live for ever drugs

Malaria is one of our planet's most widespread and deadliest diseases, and there is an ever-consistent need for new and improved pharmaceuticals. Natural products have been an essential source of hit and lead compounds for drug discovery. Antimalarial drug artemisinin (ART), a highly effective natural product, is an enantiopure sesquiterpene lactone and occurs in Artemisia annua L. The development of improved antimalarial drugs, which are highly potent and at the same time inherently fluorescent is particularly favorable and highly desirable since they can be used for live-cell imaging, avoiding the requirement of the drug's linkage to an external fluorescent label...

In this work, we report on a clinically significant response of meningeal carcinomatosis to repotrectinib in a woman with a heavily pretreated ROS1-rearranged non-small cell lung cancer (NSCLC) that harbored the concomitant solvent front G2032R mutation. Meningeal carcinomatosis has a higher incidence in oncogene addicted NSCLC due to increased life expectancy, yet no report has ever documented the activity of repotrectinib in this context. In line with its activity, we documented the presence of the drug at potentially active concentrations in the cerebrospinal fluid...

BACKGROUND AND AIMS: Treatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver-related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study. METHODS: We included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver-related mortality, as well as the yearly incidence of liver-related events in persons with at least one documented positive HCV-RNA...

With the increasing prevalence of anthelmintic resistance in animals recorded globally, and the threat of resistance in human helminths, the need for novel anthelmintic drugs is greater than ever. Most research aimed at discovering novel anthelmintic leads relies on high throughput screening (HTS) of large libraries of synthetic small molecules in industrial and academic settings in developed countries, even though it is the tropical countries that are most plagued by helminth infections. Tropical countries, however, have the advantage of possessing a rich flora that may yield natural products (NP) with promising anthelmintic activity...

PURPOSE: This study assessed real-world survival among older patients with non-small-cell lung cancer (NSCLC) and brain metastases (BMs) at diagnosis (synchronous BM [SBM]) receiving first-line immune checkpoint inhibitors (ICIs) compared with chemotherapy only. METHODS: Patients with NSCLC and SBM age 65 years or older at diagnosis from 2010 to 2019 SEER-Medicare database and received US Food and Drug Administration-approved ICIs (pembrolizumab/nivolumab/ipilimumab/atezolizumab/durvalumab/cemiplimab) and/or chemotherapy (platinum-based doublets/taxane/pemetrexed/gemcitabine) as first-line systemic treatment were included, excluding those with no cranial radiation or ever being treated with targeted therapies...

INTRODUCTION: While tremendous progress has been made in recent years to improve the health of people living in low- and middle-income countries (LMIC), significant challenges remain. Chief among these are poor health systems, which are often ill-equipped to respond to current challenges. It remains unclear whether intensive intervention at the health system level will result in improved outcomes, as there have been few rigorously designed comparative studies. We present results of a complex health system intervention that was implemented in Zambia using a cluster randomized design...

BACKGROUND: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. METHODS: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires...

Antibiotics which once a boon in medicine and saved millions of lives are now facing an ever-growing menace of antibacterial resistance, which desperately needs new antibacterial drugs which are innovative in chemistry and mode of action. For many years, the world has turned to natural plants with antibacterial properties to combat antibiotic resistance. On that basis, we aimed to identify plants with antibacterial and antibiotic potentiating properties. Seventeen different extracts of 3 plants namely Burkillanthus malaccensis, Diospyros hasseltii and Cleisthanthus bracteosus were tested against multi-drug resistant Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Methicillinresistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA)...

BACKGROUND: Providers' disrespect and abuse of patients is a recognized but understudied issue affecting quality of care and likely affecting healthcare utilization. Little research has examined this issue among people living with HIV (PWH) who inject drugs, despite high stigmatization of this population. No research has examined this issue in the context of Russia. This study assesses patients' reports of disrespect and abuse from providers as a barrier to healthcare and examines the association between these reports and HIV care outcomes...

BACKGROUND AND OBJECTIVES: In Kenya, where abortion is legally restricted, most abortions are induced using unsafe procedures, and lead to complications treated in public health facilities. The introduction of Manual Vacuum Aspiration (MVA) to treat incomplete abortion has improved the management of abortion complications. However, this technology comes with pain whose management has been a challenge. This paper explores the lived experiences of pain (management) during MVA to document the contributing factors...

BACKGROUND: Immigrants represent over one-fifth (21.9%) of the Canadian population, which is an increasing trend. Primary care is a gateway to accessing the healthcare system for the majority of Canadians seeking medical services; however, Canada reported a growing shortage of healthcare providers, mainly primary care practitioners. Canadians, including immigrants, encounter many unmet healthcare needs due to various reasons. This study aimed to assess unmet healthcare (UHC) needs and associated factors among Nepalese immigrants residing in Calgary...

