Fine particulate matter infiltration at Western Montana residences during wildfire season.

BACKGROUND/AIMS: Wildfire air pollution is a growing public health concern as wildfires increase in size, intensity, and duration in the United States. The public is often encouraged to stay indoors during wildfire smoke events to reduce exposure. However, there is limited information on how much wildfire smoke infiltrates indoors at residences and what household/behavioral characteristics contribute to higher infiltration. We assessed fine particulate matter (PM2.5) infiltration into Western Montana residences during wildfire season. METHODS: We measured continuous outdoor and indoor PM2.5 concentrations from July-October 2022 at 20 residences in Western Montana during wildfire season using low-cost PM2.5 sensors. We used paired outdoor/indoor PM2.5 data from each household to calculate infiltration efficiency (Finf; range 0-1; higher values indicate more outdoor PM2.5 infiltration to the indoor environment) using previously validated methods. Analyses were conducted for all households combined and for various household subgroups. RESULTS: Median (25th percentile, 75th percentile) daily outdoor PM2.5 at the households was 3.7 µg/m3 (2.1, 7.1) during the entire study period and 29.0 µg/m3 (19.0, 49.4) during a 2-week period in September impacted by wildfire smoke. Median daily indoor PM2.5 at the households was 2.5 µg/m3 (1.3, 5.5) overall and 10.4 µg/m3 (5.6, 21.0) during the wildfire period. Overall Finf was 0.34 (95 % Confidence Interval [95%CI]: 0.33, 0.35) with lower values during the wildfire period (0.32; 95%CI: 0.28, 0.36) versus non-wildfire period (0.39; 95%CI: 0.37, 0.42). Indoor PM2.5 concentrations and Finf varied substantially across household subgroups such as household income, age of the home, presence of air conditioning units, and use of portable air cleaners. CONCLUSIONS: Indoor PM2.5 was substantially higher during wildfire-impacted periods versus the rest of the study. Indoor PM2.5 and Finf were highly variable across households. Our results highlight potentially modifiable behaviors and characteristics that can be used in targeted intervention strategies.

Quality of life in patients with primary biliary cholangitis: A cross-geographical comparison.

BACKGROUND & AIMS: Several symptoms impair the quality of life (QoL) of patients with primary biliary cholangitis (PBC). They are reported to vary significantly in different countries. Aim of our study was to explore whether there is a geographical clustering that accounts for symptoms in PBC. METHODS: Data was analysed from four cohorts of PBC patients from the UK, Spain, Japan and Italy using the PBC-27 scale. RESULTS: Overall, 569 patients from four cohorts were identified, including 515 females (90.5%) with a mean age of 61 years. The analysis provided evidence for strict factorial invariance of the scale, a robust indicator of its validity for cross-cultural research. The mean of the fatigue domain of British patients was significantly greater than that of the Japanese (p â€‹< â€‹0.05), Italian (p â€‹< â€‹0.05), and Spanish patients (p â€‹< â€‹0.001). The mean of the cognitive domain after 54 years of age, was significantly greater in the British patients than in the Japanese (p â€‹< â€‹0.05) and Spanish patients (p â€‹< â€‹0.01). However, after 69 years of age, there were not significant differences between countries. The mean of the emotion domain after 54 years of age, was greater in the British that in the Spanish (p â€‹< â€‹0.01) and Italian patients (p â€‹< â€‹0.01). CONCLUSIONS: Differences in the four countries concerning fatigue, cognitive and emotional dysfunction were found. The association of latitude and symptoms might provide new insights into the role of sun exposure, genetics and/or cultural component into disease phenotype in PBC.

Increased sensitivity of Treg cells from patients with PBC to low dose IL-12 drives their differentiation into IFN-γ secreting cells.

