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1

Kelly, John. Principles of CNS drug development: From test tube to patient. Chichester, West Sussex: J. Wiley, 2009.

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2

Kelly, John. Principles of CNS drug development: From test tube to patient. Chichester, UK: Wiley-Blackwell, 2009.

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3

Principles of CNS drug development: From test tube to patient. Chichester, West Sussex: J. Wiley, 2009.

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4

Sullivan MD, PhD, Mark. From Patient to Agent. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780195386585.001.0001.

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In the 21st century, the primary challenge for health care is chronic illness. To meet this challenge, we need to think anew about the role of the patient in health and health care. There have been widespread calls for patient-centered care, but this model of care does not question deeply enough the goals of health care, the nature of the clinical problem, and the definition of health itself. We must instead pursue patient-centered health, which is a health perceived and produced by patients. We should not only respect, but promote patient autonomy as an essential component of this health. Objective health measures cannot capture the burden of chronic illness, so we need to draw on the patient's perspective to help define the clinical problem. We require a new definition of health as the capacity for meaningful action. It is recognized that patients play a central role in chronic illness care, but the concept of health behavior retards innovation. We seek not just an activated patient, but an autonomous patient who sets and pursues her own vital goals. To fully enlist patients, we must bridge the gap between impersonal disease processes and personal processes. This requires understanding how the roots of patient autonomy lie in the biological autonomy that allows organisms to carve their biological niche. It is time for us to recognize the patient as the primary customer for health care and the primary producer of health. Patient agency is both the primary means and primary end of health care.
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5

Gill, Steven J., and Michael H. Nathanson. Central nervous system pathologies and anaesthesia. Edited by Philip M. Hopkins. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199642045.003.0081.

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Anaesthesia induces changes in many organ systems within the body, though clearly none more so than the central nervous system. The physiology of the normal central nervous system is complex and the addition of chronic pathology and polypharmacy creates a significant challenge for the anaesthetist. This chapter demonstrates a common approach for the anaesthetist and specific considerations for a wide range of neurological conditions. Detailed preoperative assessment is essential to gain understanding of the current symptomatology and neurological deficit, including at times restrictions on movement and position. Some conditions may pose challenges relating to communication, capacity, and consent. As part of the consent process, patients may worry that an anaesthetic may aggravate or worsen their neurological disease. There is little evidence to support this understandable concern; however, the risks and benefits must be considered on an individual patient basis. The conduct of anaesthesia may involve a preference for general or regional anaesthesia and requires careful consideration of the pharmacological and physiological impact on the patient and their disease. Interactions between regular medications and anaesthetic drugs are common. Chronically denervated muscle may induce hyperkalaemia after administration of succinylcholine. Other patients may have an altered response to non-depolarizing agents, such as those suffering from myasthenia gravis. The most common neurological condition encountered is epilepsy. This requires consideration of the patient’s antiepileptic drugs, often relating to hepatic enzyme induction or less commonly inhibition and competition for protein binding, and the effect of the anaesthetic technique and drugs on the patient’s seizure risk. Postoperative care may need to take place in a high dependency unit, especially in those with limited preoperative reserve or markers of frailty, and where the gastrointestinal tract has been compromised, alternative routes of drug delivery need to be considered. Overall, patients with chronic neurological conditions require careful assessment and preparation, a considered technique with attention to detail, and often higher levels of care during their immediate postoperative period.
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6

Young, Raymond. Infection in the Patient with Sickle Cell Anemia. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199976805.003.0060.

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This chapter provides a brief overview of the clinical manifestations of and management strategies for infectious complications in the immunocompromised sickle cell disease patient. The chapter discusses infections in various organ systems, including the respiratory tract, central nervous system, bone, hematopoietic cell lineage, and blood-borne infections. Differentiating infections from noninfectious processes that often have similar presentations in the sickle cell patient may at times be difficult, and clinicians managing sickle cell patients should be keenly aware of this fact. This chapter discusses the common bacterial pathogens associated with infection and a notable viral agent known to profoundly worsen anemia in the sickle cell host, parvovirus B19. Additionally, fundamental antimicrobial regimens and primary and secondary prophylactic strategies are included in this concise summary prepared for clinicians involved in the acute care management of the sickle cell patient.
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7

Walen, Alec D. The Mechanics of Claims and Permissible Killing in War. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780190872045.001.0001.

