TMEM106B coding variant is protective and deletion detrimental in a mouse model of tauopathy.

TMEM106B is a risk modifier of multiple neurological conditions, where a single coding variant and multiple non-coding SNPs influence the balance between susceptibility and resilience. Two key questions that emerge from past work are whether the lone T185S coding variant contributes to protection, and if the presence of TMEM106B is helpful or harmful in the context of disease. Here, we address both questions while expanding the scope of TMEM106B study from TDP-43 to models of tauopathy. We generated knockout mice with constitutive deletion of TMEM106B, alongside knock-in mice encoding the T186S knock-in mutation (equivalent to the human T185S variant), and crossed both with a P301S transgenic tau model to study how these manipulations impacted disease phenotypes. We found that TMEM106B deletion accelerated cognitive decline, hind limb paralysis, tau pathology, and neurodegeneration. TMEM106B deletion also increased transcriptional correlation with human AD and the functional pathways enriched in KO:tau mice aligned with those of AD. In contrast, the coding variant protected against tau-associated cognitive decline, synaptic impairment, neurodegeneration, and paralysis without affecting tau pathology. Our findings reveal that TMEM106B is a critical safeguard against tau aggregation, and that loss of this protein has a profound effect on sequelae of tauopathy. Our study further demonstrates that the coding variant is functionally relevant and contributes to neuroprotection downstream of tau pathology to preserve cognitive function.

Identifying infection in chronic wounds in a community setting: A systematic review of diagnostic test accuracy studies.

AIM: To determine the diagnostic accuracy of different methods currently available to identify infection in chronic wounds applicable to adult patients in a community setting. DESIGN: Systematic review of diagnostic test accuracy studies. REVIEW METHODS: Two authors independently completed screening, data extraction and quality and bias assessments (QUADAS2). Eligible studies compared a method (index test) for detecting infection (diagnosis of interest) with microscopy and culture of either deep tissue biopsy or wound swab (reference test) in adult patients with wounds of >4 weeks duration (participants). The results were synthesized narratively. DATA SOURCES: We systematically searched CINAHL, Embase and Medline from 2011 to April 2022. RESULTS: Four studies were included, all recruiting from secondary care wound clinics. Two studies assessed the diagnostic accuracy of Moleculight i:X, a bacterial fluorescence imaging device against deep tissue biopsy culture. One study assessed the diagnostic accuracy of the elevation of various enzymes detected in wound fluid against wound swab microscopy of culture. One study assessed the diagnostic accuracy of bacterial protease activity against wound swab microscopy and culture. Sensitivities of these methods ranged from 50 to 75% and specificities from 47 to 100%. CONCLUSION: Only a small number of studies were included in this systematic review due to our strict inclusion criteria. We have not identified any methods for diagnosing infection in chronic wounds with either a sufficient quality of evidence to recommend their use in community settings at present. Further research is needed to develop and evaluate appropriate diagnostics for this purpose. IMPACT: This study highlights the paucity of research into wound diagnostics in a community setting and should prompt further research in this area. Accurate diagnostic tests have the potential to improve community-based wound care by optimizing antibiotic use and potentially improving healing time. REPORTING METHOD: PRISMA-DTA checklist. PATIENT OR PUBLIC CONTRIBUTION: The PPI group for the NIHR Community Healthcare MIC were supportive of this topic of work.

Motivations for completing pulmonary rehabilitation - A qualitative analysis.