IL-12 is a pro-inflammatory cytokine that induces the production of interferon-γ (IFNγ) and favours the differentiation of T helper 1 (Th1) cells. In the presence of IL-12 human Treg cells acquire a Th1-like phenotype with reduced suppressive activity in vitro. Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease characterised by high Th1 and Th17 infiltrating cells, reduced frequencies of Treg cells, and a genetic association with IL-12 signalling. Herein, we sought to evaluate the IL-12 signalling pathway in PBC pathology, by studying human samples from patients with PBC, alongside those with primary Sjögren's syndrome (pSS)(autoimmune disease with IL-12 signalling gene association), primary sclerosing cholangitis (PSC) (cholestatic liver disease without IL-12 gene association) and healthy individuals. Our data revealed that TLR stimulation of PBC (n = 17) and pSS monocytes (n = 6) resulted in significant induction of IL12A mRNA (p < 0.05, p < 0.01, respectively) compared to PSC monocytes (n = 13) and at similar levels to HC monocytes (n = 8). PSC monocytes expressed significantly less IL-12p70 (108 pg/ml, mean) and IL-23 (358 pg/ml) compared to HC (458 pg/ml and 951 pg/ml, respectively) (p < 0.01, p < 0.05). Treg cells from patients with PBC (n = 16) and pSS (n = 3) but not PSC (n = 10) and HC (n = 8) responded to low dose (10 ng/ml) IL-12 stimulation by significant upregulation of IFNγ (mean 277 and 254 pg/ml, respectively) compared to PSC and HC Treg cells (mean 22 and 77 pg/ml, respectively)(p < 0.05). This effect was mediated by the rapid and strong phosphorylation of STAT4 on Treg cells from patients with PBC and pSS (p < 0.05) but not PSC and HC. In the liver of patients with PBC (n = 7) a significantly higher proportion of IL-12Rß2+Tregs (16% on average) was detected (p < 0.05) compared to other liver disease controls (5%)(n = 18) which also showed ex vivo high IFNG and TBET expression. CONCLUSION: Our data show an increased sensitivity of PBC and pSS Treg cells to low dose IL-12 stimulation, providing ongoing support for the importance of the IL12-IL-12Rß2-STAT4 pathway on Treg cells in disease pathogenesis and potentially treatment.

Acute coronary syndrome among older patients: a review.

Ischemic heart disease is the leading cause of mortality worldwide. Due to advances in medicine in the past few decades, life expectancy has increased resulting in an aging population in developed and developing countries. Acute coronary syndrome causes greater morbidity and mortality in this group of older patients, which appears to be due to age-related comorbidities. This review examines the incidence and prevalence of acute coronary syndrome among older patients, examines current treatment strategies, and evaluates the predictors of adverse outcomes. In particular, the impact of frailty on outcomes and the need for frailty assessment in developing future research and management strategies among older patients are discussed.

A novel personal health system with integrated decision support and guidance for the management of chronic liver disease.

A personal health system platform for the management of patients with chronic liver disease that incorporates a novel approach to integrate decision support and guidance through care pathways for patients and their doctors is presented in this paper. The personal health system incorporates an integrated decision support engine that guides patients and doctors through the management of the disease by issuing tasks and providing recommendations to both the care team and the patient and by controlling the execution of a Care Flow Plan based on the results of tasks and the monitored health status of the patient. This Care Flow Plan represents a formal, business process based model of disease management designed off-line by domain experts on the basis of clinical guidelines, knowledge of care pathways and an organisational model for integrated, patient-centred care. In this way, remote monitoring and treatment are dynamically adapted to the patient's actual condition and clinical symptoms and allow flexible delivery of care with close integration of specialists, therapists and care-givers.

