Progressive pulmonary fibrosis: an expert group consensus statement.

This expert group consensus statement emphasises the need for standardising the definition of progressive fibrosing interstitial lung diseases (F-ILDs), with an accurate initial diagnosis being of paramount importance in ensuring appropriate initial management. Equally, case-by-case decisions on monitoring and management are essential, given the varying presentations of F-ILDs and the varying rates of progression. The value of diagnostic tests in risk stratification at presentation and, separately, the importance of a logical monitoring strategy, tailored to manage the risk of progression, are also stressed. The term "progressive pulmonary fibrosis" (PPF) exactly describes the entity that clinicians often face in practice. The importance of using antifibrotic therapy early in PPF (once initial management has failed to prevent progression) is increasingly supported by evidence. Artificial intelligence software for high-resolution computed tomography analysis, although an exciting tool for the future, awaits validation. Guidance is provided on pulmonary rehabilitation, oxygen and the use of non-invasive ventilation focused specifically on the needs of ILD patients with progressive disease. PPF should be differentiated from acute deterioration due to drug-induced lung toxicity or other forms of acute exacerbations. Referral criteria for a lung transplant are discussed and applied to patient needs in severe diseases where transplantation is not realistic, either due to access limitations or transplantation contraindications. In conclusion, expert group consensus guidance is provided on the diagnosis, treatment and monitoring of F-ILDs with specific focus on the recognition of PPF and the management of pulmonary fibrosis progressing despite initial management.

A Framework for Case-Based Learning in Prehospital Medicine: The London's Air Ambulance Experience.

Clinical governance is the framework around which health care organizations can maintain a higher standard of safety and care. One of the central aspects of clinical governance is continuous professional education, including case-based review and case-based learning. In this article, we present the case-based education process in use at London's Air Ambulance, a mature advanced prehospital system in London, UK. The case review process begins with an on-scene hot debrief, an informal process often involving other emergency services. This is usually followed by internal team feedback and debrief and patient follow-up. All cases are then reviewed over the next 24 to 48 hours by the duty prehospital consultant (attending) in the rapid review process. After this, certain cases are volunteered or selected for discussion in the twice weekly death and disability (D&D) meeting or the monthly dispatch meeting. A small subset of cases is highlighted through this process for full formal audit and presentation at the monthly clinical governance meetings based on their educational value. Another subset of cases involving a fatality is also discussed at the monthly clinical pathology correlation meeting with the input of local forensic pathologists. Organization of the process, structure of the meetings, and educational value are described in detail.

Methadone-Assisted Opiate Withdrawal and Subsequent Heroin Abstinence: The Importance of Psychological Preparedness.

BACKGROUND AND OBJECTIVES: Treatment guidelines emphasize patients' readiness for transitioning from opiate substitution treatment (OST) to opiate withdrawal and abstinence. Psychological preparedness indicators for this transition were examined. METHODS: Patients (all male) were recruited from three treatment settings: prison, an inpatient detoxification unit, and an outpatient clinic. Time 1 (T1) was admission to methadone-assisted withdrawal in all settings. Time 2 (T2) was a 6-month follow-up. With n = 24 at T1 for each group (N = 72), a battery of instruments relevant to psychological preparedness was administered. RESULTS: At T1, inpatients had higher self-efficacy beliefs for successful treatment completion than prison patients. For patients contactable at T2, T1 self-efficacy positively predicted T2 opiate abstinence. No other variable improved prediction. T1 SOCRATES (Stages of Change Readiness and Treatment Eagerness Scale) ambivalence scores, age, and lifetime heroin use duration predicted maintenance of contact or not with treatment services and contactability by the researcher. Measures of mood did not differ between groups at T1 or predict T2 outcomes. DISCUSSION AND CONCLUSIONS: Self-efficacy beliefs are a potentially useful indicator of readiness for transitioning from OST to a medically assisted opiate withdrawal and subsequent abstinence. Ambivalence regarding change, age, and lifetime heroin use duration are potentially useful predictors of patients maintaining contact with services, and of being retained in research. SCIENTIFIC SIGNIFICANCE: These findings advance existing literature and knowledge by highlighting the importance of self-efficacy in psychological preparedness for opiate abstinence, and the predictive utility to clinicians of this and other variables measurable at admission, in the clinical management of opiate users. (© 2020 The Authors. The American Journal on Addictions published by Wiley Periodicals LLC on behalf of The American Academy of Addiction Psychiatry). (Am J Addict 2021;30:11-20).

Outcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease. An International Multicenter Study.

Rationale: The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established.Objectives: To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population.Methods: An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non-idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death.Measurements and Main Results: Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio [HR], 1.60; confidence interval, 1.17-2.18; P = 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR, 1.72; 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39-3.71).Conclusions: Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.

A guide to behavioural experiments in bipolar disorder.

Behavioural experiments are an important component of cognitive-behavioural therapy. However, there exists little up-to-date guidance on how to conduct these in people with a diagnosis of bipolar disorder. This paper provides recommendations on how to conduct behavioural experiments in this population. The aim is to upskill and empower clinicians to conduct behavioural experiments. The paper combines the expertise of senior clinicians working in the United Kingdom. The article starts by providing general advice on conducting behavioural experiments in people with bipolar disorder. It then offers specific examples of behavioural experiments targeting cognitions around the uncontrollability and danger of affective states, and related behavioural strategies, which have been implicated in the maintenance of bipolar mood swings. The article finishes by providing examples of behavioural experiments for non-mood related difficulties that commonly occur with bipolar experiences including perfectionistic thinking, need for approval, and intrusive memories. Behavioural experiments offer a useful therapeutic technique for instigating cognitive and behavioural change in bipolar disorder. Conducted sensitively and collaboratively, in line with people's recovery-focused goals, behavioural experiments can be used to overcome mood- and non-mood related difficulties.

A graph-based approach for characterizing resident and nurse handoff conversations.

Prior research has used a variety of qualitative and quantitative approaches for studying handoff communication. Due to the dynamic and interactive nature of handoffs, characterizing the structure and content of these conversations is challenging. In this paper, we use a graph-based approach to characterize handoff communication as a conversation network. Conversation networks were used to compare the structural properties of resident-resident and nurse-nurse handoff communication. Resident (n = 149) and nurse (n = 126) handoff conversations from general medicine units were coded using a previously validated clinical content framework. The coded conversations were then translated into separate resident and nurse conversation networks, and were compared using 11 network measures. Transition probabilities were used to identify commonly repeating sub-networks within resident and nurse conversations. There were significant differences between resident and nurse conversation networks in 10 of the 11 network measures. There were also significant differences in the structure of conversations: compared to resident conversations, nurse conversations were focused on fewer clinical content categories and had more branching and switching between clinical content categories; however, there were clinically-relevant organic relationships in the order of presentation of clinical content among both resident and nurse handoff conversations. We discuss the potential for using graph-based approach as an alternative method for characterizing interactive conversations and also suggest future directions for using network-based approaches for analyzing handoff conversations.

Extraction of amino acids from aerogel for analysis by capillary electrophoresis. Implications for a mission concept to Enceladus' Plume.

Ocean worlds like Europa and Enceladus in the outer solar system are prime targets in the search for life beyond Earth. Enceladus is particularly interesting due to the presence of a water plume ejecting from the south polar region. The recent discovery of H2 in the plume, in addition to the presence of previously observed organic compounds, highlights the possibility of life in this moon. The plume provides materials from the underlying ocean that could be collected simply by flying through it. The presence of the plume means that material from the ocean is available for collection during a flyby, without the need for landing or complex sample handling operations such as scooping or drilling. An attractive approach to preserve the organics in particles collected during flyby encounters would be to utilize silica aerogel, the material used to collect particles at hypervelocity during the Stardust mission. Here we demonstrate amino acids can be extracted from aerogel simply by adding water. This simple liquid extraction method could be implemented during a mission prior to analysis with a liquid-based technique like capillary electrophoresis.

