Tuberculosis treatment spills the beans on Wilson's disease and more.

Drug-induced liver injury (DILI) is an unwarranted problem and has been a scourge in the treatment of tuberculosis (TB) infection in general and children in particular. Usually, when the Antituberculosis treatment (ATT) regime is temporarily interrupted and modified, DILI subsides, and the whole treatment can be completed under supervision. We report a case of ATT-induced DILI not improving despite modification in the ATT regime, which ultimately led to the revealing of a yet unreported constellation of syndromes that included Wilson Disease, 46 XX gonadal dysgenesis, and Mayer Rokitansky Kuster Hauser (MRKH) Syndrome.

A Digital Platform to Support HIV Case Management for Youth and Young Adults: Mixed Methods Feasibility Study.

BACKGROUND: Advances in medical treatments in recent years have contributed to an overall decline in HIV-related opportunistic infections and deaths in youth; however, mortality and morbidity rates in perinatally and nonperinatally infected adolescents and young adults (AYA) living with HIV remain relatively high today. OBJECTIVE: The goal of this project was to assess the use, utility, and cost-effectiveness of PlusCare, a digital app for HIV case management in AYA living with HIV. The app supports routine case management tasks, such as scheduling follow-up visits, sharing documents for review and signature, laboratory test results, and between-visit communications (eg, encouraging messages). METHODS: We conducted a single-group mixed methods pre-post study with HIV case management programs in 2 large urban hospitals in the Boston metro area. Case management staff (case managers [CMs], N=20) and AYA living with HIV participants (N=45) took part in the study with access to PlusCare for up to 15 and 12 months, respectively. RESULTS: The CMs and AYA living with HIV reported mean System Usability Scale scores of 51 (SD 7.9) and 63 (SD 10.6), respectively. Although marginally significant, total charges billed at 1 of the 2 sites compared with the 12 months before app use (including emergency, inpatient, and outpatient charges) decreased by 41% (P=.046). We also observed slight increases in AYA living with HIV self-reported self-efficacy in chronic disease management and quality of life (Health-Related Quality of Life-4) from baseline to the 12-month follow-up (P=.02 and P=.03, respectively) and increased self-efficacy from the 6- to 12-month follow-up (P=.02). There was no significant change in HIV viral suppression, appointment adherence, or medication adherence in this small-sample pilot study. CONCLUSIONS: Although perceived usability was low, qualitative feedback from CMs and use patterns suggested that direct messaging and timely, remote, and secure sharing of laboratory results and documents (including electronic signatures) between CMs and AYA living with HIV can be particularly useful and have potential value in supporting care coordination and promoting patient self-efficacy and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT03758066; https://clinicaltrials.gov/ct2/show/NCT03758066.

Brequinar and dipyridamole in combination exhibits synergistic antiviral activity against SARS-CoV-2 in vitro: Rationale for a host-acting antiviral treatment strategy for COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the associated global pandemic resulting in >400 million infections worldwide and several million deaths. The continued evolution of SARS-CoV-2 to potentially evade vaccines and monoclonal antibody (mAb)-based therapies and the limited number of authorized small-molecule antivirals necessitates the need for development of new drug treatments. There remains an unmet medical need for effective and convenient treatment options for SARS-CoV-2 infection. SARS-CoV-2 is an RNA virus that depends on host intracellular ribonucleotide pools for its replication. Dihydroorotate dehydrogenase (DHODH) is a ubiquitous host enzyme that is required for de novo pyrimidine synthesis. The inhibition of DHODH leads to a depletion of intracellular pyrimidines, thereby impacting viral replication in vitro. Brequinar (BRQ) is an orally available, selective, and potent low nanomolar inhibitor of human DHODH that has been shown to exhibit broad spectrum inhibition of RNA virus replication. However, host cell nucleotide salvage pathways can maintain intracellular pyrimidine levels and compensate for BRQ-mediated DHODH inhibition. In this report, we show that the combination of BRQ and the salvage pathway inhibitor dipyridamole (DPY) exhibits strong synergistic antiviral activity in vitro against SARS-CoV-2 by enhanced depletion of the cellular pyrimidine nucleotide pool. The combination of BRQ and DPY showed antiviral activity against the prototype SARS-CoV-2 as well as the Beta (B.1.351) and Delta (B.1.617.2) variants. These data support the continued evaluation of the combination of BRQ and DPY as a broad-spectrum, host-acting antiviral strategy to treat SARS-CoV-2 and potentially other RNA virus infections.

