ana

Canadian lake selected as site to mark the start of the Anthropocene

Geologists hoping to declare a new epoch dominated by humanity’s influence on Earth have chosen Crawford Lake in Canada as the location where the start of the Anthropocene is defined




ana

Stark mountain landscapes exposed in Canada as glaciers shrink

Global warming means many of the world’s ancient rivers of ice will be gone within decades, threatening ecosystems that rely on their meltwater, a looming crisis that photographer Edward Burtynsky highlights in his work




ana

DNA analysis rewrites the stories of people buried in Pompeii

Genetic analysis of five individuals preserved as plaster casts in the ruins of Pompeii contradicts established beliefs about the people and their relationships




ana

Indigenous Australians have managed land with fire for 11,000 years

Lake sediments reveal the ancient history of Aboriginal people’s use of fire to manage the landscape, a tradition that has benefits for biodiversity




ana

Stone Age network reveals ancient Paris was an artisanal trading hub

Ancient stone goods found across France may have been made by skilled craftspeople in what is now Paris, who traded along vast networks




ana

DNA analysis rewrites the stories of people buried in Pompeii

Genetic analysis of five individuals preserved as plaster casts in the ruins of Pompeii contradicts established beliefs about the people and their relationships




ana

U.S. to Reopen Borders to Vaccinated Travelers from Canada, Mexico

Title: U.S. to Reopen Borders to Vaccinated Travelers from Canada, Mexico
Category: Health News
Created: 10/13/2021 12:00:00 AM
Last Editorial Review: 10/13/2021 12:00:00 AM




ana

Pomegranate Helps Diabetic Hearts

Title: Pomegranate Helps Diabetic Hearts
Category: Health News
Created: 8/30/2006 12:00:00 AM
Last Editorial Review: 8/30/2006 12:00:00 AM




ana

Health Tip: Manage Stress to Keep Diabetes in Check

Title: Health Tip: Manage Stress to Keep Diabetes in Check
Category: Health News
Created: 8/25/2014 7:35:00 AM
Last Editorial Review: 8/25/2014 12:00:00 AM




ana

Fewer Painkiller Deaths in States With Medical Marijuana: Study

Title: Fewer Painkiller Deaths in States With Medical Marijuana: Study
Category: Health News
Created: 8/25/2014 4:35:00 PM
Last Editorial Review: 8/26/2014 12:00:00 AM




ana

American Kids Growing Fatter Than Their Canadian Cousins

Title: American Kids Growing Fatter Than Their Canadian Cousins
Category: Health News
Created: 8/25/2015 12:00:00 AM
Last Editorial Review: 8/26/2015 12:00:00 AM




ana

Medical Marijuana's Pain Relief May Work Better for Men

Title: Medical Marijuana's Pain Relief May Work Better for Men
Category: Health News
Created: 8/24/2016 12:00:00 AM
Last Editorial Review: 8/25/2016 12:00:00 AM




ana

Millions of Contigo Kids Cleanable Water Bottles Recalled

Title: Millions of Contigo Kids Cleanable Water Bottles Recalled
Category: Health News
Created: 8/28/2019 12:00:00 AM
Last Editorial Review: 8/28/2019 12:00:00 AM




ana

Pain Management

Title: Pain Management
Category: Diseases and Conditions
Created: 12/7/2006 12:00:00 AM
Last Editorial Review: 7/28/2022 12:00:00 AM




ana

Medical Marijuana for Pain Is Linked to Slight Rise in Heart Trouble

Title: Medical Marijuana for Pain Is Linked to Slight Rise in Heart Trouble
Category: Health News
Created: 8/23/2022 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM




ana

Cholesterol Management

Title: Cholesterol Management
Category: Diseases and Conditions
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 7/6/2022 12:00:00 AM




ana

New Approach Cuts Odds for Anal Cancer in People With HIV

Title: New Approach Cuts Odds for Anal Cancer in People With HIV
Category: Health News
Created: 6/16/2022 12:00:00 AM
Last Editorial Review: 6/16/2022 12:00:00 AM




ana

How to Manage Menopause Symptoms After Breast Cancer

Title: How to Manage Menopause Symptoms After Breast Cancer
Category: Diseases and Conditions
Created: 7/7/2022 12:00:00 AM
Last Editorial Review: 7/7/2022 12:00:00 AM




ana

Cyclobenzaprine vs. Xanax (alprazolam)

Title: Cyclobenzaprine vs. Xanax (alprazolam)
Category: Medications
Created: 6/6/2019 12:00:00 AM
Last Editorial Review: 8/25/2022 12:00:00 AM




ana

damiana

Title: damiana
Category: Medications
Created: 8/15/2022 12:00:00 AM
Last Editorial Review: 8/15/2022 12:00:00 AM




ana

Evidence-based management of symptoms in serious respiratory illness: what is in our toolbox?

Extract

Living with a respiratory illness requires patients to manage a wide range of symptoms, many of which will worsen as a disease progresses. Breathlessness is a hallmark feature of respiratory conditions, occurring in almost all individuals with COPD and interstitial lung disease (ILD) [1, 2]. Cough is present in 78% of people with ILD and is frequently distressing, with physical, social and emotional impacts [1, 3].




ana

Impaired lung function and associated risk factors in children born prematurely: a systematic review and meta-analysis

Background

Immature lung development and respiratory morbidity place preterm-born children at high risk of long-term pulmonary sequelae. This systematic review and meta-analysis aims to quantify lung function in preterm-born children and identify risk factors for a compromised lung function.

