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1

Lawson, Erin F., and Joel P. Castellanos, eds. Complex Regional Pain Syndrome. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-75373-3.

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2

Juris, Elena. Positive options for complex regional pain syndrome (CRPS): Self-help and treatment. Nashville, Tennessee: Hunter House, an imprint of Turner Publishing Company, 2014.

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3

Treacy, Valerie J. Gaining control of PMS: A simple approach to a complex problem. Fort Wayne, IN: V.J. Treacy, 1994.

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4

A cop doc's guide to public-safety complex trauma syndrome: Using five police personality styles. Amityville, N.Y: Baywood Pub. Co., 2009.

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5

McCleery, Robert E. Charles Harwood Complex, Saint Croix, United States, Virgin Islands. [Atlanta, Ga.?]: Dept. of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, 2001.

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6

Parenting your complex child : become a powerful advocate for the autistic, Down syndrome, PDD, bipolar, or other special-needs child. New York: AMACOM, 2006.

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7

A holistic protocol for the immune system: HIV/ARC/AIDS, candidiasis, chronic fatigue syndrome, herpes, and other oppotunistic infections. 6th ed. Joshua Tree, CA: Tree of Life Publications, 1995.

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8

C, McArthur Justin, ed. AIDS and neurology. Edinburgh: Churchill Livingstone, 1995.

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9

Brazier, Alex. A Double deficiency?: A report on the Social Security Act 1986 and people with acquired immune deficiency syndrome (AIDS), AIDS related complex (ARC) and HIV infection. London: Terrence Higgins Trust, 1989.

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10

Hickey, MichaelS. Handbook of enteral, parenteral, and ARC/AIDS nutritional therapy. St. Louis: Mosby Year Book, 1992.

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11

1955-, Leary Mark, and Boccellari Alicia A. 1955-, eds. AIDS and the impact of cognitive impairment: A treatment guide for mental health providers. San Francisco, CA: AIDS Health Project, University of California San Francisco, 1995.

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12

Handbook of enteral, parenteral, and ARC/AIDS nutritional therapy. St. Louis: Mosby year Book, 1992.

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13

Pidcock, Frank S. Complex Regional Pain Syndrome. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0121.

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Complex Regional Pain Syndrome (CRPS) is a chronic disorder that affects adults and children. It is extremely challenging to manage and results in dysfunctional patterns of behavior that have long-reaching effects on the patient and their families. New insights into the neurobiology of this condition have improved the understanding of mechanisms that alter nocioceptive perception and remodel neural circuitry in the brain and spinal cord. Traditional interventions for treating pain have little if any long-term effects. An interdisciplinary program addressing “bio-psycho-social factors” that includes graded exercise, desensitization techniques, and coping strategies has shown some success as a therapeutic approach. The reason for why certain individuals are susceptible to this condition and others are not remains elusive.
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14

Walters, Jenna L. Complex Regional Pain Syndrome. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190217518.003.0025.

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Complex regional pain syndrome (CRPS) is a neuropathic pain condition classified as type 1 and type 2. The two classifications are distinguished by the presence of documented nerve injury in CRPS type 2. The symptoms of CRPS, including cold, blue, and painful extremities, are believed to occur from vasoconstriction caused by sympathetic dysfunction. Treatment in CRPS focuses on targeting neuropathic and sympathetically maintained pain. Traditional antineuropathic pain medications include membrane stabilizers and serotonin and norepinephrine reuptake inhibitors. Corticosteroids and nonsteroidals target the inflammatory process present in the initial stages of CRPS. Bone resorption has been treated with calcium-modulating drugs. Interventional therapies include sympathetic blockade of the affected extremity, spinal cord stimulation, and intrathecal drug delivery. All these therapies have been implemented in an effort to facilitate functional restoration of the affected limb. Physical and occupational therapies have demonstrated some of the most significant improvements in pain, mobility, and function.
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15

Atkins, Roger M. Complex regional pain syndrome. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199550647.003.0011.

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♦ Complex regional pain syndrome (CRPS) is a disabling chronic pain condition of unknown aetiology♦ Traditionally it was thought to be rare; however, prospective studies demonstrate it to be common following both trauma and operative procedures involving the upper and lower limbs♦ The condition is usually self-limiting over a maximum period of 2 years, although minor abnormalities may remain♦ In a minority of cases it does not resolve and is responsible for severe chronic disability♦ Treatment is aimed at functional restoration of limb function supported by pharmacological intervention.
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16

1954-, Harden R. Norman, and Reflex Sympathetic Dystrophy Syndrome Association., eds. Complex regional pain syndrome: Treatment guidelines. Milford, CT: RSDSA Press, 2006.

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17

National Institutes of Health (U.S.) and National Institute of Neurological Disorders and Stroke (U.S.), eds. Complex regional pain syndrome: Also called reflex sympathetic dystrophy syndrome. [Bethesda, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, 2003.

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18

Riley, Bobbie, and Navil Sethna. Pediatric Complex Regional Pain Syndrome Type 1. Edited by Kirk Lalwani, Ira Todd Cohen, Ellen Y. Choi, and Vidya T. Raman. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190685157.003.0054.

