bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of occupational co-exposure to biomechanical factors and neurotoxic chemicals in French workers
Authors: Bodin Julie , Babin Jessica , Bertin Mélanie , Bonvallot Nathalie , Roquelaure Yves
Published: March 2024

Objectives

Little is known about occupational co-exposure. The objective was to assess the prevalence of exposure and co-exposure to biomechanical factors and neurotoxic chemicals in French workers in 2017.

Methods

Data from the French representative survey SUMER 2017 (SUrveillance Médicale des Expositions aux Risques professionnels) were analyzed. A total of 25 118 workers were included. Exposure to 4 biomechanical factors (manual handling of loads, forceful joint exertion, repetitive movements, and hand-arm transmitted vibrations) and 18 neurotoxic chemicals (n-hexane, perchloroethylene, trichloroethylene, etc.) were assessed using a questionnaire during face-to-face interviews with occupational physicians.

Results

Among men, 22.9% were exposed to at least one biomechanical factor and 10.2% were exposed to at least one neurotoxic chemical, mainly single exposures. Among women, 10.8% were exposed to at least one biomechanical factor and 3.1% were exposed to at least one neurotoxic chemical, also mainly single exposures. Occupational co-exposure to biomechanical factors and neurotoxic chemicals was observed among 4.8% of men and 0.7% of women. Workers under 30 yr old, blue-collar workers and those working in small companies were more co-exposed than other workers. In men, the prevalence of co-exposure was higher in the construction sector compared to other economic activities.

Discussion

This study stresses the importance of considering multiple occupational exposures while the current prevention measures are designed to focus on preventing occupational factors individually.
Upfront surgery for stage IIIA/B non-small cell lung cancer: retrospective cohort study
Authors: Deng Hongsheng , Liu Jun , Cai Xiuyu , Jiang Shunjun , Lu Weixiang , Ai Qing , Li Jianfu , Xiong Shan , Qin Xiangyun , Liang Wenhua , He Jianxing
Published: March 2024

Background

Stage III non-small cell lung cancer is a heterogeneous disease. Several international guidelines recommend neoadjuvant treatment before surgery; however, upfront surgery is the preferred approach for technically resectable non-small cell lung cancer in East Asia. The aim of this retrospective study was to evaluate the long-term outcomes of curative-intent upfront surgery in stage IIIA/B non-small cell lung cancer.

Methods

Patients who underwent curative-intent upfront surgery with stage cIIIA/B non-small cell lung cancer were identified. The clinical and pathological variables and survival outcomes were evaluated.

Results

Overall, 664 patients were identified, of whom 320 (48.8%) had N2 disease, 66.7% were males, 49.4% had a smoking history, and 61.2% had lung adenocarcinoma. Lobectomy was the most performed surgical procedure (84.9%). A total of 40 patients (6.02%) had positive margins (R1/R2). The grade III adverse event rate was 2.0% (13 of 664). The median follow-up was 30.6 (range 1.9–97.7) months. At follow-up, the mortality rate was 13.3% (88 of 664) and 37.2% of patients (247 of 664) had recurrence. Lung (101 of 247 (40.9%)) and brain (53 of 247 (21.5%)) were the most common sites of recurrence. The median overall survival was 60.0 (95% c.i. 51.5 to 67.6) months, with overall survival probability at 1, 2, 3, and 5 years being 89.6%, 77.8%, 67.2%, and 49.0% respectively. The R0 cohort showed an improved median overall survival compared with the R1/R2 cohort (67.4 versus 26.5 months respectively; P = greater than 0.001). The multivariable analysis revealed that age greater than or equal to 65 years (HR 1.51, 95% c.i. 1.08 to 2.12; reference = age less than 65 years), tumour size (greater than or equal to 5 cm (HR 2.13, 95% c.i. 1.41 to 3.21) and greater than or equal to 3 cm but less than 5 cm (HR 1.15, 95% c.i. 0.78 to 1.71); reference = less than 3 cm), and adjuvant treatment (chemotherapy (HR 0.69, 95% c.i. 0.49 to 0.96) and targeted therapy (HR 0.30, 95% c.i. 0.12 to 0.76); reference = none) significantly predicted overall survival.

Conclusion

Upfront surgery is an option for the management of stage IIIA/B non-small cell lung cancer.
Association of myocardial injury with adverse long-term survival among cancer patients
Authors: Bashar Hussein , Kobo Ofer , Curzen Nick , Mamas Mamas A
Published: March 2024

Aims

Over time, cardiovascular disease (CVD) deaths increasingly exceed those from malignancy among cancer survivors. However, the association of myocardial injury with long-term survival (beyond 3 years) in cancer patients has not been previously described.