Methods

We searched MEDLINE, Embase, Cochrane Library, Web of Science and Scopus for relevant studies published on preterm cohorts born since 1990. Studies comparing forced expiratory volume in 1 s (FEV1) in preterm-born children aged ≥5 years to term-born controls or normative data were included. Study quality was assessed using the Newcastle–Ottawa Scale for cohort studies. Standardised mean differences in FEV1 and secondary spirometry outcomes per study were pooled using meta-analysis. The impact of different demographic and neonatal variables on studies’ FEV1 effect sizes was investigated by meta-regression analyses. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework.

Results

We identified 42 studies with unique cohorts including 4743 preterm children and 9843 controls. Median gestational age in the studies was 28.0 weeks and age at assessment ranged from 6.7 to 16.7 years. Preterm children had lower FEV1 than controls (–0.58 sd, 95% CI –0.69– –0.47 sd, p<0.001) resulting in a relative risk of 2.9 (95% CI 2.4–3.4) for abnormal outcome, with high certainty of evidence. FEV1 was significantly associated with gestational age, birthweight, bronchopulmonary dysplasia and invasive mechanical ventilation in univariate meta-regression analyses (R2=36–96%).

Conclusion

This systematic review shows robust evidence of impaired lung function in preterm-born children with a high certainty of evidence.




ana

Epidemiology of severe asthma in children: a systematic review and meta-analysis

Background

Severe asthma significantly impacts a minority of children with asthma, leading to frequent symptoms, hospitalisations and potential long-term health consequences. However, accurate global data on severe asthma epidemiology is lacking. This study aims to address this gap, providing data on severe asthma epidemiology, regional differences and associated comorbidities.

Methods

We conducted a rigorous systematic review and meta-analysis following a registered protocol (PROSPERO CRD42023472845). We searched PubMed, Scopus and Web of Science for cohort or cross-sectional studies published since 2003, evaluating severe asthma incidence and prevalence in children. Study quality and risk of bias were assessed using STROBE guidelines.

Results

Nine studies investigating European children with asthma (aged 5–18 years) were included in the meta-analysis. No significant publication bias was found. The overall severe asthma prevalence in children with asthma was 3% (95% CI 1–6; I2=99.9%; p<0.001), with no significant difference between males and females. Prevalence estimates varied significantly depending on the diagnostic criteria used (Global Initiative for Asthma: 6%; European Respiratory Society/American Thoracic Society: 1%; other: 3%). Because none of the examined studies were prospectively designed, incidence rates could not be determined.

Conclusions

This systematic review and meta-analysis provide the first robust assessment of severe asthma prevalence among European children. Our findings underscore the need for comprehensive research to address knowledge gaps in severe asthma, including determining incidence rates, standardising definitions, investigating regional differences and evaluating comorbidities and treatment strategies.




ana

Patient-managed interventions for adults with bronchiectasis: evidence, challenges and prospects

Bronchiectasis is a chronic lung condition which is characterised by recurrent chest infections, chronic sputum production and cough, and limited exercise tolerance. While bronchiectasis may be caused by various aetiologies, these features are shared by most patients with bronchiectasis regardless of the cause. This review consolidates the existing evidence on patient-managed interventions for adults with bronchiectasis, while also outlining areas for future research. Airway clearance techniques and hyperosmolar agents are key components of the bronchiectasis management and consistently recommended for clinical implementation. Questions around their prescription, such as optimal sequence of delivery, are still to be answered. Pulmonary rehabilitation and exercise are also recommended for patients with bronchiectasis. Relatively strong evidence underpins this recommendation during a clinically stable stage of the disease, although the role of pulmonary rehabilitation following an exacerbation is still unclear. Additionally, self-management programmes feature prominently in bronchiectasis treatment, yet the lack of consensus regarding their definition and outcomes presents hurdles to establishing a cohesive evidence base. Moreover, cough, a cardinal symptom of bronchiectasis, warrants closer examination. Although managing cough in bronchiectasis may initially appear risky, further research is necessary to ascertain whether strategies employed in other respiratory conditions can be safely and effectively adapted to bronchiectasis, particularly through identifying patient responder populations and criteria where cough may not enhance airway clearance efficacy and its control is needed. Overall, there is a growing recognition of the importance of patient-managed interventions in the bronchiectasis management. Efforts to improve research methodologies and increase research funding are needed to further advance our understanding of these interventions, and their role in optimising patient care and outcomes.




ana

Multicomponent services for symptoms in serious respiratory illness: a systematic review and meta-analysis

Background

People living with serious respiratory illness experience a high burden of symptoms. This review aimed to determine whether multicomponent services reduce symptoms in people with serious illness related to respiratory disease.

Methods

Electronic databases were searched to identify randomised controlled trials (RCTs) evaluating multicomponent services that enrolled patients due to symptoms, rather than underlying disease, and provided at least one nonpharmacological intervention. The primary outcome was chronic breathlessness and secondary outcomes were health-related quality of life (HRQoL), cough, fatigue and adverse events. At least two authors independently screened studies, assessed risk of bias and extracted data.

Results

Five RCTs, involving 439 patients, were included. In comparison to usual care, multicomponent services improved breathlessness mastery (Chronic Respiratory Questionnaire (CRQ) mastery scale, mean difference (MD) 0.43 points, 95% CI 0.20–0.67, three RCTs, 327 participants) and HRQoL (CRQ total score, MD 0.24 points, 95% CI 0.04–0.40, two RCTs, 237 participants). Fatigue did not improve with multicomponent services and no studies evaluated cough. No serious adverse events were reported. The one study evaluating mortality found increased survival in those accessing a multicomponent service. The certainty of evidence was very low, mainly due to detection and reporting bias.

