Novel point-of-care cytokine biomarker lateral flow test for the screening for sexually transmitted infections and bacterial vaginosis: study protocol of a multicentre multidisciplinary prospective observational clinical study to evaluate the performance and feasibility of the Genital InFlammation Test (GIFT).

INTRODUCTION: A prototype lateral flow device detecting cytokine biomarkers interleukin (IL)-1α and IL-1ß has been developed as a point-of-care test-called the Genital InFlammation Test (GIFT)-for detecting genital inflammation associated with sexually transmitted infections (STIs) and/or bacterial vaginosis (BV) in women. In this paper, we describe the rationale and design for studies that will be conducted in South Africa, Zimbabwe and Madagascar to evaluate the performance of GIFT and how it could be integrated into routine care. METHODS AND ANALYSIS: We will conduct a prospective, multidisciplinary, multicentre, cross-sectional and observational clinical study comprising two distinct components: a biomedical ('diagnostic study') and a qualitative, modelling and economic ('an integration into care study') part. The diagnostic study aims to evaluate GIFT's performance in identifying asymptomatic women with discharge-causing STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG)) and BV. Study participants will be recruited from women attending research sites and family planning services. Several vaginal swabs will be collected for the evaluation of cytokine concentrations (ELISA), STIs (nucleic acid amplification tests), BV (Nugent score) and vaginal microbiome characteristics (16S rRNA gene sequencing). The first collected vaginal swab will be used for the GIFT assay which will be performed in parallel by a healthcare worker in the clinic near the participant, and by a technician in the laboratory. The integration into care study aims to explore how GIFT could be integrated into routine care. Four activities will be conducted: user experiences and/or perceptions of the GIFT device involving qualitative focus group discussions and in-depth interviews with key stakeholders; discrete choice experiments; development of a decision tree classification algorithm; and economic evaluation of defined management algorithms. ETHICS AND DISSEMINATION: Findings will be reported to participants, collaborators and local government for the three sites, presented at national and international conferences, and disseminated in peer-reviewed publications.The protocol and all study documents such as informed consent forms were reviewed and approved by the University of Cape Town Human Research Ethics Committee (HREC reference 366/2022), Medical Research Council of Zimbabwe (MRCZ/A/2966), Comité d'Ethique pour la Recherche Biomédicale de Madagascar (N° 143 MNSAP/SG/AMM/CERBM) and the London School of Hygiene and Tropical Medicine ethics committee (LSHTM reference 28046).Before the start, this study was submitted to the Clinicaltrials.gov public registry (NCT05723484). TRIAL REGISTRATION NUMBER: NCT05723484.

Clinical assessment and management of lumbar spinal stenosis: clinical dilemmas and considerations for surgical referral.

Lumbar spinal stenosis is the leading indication for spine surgery in older adults. Surgery is recommended in clinical guidelines if non-surgical treatments have been provided with insufficient benefit. The difficulty for clinicians is that the current number of randomised controlled trials is low, which creates uncertainty about which treatments to provide. For non-surgical clinicians this paucity of data leads to a clinical dilemma of whether to continue managing the patient or refer to a spine surgeon. This Viewpoint aims to provide an update on the assessment of lumbar spinal stenosis, treatment recommendations, indications for referral to a spine surgeon, and current clinical dilemmas facing non-surgical clinicians and spinal surgeons.

Validation of an Organ Mapping Antibody Panel for Cyclical Immunofluorescence Microscopy on Normal Human Kidneys.

