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Rapid technological advancements in molecular pathology and a continuously growing body of knowledge have resulted in an unprecedented increase in diagnostic complexity for pathologists. (1) This presents a challenge for [...], * Context.-Artificial intelligence algorithms hold the potential to fundamentally change many aspects of society. Application of these tools, including the publicly available ChatGPT, has demonstrated impressive domain-specific knowledge in many areas, including medicine. Objectives.-To understand the level of pathology domain-specific knowledge for ChatGPT using different underlying large language models, GPT-3.5 and the updated GPT-4. Design.-An international group of pathologists (n = 15) was recruited to generate pathology-specific questions at a similar level to those that could be seen on licensing (board) examinations. The questions (n = 15) were answered by GPT-3.5, GPT-4, and a staff pathologist who recently passed their Canadian pathology licensing exams. Participants were instructed to score answers on a 5-point scale and to predict which answer was written by ChatGPT. Results.-GPT-3.5 performed at a similar level to the staff pathologist, while GPT-4 outperformed both. The overall score for both GPT-3.5 and GPT-4 was within the range of meeting expectations for a trainee writing licensing examinations. In all but one question, the reviewers were able to correctly identify the answers generated by GPT-3.5. Conclusions.-By demonstrating the ability of ChatGPT to answer pathology-specific questions at a level similar to (GPT-3.5) or exceeding (GPT-4) a trained pathologist, this study highlights the potential of large language models to be transformative in this space. In the future, more advanced iterations of these algorithms with increased domain-specific knowledge may have the potential to assist pathologists and enhance pathology resident training. (Arch Pathol Lab Med. 2024;148:1152-1158; doi: 10.5858/arpa.2023-0296-OA)

Academic culture now places high expectations on researchers to demonstrate research productivity alongside teaching, leadership and knowledge exchange. In two studies of researchers across career stages in UK higher education institutions (HEIs), we examined workplace climate within academic departments as (1) supportive of researchers' needs for autonomy, competence and relatedness, (2) publish-or-perish focused and (3) hyper-competitive. In Study 1 (multiwave from 2018 to 2020), need support predicted researchers' lower turnover intention 2 years later, even when controlling for concurrent need support, and career and economic conditions. In Study 2, need support correlated with academic well-being (lower job strain and turnover intention, greater job satisfaction) in a nationwide sample of 2951 researchers. Study 2 found that need support related to improved, and a hyper-competitive motivational climate related to undermined, well-being. Results were mixed for publish-or-perish climate. Performative demands can have deleterious effects on researcher well-being.

We outline essential considerations for any study of partial randomisation of research funding, and consider scenarios in which randomised controlled trials (RCTs) would be feasible and appropriate. We highlight the interdependence of target outcomes, sample availability and statistical power for determining the cost and feasibility of a trial. For many choices of target outcome, RCTs may be less practical and more expensive than they at first appear (in large part due to issues pertaining to sample size and statistical power). As such, we briefly discuss alternatives to RCTs. It is worth noting that many of the considerations relevant to experiments on partial randomisation may also apply to other potential experiments on funding processes (as described in The Experimental Research Funder’s Handbook. RoRI, June 2022).

In the UK, the first 'lockdown' of the COVID-19 pandemic necessitated a rapid shift to online learning and digital technologies in Higher Education (HE). While the situation was unprecedented, extant literature on online learning suggested there would be challenges, opportunities, and benefits to this transition, and we sought to understand these via a case study of one UK HEI department at this time. To draw out in-depth and nuanced accounts of this (at time of investigation--unstudied) scenario, qualitative data were collected via semi-structured online interview or written reflection. To explore, identify and understand the experiences from both sides, and with a diverse sample, we purposively recruited both staff (n = 10) and students (n = 12), from various roles and backgrounds, including those with additional learning and/or mental health needs. The 'bricolage' data were analysed inductively, utilising a latent reflexive approach, and organised into a framework around five core themes: 'methods and means of engagement'; 'learning maintenance, destruction and construction'; 'remote education and resource accessibility and literacy'; 'support and communication'; and 'life and learning: responses, adaptations and impacts'. Within these, a range of challenges, successes and, most importantly, future learning and innovation outcomes were identified by staff and students, particularly relevant to working with and supporting students with additional needs in the online learning forum. These discoveries informed a set of practical recommendations, provided here in Box 1, for (rapid implementation of) online learning (in times of stress).