Conclusion

Multicomponent services improve breathlessness mastery and HRQoL, with minimal risk. These findings support the use of multicomponent symptom-directed services for people living with serious respiratory illness.




ana

Opioids for the palliation of symptoms in people with serious respiratory illness: a systematic review and meta-analysis

Background

People living with serious respiratory illness experience a high burden of distressing symptoms. Although opioids are prescribed for symptom management, they generate adverse events, and their benefits are unclear.

Methods

We examined the efficacy and safety of opioids for symptom management in people with serious respiratory illness. Embase, MEDLINE and the Cochrane Central Register of Controlled Trials were searched up to 11 July 2022. Reports of randomised controlled trials administering opioids to treat symptoms in people with serious respiratory illness were included. Key exclusion criteria included <80% of participants having a nonmalignant lung disease. Data were extracted regarding study characteristics, outcomes of breathlessness, cough, health-related quality of life (HRQoL) and adverse events. Treatment effects were pooled using a generic inverse variance model with random effects. Risk of bias was assessed using the Cochrane Risk of Bias tool version 1.

Results

Out of 17 included trials, six were laboratory-based exercise trials (n=70), 10 were home studies measuring breathlessness in daily life (n=788) and one (n=18) was conducted in both settings. Overall certainty of evidence was "very low" to "low". Opioids reduced breathlessness intensity during laboratory exercise testing (standardised mean difference (SMD) –0.37, 95% CI –0.67– –0.07), but not breathlessness measured in daily life (SMD –0.10, 95% CI –0.64–0.44). No effects on HRQoL (SMD –0.42, 95% CI –0.98–0.13) or cough (SMD –1.42, 95% CI –3.99–1.16) were detected. In at-home studies, opioids led to increased frequency of nausea/vomiting (OR 3.32, 95% CI 1.70–6.51), constipation (OR 3.08, 95% CI 1.69–5.61) and drowsiness (OR 1.37, 95% CI 1.01–1.86), with serious adverse events including hospitalisation and death identified.

Conclusions

Opioids improved exertional breathlessness in laboratory exercise studies, but did not improve breathlessness, cough or HRQoL measured in daily life at home. There were significant adverse events, which may outweigh any benefits.




ana

Seamless, rapid, and accurate analyses of outbreak genomic data using split k-mer analysis [METHODS]

Sequence variation observed in populations of pathogens can be used for important public health and evolutionary genomic analyses, especially outbreak analysis and transmission reconstruction. Identifying this variation is typically achieved by aligning sequence reads to a reference genome, but this approach is susceptible to reference biases and requires careful filtering of called genotypes. There is a need for tools that can process this growing volume of bacterial genome data, providing rapid results, but that remain simple so they can be used without highly trained bioinformaticians, expensive data analysis, and long-term storage and processing of large files. Here we describe split k-mer analysis (SKA2), a method that supports both reference-free and reference-based mapping to quickly and accurately genotype populations of bacteria using sequencing reads or genome assemblies. SKA2 is highly accurate for closely related samples, and in outbreak simulations, we show superior variant recall compared with reference-based methods, with no false positives. SKA2 can also accurately map variants to a reference and be used with recombination detection methods to rapidly reconstruct vertical evolutionary history. SKA2 is many times faster than comparable methods and can be used to add new genomes to an existing call set, allowing sequential use without the need to reanalyze entire collections. With an inherent absence of reference bias, high accuracy, and a robust implementation, SKA2 has the potential to become the tool of choice for genotyping bacteria. SKA2 is implemented in Rust and is freely available as open-source software.




ana

Theoretical framework for the difference of two negative binomial distributions and its application in comparative analysis of sequencing data [METHODS]

High-throughput sequencing (HTS) technologies have been instrumental in investigating biological questions at the bulk and single-cell levels. Comparative analysis of two HTS data sets often relies on testing the statistical significance for the difference of two negative binomial distributions (DOTNB). Although negative binomial distributions are well studied, the theoretical results for DOTNB remain largely unexplored. Here, we derive basic analytical results for DOTNB and examine its asymptotic properties. As a state-of-the-art application of DOTNB, we introduce DEGage, a computational method for detecting differentially expressed genes (DEGs) in scRNA-seq data. DEGage calculates the mean of the sample-wise differences of gene expression levels as the test statistic and determines significant differential expression by computing the P-value with DOTNB. Extensive validation using simulated and real scRNA-seq data sets demonstrates that DEGage outperforms five popular DEG analysis tools: DEGseq2, DEsingle, edgeR, Monocle3, and scDD. DEGage is robust against high dropout levels and exhibits superior sensitivity when applied to balanced and imbalanced data sets, even with small sample sizes. We utilize DEGage to analyze prostate cancer scRNA-seq data sets and identify marker genes for 17 cell types. Furthermore, we apply DEGage to scRNA-seq data sets of mouse neurons with and without fear memory and reveal eight potential memory-related genes overlooked in previous analyses. The theoretical results and supporting software for DOTNB can be widely applied to comparative analyses of dispersed count data in HTS and broad research questions.




ana

Cannabis and Pain Management

Family physicians are fielding questions about cannabis --particularly for the use of cannabis for treatment of pain. Like about every substance ingested to treat medical conditions, cannabis has risks and benefits. But regarding evidence-based practice and practice-based recommendations for patients about cannabis use, the cart is in front of the horse. Cannabis use is still illegal at a federal level and a Schedule 1 drug, but most states have challenged federal law by decriminalizing or legalizing cannabis for a variety of uses. Research is difficult due to this federal status as a Schedule 1 drug since federal funding is not readily available to support research. As a result, physicians have little to no guidance about the clinical usefulness of the product. This article explores what we know and what we are learning about cannabis, and the authors provide clinical guidance for patient care based on this evidence.




