A retrospective evaluation of the use of video-capable double-lumen endotracheal tubes in thoracic surgery.

OBJECTIVE: The objective of this study was to evaluate whether the use of a video double-lumen tube reduced the need for fiberoptic bronchoscopy for (1) verification of initial tube placement and for (2) reverification of correct placement after repositioning for thoracotomy. DESIGN: A single-center retrospective study. SETTING: Thoracic surgery in a medical university hospital. PARTICIPANTS & INTERVENTIONS: After institutional review board approval, 29 patients who underwent thoracic surgical procedures using video double-lumen tubes were included in the final retrospective analysis. MEASUREMENTS AND MAIN RESULTS: For 27 (93.2%) patients, the use of fiberoptic bronchoscopy was not needed either for initial placement or for verification of correct video double-lumen tube placement upon final positioning of the patient. However, for two patients, fiberoptic bronchoscopy was needed: for (1) one patient with severe left mainstem bronchus distortion as a result of a large left upper lobe tumor, and (2) a second patient with secretions that were difficult to clear. CONCLUSION: This study demonstrates that the video double-lumen tube requires significantly less (6.8%) fiberoptic use for both initial placement and verification of final position, in stark contrast to standard practice in which bronchoscopy is always used to verify final positioning of the double-lumen tube. As opposed to intermittent bronchoscopy, the continuous visualization offered by an embedded camera may confer an added measure of safety.

Trunk postural control during unstable sitting among individuals with and without low back pain: A systematic review with an individual participant data meta-analysis.

INTRODUCTION: Sitting on an unstable surface is a common paradigm to investigate trunk postural control among individuals with low back pain (LBP), by minimizing the influence lower extremities on balance control. Outcomes of many small studies are inconsistent (e.g., some find differences between groups while others do not), potentially due to confounding factors such as age, sex, body mass index [BMI], or clinical presentations. We conducted a systematic review with an individual participant data (IPD) meta-analysis to investigate whether trunk postural control differs between those with and without LBP, and whether the difference between groups is impacted by vision and potential confounding factors. METHODS: We completed this review according to PRISMA-IPD guidelines. The literature was screened (up to 7th September 2023) from five electronic databases: MEDLINE, CINAHL, Embase, Scopus, and Web of Science Core Collection. Outcome measures were extracted that describe unstable seat movements, specifically centre of pressure or seat angle. Our main analyses included: 1) a two-stage IPD meta-analysis to assess the difference between groups and their interaction with age, sex, BMI, and vision on trunk postural control; 2) and a two-stage IPD meta-regression to determine the effects of LBP clinical features (pain intensity, disability, pain catastrophizing, and fear-avoidance beliefs) on trunk postural control. RESULTS: Forty studies (1,821 participants) were included for the descriptive analysis and 24 studies (1,050 participants) were included for the IPD analysis. IPD meta-analyses revealed three main findings: (a) trunk postural control was worse (higher root mean square displacement [RMSdispl], range, and long-term diffusion; lower mean power frequency) among individuals with than without LBP; (b) trunk postural control deteriorated more (higher RMSdispl, short- and long-term diffusion) among individuals with than without LBP when vision was removed; and (c) older age and higher BMI had greater adverse impacts on trunk postural control (higher short-term diffusion; longer time and distance coordinates of the critical point) among individuals with than without LBP. IPD meta-regressions indicated no associations between the limited LBP clinical features that could be considered and trunk postural control. CONCLUSION: Trunk postural control appears to be inferior among individuals with LBP, which was indicated by increased seat movements and some evidence of trunk stiffening. These findings are likely explained by delayed or less accurate corrective responses. SYSTEMATIC REVIEW REGISTRATION: This review has been registered in PROSPERO (registration number: CRD42021124658).

The lived experience of depression: a bottom-up review co-written by experts by experience and academics.

