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Diagnostic theories are fundamental to information system (IS) practice and are represented as trees. While there are approaches for validating diagnostic trees, these validate the overall performance of the tree rather than identifying ways incorrect diagnoses can occur. It is important to fully validate diagnostic trees because even if the tree gives the correct decision “most of the time,” it is possible for incorrect decisions traveling down little-used branches of the tree to result in catastrophic decisions. In this article, we describe the process of using a variant of q-sorting to validate diagnostic trees. In this methodology, diagnostic trees that independent experts develop are transformed into a quantitative form, and that quantitative form is tested to determine the inter-rater reliability of the individual branches in the tree. The trees are then successively transformed to incrementally test if they branch in the same way. The results help researchers not only identify quality items for use in a diagnostic tree but also facilitate diagnoses of problems with those items and facilitate the reconciliation of discrepant trees by experts. The methodology validates not only the whole tree but also its subparts.

A 61-year-old gentleman presented with small bowel intussusception from small bowel melanoma intussusceptum. He complains of intermittent abdominal distension but no history of intestinal obstruction. Apart from this, he was also symptomatic anemia which required repeated transfusion for the past few months. The contrast-enhanced computed tomography of the abdomen shows an omental mass with small bowel intussusception. He then underwent an exploratory laparotomy with segmental resection of the affected segment. Histopathological examination confirmed primary gastrointestinal melanoma. Multiple small bowel malignant melanoma is a rare disease. It remains a controversial diagnosis as it may be a primary or metastasis from an unidentified or regressed primary cutaneous melanoma. Prompt surgical intervention enables us to obtain tissue diagnosis, prevent complete intestinal obstruction and strategize the goals of treatment for the patient.

Disparities in cardiovascular outcomes between Aboriginal and Torres Strait Islander Australians and non-Indigenous Australians persist. This has previously been attributed to a combination of differences in burden of cardiovascular disease risk factors, and inpatient access to guideline-recommended care.To assess differences in inpatient access to guideline-recommended acute coronary syndrome (GR-ACS) treatment between Aboriginal and Torres Strait Islander and non-indigenous patients admitted to Royal Darwin Hospital (RDH) with index ACS event.This retrospective study included index ACS admissions (n = 288) to RDH between January 2016 and June 2017. Outcomes included rates of coronary angiography, percutaneous coronary intervention (PCI), surgical revascularisation, GR-ACS medications prescribed on discharge and short-term outcomes (30-day mortality and ACS readmissions; 12-month all cardiac-related readmissions).Two hundred and eighty-eight patients, including 109 (37.85%) Aboriginal and Torres Strait Islander patients, were included. Compared with non-indigenous patients, they were younger (median age 48 years vs 60 years; P 0.01), with a greater burden of comorbidities, including diabetes (39% vs 19%; P 0.01), smoking (68% vs 35%; P 0.01) and chronic kidney disease (29% vs 5%; P 0.01). There were no differences in rates of coronary angiography (98% vs 96%; P = 0.24) or PCI (47% vs 57%; P = 0.12), although there was a trend towards surgical revascularisation in Aboriginal and Torres Strait Islander patients (16% vs 8%; P = 0.047). There were no differences in 30-day mortality (1.8% vs 1.7%; P = 0.72), 12-month ACS readmissions (7% vs 4%; P = 0.20) or 12-month cardiac-related readmissions (7% vs 13%; P = 0.11).Aboriginal and Torres Strait Islander patients received similar inpatient ACS care and secondary prevention medication at discharge, with similar short-term mortality outcomes as non-indigenous patients. While encouraging, these outcomes may not persist long term. Further outcomes research is required, with differences compelling consideration of other primary and secondary prevention contributors.

This paper presents three dimensional (3-D) Hall sensors that are capable of detecting magnetic fields in three axis directions and are realized on 180BCDLite® technology with one or two mask adders. The 3-D Hall sensor architecture adopts a modular approach that enables optimization of the planar and vertical Hall devices. The geometries and doping profiles of the Hall devices can be designed for various performance specifications. The planar Hall devices are engineered independently to achieve either a high current–related sensitivity SI >385 V/(A.T) or a high voltage–related sensitivity SV >50 mV/(V.T). For the vertical Hall devices, SV up to 50 mV/(V.T) are demonstrated. The modular design enables flexibility for designers to provide a System-on-Chip (SoC) to meet the needs for a variety of magnetic sensing applications at a low-cost.

This paper describes a modularized smart system architecture which is integrated with Internet of Thing (IoT) into the DC-DC converters to build a programmable technique to leverage machine learning algorithms to predict possible future faults to the system. In addition, it facilitates the performance optimization of the boost converter. This system can be established with low computing hardware to simulates the control behavior and data-driven method of IoT-based, due to the unreliability initiated from the integration of IoT technology and power electronic converters. In response to these challenges, the current paper addresses a scientific approach using small signal analysis of dc-dc boost converter (non-Ideal) with closed loop control to analyze the small deviations or abnormalities in transient region and the steady-state operating point. Complete state-space analysis is done to obtain output voltage using pulse width modulation techniques for boosting the voltage of the input voltage to a higher level by momentarily storing and release the energy in the conductor. The model of the converter is designed and simulated using voltage mode controlling method. Digital implementation based on Arduino platform was implemented to compensate perturbations of sudden load variation either on voltage or current loads. A Simulation study is conducted to validate the result of the step-up dc-dc converter using MATLAB.

Background There exists scant evidence on the optimal approaches to integrating patient-reported outcomes (PROs) in clinical practice. This study gathered oncology practitioners’ experiences with implementing PROs in cancer care. Methods Between December 2019 and June 2020, we surveyed practitioners who reported spending > 5% of their time providing clinical care to cancer patients. Respondents completed an online survey describing their experiences with and barriers to using PROs in clinical settings. Results In total, 362 practitioners (physicians 38.7%, nurses 46.7%, allied health professionals 14.6%) completed the survey, representing 41 countries (Asia–Pacific 42.5%, North America 30.1%, Europe 24.0%, others 3.3%). One quarter (25.4%) identified themselves as “high frequency users” who conducted PRO assessments on > 80% of their patients. Practitioners commonly used PROs to facilitate communication (60.2%) and monitor treatment responses (52.6%). The most commonly reported implementation barriers were a lack of technological support (70.4%) and absence of a robust workflow to integrate PROs in clinical care (61.5%). Compared to practitioners from high-income countries, more practitioners in low-middle income countries reported not having access to a local PRO expert (P