ana

Be SMART About Asthma Management: Single Maintenance and Reliever Therapy

Single maintenance and reliever therapy (SMART) is an asthma treatment approach that utilizes combined inhaled corticosteroids and long-acting β-agonists for maintenance and quick relief therapy. Despite the evidence for its benefits in asthma treatment and its adoption into American and international asthma guidelines and recommendations, SMART remains a practice of some debate. This article reviews the available evidence for SMART and offers guidance for its integration into comprehensive asthma management. Overall, short-acting β-agonist-only asthma therapy regimens should be avoided, regardless of condition severity (SOR A Recommendation). Family medicine clinicians should start SMART for patients requiring either GINA Step 3 or 4 therapy, especially if they have signs of poor adherence (SOR B Recommendation). Finally, use budesonide-formoterol over other inhaled corticosteroid/long-acting β-agonist combinations when implementing SMART (SOR B Recommendation).




ana

Assessing Patient Readiness for Hospital Discharge, Discharge Communication, and Transitional Care Management

Background:

Discharge communication between hospitalists and primary care clinicians is essential to improve care coordination, minimize adverse events, and decrease unplanned health services use. Health-related social needs are key drivers of health, and hospitalists and primary care clinicians value communicating social needs at discharge.

Objective:

To 1) characterize the current state of discharge communications between an academic medical center hospital and primary care clinicians at associated clinics; 2) seek feedback about the potential usefulness of discharge readiness information to primary care clinicians.

Design:

Exploratory, convergent mixed methods.

Participants:

Primary care clinicians from Family Medicine and General Internal Medicine of an academic medical center in the US Intermountain West.

Approach:

Literature-informed REDCap survey. Semistructured interview guide developed with key informants, grounded in current literature. Survey data were descriptively summarized; interview data were deductively and inductively coded, organized by topics.

Results:

Two key topics emerged: 1) discharge communication, with interrelated topics of transitional care management and follow-up appointment challenges, and recommendations for improving discharge communication; and 2) usefulness of the discharge readiness information, included interrelated topics related to lack of shared understanding about roles and responsibilities across settings and ethical concerns related to identifying problems that may not have solutions.

Conclusions:

While reiterating perennial discharge communication and transitional care management challenges, this study reveals new evidence about how these issues are interrelated with assessing and responding to patients’ lack of readiness for discharge and unmet social needs during care transitions. Primary care clinicians had mixed views on the usefulness of discharge readiness information. We offer recommendations for improving discharge communication and transitional care management (TCM) processes, which may be applicable in other care settings.




ana

A Qualitative Analysis of a Primary Care Medical-Legal Partnership: Impact, Barriers, and Facilitators

Background:

Certain health-related risk factors require legal interventions. Medical-legal partnerships (MLPs) are collaborations between clinics and lawyers that address these health-harming legal needs (HHLNs) and have been shown to improve health and reduce utilization.

Objective:

The objective of this study is to explore the impact, barriers, and facilitators of MLP implementation in primary care clinics.

Methods:

A qualitative design using a semistructured interview assessed the perceived impact, barriers, and facilitators of an MLP, among clinicians, clinic and MLP staff, and clinic patients. Open AI software (otter.ai) was used to transcribe interviews, and NVivo was used to code the data. Braun & Clarke’s framework was used to identify themes and subthemes.

Results:

Sixteen (n = 16) participants were included in this study. Most respondents were women (81%) and white (56%). Four respondents were clinic staff, and 4 were MLP staff while 8 were clinic patients. Several primary themes emerged including: Patients experienced legal issues that were pernicious, pervasive, and complex; through trusting relationships, the MLP was able to improve health and resolve legal issues, for some; mistrust, communication gaps, and inconsistent staffing limited the impact of the MLP; and, the MLP identified coordination and communication strategies to enhance trust and amplify its impact.

Conclusion:

HHLNs can have a significant, negative impact on the physical and mental health of patients. Respondents perceived that MLPs improved health and resolved these needs, for some. Despite perceived successes, integration between the clinical and legal organizations was elusive.




ana

A Review of Artificial Intelligence and Machine Learning in Product Life Cycle Management

The pursuit of harnessing data for knowledge creation has been an enduring quest, with the advent of machine learning (ML) and artificial intelligence (AI) marking significant milestones in this journey. ML, a subset of AI, emerged as the practice of employing mathematical models to enable computers to learn and improve autonomously based on their experiences. In the pharmaceutical and biopharmaceutical sectors, a significant portion of manufacturing data remains untapped or insufficient for practical use. Recognizing the potential advantages of leveraging the available data for process design and optimization, manufacturers face the daunting challenge of data utilization. Diverse proprietary data formats and parallel data generation systems compound the complexity. The transition to Pharma 4.0 necessitates a paradigm shift in data capture, storage, and accessibility for manufacturing and process operations. This paper highlights the pivotal role of AI in converting process data into actionable knowledge to support critical functions throughout the whole product life cycle. Furthermore, it underscores the importance of maintaining compliance with data integrity guidelines, as mandated by regulatory bodies globally. Embracing AI-driven transformations is a crucial step toward shaping the future of the pharmaceutical industry, ensuring its competitiveness and resilience in an evolving landscape.




ana

Identification and Root Cause Analysis of the Visible Particles Commonly Encountered in the Biopharmaceutical Industry