Strong evidence of lung cancer screening’s effectiveness in mortality reduction, as demonstrated in the National Lung Screening Trial (NLST) in the US and the Dutch–Belgian Randomized Lung Cancer Screening Trial (NELSON), has prompted countries to implement formal lung cancer screening programs. However, adoption rates remain largely low. This study aims to understand how lung cancer screening programs are currently performing. It also identifies the barriers and enablers contributing to adoption of lung cancer screening across 10 case study countries: Canada, China, Croatia, Japan, Poland, South Korea and the United States. Adoption rates vary significantly across studied countries. We find five main factors impacting adoption: (1) political prioritization of lung cancer (2) financial incentives/cost sharing and hidden ancillary costs (3) infrastructure to support provision of screening services (4) awareness around lung cancer screening and risk factors and (5) cultural views and stigma around lung cancer. Although these factors have application across the countries, the weighting of each factor on driving or hindering adoption varies by country. The five areas set out by this research should be factored into policy making and implementation to maximize effectiveness and outreach of lung cancer screening programs.

Objectives To develop an engagement method to identify and prioritise local evidence gaps around child and maternal health, that could be addressed using linked routinely collected data from the Born and Bred in (BaBi) studies. Methods We developed a pragmatic, 2-hour online workshop method to engage local stakeholders and members of the public to identify research priorities. Stakeholder groups included parents, early years practitioners, commissioners, and service providers. The workshop involves two parts. The first part places attendees into groups with people from similar stakeholder type backgrounds to discuss areas of child and maternal health they think are important for research using linked routinely collected data. The second part places attendees into new, multidisciplinary groups to prioritise the suggestions put forward in the first part, based on criteria of urgency and importance. Results A pilot workshop identified 17 important and urgent research priorities. Key themes included maternal and infant mental health, diet and childhood obesity, Covid-19, inequalities, infant feeding and labour and delivery. This engagement method has successfully been applied in five local areas that are BaBi study sites. The outputs from these workshops have informed a pipeline of projects for the BaBi Network. Research is currently being carried out that addresses one of these research priorities. Many of the identified research priorities were not suitable for linked data research. Based on the workshop discussions, it is recommended that an understanding of the information captured in routine datasets is developed amongst stakeholders and members of the public, to allow them to better engage with linked data research. Conclusion It is possible to engage a wide range of stakeholders including practitioners, commissioners, service providers and parents in a 2-hour workshop to prioritise research questions to be answered using linked routine data. This is important if research using these data is to inform local decision-making."

Background: Although biosimilar uptake has increased (at a variable pace) in many countries, there have been recent concerns about the long-term sustainability of biosimilar markets. The aim of this manuscript is to assess the sustainability of policies across the biosimilar life cycle in selected countries with a view to propose recommendations for supporting biosimilar sustainability.Methods: The study conducted a comparative analysis across 17 countries from North America, South America, Asia-Pacific, Europe and the Gulf Cooperation Council. Biosimilar policies were identified and their sustainability was assessed based on country-specific reviews of the scientific and grey literature, validation by industry experts and 23 international and local non-industry experts, and two advisory board meetings with these non-industry experts.Results: Given that European countries tend to have more experience with biosimilars and more developed policy frameworks, they generally have higher sustainability scores than the other selected countries. Existing approaches to biosimilar manufacturing and R&D, policies guaranteeing safe and high-quality biosimilars, exemption from the requirement to apply health technology assessment to biosimilars, and initiatives counteracting biosimilar misconceptions are considered sustainable. However, biosimilar contracting approaches, biosimilar education and understanding can be ameliorated in all selected countries. Also, similar policies are sometimes perceived to be sustainable in some markets, but not in others. More generally, the sustainability of the biosimilar landscape depends on the nature of the healthcare system and existing pharmaceutical market access policies, the experience with biosimilar use and policies. This suggests that a general biosimilar policy toolkit that ensures sustainability does not exist, but varies from country to country.Conclusion: This study proposes a set of elements that should underpin sustainable biosimilar policy development over time in a country. At first, biosimilar policies should guarantee the safety and quality of biosimilars, healthy levels of supply and a level of cost savings. As a country gains experience with biosimilars, policies need to optimise uptake and combat any misconceptions about biosimilars. Finally, a country should implement biosimilar policies that foster competition, expand treatment options and ensure a sustainable market environment.

