Conjugation Chemistry Markedly Impacts Toxicity and Biodistribution of Targeted Nanoparticles, Mediated by Complement Activation.

Conjugation chemistries are a major enabling technology for the development of drug delivery systems, from antibody-drug conjugates to antibody-targeted lipid nanoparticles inspired by the success of the COVID-19 vaccine. However, here it is shown that for antibody-targeted nanoparticles, the most popular conjugation chemistries directly participate in the activation of the complement cascade of plasma proteins. Their activation of complement leads to large changes in the biodistribution of nanoparticles (up to 140-fold increased uptake into phagocytes of the lungs) and multiple toxicities, including a 50% drop in platelet count.

Current out of pocket care costs among HIV and hypertension co-morbid patients in urban and peri-urban Uganda.

Background: Despite improvements to the cascade of HIV care in East Africa, access to care for non-communicable disease co-morbidities like hypertension (HTN) remains a persistent problem. The integration of care for these conditions presents an opportunity to achieve efficiencies in delivery as well as decrease overall costs for patients. This study aims to build evidence on the burden of current out-of-pocket costs of care among HIV-HTN co-morbid patients.

Tackling syndemics by integrating infectious and noncommunicable diseases in health systems of low- and middle-income countries: A narrative systematic review.

The co-occurrence of infectious diseases (ID) and non-communicable diseases (NCD) is widespread, presenting health service delivery challenges especially in low-and middle-income countries (LMICs). Integrated health care is a possible solution but may require a paradigm shift to be successfully implemented. This literature review identifies integrated care examples among selected ID and NCD dyads.

Automated measurement of distance-walked as a "sixth vital sign" for detecting infusion reactions during preclinical testing.

Infusion reactions are a major risk for advanced therapeutics (e.g., engineered proteins nanoparticles, etc.

Impact of the COVID-19 Pandemic on Community Antibiotic Prescribing and Stewardship: A Qualitative Interview Study with General Practitioners in England.

The COVID-19 pandemic has had a profound impact on the delivery of primary care services. We aimed to identify general practitioners' (GPs') perceptions and experiences of how the COVID-19 pandemic influenced antibiotic prescribing and antimicrobial stewardship (AMS) in general practice in England. Twenty-four semi-structured interviews were conducted with 18 GPs at two time-points: autumn 2020 (14 interviews) and spring 2021 (10 interviews).

Public preferences for delayed or immediate antibiotic prescriptions in UK primary care: A choice experiment.

Background: Delayed (or "backup") antibiotic prescription, where the patient is given a prescription but advised to delay initiating antibiotics, has been shown to be effective in reducing antibiotic use in primary care. However, this strategy is not widely used in the United Kingdom. This study aimed to identify factors influencing preferences among the UK public for delayed prescription, and understand their relative importance, to help increase appropriate use of this prescribing option.

What Aspects of Illness Influence Public Preferences for Healthcare Priority Setting? A Discrete Choice Experiment in the UK.

Background: Decisions on funding new healthcare technologies assume that all health improvements are valued equally. However, public reaction to health technology assessment (HTA) decisions suggests there are health attributes that matter deeply to them but are not currently accounted for in the assessment process. We aimed to determine the relative importance of attributes of illness that influence the value placed on alleviating that illness.

Sex Differences in Laterality Are Associated with Reproduction in Threespine Stickleback.

AbstractLaterality, the partitioning of information processing into specific brain hemispheres, is widespread across animal taxa. Substantial unexplained variation in this trait exists, particularly between the sexes, despite multiple identified advantages of lateralization. Here, we demonstrate a relationship among laterality (measured as directional biases), reproduction, and experience of mating and parenting.

Preferences for Medical Consultations from Online Providers: Evidence from a Discrete Choice Experiment in the United Kingdom.

Background: In the UK, consultations for prescription medicines are available via private providers such as online pharmacies. However, these providers may have lower thresholds for prescribing certain drugs. This is a particular concern for antibiotics, given the increasing burden of antimicrobial resistance.

Awareness of Appropriate Antibiotic Use in Primary Care for Influenza-Like Illness: Evidence of Improvement from UK Population-Based Surveys.

Influenza-like illnesses (ILI) account for a significant portion of inappropriate antibiotic use. Patient expectations for antibiotics for ILI are likely to play a substantial role in 'unnecessary' antibiotic consumption. This study aimed to investigate trends in awareness of appropriate antibiotic use and antimicrobial resistance (AMR).