Methods and results

The high-sensitivity cardiac troponin (hs-cTn) and morbidities databases from the National Health and Nutrition Examination Survey (1999–2004) were linked with the latest mortality dataset isolating records were respondents reported cancer diagnosis by a healthcare professional. Myocardial injury was then determined by elevated hs-cTn. A total of 16 225 560 weighted records (1058 unweighted) were included in this observational study, with myocardial injury identified in 14.2%. Those with myocardial injury had progressively worse survival at 5 (51.6 vs. 89.5%), 10 (28.3 vs. 76.0%), and 15 years (12.6 vs. 61.4%) compared with those without myocardial injury. After adjusting for baseline characteristics, those with myocardial injury had an adjusted hazard ratio (aHR) of 2.10 [95% confidence interval (CI) 2.09–2.10, P < 0.001] for all-cause mortality, 2.23 (2.22–2.24, P < 0.001) for cardiovascular mortality, and 1.59 (95% CI 1.59–1.60, P < 0.001) for cancer mortality compared with those without myocardial injury. Among patients with no pre-existing CVD, the hs-cTn I Ortho assay was a strong independent predictor of all-cause (aHR 6.29, 95% CI 6.25–6.33, P < 0.001), CVD (aHR 11.38, 95% CI 11.23–11.54, P < 0.001), and cancer (aHR 5.02, 95% CI 4.96–5.07, P < 0.001) mortalities.

Conclusion

As a marker for myocardial injury, hs-cTns were independently associated with worse long-term survival among cancer patients with a stronger relationship with all-cause, cardiovascular, and cancer mortalities using hs-cTn I Ortho assay.
Effect of heart failure pharmacotherapies in patients with heart failure with mildly reduced ejection fraction
Authors: Schupp Tobias , Bertsch Thomas , Reinhardt Marielen , Abel Noah , Schmitt Alexander , Lau Felix , Abumayyaleh Mohammad , Akin Muharrem , Weiß Christel , Weidner Kathrin , Behnes Michael , Akin Ibrahim
Published: March 2024

Aims

The study sought to comprehensively investigate the effect of heart failure (HF) pharmacotherapies in patients with HF with mildly reduced ejection fraction (HFmrEF). In the absence of randomized controlled trials, guideline recommendations concerning HF-related therapies in patients with HFmrEF are limited.

Methods and results

Consecutive patients hospitalized with HFmrEF were retrospectively included at one institution from 2016 to 2022. The prognostic value of treatment with beta-blockers (BB), angiotensin-converting enzyme inhibitors, receptor blockers, or receptor-neprilysin inhibitor (ACEi/ARB/ARNI), mineralocorticoid receptor antagonists (MRA), and sodium–glucose-linked transport protein 2 inhibitors (SGLT2i) was investigated for all-cause mortality at 30 months (a median follow-up) and HF-related rehospitalization. A total of 2109 patients with HFmrEF were included. Treatment with BB [27.0 vs. 35.0%; hazard ratio (HR) = 0.737; 95% confidence interval (CI) 0.617–0.881; P = 0.001], ACEi/ARB/ARNI (25.9 vs. 37.6%; HR = 0.612; 95% CI 0.517–0.725; P = 0.001), and SGLT2i (11.9 vs. 29.5%; HR = 0.441; 95% CI 0.236–0.824; P = 0.010) was associated with a lower risk of 30-month all-cause mortality, which was still demonstrated after multivariable adjustment and propensity score matching. In contrast, MRA treatment was not associated with long-term prognosis. The risk of HF-related rehospitalization was not affected by HF pharmacotherapies. Finally, the lowest risk of long-term all-cause mortality was observed in patients with combined use of BB, ACEi/ARB/ARNI, and SGLT2i (HR = 0.456; 95% CI 0.227–0.916; P = 0.027).

Conclusion

Beta-blockers, ACEi/ARB/ARNI, and SGLT2i were independently associated with a lower risk of all-cause mortality in patients with HFmrEF, specifically when applied as combined ‘HF triple therapy’. Randomized studies are needed to investigate the effect of HF-related pharmacotherapies in patients with HFmrEF.
☐ and ◇ in eight-valued non-deterministic semantics for modal logics
Authors: Pawlowski Pawel , Skurt Daniel
Published: March 2024

In this paper we study several extensions of the minimal modal logic M. This minimal modal logic is formulated in the language of classical propositional logic together with two modal operators $\Box $ and $\Diamond $, which have no deductive power. By extending the Hilbert calculus for M with various axioms for $\Box $ and $\Diamond $ and/or the rule of necessitation, we obtain several well-known normal modal logics, as well as systems that are of pure theoretical interest. Those systems are shown to be sound and complete wrt to eight-valued semantics. Those semantics are obtained by refinements of an eight-valued semantics for M. Furthermore, we will briefly discuss some limitations of the method presented in this article.
Introduction
Authors: Kerns Connor M. , Albano Anne Marie , Silverman Wendy K.
Published: March 2024

This chapter discusses the first part of the Anxiety and Related Disorders Interview Schedule for DSM-5, Child Version, with Autism Spectrum Addendum (ADIS/ASA): Parent Interview Schedule (PIS). The interviewer should begin with a brief introduction and explanation of what symptoms of anxiety disorder can look like and how these symptoms can be difficult to distinguish from symptoms of Autism Spectrum Disorder or other common difficulties that co-occur with ASD, such as Attention-Deficit/Hyperactivity Disorder (ADHD). With this in mind, the interviewer should then share the purpose of the interview, obtain a brief description of the difficulties the parent believes may be due to anxiety, and ascertain the reasons for seeking professional help at this time. It is also important to briefly explain the Feelings Thermometer. The chapter provides a guiding script for communication with the parent or guardian.
Generalized Anxiety Disorder
Authors: Kerns Connor M. , Albano Anne Marie , Silverman Wendy K.
Published: March 2024