We provide here the first bottom-up review of the lived experience of depression, co-written by experts by experience and academics. First-person accounts within and outside the medical field were screened and discussed in collaborative workshops involving numerous individuals with lived experience of depression, family members and carers, representing a global network of organizations. The material was enriched by phenomenologically informed perspectives and shared with all collaborators in a cloud-based system. The subjective world of depression was characterized by an altered experience of emotions and body (feeling overwhelmed by negative emotions, unable to experience positive emotions, stuck in a heavy aching body drained of energy, detached from the mind, the body and the world); an altered experience of the self (losing sense of purpose and existential hope, mismatch between the past and the depressed self, feeling painfully incarcerated, losing control over one's thoughts, losing the capacity to act on the world; feeling numb, empty, non-existent, dead, and dreaming of death as a possible escape route); and an altered experience of time (experiencing an alteration of vital biorhythms, an overwhelming past, a stagnation of the present, and the impossibility of the future). The experience of depression in the social and cultural context was characterized by altered interpersonal experiences (struggling with communication, feeling loneliness and estrangement, perceiving stigma and stereotypes), and varied across different cultures, ethnic or racial minorities, and genders. The subjective perception of recovery varied (feeling contrasting attitudes towards recovery, recognizing recovery as a journey, recognizing one's vulnerability and the need for professional help), as did the experience of receiving pharmacotherapy, psychotherapy, and social as well as physical health interventions. These findings can inform clinical practice, research and education. This journey in the lived experience of depression can also help us to understand the nature of our own emotions and feelings, what is to believe in something, what is to hope, and what is to be a living human being.

Machine-supported decision-making to improve agricultural training participation and gender inclusivity.

Women comprise a significant portion of the agricultural workforce in developing countries but are often less likely to attend government sponsored training events. The objective of this study was to assess the feasibility of using machine-supported decision-making to increase overall training turnout while enhancing gender inclusivity. Using data obtained from 1,067 agricultural extension training events in Bangladesh (130,690 farmers), models were created to assess gender-based training patterns (e.g., preferences and availability for training). Using these models, simulations were performed to predict the top (most attended) training events for increasing total attendance (male and female combined) and female attendance, based on gender of the trainer, and when and where training took place. By selecting a mixture of the top training events for total attendance and female attendance, simulations indicate that total and female attendance can be concurrently increased. However, strongly emphasizing female participation can have negative consequences by reducing overall turnout, thus creating an ethical dilemma for policy makers. In addition to balancing the need for increasing overall training turnout with increased female representation, a balance between model performance and machine learning is needed. Model performance can be enhanced by reducing training variety to a few of the top training events. But given that models are early in development, more training variety is recommended to provide a larger solution space to find more optimal solutions that will lead to better future performance. Simulations show that selecting the top 25 training events for total attendance and the top 25 training events for female attendance can increase female participation by over 82% while at the same time increasing total turnout by 14%. In conclusion, this study supports the use of machine-supported decision-making when developing gender inclusivity policies in agriculture extension services and lays the foundation for future applications of machine learning in this area.

Ventilatory Strategy to Prevent Atelectasis During Bronchoscopy Under General Anesthesia: A Multicenter Randomized Controlled Trial (Ventilatory Strategy to Prevent Atelectasis -VESPA- Trial).