Visible particle is an important issue in the biopharmaceutical industry, and it may occur across all the stages in the life cycle of biologics. Upon the occurrence of visible particles, it is often necessary to conduct chemical identification and root cause analysis to safeguard the safety and efficacy of the biotherapeutic products. In this article, we present a number of typical particles and relevant root cause analysis in the categories of extrinsic, intrinsic, and inherent particles that are commonly encountered in the biopharma industry. In particular, the optical images of particles obtained both in situ and after isolation are provided, along with spectral and elemental information. The particle identification was carried out with multiple microscopic and microspectroscopic techniques, including stereo optical microscopy, Fourier-transform infrared microscopy, confocal Raman microscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy. Both commercial and in-house spectral databases were used for comparison and identification. In addition to particle identification, we placed significant efforts on the root cause analysis of the addressed particles with the intention to provide a relatively whole picture of the particle-related issues and practical references to particle mitigation for our peers in the biopharmaceutical industry.




ana

Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: implications to alternative conformations and their statistical structural analyses [ARTICLE]

The SARS-CoV-2 frameshifting element (FSE) has been intensely studied and explored as a therapeutic target for coronavirus diseases, including COVID-19. Besides the intriguing virology, this small RNA is known to adopt many length-dependent conformations, as verified by multiple experimental and computational approaches. However, the role these alternative conformations play in the frameshifting mechanism and how to quantify this structural abundance has been an ongoing challenge. Here, we show by DMS and dual-luciferase functional assays that previously predicted FSE mutants (using the RAG graph theory approach) suppress structural transitions and abolish frameshifting. Furthermore, correlated mutation analysis of DMS data by three programs (DREEM, DRACO, and DANCE-MaP) reveals important differences in their estimation of specific RNA conformations, suggesting caution in the interpretation of such complex conformational landscapes. Overall, the abolished frameshifting in three different mutants confirms that all alternative conformations play a role in the pathways of ribosomal transition.




ana

A worldwide perspective of long COVID management: how can we END-COVID?

Extract

As of 15 May 2024, >775 million confirmed cases of COVID-19 and >7 million deaths have been reported to the World Health Organization [1]. Although most patients with COVID-19 survive, survivors are at risk of long COVID, the sequelae of the viral infection affecting multiple organ systems [2]. Long COVID poses a substantial burden to individuals and society, even with a conservative estimate of 10% prevalence among COVID-19 survivors [3–5]. However, as the symptoms of long COVID vary substantially, ranging from respiratory symptoms, such as dyspnoea and cough, to fatigue and cognitive impairment [6], developing a standard set of investigations and management protocols for patients with long COVID is challenging.




ana

A worldwide look into long COVID-19 management: an END-COVID survey

Background

Long COVID is a heterogeneous clinical syndrome characterised by a variety of reported symptoms and signs. Its clinical management is expected to differ significantly worldwide.

Methods

A survey-based study investigating long COVID-related standard operating procedures (SOPs) has been conducted by the European Respiratory Society (ERS) END-COVID clinical research collaboration with the support of other international societies (ALAT, APSR, CHEST, ESCMID and PATS). A global analysis of the results is provided here, alongside sub-population analysis based on continents, national income levels, type of involved healthcare professional and inclusion or exclusion of paediatric patients.

Findings

1015 healthcare professionals from 110 different countries worldwide participated in this study, the majority of them being respiratory physicians (60.6%). A dedicated long COVID programme was present in 55.4% of the investigated institutions, with hospital admission during the acute infection being the main inclusion criteria to access them. Consistent differences in long COVID-related procedures were identified among centres, mainly regarding the multidisciplinary approach, the availability of telemedicine and psychological support, the type of requested exams and the total amount of visits in the centre.

Interpretation

Long COVID management shows important differences related to geographical areas and national income levels. SOPs were significantly different when centres were managed by a pulmonologist or when paediatric patients were included.




ana

Multidisciplinary management of adult patients with chylothorax: a consensus statement

The management of chylothorax remains challenging given the limited evidence and significant heterogeneity in practice. In addition, there are no practical guidelines on the optimal approach to manage this complex condition. We convened an international group of 27 experts from 20 institutions across five countries and four specialties (pulmonary, interventional radiology, thoracic surgery and nutrition) with experience and expertise in managing adult patients with chylothorax. We performed a literature and internet search for reports addressing seven clinically relevant PICO (Patient, Intervention, Comparison and Outcome) questions pertaining to the management of adult patients with chylothorax. This consensus statement, consisting of best practice statements based on expert consensus addressing these seven PICO questions, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with provider experience. Panel members participated in the development of the final best practice statements using the modified Delphi technique. Our consensus statement aims to offer guidance in clinical decision making when managing patients with chylothorax while also identifying gaps in knowledge and informing future research.




ana

Reassessing Halm's clinical stability criteria in community-acquired pneumonia management

Background

Halm's clinical stability criteria have long guided antibiotic treatment and hospital discharge decisions for patients hospitalised with community-acquired pneumonia (CAP). Originally introduced in 1998, these criteria were established based on a relatively small and select patient population. Consequently, our study aims to reassess their applicability in the management of CAP in a contemporary real-world setting.

Methods

This cohort study included 2918 immunocompetent patients hospitalised with CAP from three hospitals in Denmark between 2017 and 2020. The primary outcome was time to achieve clinical stability as defined by Halm's criteria. Additionally, we examined recurrence of clinical instability and severe complications. Cumulative incidence function or Kaplan–Meier survival curves were used to analyse these outcomes, considering competing risks.

