Physicians’ attitudes, beliefs and barriers to a pulmonary rehabilitation for COPD patients in Saudi Arabia: a cross-sectional study

This study aimed to assess physicians’ attitudes toward delivering pulmonary rehabilitation (PR) to chronic obstructive pulmonary disease (COPD) patients and identify factors and barriers that might influence referral decisions. Between September 2021 and January 2022, a cross-sectional online survey was distributed to all physicians in Saudi Arabia. A total of 502 physicians completed the online survey, of which 62.0% (n = 312) were male. General physicians accounted for 51.2%, while internal-medicine specialists and pulmonologists accounted for 26.9% and 6.6%, respectively. Only 146 (29%) physicians had referred COPD patients to a PR program. The difference in referral rates between all specialties (p = 0.011) was statistically significant. Physicians with more years of experience were more likely to refer COPD patients to PR (p < 0.001). Moreover, a home-based PR program was preferred by 379 physicians (75.5%), and 448 (89.2%) perceived smoking cessation as an essential component of PR. Availability of PR centers (69%) was the most common barrier for not referring patients to PR. The overall referral rate was low among all physicians, owing to a lack of PR centers and trained staff. Home-based delivery was the preferred method of delivering PR, with smoking cessation as an essential component

Functional analysis of germline <em>VANGL2</em> variants using rescue assays of <em>vangl2</em> knockout zebrafish

\ua9 The Author(s) 2023. Published by Oxford University Press. Developmental studies have shown that the evolutionarily conserved Wnt Planar Cell Polarity (PCP) pathway is essential for the development of a diverse range of tissues and organs including the brain, spinal cord, heart and sensory organs, as well as establishment of the left-right body axis. Germline mutations in the highly conserved PCP gene VANGL2 in humans have only been associated with central nervous system malformations, and functional testing to understand variant impact has not been performed. Here we report three new families with missense variants in VANGL2 associated with heterotaxy and congenital heart disease p.(Arg169His), non-syndromic hearing loss p.(Glu465Ala) and congenital heart disease with brain defects p.(Arg135Trp). To test the in vivo impact of these and previously described variants, we have established clinically-relevant assays using mRNA rescue of the vangl2 mutant zebrafish. We show that all variants disrupt Vangl2 function, although to different extents and depending on the developmental process. We also begin to identify that different VANGL2 missense variants may be haploinsufficient and discuss evidence in support of pathogenicity. Together, this study demonstrates that zebrafish present a suitable pipeline to investigate variants of unknown significance and suggests new avenues for investigation of the different developmental contexts of VANGL2 function that are clinically meaningful

SPARC 2018 Internationalisation and collaboration : Salford postgraduate annual research conference book of abstracts

Welcome to the Book of Abstracts for the 2018 SPARC conference. This year we not only celebrate the work of our PGRs but also the launch of our Doctoral School, which makes this year’s conference extra special. Once again we have received a tremendous contribution from our postgraduate research community; with over 100 presenters, the conference truly showcases a vibrant PGR community at Salford. These abstracts provide a taster of the research strengths of their works, and provide delegates with a reference point for networking and initiating critical debate. With such wide-ranging topics being showcased, we encourage you to take up this great opportunity to engage with researchers working in different subject areas from your own. To meet global challenges, high impact research inevitably requires interdisciplinary collaboration. This is recognised by all major research funders. Therefore engaging with the work of others and forging collaborations across subject areas is an essential skill for the next generation of researchers

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Drug dosing during pregnancy—opportunities for physiologically based pharmacokinetic models

Drugs can have harmful effects on the embryo or the fetus at any point during pregnancy. Not all the damaging effects of intrauterine exposure to drugs are obvious at birth, some may only manifest later in life. Thus, drugs should be prescribed in pregnancy only if the expected benefit to the mother is thought to be greater than the risk to the fetus. Dosing of drugs during pregnancy is often empirically determined and based upon evidence from studies of non-pregnant subjects, which may lead to suboptimal dosing, particularly during the third trimester. This review collates examples of drugs with known recommendations for dose adjustment during pregnancy, in addition to providing an example of the potential use of PBPK models in dose adjustment recommendation during pregnancy within the context of drug-drug interactions. For many drugs, such as antidepressants and antiretroviral drugs, dose adjustment has been recommended based on pharmacokinetic studies demonstrating a reduction in drug concentrations. However, there is relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Examples of using pregnancy PBPK models to predict feto-maternal drug exposures and their applications to facilitate and guide dose assessment throughout gestation are discussed

Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

Background The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38)

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Sleep quality, insomnia, anxiety, fatigue, stress, memory and 2 active coping during the COVID-19 pandemic