Background: Previous studies have focused on demographic factors that might predict non-completion of pulmonary rehabilitation (PR). We aimed to identify key modifiable factors that promote completion of PR. Methods: A mixed methods survey was offered to participants completing a discharge assessment following PR. Descriptive statistics and inductive thematic analysis were used to analyse the survey responses, with investigator triangulation. Results: 62 of 187 (33%) patients attending a PR discharge assessment between November 2022 and April 2023 returned the anonymised survey. Desire to improve health and wellbeing was the main reason for both initially committing to a course and for continuing with PR past transient thoughts of leaving. The positive impact of staff was the second most common reason. The enjoyment of the PR programme, being held accountable to attend classes, and the importance of other group members were other key themes identified. Conclusions: In conclusion, our findings suggest PR services need to implement strategies which ensure regular promotion and reinforcement of the health benefits of PR as well as implementation of PR modalities which best monopolise on the positive impact skilled staff have on motivating patients to complete PR.

What are important areas where better technology would support women's health? Findings from a priority setting partnership.

BACKGROUND: Women's health has historically lacked investment in research and development. Technologies that enhance women's health ('FemTech') could contribute to improving this. However, there has been little work to understand which priority unmet needs should be a focus for women's health technology development. The voices of clinicians and those who experience and utilise these technologies (including those used at home or encountered in clinical settings) are needed to ensure that device development aligns with need, without risking exacerbating or creating health inequities. METHOD: We undertook a priority setting partnership project exploring unmet needs in women's health and well-being where physical technologies or innovations could help. This comprised gathering feedback from: patients and clinicians using both qualitative surveys and discussions; collating and publishing these responses and asking for feedback; evidence checking unmet needs identified, and holding a partnership priority setting event to agree a top 10 and top 20 list of priorities. RESULTS: We generated a 'longlist' of 54 suggestions for areas where better kit, devices or equipment could support women's health. For three, we found evidence of existing technologies which mitigated against that need. We took the remaining 51 suggestions to a partnership priority setting meeting which brought together clinicians and service users. Through discussion as this group, we generated a list of the top 10 areas identified as priorities for technological development and improvement. These included better devices to manage examination, diagnosis and treatment of pelvic pain (including endometriosis), prolapse care, continence (treatment and prevention, related to pregnancy and beyond), menstruation, vaginal pain and vaginismus, point of care tests for common infections, and nipple care when breastfeeding. CONCLUSION: The top priorities suggest far-reaching areas of unmet need across women's life course and across multiple domains of health and well-being, and opportunities where innovation in the devices that people use themselves or encounter in health settings could potentially enhance health and healthcare experiences.

Gluten-induced Neurocognitive Impairment: Results of a Nationwide Study.

GOALS: This study aimed to understand the neurocognitive symptoms associated with gluten exposure in individuals with self-reported celiac disease (CD) and nonceliac gluten sensitivity (NCGS). BACKGROUND: While gluten-induced neurocognitive impairment (GINI; eg, "celiac fog" or "brain fog") is commonly described by individuals with CD and NCGS, there are little data regarding the prevalence and symptoms associated with these experiences. STUDY: A 9-question online survey was accessed by 1396 individuals (1143 with CD; 253 with NCGS). Forced choice and free-response questions were asked of participants to obtain a description of neurocognitive symptoms experienced after gluten ingestion. Free-response answers were coded using a coding structure developed based on the Health-Related Quality of Life Instrument. RESULTS: The majority of survey participants (89% of CD and 95% of NCGS) reported having GINI symptoms. When describing symptoms, the most common word descriptors for both groups were difficulty concentrating, forgetfulness, and grogginess. Timing of symptoms, including onset and symptom peak, were similar across the 2 groups. Coding of free responses found the most common references were to cognitive, physical, psychological, and overall quality of life impacts. CONCLUSIONS: This survey suggests that GINI is common and may be severe in both individuals with CD and NCGS. Cognitive impairment and decline in physical functioning may be similar to that occurring in other illnesses, such as lupus. Clinical follow-up with both individuals with CD and NCGS should include assessment of GINI symptoms. Further research is warranted, including the development of a patient-reported outcome measure including neurocognitive effects of gluten exposure.

Primary care preparedness for the SARS-CoV-2 pandemic: a survey of NHS GPs.