BACKGROUND: Atelectasis negatively influences peripheral bronchoscopy, increasing CT scan-body divergence, obscuring targets, and creating false-positive radial-probe endobronchial ultrasound (RP-EBUS) images. RESEARCH QUESTION: Can a ventilatory strategy reduce the incidence of atelectasis during bronchoscopy under general anesthesia? STUDY DESIGN AND METHODS: Randomized controlled study (1:1) in which patients undergoing bronchoscopy were randomized to receive standard ventilation (laryngeal mask airway, 100% Fio2, zero positive end-expiratory pressure [PEEP]) vs a ventilatory strategy to prevent atelectasis (VESPA) with endotracheal intubation followed by a recruitment maneuver, Fio2 titration (< 100%), and PEEP of 8 to 10 cm H2O. All patients underwent chest CT imaging and a survey for atelectasis with RP-EBUS bilaterally on bronchial segments 6, 9, and 10 after artificial airway insertion (time 1) and 20 to 30 min later (time 2). Chest CT scans were reviewed by a blinded chest radiologist. RP-EBUS images were assessed by three independent, blinded readers. The primary end point was the proportion of patients with any atelectasis (either unilateral or bilateral) at time 2 according to chest CT scan findings. RESULTS: Seventy-six patients were analyzed, 38 in each group. The proportion of patients with any atelectasis according to chest CT scan at time 2 was 84.2% (95% CI, 72.6%-95.8%) in the control group and 28.9% (95% CI, 15.4%-45.9%) in the VESPA group (P < .0001). The proportion of patients with bilateral atelectasis at time 2 was 71.1% (95% CI, 56.6%-85.5%) in the control group and 7.9% (95% CI, 1.7%-21.4%) in the VESPA group (P < .0001). At time 2, 3.84 ± 1.67 (mean ± SD) bronchial segments in the control group vs 1.21 ± 1.63 in the VESPA group were deemed atelectatic (P < .0001). No differences were found in the rate of complications. INTERPRETATION: VESPA significantly reduced the incidence of atelectasis, was well tolerated, and showed a sustained effect over time despite bronchoscopic nodal staging maneuvers. VESPA should be considered for bronchoscopy when atelectasis is to be avoided. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04311723; URL: www. CLINICALTRIALS: gov.

Identification and analyses of the chemical composition of a naturally occurring albino mutant chanterelle.

White chanterelles (Basidiomycota), lacking the orange pigments and apricot-like odour of typical chanterelles, were found recently in the Canadian provinces of Québec (QC) and Newfoundland & Labrador (NL). Our phylogenetic analyses confirmed the identification of all white chanterelles from NL and QC as Cantharellus enelensis; we name these forma acolodorus. We characterized carotenoid pigments, lipids, phenolics, and volatile compounds in these and related chanterelles. White mutants of C. enelensis lacked detectable ß-carotene, confirmed to be the primary pigment of wild-type, golden-orange individuals, and could also be distinguished by their profiles of fatty acids and phenolic acids, and by the ketone and terpene composition of their volatiles. We detected single base substitutions in the phytoene desaturase (Al-1) and phytoene synthase (Al-2) genes of the white mutant, which are predicted to result in altered amino acids in their gene products and may be responsible for the loss of ß-carotene synthesis in that form.

Quantitative assessment of the subepithelial collagen band does not increase the accuracy of diagnosis of collagenous colitis.

The thickness of eosinophilic band in collagenous colitis (CC) was assessed by 3 methods: histologic estimates (22 observers), conventional measurements using a calibrated micrometric scale (1 observer), and semiautomatic micrometric measurements (1 observer). By the histologic estimate technique, 7.4% of the results failed to diagnose CC; by calibrated micrometry, the failure was 6% and by semiautomatic micrometry, 6%. The main difficulty in measuring the thickness of the CC band is that the deeper border of the band appears fuzzy and hairy-irregular. CC should be defined not exclusively on the basis of the thickness of the collagen table, but as a microscopic constellation characterized by a distorted superficial cell arrangement, with areas of epithelial denudation and inflammatory cells in the superficial epithelium and the lamina propria. In agreement with Lazenby's statement: "Focusing solely on the collagen band can result in both over- and underdiagnosis"

Mecasermin Tercica.

Tercica, under license from Genentech, has developed and launched mecasermin, recombinant human insulin-like growth factor-1 (rhIGF-1), for the treatment of growth failure in children with primary IGF deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.

Humira: the impending patent battles over adalimumab biosimilars.

The world's top selling drug, adalimumab (AbbVie's Humira), generated sales in excess of US$13 billion in 2015. The primary product patent expires in 2016 in the USA and 2018 in Europe. This has resulted in a rush by companies to develop adalimumab biosimilars and Amgen submitted regulatory filings for its product ABP-501 in late 2015 in both the USA and Europe. AbbVie has claimed its patent portfolio provides product protection until 2022, but an increasing number of patent challenges are being made and the filings for approval of biosimilars will see more challenges made over the next few years.