This study aimed to provide preliminary evidence on feasibility of the inaugural use of teleconsultation between acute hospitals and primary care for acute wound management in Singapore. Post-surgical patients with carbuncle wounds, perianal abscess wounds or surgical abdominal dehiscence wounds were recruited from an acute hospital. Instead of receiving their follow up care at the acute care tertiary hospital, patients were given the option to receive their care at primary care facilities instead, supported by teleconsultation wound services provided by wound care nurses from the hospital. The following outcome measures were collected: number of care sessions required (until wound healed), readmissions or referrals back to hospital, cost (patient's and healthcare provider's perspective), patients' and nurses' satisfaction. In total, 18 patients were recruited and completed the study (teleconsult group = 5; tertiary care clinic group = 13). The mean age (SD) of patients were 63.2 (SD 11.5) years old in the teleconsult group and 47.9 years old (SD 11.5) in the tertiary care clinic group. There were 7 female (54%), and 6 male (46%) in the tertiary care clinic group whereas teleconsult group consisted of male only (n = 5). Most had carbuncle wounds (teleconsult group: n = 4; 80%); tertiary care clinic group: (n = 10; 77%). For patients with carbuncle wounds, the average number of care sessions required were 21 and 33 for the tertiary care clinic and teleconsult respectively. None of the patients in the teleconsult group were referred back to the tertiary care hospital. All 16 nurses (n = 6 from acute care hospital, n = 10 from polyclinics) who participated in the feedback survey cited convenience, ease of tracking wound sizes, and closer collaboration between the acute care and primary care nurses as advantages of the service. Wound teleconsultation is feasible and potentially cost savings for patients with acute complex wounds.

Multimorbidity is associated with increased depression risks. Little research examines how physical exercise moderates this association. From an existing cohort of community-dwelling older adults in Hong Kong recruited in 2001–2003, the authors included participants who were successfully interviewed after 14 years (2015–2017). Geriatric depressive symptoms were used as the primary outcome and measured by the 15-item Geriatric Depression Scale, while multimorbidity was operationalized using a list of 19 conditions. Subscores of the Physical Activity Scale for the Elderly measuring light, moderate, and strenuous sport/recreational activities were included as moderators. In total, 1,056 participants were included, of whom 50.7% were multimorbid. Multimorbidity was associated with 12% more geriatric depressive symptoms, but strenuous physical activities were associated with a smaller risk elevation only among multimorbid patients (adjusted relative risk = 0.99, 95% confidence interval [0.98, 0.99]; p = .001). In conclusion, strenuous sport and recreational activities may attenuate the association between multimorbidity and geriatric depressive symptoms.

Background Pes planus is associated with hallux valgus development. This study evaluated the impact of pes planus on clinical outcomes following hallux valgus surgery. Methods 191 patients underwent Scarf osteotomy for hallux valgus. Pes planus angles including talonavicular coverage angle, lateral talus-first metatarsal angle (Meary’s angle) and lateral talocalcaneal angle were measured. The cohort was stratified into control (0°–4.0°), mild (4.1°–14.9°), moderate (15.0°–30.0°) and severe (> 30.0°) pes planus groups according to Meary’s angle. Clinical outcomes were compared at baseline, 6 months and 24 months. Results There were 78 controls, 95 mild and 18 moderate cases of pes planus. Meary’s angle was independently associated with preoperative hallux valgus angle. Pes planus angles were not associated with pain, AOFAS, SF-36 physical or mental scores. All three groups had similar clinical outcomes and patient satisfaction. Conclusion Compared to patients with neutral foot arches, those with pes planus presented with more severe hallux valgus deformity but had similar clinical outcomes following surgical correction.

A compact tag antenna, which has a geometrical dimension of 31.5 mm × 31.5 mm × 3.2 mm, is constructed using a stacked PILA for metal-mountable applications in the UHF RFID passband. The new antenna is formed by inserting a shorted patch into a PILA structure to create a double-layered inverted antenna, which can be viewed as a cascade of two parallel resonant tanks. An increase in electric field intensity in the antenna structure has brought in sufficient capacitance for reducing the tag resonant frequency effectively to the useful UHF RFID passband. Due to the increase in the antenna reactance, conjugate impedance matching can be easily achieved between the antenna and the microchip. Fine-tuning schemes such as stubs and slits are also incorporated with the proposed tag antenna for adjusting the operating frequency to an exact precision. Measurements show that the proposed tag antenna can achieve a read distance of 7.25 m at an EIRP power of 4 W. The resonance of the proposed tag antenna is found to be very stable and it is insensitive to changes in the backing metal platform.

There are limited studies looking at longer-term outcomes of the total ankle replacement (TAR) in the Asian cohort. Asian ankles are smaller in size and are more varus compared to Western cohorts. Cultural differences also require increased ankle range of motion demands. Therefore, assessment of longer-term functional and radiological outcomes in the Asian cohort is warranted. Between 2007 and 2015, 43 consecutive patients received a 3-component, cementless, unconstrained, fully congruent TAR. Patients were followed up over a mean 8 (range 5-14 years). Preoperative and postoperative AOFAS ankle-hindfoot score (AOFAS-AHS), visual analogue score (VAS), physical and mental component scores of the SF-36 (PCS and MCS respectively) were calculated. European Foot and Ankle Score was also recorded at 8 years. Radiographs were reviewed postoperatively to assess implant position and study evidence of implant loosening and impingement. At 8 years, survivorship was 83.5%. Reasons for implant removal included infection (n = 2) and aseptic loosening (n = 5). AOFAS-AHS, VAS MCS at 8 years postoperatively were comparable to outcomes at 2 years postoperatively (p > .05). PCS at 8 years demonstrated improvement compared to 2 years postoperatively (49 ± 7 vs 42 ± 11, p = .048). Radiographic impingement was noted in 9 cases (20.9%). Radiological loosening was noted in 8 cases with 5 cases requiring revision surgery. At 8 years postoperatively, clinical outcomes, radiological outcomes and survivorship following TAR in an Asian cohort are satisfactory and comparable to that found in existing literature. Long-term studies are required to ascertain survivorship of TAR. Implant design with the Asian cohort in mind may yield improved outcomes.