We outline essential considerations for any study of partial randomisation of research funding, and consider scenarios in which randomised controlled trials (RCTs) would be feasible and appropriate. We highlight the interdependence of target outcomes, sample availability and statistical power for determining the cost and feasibility of a trial. For many choices of target outcome, RCTs may be less practical and more expensive than they at first appear (in large part due to issues pertaining to sample size and statistical power). As such, we briefly discuss alternatives to RCTs. It is worth noting that many of the considerations relevant to experiments on partial randomisation may also apply to other potential experiments on funding processes (as described in The Experimental Research Funder’s Handbook. RoRI, June 2022).

Little is known about how researchers in higher education institutions (HEIs) experience and respond to support received from their departments. The present study investigated how support for researchers' autonomy (choice and self-expression), relatedness (through connections with colleagues) and competence (feeling effective in one's work) influenced their attitudes towards an external assessment of research. To do so, we surveyed 598 academics from four HEIs in the UK about their attitudes towards one such external assessment: the Research Excellence Framework (REF), a nationwide assessment of research quality and the subject of debate about research evaluation. Our findings, drawing on self-determination theory, show that departments can shape responses to the REF: individuals whose psychological needs were supported by their academic departments held more positive, and less negative, attitudes towards the REF. This occurred both directly and indirectly through researchers' recognition that the REF had a more positive influence on their research activities and outputs.

Congenital heart disease (CHD) has an incidence of approximately 1%. Over the last decade, sequencing studies including large cohorts of individuals with CHD have begun to unravel the genetic mechanisms underpinning CHD. This includes the identification of variants in cyclin‐dependent kinase 13 (CDK13), in individuals with syndromic CHD. CDK13 encodes a serine/threonine protein kinase. The cyclin partner of CDK13 is cyclin K; this complex is thought to be important in transcription and RNA processing. Pathogenic variants in CDK13 cause CDK13‐related disorder in humans, characterised by intellectual disability and developmental delay, recognisable facial features, feeding difficulties and structural brain defects, with 35% of individuals having CHD. To obtain a greater understanding for the role that this essential protein kinase plays in embryonic heart development, we have analysed a presumed loss of function Cdk13 transgenic mouse model (Cdk13tm1b). The homozygous mutants were embryonically lethal in most cases by E15.5. X‐gal staining showed Cdk13 expression localised to developing facial regions, heart and surrounding areas at E10.5, whereas at E12.5, it was more widely present. In the E15.5 heart, staining was seen throughout. RT‐qPCR showed significant reduction in Cdk13 transcript expression in homozygous compared with WT and heterozygous hearts at E10.5 and E12.5. Detailed morphological 3D analysis of embryonic and postnatal hearts was performed using high‐resolution episcopic microscopy, which affords a more detailed analysis of structures such as cardiac valve leaflets and endocardial cushions, compared with more traditional histological techniques. We show that both the homozygous and heterozygous Cdk13tm1b mutants exhibit a range of CHD, including ventricular septal defects, bicuspid aortic valve, double outlet right ventricle and atrioventricular septal defects. 100% (n = 4) of homozygous hearts displayed CHD. Differential expression was seen in Cdk13tm1b homozygous mutants for two genes known to be necessary for normal heart development. The types of defects, and the presence of CHD in heterozygous mice (17.02%, n = 8/47), are consistent with the CDK13‐related disorder phenotype in humans. This study provides important insights into the effects of reduced function of CDK13 in the mouse heart and contributes to our understanding of the mechanism behind this disorder as a cause of CHD. [ABSTRACT FROM AUTHOR]