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This book operates on two levels. On the more practical level, its overarching concern is to answer the question, When is it permissible to use lethal force to defend people against threats? The deeper concern of the book, however, is to lay out and defend a new account of rights, the mechanics of claims. This framework constructs rights from the premise that rights provide a normative space in which people can pursue their own ends while treating each other as free and equal fellow-agents whose welfare morally matters. According to the mechanics of claims, rights result from first weighing competing patient-claims on an agent, then determining if the agent has a strong enough agent-claim to act contrary to the balance of patient-claims on her, and then looking to see if special claims limit her freedom. The strength of claims in this framework reflects not just the interest in play but the nature of the claims. Threats who have no right to threaten have weaker claims not to be harmed than bystanders who might be harmed as a side effect, all else equal. With this model, a central problem in just war theory can be pushed to the margins: determining when people have forfeited their rights and are liable to harm. Threats may lack a right not to be killed even if they have done nothing to forfeit it.
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8

Mythen, Monty, and Michael P. W. Grocott. Peri-operative optimization of the high risk surgical patient. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0361.

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Flow-based cardiovascular variables, such as cardiac output and oxygen delivery predict peri-operative outcome better than alternative, predominantly pressure-based measures. Targeting flow-based goals, using fluid boluses with or without additional blood or vasoactive agents in patients undergoing major surgery has been shown to improve outcome in some studies. However, the literature is limited due to a large number of small single-centre studies, and heterogeneity of interventions and outcomes evaluated. Early studies used pulmonary artery catheters to monitor blood flow, but newer studies have used less invasive techniques, such as oesophageal Doppler monitoring or pulse contour analysis. Meta-analysis of the current evidence base suggests that this approach is unlikely to cause harm and may not reduce mortality, but reduces complications and duration of hospital stay. Goal-directed therapy is considered an important element of enhanced recovery packages that have been shown to improve outcome after several types of major elective surgery.
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9

Bleck, Thomas P. Assessment and management of seizures in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0232.

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In previously conscious patients seizures are usually easily detected. Critically-ill patients are frequently sedated and a proportion are paralysed with neuromuscular blocking agents, in such patients it may be hard or impossible to detect seizures clinically. An urgent electroencephalogram (EEG) should be obtained whenever seizures are witness or suspected, especially if the patient does not rapidly return to baseline, when non-convulsive status epilepticus must be excluded. Unless the cause of the seizure activity is already known, an urgent CT, or MRI is indicated. If central nervous system infection is suspected a lumbar puncture may be needed. Status epilepticus is diagnosed when there is recurrent or continued seizure activity without intervening recovery. Most seizures are self-limiting and stop after 1–2 minutes, seizures that continue for more than 5 minutes should be treated. Treatment priorities for any seizure are to stop the patient hurting either themselves or anyone else. General supportive measures include attention to the airway, breathing, circulation, exclusion of hypoglycaemia and an EEG to exclude non-convulsive status epilepticus. A variety of drugs can be used to terminate seizures; parenteral benzodiazepines are the most commonly used agents although propofol and barbiturates are alternatives. Emergent endotracheal intubation may well be necessary, hypotension can be expected and may need treatment with intravenous fluids and vasopressors.
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10

van Hooijdonk, Roosmarijn T. M., and Marcus J. Schultz. Insulin and oral anti-hyperglycaemic agents in critical illness. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0050.

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Dysglycaemia is frequently seen in the intensive care unit (ICU). Hyperglycaemia, hypoglycaemia and glycaemic variability are all independently associated with mortality and morbidity in critically-ill patients. It is common practice to treat hypergycaemia in these patients, while at the same time preventing hypoglycaemia and glycaemic variability. Insulin infusion is preferred over oral anti–hyperglycaemic agents for glucose control in the ICU because of the highly unpredictable biological availability of oral anti-hyperglycaemic agents during critical illness. Many oral anti–hyperglycaemic agents are relatively contraindicated in critically-ill patients. Intravenously-administered insulin has a predictable effect on blood glucose levels, in particular because of its short half-life. Notably, effective and safe insulin titration requires frequent blood glucose measurements, a dedicated lumen of a central venous catheter for infusion of insulin, an accurate syringe pump, and trained nurses for delicate adoptions of the infusion rate. Insulin infusion increases the risk of hypoglycaemia, which should be prevented at all times. In addition, precautions should be taken against overcorrection of hypoglycaemia, using only small amounts of glucose. Whether glycaemic variability can be kept minimal is uncertain. Use of continuous glucose measuring devices has the potential to improve glycaemic control in critically-ill patients.
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11

Bonnet, Francis, Marc E. Gentili, and Christophe Aveline. Post-surgical analgesia and acute pain management. Edited by Jonathan G. Hardman. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199642045.003.0046.