Results

The study population primarily comprised elderly individuals (median age 75 years) with significant comorbidities. The median time to clinical stability according to Halm's criteria was 4 days, with one-fifth experiencing recurrence of instability after early clinical response (stability within 3 days). Severe complications within 30 days mainly comprised mortality, with rates of 5.1% (64/1257) overall in those with early clinical response, 1.7% (18/1045) in the subgroup without do-not-resuscitate orders and 17.3% (276/1595) among the rest.

Conclusion

Halm's clinical stability criteria effectively classify CAP patients with different disease courses, yet achieving stability required more time in this ageing population with substantial comorbidities and more severe disease. Early clinical response indicates reduced risk of complications, especially in those without do-not-resuscitate orders.




ana

Evaluating Drug-Drug Interaction Risk Associated with Peptide Analogs Using advanced In Vitro Systems [Special Section on New and Emerging Areas and Technologies in Drug Metabolism and Disposition, Part II]

Drug–drug interaction (DDI) assessment of therapeutic peptides is an evolving area. The industry generally follows DDI guidelines for small molecules, but the translation of data generated with commonly used in vitro systems to in vivo is sparse. In the current study, we investigated the ability of advanced human hepatocyte in vitro systems, namely HepatoPac, spheroids, and Liver-on-a-chip, to assess potential changes in regulation of CYP1A2, CYP2B6, CYP3A4, SLCO1B1, and ABCC2 in the presence of selected therapeutic peptides, proteins, and small molecules. The peptide NN1177, a glucagon and GLP-1 receptor co-agonist, did not suppress mRNA expression or activity of CYP1A2, CYP2B6, and CYP3A4 in HepatoPac, spheroids, or Liver-on-a-chip; these findings were in contrast to the data obtained in sandwich cultured hepatocytes. No effect of NN1177 on SLCO1B1 and ABCC2 mRNA was observed in any of the complex systems. The induction magnitude differed across the systems (e.g., rifampicin induction of CYP3A4 mRNA ranged from 2.8-fold in spheroids to 81.2-fold in Liver-on-a-chip). Small molecules, obeticholic acid and abemaciclib, showed varying responses in HepatoPac, spheroids, and Liver-on-a-chip, indicating a need for EC50 determinations to fully assess translatability data. HepatoPac, the most extensively investigated in this study (3 donors), showed high potential to investigate DDIs associated with CYP regulation by therapeutic peptides. Spheroids and Liver-on-a-chip were only assessed in one hepatocyte donor and further evaluations are required to confirm their potential. This study establishes an excellent foundation toward the establishment of more clinically-relevant in vitro tools for evaluation of potential DDIs with therapeutic peptides.

SIGNIFICANT STATEMENT

At present, there are no guidelines for drug–drug interaction (DDI) assessment of therapeutic peptides. Existing in vitro methods recommended for assessing small molecule DDIs do not appear to translate well for peptide drugs, complicating drug development for these moieties. Here, we establish evidence that complex cellular systems have potential to be used as more clinically-relevant tools for the in vitro DDI evaluation of therapeutic peptides.




ana

National Politics&#x2019; Role in Developing Primary Health Care Policy for Maternal Health in Papua New Guinea: A Qualitative Document Analysis

ABSTRACTPolitics is one of the critical factors that influence health policy agendas. However, scholarly efforts, especially in low- and middle-income countries, rarely focus on how politics influence health policy agenda-setting. We conducted a qualitative document review to examine the factors that led to developing the free primary health care policy for maternal health in Papua New Guinea. We also discuss mechanisms through which national politics, as an overriding factor, influenced the development of the policy. The review draws on Kingdon’s multiple-stream model for agenda-setting and incorporates theoretical insights from Fox and Reich’s framework for analyzing the politics of health reform for universal health coverage in low- and middle-income countries.




ana

Proteomic Analysis of Signaling Pathways Modulated by Fatty Acid Binding Protein 5 (FABP5) in Macrophages [Special Section: Cannabinoid Signaling in Human Health and Disease]

Although acute inflammation serves essential functions in maintaining tissue homeostasis, chronic inflammation is causally linked to many diseases. Macrophages are a major cell type that orchestrates inflammatory processes. During inflammation, macrophages undergo polarization and activation, thereby mobilizing pro-inflammatory and anti-inflammatory transcriptional programs that regulate ensuing macrophage functions. Fatty acid binding protein 5 (FABP5) is a lipid chaperone highly expressed in macrophages. FABP5 deletion is implicated in driving macrophages toward an anti-inflammatory phenotype, yet signaling pathways regulated by macrophage-FABP5 have not been systematically profiled. We leveraged proteomic and phosphoproteomic approaches to characterize pathways modulated by FABP5 in M1 and M2 polarized bone marrow-derived macrophages (BMDMs). Stable isotope labeling by amino acids-based analysis of M1 and M2 polarized wild-type and FABP5 knockout BMDMs revealed numerous differentially regulated proteins and phosphoproteins. FABP5 deletion impacted downstream pathways associated with inflammation, cytokine production, oxidative stress, and kinase activity. Toll-like receptor 2 (TLR2) emerged as a novel target of FABP5 and pharmacological FABP5 inhibition blunted TLR2-mediated activation of downstream pathways, ascribing a novel role for FABP5 in TLR2 signaling. This study represents a comprehensive characterization of the impact of FABP5 deletion on the proteomic and phosphoproteomic landscape of M1 and M2 polarized BMDMs. Loss of FABP5 altered pathways implicated in inflammatory responses, macrophage function, and TLR2 signaling. This work provides a foundation for future studies seeking to investigate the therapeutic potential of FABP5 inhibition in pathophysiological states resulting from dysregulated inflammatory signaling.