Abstract Type 2 diabetes mellitus (T2DM) increases cardiac inflammation which promotes the development of cardiac fibrosis. We sought to determine the impact of circadian disruption on the induction of hyperglycaemia, inflammation and cardiac fibrosis. Methods: Psammomys obesus (P. obesus) were exposed to neutral (12 h light:12 h dark) or short (5 h light:19 h dark) photoperiods and fed a low energy (LE) or high energy (HE) diet for 8 or 20 weeks. To determine daily rhythmicity, P. obesus were euthanised at 2, 8, 14, and 20 h after ‘lights on’. Results: P. obesus exposed to a short photoperiod for 8 and 20 weeks had impaired glucose tolerance following oral glucose tolerance testing, compared to a neutral photoperiod exposure. This occurred with both LE and HE diets but was more pronounced with the HE diet. Short photoperiod exposure also increased myocardial perivascular fibrosis after 20 weeks on LE (51%, P

Abstract Background Congenital heart disease (CHD) occurs in almost 1% of newborn children and is considered a multifactorial disorder. CHD may segregate in families due to significant contribution of genetic factors in the disease etiology. The aim of the study was to identify pathophysiological mechanisms in families segregating CHD. Methods We used whole exome sequencing to identify rare genetic variants in ninety consenting participants from 32 Danish families with recurrent CHD. We applied a systems biology approach to identify developmental mechanisms influenced by accumulation of rare variants. We used an independent cohort of 714 CHD cases and 4922 controls for replication and performed functional investigations using zebrafish as in vivo model. Results We identified 1785 genes, in which rare alleles were shared between affected individuals within a family. These genes were enriched for known cardiac developmental genes, and 218 of these genes were mutated in more than one family. Our analysis revealed a functional cluster, enriched for proteins with a known participation in calcium signaling. Replication in an independent cohort confirmed increased mutation burden of calcium-signaling genes in CHD patients. Functional investigation of zebrafish orthologues of ITPR1, PLCB2, and ADCY2 verified a role in cardiac development and suggests a combinatorial effect of inactivation of these genes. Conclusions The study identifies abnormal calcium signaling as a novel pathophysiological mechanism in human CHD and confirms the complex genetic architecture underlying CHD.

The world is currently dealing with one of the most severe health, economic and social crises in recent memory, through coronavirus disease 2019 (COVID-19). Scholars are converging on the perspective that traditional means of addressing these crises have served their time. On the additional backdrop of a global political landscape in transition, realising a post-pandemic recovery will require new modes of international collaboration with scientific knowledge and expertise figuring more prominently. A smart approach to science diplomacy—to global resilience through knowledge-based cooperation—does not prescribe the content, but rather focuses on the process of science-based international exchange. The new Protocol for Science Diplomacy presented in this policy brief inspires the alignment of shared, cosmopolitan interests and their application to cross-border societal challenges. It comprises a set of 12 procedural and infrastructural principles with which actors can create a space for constructive and productive science diplomacy interactions. These principles are: sensitivity; inclusiveness; transparency; deliberation; reciprocity; complementarity & manoeuvrability; legitimacy; alignment; evaluation; capacities; capabilities; trust. Our Protocol for Science Diplomacy identifies ground rules for international scientific and policy collaboration that enable us, inter alia, to make meaningful steps towards tackling the United Nations’ (UN) Sustainable Development Goals (SDGs) by their 2030 deadline. As such, it offers a roadmap for science diplomacy in the next decade and beyond.