This chapter focuses on the Generalized Anxiety Disorder section of the Anxiety and Related Disorders Interview Schedule for DSM-5, Child Version, with Autism Spectrum Addendum (ADIS/ASA): Parent Interview Schedule (PIS). This section offers some guidelines and special considerations for differentiating symptoms of generalized anxiety from behavioral difficulties secondary to Autism Spectrum Disorder (ASD). Some children on the autism spectrum present with intense fears and worries about even small changes to their environment, schedule, or activities. They may also present with intense resistance to novel or unstructured situations and worries that are specifically focused on an area or activity about which they are intensely interested. Clinicians should assess if the child’s fears are realistic given the particular circumstances of their life and abilities. Behavioral examples of anticipatory worries and fears should be clear and compelling in order to diagnose Generalized Anxiety Disorder in a child who cannot or does not verbally express these concerns. When assessing generalized anxiety, clinicians should also assess and help parents to focus on the child’s worries rather than on other forms of perseverative thinking.
Obsessive-Compulsive Disorder and Other Compulsive Behaviors
Authors: Kerns Connor M. , Albano Anne Marie , Silverman Wendy K.
Published: March 2024

This chapter discusses the section on Obsessive-Compulsive Disorder (OCD) and Other Compulsive Behaviors in the Anxiety and Related Disorders Interview Schedule for DSM-5, Child Version, with Autism Spectrum Addendum (ADIS/ASA): Parent Interview Schedule (PIS). This section provides some guidelines and special considerations for distinguishing obsessions and compulsions from behaviorally similar symptoms in Autism Spectrum Disorder (ASD). Obsessions in OCD are unwanted thoughts/images that are anxiety-provoking and upsetting to the child. Whereas children are upset and wish to get rid of obsessions, the opposite is true of focused interests in ASD, which are typically associated with enjoyment and excitement and may even be soothing or used by some children to reduce feelings of anxiety. Meanwhile, compulsions are actions or thoughts that a child feels driven to complete in a specific order or manner. Compulsions have several defining features relative to other repetitive behaviors. Compulsions typically result in short-term relief but are driven by discomfort and/or fear rather than being inherently enjoyable. By comparison, some repetitive behaviors are soothing or enjoyable for children. Compulsions are also typically associated with and designed to “undo,” “correct,” or neutralize obsessions. In contrast to repetitive self-soothing behaviors like rocking or pacing, compulsions have a specific relationship to obsessions and thus must be performed in a specific manner or order before the child can move on to something else.
School Refusal Behavior
Authors: Albano Anne Marie , Silverman Wendy K.
Published: March 2024

This chapter focuses on the School Refusal Behavior section of the Anxiety and Related Disorders Interview Schedule for DSM-5, Child and Parent Version: Child Interview Schedule (CIS). The interviewer should inquire for school “withdrawal,” where the child is kept home to meet the needs of other family members (e.g., an ill adult, assist in childcare, or due to child neglect). The next step is to inquire using the concept(s) identified by the child in Questions 1 and 2: fear, anxiety, sadness, or depression. The focus is on internalizing conditions that motivate the school refusal, as opposed to externalizing problems such as truancy. It is also important to inquire about patterns of reassurance seeking. In addition, the interviewer may show the child the Feelings Thermometer and obtain an overall rating of interference from the child. Evidence of significant school refusal behavior warrants clarification and further examination within each of the DSM-5 diagnostic categories. School refusal is not a diagnostic category by itself but might be a behavioral manifestation of a clinical disorder.
Bipolar Disorder
Authors: Albano Anne Marie , Silverman Wendy K.
Published: March 2024

This chapter discusses the Bipolar Disorder module in the Anxiety and Related Disorders Interview Schedule for DSM-5, Child and Parent Version: Child Interview Schedule (CIS). The elevated mood or irritability is not accounted for by other disorders such as Oppositional Defiant Disorder (ODD), attention-deficit/hyperactivity disorder (ADHD), or Substance Use Disorder. If the child endorsed a Major Depressive Episode, the interviewer should inquire whether these symptoms occurred during the same 2-week period. If criteria are met for a Manic or Hypomanic Episode, the interviewer should consider a diagnosis of Bipolar Disorder. If the child’s symptoms do not meet the full criteria for a Manic or Hypomanic Episode, the interviewer should consider a diagnosis of Bipolar Disorder, NOS. These children may have typical bipolar symptoms but not the duration required by DSM. In addition, these children may be characterized by severe irritability, aggressiveness, agitation, and/or mood lability. There may also be more rapid cycling of mood.
Attention-Deficit/Hyperactivity Disorder (ADHD)
Authors: Albano Anne Marie , Silverman Wendy K.
Published: March 2024

This chapter details the Attention-Deficit/Hyperactivity Disorder (ADHD) module in the Anxiety and Related Disorders Interview Schedule for DSM-5, Child and Parent Version: Child Interview Schedule (CIS). To meet criteria for a diagnosis of ADHD, the child must respond “yes” to at least six of Questions 1–9 in the Attention Deficit section or “yes” to at least six of Questions 1–9 in the Hyperactivity and Impulsivity section. Also, the child must have indicated that the problem has been going on for at least 6 months, began before age 12, and occurs in more than one setting. For ages 17 and older, at least five symptoms are required for the diagnosis. It is also important to measure interference through the Feelings Thermometer.
Endocrinology
Authors: Phylactou Maria
Published: March 2024