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Postoperative and acute pain remains uncontrolled in many instances, leading to the risk of development of chronic pain syndromes. After tissue damage, activation of postsynaptic NMDA receptors, also induced by opioid administration, plays a key role in postoperative pain sensitization, allodynia, and hyperalgesia. Pain intensity may depend on sex, age, anxiety, and genetic factors but in clinical practice, surgical procedure is the main determinant of pain, although pain may vary from one patient to one another. Serial pain measurements are mandatory to assess pain intensity and to guide pain treatment. They are based on unidimensional simple pain scales. Multimodal analgesia combining opioid and non-opioid agent and regional block or infiltration is the rule postoperatively, although evidence is sometimes lacking to support all the combinations commonly used. Opioids should be used on demand while other agents are administered systematically. Non-steroidal anti-inflammatory drugs decrease opioid demand as well as paracetamol although to a less extend. Antihyperalgesic agents including NMDA blockers (ketamine) and α‎2-δ‎ ligands (gabapentin, pregabalin) have an opioid-sparing effect and may prevent the occurrence of chronic pain syndrome after surgery. Regional blocks and infiltration provide good quality analgesia but the balance between advantages and drawbacks of central block need to be evaluated carefully for each surgical procedure.
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12

Diaz, Roberto Jose, Gregory W. Basil, and Ricardo J. Komotar. Primary CNS Lymphoma. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190696696.003.0008.

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Central nervous system (CNS) lymphoma must be considered in the differential diagnosis of any immunocompromised patient with a solid brain lesion. In such patients, diagnosis can be made via a careful review of important signs, symptoms, and classic radiologic findings. While there is no single physical exam finding classic for lymphoma, the clinician must carefully evaluate patients for the presence or absence of findings that may suggest an alternative diagnosis. Such findings include the stigmata of endocarditis, symptoms suggestive of pneumonia, or additional non-CNS mass lesions. Additionally, several imaging modalities including magnetic resonance imaging, diffusion-weighted magnetic resonance imaging, susceptibility weighted imaging, and dynamic contrast-enhanced imaging can be useful in identifying this condition. While steroids can be helpful in reducing the disease burden and decreasing edema, they may also hinder diagnosis. Surgery may be indicated for either diagnostic or decompressive purposes; however, the mainstay of treatment is chemotherapeutic and immunotherapeutic agents with radiation reserved for refractory cases.
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13

Kemper, Carol A., and Stanley C. Deresinski. Fungal arthritis. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0106.

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Fungal infections of the musculoskeletal system are uncommon and diagnosis is often delayed. Infection is more common in the immunocompromised patient. The most important infections are due to candida species, Histoplasmosis capsulatum, Blastomycosis dermatiditis, and Coccidioides immitis. Amphotericin B remains the initial therapeutic agent of choice for many serious fungal infections, especially for those who are severely immunosuppressed, have life-threatening or central nervous system disease, or who have failed azole therapy.
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14

Hoff, Scott, and Nancy A. Collop. Sleep Disorders and Recovery from Critical Illness. Oxford University Press, 2014. http://dx.doi.org/10.1093/med/9780199653461.003.0022.

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Many factors contribute to sleep disruption in critically ill patients. Sleep is a complex process, with broad effects on diverse physiologic systems. Environmental factors, such as light exposure, noise from diverse sources, and sleep interruptions related to patient care, have all received considerable investigational attention. Critical illness can affect elements involved in sleep initiation and maintenance. The various modes of mechanical ventilation may have different effects on sleep fragmentation and on the propensity to cause central apnoeas, thereby potentially prolonging the time on the ventilator. Pharmacologic agents, especially sedatives, can directly affect sleep architecture and may contribute to the incidence of intensive care unit delirium. Additional research is needed on the biological effects of critical illness on sleep, how sleep disruption affects systemic physiology and outcomes, and how these interactions can be modulated for therapeutic purposes.
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15

Alhazzani, Waleed, and Deborah J. Cook. Stress ulcer prophylaxis and treatment drugs in critical illness. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0041.