BACKGROUND: Primary care manages a significant proportion of healthcare in the United Kingdom and should be a key part of the SARS-CoV-2 pandemic response. AIM: To assess preparedness for the SARS-CoV-2 pandemic by understanding GPs' perception of their ability to manage current and future service demand, set-up of triage processes, and training in Covid-19 infection prevention and control procedures. DESIGN AND SETTING: Cross-sectional survey of practicing GPs in the United Kingdom, with 2 rounds of data collection early in the pandemic. METHODS: Online survey, scripted and hosted by medeConnect Healthcare, comprising 6 closed prompts on 7-point Likert scales, and an optional free-text component. Quantitative data were analysed using descriptive statistics. Free-text data were analysed thematically. RESULTS: One thousand two GPs completed each round; 51 GPs completed free-text responses in March, and 64 in April. Quantitative data showed greatest confidence in triage of Covid-19 patients, and GPs were more confident managing current than future Covid-19 demand. GPs' responses were more optimistic and aligned in April than March. Free-text data highlighted that GPs were concerned about lack of appropriate personal protective equipment and personal risk of Covid-19 infection in March, and unmet needs of non-Covid-19 patients in April. In both rounds, GPs expressed feeling overlooked by government and public health bodies. CONCLUSION: Guidance to support general practice clinicians to manage future waves of Covid-19 or other health emergencies must be tailored to general practice from the outset, to support clinicians to manage competing health demands, and mitigate impacts on primary care providers' wellbeing.

The SARS-CoV-2 pandemic has posed significant challenges for the health services in the United Kingdom and abroad. A Doctors Association UK poll published in early March 2020 found that only 1% of 800 GPs believed the NHS was well prepared for the SARS-CoV-2 pandemic. We surveyed 1,002 GPs across the United Kingdom to gauge how well prepared they felt to cope with the challenges posed by Covid-19. We conducted surveys in March and April 2020, an important time early in the pandemic with rapid changes and uncertainty. We found that GPs were more confident about their ability to manage Covid-19 patients, and do so safely, in April. GPs were most confident that they would be able to triage Covid-19 patients but were concerned about future Covid-19 demand. GPs expressed frustration about a lack of personal protective equipment in March. In April, GPs' primary concern was that patients with other health concerns were not being seen. In both samples, GPs expressed feelings of being overlooked by the government. Primary care needs tailored guidance from as early as possible in a health crisis to support clinicians to manage the competing demands of responding to emergency situations, maintain usual care and their own wellbeing.

Parents' concerns and beliefs about temperature measurement in children: a qualitative study.

BACKGROUND: Nearly 40% of parents with children aged 6 to 17 months consult a healthcare professional when their child has a high temperature. Clinical guidelines recommend temperature measurement in these children, but little is known about parents' experiences of and beliefs about temperature measurement. This study aimed to explore parents' concerns and beliefs about temperature measurement in children. METHODS: Semi-structured qualitative interviews were conducted from May 2017 to June 2018 with 21 parents of children aged 4 months to 5.5 years, who were purposively sampled from the METRIC study (a method comparison study comparing non-contact infrared thermometers to axillary and tympanic thermometers in acutely ill children). Data analysis followed a thematic approach. RESULTS: Parents described the importance of being able to detect fever, in particular high fevers, and how this then influenced their actions. The concept of "accuracy" was valued by parents but the aspects of performance which were felt to reflect accuracy varied. Parents used numerical values of temperature in four main ways: determining precision of the thermometer on repeat measures, detecting a "bad" fever, as an indication to administer antipyretics, or monitoring response to treatment. Family and social networks, the internet, and medical professionals and resources, were all key sources of advice for parents regarding fever, and guiding thermometer choice. CONCLUSIONS: Temperature measurement in children has diagnostic value but can either empower, or cause anxiety and practical challenges for parents. This represents an opportunity for both improved communication between parents and healthcare professionals, and technological development, to support parents to manage febrile illness with greater confidence in the home.