The lack of standardization in antibody validation remains a major contributor to irreproducibility of human research. To address this, we have applied a standardized approach to validate a panel antibodies to identify 18 major cell types and 5 extracellular matrix compartments in the human kidney by immunofluorescence (IF) microscopy. We have used these to generate an organ mapping antibody panel for 2-D and 3-D Cyclical Immunofluorescence (CyCIF) to provide a more detailed method to evaluate of tissue segmentation and volumes using a larger panel of markers than would normally be possible using standard fluorescence microscopy. CyCIF also makes it possible to perform multiplexed IF microscopy of whole slide images, which is a distinct advantage over other multiplexed imaging technologies that are applicable to limited fields of view. This enables a broader view of cell distributions across larger anatomical regions, allowing a better chance to capture localized regions of dysfunction in diseased tissues. These methods are broadly accessible to any laboratory with a fluorescence microscope, enabling spatial cellular phenotyping in normal and disease states. We also provide a detailed solution for image alignment between CyCIF cycles that can be used by investigators to perform these studies without programming experience using open-sourced software. This ability to perform multiplexed imaging without specialized instrumentation or computational skills, opens the door to integration with more highly dimensional molecular imaging modalities such as spatial transcriptomics and imaging mass spectrometry, enabling the discovery of molecular markers of specific cell types and how these are altered in disease.

Variability in the prevalence of depression among adults with chronic pain: UK Biobank analysis through clinical prediction models.

BACKGROUND: The prevalence of depression among people with chronic pain remains unclear due to the heterogeneity of study samples and definitions of depression. We aimed to identify sources of variation in the prevalence of depression among people with chronic pain and generate clinical prediction models to estimate the probability of depression among individuals with chronic pain. METHODS: Participants were from the UK Biobank. The primary outcome was a "lifetime" history of depression. The model's performance was evaluated using discrimination (optimism-corrected C statistic) and calibration (calibration plot). RESULTS: Analyses included 24,405 patients with chronic pain (mean age 64.1 years). Among participants with chronic widespread pain, the prevalence of having a "lifetime" history of depression was 45.7% and varied (25.0-66.7%) depending on patient characteristics. The final clinical prediction model (optimism-corrected C statistic: 0.66; good calibration on the calibration plot) included age, BMI, smoking status, physical activity, socioeconomic status, gender, history of asthma, history of heart failure, and history of peripheral artery disease. Among participants with chronic regional pain, the prevalence of having a "lifetime" history of depression was 30.2% and varied (21.4-70.6%) depending on patient characteristics. The final clinical prediction model (optimism-corrected C statistic: 0.65; good calibration on the calibration plot) included age, gender, nature of pain, smoking status, regular opioid use, history of asthma, pain location that bothers you most, and BMI. CONCLUSIONS: There was substantial variability in the prevalence of depression among patients with chronic pain. Clinically relevant factors were selected to develop prediction models. Clinicians can use these models to assess patients' treatment needs. These predictors are convenient to collect during daily practice, making it easy for busy clinicians to use them.

Are there Sensitive Periods for Skill Development in Male Adolescent Basketball Players?

PURPOSE: Although spurts in physical capacities during adolescence are well-known, little is known about the existence of such spurts in sport-specific skill development, especially during the period of rapid growth in stature. Our aims were to examine the timing, intensity, and sequence of basketball-specific skill spurts aligned with biological [years from peak height velocity (PHV)] rather than chronological age. We then defined putative sensitive periods (windows of optimal development) for each skill aligned to the adolescent growth spurt. METHODS: Altogether, 160 adolescent male basketballers, aged 11-15 years, were tested bi-annually over three consecutive years. The years from attainment of PHV were estimated and six skill tests were aligned to each year from PHV in 3-month intervals. Skill velocities were estimated using a non-smooth polynomial model. RESULTS: Maximal gains in slalom dribble occurred 12 months prior to PHV attainment (intensity = 0.18 m·s-1·year-1), whereas in speed shot shooting (intensity = 9.91 pts·year-1), passing (intensity = 19.13 pts·year-1), and slalom sprint (intensity = 0.19 m·s-1·year-1) these skill spurts were attained 6 months prior to PHV attainment. The mean gains in control dribble (intensity = 0.10 m·s-1·year-1) and defensive movement (intensity = 0.12 m·s-1·year-1) peaks coincided with attainment of PHV. We identified different sized windows for optimal development for each skill. CONCLUSIONS: Peak spurts in skill development, for most basketball skills, were attained at the same time as PHV. The multiple peaks observed within the defined windows of optimal development suggest that there is room for skill improvement even if gains might be greater earlier rather than later in practice. Our findings highlight the need to make coaches aware of where their players are relative to the attainment of PHV since different skills appear to develop differently relative to PHV. Such knowledge may help in designing more relevant training regimes that incorporate the athlete's current growth status so that skill development can be maximized.

