Mapping patient pathways and understanding clinical decision-making in dengue management to inform the development of digital health tools

Background Dengue is a common viral illness and severe disease results in life-threatening complications. Healthcare services in low- and middle-income countries treat the majority of dengue cases worldwide. However, the clinical decision-making processes which result in effective treatment are poorly characterised within this setting. In order to improve clinical care through interventions relating to digital clinical decision-support systems (CDSS), we set out to establish a framework for clinical decision-making in dengue management to inform implementation. Methods We utilised process mapping and task analysis methods to characterise existing dengue management at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. This is a tertiary referral hospital which manages approximately 30,000 patients with dengue each year, accepting referrals from Ho Chi Minh city and the surrounding catchment area. Initial findings were expanded through semi-structured interviews with clinicians in order to understand clinical reasoning and cognitive factors in detail. A grounded theory was used for coding and emergent themes were developed through iterative discussions with clinician-researchers. Results Key clinical decision-making points were identified: (i) at the initial patient evaluation for dengue diagnosis to decide on hospital admission and the provision of fluid/blood product therapy, (ii) in those patients who develop severe disease or other complications, (iii) at the point of recurrent shock in balancing the need for fluid therapy with complications of volume overload. From interviews the following themes were identified: prioritising clinical diagnosis and evaluation over existing diagnostics, the role of dengue guidelines published by the Ministry of Health, the impact of seasonality and caseload on decision-making strategies, and the potential role of digital decision-support and disease scoring tools. Conclusions The study highlights the contemporary priorities in delivering clinical care to patients with dengue in an endemic setting. Key decision-making processes and the sources of information that were of the greatest utility were identified. These findings serve as a foundation for future clinical interventions and improvements in healthcare. Understanding the decision-making process in greater detail also allows for development and implementation of CDSS which are suited to the local context

Quantum Criticality in Heavy Fermion Metals

Quantum criticality describes the collective fluctuations of matter undergoing a second-order phase transition at zero temperature. Heavy fermion metals have in recent years emerged as prototypical systems to study quantum critical points. There have been considerable efforts, both experimental and theoretical, which use these magnetic systems to address problems that are central to the broad understanding of strongly correlated quantum matter. Here, we summarize some of the basic issues, including i) the extent to which the quantum criticality in heavy fermion metals goes beyond the standard theory of order-parameter fluctuations, ii) the nature of the Kondo effect in the quantum critical regime, iii) the non-Fermi liquid phenomena that accompany quantum criticality, and iv) the interplay between quantum criticality and unconventional superconductivity.Comment: (v2) 39 pages, 8 figures; shortened per the editorial mandate; to appear in Nature Physics. (v1) 43 pages, 8 figures; Non-technical review article, intended for general readers; the discussion part contains more specialized topic

Estimation of coronary artery hyperemic blood flow based on arterial lumen volume using angiographic images

The purpose of this study is to develop a method to estimate the hyperemic blood flow in a coronary artery using the sum of the distal lumen volumes in a swine animal model. The limitations of visually assessing coronary artery disease are well known. These limitations are particularly important in intermediate coronary lesions where it is difficult to determine whether a particular lesion is the cause of ischemia. Therefore, a functional measure of stenosis severity is needed using angiographic image data. Coronary arteriography was performed in 10 swine (Yorkshire, 25–35 kg) after power injection of contrast material into the left main coronary artery. A densitometry technique was used to quantify regional flow and lumen volume in vivo after inducing hyperemia. Additionally, 3 swine hearts were casted and imaged post-mortem using cone-beam CT to obtain the lumen volume and the arterial length of corresponding coronary arteries. Using densitometry, the results showed that the stem hyperemic flow (Q) and the associated crown lumen volume (V) were related by Q = 159.08 V3/4 (r = 0.98, SEE = 10.59 ml/min). The stem hyperemic flow and the associated crown length (L) using cone-beam CT were related by Q = 2.89 L (r = 0.99, SEE = 8.72 ml/min). These results indicate that measured arterial branch lengths or lumen volumes can potentially be used to predict the expected hyperemic flow in an arterial tree. This, in conjunction with measured hyperemic flow in the presence of a stenosis, could be used to predict fractional flow reserve based entirely on angiographic data

Effect of magnetic resonance imaging characteristics on uterine fibroid treatment

Nguyen Minh Duc, Huynh Quang HuyDepartment of Radiology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, VietnamAbstract: Uterine fibroids are the most common gynecological benign tumors adversely affecting the quality of life of women of a reproductive age. Magnetic resonance imaging (MRI) is efficient at localizing the site of lesions and characterizing uterine fibroids before treatment. Understanding the different characteristics of uterine fibroids on MRI is essential, because it not only enables prompt diagnosis, but also guides the development of suitable therapeutic methods. This pictorial review demonstrates the effect of MRI features on uterine fibroid treatment. Keywords: uterine fibroids, characteristics, magnetic resonance imaging, treatment

Influences of screening magnetic resonance imaging parameters on high-intensity focused ultrasound outcome for adenomyosis