[This corrects the article DOI: 10.1371/journal.pgen.1009679.].

This study investigates the psychological impact of viewing user-generated content depicting extreme real-world violence. Eight threads were harvested from a publicly accessible online discussion forum in which people discussed their experiences of witnessing real-world torture, maiming or death online. Reflexive thematic analysis was used to systematically analyse these threads. The themes capture the contradictory ways in which people react to viewing extreme real-world violence online, with some finding it intensely distressing and others using it as a resource for psychological grounding or (perceived) strengthening. Based on this analysis, we highlight pathways that may lead to the cessation or continuation of viewing such content and argue that greater research on this seemingly common but under-studied experience is warranted. [ABSTRACT FROM AUTHOR]

Numerous genetic studies have established a role for rare genomic variants in Congenital Heart Disease (CHD) at the copy number variation (CNV) and de novo variant (DNV) level. To identify novel haploinsufficient CHD disease genes, we performed an integrative analysis of CNVs and DNVs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm. We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. In addition, we performed variation rate testing for DNVs identified in 2,489 parent-offspring trios. Our analysis revealed 21 genes which were significantly affected by rare CNVs and/or DNVs in probands. Fourteen of these genes have previously been associated with CHD while the remaining genes (FEZ1, MYO16, ARID1B, NALCN, WAC, KDM5B and WHSC1) have only been associated in small cases series or show new associations with CHD. In addition, a systems level analysis revealed affected protein-protein interaction networks involved in Notch signaling pathway, heart morphogenesis, DNA repair and cilia/centrosome function. Taken together, this approach highlights the importance of re-analyzing existing datasets to strengthen disease association and identify novel disease genes and pathways.

BackgroundChronic obstructive lung disease frequently leads to disability. Older patients may experience transitions between states of disability and independence over time.ObjectiveTo identify factors associated with transition between states of disability and independent function in obstructive lung disease.MethodsWe analyzed data on 4,394 participants in the Cardiovascular Health Study who completed prebronchodilator spirometry. We calculated the 1-year probability of developing and resolving impairment in ≥1 instrumental activity of daily living (IADL) or ≥1 activity of daily living (ADL) using transition probability analysis. We identified factors associated with resolving disability using relative risk (RR) regression.ResultsThe prevalence of IADL impairment was higher with moderate (23.9%) and severe (36.9%) airflow obstruction compared to normal spirometry (22.5%; p < 0.001). Among participants with severe airflow obstruction, 23.5% recovered independence in IADLs and 40.5% recovered independence in ADLs. In the adjusted analyses, airflow obstruction predicted the development of IADL, but not ADL impairment. Participants with severe airflow obstruction were less likely to resolve IADL impairment [RR 0.67 and 95% confidence interval (CI) 0.49-0.94]. Compared to the most active individuals (i.e. who walked ≥28 blocks per week), walking less was associated with a decreased likelihood of resolving IADL impairment (7-27 blocks: RR 0.81 and 95% CI 0.69-0.86 and