Whilst the main aim of this chapter on endocrinology is to arrive at a working practical knowledge of diabetes, it will also raise awareness of the other glands, so that their dysfunction can be recognized and investigated where appropriate. This chapter contains 44 questions that encompass all of the important areas of this subject, with detailed explanations. Unique to this series, questions are rated by difficulty and are cross-referenced to the eleventh edition of Oxford Handbook of Clinical Medicine to track revision progress and revise effectively.
Rheumatology
Authors: Sinharay Rudy
Published: March 2024

It is a core skill for the budding physician to be able to assess and diagnose inflammatory arthritis, autoimmune disorders, vasculitis, soft tissue disorders, spinal problems, and metabolic bone disease. Rheumatological disease covers extremely common conditions like gout and osteoarthritis to rare conditions like sceleroderma and a systematic approach to history, physical examination and investigation is vital. This chapter contains 26 questions that encompass all of the important areas of rheumatology, with detailed explanations. Unique to this series, questions are rated by difficulty and are cross-referenced to the eleventh edition of Oxford Handbook of Clinical Medicine to track revision progress and revise effectively.
Geriatric medicine
Authors: Furmedge Dan
Published: March 2024

Geriatric medicine is the largest ‘medical’ specialty in the United Kingdom, with the number of geriatricians expanding due to and ageing population. Managing frailty and complex medical comorbidity is the core skill of a geriatrician. In this chapter, questions give a taste of some of the common clinical areas in geriatric medicine and will demonstrate how geriatric medicine crosses almost every specialty. This chapter contains 18 questions that encompass many of the important areas of this subject, with detailed explanations. Unique to this series, questions are rated by difficulty and are cross-referenced to the eleventh edition of Oxford Handbook of Clinical Medicine to track revision progress and revise effectively.
History of Mechanical Ventilation
Authors: Griffiths Mark , White Mary , Chakkalakal Nirmala Mary
Published: March 2024

Summary

The evolution of artificial mechanical ventilation has been very influential in the development of respiratory and critical care medicine. Mechanical ventilation is a crucial aspect of resuscitation, intensive care medicine, and anaesthesia. It has evolved from simple mechanically delivered support to advanced, patient-triggered, micro-processor-controlled systems. Progress along this path has furthered the aims of achieving effective life support with reduced risk and increased comfort. Advances in our understanding of respiratory disease and physiology have occurred alongside, and frequently been synergistic with, the evolution of mechanical ventilation. Understanding how mechanical ventilation developed from its earliest stages to its current and future incarnations provides a key underpinning to the understanding of respiratory critical care.
Gas Exchange
Authors: Cumpstey Andrew , Grocott Mike
Published: March 2024

Summary

Inadequate gas exchange (respiratory failure) is the most common reason for admission to critical care and associated with high mortality rates. Effective gas exchange requires adequate ventilation, diffusion, and perfusion. Hypoxaemia (low blood oxygen saturation) will result if any of these are inadequate, whereas hypercapnia typically results from inadequate ventilation. Two different types of respiratory failure can be considered clinically—normocapnic (sometimes called ‘Type 1’), where oxygenation is impaired but ventilation and therefore clearance of carbon dioxide (CO2) is not, and hypercapnic (‘Type 2’), where inadequate ventilation impairs CO2 clearance as well as oxygenation. In physiological terms—and regardless of the underlying disease process—hypoxaemia always results from one of five possible causes: less inspired oxygen (e.g. high altitude), hypoventilation, impaired diffusion across the alveolar membrane, inequality of ventilation and perfusion (‘V/Q mismatch’), and shunting (blood flow that does not participate in gas exchange). Increasing the inspired oxygen may seem the obvious treatment for respiratory failure; however, unnecessary hyperoxia likely also carries inherent risk of harm and may not fully resolve the situation either. This chapter reviews these topics in detail and considers how investigations (e.g. arterial blood gases) can be used to target respiratory failure treatment.
Non-invasive Ventilation in Critical Care
Authors: Gregoretti Cesare , Cortegiani Andrea , Russotto Vincenzo , Pisani Lara
Published: March 2024

Summary

Acute respiratory failure (ARF) is characterized by impaired gas exchange and increased work of breathing, secondary to an acute lung and/or respiratory pump failure. Ventilatory assistance to respiratory function can be applied either invasively through an endotracheal tube or by means of external interfaces, such as masks, mouthpieces, prongs, and helmets, referred to as non-invasive ventilation (NIV). Acute NIV needs to be provided in an appropriately skilled and equipped environment, with ready access to advanced respiratory therapies, including invasive mechanical ventilation. Effective use of NIV requires understanding of the ventilator system and interfaces. Key ventilator features include the nature of gas delivery (high-pressure or turbine-driven), the variables used for setting gas delivery, and the timing of breaths and the circuits. Ventilators can deliver either non-invasive continuous positive airway pressure (CPAP) or vary the positive pressure, at different levels (nPPV) to facilitate ventilation. A wide variety of interfaces are available, although those commonly used for acute NIV include orofacial masks, total face masks, and helmets. The type of ventilator, the settings on that ventilator, and the interface all need to be individualized to the patient dependent on their underlying pathology, physiological features, and capacity to tolerate NIV, and a careful approach to patient optimization is critical to successful use of NIV.
Clinical Applications of Non-invasive Ventilation in Critical Care
Authors: Longhini Federico , Vaschetto Rosanna , Navalesi Paolo
Published: March 2024