The prevalence of hallux valgus increases with age. However, few studies have compared the effectiveness of surgical correction among different age groups. The authors present a retrospective evaluation of the influence of age on clinical outcomes. Patients who underwent corrective surgery for hallux valgus at an academic hospital were stratified into 2 age groups: ≥70 years old (Group 1) and70 years old (Group 2). Following propensity score matching there were 106 patients: 53 patients in each group. Clinical outcomes, quality of life, and satisfaction questionnaires were collected preoperatively and at 6 months and 24 months postoperatively. There were no differences between both patient groups in preoperative biodata and clinical parameters. However, elderly patients had significantly poorer Physical Component Summary scores postoperatively at both 6 months (p = .001) and 24 months (p.001), and significantly poorer American Orthopaedic Foot and Ankle Society Hallux Metatarsophalangeal- Interphalangeal Scale at 24 months (p = .026). There was no difference between the 2 groups in patient satisfaction rates at 24 months postoperatively (70% vs 85%, p.05). Elderly patients display significant improvements in their clinical scores 24 months postoperatively with no significant difference between satisfaction rates with their younger counterparts. Elderly patients can stand to benefit from hallux valgus surgery.

Background: Hand hygiene is paramount in preventing the spread of healthcare-associated infections especially during disease epidemics. Compliance rates with hand hygiene policies remain below 50% internationally and may be lower in the outpatient care setting. This study assessed the impact of the patient empowerment model on hand hygiene compliance among healthcare providers. Methods: From October 2016 to May 2017, patients from a large ambulatory oncology centre were prospectively enrolled. Patients were instructed to observe healthcare providers for hand hygiene compliance and to remind healthcare providers where it was not observed during at least three consecutive encounters. Healthcare provider reactions to this intervention were rated by patients. Patients’ hand hygiene knowledge and beliefs were objectively elicited pre and post-study. Results: Thirty patients with a median age of 52 years (range 5–91) completed the study for a total of 190 healthcare provider encounters. When initial hand hygiene was not observed, patients offered a reminder in 71 (37.4%) encounters, did not offer a reminder in 73 (38.4%) encounters and forgot to offer a reminder in 24 (14.2%) encounters. Patients perceived positive or neutral reactions in 76.8% of encounters and negative or surprised reactions in 23.2% of encounters. Healthcare provider compliance improved from 11.6% to 48.9% with intervention. Patient hand hygiene knowledge improved by 16% following the study. Conclusions: Patient-empowered hand hygiene may be a useful adjunct for improving hand hygiene compliance among healthcare providers and improving patient hand hygiene knowledge, although it may confer an emotional burden on patients.

In this paper, a same-sense circularly polarized grid-slotted patch antenna with wide axial ratio bandwidth is proposed. The rectangular grid-slotted patch on top and bottom planes are excited through flipped Z-shaped slots pair using a stripline feed to generate same-sense circular polarization with wider axial ratio bandwidth. Characteristic mode analysis is used in the design of the antenna to analyze the desired orthogonal modes. Variations of the resonant frequencies, axial ratio bandwidths and local minimas with the design parameters are discussed. The antenna has a 3 dB axial ratio bandwidth of about 21% from 4.07 GHz to 5.02 GHz, with the realized gain ranging from 2 to 3.5 dBic.

Backgroud/purpose Bloodstream infections (BSI) are common in patients with major burns, but its effect on mortality remains controversial. This study was aimed to investigate if BSI is significant risk factor of mortality? Methods This is a retrospective chart review study included 266 adult patients admitted to our burn center from 2000 to 2019. Age, sex, inhalation injuries, total burn surface area (TBSA), duration of stay in intensive care unit, BSI and mortality were variables studied. Fisher exact test, Mann-Whitney test and logistic regression was used for statistical analysis. Results There were 234 survivors and 32 non-survivors. Male was predominant. The overall incidence of BSI was 18.8%, and the overall crude mortality was 12%. Burns ≥ 30% TBSA and BSI were significant risk factors. A predictive function based on 30% TBSA and BSI within 14 days after the onset of burns (BSI-14) was derived. The function has a sensitivity of 0.97, specificity of 0.42 and achieved a maximum Youden Index at functional value ≥ 0.05727. The mortality probability of BSI-14 in burns ≥ 30% TBSA was 40.8%. Conclusions BSI and burns ≥ 30% TBSA were significant risk factors of mortality. Early detection of BSI-14 is critical in burn care as its probability of mortality can be as high as 40% in patients ≥ 30% TBSA of burns. To reduce the risk of mortality, early in ventilator withdrawal, invasive lines and tubes removal, and early grafting should be emphasized besides infection control and appropriate use of antibiotics.

Automated brain tumour segmentation from post-operative images is a clinically relevant yet challenging problem. In this study, an automated method for segmenting brain tumour into its subregions has been developed. The dataset consists of multimodal post-operative brain scans (T1 MRI, post-Gadolinium T1 MRI, and T2-FLAIR images) of 15 patients who were treated with post-operative radiation therapy, along with manual annotations of their tumour subregions. A 3D densely-connected U-net was developed for segmentation of brain tumour regions and extensive experiments were conducted to enhance model accuracy. A model was initially developed using the publicly available BraTS dataset consisting of pre-operative brain scans. This model achieved Dice Scores of 0.90, 0.83 and 0.78 for predicting whole tumour, tumour core, and enhancing tumour subregions when tested on BraTS20 blind validation dataset. The acquired knowledge from BraTS was then transferred to the local dataset. For augmentation purpose, the local dataset was registered to a dataset of MRI brain scans of healthy subjects. To improve the robustness of the model and enhance its accuracy, ensemble learning was used to combine the outputs of all the trained models. Even though the size of the dataset is very small, the final model can segment brain tumours with a high Dice Score of 0.83, 0.77 and 0.60 for whole tumour, tumour core and enhancing core respectively.

The initial evaluation of maxillofacial trauma in athletes should first focus on the management of life-threatening injuries that require emergent care. Airway, breathing, and circulation are the 3 areas to be addressed first and foremost, as set forth by Advanced Trauma Life Support (ATLS) guidelines. Following the stabilization of the patient, a thorough physical examination and systematic review of any relevant imaging studies are imperative to ensure that injuries are not missed. Ultimately, management by the facial plastic surgeon should balance the goals of facial trauma restoration with the overall needs of the patient.