Paediatric contacts with the UK out-of-hours primary care service and contact outcomes: a regional service evaluation.

BACKGROUND: Demand on hospital emergency departments for paediatric problems is increasing. However, the volume and nature of paediatric health demands placed on other parts of the urgent care system have not been explored. This understanding is an important first step in developing and improving out-of-hospital care. We aimed to describe the volume, nature, and outcomes of paediatric contacts with out-of-hours general practice (OOH GP). We performed a retrospective service evaluation using data from 12 months of paediatric patient contacts with the Oxfordshire OOH GP service. METHODS: A database of contacts with the Oxfordshire OOH GP service was created for a 12 month period from December 2014 to November 2015. Descriptive statistics were calculated using SPSS Version 25. RESULTS: 27,455 contacts were made by 18,987 individuals during a 12 month period. The majority of these were for children aged under 5. Over 70% of contacts were at the weekend. The peak contact period was between 18:30 and 21:30. Over 40% of contacts resulted in advice only (no onward referral, requirement for GP follow up, or prescription). 19.7% of contacts resulted in an antibiotic prescription, most commonly those linked with ear, chest, and throat infections. DISCUSSION: Paediatric contacts with the Oxfordshire OOH GP service were predominantly in younger age groups and in the evening, with 19.7% resulting in an antibiotic prescription. Almost half of the contacts had no follow up or prescription, suggesting non-prescribing health care professionals could be involved in providing care in OOH GP. Further research should consider how children and their parents can be best supported to optimise OOH consulting.

Amyloid-beta and tau pathology following repetitive mild traumatic brain injury.

Neurodegenerative diseases are characterized by distinctive neuropathological alterations, including the cerebral accumulation of misfolded protein aggregates, neuroinflammation, synaptic dysfunction, and neuronal loss, along with behavioral impairments. Traumatic brain injury (TBI) is believed to be an important risk factor for certain neurodegenerative diseases, such as Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). TBI represents a ubiquitous problem in the world and could play a major role in the pathogenesis and etiology of AD or CTE later in life. TBI events appear to trigger and exacerbate some of the pathological processes in these diseases, in particular, the formation and accumulation of misfolded protein aggregates composed of amyloid-beta (Aß) and tau. Here, we describe the relationship between repetitive mild TBI and the development of Aß and tau pathology in patients affected by AD or CTE on the basis of epidemiological and pathological studies in human cases, and a thorough overview of data obtained in experimental animal models. We also discuss the possibility that TBI may contribute to initiate the formation of misfolded oligomeric species that may subsequently spread the pathology through a prion-like process of seeding of protein misfolding.

Deficits in hippocampal-dependent transfer generalization learning accompany synaptic dysfunction in a mouse model of amyloidosis.

Elevated ß-amyloid and impaired synaptic function in hippocampus are among the earliest manifestations of Alzheimer's disease (AD). Most cognitive assessments employed in both humans and animal models, however, are insensitive to this early disease pathology. One critical aspect of hippocampal function is its role in episodic memory, which involves the binding of temporally coincident sensory information (e.g., sights, smells, and sounds) to create a representation of a specific learning epoch. Flexible associations can be formed among these distinct sensory stimuli that enable the "transfer" of new learning across a wide variety of contexts. The current studies employed a mouse analog of an associative "transfer learning" task that has previously been used to identify risk for prodromal AD in humans. The rodent version of the task assesses the transfer of learning about stimulus features relevant to a food reward across a series of compound discrimination problems. The relevant feature that predicts the food reward is unchanged across problems, but an irrelevant feature (i.e., the context) is altered. Experiment 1 demonstrated that C57BL6/J mice with bilateral ibotenic acid lesions of hippocampus were able to discriminate between two stimuli on par with control mice; however, lesioned mice were unable to transfer or apply this learning to new problem configurations. Experiment 2 used the APPswe PS1 mouse model of amyloidosis to show that robust impairments in transfer learning are evident in mice with subtle ß-amyloid-induced synaptic deficits in the hippocampus. Finally, Experiment 3 confirmed that the same transfer learning impairments observed in APPswePS1 mice were also evident in the Tg-SwDI mouse, a second model of amyloidosis. Together, these data show that the ability to generalize learned associations to new contexts is disrupted even in the presence of subtle hippocampal dysfunction and suggest that, across species, this aspect of hippocampal-dependent learning may be useful for early identification of AD-like pathology.