Summary

Non-invasive ventilation (NIV) is the first-line treatment in patients with an exacerbation of severe chronic obstructive pulmonary disease causing hypercapnic acute respiratory failure (ARF). NIV (in particular, non-invasive continuous positive airway pressure, CPAP) is strongly recommended for patients with ARF due to cardiogenic pulmonary oedema. NIV may be indicated to treat hypoxaemic ARF secondary to surgical procedures, chest trauma, neuromuscular disorders or occurring in immunocompromised patients, to prevent further deterioration and need for endotracheal intubation, or with a palliative intent in patients with end-stage disease. NIV may help to speed up the weaning process in hypercapnic patients, while its use in hypoxaemic ARF requires further investigations. NIV should be considered after extubation to prevent the development of post-extubation respiratory failure in ‘at-risk’ patients, while it is presently not advised in established post-extubation respiratory failure. NIV is controversial in de novo hypoxaemic ARF. Given the uncertainty of evidence there is presently no clear strong recommendation on the use of NIV for de novo hypoxaemic ARF and acute asthma.
Monitoring Cardiovascular Function in Critically Ill Patients
Authors: Gabriel Rodney A , Pinsky Michael R
Published: March 2024

Summary

Haemodynamic monitoring is an essential aspect of the care of patients with respiratory failure because cardiovascular compromise may occur as a result of respiratory failure and mechanical ventilation. Monitoring needs to be personalized based on the severity of respiratory failure, its aetiologies, and concerns of either too much or too little fluid resuscitation on gas exchange. Monitoring includes non-invasive and invasive measures that can be both intermittent and continuous in their recordings. In general, one starts with the least invasive monitoring and escalates to more invasive one as the level of cardio-respiratory insufficiency and management intensify. Non-invasive vital signs are often adequate in an otherwise stable subject. However, the assessment of the adequacy of the circulation requires estimates of the effective blood flow and end-organ function. Invasive measures include central venous pressure, which is only useful as a stopping rule to fluid infusion, if it increases. Arterial pressure defines the input pressure of organ perfusion and on a beat-to-beat basis forms the dynamic measures of volume responsiveness. Pulmonary artery pressures are useful to monitor when pulmonary hypertension is present or anticipated. Finally, cardiac output can easily be estimated by a variety of techniques and devices, making its use commonplace.
Bronchoscopy in Critical Care
Authors: Singh Suveer
Published: March 2024

Summary

Bronchoscopy in the intensive care unit was developed in the early 1970s. Its flexibility and versatility provide diagnostic and therapeutic value. Common indications are to facilitate placement of a definitive airway, airway sampling for infection, and clearance of secretions. More complex situations such as airway haemorrhage, percutaneous tracheostomy insertion, foreign body removal, burn inhalation injury, tracheal tears, and persistent air leaks in mechanically ventilated patients are amenable to diagnostic and therapeutic bronchoscopy. However, published evidence is limited, and when available does not necessarily demonstrate overall benefit of bronchoscopy in intensive care. Single-use disposable bronchoscopes are increasingly important in the acute. care setting, where a quick set up, rapid visualization, and avoidance of contamination are intrinsic advantages. Further, the quality of optics is approaching that of the standard of reusable bronchoscopes. Bronchoscopy of the acutely sick awake patient is a valuable skill, requiring expertise and experience. A working understanding of endobronchial anatomy, physiological effects, and risks and complications of bronchoscopy in this setting is necessary. Bronchoscopy in the intensive care unit is safe, although well-known complications such as hypoxaemia, hypotension, cardiac arrhythmias, and pneumothorax must be anticipated. Simulated training is shown to improve patient-related outcomes, while offering an understanding of ventilatory physiological changes peri-procedurally. Protocols for preparation, documentation, and World Health Organization–style surgical ‘timeouts’ should be encouraged. Training programmes still require significant development to ensure maintenance of satisfactory contextual and experiential skills and competencies.
Gastric Protection
Authors: Krag Mette , Møller Morten Hylander , Singh Suveer , Wise Matthew P
Published: March 2024

Summary

Critically ill patients are at risk of gastrointestinal bleeding with stress ulcer prophylaxis being widely and somewhat uncritically used. In recent years, the evidence base has grown, and data on stress ulcer prophylaxis versus placebo as well as data comparing different agents are now available. High-quality trials and systematic reviews indicate that acid suppressants reduce the risk of gastrointestinal bleeding without obvious side effects. The overall mortality seems unaffected by the use of stress ulcer prophylaxis. The most severely ill patients are also the patients at highest risk of stress ulceration. Hence, the use of stress ulcer prophylaxis and the choice of agent should be decided following an individual assessment. Data on the effect of enteral feeding is needed, as well as data comparing use of histamine-2-receptor antagonists versus placebo and data on the effect of proton pump inhibitors on mortality amongst the most severely ill patients.
Mucus and Bronchopulmonary Clearance
Authors: Leaver Susannah , Ball Jonathan
Published: March 2024