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Many changes have occurred over the last three decades in the field of stress ulcer gastrointestinal bleeding and its prevention. The topic is controversial, fuelled by disparate data, studies at risk of bias, and the impression that the problem is not as serious as it once was. Indeed, compared with over four decades ago when mucosal ulceration of the stomach causing serious bleeding was first described, a relatively small proportion of critically-ill patients now develop clinically important bleeding. Acid suppression is commonly prescribed for stress ulcer prophylaxis (SUP), targeting subgroups of patients at high risk in the intensive care unit (ICU), rather than universal prevention. The randomized clinical trials to date suggest a significant reduction in CIB with use of histamine-2-receptor antagonists (H2RAs) compared with no SUP, with no impact on pneumonia, ICU mortality, or length of stay. However, these trials are of moderate quality. More recent RCTs suggest proton pump inhibitors compared with H2RAs may significantly reduce the risk of CIB without influencing the risk of pneumonia, ICU mortality, or length of stay. These trials are also of moderate quality. Today, the decision whether to use SUP, and which agent to use, is complex. Clinical considerations include local epidemiological data (for centres documenting these outcomes), and patient-specific risks of gastrointestinal bleeding and infection, indexed to case mix.
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16

Dalbeth, Nicola. Gout. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0141.

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Gout is a common and treatable disorder of purine metabolism. Gout typically presents as recurrent self-limiting episodes of severe inflammatory arthritis affecting the foot. In the presence of persistent hyperuricaemia, tophi, chronic synovitis, and joint damage may develop. Diagnosis of gout is confirmed by identification of monosodium urate (MSU) crystals using polarizing light microscopy. Hyperuricaemia is the central biochemical cause of gout. Genetic variants in certain renal tubular urate transporters including SLC2A9 and ABCG2, and dietary factors including intake of high-purine meats and seafood, beer, and fructose, contribute to development of hyperuricaemia and gout. Gout treatment includes: (1) management of the acute attack using non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or low-dose colchicine; (2) prophylaxis against gout attacks when commencing urate-lowering therapy (ULT), with NSAIDs or colchicine; and (3) long-term ULT to achieve a target serum urate of less than 0.36 mmol/litre. Interleukin (IL)-1β‎ is a central mediator of acute gouty inflammation and anti-IL-1β‎ therapies show promise for treatment of acute attacks and prophylaxis. The mainstay of ULT remains allopurinol. However, old ULT agents such as probenecid and benzbromarone and newer agents such as febuxostat and pegloticase are also effective, and should be considered in patients in whom allopurinol is ineffective or poorly tolerated. Management of gout should be considered in the context of medical conditions that frequently coexist with gout, including type 2 diabetes, hypertension, dyslipidaemia, and chronic kidney disease. Patient education is essential to ensure that acute gout attacks are promptly and safely managed, and long-term ULT is maintained.
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17

Dalbeth, Nicola. Gout. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199642489.003.0141_update_003.

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Gout is a common and treatable disorder of purine metabolism. Gout typically presents as recurrent self-limiting episodes of severe inflammatory arthritis affecting the foot. In the presence of persistent hyperuricaemia, tophi, chronic synovitis, and joint damage may develop. Diagnosis of gout is confirmed by identification of monosodium urate (MSU) crystals using polarizing light microscopy. Hyperuricaemia is the central biochemical cause of gout. Genetic variants in certain renal tubular urate transporters including SLC2A9 and ABCG2, and dietary factors including intake of high-purine meats and seafood, beer, and fructose, contribute to development of hyperuricaemia and gout. Gout treatment includes: (1) management of the acute attack using non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or low-dose colchicine; (2) prophylaxis against gout attacks when commencing urate-lowering therapy (ULT), with NSAIDs or colchicine; and (3) long-term ULT to achieve a target serum urate of less than 0.36 mmol/litre. Interleukin (IL)-1β‎ is a central mediator of acute gouty inflammation and anti-IL-1β‎ therapies show promise for treatment of acute attacks and prophylaxis. The mainstay of ULT remains allopurinol. However, old ULT agents such as probenecid and benzbromarone and newer agents such as febuxostat and pegloticase are also effective, and should be considered in patients in whom allopurinol is ineffective or poorly tolerated. Management of gout should be considered in the context of medical conditions that frequently coexist with gout, including type 2 diabetes, hypertension, dyslipidaemia, and chronic kidney disease. Patient education is essential to ensure that acute gout attacks are promptly and safely managed, and long-term ULT is maintained.
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18

Bramham, Kate, and Catherine Nelson-Piercy. Pregnancy after renal transplantation. Edited by Norbert Lameire and Neil Turner. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0299_update_001.