Clinical profile of hand, foot, and mouth disease and its associated complications among children in Shimoga City, southern Karnataka: A hospital-based study.

Hand, foot, and mouth disease (HFMD) is one of the important public health problems. It has become a common childhood illness in our part of the country. In most instances, this is a mild self-limiting illness. The affected children are often given outpatient care. However, over the last decade, HFMD has emerged as a growing health problem in Asian countries following frequent outbreaks of deaths associated with HFMD caused by a more virulent member of human enterovirus (HEV), namely, HEV71. A hospital-based descriptive study about the clinical presentations and complications of HFMD at the hospitals of Shimoga city between March 2013 and August 2013 is documented and presented here. HFMD was more common in the 1-3-year old age group, with aseptic meningitis being the most common complication. Surveillance of HFMD must be maintained as there is no effective chemoprophylaxis or vaccine available.

Patient and provider perspectives on cellular phone-based technology to improve HIV treatment adherence.

Innovative techniques, potentially using technology, to improve adherence to antiretroviral therapy (ART) may help patients with HIV who struggle with self-care. This qualitative study compared patient and provider participants' perspectives on ART adherence and text messaging as a tool to promote adherence. Thirteen providers and 14 HIV-infected patients identified four main themes: (1) facilitators, (2) barriers to using text message reminders as a medium for ART medication reminders, (3) framing of text message reminders, and (4) patient responsibility and autonomy in the management of their health and wellness. Ease of use, access, convenience, and confidentiality were cited as benefits of a text message-based adherence intervention; while access, cost, difficulty manipulating cellular phones, lack of knowledge/education, and confidentiality were cited as potential barriers. Providers, but not patients, also identified patient apathy and time burden as potential barriers to a text message-based adherence reminder system. Patients and providers felt that personalization of messages, attention to timing, and confidentiality of messages were key factors for a successful text message-based adherence reminder system. Both providers and patients felt that patient responsibility and autonomy over an individual's own health care is an important issue in adherence to medical care. The majority of patients and providers felt that a text message-based adherence reminder system would be beneficial. While patients and providers had many similar views on factors influencing adherence with ART and the use of text messaging to improve adherence, there were some divergent views between the two groups.

Mobile phone tools for field-based health care workers in low-income countries.

In low-income regions, mobile phone-based tools can improve the scope and efficiency of field health workers. They can also address challenges in monitoring and supervising a large number of geographically distributed health workers. Several tools have been built and deployed in the field, but little comparison has been done to help understand their effectiveness. This is largely because no framework exists in which to analyze the different ways in which the tools help strengthen existing health systems. In this article we highlight 6 key functions that health systems currently perform where mobile tools can provide the most benefit. Using these 6 health system functions, we compare existing applications for community health workers, an important class of field health workers who use these technologies, and discuss common challenges and lessons learned about deploying mobile tools.

Liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for monitoring methotrexate in the setting of carboxypeptidase-G2 therapy.

Medications that have a narrow therapeutic window must be regularly monitored to assist in clinical dosing. Methotrexate (MTX) is one such chemotherapeutic agent that is closely monitored using various standard assays. Patients who have renal failure and who are treated using high-dose protocols are often given carboxypeptidase-G2 (CPDG(2)) as a chemoprotective agent. In this setting an inactive metabolite of MTX, 2, 4-diamino-N(10)-methylpteroic acid (DAMPA) is produced. DAMPA cross-reacts with MTX in most immunoassays, thus making them unsuitable for the monitoring of MTX in the setting of CPDG(2) therapy. We describe a rapid LC-MS-MS method that can be used to determine MTX levels in these cases.