BACKGROUND: E-cigarettes are a popular smoking-cessation tool. Although less harmful than tobacco, use of e-cigarettes by non-smokers should be prevented. There is concern about the use of e-cigarettes by young people and that e-cigarettes may renormalise smoking. In May 2016, Tobacco Products Directive regulations aimed to reduce e-cigarettes' appeal to young people. AIMS: To examine the effects of the Tobacco Products Directive regulations on young people's use of e-cigarettes, and the role of e-cigarettes in renormalising smoking...

BACKGROUND: Dolutegravir (DTG) was scaled up globally to optimize treatment for children living with HIV. We evaluated the rollout and virological outcomes after DTG introduction in Mozambique. METHODS: Data from children 0-14 years with visits from September 2019 to August 2021 were extracted from records in 16 facilities in 12 districts. Among children ever on DTG, we report treatment switches, defined as changes in anchor drug, regardless of changes to nucleoside reverse transcriptase inhibitor (NRTI) backbones...

BACKGROUND: Laparoscopic sacrocolpopexy for pelvic organ prolapse (POP) is a new and widely used approach; however, ever since the United States Food and Drug Administration warned against the use of surgical mesh, repairs performed using patients' tissues [ i.e. native tissue repair (NTR)] instead of mesh have attracted much attention. At our hospital, laparoscopic sacrocolpopexy (the Shull method) was introduced in 2017. However, patients with more severe POP who have a long vaginal canal and overextended uterosacral ligaments may not be candidates for this procedure...

Fungal-derived drugs include some of the most important medicines ever discovered, and have proved pivotal in treating chronic diseases. Not only have they saved millions of lives, but they have in some cases changed perceptions of what is medically possible. However, now the low-hanging fruit have been discovered it has become much harder to make the kind of discoveries that have characterised past eras of fungal drug discovery. This may be about to change with new commercial players entering the market aiming to apply novel genomic tools to streamline the discovery process...

INTRODUCTION: Antimicrobial resistance (AMR) is a global challenge that has raised concern globally due to its detrimental effects on the health and economy of countries. The ever-growing threat of AMR and sources of AMR are still being investigated. Wastewater plays an important role as a habitat for bacteria and an environment conducive to gene transfer. OBJECTIVES: The primary aim of this review was to highlight the contribution of wastewater to antimicrobial resistance...

Background South Africa has a high prevalence of people living with human immunodeficiency virus (HIV; PLWH) who have shown to affect the prevalence and severity of infection and sepsis particularly gallbladder disease.  Empirical Antimicrobial (EA) therapy for acute cholecystitis (AC) is based largely on bacteria colonisation of bile (bacteriobilia) and antimicrobial susceptibility patterns (antibiograms) obtained from the developed world where the prevalence of PLWH is very low. In an ever-emerging era of increasing antimicrobial resistance, monitoring and updating local antibiograms is underscored...

IMPORTANCE: People with serious mental illness (SMI), defined as a diagnosis of schizophrenia spectrum disorder, bipolar disorder, or disabling major depressive disorder) die approximately 10 to 25 years earlier than the general population. OBJECTIVE: To develop the first-ever lived experience-led research agenda to address early mortality in people with SMI. EVIDENCE REVIEW: A virtual 2-day roundtable comprising 40 individuals convened on May 24 and May 26, 2022, and used a virtual Delphi method to arrive at expert group consensus...

PURPOSE: Adolescent refugees are at risk of mental health disorders and underdiagnosed risky behaviors. Limited research exists in the Middle East and North Africa. This study aims to assess psychosocial wellbeing and risk-taking behaviors among adolescent refugees displaced to South Beirut following a standardized framework. METHODS: A cross-sectional study using face-to-face confidential HEEADSSS (Home, Education/Employment, Eating, Activities, Drugs, Sexuality, Safety and Suicide/Depression) interviews was conducted among 52 Syrian adolescent refugees, between the ages of 14 and 21, in a health center in South Beirut...

We conducted a mixed-methods study to understand current drug use practices and access to healthcare services for people who use injection drugs in KwaZulu-Natal, South Africa. We used respondent-driven sampling to recruit 45 people who used injection drugs within the past 6 months from KwaZulu-Natal, South Africa. We found high rates of practices that increase HIV/viral hepatitis risk including the use of shared needles (43%) and direct blood injections (bluetoothing) (18%). Despite 35% living with HIV, only 40% accessed antiretroviral therapy within the past year, and one accessed PrEP...