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There is now experience of many thousands of pregnancies over more than 50 years of renal transplantation. Most such patients have some degree of hypertension and chronic kidney disease, and as expected their rates of complications are substantially higher than those of age-matched controls. However, rates of successful pregnancy are now high and pregnancy is no longer an unusual event in transplanted patients. As for other patients with chronic kidney disease, additional risks depend on pre-pregnancy glomerular filtration rate, proteinuria, and hypertension. Fertility returns rapidly after transplantation but delay of at least a year is usually recommended to be sure of stable graft function and drug dosage. Early discussion of these issues with women of childbearing age is essential as drug regimens may need to be altered to agents of known safety, and to stress the importance of planning the pregnancy. The combination of tacrolimus and azathioprine with or without low-dose prednisolone is probably the most common, but in many centres agents such as mycophenolate mofetil, which is teratogenic, are commonly used. Blood pressure should be well controlled as outside pregnancy but some drugs are contraindicated and others are best avoided.
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19

Matiello, Marcelo, and Tamara B. Kaplan. A Mother Who Could Not See Her Baby. Edited by Angela O’Neal. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190609917.003.0027.

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Neuromyelitis optica spectrum disorders (NMOSD) belong to a group of relapsing neurological syndromes characterized by significant morbidity and mortality due to central nervous system (CNS) inflammation and necrosis. Most patients are seropositive for pathogenic antibodies targeting Aquaporin-4, and while this water channel is mostly expressed on the foot processes of astrocytes, it is also expressed in placental tissues. On planning a pregnancy, patients should be well informed about the increased risk of preeclampsia and miscarriages, and that most medications used to treat NMOSD have potentially severe toxicities to the fetus. There is also increased risk of relapses in the postpartum period, and immunosuppressive agents are the mainstream method of preventing attacks.
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20

Lheureux, Philippe, and Marc Van Nuffelen. Management of benzodiazepine poisoning. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0320.

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The wide use of benzodiazepines is associated with some inconveniences and are most frequently implicated in acute self-poisoning and accidental poisoning in children. Some of them are recognized as submission drugs, used to commit date rape or robbery. Prolonged use of a benzodiazepine leads to dependence, with a risk of developing a life-threatening withdrawal syndrome. Overdose has usually a good prognosis—most patients recover well with careful observation and prevention of complications, although care should be taken with elderly people, and patients with chronic obstructive pulmonary disease or liver dysfunction. Fast-acting agents and co-ingestion of other central nervous system depressants may be present greater risk. Early administration of activated charcoal in patients able to protect their airway is only needed if there are co-ingestants. Flumazenil may help confirm the diagnosis, improve alertness, and prevent the need for respiratory support in some patients, especially after accidental poisoning in children. Contraindications include patients on long-term treatment and/or dependent on benzodiazepines, or those who have simultaneously ingested proconvulsant or prodysrhythmic substances or at risk of increased intracranial pressure.
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21

Queixalós, Francesc. What being a Syntactically Ergative Language means for Katukina-Kanamari. Edited by Jessica Coon, Diane Massam, and Lisa Demena Travis. Oxford University Press, 2017. http://dx.doi.org/10.1093/oxfordhb/9780198739371.013.42.

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The structure of the basic clause in Katukina-Kanamari is, to a significant extent, conditioned by the internal structure of the verb phrase, which is starkly parallel to that of noun and adposition phrases. Depending on its internal make up, the verb phrase generates, for the same verbs, two patterns of transitive clauses, ergative and accusative, neither of which is synchronically derived from the other, but the latter appears as highly restricted in distribution. It also yields two patterns of intransitive clauses, one primary, the other resulting from an intransitivizing voice process. Since the basic transitive clause shows a clear syntactic hierarchy between its two arguments, intransitivizing voice is seen as of primary formal motivation: promoting the agent participant to subject status, a far more central need in this language than the functional motivation for relegating the patient participant to either adjunct status or no expression at all.
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22

Williams, John, and Francis Bonnet. Analgesics in anaesthetic practice. Edited by Michel M. R. F. Struys. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199642045.003.0018.