Major complications associated with fork-based and screw-based tibial tuberosity advancement implants: 438 cases.

This study reports major complications in a large cohort of dogs following tibial tuberosity advancement using either a fork-based or a screw-based implant system. Four hundred thirty-eight stifles were included in the study and major complications occurred in 51 stifles. Explanatory variables evaluated included implant type and body weight. No variables evaluated were associated with major complications.

Complications majeures associées à des implants à base de fourche et de vis lors de chirurgie d'avancement de la tubérosité tibiale antérieure : 438 cas. Cette étude présente un rapport sur les complications majeures dans une grande cohorte de chiens après une chirurgie d'avancement de la tubérosité tibiale à l'aide d'un système d'implant à base de fourche ou de vis. Quatre cent trente-huit grassets ont été inclus dans l'étude et des complications majeures se sont produites dans 51 grassets. Les variables explicatives comprenaient le type d'implant et le poids corporel. Aucune variable évaluée n'a été associée à des complications majeures.(Traduit par Isabelle Vallières).

Attitudes to mesalamine questionnaire: a novel tool to predict mesalamine nonadherence in patients with IBD.

OBJECTIVES: Poor adherence to mesalamine is common and driven by a combination of lifestyle and behavioral factors, as well as health beliefs. We sought to develop a valid tool to identify barriers to patient adherence and predict those at risk for future nonadherence. METHODS: A 10-item survey was developed from patient-reported barriers to adherence. The survey was administered to 106 patients with ulcerative colitis who were prescribed mesalamine, and correlated with prospectively collected 12-month pharmacy refills (medication possession ratio (MPR)), urine levels of salicylates, and self-reported adherence (Morisky Medication Adherence Scale (MMAS)-8). RESULTS: From the initial 10-item survey, 8 items correlated highly with the MMAS-8 score at enrollment. Computer-generated randomization produced a derivation cohort of 60 subjects and a validation cohort of 46 subjects to assess the survey items in their ability to predict future adherence. Two items from the patient survey correlated with objective measures of long-term adherence: their belief in the importance of maintenance mesalamine even when in remission and their concerns about side effects. The additive score based on these two items correlated with 12-month MPR in both the derivation and validation cohorts (P<0.05). Scores on these two items were associated with a higher risk of being nonadherent over the subsequent 12 months (relative risk (RR) =2.2, 95% confidence interval=1.5-3.5, P=0.04). The area under the curve for the performance of this 2-item tool was greater than that of the 10-item MMAS-8 score for predicting MPR scores over 12 months (area under the curve 0.7 vs. 0.5). CONCLUSIONS: Patients' beliefs about the need for maintenance mesalamine and their concerns about side effects influence their adherence to mesalamine over time. These concerns could easily be raised in practice to identify patients at risk of nonadherence (Clinical Trial number NCT01349504).

Five-Repetition Sit-to-Stand Test: Responsiveness and Minimal Important Difference in Idiopathic Pulmonary Fibrosis.