Tooth Root Abscess and Mandibular Infections in Old World Camelids: 3 Cases.

There are limited reports of mandibular infections and tooth root abscesses in camels (Old World Camelids). This is in contrast to multiple reports and case series detailing diagnosis, management, and therapy of similar infections in New World Camelids such as llamas and alpacas. The purpose of this case series is to present three cases of camels in North America with these infections and to detail the diagnostics, therapeutic interventions, management, and follow-up of these cases. Radiography was utilized in all three cases, as was sedation and/or anesthesia. Similar to llamas, florfenicol was used for antimicrobial therapy and flunixin meglumine was utilized as a nonsteroidal anti-inflammatory. Some degree of lavage was required for the management of each case. Clinicians should be aware of the potential need for sedation, diagnostic imaging, culture, and extended therapies for the treatment of mandibular and tooth root infections in camels as comparatively described for llamas and alpacas.

Development of a patient decision aid for children and adolescents following anterior cruciate ligament rupture: an international mixed-methods study.

AIM: To develop and user test an evidence-based patient decision aid for children and adolescents who are considering anterior cruciate ligament (ACL) reconstruction. DESIGN: Mixed-methods study describing the development of a patient decision aid. SETTING: A draft decision aid was developed by a multidisciplinary steering group (including various types of health professionals and researchers, and consumers) informed by the best available evidence and existing patient decision aids. PARTICIPANTS: People who ruptured their ACL when they were under 18 years old (ie, adolescents), their parents, and health professionals who manage these patients. Participants were recruited through social media and the network outreach of the steering group. PRIMARY AND SECONDARY OUTCOMES: Semistructured interviews and questionnaires were used to gather feedback on the decision aid. The feedback was used to refine the decision aid and assess acceptability. An iterative cycle of interviews, refining the aid according to feedback and further interviews, was used. Interviews were analysed using reflexive thematic analysis. RESULTS: We conducted 32 interviews; 16 health professionals (12 physiotherapists, 4 orthopaedic surgeons) and 16 people who ruptured their ACL when they were under 18 years old (7 were adolescents and 9 were adults at the time of the interview). Parents participated in 8 interviews. Most health professionals, patients and parents rated the aid's acceptability as good-to-excellent. Health professionals and patients agreed on most aspects of the decision aid, but some health professionals had differing views on non-surgical management, risk of harms, treatment protocols and evidence on benefits and harms. CONCLUSION: Our patient decision aid is an acceptable tool to help children and adolescents choose an appropriate management option following ACL rupture with their parents and health professionals. A clinical trial evaluating the potential benefit of this tool for children and adolescents considering ACL reconstruction is warranted.

Advanced MRI metrics improve the prediction of baseline disease severity for individuals with degenerative cervical myelopathy.