Comparison of trailside degradation across a gradient of trail use in the Sonoran Desert.

As recreational visitation to the Sonoran Desert increases, the concern of scientists, managers and advocates who manage its natural resources deepens. Although many studies have been conducted on trampling of undisturbed vegetation and the effects of trails on adjacent plant and soil communities, little such research has been conducted in the arid southwest. We sampled nine 450-m trail segments with different visitation levels in Scottsdale's McDowell Sonoran Preserve over three years to understand the effects of visitation on soil erosion, trailside soil crusts and plant communities. Soil crust was reduced by 27-34% near medium and high use trails (an estimated peak rate of 13-70 visitors per hour) compared with control plots, but there was less than 1% reduction near low use trails (peak rate of two to four visitors per hour). We did not detect soil erosion in the center 80% of the trampled area of any of the trails. The number of perennial plant species dropped by less than one plant species on average, but perennial plant cover decreased by 7.5% in trailside plots compared with control plots 6 m off-trail. At the current levels of visitation, the primary management focus should be keeping people on the originally constructed trail tread surface to reduce impact to adjacent soil crusts.

FORGE Canada Consortium: outcomes of a 2-year national rare-disease gene-discovery project.

Inherited monogenic disease has an enormous impact on the well-being of children and their families. Over half of the children living with one of these conditions are without a molecular diagnosis because of the rarity of the disease, the marked clinical heterogeneity, and the reality that there are thousands of rare diseases for which causative mutations have yet to be identified. It is in this context that in 2010 a Canadian consortium was formed to rapidly identify mutations causing a wide spectrum of pediatric-onset rare diseases by using whole-exome sequencing. The FORGE (Finding of Rare Disease Genes) Canada Consortium brought together clinicians and scientists from 21 genetics centers and three science and technology innovation centers from across Canada. From nation-wide requests for proposals, 264 disorders were selected for study from the 371 submitted; disease-causing variants (including in 67 genes not previously associated with human disease; 41 of these have been genetically or functionally validated, and 26 are currently under study) were identified for 146 disorders over a 2-year period. Here, we present our experience with four strategies employed for gene discovery and discuss FORGE's impact in a number of realms, from clinical diagnostics to the broadening of the phenotypic spectrum of many diseases to the biological insight gained into both disease states and normal human development. Lastly, on the basis of this experience, we discuss the way forward for rare-disease genetic discovery both in Canada and internationally.

Application of Human Augmentics: A Persuasive Asthma Inhaler.

This article describes a tailored health intervention delivered on a mobile phone platform, integrating low-literacy design strategies and basic principles of behavior change, to promote increased adherence and asthma control among underserved minority adolescents. We based the intervention and design principles on theories of Human Augmentics and the Elaboration Likelihood Model. We tested the efficacy of using electronic monitoring devices that incorporate informative and persuasive elements to improve adherence to a prescribed daily medication regimen intended to reduce use of asthma rescue medications. We describe the theoretical framework, hardware and software systems, and results of user testing for design purposes and a clinical pilot study incorporating use of the device and software by the targeted population. The results of the clinical pilot study showed an 83% completion rate for the treatment as well as improved adherence. Of note, 8% and 58% of participants achieved clinically significant adherence targets at baseline and last week of the study, respectively. Rescue asthma medication use decreased from a median of 3 puffs per week at baseline to 0 puffs per week during the last week of the study.

Recommendations for the management of patients with familial hypercholesterolemia.