For the first time, the ionic polymer metal composite (IPMC) actuator is integrated with a RFID (Radio-Frequency Identification) tag antenna for achieving frequency reconfiguration in the UHF (Ultra-High-Frequency) band. Here, the IPMC movable flap serves as an actuator that can effectively tune the tag resonant frequency. By applying a 2-layer crenellated structure and employing a surface patterned electrode for restraining back relaxation, the deflection of the IPMC actuator can be significantly improved. The IPMC actuator can move in two directions, enabling two-degree frequency tuning. Numerical and experimental data confirm that the tip displacement of the IPMC actuator can be enhanced up to 266% with the use of the 2-layer crenellated structure. The IPMC actuator allows the resonant frequency of the tag antenna to be tuned back by as much as 35 MHz, after deviating due to placing on an unintended object. UHF RFID application is also performed using a portable commercial RFID reader. Good frequency reconfiguration and broad tuning range, along with far read distances, have been achieved with our tunable UHF RFID tag antenna.

Background Airway surgery presents a unique environment for operating room fire to occur. This study aims to explore the factors of combustion when using KTP laser with high flow oxygen in an ex-vivo model. MethodsThe variables tested were varying tissue type, tissue condition, oxygen concentration, laser setting, and smoke evacuation in a stainless-steel model. Outcome measures were time of lasing to the first spark and/or flame. A multivariate Cox proportional hazard model was used to determine the risk of spark and flame across the different risk factors. ResultsFor every 10% increase in oxygen concentration above 60% the risk of flame increased by a factor of 2.3. Continuous laser setting at 2.6W increased the risk by a factor of 72.8. The risk of lasing adipose tissue is 7.3 times higher than that of muscle. Charred tissue increases the risk of flame by a factor of 92.8. Flame occurred without a preceding spark 93.6% of the time. Conclusions Using KTP laser in the pulsed mode with low wattages, minimising lasing time, reducing the oxygen concentration and avoiding lasing adipose or charred tissue produce a relatively low estimated risk of spark or flame.

Objectives Little empirical research exists on how key stakeholders involved in the provision of care for chronic conditions and policy planning perceive the indirect or ‘spillover’ effects of the COVID-19 on non-COVID patients. This study aims to explore stakeholder experiences and perspectives of the impact of COVID-19 on the provision of care for chronic conditions, evolving modalities of care and stakeholder suggestions for improving health system resilience to prepare for future pandemics. Design Qualitative study design. Setting and participants This study was conducted during and after COVID-19 lockdown period in Singapore. We recruited a purposive sample of 51 stakeholders involved in care of non-COVID patients and/or policy planning for chronic disease management. They included healthcare professionals (micro-level), hospital management officers (meso-level) and government officials (macro-level). Methods In-depth semi-structured interviews were conducted. All interviews were digitally recorded, transcribed verbatim and thematically analyzed. Results Optimal provision of care for chronic diseases may be compromised through the following processes: lack of ‘direct’ communication between colleagues on clinical cases resulting in rescheduling of patient visits; uncertainty in diagnostic decisions due to protocol revision and lab closure; and limited preparedness to handle non-COVID patients’ emotional reactions. While various digital innovations enhanced access to care, a digital divide exists due to uneven digital literacy and perceived data security risks, thereby hampering wider implementation. To build health system resilience, stakeholders suggested the need to integrate digital care into the IT ecosystem, develop strategic public-private partnerships for chronic disease management, and give equal attention to the provision of holistic psychosocial and community support for vulnerable non-COVID patients. Conclusions and Implications Findings highlight that strategies to deliver quality chronic care for non-COVID patients in times of public health crisis should include innovative care practices and institutional reconfiguration within the broader health system context., To mitigate spillover effects of COVID-19 on chronic care, more attention should be devoted to digital care ecosystem, strategic public-private partnerships and psychosocial support for vulnerable non-COVID patients.

Tricuspid valve surgery has high mortality for first-time operations and repeat surgery is fraught with even higher rates. When failed tricuspid surgical prostheses and repairs are present, physicians look toward transcatheter tricuspid valve replacement (TTVR) as a tangible solution. Using balloon-expandable bioprosthetic valves in an off-label fashion, tricuspid valve-in-valve (TViV) procedures can be performed reliably; however, valve-in-ring cases are more nuanced and have higher risks of paravalvular leak and valve malpositioning. TTVR specific issues include THV anchoring, management of preexisting pacing leads, postprocedure thromboembolic prophylaxis, and possible tricuspid reintervention.

Path to another drug against COVID-19 The rapid development of vaccines has been crucial in battling the ongoing COVID-19 pandemic. However, access challenges remain, breakthrough infections occur, and emerging variants present increased risk. Developing antiviral therapeutics is therefore a high priority for the treatment of COVID-19. Some drug candidates in clinical trials act against the viral RNA-dependent RNA polymerase, but there are other viral enzymes that have been considered good targets for inhibition by drugs. Owen et al . report the discovery and characterization of a drug against the main protease involved in the cleavage of polyproteins involved in viral replication. The drug, PF-07321332, can be administered orally, has good selectivity and safety profiles, and protects against infection in a mouse model. In a phase 1 clinical trial, the drug reached concentrations expected to inhibit the virus based on in vitro studies. It also inhibited other coronaviruses, including severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome coronavirus, and could be in the armory against future viral threats. —VV

Among the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4- and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1, the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44). But despite the poor MRD, outcome of DUX4 B-ALL was excellent (5-year cumulative risk of relapse [CIR], 8.9%; 95% confidence interval [CI], 2.8%-19.5% and 5-year overall survival, 97.8%; 95% CI, 85.3%-99.7%). In MS2003, 21% of patients with DUX4 B-ALL had poor peripheral blood response to prednisolone at day 8, higher than other subtypes (8%; P = .03). In MS2010, with vincristine at day 1, no day-8 poor peripheral blood response was observed in the DUX4 subtype (P = .03). The PAX5alt group had an intermediate risk of relapse (5-year CIR, 18.1%) but when IKZF1 was not deleted, outcome was excellent with no relapse among 23 patients. Compared with MS2003, outcome of PAX5alt B-ALL with IKZF1 codeletion was improved by treatment intensification in MS2010 (5-year CIR, 80.0% vs 0%; P = .05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 codeletion.