Investigational Bruton's tyrosine kinase inhibitors for the treatment of rheumatoid arthritis.

INTRODUCTION: The Tec family of non-receptor tyrosine kinases comprises five members. The cellular expression and function of these kinases has implicated them as potential drug targets for the treatment of both malignant and autoimmune diseases. Most attention has focused on inhibitors of BTK kinase with ibrutinib already approved for the treatment of mantle cell lymphoma and chronic lymphocytic leukaemia. Multiple BTK inhibitors are being developed for both oncology and autoimmune disease indications. AREAS COVERED: BTK inhibitors being evaluated in rheumatoid arthritis are considered. Both inhibitors which have progressed to early clinical development, and those demonstrating activity in rodent models of arthritis are reviewed. These include both reversible and irreversible inhibitors of the kinase, most of which target the cysteine-481 residue of BTK. The selectivity of these inhibitors for Tec family kinases is considered. EXPERT OPINION: Developing inhibitors of any kinase to treat of rheumatoid arthritis has proved problematic with regard to both efficacy and selectivity. It is anticipated that the more selective BTK inhibitors may prove more useful in treating arthritis, with the use of reversible inhibitors possibly offering a better strategy. Chronic dosing may exacerbate the emergence of drug resistance, with resistant mutations already observed in ibrutinib-treated patients.

Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary disease.

INTRODUCTION: The p38 protein kinases, in particular p38α and p38ß, regulate the production of multiple inflammatory mediators. Consequentially, considerable effort has been focused on trying to develop p38 inhibitors for the treatment of inflammatory diseases. Some 20 p38 inhibitors have progressed to clinical development, mostly for the treatment of rheumatoid arthritis, but with little success. Increasingly, interest has turned to their use in other indications and notably chronic obstructive pulmonary disease (COPD). AREAS COVERED: In this review, the author discusses the eight p38 inhibitors that have been clinically evaluated. Acumapimod is the only one of four orally delivered inhibitors that remains in active development while Phase II results of PH-797804 and losmapimod are compared. The activity of two inhibitors designed for inhaled delivery, RV-568 and PF-03715455, is compared but little is known about AZD-7624 or the discontinued GSK-610677. EXPERT OPINION: Results from animal models provide a clear rationale for developing p38 inhibitors for COPD, and appear to be (partially) validated by the efficacy seen with PH-797804 and losmapimod. Inhaled delivery provides the opportunity to enhance p38 inhibition in the lung while reducing unwanted systemic effects of p38 inhibition. Validation of this hypothesis should come from the results of the recently completed Phase II study with RV-568.

Evaluation of WO-2014132220, selective PDGFR inhibitors for the treatment of pulmonary arterial hypertension.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare disease currently treated by a range of vasodilator agents and/or endothelin antagonists. Inhibition of platelet derived growth factor receptor (PDGFR) kinases has been suggested to provide an additional therapeutic modality, and clinical studies with the non-selective PDGFR inhibitor imatinib appear to validate this hypothesis. However, side-effects associated with a lack of selectivity suggest clinical utility requires the identification and development of selective PDGFR inhibitors. AREAS COVERED: This application claims derivatives and crystalline forms of two previously claimed PDGFR inhibitors and their use for the treatment of PAH. N-(5-(2-(2,2-dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide and N-(5-(2-(2,6-cis-dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide have respective IC50 values of 3 and 45 nM in a cellular proliferation assay. EXPERT OPINION: These two compounds are likely to be selective PDGFR inhibitors. The nature of this filing suggests that Novartis intends to develop at least one of these compounds for the treatment of PAH.

Evaluation of US20150011555. An inhaled IP receptor agonist for the treatment of pulmonary arterial hypertension.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare disease for which IP receptor agonists provide one of the main classes of treatment. Currently available agents tend to lack receptor selectivity. AREAS COVERED: Four salts of 7-(2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid, crystalline forms and compositions of each of these salts, and their use to treat conditions mediated by IP receptor activation, in particular PAH, are claimed. The claimed salts are particularly suited for delivery via inhalation and inhalation devices for their administration are claimed. EXPERT OPINION: This IP receptor agonist represents the first example of selecting a compound to treat PAH that was designed for delivery via inhalation. It indicates Novartis' desire to establish a broad portfolio of respiratory products.