SIGNIFICANCE STATEMENT

This research offers a comprehensive analysis of fatty acid binding protein 5 (FABP5) in macrophages during inflammatory response. The authors employed quantitative proteomic and phosphoproteomic approaches to investigate this utilizing bone marrow-derived macrophages that were M1 and M2 polarized using lipopolysaccharide with interferon and interleukin-4, respectively. This revealed multiple pathways related to inflammation that were differentially regulated due to the absence of FABP5. These findings underscore the potential therapeutic significance of macrophage-FABP5 as a candidate for addressing inflammatory-related diseases.




ana

KLS-13019, a Novel Structural Analogue of Cannabidiol and GPR55 Receptor Antagonist, Prevents and Reverses Chemotherapy-Induced Peripheral Neuropathy in Rats [Special Section: Cannabinoid Signaling in Human Health and Disease]

Neuropathic pain is a form of chronic pain that develops because of damage to the nervous system. Treatment of neuropathic pain is often incompletely effective, and most available therapeutics have only moderate efficacy and present side effects that limit their use. Opioids are commonly prescribed for the management of neuropathic pain despite equivocal results in clinical studies and significant abuse potential. Thus, neuropathic pain represents an area of critical unmet medical need, and novel classes of therapeutics with improved efficacy and safety profiles are urgently needed. The cannabidiol structural analog and novel antagonist of GPR55, KLS-13019, was screened in rat models of neuropathic pain. Tactile sensitivity associated with chemotherapy exposure was induced in rats with once-daily 1-mg/kg paclitaxel injections for 4 days or 5 mg/kg oxaliplatin every third day for 1 week. Rats were then administered KLS-13019 or comparator drugs on day 7 in an acute dosing paradigm or days 7–10 in a chronic dosing paradigm, and mechanical or cold allodynia was assessed. Allodynia was reversed in a dose-dependent manner in the rats treated with KLS-13019, with the highest dose reverting the response to prepaclitaxel injection baseline levels with both intraperitoneal and oral administration after acute dosing. In the chronic dosing paradigm, four consecutive doses of KLS-13019 completely reversed allodynia for the duration of the phenotype in control animals. Additionally, coadministration of KLS-13019 with paclitaxel prevented the allodynic phenotype from developing. Together, these data suggest that KLS-13019 represents a potential new drug for the treatment of neuropathic pain.

SIGNIFICANCE STATEMENT

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect of cancer treatment with no known cure. The GPR55 antagonist KLS-13019 represents a novel class of drug for this condition that is a potent, durable inhibitor of allodynia associated with CIPN in rats in both prevention and reversal-dosing paradigms. This novel therapeutic approach addresses a critical area of unmet medical need.




ana

Analgesic Properties of Next-Generation Modulators of Endocannabinoid Signaling: Leveraging Modern Tools for the Development of Novel Therapeutics [Special Section: Cannabinoid Signaling in Human Health and Disease-Minireview]

Targeting the endocannabinoid (eCB) signaling system for pain relief is an important treatment option that is only now beginning to be mechanistically explored. In this review, we focus on two recently appreciated cannabinoid-based targeting strategies, treatments with cannabidiol (CBD) and α/β-hydrolase domain containing 6 (ABHD6) inhibitors, which have the exciting potential to produce pain relief through distinct mechanisms of action and without intoxication. We review evidence on plant-derived cannabinoids for pain, with an emphasis on CBD and its multiple molecular targets expressed in pain pathways. We also discuss the function of eCB signaling in regulating pain responses and the therapeutic promises of inhibitors targeting ABHD6, a 2-arachidonoylglycerol (2-AG)-hydrolyzing enzyme. Finally, we discuss how the novel cannabinoid biosensor GRABeCB2.0 may be leveraged to enable the discovery of targets modulated by cannabinoids at a circuit-specific level.

SIGNIFICANCE STATEMENT

Cannabis has been used by humans as an effective medicine for millennia, including for pain management. Recent evidence emphasizes the therapeutic potential of compounds that modulate endocannabinoid signaling. Specifically, cannabidiol and inhibitors of the enzyme ABHD6 represent promising strategies to achieve pain relief by modulating endocannabinoid signaling in pain pathways via distinct, nonintoxicating mechanisms of action.




ana

Low-Efficacy Mu Opioid Agonists as Candidate Analgesics: Effects of Novel C-9 Substituted Phenylmorphans on Pain-Depressed Behavior in Mice [Behavioral Pharmacology]

Low-efficacy mu opioid receptor (MOR) agonists may serve as novel candidate analgesics with improved safety relative to high-efficacy opioids. This study used a recently validated assay of pain-depressed behavior in mice to evaluate a novel series of MOR-selective C9-substituted phenylmorphan opioids with graded MOR efficacies. Intraperitoneal injection of dilute lactic acid (IP acid) served as a noxious stimulus to depress locomotor activity by mice in an activity chamber composed of two compartments connected by an obstructed door. Behavioral measures included (1) crosses between compartments (vertical activity over the obstruction) and (2) movement counts quantified as photobeam breaks summed across compartments (horizontal activity). Each drug was tested alone and as a pretreatment to IP acid. A charcoal-meal test and whole-body-plethysmography assessment of breathing in 5% CO2 were also used to assess gastrointestinal (GI) inhibition and respiratory depression, respectively. IP acid produced a concentration-dependent depression in crosses and movement that was optimally alleviated by intermediate- to low-efficacy phenylmorphans with sufficient efficacy to produce analgesia with minimal locomotor disruption. Follow-up studies with two low-efficacy phenylmorphans (JL-2-39 and DC-1-76.1) indicated that both drugs produced naltrexone-reversible antinociception with a rapid onset and a duration of ~1 h. Potency of both drugs increased when behavior was depressed by a lower IP-acid concentration, and neither drug alleviated behavioral depression by a non-pain stimulus (IP lithium chloride). Both drugs produced weaker GI inhibition and respiratory depression than fentanyl and attenuated fentanyl-induced GI inhibition and respiratory depression. Results support further consideration of selective, low-efficacy MOR agonists as candidate analgesics.