In this article, we demonstrate the Ti/TiN/Al (15/50/50 nm) ohmic contact on InGaP/GaAs heterojunction bipolar transistors (HBTs) epitaxially grown on 200-mm Si substrate. We study the rapid thermal annealing (RTA) effect of the metal stack on both n-type InGaAs and p-type GaAs. The dc characteristics of the HBT devices fabricated using the Ti/TiN/Al metal contacts have been analyzed. Contact resistances (R-c)

Objective To investigate the agreement of measurements of the three diameters of rectosigmoid deep endometriosis (DE) lesions between presurgical evaluation using transvaginal sonography (TVS) and postsurgical specimen measurement (PSM). Methods This was a prospective observational multicenter study including symptomatic women undergoing surgical treatment for DE involving the rectosigmoid, by either discoid or segmental resection, from April 2017 to December 2019. TVS was performed presurgically to evaluate lesion size (craniocaudal–midsagittal length, anteroposterior thickness and transverse diameter), in accordance with the International Deep Endometriosis Analysis (IDEA) group consensus statement, and was compared with PSM. The agreement of lesion dimensions between the two methods was assessed by Bland–Altman plots and limits of agreement and additionally by the intraclass correlation coefficient (ICC) and Pearson's correlation coefficient. Systematic and proportional bias was assessed using the paired t-test. Results A total of 207 consecutive women were eligible for inclusion. Forty-one women were excluded, leaving 166 women for final analysis. A total of 123 segmental resections and 46 discoid resections were performed (both procedures were performed in three women). The mean difference between TVS and PSM was 0.90 (95% CI, 0.85–0.95) mm for lesion length measurements, 1.03 (95% CI, 0.98–1.09) mm for lesion thickness measurements and 0.84 (95% CI, 0.79–0.89) mm for transverse diameter measurements. Bland–Altman analysis demonstrated good agreement between the two methods for measurements of lesion length. Furthermore, there was good reliability and correlation between TVS and PSM for lesion length measurements, as demonstrated by an ICC of 0.82 (95% CI, 0.75–0.87) and Pearson's correlation coefficient of 0.72 (95% CI, 0.62–0.80), moderate-to-good reliability and correlation for lesion thickness measurements, with an ICC of 0.76 (95% CI, 0.67–0.82) and Pearson's correlation coefficient of 0.61 (95% CI, 0.51–0.70), and poor-to-moderate reliability and correlation for transverse diameter measurements, with an ICC of 0.58 (95% CI, 0.39–0.71) and Pearson's correlation coefficient of 0.46 (95% CI, 0.33–0.58). Conclusion Preoperative TVS determines accurately rectosigmoid DE lesion length. TVS can thereby contribute to optimal planning of surgical treatment options in women with rectosigmoid DE. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Leishmaniasis is prevalent in Southern Europe, the Middle East, India, Africa, and Central and South America. Cutaneous leishmaniasis may spontaneously heal over time without treatment; however, risk of visceral dissemination and the impact of cosmetic defect are important concerns. We report a Case of cutaneous leishmaniasis in a patient who ever traveled to Mexico before the onset of a deteriorating wound around the swollen left eyebrow. A diagnosis of infection with Leishmania mexicana was made based on histopathological examination and molecular identification. Systemic treatment with liposomal amphotericin B and ketoconazole were administered with gradual healing of the lesion. Also, this traveler case implicates that the spread of endemic parasitic diseases may be a concealed risk on the public health for Taiwan underlying globalization.

Background Telemedicine services have been increasingly used to facilitate post-treatment cancer survivorship care, including improving access; monitoring health status, health behaviors, and symptom management; enhancing information exchange; and mitigating the costs of care delivery, especially since the COVID-19 pandemic. To inform guidance for the use of telemedicine in the post-COVID era, the aim of this overview of systematic reviews (SRs) was to evaluate the efficacy of, and survivor engagement in, telemedicine interventions in the post-treatment survivorship phase, and to consider implementation barriers and facilitators. Methods PubMed, Cochrane CENTRAL, CINAHL, Embase, and Web of Science databases were searched. SRs that examined the use of telemedicine in the post-treatment phase of cancer survivorship, published between January 2010 and April 2021, were included. Efficacy data were synthesized narratively. Implementation barriers and facilitators were synthesized using the Consolidated Framework for Implementation Research. Results Twenty-nine SRs were included. A substantive body of evidence found telemedicine to benefit the management of psychosocial and physical effects, particularly for improving fatigue and cognitive function. There was a lack of evidence on the use of telemedicine in the prevention and surveillance for recurrences and new cancers as well as management of chronic medical conditions. This overview highlights a range of diverse barriers and facilitators at the patient, health service, and system levels. Conclusions This review highlights the benefits of telemedicine in addressing psychosocial and physical effects, but not in other areas of post-treatment cancer survivorship care. This large review provides practical guidance for use of telemedicine in post-treatment survivorship care.

Clinical Practice Points • Cutaneous lymphangitic carcinomatosis is a rare form of cutaneous metastatic disease which can appear to be a variety of different dermatologic conditions. Clinicians should maintain a high index of suspicion in order to avoid delays in diagnosis and treatment given the poor prognosis of cutaneous metastatic disease. • While the skin is an uncommon site of metastatic disease, it is important to remember that cutaneous metastases can be the sole presenting sign of malignancy or extra nodal disease. • Skin metastases more commonly present within the first 3 years after discovery of a primary tumor. However, they can occur at any time and have been reported up to 22 years after an initial cancer diagnosis. Clinicians should consider this with any new skin lesion in a patient with a history of malignancy.

BACKGROUND Enzyme replacement therapy significantly reduces morbidity and mortality in patients with Pompe disease. Development of hypersensitivity reactions to enzyme replacement therapy is common and can adversely affect disease outcomes when treatment is halted or delayed. OBJECTIVE Our institution reports a case of successful alglucosidase alfa enzyme replacement therapy desensitisation in a 9-year-old girl with infantile onset Pompe disease. METHODS A desensitisation protocol was tailored to our patient with the help of a multidisciplinary team including the allergist, geneticist, nurses and pharmacists. RESULTS For our patient, desensitisation was successful using a multi-step three-fold dose escalation protocol. CONCLUSION Desensitisation is possible in individuals with hypersensitivity reactions to enzyme replacement. Desensitisation protocols need to be tailored according to the patient's needs and responses to find a protocol that is safe, effective and simple.

The Beliefs about Medicines Questionnaire (BMQ) and Adherence Starts with Knowledge (ASK-12) questionnaire were originally developed and validated in Western populations to assess beliefs and barriers to medication adherence. The study aim is to validate the BMQ and ASK-12 questionnaire for use in a Singapore population with early stage breast cancer. English-speaking women on adjuvant endocrine therapy ( n = 157) were recruited. The BMQ-Specific showed good internal consistency with structural validity. The internal consistency of BMQ-General and ASK-12 Behaviour scale improved with the new factor structure obtained from exploratory factor analysis. Further studies are needed to confirm these factor structures.