Autoimmune pancreatitis - diagnosis, management and longterm follow-up.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is a fibroinflammatory condition affecting the pancreas and could present as a multisystem disorder. Diagnosis and management can pose a diagnostic challenge in certain groups of patients. We report our experience of managing this condition in a tertiary pancreaticobiliary centre in the North East of England. METHODS: Patients were identified from a prospectively maintained database of patients diagnosed with AIP between 2005 and 2013. Diagnosis of definite/probable AIP was based on the revised HISORt criteria. When indicated, patients were treated with steroids and relapses were treated with azathioprine. All patients have been followed up to date. RESULTS: Twenty-two patients were diagnosed with AIP during this period. All patients had pancreatic protocol CT performed while some patients had either MR or EUS as part of the work up. Fourteen out of 22 (64%) had an elevated IgG4 level (mean: 10.9 g/L; range 3.4 - 31 g/L). Four (18%) patients underwent surgery. Extrapancreatic involvement was seen in 15 (68%) patients, with biliary involvement being the commonest. Nineteen (86%) were treated with steroids and five (23%) required further immunosuppression for treatment of relapses. The mean follow up period was 36.94 months (range 7 - 94). CONCLUSION: Autoimmune pancreatitis is being increasingly recognized in the British population. Extrapancreatic involvement, particularly extrahepatic biliary involvement seems to be a frequent feature. Diagnosis should be based on accepted criteria as this significantly reduces the chances of overlooking malignancy. Awareness of this relatively rare condition and a multi-disciplinary team approach will help us to diagnose and treat this condition more effectively thereby reducing unnecessary interventions.

Cardiorespiratory fitness predicts mortality and hospital length of stay after major elective surgery in older people.

OBJECTIVE: This study aimed to define the relationship between cardiorespiratory fitness and age in the context of postsurgery mortality and morbidity in older people. BACKGROUND: Postsurgery mortality and morbidity increase with age. Cardiorespiratory fitness also declines with age, and the independent and linked associations between cardiorespiratory fitness and age on postsurgical mortality and morbidity remain to be determined. METHODS: An unselected consecutive group of 389 adults with a mean age of 66 years (range 26-86 years) underwent cardiorespiratory exercise testing before major hepatobiliary surgery at a single center. Mortality and critical care unit and hospital lengths of stay were collected from patient records. Primary outcomes were in-hospital all-cause mortality after surgery and hospital and critical care lengths of stay. RESULTS: Anaerobic threshold was the most significant independent predictor for postoperative mortality (P = 0.003; ß = -0.657 and odds ratio = 0.52) in 18 of 389 (4.6%) patients who died during their in-hospital stay. Age was not a significant predictor in this model. Older people with normal cardiorespiratory fitness spent the same number of days in the hospital or critical care unit as younger people with similar cardiorespiratory fitness (13 vs 12; P = 0.08 and 1 vs 1; P = 0.103). Patients older than 75 years with low cardiorespiratory fitness spent a median of 11 days longer in hospital (23 vs 12; P < 0.0001) and 2 days longer in critical care (2.9 vs 0.9; P < 0.0001) when compared with patients with adequate cardiorespiratory fitness. CONCLUSIONS: Cardiorespiratory fitness is an independent predictor of mortality and length of hospital stay and provides significantly more accurate prognostic information than age alone. Clinicians should consider both the prognostic value of cardiorespiratory testing and techniques to preserve cardiorespiratory function before elective surgery in older people.

A validated clinical tool for the prediction of varices in PBC: the Newcastle Varices in PBC Score.

BACKGROUND & AIMS: Gastro-oesophageal varices (GOV) can occur in early stage primary biliary cirrhosis (PBC), making it difficult to identify the appropriate time to begin screening with oesophageo-gastro-duodenoscopy (OGD). Our aim was to develop and validate a clinical tool to predict the probability of finding GOV in PBC patients. METHODS: A cross-sectional retrospective study analysing clinical data of 330 PBC patients who underwent an OGD at the Freeman Hospital, Newcastle was used to create a predictive tool, the Newcastle Varices in PBC (NVP) Score, that was externally validated in PBC patients from Cambridge (UK) and Toronto (Canada). RESULTS: 48% of the Newcastle, 31% of the Cambridge, and 22% of the Toronto cohorts of PBC patients had GOV. Twenty-five percent (95% CI 18-32%) of the Newcastle cohort had GOV diagnosed at an index variceal bleed. Of the others, 37% (95% CI 28-46%) bled after a median of 1.5 years (IQR 3.75). Transplant-free survival was significantly better in those without GOV than in those with GOV (p<0.001), but similar in patients with GOV that bled and those that did not (p=0.1). The NVP score (%Probability)=1/[1+exp^-(9.186+0.001*alkaline phosphatase in IU-0.178*albumin in g/L-0.015*platelet × 10(9)) was validated in 2 external cohorts and was highly discriminant (AUROC 0.86). Cost consequences analyses revealed the NVP score to be as accurate as, but more economical than using either OGD directly or other risk scores for screening PBC patients. CONCLUSIONS: The NVP score is an inexpensive, non-invasive, externally validated tool that accurately predicts GOV in PBC.