Rationale: Standing from a sitting position is an important activity of daily living. The five-repetition sit-to-stand test (5STS) is a simple physical performance test that measures the fastest time taken to stand five times from a chair with arms folded. It can be measured in most healthcare settings and at home, where traditional field walking tests may not be possible. The 5STS has been validated in community-dwelling older adults and people with chronic obstructive pulmonary disease, but data in idiopathic pulmonary fibrosis (IPF) are limited.Objectives: The aims of this cohort study were to establish the construct validity, responsiveness to pulmonary rehabilitation (PR), and minimal important difference (MID) of the 5STS in IPF.Methods: In 149 people with IPF, we compared the 5STS with measures of lung function, exercise capacity, quadriceps strength, breathlessness, and health-related quality of life. Responsiveness and effect sizes were determined by measuring the 5STS before and after PR. The MID was estimated using anchor- and distribution-based methods.Results: The 5STS correlated significantly with incremental shuttle walk test (ISW) (r = -0.55), isometric quadriceps maximum voluntary contraction (QMVC) (r = -0.45), Medical Research Council dyspnea scale score (r = 0.40), Chronic Respiratory Questionnaire-Total (r = -0.21), and King's Brief Interstitial Lung Disease Questionnaire-Total (r = -0.21) but not forced vital capacity percentage predicted or quadriceps one-repetition maximum (1RM). There was a significant but very weak correlation between change in 5STS and changes in Medical Research Council (r = 0.18), ISW (r = -0.21), and Chronic Respiratory Questionnaire-Total (r = -0.26) but no significant correlation with change in 1RM (r = -0.12) or QMVC (r = -0.18). 5STS time improved with PR (median [25th percentile, 75th percentile] change, -1.97 [-3.47, -0.62] s; P < 0.001). The effect size for the 5STS was 0.66 and higher than quadriceps 1RM, QMVC, and ISW. The mean (range) MID estimate was -1.93 (-1.85 to -2.10) seconds.Conclusions: In people with IPF, the 5STS is a valid physical performance measure that is responsive to exercise-based interventions and suitable for use in most healthcare settings.

MerTK Induces Dysfunctional Dendritic Cells by Metabolic Reprogramming.

Checkpoint inhibitors, specifically anti-PD-1, have shown success in treating metastatic melanoma; however, some patients develop resistance. Dendritic cells (DCs) play a key role in initiating an immune response but in certain circumstances they become ineffective. We investigated the role of MerTK, a receptor tyrosine kinase responsible for myeloid cell clearance of dead cells, in the regulation of DC function and metabolism in the tumor microenvironment. Tumors resistant to anti-PD-1 exhibited increased levels of MerTK+ DCs. Treating wild-type DCs with apoptotic dead melanoma cells in vitro resulted in increased MerTK expression, elevated mitochondrial respiration and fatty acid oxidation, and reduced T-cell stimulatory capacity, all characteristics of dysfunctional DCs. In contrast, dead cells had only limited effect on the metabolism of MerTK-deficient DCs, which instead maintained an antigen presenting, stimulatory phenotype. The efficacy of anti-PD-1 to slow tumor progression and induce specific T-cell infiltration was markedly increased in mice with selective ablation of MerTK in the DC compartment, suggesting the possibility of therapeutically targeting MerTK to modulate DC metabolism and function and enhance anti-PD-1 therapy.

Malignant mixed mullerian tumors: a SEER database review of rurality and treatment modalities on disease outcome.

Introduction: Malignant Mixed Mullerian Tumors (MMMT) are rare and poorly understood sarcomas with limited research on risk factors, pathogenesis, and optimal treatments. This study aimed to address this knowledge gap and explore the impact of community size, patient characteristics, disease characteristics, and treatment modalities on MMMT outcomes. Methods: Using the Surveillance, Epidemiology, and End Results database (SEER), the largest SEER cohort to date of 3,352 MMMT patients was analyzed for demographic factors, treatment modalities, and histologic characteristics. Data was processed, including the removal of incomplete entries, and analyzed in Python 3.1 using packages scikit-learn, lifelines, and torch; log-rank analysis and Cox proportional hazards models were used to evaluate a number of demographic characteristics and disease characteristics for significance in regard to survival. Results: Our study found adjuvant radiotherapy and chemotherapy significantly improved survival, with modest benefits from neoadjuvant chemotherapy. Our findings also suggest age at diagnosis, disease grade, and suburban versus rural geographic locations may play key roles in patient prognosis. On multivariable analysis both disease Grade and surgical treatment were significant factors. Discussion: MMMTs remain challenging, but appropriate treatment appears to enhance survival. The present findings suggest opportunities for improved outcomes and treatment strategies for patients with MMMTs.