Developments in inhaled combination therapies: patent activity 2013-2014.

INTRODUCTION: Since the 1970s, the treatment options for asthma and chronic obstructive pulmonary disease have increasingly relied upon the use of inhaled drug formulations, generally from handheld inhaler devices. The introduction of combinations of a corticosteroid with a long-acting ß2 agonist has dramatically transformed the accepted treatment paradigm. This has led to a dramatic increase in the development of novel combinations of inhaled drugs, including long-acting muscarinic antagonists with long-acting ß2 agonists, as well as triple combinations, and of devices for their delivery. AREAS COVERED: This review considers recent patent filings claiming inhaled drug combinations, or devices delivering them, that are useful in the treatment of asthma and/or chronic obstructive pulmonary disease. EXPERT OPINION: The modest level of activity in patent filings relating to inhaled combinations is surprising. Many of the patents are from the major players in the respiratory market segment, with only one inhalation technology specialist showing significant activity. The limited activity from generics companies is explained by the limited range of active ingredients whose use they can usefully claim.

Gastrointestinal stromal tumour metastatic to the epididymis.

Gastrointestinal stromal tumours (GIST) are mesenchymal neoplasms with a propensity to metastasise to the liver and peritoneal cavity. Since the advent of tyrosine kinase inhibitors, outcomes for patients with metastatic GIST have improved dramatically. Secondary to the longevity in survival, patients may develop metastatic disease in very unusual locations, which poses significant diagnostic dilemmas and management challenges. We report a case of a patient with GIST who presented with an epididymal metastasis manifesting as a scrotal mass. Resistance to targeted medical therapies continues to pose a challenge, and our case highlights the importance of a multidisciplinary approach in such patients, including long-term follow-up.

SomatoKine. Insmed.

SomatoKine, a recombinant fusion of insulin-like growth factor-1 and its binding protein, BP-3, is being developed by Insmed (formerly Celtrix Pharmaceuticals) for the potential treatment of growth hormone insensitivity syndrome (GHIS), and as a potential injectable insulin sensitizer for the management of type 1 and type 2 diabetes in patients who are less sensitive to insulin therapy. By July 2002, the FDA had granted SomatoKine Orphan Drug status for the treatment of GHIS. Also at this time, a phase II trial in children suffering from GHIS was initiated. In September 2002, Insmed expected to initiate a further clinical trial in GHIS in early 2003, and planned to continue phase II development in type 1 and type 2 diabetes.

Atrasentan Abbott.

Atrasentan is a selective endothelin ET(A) receptor antagonist under development by Abbott for the potential treatment of cancer, particularly prostate cancer, for which it is in phase III trials [413197]. In July 2002, phase II trials for renal, ovarian, lung, colorectal, breast and brain cancers were being initiated [457800]. Atrasentan has been granted Fast Track status, allowing for a rolling NDA [414666], [443479]; the company was planning to begin filing for prostate cancer in late 2003. Atrasentan has also been in phase I trials for hypertension [319405], [326268], but development for this indication had been halted by 2001 [407049].

Tipifarnib (Janssen Pharmaceutica).

Janssen is developing tipifarnib (formerly known as R-1 15777), an inhibitor of RAS farnesylation, for the potential treatment of neoplasia [287030], [289610]. Janssen commenced clinical trials in the US, in conjunction with the National Cancer Institute, in April 1997 [287030], [289610], and by May 1999, phase II trials in patients with advanced non-small cell lung cancer were being planned [325960]. By February 2001, phase III trials for the potential treatment of pancreatic cancer and leukemia had been initiated [399065], and by June 2001, it was in phase II trials for RAS-dependent solid tumors [412618]. In November 2001, Credit Lyonnais Securities predicted NDAfilings in 2002 and 2003 for pancreatic cancer and other cancers, respectively, and projected US introductions for these indications in 2004 and 2005, respectively [436939].