BACKGROUND CONTEXT: Degenerative cervical myelopathy (DCM) is the most common form of atraumatic spinal cord injury globally. Degeneration of spinal discs, bony osteophyte growth and ligament pathology results in physical compression of the spinal cord contributing to damage of white matter tracts and grey matter cellular populations. This results in an insidious neurological and functional decline in patients which can lead to paralysis. Magnetic resonance imaging (MRI) confirms the diagnosis of DCM and is a prerequisite to surgical intervention, the only known treatment for this disorder. Unfortunately, there is a weak correlation between features of current commonly acquired MRI scans ("community MRI, cMRI") and the degree of disability experienced by a patient. PURPOSE: This study examines the predictive ability of current MRI sequences relative to "advanced MRI" (aMRI) metrics designed to detect evidence of spinal cord injury secondary to degenerative myelopathy. We hypothesize that the utilization of higher fidelity aMRI scans will increase the effectiveness of machine learning models predicting DCM severity and may ultimately lead to a more efficient protocol for identifying patients in need of surgical intervention. STUDY DESIGN/SETTING: Single institution analysis of imaging registry of patients with DCM. PATIENT SAMPLE: A total of 296 patients in the cMRI group and 228 patients in the aMRI group. OUTCOME MEASURES: Physiologic measures: accuracy of machine learning algorithms to detect severity of DCM assessed clinically based on the modified Japanese Orthopedic Association (mJOA) scale. METHODS: Patients enrolled in the Canadian Spine Outcomes Research Network registry with DCM were screened and 296 cervical spine MRIs acquired in cMRI were compared with 228 aMRI acquisitions. aMRI acquisitions consisted of diffusion tensor imaging, magnetization transfer, T2-weighted, and T2*-weighted images. The cMRI group consisted of only T2-weighted MRI scans. Various machine learning models were applied to both MRI groups to assess accuracy of prediction of baseline disease severity assessed clinically using the mJOA scale for cervical myelopathy. RESULTS: Through the utilization of Random Forest Classifiers, disease severity was predicted with 41.8% accuracy in cMRI scans and 73.3% in the aMRI scans. Across different predictive model variations tested, the aMRI scans consistently produced higher prediction accuracies compared to the cMRI counterparts. CONCLUSIONS: aMRI metrics perform better in machine learning models at predicting disease severity of patients with DCM. Continued work is needed to refine these models and address DCM severity class imbalance concerns, ultimately improving model confidence for clinical implementation.

Tranexamic acid versus placebo in individuals with intracerebral haemorrhage treated within 2 h of symptom onset (STOP-MSU): an international, double-blind, randomised, phase 2 trial.

BACKGROUND: Tranexamic acid, an antifibrinolytic agent, might attenuate haematoma growth after an intracerebral haemorrhage. We aimed to determine whether treatment with intravenous tranexamic acid within 2 h of an intracerebral haemorrhage would reduce haematoma growth compared with placebo. METHODS: STOP-MSU was an investigator-led, double-blind, randomised, phase 2 trial conducted at 24 hospitals and one mobile stroke unit in Australia, Finland, New Zealand, Taiwan, and Viet Nam. Eligible participants had acute spontaneous intracerebral haemorrhage confirmed on non-contrast CT, were aged 18 years or older, and could be treated with the investigational product within 2 h of stroke onset. Using randomly permuted blocks (block size of 4) and a concealed pre-randomised assignment procedure, participants were randomly assigned (1:1) to receive intravenous tranexamic acid (1 g over 10 min followed by 1 g over 8 h) or placebo (saline; matched dosing regimen) commencing within 2 h of symptom onset. Participants, investigators, and treating teams were masked to group assignment. The primary outcome was haematoma growth, defined as either at least 33% relative growth or at least 6 mL absolute growth on CT at 24 h (target range 18-30 h) from the baseline CT. The analysis was conducted within the estimand framework with primary analyses adhering to the intention-to-treat principle. The primary endpoint and secondary safety endpoints (mortality at days 7 and 90 and major thromboembolic events at day 90) were assessed in all participants randomly assigned to treatment groups who did not withdraw consent to use any data. This study was registered with ClinicalTrials.gov, NCT03385928, and the trial is now complete. FINDINGS: Between March 19, 2018, and Feb 27, 2023, 202 participants were recruited, of whom one withdrew consent for any data use. The remaining 201 participants were randomly assigned to either placebo (n=98) or tranexamic acid (n=103; intention-to-treat population). Median age was 66 years (IQR 55-77), and 82 (41%) were female and 119 (59%) were male; no data on race or ethnicity were collected. CT scans at baseline or follow-up were missing or of inadequate quality in three participants (one in the placebo group and two in the tranexamic acid group), and were considered missing at random. Haematoma growth occurred in 37 (38%) of 97 assessable participants in the placebo group and 43 (43%) of 101 assessable participants in the tranexamic acid group (adjusted odds ratio [aOR] 1·31 [95% CI 0·72 to 2·40], p=0·37). Major thromboembolic events occurred in one (1%) of 98 participants in the placebo group and three (3%) of 103 in the tranexamic acid group (risk difference 0·02 [95% CI -0·02 to 0·06]). By 7 days, eight (8%) participants in the placebo group and eight (8%) in the tranexamic acid group had died (aOR 1·08 [95% CI 0·35 to 3·35]) and by 90 days, 15 (15%) participants in the placebo group and 19 (18%) in the tranexamic acid group had died (aOR 1·61 [95% CI 0·65 to 3·98]). INTERPRETATION: Intravenous tranexamic acid did not reduce haematoma growth when administered within 2 h of intracerebral haemorrhage symptom onset. There were no observed effects on other imaging endpoints, functional outcome, or safety. Based on our results, tranexamic acid should not be used routinely in primary intracerebral haemorrhage, although results of ongoing phase 3 trials will add further context to these findings. FUNDING: Australian Government Medical Research Future Fund.