Comparing performance of primary care clinicians in the interpretation of SPIROmetry with or without Artificial Intelligence Decision support software (SPIRO-AID): a protocol for a randomised controlled trial.

INTRODUCTION: Spirometry is a point-of-care lung function test that helps support the diagnosis and monitoring of chronic lung disease. The quality and interpretation accuracy of spirometry is variable in primary care. This study aims to evaluate whether artificial intelligence (AI) decision support software improves the performance of primary care clinicians in the interpretation of spirometry, against reference standard (expert interpretation). METHODS AND ANALYSIS: A parallel, two-group, statistician-blinded, randomised controlled trial of primary care clinicians in the UK, who refer for, or interpret, spirometry. People with specialist training in respiratory medicine to consultant level were excluded. A minimum target of 228 primary care clinician participants will be randomised with a 1:1 allocation to assess fifty de-identified, real-world patient spirometry sessions through an online platform either with (intervention group) or without (control group) AI decision support software report. Outcomes will cover primary care clinicians' spirometry interpretation performance including measures of technical quality assessment, spirometry pattern recognition and diagnostic prediction, compared with reference standard. Clinicians' self-rated confidence in spirometry interpretation will also be evaluated. The primary outcome is the proportion of the 50 spirometry sessions where the participant's preferred diagnosis matches the reference diagnosis. Unpaired t-tests and analysis of covariance will be used to estimate the difference in primary outcome between intervention and control groups. ETHICS AND DISSEMINATION: This study has been reviewed and given favourable opinion by Health Research Authority Wales (reference: 22/HRA/5023). Results will be submitted for publication in peer-reviewed journals, presented at relevant national and international conferences, disseminated through social media, patient and public routes and directly shared with stakeholders. TRIAL REGISTRATION NUMBER: NCT05933694.

A SEER database retrospective cohort of 547 patients with penile non-squamous cell carcinoma: demographics, clinical characteristics, and outcomes.

Introduction: Little research has investigated the prevalence and distribution of the diverse pathologies of non-squamous cell carcinoma (non-SCC) of the penis. Although rare in clinical practice, these cancers have become a focus of greater importance among patients, clinicians, and researchers, particularly in developing countries. The principal objective of this study was to analyze the major types of penile non-SCC, elucidate common treatment pathways, and highlight outcomes including 5-year survival. Materials/methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried between 2000 and 2018 to identify a retrospective cohort of patients with penile non-SCC. Demographic information, cancer characteristics, diagnostic methods, treatments administered, and survival were investigated. Results: A total of 547 cases of penile non-SCC were included in the analysis. The most prevalent non-SCC cancers included epithelial neoplasms, not otherwise specified (NOS) (15.4%), unspecified neoplasms (15.2%), basal cell neoplasms (13.9%), blood vessel tumors (13.0%), nevi and melanomas (11.7%), and ductal and lobular neoplasms (9.9%). Over half (56.7%) of patients elected to undergo surgical intervention. Patients rarely received systemic therapy (3.8%) or radiation (4.0%). Five-year survival was 35.5%. Patients who underwent surgery had greater annual survival for 0-10 years compared to those who did not have surgery. Significant differences in survival were found between patients who had regional, localized, and distant metastases (p < 0.05). A significant difference in survival was found for patients married at diagnosis versus those who were unmarried at diagnosis (p < 0.05). Lower survival rates were observed for patients older than 70 years. Discussion: Although less prevalent than SCC, penile non-SCC encompasses a diverse set of neoplasms. Patients in this cohort had a high utilization of surgical management leading to superior outcomes compared to those not receiving surgery. Radiation is an uncommonly pursued treatment pathway. Patient demographics and socioeconomic variables such as marital status may be valuable when investigating cancer outcomes. This updated database analysis can help inform diagnosis, management, and clinical outcomes for this rare group of malignancies.