Summary

This chapter covers the roles of airway surface liquid (ASL), the mucociliary escalator, and cough reflex in protecting the respiratory tract in health. The injurious result of certain disease processes and the negative impact of endotracheal intubation and mechanical ventilation on bronchopulmonary clearance are also discussed. Numerous mucolytic agents are currently used in clinical practice to combat these deleterious effects. These work by modifying ASL production, secretion, and composition, and may have an effect on the mucociliary escalator. Since there is a paucity of evidence in this area, their effects are extrapolated from their use in other respiratory conditions.
Human Factors
Authors: Hingston Christopher D
Published: March 2024

Summary

Despite advances in medical therapies, around 10% of patients admitted to hospital will suffer a serious adverse incident. Half are thought preventable with ordinary standards of care.1 In the United States of America, medical error is the third leading cause of death.2 Patients admitted to the intensive care unit experience on average 1.7 medical errors a day.3 Fortunately, the majority of these do not lead to significant patient harm, being trapped before they can do so. Human factors or ergonomics is the scientific study of humans and the systems in which they work in order to optimize performance. A number of cognitive skills and behaviours, known as non-technical skills can influence team performance. These include situational awareness, decision-making, communication, teamworking, leadership, as well as fatigue and stress management. Many high-risk industries have recognized the importance of developing these skills to mitigate error. Such teachable and trainable skills are also relevant to healthcare professionals. In doing so team performance can be enhanced, with resultant reduction in medical error and associated patient harm.
Ventilator-associated Pneumonia
Authors: Grover Vimal , Singh Suveer
Published: March 2024

Summary

Ventilator-associated pneumonia (VAP) is a lower-respiratory-tract infection that develops in those patients mechanically ventilated by way of a cuffed endotracheal tube within the trachea. It is associated with significant morbidity and mortality. VAP develops through a combination of factors—host, environmental, and those related to the infectious agent. It is unclear why some patients do not get VAP despite similar circumstances to others. This highlights currently unknown aspects of its aetiology including genetic and epigenetic factors. Potentially pathogenic microorganisms gain access to the lower airway, by micro-aspiration of pooled oropharyngeal secretions beyond the cuff. The diagnosis of VAP does not have a universally accepted clinical gold standard. However, a practically accepted definition incorporates elements of new fever, purulent secretions, radiographic lung deterioration, worsening blood, and/or bronchoalveolar biomarkers of inflammation and physiological deterioration, together with grades of quantitative microbiology. Prevention of VAP is dependent on measures to reduce the duration of mechanical ventilation, reduce the microbial burden in the airway, as well as improvements in reducing micro-aspiration of secretions. Standardization of specific ventilator care bundles, through a series of good practice measures, can reduce the incidence of VAP.
Bacterial Pneumonia
Authors: Woods David R , José Ricardo J
Published: March 2024

Summary

Bacterial pneumonia is lung parenchymal inflammation due to infection by a bacterial pathogen and it manifests with infective symptoms including cough productive of purulent sputum, dyspnoea, hypoxia, and pyrexia. This correlates clinically with bronchial breath sounds, radiological evidence of new pulmonary infiltrates, and often raised blood markers of inflammation. Both, community-acquired pneumonia (CAP, infection contracted outside of a hospital setting) and hospital-acquired pneumonia (HAP, an infection developing at least 48 h following hospitalization and not incubating at the time of admission) are accountable for increased morbidity, mortality, and use of healthcare resources worldwide. Here, we discuss the microbiology, current practice, evidence base, as well as the controversies and future directions of the management of CAP and HAP, excluding ventilator-associated pneumonia.
Pleural Infection
Authors: Lang-Lazdunski Loïc
Published: March 2024

Summary

Pleural infection is a common and increasing clinical problem in respiratory and critical care medicine. It carries significant morbidity and mortality and, despite optimal medical management, up to 30% of patients will die or require surgery. Chest X-ray remains the cornerstone of identification of pleural effusions in the setting of infection, but real-time pleural ultrasound now plays a critical role in the assessment of and guidance of drainage in pleural effusion or empyema. Emerging biomarkers together with currently available markers of inflammation may help identify infection in the setting of pleural effusion. Pleural fluid pH, LDH, and glucose remain key elements in the decision-making process regarding drainage of the pleural space. Traditionally, pleural infections have been managed by thoracocentesis, appropriate antibiotic therapy, placement of a chest tube, adequate nutrition, and chest physiotherapy. Surgery (thoracoscopic debridement or thoracotomy and decortication) was reserved for patients failing initial medical management. Recently published clinical trials as well as new guidelines have modified significantly approaches to radiological assessment, use of biomarkers, management algorithms, intrapleural therapies, and pleural drainage techniques whilst clarifying the role and ideal timing of surgery in pleural infections.
Travellers’ Pneumonia
Authors: Chaudhry Dhruva , Singh Pawan Kumar , Govindagoudar Manjunath B
Published: March 2024