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Each year, approximately 230 million major surgical procedures are undertaken worldwide, with over three-quarters of the patients complaining of pain postoperatively and 10% complaining of severe pain. Pain is not, however, just an unpleasant sensory consequence of surgery, but can also have significant physiological implications impacting negatively on well-being and postoperative outcome. Postoperative pain may also result in changes within the central nervous system, leading to the development of chronic pain states lasting in excess of 3–6 months. Adequate analgesia has proven to be effective when employed in the perioperative period at combating many of these adverse effects. An understanding of the basic physiological and pharmacological mechanisms responsible for producing, transmitting, and sustaining pain has allowed for a variety of effective analgesic agents to be fashioned and used clinically to treat pain. Morphine, the archetypal opioid analgesic, is the most familiar of these agents with a long history of use and evidence of effectiveness; morphine possesses a number-needed-to-treat (NNT) to reduce pain by 50% of around 3 when given in doses of between 10 and 15 mg. Non-steroidal agents and paracetamol are similarly effective in the immediate postoperative period with NNTs of between 2 and 4. More recently, a number of analgesic adjuncts such as gabapentin, pregabalin, ketamine, clonidine, and nefopam have found favour for the treatment of acute postoperative pain. None of these agents, however, are without side-effects, ensuring that the search for effective analgesic agents continues to be a vibrant area of research with new analgesic agents continuing to be developed.
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Ferini-Strambi, Luigi, and Sara Marelli. Restless legs syndrome/Willis–Ekbom disease. Edited by Sudhansu Chokroverty, Luigi Ferini-Strambi, and Christopher Kennard. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199682003.003.0024.

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Restless legs syndrome (RLS)/Willis–Ekbom disease (WED), is a common neurological disorder characterized by uncomfortable and unpleasant sensations in the legs, with an urge to move. The general population prevalence has been estimated at approximately 5%. In 1995, the International RLS/WED Study Group established four clinical criteria for RLS/WED diagnosis, and in 2012 introduced a fifth (that symptoms are not due to another medical or behavioral condition) to improve differential diagnosis. Periodic leg movements causing sleep fragmentation may be observed in almost 80% of RLS/WED patients. Genetics, central nervous system dopamine dysregulation, and brain iron deficiency seem to be the primary involved factors, but peripheral phenomena may also contribute to the pathophysiology. Several medications have demonstrated efficacy in treating RLS/WED, including dopaminergic agents, alpha-2-delta ligands, and opioids. Pharmacological therapy should be limited to those patients who suffer from clinically relevant symptoms with impaired sleep quality or quality of life.
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24

Gibson, Alistair A., and Peter J. D. Andrews. Management of traumatic brain injury. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0343.

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Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and although young male adults are at particular risk, it affects all ages. TBI often occurs in the presence of significant extracranial injuries and immediate management focuses on the ABCs—airway with cervical spine control, breathing, and circulation. Best outcomes are achieved by management in centres that can offer comprehensive neurological critical care and appropriate management for extracranial injuries. If patients require transfer from an admitting hospital to a specialist centre, the transfer must be carried out by an appropriately skilled and equipped transport team. The focus of specific TBI management is on the avoidance of secondary injury to the brain. The principles of management are to avoid hypotension and hypoxia, control intracranial pressure and maintain cerebral perfusion pressure above 60 mmHg. Management of increased intracranial pressure is generally by a stepwise approach starting with sedation and analgesia, lung protective mechanical ventilation to normocarbia in a 30° head-up position, maintenance of oxygenation, and blood pressure. Additional measures include paralysis with a neuromuscular blocking agent, CSF drainage via an external ventricular drain, osmolar therapy with mannitol or hypertonic saline, and moderate hypothermia. Refractory intracranial hypertension may be treated surgically with decompressive craniectomy or medically with high dose barbiturate sedation. General supportive measures include provision of adequate nutrition preferably by the enteral route, thromboembolism prophylaxis, skin and bowel care, and management of all extracranial injuries.
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Levtchenko, Elena N., and Mirian C. Janssen. Cystinosis. Edited by Neil Turner. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0339_update_001.