Akkas gas field is the biggest natural gas field in Iraq that is located in the western desert area. The field contains around (9 BSCF) of approved gas reserve from the conventional rock source. This paper presents field development planning process combined with economic analysis comprises, the number of wells that yields in maximum net present value (NPV), the recovery factor and raw gas production rates for the total number of suggested wells that have been estimated, as well as the cumulative gas produced with time. The development plans were elaborated concerning different types of well geometries and operational constraints. Full comparison analysis for all presented plans regarding NPV, recovery factor, discounted cash flow versus production time, forecasted production rate, as well as forecasted cumulative production with time have been presented. Sensitivity analysis has been made to determine well and reservoir controlling parameters that leads for best operating field development plans. The study shows the effectiveness of horizontal well type compared with vertical wells; as well as, the effect of reservoir permeability on field development plans, the results show that the field could be operated at target plateau rates of (250, 500 and 750 MMSCF/D). It also shows the superior effect of stimulation processes in increasing the NPV and field recovery factor using less number of wells

Background Medication adherence is crucial for improving clinical outcomes in the treatment of patients. We evaluate the effect of short message service (SMS) reminder on medication adherence and serum hormones in patients with breast cancer on aromatase inhibitors. Methods An open-label, multi-centre, prospective randomised controlled trial of SMS versus Standard Care was conducted. Medication adherence was assessed via self-report using the Simplified Medication Adherence Questionnaire at baseline, 6 month, and 1 year. Androstenedione, estradiol, and estrone were measured at baseline and 1 year. The χ2 test and mixed effects logistic regression was performed to compare medication adherence between groups. Difference in androstenedione and estrone levels were assessed using analysis of covariance, whereas χ2 test and logistic regression was used for estradiol. Analysis was based on intention-to-treat. Results A total of 244 patients were randomised to receive weekly SMS reminder (n = 123) or Standard Care (n = 121) between May 2015 and December 2018. The odds of adherence was higher at 6-month in SMS (OR = 1.78, 95% CI 1.04–3.05, p = 0.034), and not significantly different at 1-year (OR = 1.15, 95% CI: 0.67–1.96 p = 0.617). Mixed effects logistic regression analysis showed higher odds of adherence in SMS over the 1-year period (OR = 2.35, 95% CI: 1.01–5.49, p = 0.048). There was no difference in serum hormone levels between groups. Conclusion SMS reminder improved medication adherence in the short-term but had no effect on serum hormones levels in the longer term. Future studies could investigate the use of tailored SMS intervention according to patient preference to improve its sustainability., Highlights • Patients on aromatase inhibitors were randomised to SMS reminder or Standard Care. • SMS reminder improved medication adherence in the short-term. • There was no effect on serum hormones levels in the longer term.

Introduction: We used data from MOBI-Kids, a 14-country international collaborative case-control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children (10 years or older), adolescents and young adults (up to the age of 24). Methods: Information from clinical records was obtained for 899 BT cases, including signs and symptoms, symptom onset, diagnosis date, tumor type and location. Results: Overall, 64% of all tumors were low-grade, 76% were neuroepithelial tumors and 62% gliomas. There were more males than females among neuroepithelial and embryonal tumor cases, but more females with meningeal tumors. The most frequent locations were cerebellum (22%) and frontal (16%) lobe. The most frequent symptom was headaches (60%), overall, as well as for gliomas, embryonal and 'non-neuroepithelial' tumors; it was convulsions/seizures for neuroepithelial tumors other than glioma, and visual signs and symptoms for meningiomas. A cluster analysis showed that headaches and nausea/vomiting was the only combination of symptoms that exceeded a cutoff of 50%, with a joint occurrence of 67%. Overall, the median time from first symptom to diagnosis was 1.42 months (IQR 0.53-4.80); it exceeded 1 year in 12% of cases, though no particular symptom was associated with exceptionally long or short delays.Conclusions: This is the largest clinical epidemiology study of BT in young people conducted so far. Many signs and symptoms were identified, dominated by headaches and nausea/vomiting. Diagnosis was generally rapid but in 12% diagnostic delay exceeded 1 year with none of the symptoms been associated with a distinctly long time until diagnosis. This work was supported by the MOBI-Kids study and the work in this study was obtained from the European Community's Seventh Framework Programme under Grant Agreements Number 226873—the MOBI-Kids Project—and 603794—the GERoNiMO project. Additional funds for the coordination of MOBI-Kids were obtained from the Spanish Ministry of Science and Innovation (MINECO), while complementary funds for the conduct of MOBI-Kids in Spain were obtained from the Spanish Health Research Fund (FIS) of the National Institute for Health Carlos III. Italian participation is partially supported by a Ministry of Health grant (RF-2009-1546284). In Canada, funding was provided by a grant from the Canadian Institutes for Health Research under a peer-reviewed university-industry partnership program that involved the Canadian Wireless Telecommunications Association, who provided technical data on wireless telecommunications practices in Canada. The German study centre received additional support by the Federal Office for Radiation Protection (BfS). Japanese participation in MOBI-Kids was supported by the Ministry of Internal Affairs and Communications. New Zealand participation was supported by Health Research Council and Cure Kids. In France, this study received funds from the French National Agency for Sanitary Safety of Food, Environment and Labour (ANSES, contract FSRF2008-3), French National Cancer Institute (INCa), Pfizer Foundation and League against cancer. India received funding from Board of Research in Nuclear Sciences (BRNS). The funding sources had no role in: the study design; the collection, analysis, and interpretation of data; the writing of the report; and the decision to submit the article for publication.

Children nowadays are overwhelming with luxurious things and have only little or even no money concepts where most of the kids just reach out to their parents for buying anything they want. This could be an issue for parents, hence kids should be taught the value of money and knowing that save their own money is important to purchase anything they desired. This project proposed an innovative way to inculcate saving behaviours in children using an IoT Piggy Bank. This goal-directed approach allows children to set their saving goals (values of their desired items) and form a saving habit slowly through their saving routines toward their saving goals. Every saving made by the children will be tracked in a mobile app and a buzzer will be triggered as a reinforcer to alert children when they do not save regularly. The user acceptance testing (UAT) of the proposed prototype has shown the majority of the parents (90%) agreed that the proposed IoT piggy bank is very suitable for children to instil saving habit. Most of the children have reacted positively where they were having lots of fun when trying on the IoT piggy bank and expressed that they would continue to use it for saving in the future.