Delayed Antibiotic Prescription by General Practitioners in the UK: A Stated-Choice Study.

Delayed antibiotic prescription in primary care has been shown to reduce antibiotic consumption, without increasing risk of complications, yet is not widely used in the UK. We sought to quantify the relative importance of factors affecting the decision to give a delayed prescription, using a stated-choice survey among UK general practitioners. Respondents were asked whether they would provide a delayed or immediate prescription in fifteen hypothetical consultations, described by eight attributes.

Why do hospital prescribers continue antibiotics when it is safe to stop? Results of a choice experiment survey.

Background: Deciding whether to discontinue antibiotics at early review is a cornerstone of hospital antimicrobial stewardship practice worldwide. In England, this approach is described in government guidance ('Start Smart then Focus'). However, < 10% of hospital antibiotic prescriptions are discontinued at review, despite evidence that 20-30% could be discontinued safely.

Consistency in the strength of laterality in male, but not female, guppies across different behavioural contexts.

Laterality, the division of brain functions into separate hemispheres, is widespread across animal taxa. Lateralized individuals exhibit cognitive advantages yet substantial variation in laterality exists, particularly between the sexes. Why variation is maintained is unknown as few studies consider differences in lateralized behaviours between the sexes, and their underlying selection pressures, across different contexts.

Mind the gap? The platform trial as a working environment.

Background: Trials have become bigger and more complicated due to the complexity introduced by biomarker stratification, and the advent of multi-arm multi-stage trials, and umbrella and basket platform designs. The trials unit at University College London has been at the forefront of this work, with ground-breaking trials such as STAMPEDE and FOCUS4. The trial management and data management teams on these trials have summarised the operational challenges, to enable the broader clinical trials community to learn from their experiences.

Cancer as the "perfect storm"? A qualitative study of public attitudes to health conditions.

Aims: Our aim is to identify important attributes of major diseases that shape how they are perceived by the public.

Methods And Results: Four focus groups among members of the public were recruited, in March and October 2016, and used semistructured discussion to explore important attributes of cancer, heart disease, stroke, dementia, mental illness, and infectious disease. Common themes were identified by using inductive thematic analysis.

Will the reformed Cancer Drugs Fund address the most common types of uncertainty? An analysis of NICE cancer drug appraisals.

Background: One of the functions of the reformed Cancer Drugs Fund in England is as a managed access fund, providing conditional funding for cancer drugs where there is uncertainty in the economic case, and where that uncertainty can be addressed by data collection during two years' use in the NHS. Our study characterises likely sources of such uncertainty, through a review of recent NICE Technology Appraisals.

Methods: Discussions of uncertainty in NICE Appraisal Committees were extracted from published Single Technology Appraisals of cancer drugs, 2014-2016, and categorised inductively.

Emerging recombinant noroviruses identified by clinical and waste water screening.

Norovirus is estimated to cause 677 million annual cases of gastroenteritis worldwide, resulting in 210,000 deaths. As viral gastroenteritis is generally self-limiting, clinical samples for epidemiological studies only partially represent circulating noroviruses in the population and is biased towards severe symptomatic cases. As infected individuals from both symptomatic and asymptomatic cases shed viruses into the sewerage system at a high concentration, waste water samples are useful for the molecular epidemiological analysis of norovirus genotypes at a population level.

A study protocol for a non-randomised comparison trial evaluating the feasibility and effectiveness of a mobile cognitive-behavioural programme with integrated coaching for anxious adults in primary care.

Introduction: Generalised anxiety disorder (GAD) and subclinical GAD are highly prevalent in primary care. Unmanaged anxiety worsens quality of life in patients seen in primary care practices and leads to increased medical utilisation and costs. Programmes that teach patients cognitive-behavioural therapy (CBT) techniques have been shown to improve anxiety and to prevent the evolution of anxiety symptoms to disorders, but access and engagement have hampered integration of CBT into medical settings.

The 'molecularly unstratified' patient: a focus for moral, psycho-social and societal research.

The biomedical paradigm of personalised precision medicine - identification of specific molecular targets for treatment of an individual patient - offers great potential for treatment of many diseases including cancer. This article provides a critical analysis of the promise, the hype and the pitfalls attending this approach. In particular, we focus on 'molecularly unstratified' patients - those who, for various reasons, are not eligible for a targeted therapy.