Nguyen Minh Duc, Huynh Quang Huy Department of Radiology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam Abstract: Uterine adenomyosis is one of the most common benign pelvic diseases that adversely affects the quality of a woman’s life. High-intensity focused ultrasound is an effective noninvasive treatment option for symptomatic adenomyosis. Clinical studies showed that the prediction of immediate treatment outcome, defined as nonperfused volume ratio for adenomyosis, is one of the key parameters for determining the therapeutic efficacy. MRI parameters of adenomyosis in the screening phase, such as type, location, abdominal subcutaneous fat thickness, signal intensity of adenomyosis, size, number of foci inside the lesion, and perfusion, manifest the impact on nonperfused volume ratio. Therefore, in this article, we performed a literature review of the influential screening MRI parameters on the immediate high-intensity focused ultrasound outcome. Keywords: adenomyosis, high-intensity focused ultrasound, magnetic resonance imaging, nonperfused volume ratio, treatment outcom

Adverse events of focused ultrasound surgery for uterine fibroids and adenomyosis

Nguyen Minh Duc,1,* Huynh Quang Huy,1,* Bilgin Keserci2,3 1Department of Radiology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam; 2Department of Radiology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia; 3Department of Radiology, Hospital Universiti Sains Malaysia, USM 16150 Kubang Kerian, Kelantan, Malaysia *These authors contributed equally to this work Abstract: Uterine fibroids and adenomyosis are two common gynecological benign tumors that deteriorate women’s quality of life. The prevalence of uterine fibroid and adenomyosis is approximately 70%–80% and 5%–70%, respectively. The efficacy and safety of focused ultrasound surgery (FUS) therapy for treating uterine fibroid and adenomyosis patients has been proved. Regardless of this fact, there are still some potential adverse events that may arise during and after the provision of FUS treatment, which can degrade patients’ quality of life. Understanding the possible adverse events of FUS treatment can improve the confidence in the selection of eligible patients, optimization of treatment strategy, and monitoring of the treatment procedure to ensure patients’ safety. Keywords: adenomyosis, leiomyoma, adverse events, focused ultrasound surger

Neutralizing antibodies against enteroviruses in patients with hand, foot and mouth disease

Hand, foot and mouth disease (HFMD) is an emerging infection with pandemic potential. Knowledge of neutralizing antibody responses among its pathogens is essential to inform vaccine development and epidemiologic research. We used 120 paired-plasma samples collected at enrollment and >7 days after the onset of illness from HFMD patients infected with enterovirus A71 (EV-A71), coxsackievirus A (CVA) 6, CVA10, and CVA16 to study cross neutralization. For homotypic viruses, seropositivity increased from <60% at enrollment to 97%–100% at follow-up, corresponding to seroconversion rates of 57%–93%. Seroconversion for heterotypic viruses was recorded in only 3%–23% of patients. All plasma samples from patients infected with EV-A71 subgenogroup B5 could neutralize the emerging EV-A71 subgenogroup C4. Collectively, our results support previous reports about the potential benefit of EV-A71 vaccine but highlight the necessity of multivalent vaccines to control HFMD

Trafficking of Systemic Fluorescent Gentamicin into the Cochlea and Hair Cells

Aminoglycosides enter inner ear hair cells across their apical membranes via endocytosis, or through the mechanoelectrical transduction channels in vitro, suggesting that these drugs enter cochlear hair cells from endolymph to exert their cytotoxic effect. We used zebrafish to determine if fluorescently tagged gentamicin (GTTR) also enters hair cells via apically located calcium-sensitive cation channels and the cytotoxicity of GTTR to hair cells. We then examined the serum kinetics of GTTR following systemic injection in mice and which murine cochlear sites preferentially loaded with systemically administered GTTR over time by confocal microscopy. GTTR is taken up by, and is toxic to, wild-type zebrafish neuromast hair cells. Neuromast hair cell uptake of GTTR is attenuated by high concentrations of extracellular calcium or unconjugated gentamicin and is blocked in mariner mutant zebrafish, suggestive of entry via the apical mechanotransduction channel. In murine cochleae, GTTR is preferentially taken up by the stria vascularis compared to the spiral ligament, peaking 3 h after intra-peritoneal injection, following GTTR kinetics in serum. Strial marginal cells display greater intensity of GTTR fluorescence compared to intermediate and basal cells. Immunofluorescent detection of gentamicin in the cochlea also revealed widespread cellular labeling throughout the cochlea, with preferential labeling of marginal cells. Only GTTR fluorescence displayed increasing cytoplasmic intensity with increasing concentration, unlike the cytoplasmic intensity of fluorescence from immunolabeled gentamicin. These data suggest that systemically administered aminoglycosides are trafficked from strial capillaries into marginal cells and clear into endolymph. If so, this will facilitate electrophoretically driven aminoglycoside entry into hair cells from endolymph. Trans-strial trafficking of aminoglycosides from strial capillaries to marginal cells will be dependent on as-yet-unidentified mechanisms that convey these drugs across the intra-strial electrical barrier and into marginal cells