Introduction: The rising prevalence of multiple chronic diseases is an important public health issue as it is associated with increased healthcare utilisation. This paper aimed to explore the annual per capita healthcare cost in primary care for patients with multiple chronic diseases (multimorbidity). Methods: This was a retrospective cohort study conducted in a cluster of public primary care clinics in Singapore. De-identified data from electronic medical records were extracted from July 2015 to June 2017. Only patients with at least 1 chronic disease were included in the study. Basic demographic data and healthcare cost were extracted. A list of 20 chronic diseases was considered for multimorbidity. Results: There were 254,377 patients in our study population, of whom 52.8% were female. The prevalence of multimorbidity was 62.4%. The median annual healthcare cost per capita for patients with multimorbidity was about twice the amount compared to those without multimorbidity (SGD683 versus SGD344). The greatest percentage increment in cost was when the number of chronic diseases increased from 2 to 3 (43.0%). Conclusion: Multimorbidity is associated with higher healthcare cost in primary care. Since evidence for the optimal management of multimorbidity is still elusive, prevention or delay in the onset of multimorbidity in the general population is paramount. Keywords: Chronic disease, healthcare cost, multimorbidity, primary care

Although rare, the rate of squamous cell carcinoma of the anus (SCCA) is rising globally. Most patients present with nonmetastatic disease and are curable with appropriate treatment, which has evolved significantly over the last several decades. Before the 1970s, SCCA was managed with radical surgery, resulting in a permanent colostomy. Researchers found that preoperative treatment with chemotherapy and concurrent radiation could achieve a pathologic complete response. After this observation, definitive therapy shifted from radical surgery to sphincter-preserving chemoradiation. Investigations into the necessity of chemotherapy and the optimal regimen found that chemotherapy with mitomycin-C and 5-fluorouracil is required for cure. Further studies evaluating the addition of induction or maintenance chemotherapy, monoclonal antibody therapy, or higher radiation doses have demonstrated no significant benefit to disease control. Advanced radiation delivery with intensity-modulated radiotherapy techniques is now considered the standard of care because of its prospectively determined, favorable acute toxicity profile compared with 3-dimensional conformal radiation. It is important to note that chemoradiation treatment response may be slow (up to 26 weeks) and should be assessed through serial clinical examinations. Today, surgical management of SCCA is reserved only for the lowest risk, early stage tumors or for recurrent/persistent disease. Current studies are evaluating radiation dose de-escalation in early stage disease and radiation dose escalation and the addition of immune checkpoint inhibitors in locally advanced cancers. In reviewing how and why modern-day treatment of SCCA was established, the objective of this report is to reenforce adherence to current treatment paradigms to assure the best possible outcomes for patients.

Objective Determine efficacy of the novel WiiNWalk intervention on walking-related outcomes in older adults with lower limb amputation. Design Multi-site, parallel, evaluator-masked randomized controlled trial. Setting Home-setting in three Canadian cities. Participants Community-dwelling lower limb prosthesis users over 50 years of age. Interventions The WiiNWalk group (n = 38) used modified Wii Fit activities for prosthetic rehabilitation. The attention control group (n = 33) used Big Brain Academy: Wii Degree, comprising of cognitive activities. Both groups completed a 4-week supervised phase with three 1-h sessions/week in groups of three overseen by a clinician via videoconferencing and a 4-week unstructured and unsupervised phase. Main Measures Primary outcome was walking capacity (2 min walk test); secondary outcomes were balance confidence (activities-specific balance confidence scale), dynamic balance (four-step square test), and lower limb functioning (short physical performance battery). Outcomes were compared across time points with repeated measures analysis of covariance, adjusting for baseline and age. Results Mean age was 65.0 (8.4) years, with 179.5 (223.5) months post-amputation and 80% transtibial amputation. No group difference in a 2 min walk test with an effect size: 1.53 95% CI [−3.17, 6.23] m. Activities balance confidence was greater in the WiiNWalk group by 5.53 [2.53, 8.52]%. No group difference in the four-step square test −0.16 [−1.25, 0.92] s, nor short physical performance battery 0.48 [−0.65, 1.61]. A post-hoc analysis showed the greatest difference in balance confidence immediately after an unsupervised phase. Conclusions The WiiNWalk intervention improved balance confidence, but not walking-related physical function in older adult lower limb prosthesis users. Future rehabilitation games should be specific to the amputation context. Clinical Trial Registration number, NCT 01942798.

COVID-19 has resulted in significant disruptions in cancer care. The Illinois Cancer Collaborative (ILCC), a statewide multidisciplinary cancer collaborative, has developed expert recommendations for triage and management of colorectal cancer when disruptions occur in usual care. Such recommendations would be applicable to future outbreaks of COVID-19 or other large-scale disruptions in cancer care.

OBJECTIVE To gather and evaluate veterinarians' perspectives about the impacts of the COVID-19 pandemic on the use of veterinary telehealth and on cat owners' versus dog owners' attitudes toward transmission of the SARS-CoV-2 virus from their pets. SAMPLE 93 respondent veterinarians (47 in primary care practice and 46 in specialty practice). PROCEDURES An online survey was conducted between June 15 and July 15, 2020, and included 21 questions concerning demographics, use of telehealth before and after the onset of the pandemic (before March 15, 2020, and between March 15 and June 15, 2020, respectively), changes in caseloads, and perception of clients' concerns about potential for transmission of the SARS-CoV-2 virus from pets. Reported zip codes informed the collection of census data. RESULTS The level of poverty was significantly lower in zip code areas for respondents who reported telehealth services were (vs were not) offered before the pandemic. The percentage of respondents who reported their practice offered telehealth services increased from 12% (11/93) before the pandemic to 38% (35/93) between March 15 and June 15, 2020. Although most respondents reported owner-expressed concerns over SARS-CoV-2 virus transmission from their pets, most also reported increased caseloads, seeing newly adopted pets, and few discussions of surrender of pets for reasons related to the SARS-CoV-2 virus. CONCLUSIONS AND CLINICAL RELEVANCE Findings indicated that caseloads increased and telehealth services expanded during the pandemic but that there was no evidence of differences in respondent-reported owner concern for SARS-CoV-2 virus transmission from cats versus dogs.