Summary

With an increase in international travel, infectious agents are migrating frequently and changing the epidemiology of airborne infectious diseases in particular. Respiratory infection including pneumonia in returned travellers is an important cause for sought healthcare. Risk of contracting the infections depends on destination, trip duration, type of trip, etc., and the host factors such as age, gender, and co-morbid conditions. The aetiology of pneumonia in returned travellers is diverse and requires an index of clinical suspicion with the appropriate, sometimes special testing. Critical care management is supportive and predominantly for respiratory failure. Respiratory infections due to H1N1, SARS, MERS, and SARS-CoV-2 have posed a global threat and need constant reconnaissance of travellers. Infection control measures and personal protective equipment (PPE) should be deployed while treating these highly infectious diseases. Specific treatments are available for influenza viruses and relevant bacterial pneumonias.
Pharmacology of Anti-infective Drugs in Critical Illness
Authors: Gant Vanya
Published: March 2024

Summary

The disturbed physiology of critical illness considerably impacts blood and tissue concentrations of antimicrobials. In addition, the antimicrobials themselves vary enormously in chemical structure (and therefore charge, solubility, hydrophilicity, etc.), adding yet more complexity to effective and correct calculation of appropriate dose and interval timing. Examples here include on the one hand increased concentrations of hydrophilic beta-lactam antibiotics secondary to poor renal function and/or acute kidney injury, and on the other decreased antibiotic concentrations from increased volumes of distribution, decreased protein binding, and (sometimes artificially augmented by filtration or haemodialysis) renal clearance. Lipophilic antibiotics such as macrolides are less affected by physiological changes—although issues such as obesity influence dosing for optimal outcomes. Some antibiotics also have a narrow efficacy range and therapeutic index. Accordingly, aminoglycosides work best when used in high, once-daily dosing strategies with mandatory therapeutic drug monitoring. On the other hand, beta-lactam antimicrobials often have very short half-lives and are either bactericidal or entirely ineffective when only just below therapeutic concentrations. With such drugs, the most important pharmacodynamic parameter is therefore a ‘time above minimal inhibitory concentration’ optimized with shorter administration regimens, extended or even continuous infusions. None of these considerations should absolve treating physicians from deciding whether individual cases of infection are not better treated by removing the source of infection, as antibiotics alone cannot be expected to deal with large, undrained infected collections for instance.
Pulmonary Haemorrhage
Authors: Kouranos Vasilis
Published: March 2024

Summary

Diffuse alveolar haemorrhage is an acute condition associated with high morbidity and mortality. Among many conditions it can accompany, antineutrophil cytoplasmic antibody associated vasculitis, Goodpasture syndrome, connective tissue diseases, infections, and drug exposure seem to be the most common ones. Haemosiderin-laden macrophages are usually identified in the bronchoalveolar lavage, and histopathologic findings usually include evidence of pulmonary capillaritis. Despite the severity and high mortality, the current treatment options remain empirical targeting the control of inflammatory/infectious component, haemostasis, and supportive care. The various causes, acute and often life-threatening original presentation, and lack of evidence-based treatment options pose an important challenge to the clinicians.
Pulmonary Hypertension and Cor Pulmonale
Authors: Price Laura C , John Wort S , Finney Simon J
Published: March 2024

Summary

Intensive care management of pulmonary hypertension (PH) and acute cor pulmonale or right ventricular (RV) failure can be challenging, with the high risk of pulmonary hypertensive crises, cardiovascular collapse, and associated high mortality. Indeed, the presence of PH and RV dysfunction predicts mortality in patients with pre-existing PH, as well as acute respiratory distress syndrome, acute pulmonary embolism, and following surgical procedures (including certain cardiothoracic procedures and surgery in patients with pre-existing PH). The key to managing PH in the intensive care unit setting is early recognition and prevention of RV failure. Patients with chronic PH should have elective interventions carefully planned, with provision for management of PH crises in experienced centres. Management of acute PH and RV dysfunction often lies outside a clear evidence base and is based on physiological principles, with novel interventions including the impact of extracorporeal circuits such as extracorporeal membrane oxygenation considered in this chapter.
Organizing Pneumonia
Authors: George Peter M , Singh Suveer , Chua Felix
Published: March 2024

Summary

Organizing pneumonia (OP) is an important and relatively common cause for patients to present acutely with respiratory failure. Although it is considered within the umbrella of interstitial lung diseases and has the potential for fibrotic transformation if identified late or under-treated, it has distinct clinico-pathological hallmark features that separate it from the wider array of fibrosing lung diseases. Much of the challenge when treating patients with suspected OP comes from the diagnostic uncertainty as in many cases there is radiological overlap with bacterial pneumonia and the diagnosis is only considered after a failed trial of antimicrobial therapy. OP can be idiopathic with no identified aetiology, so-called ‘cryptogenic OP’, or associated with autoimmune conditions, drugs, or infections—most notably severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It can take a variable course from full resolution to progressive acute respiratory distress syndrome—much of the key to the best outcomes is a raised index of suspicion within the correct clinical context, rapid diagnosis, and definitive treatment at the earliest possible stage. In this chapter, we describe the clinical, radiological, and pathological hallmarks of OP. We explore the disease associations and critical diagnostic tests. Finally, we provide a framework on which to base treatment decisions for patients with OP on the intensive care unit.
Interstitial Lung Disease
Authors: Molyneaux Philip L , Wells Athol U
Published: March 2024