Mood disorder in idiopathic pulmonary fibrosis: response to pulmonary rehabilitation.

Background: Pulmonary rehabilitation improves mood disorder in COPD, but there are limited data in idiopathic pulmonary fibrosis (IPF). The aims of this cohort study were to investigate whether pulmonary rehabilitation reduces mood disorder in IPF, and estimate the minimal important difference (MID) of the Hospital Anxiety and Depression Scale (HADS). Methods: HADS and core pulmonary rehabilitation outcomes were measured in 166 participants before and after an 8-week, in-person, outpatient pulmonary rehabilitation programme. Anchor- and distribution-based methods were used to calculate the MID of HADS-Anxiety (A) and HADS-Depression (D). Results: Suggestive or probable anxiety and depression (HADS ≥8) were present in 35% and 37% of participants, respectively, at baseline, and this reduced significantly following pulmonary rehabilitation (post-pulmonary rehabilitation: HADS-A 23%, HADS-D 26%). Overall, there was a significant reduction in HADS-D (mean change -1.1, 95% CI -1.6- -0.5), but not HADS-A (-0.6, -1.3-0.15) with pulmonary rehabilitation. Subgroup analysis of those with HADS ≥8 revealed significant improvements in HADS domains (mean change: HADS-A -4.5, 95% CI -5.7- -3.4; median change: HADS-D -4.0, interquartile range -6.0- -1.0). The mean (range) MID estimates for HADS-A and HADS-D were -2 (-2.3- -1.7) and -1.2 (-1.9- -0.5), respectively. Conclusion: In people with IPF and suggestive or probable mood disorder, pulmonary rehabilitation reduces anxiety and depression.

Re-examining advice to complete antibiotic courses: a qualitative study with clinicians and patients.

BACKGROUND: Antibiotic treatment duration may be longer than sometimes needed. Stopping antibiotics early, rather than completing pre-set antibiotic courses, may help reduce unnecessary exposure to antibiotics and antimicrobial resistance (AMR). AIM: To identify clinicians' and patients' views on stopping antibiotics when better (SAWB) for urinary tract infections (UTIs), and to explore comparisons with other acute infections. DESIGN & SETTING: An exploratory qualitative study with general practice clinicians and patients in England. METHOD: Primary care clinicians and patients who had recent UTI experience were recruited in England. Remote one-to-one interviews with clinicians and patients, and one focus group with patients, were conducted. Data were audiorecorded, transcribed, and analysed thematically. RESULTS: Eleven clinicians (seven GPs) and 19 patients (14 with experience of recurrent and/or chronic UTIs) were included. All participants considered SAWB unfamiliar and contradictory to well-known advice to complete antibiotic courses, but were interested in the evidence for risks and benefits of SAWB. Clinicians were amenable if evidence and guidelines supported it, whereas patients were more averse because of concerns about the risk of UTI recurrence and/or complications and AMR. Participants viewed SAWB as potentially more appropriate for longer antibiotic courses and other infections (with longer courses and lower risk of recurrence and/or complications). Participants stressed the need for unambiguous advice and SAWB as part of shared decision making and personalised advice. CONCLUSION: Patients were less accepting of SAWB, whereas clinicians were more amenable to it. Patients and clinicians require good evidence that this novel approach to self-determining antibiotic duration is safe and beneficial. If evidence based, SAWB should be offered with an explanation of why the advice differs from the 'complete the course' instruction, and a clear indication of when exactly to stop antibiotics should be given.