Dual Basicity and Nucleophilicity of Organosodium Reagents in Benzylic C-H Additions of Toluenes to Diarylethenes and Ketones.

Profiting from the dual high basicity and nucleophilicity of organosodium complexes, here we report the stepwise lateral metalation of a wide range of alkyl arenes (MeAr), mediated by hydrocarbon-soluble NaCH2SiMe3.PMDETA (PMDETA = N,N,N',N'',N''-pentamethyldiethylenetriamine), followed by nucleophilic addition to olenfins of the newly generated NaCH2Ar.PMDETA complexes. This method grants access to a range of functionalised hydrocarbons in excellent yields and can be upgraded to catalytic regimes when using trans-stilbene, a 10 mol% of the alkyl sodium base and toluene as a solvent. Extending this approach to aromatic ketones leads to the formation of stilbenes under mild reaction conditions, resulting from the deprotonative coupling of toluenes with ketones. Combining spectroscopic studies with the trapping and characterisation of key reaction intermediates, mechanistic insights have been gained, advancing the understanding of coordination effects in organosodium chemistry, and shedding light on their special reactivity profiles.

Nasolacrimal duct obstruction prevalence is 0.3% among alpacas evaluated with ophthalmic disease at a veterinary teaching hospital between 2000 and 2023.

OBJECTIVE: To examine the prevalence of nasolacrimal duct (NLD) obstruction in hospital populations and assess signalment, diagnostics, and clinical approaches for alpacas and llamas diagnosed with NLD atresia or obstruction. ANIMALS: 29 alpacas and 2 llamas. CLINICAL PRESENTATION: Medical records were reviewed to identify camelids with NLD evaluated between 2000 and 2023. Signalment, history, physical examination data, diagnosis, and treatments were recorded. Follow-up information was gathered via phone and email questionnaire. Data were evaluated to determine prevalence and describe signalment and treatments for NLD disease. RESULTS: 31 camelids met the inclusion criteria. A total of 8,027 alpacas and 1,998 llamas were seen within the study period at 1 teaching institution. The prevalence of NLD obstruction for this population of alpacas was 0.3% (26/8,027). Nineteen of 31 (61%) camelids presented at 1 year of age or younger. The most common physical exam finding was ocular discharge (68%). The most common diagnosis was NLD atresia (16/31 [51%]). Patency was established by surgical opening or lavage of the NLD. Long-term follow-up was available for 13 alpacas and 2 llamas, of which 11 (73%) had successful outcomes. CLINICAL RELEVANCE: Results indicate that NLD obstruction is a condition that most commonly affects alpacas < 1 year of age and is associated with a good prognosis for treatment success.

Healthcare and economic cost burden of emergency medical services treated non-traumatic shock using a population-based cohort in Victoria, Australia.