Background: The current study aimed to evaluate the impact of the coronavirus (COVID-19) pandemic on sleep quality, insomnia, anxiety, stress, fatigue and active coping in the United States. Methods: This was a cross-sectional study using a publicly available database taken from the Boston College COVID-19 Sleep and Well-Being Dataset. We have selected the most recent data that included information about sleep quality and other measures, including insomnia, anxiety, stress, fatigue and coping, collected between February 22–March 8, 2021. Results: A total of 476 subjects were included in the analysis. The mean (SD) age of the study population was 38.8 (17.8) years, and there were more females (85%) than males. The population had a mean (SD) score of the Pittsburgh Sleep Quality Index (PSQI) of 6 (3.2), with 65% having the prevalence of poor sleep quality (defined as PSQ ≥ 5; n = 311). The mean (SD) score for Insomnia Severity Index (ISI) was 6.9 (5.2), with 55 subjects (11.5%) having clinical insomnia (defined as ISI ≥ 15); of whom 9% had severe clinical in-somnia. There were positive correlations between PSQI and ISI (r = 0.76, p < 0.001; Figure 1), PRO- MIS fatigue scale (r = 0.53, p < 0.001), Generalized Anxiety Disorder-7 (GAD-7) (r = 0.46, p < 0.001), and Perceived Stress Scale (PSS) (r = 0.44, p < 0.001). The PSQI was inversely correlated with the John Henryism Active Coping Scale (JHACS) and memory scale. In the multivariate regression model, JHACS, ISI, fatigue, PSS and GAD-7 were significant predictors of PSQI, and these variables accounted for 62% of the variance of PSQI, adjusted for age and gender. Conclusion: An important contribution to the literature is made by this research, which demonstrates the significant prevalence of poor sleep quality and its association with insomnia and other mental and physical well- being. It also underlines the need to prioritise policy and public health efforts to address sleep issues that have substantial health and economic effects for both individuals and the population at large

Trends in hospital admissions due to neoplasms in England and Wales between 1999 and 2019: an ecological study

Objectives: This study aimed to investigate the trends in neoplasm-related hospital admissions (NRHA) in England and Wales between 1999 and 2019. Methods: This is an ecological study using publicly available data taken from the two main medical databases in England and Wales; the Hospital Episode Statistics database in England and the Patient Episode Database in Wales. Hospital admissions data were collected for the period between April 1999 and March 2019. Results: A total of 35,704,781 NRHA were reported during the study period. Females contributed to 50.8% of NRHA. The NRHA rate among males increased by 50.0% [from 26.62 (95% CI 26.55–26.68) in 1999 to 39.93 (95% CI 39.86–40.00) in 2019 per 1000 persons, trend test, p < 0.001]. The NRHA rate among females increased by 44.1% [from 27.25 (95% CI 27.18–27.31) in 1999 to 39.25 (95% CI 39.18–39.32) in 2019 per 1000 persons, trend test, p < 0.001]. Overall, the rate of NRHA rose by 46.2% [from 26.93 (95% CI 26.89–26.98) in 1999 to 39.39 (95% CI 39.34–39.44) in 2019 per 1000 persons, trend test, p < 0.001]. Conclusion: Hospital admission rates due to neoplasms increased between 1999 and 2019. Our study demonstrates a variation in NRHA influenced by age and gender. Further observational studies are needed to identify other factors associated with increased hospital admissions among patients with different types of neoplasms

Inhaled therapies targeting prostacyclin pathway in pulmonary hypertension due to COPD: Systematic review

Background: Pulmonary hypertension due to chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) is classified as group 3 pulmonary hypertension. Inhaled treprostinil, a prostaglandin I2 analogue also known as prostacyclin, has recently been approved as a first drug for patients with pulmonary hypertension secondary to ILD. However, due to a lack of evidence, no therapies are currently approved for those with COPD-associated pulmonary hypertension. Thus, this systematic review aims to summarise the current evidence to assess the impact of inhaled prostaglandin I2 analogue use on the pulmonary hemodynamics, exercise function, lung function, and gas exchange in patients with pulmonary hypertension due to COPD.We systematically searched the electronic databases of Medline, Embase, Scopus and Cochrane from inception to 1 February 2023. Studies of adult patients with a confirmed diagnosis of COPD-associated pulmonary hypertension who received inhaled drugs targeting the prostacyclin pathway were included in the systematic review. Case reports, systematic reviews, conference abstracts with no full text, non-full-text articles, non-English manuscripts and book chapters were excluded from this systematic review. A risk-of-bias assessment was carried out for the studies included in this review, using two different Cochrane risk-of-bias tools for randomised and non-randomised clinical trials.Results: A total of four studies met our inclusion criteria and were included in this systematic review.The results of one prospective clinical trial showed an improvement in the pulmonary hemodynamics (e.g., cardiac index, cardiac output and mean pulmonary artery pressure) in response to inhaled prostacyclin use in patients with pulmonary hypertension secondary to COPD. However, the severity of dyspnoea, lung function, exercise capacity and gas exchange were not affected when inhaled prostacyclin was used for patients with COPD-related pulmonary hypertension. Deleted: hemodynamic index 55 Deleted: hemodynamic index Conclusion: This systematic review demonstrated that although inhaled prostacyclin does not seem to improve COPD-related outcomes (e.g., lung function and exercise capacity), short-term use of inhaled prostacyclin has the potential to reduce mean pulmonary artery pressure and pulmonary vascular resistance without impairing ventilation-perfusion mismatch. Further studies with larger sample sizes are warranted