Familial hypercholesterolemia (FH), characterized by congenitally elevated low-density lipoprotein cholesterol levels, is estimated to affect 20 million people worldwide. In patients with heterozygous FH, coronary artery disease manifests in about half of men by age 50 and one third of women by age 60, while homozygous FH patients often suffer coronary events in the first or second decade of life. Early diagnosis and aggressive treatment are paramount. However, many FH patients remain undiagnosed and/or inadequately treated. There is a considerable need for more effective screening and diagnosis of FH in the United States. Our objective herein is to provide concise overviews of how to screen for and diagnose FH and summarize international consensus recommendations for managing adults and children with available treatments.

Single whole-leg compression ultrasound for exclusion of deep vein thrombosis in symptomatic ambulatory patients: a prospective observational cohort study.

International guidance has recently recommended serial proximal compression ultrasound (CUS) as first line imaging for suspected deep vein thrombosis (DVT). Single whole-leg CUS is a routine alternative diagnostic strategy that can reduce repeated attendances and identify alternative pathology. We conducted a prospective observational cohort study. Consecutive ambulatory, adult patients with suspected DVT and negative or inconclusive whole-leg CUS had anticoagulation withheld and were followed for 3 months. The primary outcome was a predefined clinically relevant adverse event rate. Secondary outcomes included technical failure, alternative diagnoses and all cause mortality. 212 patients agreed to participate and completed follow up. One patient was subsequently diagnosed with an isolated distal DVT. The adverse event rate was thus 1/212, 0·47% (95% confidence interval [CI] 0·08-2·62). Technical imaging failure occurred in 11·3% of cases (95% CI 7·7-16·3). Several potential predictors of an inconclusive result were identified on multivariate analysis. 150 (70·8%) patients were provided with a documented alternative diagnosis. Patients who have anticoagulation withheld following a negative or inconclusive whole-leg CUS for suspected DVT have a low rate of adverse events. Technical failure remains an issue: several factors were significantly associated with inconclusive results and may warrant an alternative diagnostic approach.

The European Voice of the Patient living with pulmonary hypertension associated with interstitial lung disease: Diagnosis, symptoms, impacts, and treatments.

Pulmonary hypertension (PH) adds a substantial disease burden, including higher mortality, when associated with interstitial lung disease (ILD), a severe, chronic, progressive condition. Yet little is known of the lived experiences, perspectives, priorities, and viewpoints of patients and carers living with PH-ILD. The Voice of the Patient meeting at the center of this qualitative research study aims to provide these difficult-to-obtain insights from a European perspective for the first time. The multistakeholder approach brought together four PH-ILD patients, three primary caregivers, two patient associations, clinical experts, sponsor representatives, and a facilitator. Of the six major themes identified in the thematic analysis, symptoms, and physical limitations were the most impactful. Shortness of breath was the most bothersome symptom affecting patients daily. Further symptoms included fatigue, cough, dizziness, syncope, edema, and palpitations. Physical limitations focused on reduced mobility, impacting patients' ability to perform daily tasks, hobbies, sports, and to enjoy travel. Existing antifibrotic and pulmonary arterial hypertension-targeted treatments were perceived as beneficial. However, despite advances in treatment, severe disease burdens and high unmet medical needs persist from the perspectives of patients. Most meaningful to patients' daily wellbeing was supplemental oxygen, enabling greater mobility. Patients and carers reported difficulties and barriers in navigating the healthcare system and obtaining adequate information to reduce their considerable uncertainties, documenting the substantial challenges that rare and complex conditions such as PH-ILD pose for routine clinical practice beyond PH expert centers and indicating an urgent need for high-quality patient- and clinician-directed information to support patient-centered care.

Clinical effectiveness of drop-in mental health services at paediatric hospitals: A non-randomised multi-site study for children and young people and their families - study protocol.