Submaximal exercise testing predicts perioperative hospitalization after aortic aneurysm repair.

BACKGROUND: Aortic aneurysm repair is a high-risk surgical procedure. Patients are often elderly, with multiple comorbidities that predispose them to perioperative morbidity. Use of endovascular aneurysm repair (EVAR) has increased due to reduced early perioperative risk. This study assessed whether preoperative cardiopulmonary exercise testing (CPET) could be used to predict morbidity and hospital length of stay (LOS) after aortic aneurysm repair. METHODS: A total of 185 patients underwent surgical repair (84 open repairs, 101 EVAR) and had adequate determination of a submaximal CPET parameter (anaerobic threshold). RESULTS: Patient comorbidities and cardiorespiratory fitness, derived from CPET, were similar between surgical procedures. Patients undergoing EVAR had fewer complications (10% vs 32%; P<.0001) and shorter mean (standard deviation [SD]) hospital LOS of 5.7 (9.3) days vs 14.4 (10.9) days compared with open repair (P<.0001). The hospital LOS was significantly increased in patients with one or more complications in both groups compared with those with no complications. In the open repair group, the level of fitness, as defined by anaerobic threshold, was an independent predictor of postoperative morbidity and hospital LOS. When the optimal anaerobic threshold (10 mL/min/kg) derived from receiver operator curve analysis was used as a cutoff value, unfit patients stayed significantly longer than fit patients in critical care (mean, 6.4 [SD, 6.9] days vs 2.4 [SD, 2.9] days; P=.002) and in the hospital (mean, 23.1 [SD, 14.8] days vs 11.0 [SD, 6.1] days; P<.0001). In contrast, fitness in the EVAR group was not predictive of postoperative morbidity but did have predictive value for hospital LOS. CONCLUSIONS: Cardiorespiratory fitness holds significant clinical value before aortic aneurysm repair in predicting postsurgical complications and duration of critical care and hospital LOS. Preoperative measurement of fitness could then direct clinical management with regard to operative choice, postoperative resource allocation, and informed patient decision making.

Patient-reported outcomes: assessment and current perspectives of the guidelines of the Food and Drug Administration and the reflection paper of the European Medicines Agency.

AIMS: Patient-reported outcomes (PROs) have recently gained greater credibility with regulatory bodies aiming to standardise their use and interpretation in RCTs, thereby supporting medicinal product submissions. For this reason, the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) have released guidelines. This review paper provides an overview of the current perspectives and views on these guidelines. METHOD: To evaluate the FDA and EMEA PRO guidelines, 47 expert responses to the FDA guidance were qualitatively reviewed. Two reviewers independently extracted data from these letters and checked these responses to warrant consistency and agreement in the evaluation process. A PubMed literature review was systematically examined to obtain supporting evidence or related articles for both the guidance documents. RESULTS: Generally, there is agreement between regulatory authorities and the research community on the contents of the FDA and EMEA PRO draft guidance. However, disagreements exist on significant philosophical topics (e.g. the FDA focuses more on conceptual models and symptoms than the EMEA) and design topics (e.g. the FDA is more restrictive on issues of recall bias, blinding of oncology trials and degrees of psychometric validation than researchers and the EMEA). This could influence the approval of PRO claims. CONCLUSION: PRO guidance from the EMEA and FDA has been valuable, and has raised the profile and active debate of PROs in oncology. However, our review of the current opinion shows that there are controversial aspects of the guidance. Consequently, greater latitude should be given to how the guidance is interpreted and applied.