SIGNIFICANCE STATEMENT

This study used a novel set of mu opioid receptor (MOR)-selective opioids with graded MOR efficacies to examine the lower boundary of MOR efficacy sufficient to relieve pain-related behavioral depression in mice. Two novel low-efficacy opioids (JL-2-39, DC-1-76.1) produced effective antinociception with improved safety relative to higher- or lower-efficacy opioids, and results support further consideration of these and other low-efficacy opioids as candidate analgesics.




ana

The Dawning of a New Age of Preclinical Analgesic Drug Screening [Viewpoint]




ana

Impact of 18F-FES PET/CT on Clinical Decisions in the Management of Recurrent or Metastatic Breast Cancer

The clinical impact of 16α-18F-fluoro-17β-estradiol (18F-FES) PET/CT on patient management has not been well investigated. The aim of this study was to assess the clinical impact of 18F-FES PET/CT on the management of patients with recurrent or metastatic breast cancer. Methods: Study subjects were identified retrospectively from a database of a prospective trial for postmarketing surveillance of 18F-FES between 2021 and 2023. Patients who were suspected or known to have recurrent or metastatic estrogen receptor–positive breast cancer based on a routine standard workup were included. Planned management before and actual management after 18F-FES PET/CT were assessed by 2 experienced medical oncologists via medical chart review. A 5-point questionnaire was provided to evaluate the value of 18F-FES PET/CT for management planning. The rate of intention-to-treat and interdisciplinary changes, and the impact of 18F-FES PET/CT according to PET/CT result or clinical indication, were examined. Results: Of the 344 included patients, 120 (35%) experienced a change in management after 18F-FES PET/CT. In 139 (40%) patients,18F-FES PET/CT supported the existing management decision without a change in management. Intention-to-treat and interdisciplinary changes accounted for 64% (77/120) and 68% (82/120) of all changes, respectively. A higher rate of change was observed when lesions were 18F-FES–negative (44% [36/81]) than 18F-FES–positive (30% [51/172]) or mixed 18F-FES–positive/negative (36% [33/91]). Regarding clinical indications, the highest rate of change was shown when evaluating the origins of metastasis of double primary cancers (64% [9/14]). Conclusion: 18F-FES PET/CT modified the management of recurrent or metastatic breast cancer, serving as an impactful imaging modality in clinical practice.




ana

Is the Clinical Application of CXCR4 Imaging in the Diagnosis and Management of Primary Aldosteronism Really Happening?




ana

Precautions to Consider in the Analysis of Prognostic and Predictive Indices

Understanding the differences between prognostic and predictive indices is imperative for medical research advances. We have developed a new prognostic measure that will identify the strengths, limitations, and potential applications in clinical practice.




ana

Diffusion Analysis of Intracranial Epidermoid, Head and Neck Epidermal Inclusion Cyst, and Temporal Bone Cholesteatoma [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Intracranial epidermoids temporal bone cholesteatomas, and head and neck epidermal inclusion cysts are typically slow-growing, benign conditions arising from ectodermal tissue. They exhibit increased signal on DWI. While much of the imaging literature describes these lesions as showing diffusion restriction, we investigated these qualitative signal intensities and interpretations of restricted diffusion with respect to normal brain structures. This study aimed to quantitatively evaluate the ADC values and histogram features of these lesions.

MATERIALS AND METHODS:

This retrospective study included children with histologically confirmed diagnoses of intracranial epidermoids, temporal bone cholesteatomas, or head and neck epidermal inclusion cysts. Lesions were segmented, and voxelwise calculation of ADC values was performed along with histogram analysis. ADC calculations were validated with a second analysis software to ensure accuracy. Normal brain ROIs—including the cerebellum, white matter, and thalamus—served as normal comparators. Correlational analysis and Bland-Altman plots assessed agreement among software tools for ADC calculations. Differences in the distribution of values between the lesions and normal brain tissues were assessed using the Wilcoxon rank sum and Kruskal-Wallis tests.

RESULTS:

Forty-eight pathology-proved cases were included in this study. Among them, 13 (27.1%) patients had intracranial epidermoids 14 (29.2%) had head and neck epidermal inclusion cysts, and 21 (43.7%) had temporal bone cholesteatomas. The mean age was 8.67 (SD, 5.30) years, and 27 (56.3%) were female. The intraclass correlation for absolute agreement for lesional ADC between the 2 software tools was 0.997 (95% CI, 0.995–0.998). The intracranial epidermoid head and neck epidermal inclusion cyst, and temporal bone cholesteatoma median ADC values were not significantly different (973.7 versus 875.7 versus 933.2 x 10–6 mm2/s, P = .265). However, the ADCs of the 3 types of lesions were higher than those of 3 normal brain tissue types (933 versus 766, x 10–6 mm2/s, P < .001).

CONCLUSIONS:

The ADC values of intracranial epidermoids, temporal bone cholesteatomas, and head and neck epidermal inclusion cysts are higher than those of normal brain regions. It is not accurate to simply classify these lesions as exhibiting restricted diffusion or reduced diffusivity without considering the tissue used for comparison. The observed hyperintensity on DWI compared with the brain is likely attributable to a relatively higher contribution of the T2 shinethrough effect.