet to come and what has been achieved so far.     

Exploring peer coaches’ outcomes: Findings from a clinical trial of patients with chronic pain

ObjectiveAlthough peer coaching can help patients manage chronic conditions, few studies have evaluated the effects of peer coaching on coaches, and no studies have systematically examined these effects in the context of chronic pain coaching.MethodsPeer coach outcomes were assessed as part of a randomized trial of peer coaching for chronic pain. In this exploratory analysis, linear mixed models were used to evaluate changes in peer coaches’ pain and related outcomes from baseline to 6 and 9 months. The Šidák method was used to account for multiple comparisons.ResultsPeer coaches (N = 55) experienced statistically significant increases in anxiety and pain catastrophizing from baseline to 6 months, which were no longer significant after adjustment. All other changes were not statistically significant.ConclusionsDespite prior studies suggesting that peer coaches benefit from serving as a coach, the current study failed to support that conclusion.Practice ImplicationsPeer coaching remains a promising model, with high potential for implementation, for a number of chronic conditions requiring self-management. However, to maximize the benefits of such interventions, it is essential to monitor both those being coached and the coaches themselves, and not to assume that serving as a coach is inherently beneficial.     

Can we predict sleep‐disordered breathing in pregnancy? The clinical utility of symptoms

Sleep‐disordered breathing (SDB) is reported commonly during pregnancy and is associated with an increased risk of adverse maternal and fetal outcomes, but the majority of these data are based upon self‐report measures not validated for pregnancy. This study examined the predictive value of screening questionnaires for SDB administered at two time‐points in pregnancy, and attempted to develop an ‘optimized predictive model’ for detecting SDB in pregnancy. A total of 380 women were recruited from an antenatal clinic in the second trimester of pregnancy. All participants completed the Berlin Questionnaire and the Multivariable Apnea Risk Index (MAP Index) at recruitment, with a subset of 43 women repeating the questionnaires at the time of polysomnography at 37 weeks' gestation. Fifteen of 43 (35%) women were confirmed to have a respiratory disturbance index (RDI) > 5 h^?1. Prediction of an RDI > 5 h^?1 was most accurate during the second trimester for both the Berlin Questionnaire (sensitivity 0.93, specificity 0.50, positive predictive value 0.50 and negative predictive value 0.93), and the MAP Index [area under the receiver operating characteristic (ROC) curve of 0.768]. A stepwise selection model identified snoring volume, a body mass index (BMI)≥32 kg m^?2 and tiredness upon awakening as the strongest independent predictors of SDB during pregnancy; this model had an area under the ROC curve of 0.952. We conclude that existing clinical prediction models for SDB perform inadequately as a screening tool in pregnancy. The development of a highly predictive model from our data shows promise for a quick and easy screening tool to be validated for future use in pregnancy.     

Medical simulation-based education improves medicos’ clinical skills

Clinical skill is an essential part of clinical medicine and plays quite an important role in bridging medicos and physicians. Due to the realities in China, traditional medical education is facing many challenges. There are few opportunities for students to practice their clinical skills and their dexterities are generally at a low level. Medical simulation-based education is a new teaching modality and helps to improve medicos’ clinical skills to a large degree. Medical simulation-based education has many significant advantages and will be further developed and applied.     

Human endogenous retroviruses: transposable elements with potential?

Human endogenous retroviruses (HERVs) are a significant component of a wider family of retroelements that constitute part of the human genome. These viruses, perhaps representative of previous exogenous retroviral infection, have been integrated and passed through successive generations within the germ line. The retention of HERVs and isolated elements, such as long-terminal repeats, could have the potential to harm. In this review we describe HERVs within the context of the family of known transposable elements and survey these viruses in terms of superantigens and molecular mimics. It is entirely possible that these mechanisms provide the potential for undesired immune responses.     

Quantification of bradykinesia during clinical finger taps using a gyrosensor in patients with Parkinson’s disease

This study aims to develop a quantitative measure of bradykinesia which can be conveniently used during clinical finger taps test in patients with Parkinson’s disease. A miniature, light-weight gyrosensor free from gravitational artifact was used for measurement of finger taps in order to impose minimal constraint on patients. Forty Parkinson’s disease patients and 14 age-matched control subjects participated in the experiments. Subjects’ finger taps in both right and left hands were scored by two independent neurologists according to the unified Parkinson’s disease rating scale and were also measured by a gyrosensor. Four performance indices were derived from the gyrosensor signal of the index finger. All indices showed significant differences between control and patients (P < 0.001) and also significant correlations with the clinical finger taps score (r = –0.73 to −0.80, P < 0.001). ANOVA showed significant differences in all indices among different finger taps scores (P < 0.001), and post hoc tests showed significant differences in indices between most pairs of non-neighboring and part of neighboring pairs of finger taps scores (P < 0.01). The results suggest that indices from a gyrosensor can be used as quantitative measures of bradykinesia during the finger taps test.