A Man with Altered Mental Status and New Onset of Seizures A 38-year-old man was evaluated in the emergency department because of altered mental status and a first seizure. Examination revealed an ...

Background Cryoballoon pulmonary vein isolation (PVI) is a common therapy for atrial fibrillation (AF). While moderately increased sinus rhythm heart rate (HR) after PVI has been observed, inappropriate sinus tachycardia (IST) is a rare phenomenon. We aimed to investigate the prevalence and natural history of an abnormal sinus HR response after cryoballoon PVI. Methods We included 169/646 (26.2%) patients with AF undergoing PVI with available Holter recordings before and 3, 6 and 12 months after the procedure. Patients with AF on Holter monitoring were excluded. Mean HR increase ≥ 20 bpm or an IST-like pattern (mean HR > 90 bpm or > 80 bpm when beta-blocking agents were used) following PVI was categorised as abnormal sinus HR response. Results Following PVI, mean HR ± standard deviation increased in the entire group from 63.5 ± 8.4 to 69.1 ± 9.9 bpm at 3 months (p p p p = 0.033). However, in patients meeting IST-like pattern criteria, mean HR at 12 months was no longer significantly different from that pre-ablation. Conclusion Few patients had an abnormal sinus HR response after PVI. Peak HR was observed 3 months after PVI, but HR was still significantly increased 12 months post-ablation compared with pre-ablation. An IST-like pattern was rarely observed. In these patients, HR decreased to pre-ablation values within a year.

INTRODUCTION: The COVID-19 pandemic has brought a relatively significant impact on the world. Malaysia implemented a countrywide social isolation strategy to flatten the epidemic curve. As limits on movement and social interaction have come into force, more individuals appear less physically active. OBJECTIVE: To determine the perceived barriers to physical activity among Malaysian young adults during the Covid-19 Pandemic. METHODS AND MATERIALS: Total 217 participants included with age group from 18-40 years old voluntarily participated in this study. Participants were excluded if they were non-Malaysian and had any psychological problems and physical impairment that hindered physical activity. Barrier to Being Active quiz (BBAQ) questionnaire was circulated through various social media platforms from January 2021 to May 2021. Categorical data were presented using simple and absolute frequency on the distribution of sociodemographic profiles and BBAQ responses. Pearson Chi-square with 95% confidence level, p

PURPOSE Precision oncology has transformed the management of advanced cancers through implementation of advanced molecular profiling technologies to identify increasingly defined subsets of patients and match them to appropriate therapy. We report outcomes of a prospective molecular profiling study in a high-volume Asian tertiary cancer center. PATIENTS AND METHODS Patients with advanced cancer were enrolled onto a prospective protocol for genomic profiling, the Individualized Molecular Profiling for Allocation to Clinical Trials Singapore study, at the National Cancer Center Singapore. Primary objective was to identify molecular biomarkers in patient's tumors for allocation to clinical trials. The study commenced in February 2012 and is ongoing, with the results of all patients who underwent multiplex next-generation sequencing (NGS) testing until December 2018 presented here. The results were discussed at a molecular tumor board where recommendations for allocation to biomarker-directed trials or targeted therapies were made. RESULTS One thousand fifteen patients were enrolled with a median age of 58 years (range 20-83 years). Most common tumor types were lung adenocarcinoma (26%), colorectal cancer (15%), and breast cancer (12%). A total of 1,064 NGS assays were performed, on fresh tumor tissue for 369 (35%) and archival tumor tissue for 687 (65%) assays. TP53 (39%) alterations were most common, followed by EGFR (21%), KRAS (14%), and PIK3CA (10%). Of 405 NGS assays with potentially actionable alterations, 111 (27%) were allocated to a clinical trial after molecular tumor board and 20 (4.9%) were enrolled on a molecularly matched clinical trial. Gene fusions were detected in 23 of 311 (7%) patients tested, including rare fusions in new tumor types and known fusions in rare tumors. CONCLUSION Individualized Molecular Profiling for Allocation to Clinical Trials Singapore demonstrates the feasibility of a prospective broad molecular profiling program in an Asian tertiary cancer center, with the ability to develop and adapt to a dynamic landscape of precision oncology.

Tensor factorization has emerged as a powerful method to address the challenges of high dimensionality and sparsity regarding disease development and comorbidity. Chronic diseases have a high likelihood to co-occur, making patients suffering from one chronic disease to have an elevated risk for other diseases in the course of aging. Despite rich results of risk assessment models for chronic diseases, risk prediction considering the complex mechanisms of disease development and comorbidity remains to be under-researched. This research aims to develop tensor factorization-based methods to predict the onset of new chronic diseases through incorporating the comorbidity patterns with the clinical and sequential factors revealed in the electronic health records (EHRs). The efficacy of the proposed methods was validated through predicting the onset of new chronic diseases using the EHRs data for 23 years from a major hospital in Hong Kong. The proposed methods could inform proactive health management programs for at-risk patients with different chronic conditions.

Despite their limitations, unfractionated heparin (UFH) and bivalirudin remain standard-of-care parenteral anticoagulants for percutaneous coronary intervention (PCI). We discovered novel direct thrombin inhibitors (DTIs) from tick salivary transcriptomes and optimised their pharmacologic activity. The most potent, ultravariegin, inhibits thrombin with a Ki of 4.0 pM, 445-fold better than bivalirudin. Unexpectedly, despite their greater antithrombotic effect, variegin/ultravariegin demonstrated less bleeding, achieving a 3-to-7-fold wider therapeutic index in rodent thrombosis and bleeding models. When used in combination with aspirin and ticagrelor in a porcine model, variegin/ultravariegin reduced stent thrombosis compared with antiplatelet therapy alone but achieved a 5-to-7-fold lower bleeding time than UFH/bivalirudin. Moreover, two antibodies screened from a naïve human antibody library effectively reversed the anticoagulant activity of ultravariegin, demonstrating proof-of-principle for antidote reversal. Variegin and ultravariegin are promising translational candidates for next-generation DTIs that may reduce peri-PCI bleeding in the presence of antiplatelet therapy., Bleeding complications limits the use of effective antithrombotics therapeutics. Here, the authors developed next-generation direct thrombin inhibitors with low bleeding risks as safe peri-percutaneous coronary intervention anticoagulants when used in combination with antiplatelets.