Summary

Patients with interstitial lung disease (ILD) requiring critical care support present the intensivist with difficult diagnostic and management challenges. This is partly due to many diseases falling under the umbrella term ‘ILD’. The commonest presentation is acute deterioration in a patient with previously diagnosed ILD. However, occasionally the initial presentation is that of rapidly progressive de novo disease. In both cases, rapid exclusion of potentially treatable triggers such as infection, cardiac decompensation, drug-induced disease, and pulmonary embolism must be considered. The assimilation of clinical, radiological, and serological data by the multi-disciplinary team is key to the management of these patients and directs the need for invasive diagnostic techniques including bronchoscopy, bronchoalveolar lavage, and, even, lung biopsy. There is a paucity of evidence on which to base the treatment of acute ILD presenting with respiratory failure. High doses of corticosteroids, with or without other immunosuppressive therapy, are generally adopted based on case series and anecdotal data. In the absence of reversible disease, the prognosis for patients with ILD requiring mechanical ventilation is extremely poor, and the importance of early decision-making, communication, effective palliation, and end-of-life care management is also discussed.
Neuromuscular Disease
Authors: Polkey Michael I
Published: March 2024

Summary

Blood gas homeostasis depends on adequate functioning of the respiratory muscles. Respiratory muscle function can be impaired by diseases or pathophysiological processes that cause weakness, while contractile activity is reduced physiologically during sleep (especially rapid eye movement sleep) and pathologically by sedative drugs or central nervous system disease. In most long-term neurological conditions causing respiratory muscle weakness, the diagnosis is apparent long before respiratory muscle weakness is present (e.g. as in Duchenne muscular dystrophy). However, in a few situations, most notably late onset Pompe’s disease, respiratory muscle weakness may be the presenting feature. Respiratory muscle weakness is also common in patients with extended intensive care unit (ICU) stays for any reason. In patients with neurological disease, respiratory muscle strength is best assessed and followed using maximum sniff nasal inspiratory pressure although the vital capacity has been commonly used historically. Identification of weakness should prompt discussion of the patient’s wishes in order to formulate an advanced care plan appropriate for their underlying condition. The ICU identification is more difficult although the finding of low airway pressures with low oxygen requirements should raise neuromuscular impairment as a differential. Measurement of vital capacity can be made on ICU, and most modern ventilators also allow the measurement of negative inspiratory effort and force by occlusion pressures (P0.1) or oesophageal pressure monitoring. In specialized units, phrenic nerve stimulation or, increasingly, diaphragm ultrasound may also be used.
Pleural Disease
Authors: Brims Fraser , Fysh Edward TH
Published: March 2024

Summary

Pleural effusions are common in patients admitted to the intensive care unit (ICU), with heart failure/fluid overload and proinflammatory conditions such as parapneumonic or malignant effusion being common causes. Failure of oxygenation, prolonged mechanical ventilation, prolonged ICU stay, and increased mortality have all been reported to be associated with pleural effusions. The presence of a pleural effusion should be suspected and investigated in the context of severe pneumonia, unexplained sepsis, unexplained or refractory hypoxaemia, deteriorating respiratory function, or difficulty weaning from mechanical ventilation. Point-of-care thoracic ultrasound has been shown to be superior to supine chest radiographs for the identification of pleural effusions in ICU. Drainage of a pleural effusion may improve oxygenation and potentially reduce dependency on ventilatory support. However, high-quality data to inform thresholds on effusion size or ventilatory parameters above which patients will benefit from pleural drainage is lacking. Chest drains below 16F are likely to be adequate for most indications, with the exception of significant haemothorax and post-trauma or instrumentation. Randomized trials are urgently required to inform clinical treatment guidelines of this common condition with significant associated adverse outcomes. The optimal selection of clinically important patient-reported outcome measures for such studies is required.
Transfusion
Authors: Honickel Markus , Grottke Oliver , Rossaint Rolf
Published: March 2024

Summary

This chapter provides brief information about transfusion and shows the impact of transfusion on the respiratory system. Transfusion reactions and associated adverse events involve severe and potentially life-threatening impairments of the respiratory system. Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) accounted for 63% of all fatal transfusion reactions reported to the United States Food and Drug Administration between 2010 and 2014. Secondary impairments of the respiratory system, potentially caused by transfusion, include anaphylactic dyspnoea and pneumonia. Due to their prominence, this chapter focuses on the prophylaxis and treatment of TRALI and TACO. Differential diagnosis of both entities and the underlying pathophysiology are also summarized.
Anaphylaxis
Authors: Soar Jasmeet , Moghaddas Fiona , Robinson Stephen M
Published: March 2024

Summary

Anaphylaxis is a serious systemic hypersensitivity reaction that is usually rapid in onset and may cause death. It is characterized by rapidly developing life-threatening airway, breathing, and/or circulation problems, usually associated with skin and mucosal changes. Anaphylaxis admissions to the intensive care unit (ICU) are uncommon, and the ICU mortality is 5%–10%. Intramuscular adrenaline and supportive treatment based on an Airway Breathing Circulation Disability Exposure approach are the key immediate interventions. Most reactions respond to a single dose of intramuscular adrenaline, 10% require more than one dose, and about 2% require three or more doses. An adrenaline infusion should be started in refractory anaphylaxis. A raised serum mast cell tryptase at the time of the reaction can help confirm the diagnosis. A normal serum mast cell tryptase does not exclude anaphylaxis. Patients with suspected anaphylaxis should be referred to a specialist allergy clinic to help identify the trigger and avoid future reactions.