OBJECTIVES: We aimed to assess the healthcare costs and impact on the economy at large arising from emergency medical services (EMS) treated non-traumatic shock. DESIGN: We conducted a population-based cohort study, where EMS-treated patients were individually linked to hospital-wide and state-wide administrative datasets. Direct healthcare costs (Australian dollars, AUD) were estimated for each element of care using a casemix funding method. The impact on productivity was assessed using a Markov state-transition model with a 3-year horizon. SETTING: Patients older than 18 years of age with shock not related to trauma who received care by EMS (1 January 2015-30 June 2019) in Victoria, Australia were included in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome assessed was the total healthcare expenditure. Secondary outcomes included healthcare expenditure stratified by shock aetiology, years of life lived (YLL), productivity-adjusted life-years (PALYs) and productivity losses. RESULTS: A total of 21 334 patients (mean age 65.9 (±19.1) years, and 9641 (45.2%) females were treated by EMS with non-traumatic shock with an average healthcare-related cost of $A11 031 per episode of care and total cost of $A280 million. Annual costs remained stable throughout the study period, but average costs per episode of care increased (Ptrend=0.05). Among patients who survived to hospital, the average cost per episode of care was stratified by aetiology with cardiogenic shock costing $A24 382, $A21 254 for septic shock, $A19 915 for hypovolaemic shock and $A28 057 for obstructive shock. Modelling demonstrated that over a 3-year horizon the cohort lost 24 355 YLLs and 5059 PALYs. Lost human capital due to premature mortality led to productivity-related losses of $A374 million. When extrapolated to the entire Australian population, productivity losses approached $A1.5 billion ($A326 million annually). CONCLUSION: The direct healthcare costs and indirect loss of productivity among patients with non-traumatic shock are high. Targeted public health measures that seek to reduce the incidence of shock and improve systems of care are needed to reduce the financial burden of this syndrome.

Episode-Based Cost Sharing to Prospectively Guarantee Patients' Out-of-Pocket Costs.

This Viewpoint proposes episode-based cost sharing as a way to prospectively guarantee out-of-pocket costs for patients while also preventing insurers from absorbing cost differentials created by unexpected complications of care.

Socioeconomic disparities and health literacy: Unraveling the impact on diagnostic and cancer care in Uruguay.

BACKGROUND: Disparities in the timely diagnosis and care of cancer patients, particularly concerning geographical, racial/ethnic, and economic factors, remain a global health challenge. This study explores the multifaceted interplay between socioeconomic status, health literacy, and specific patient perceptions regarding care access and treatment options that impact cancer care in Uruguay. METHODS: Using the Cancer Health Literacy Test, Spanish Version (CHLT-30-DKspa), and a highly comprehensive questionnaire, we dissected the factors influencing the pathway to diagnosis and route of cancer care. This was done to identify delays by analyzing diverse socioeconomic and sex subgroups across multiple healthcare settings. RESULTS: Patients with lower income took longer to get an appointment after showing symptoms (p = 0.02) and longer to get a diagnosis after having an appointment (p = 0.037). Race/ethnicity also had a significant impact on the length of time from symptoms to first appointment (p =0.019), whereas employment status had a significant impact on patients being susceptible to diagnostic delays beyond the advocated 14-day window (p = 0.02). Higher educational levels were positively associated with increased cancer health literacy scores (p = 0.043), revealing the potential to mitigate delays through health literacy-boosting initiatives. Women had significantly higher self-reported symptom duration before seeking an intervention (p = 0.022). We also found many other significant factors effecting treatment delays and cancer health literacy. CONCLUSIONS: While affirming the global pertinence of socioeconomic- and literacy-focused interventions in enhancing cancer care, the findings underscore a complex, gendered, and perceptually influenced healthcare navigation journey. The results highlight the urgent necessity for strategically crafted, globally relevant interventions that transcend equitable access to integrate literacy, gender sensitivity, and patient-perception alignments in pursuit of optimized global cancer care outcomes.

Georgia's Reinsurance Waiver Associated With Decreased Premium Affordability And Enrollment.