RationaleRelationships between chronic health conditions and acute infections remain poorly understood. Preclinical studies suggest crosstalk between nervous and immune systems.ObjectivesTo determine bidirectional relationships between cognition and pneumonia.MethodsWe conducted longitudinal analyses of a population-based cohort over 10 years. We determined whether changes in cognition increase risk of pneumonia hospitalization by trajectory analyses and joint modeling. We then determined whether pneumonia hospitalization increased risk of subsequent dementia using a Cox model with pneumonia as a time-varying covariate.Measurements and main resultsOf the 5,888 participants, 639 (10.9%) were hospitalized with pneumonia at least once. Most participants had normal cognition before pneumonia. Three cognition trajectories were identified: no, minimal, and severe rapid decline. A greater proportion of participants hospitalized with pneumonia were on trajectories of minimal or severe decline before occurrence of pneumonia compared with those never hospitalized with pneumonia (proportion with no, minimal, and severe decline were 67.1%, 22.8%, and 10.0% vs. 76.0%, 19.3%, and 4.6% for participants with and without pneumonia, respectively; P < 0.001). Small subclinical changes in cognition increased risk of pneumonia, even in those with normal cognition and physical function before pneumonia (β = -0.02; P < 0.001). Participants with pneumonia were subsequently at an increased risk of dementia (hazard ratio, 2.24 [95% confidence interval, 1.62-3.11]; P = 0.01). Associations were independent of demographics, health behaviors, other chronic conditions, and physical function. Bidirectional relationship did not vary based on severity of disease, and similar associations were noted for those with severe sepsis and other infections.ConclusionsA bidirectional relationship exists between pneumonia and cognition and may explain how a single episode of infection in well-appearing older individuals accelerates decline in chronic health conditions and loss of functional independence.

Background: In recent years, innovation in oncology has created new challenges for pricing and reimbursement systems. Oncology medicines with multiple indications face a number of access challenges: (1) the number of assessments and administrative burden; (2) aligning price to different values of the same product; (3) managing clinical uncertainty at time of launch; and (4) managing budget uncertainty. These challenges impact a range of stakeholders and can result in delayed patient access to life-saving treatments. Consequently, countries have taken steps to facilitate patient access. Methods: Drawing on the experience across Europe we have reviewed different mechanisms countries have adopted that address these challenges. These include approaches aimed directly at the issue, multi-year-multi-indication (MYMI) agreements (BE, NL), and other approaches to manage access: flexible access agreements for new indications with clinical uncertainty (UK); development of a new agreement for each new indication (IT); and immediate access for new indications and bundled assessments (DE). Results: MYMI agreements are valuable where existing rules mean that every indication faces the same upfront evaluation process that delays patient access. They are also useful in managing budget impact and uncertainty. Other approaches that adopt an indication-specific approach helps manage clinical uncertainty at the time of launch and realise different values for the same product. They can help align price to value, even though indication-based pricing does not exist. Bundled assessments reduce the administrative burden for stakeholders, and the benefits of immediate reimbursement is that patient access is not delayed. Conclusion: The challenges for medicines with multiple indications impact a range of stakeholders and can result in delayed patient access to life-saving treatments. MYMI agreements have created a more pragmatic approach to HTA for medicines with multiple indications to ensure both fast and broad patient access. Continued innovation in oncology will require further innovative approaches in pricing and reimbursement. It is important that policymakers, payers and manufacturers engage in early discussions and are willing to find new solutions to help accelerate patient access to innovative therapies.

Background Sudden cardiac death (SCD) is associated with severe coronary heart disease in the great majority of cases. Whether carotid intima‐media thickness (C‐IMT), a known surrogate marker of subclinical atherosclerosis, is associated with risk of SCD in a general population remains unknown. The objective of this study was to investigate the association between C‐IMT and risk of SCD. Methods and Results We examined a total of 20 862 participants: 15 307 participants of the ARIC (Atherosclerosis Risk in Communities) study and 5555 participants of the CHS (Cardiovascular Health Study). C‐IMT and common carotid artery intima‐media thickness was measured at baseline by ultrasound. Presence of plaque was judged by trained readers. Over a median of 23.5 years of follow‐up, 569 participants had SCD (1.81 cases per 1000 person‐years) in the ARIC study. Mean C‐IMT and common carotid artery intima‐media thickness were associated with risk of SCD after adjustment for traditional risk factors and time‐varying adjustors: hazard ratios (HRs) with 95% CIs for fourth versus first quartile were 1.64 (1.15–2.63) and 1.49 (1.05–2.11), respectively. In CHS, 302 participants developed SCD (4.64 cases per 1000 person‐years) over 13.1 years. Maximum C‐IMT was associated with risk of SCD after adjustment: HR (95% CI) for fourth versus first quartile was 1.75 (1.22–2.51). Presence of plaque was associated with 35% increased risk of SCD: HR (95% CI) of 1.37 (1.13–1.67) in the ARIC study and 1.32 (1.04–1.68) in CHS. Conclusions C‐IMT was associated with risk of SCD in 2 biracial community‐based cohorts. C‐IMT may be used as a marker of SCD risk and potentially to initiate early therapeutic interventions to mitigate the risk.