BACKGROUND: Despite the high prevalence of mental health difficulties in children and young people with long-term health conditions (LTCs), these difficulties and experiences are often overlooked and untreated. Previous research demonstrated the effectiveness of psychological support provided via a drop-in mental health centre located in a paediatric hospital. The aim of this prospective non-randomised single-arm multi-centre interventional study is to determine the clinical effectiveness of drop-in mental health services when implemented at paediatric hospitals in England. METHODS: It is hypothesised that families who receive psychological interventions through the drop-in services will show improved emotional and behavioural symptoms. Outcomes will be measured at baseline and at 6-month follow-up. The primary outcome is the difference in the total difficulties score on the Strengths and Difficulties Questionnaire (SDQ) reported by parent or child at 6 months. Secondary outcomes include self and parent reported Paediatric Quality of Life Inventory (PedsQL), self-reported depression (PHQ-9) and anxiety measures (GAD-7) and family satisfaction (CSQ-8). DISCUSSION: This trial aims to determine the clinical effectiveness of providing psychological support in the context of LTCs through drop-in mental health services at paediatric hospitals in England. These findings will contribute to policies and practice addressing mental health needs in children and young people with other long-term health conditions. TRIAL REGISTRATION: ISRCTN15063954, Registered on 9 December 2022.

Elderly postmenopausal patients with breast cancer are at increased risk for distant recurrence: a tamoxifen exemestane adjuvant multinational study analysis.

INTRODUCTION: For postmenopausal patients with hormone-sensitive breast cancer, outcome is worse with increasing age at diagnosis. The aim of this study was to assess the incidence of breast cancer recurrence (locoregional and distant), and contralateral breast cancer by age at diagnosis. METHODS: Patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were included. Primary endpoints were locoregional recurrence, distant recurrence, and contralateral breast cancer. Age at diagnosis was categorized as younger than 65 years, 65-74 years, and 75 years or older. RESULTS: Overall, 9,766 patients were included, of which 5,349 were younger than 65 years (reference group), 3,060 were 65-74 years, and 1,357 were 75 years or older. With increasing age, a decreased administration of radiotherapy after breast conserving surgery (94%, 92%, and 88%, respectively) and adjuvant chemotherapy (51%, 23%, and 5%, respectively) was observed. Risk of distant recurrence increased with age at diagnosis; multivariable hazard ratio for patients aged 65-74 years was 1.20 (95% confidence interval [CI]: 1.00-1.44), hazard ratio for patients aged 75 years or older was 1.39 (95% CI: 1.08-1.79). Risks of locoregional recurrence and contralateral breast cancer were not significantly different across age groups. CONCLUSION: Elderly patients with breast cancer were at increased risk for distant recurrence. Other studies have shown that the risk of distant recurrence is mainly affected by adjuvant systemic therapy. All TEAM patients received adjuvant endocrine treatment; however, chemotherapy was administered less often in elderly patients. These findings are suggestive for consideration of chemotherapy in relatively fit elderly breast cancer patients with hormone-sensitive disease.

Validation and application of a liquid chromatography-tandem mass spectrometric method for the determination of GDC-0152 in human plasma using solid-phase extraction.

A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of GDC-0152 in human plasma to support clinical development. The method consisted of a solid-phase extraction for sample preparation and LC-MS/MS analysis in the positive ion mode using TurboIonSpray(TM) for analysis. d(7) -GDC-0152 was used as the internal standard. A linear regression (weighted 1/concentration(2) ) was used to fit calibration curves over the concentration range of 0.02-10.0 ng/mL for GDC-0152. There were no endogenous interference components in the blank human plasma tested. The accuracy at the lower limit of quantitation was 99.3% with a precision (%CV) of 13.9%. For quality control samples at 0.0600, 2.00 and 8.00 ng/mL, the between-run %CV was ≤8.64. Between-run percentage accuracy ranged from 98.2 to 99.6%. GDC-0152 was stable in human plasma for 363 days at -20°C and for 659 days at -70°C storage. GDC-0152 was stable in human plasma at room temperature for up to 25 h and through three freeze-thaw cycles. In whole blood, GDC-0152 was stable for 12 h at 4°C and at ambient temperature. This validated LC-MS/MS method for determination of GDC-0152 was used to support clinical studies.