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Cystinosis is a rare autosomal recessive disease caused by mutations in the lysosomal cystine transporter cystinosin encoded by the CTNS gene (17p.13.2). Cystinosis is characterized by lysosomal cystine accumulation throughout the body with renal Fanconi syndrome being the most common presenting symptom of a multisystem disorder. It must be distinguished from cystinuria in which formation of cystine stones is the core problem. When left untreated, kidney dysfunction gradually progresses towards end-stage renal failure during the first 10 years of life. The advent of renal replacement therapy allowed cystinosis patients to survive into adulthood, but revealed numerous extrarenal manifestations of the disease, affecting eyes, endocrine organs, gastrointestinal tract, muscles, and central and peripheral nervous systems. The disease mechanism of cystinosis is not fully understood. The administration of the cystine-depleting agent cysteamine slows down renal and extrarenal organ damage, pointing to the pivotal role of cystine accumulation in the disease pathogenesis. Treatment with cysteamine should be initiated as early as possible and continued lifelong, and also after kidney transplantation for protecting extrarenal organs. Cysteamine eye drops are an indispensable part of the treatment of corneal cystine accumulation. Life expectancy of cystinosis patients has substantially improved and is now above 50 years.
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Vranckx, Pascal, Wilfried Mullens, and Johan Vijgen. Non-pharmacological therapy of acute heart failure: when drugs alone are not enough. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199687039.003.0053.

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Acute heart failure syndrome has been defined as new-onset or a recurrence of worsening signs and symptoms of heart failure, necessitating urgent or emergency management. The management of acute heart failure syndrome is challenging, given the heterogeneity of the patient population, in terms of the clinical presentation, pathophysiology, prognosis, and therapeutic options. The management of acute heart failure syndrome is a dynamic process, requiring ongoing simultaneous diagnosis (monitoring) and treatment. Pharmacological agents remain the mainstay of therapy for acute heart failure syndrome. However, at all time, during the early diagnostic, aetiologic, and therapeutic work-up, non-pharmacologic therapy may be indicated and should be considered. The management of the complex cardiac patient with acute heart failure syndrome and/or (potential) haemodynamic compromise has become a special dimension for specialized myocardial intervention centres, providing 24 hours per day and 7 days per week state-of-the-art facilities for (primary) percutaneous coronary intervention and cardiac intensive care, including mechanical ventilation, ultrafiltration, with or without dialysis, and short-term percutaneous mechanical circulatory support. Through the understanding of the underlying pathophysiology and approaches into the problems of acute heart failure syndrome, one should be better prepared to understand and treat its many facets.
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27

Field, John. Therapeutic strategies in managing cardiac arrest. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0064.

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Emergency and critical care specialists are important interdisciplinary physicians who often impact on the long-term survival of patients sustaining cardiac arrest, as well as immediate outcomes. These specialists are often at the crossroads of survival for patients achieving return of spontaneous circulation, and it is important to appreciate that out-of-hospital and in-hospital cardiac arrest patients represent different pathophysiological subgroups with respect to aetiology and pathophysiology. Important time-dependent triage and therapy are crucial, and efforts to identify and treat pathophysiological triggers share priority with the initiation of hypothermia protocols and other targeted interventions, such as coronary angiography and percutaneous coronary intervention. Updated basic life support (BLS) and advanced life support (ACLS) protocols emphasize the importance of high quality chest compressions as central to achieving return of spontaneous circulation and emphasize that airway interventions should not detract from this objective. No specific ACLS intervention including intubation, vasopressor therapy or use of anti-arrhythmic agents has been found to improve outcome. The goal of both BLS and ACLS protocols is the achievement of return of spontaneous circulation, the prevention of re-arrest and the initiation of immediate post-resuscitation interventions associated with improved outcome. These include targeted temperature management (induced hypothermia) and coronary angiography for appropriate patients and ‘bundled’ critical care for all recognizing that the post-arrest state is a systemic inflammatory condition requiring multidisciplinary care beyond hypothermia and cardiovascular support.
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28

Dewhurst, Alexander Timothy, and Brigitta Brandner. Intensive care management after vascular surgery. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0370.

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Vascular patients require admission to an intensive care unit at a number of stages during their hospital stay. They often have multiple co-morbidities and are at risk of major complications. Their management strategy requires a multidisciplinary approach with locally agreed pathways taking national frameworks into account. Vascular emergencies require immediate resuscitation and transfer to a tertiary cardiovascular centre. Vascular disease occurs throughout the arterial vascular tree, affecting both large and small vessels. The major cause is atherosclerosis. The management of vascular conditions is complex, and includes both medical and surgical interventions. Disease can be classified as non-occlusive where there is restricted blood flow or occlusive where the vessels are completely obstructed. Aneurysmal disease occurs when vessels walls weaken. The surgical treatment of these lesions is to either replace the diseased segment of artery with a vascular graft or to exclude it with an endovascular stent. Occlusive vascular disease can occur because of atherosclerotic emboli or thrombosis, and can be treated by embolectomy, bypass, or endovascular procedures. Medical therapy with β‎-blockade, lipid-lowering agents, anti-hypertensives agents, and control of diabetes reduces cardiovascular risk. Recent advances in medical technology have shifted treatment options from open surgical to endovascular procedures. The long-term outcome and cost benefit of endovascular procedures is yet to be established.
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29

Rodríguez-Iturbe, Bernardo, and Mark Haas. Post-streptococcal glomerulonephritis. Edited by Neil Turner. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0077_update_001.