Sixteen states have used Section 1332 waivers to implement reinsurance programs that aim to reduce premiums and increase enrollment in the Affordable Care Act's health insurance Marketplaces. Although reinsurance programs have successfully reduced premiums for unsubsidized enrollees, little is known about how reinsurance affects Marketplace premiums, minimum cost of coverage, and enrollment for the large majority of Marketplace enrollees who receive premium subsidies. Using a difference-in-differences analysis of matched counties straddling Georgia's borders to examine Georgia's 2022 implementation of its reinsurance program, we found that reinsurance increased the minimum cost of enrolling in subsidized Marketplace coverage by approximately 30 percent and decreased enrollment by roughly a third for Marketplace enrollees with incomes of 251-400 percent of the federal poverty level. Marketplace reinsurance programs may have the unintended consequences of increasing the minimum cost of subsidized coverage and reducing enrollment. These outcomes are especially relevant in the present policy context of enhanced subsidies, which have substantially reduced the number of unsubsidized enrollees who would benefit most from reinsurance.

The experience of being in acute emergency care following an overdose with suicidal intent: A hermeneutic phenomenological study.

INTRODUCTION: Nurses working within Emergency Departments are frequently required to care for individuals impacted by suicidal behaviour. LITERATURE REVIEW: Published research into the experience of such individuals in emergency care, is limited. Studies identified do not distinguish between self-harming and suicidal behaviour and do not reveal the lived experience in depth. AIM AND METHODOLOGY: This research reveals the lived experience of being in emergency care following an overdose with suicidal intent, through the collection of data while patients are still in hospital. Sixteen semi-structured interviews were conducted with patients on a medical admission ward. The research uses an interpretive hermeneutic phenomenological approach. ANALYSIS: A thematic analysis indicated six key themes: The fear of death and dying, The hospital - a place of safety, Loved ones a reason to live, Feelings of hopelessness, Eclipsed as a suicidal patient, and the Impact of human relationships. DISCUSSION: The findings are discussed and contextualized within wider literature: The fear of death, hopelessness, the role of stigma and shame, including anticipatory stigma, and the impact of kindness and relationships. Implications for practice are outlined, informing how care can be enhanced by nursing staff.

ATI-1777, a Topical Jak1/3 Inhibitor, May Benefit Atopic Dermatitis without Systemic Drug Exposure: Results from Preclinical Development and Phase 2a Randomized Control Study ATI-1777-AD-201.

Introduction: Atopic dermatitis, a chronic, pruritic skin disease, affects 10-30% of children and up to 14% of adults in developed countries. ATI-1777, a potent and selective Jak1/3 inhibitor, was designed with multiple sites of metabolism to deliver local efficacy in the skin and limit systemic exposure. In preclinical studies, ATI-1777 selectively inhibited Jak1/3 with limited systemic exposure and without any adverse effects. Primary objective: The primary goal of this study was to assess the preliminary clinical efficacy of ATI-1777 topical solution in adults with moderate or severe atopic dermatitis. Design: ATI-1777-AD-201, a phase 2a, first-in-human, randomized, double-blind, vehicle-controlled, parallel-group study, evaluated the efficacy, safety, tolerability, and pharmacokinetics of ATI-1777 topical solution in 48 participants with atopic dermatitis over 4 weeks. Primary endpoint: The primary endpoint was a reduction of a modified Eczema Area and Severity Index score from baseline. Results: Reduction was significantly greater in the ATI-1777-treated group on day 28 than in vehicle-treated group (percentage reduction from baseline = 74.45% [standard error = 6.455] and 41.43% [standard error = 6.189], respectively [P < .001]). Average plasma concentrations of ATI-1777 were <5% of the half-maximal inhibitory concentration of ATI-1777 for inhibiting Jak1/3. No deaths or serious adverse events were reported. Conclusion: Topical ATI-1777 does not lead to pharmacologically relevant systemic drug exposure and may reduce clinical signs of atopic dermatitis. Trial Registration: The study was registered at ClinicalTrials.gov with the number NCT04598269.