Background Immune checkpoint inhibitors (ICIs) are associated with rheumatic and musculoskeletal immune-related adverse events (irAEs) in 5%–20% of patients. Currently, patients refractory to corticosteroids and conventional disease-modifying antirheumatic drugs (cDMARD) are treated with biological DMARDs (bDMARDs) targeting tumor necrosis factor α (TNFα) and interleukin-6, although without a clear biological rationale. Synovial tissue (ST) biopsy presents a valuable opportunity to investigate irAE pathogenesis and appropriately stratify bDMARD use in refractory irAE patients.Case presentation We provide the first report of comparative, parallel ST and synovial fluid (SF) analyses of severe, cDMARD-refractory, seronegative polyarthritis, classified as a grade 3 irAE occurring in response to nivolumab treatment for metastatic squamous cell lung cancer, in comparison with ST and SF from patients with untreated rheumatoid arthritis (RA). We investigated immunohistochemical labeling of ST cytokine expression as a biological rationale for selecting therapy. Flow cytometric analysis of lymphocytes from ST, SF and blood collected before and after synovial biopsy-guided therapy, in comparison with RA, were evaluated for insights into the immunopathogenesis of irAE. Immunolabeling of ST demonstrated an excess of TNFα cytokine expression. Subsequent treatment with infliximab resulted in resolution of inflammatory symptoms and a significant reduction in C reactive protein levels. Flow cytometric analysis of synovial infiltrates indicated absence of programmed cell death protein-1 (PD-1) receptor positivity despite cessation of nivolumab approximately 200 days prior to the analyzes.Conclusions A deeper understanding of the immunopathogenetic basis of immune activation in irAEs is required in order to select therapy that is likely to be the most effective. This is the first report investigating parallel blood, ST and SF in ICI-induced severe rheumatic irAE. Use of a bDMARD directed by the dominant inflammatory cytokine achieved resolution of synovitis while maintaining cancer remission.

Selective laser sintering (SLS) 3D printing is capable of revolutionising pharmaceutical manufacturing, by producing amorphous solid dispersions in a one-step manufacturing process. Here, 3D-printed formulations loaded with a model BCS class II drug (20% w/w itraconazole) and three grades of hydroxypropyl cellulose (HPC) polymer (-SSL, -SL and -L) were produced using SLS 3D printing. Interestingly, the polymers with higher molecular weights (HPC-L and -SL) were found to undergo a uniform sintering process, attributed to the better powder flow characteristics, compared with the lower molecular weight grade (HPC-SSL). XRPD analyses found that the SLS 3D printing process resulted in amorphous conversion of itraconazole for all three polymers, with HPC-SSL retaining a small amount of crystallinity on the drug product surface. The use of process analytical technologies (PAT), including near infrared (NIR) and Raman spectroscopy, was evaluated, to predict the amorphous content, qualitatively and quantitatively, within itraconazole-loaded formulations. Calibration models were developed using partial least squares (PLS) regression, which successfully predicted amorphous content across the range of 0–20% w/w. The models demonstrated excellent linearity (R2 = 0.998 and 0.998) and accuracy (RMSEP = 1.04% and 0.63%) for NIR and Raman spectroscopy models, respectively. Overall, this article demonstrates the feasibility of SLS 3D printing to produce solid dispersions containing a BCS II drug, and the potential for NIR and Raman spectroscopy to quantify amorphous content as a non-destructive quality control measure at the point-of-care.