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Post-streptococcal glomerulonephritis is a complication of Streptococcal infections that is responsible for classic acute nephritic syndrome, mostly seen in children. This is an acute nephritis associated with prominent fluid retention and oedema, hypertension and haematuria. Serum complement levels are diagnostically helpful as C3 levels are characteristically very low. However, many cases are much less severe and may pass unrecognized, only being identified by screening for dipstick haematuria. In children recovery is the rule but in adults, often with comorbid conditions, the prognosis is significantly worse. Management centres on loop diuretics plus treatment of the infection if still present, and additional hypotensive agents if required. Severe cases may require dialysis. High-dose corticosteroids have often been given in severe crescentic disease but there is no evidence that they are effective. In children, recovery of renal function is often excellent, though long-term studies now suggest that it may represent a risk factor for the development of chronic kidney disease. When it occurs in developed societies it is often in older patients with comorbid conditions and atypical presentations. Resolution may be less complete than in children.
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30

Visweswara Rao, Pasupuleti, Balam Satheesh Krishna, and Mohammad Saffree Jeffree, eds. Coronaviruses Transmission, Frontliners, Nanotechnology and Economy. UMS Press, 2022. http://dx.doi.org/10.51200/coronavirusesdrraoums2021.

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Coronaviruses are the viruses which cause different types of diseases in humans and animals. They belong to Coronaviridae family. Coronaviruses have unique shape which consists of spiked rings and sometimes to deal with them is a tough task. They are the tiny organisms which can only be seen under the microscopes. Even though the corona viruses exist in nature since decades, however the seriousness is only seen with the pandemic SARS-CoV II or COVID-19. It has taken so many lives away and the loss of various businesses. Keeping in view these situations, the authors and editors try to bring few of the important aspects together and compiled this book. The transmissions occur through different means and the vaccines are under production by various giant companies. Second chapter deals with animals as sources of transmitting agents to spread corona virus. Up to date the Centre for Disease Control and Prevention (CDC) recognizes 7 species of coronaviruses that infect humans, with the earliest known species identified in the mid-1960s. The known human coronaviruses are 229E (alpha coronavirus), NL63 (alpha coronavirus), OC43 (beta coronavirus), HKU1 (beta coronavirus), MERS-CoV (causes Middle East Respiratory Syndrome, MERS), SARS-CoV (causes Severe Acute Respiratory Syndrome, SARS) and SARS-CoV-2 (causes the coronavirus disease also in 2019, also known as COVID-19). Third chapter dealt with risk assessment for front liners during COVID-19 pandemic and clearly explained about the risk assessment factors. Healthcare workers (HCWs) are on the frontline of treating patients infected with COVID-19. However, data related to its infection rate among HCWs are limited. Chapter 4 deals with the nanotechnology and its applications on viral diseases. Nanobiotechnology is science of nanoparticle synthesis by using biotechnological applications in biology, physics, engineering, drug delivery, diagnostics, and chemistry. The use of metal/ polymeric nanoparticles as drug delivery systems has become extensive in last two decades. The commercialization of developed novel nanoparticles/drug loaded polymeric nanoparticles delivery systems are required to eradicate virus with improved safety measures in the humans with affordable cost. Chapter 5 mainly focused on the impact of COVID -19 on China, Malaysia, Indonesia, and India. The outbreak of the Covid-19 pandemic is an unprecedented shock to the Emerging economies. The evidence reported in various studies indicates that epidemic disease impacts on a country's economy through several channels, including the health, transportation, agricultural and tourism sectors. In the chapter 6, the authors discussed the psychological response, ranges from adaptive to maladaptive spectrum. We wish to express our gratitude to all the authors and contributors from Malaysia, Indonesia, and India for readily accepting our invitation and timely contributions without any delay. We greatly appreciate their commitment. We also thank Universiti Malaysia Sabah and Universitas Abdurrab for the great collaboration and collaborative efforts.
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