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Complex regional pain syndrome type 1 (CRPS-1) is a condition that affects adolescents and children under the age of 7. It usually follows minor injury and rarely occurs spontaneously. The pain is usually out of proportion to the inciting injury. Pain, allodynia, and/or hyperalgesia are severe enough to inhibit use of the affected limb. Delay in diagnosis and self and/or iatrogenic immobilization of the affected limb may lead to worsening pain, skin hypersensitivity and discoloration, swelling, and vasomotor and dystrophic abnormalities. The diagnosis of CRPS-1 and 2 is based on symptoms. There are no diagnostic tests that can confirm the presence or absence of CRPS-1. CRPS-2 diagnosis is established by nerve conduction test and electromyography. Clinical practice neuropathic guidelines are most effective for CRPS-2 treatment. Pharmacological and interventional treatment options for CRPS-1 are limited and usually ineffective because the underlying mechanism(s) are yet to be determined.
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19

Scott, Naomi. The epidemiology of complex regional pain syndrome. Edited by Paul Farquhar-Smith, Pierre Beaulieu, and Sian Jagger. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198834359.003.0062.

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The landmark paper discussed in this chapter describes a retrospective study examining the epidemiology of complex regional pain syndrome in the Dutch general population. The researchers accessed patient data by means of the Integrated Primary Care Information project, which provided a large representative sample of the general population inclusive of all ages. They found an incidence of 26.2 per 100,000 person-years from a source population of 190,902 people. In those patients diagnosed by a specialist, three contemporaneous diagnostic criteria were applied, one of which was that of the International Association for the Study of Pain (IASP). The authors demonstrated that there were marked differences in the proportions of cases fulfilling different criteria and thus highlighted problems with case diagnosis. When the 1994 IASP criteria were strictly applied, the incidence was found to be 16.8 per 100,000 person-years.
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20

Monico, Caro. Complex Regional Pain Syndrome for Ambulatory Surgery. Edited by Erin S. Williams, Olutoyin A. Olutoye, Catherine P. Seipel, and Titilopemi A. O. Aina. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190678333.003.0055.

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Complex regional pain syndrome (CRPS) is a disease of the nervous system characterized by pain localized in an extremity. This pain is typically out of proportion to the inciting event and is accompanied by sensory disturbances, as well as motor, vasomotor, and sudomotor signs and symptoms. CRPS is a challenging clinical presentation and diagnosis. The etiology of this previously rare condition in children, is typically post-traumatic. It’s management requires a biopsychosocial approach. The principal modality that will improve pain and function in children with CRPS is physical therapy together with an interdisciplinary approach to management. The key to successful treatment involves early appropriate intervention, education for the child and family, and excellent communication between team members. This chapter uses a case study of a 12-year-old girl with CRPS to illustrate these concepts.
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21

Hooshmand, Hooshang M. D. Complex Regional Pain Syndrome: Diagnosis and Therapy. 2nd ed. Crc Pr I Llc, 2005.

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22

Nader, Nader D., and Ognjen Visnjevac. Complex Regional Pain Syndrome: Past, Present and Future. Nova Science Publishers, Incorporated, 2015.

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23

Martin, Douglas W., James B. Talmage, and Robert J. Barth. Complex Regional Pain Syndrome - What is the Evidence? Martin Occupational Medicine, PC, 2015.

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24

Lauder, Gillian R. Complex Regional Pain Syndrome in the Emergency Department. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199764495.003.0061.

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Acute exacerbation of an ongoing chronic pain can be a diagnostic and clinical dilemma. Chronic pain in children requires an interdisciplinary approach to assessment and treatment. Further, the child must commit to taking an active role in therapy. When this approach is not working, or there is an acute trauma to the affected region, children with chronic pain may present to the emergency department with extreme pain. Acute care health professionals may find themselves unable to modify the pain intensity with standard analgesic medications. The analgesic approach requires careful clinical management and liaison with the chronic pain team supervising the ongoing management of pain.
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25

Complex Regional Pain Syndrome (CRPS) explained: For teenagers, by teenagers. Bloomington, Indiana: Xlibris Corporation, 2010.

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26

Complex Regional Pain Syndrome (CRPS) explained: For teenagers, by teenagers. Xlibris Corporation, 2010.

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27

A Cop Doc's Guide to Public Safety Complex Trauma Syndrome. Routledge, 2017. http://dx.doi.org/10.4324/9781315225142.

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28

Stogicza, Agnes, Bartha Peter Tohotom, Edit Racz, Andrea Trescot, and Alan Berkman. Complex Regional Pain Syndrome of the Upper and Lower Extremity. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190271787.003.0011.

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Complex regional pain syndrome (CRPS) is a chronic debilitating pain condition of the extremities; it can affect, less commonly, other areas of the body (face, pelvis, abdomen). Its early presentation—pain disproportionate to the injury, skin temperature changes, hyperalgesia, allodynia—is often not recognized, delaying treatment. In later phases, with sympathetic nervous system involvement, it presents with skin and muscle atrophy, hair loss, allodynia, loss of function, and decreased range of motion. In severe cases, it can spread from one area to the other. Imaging findings (X-ray, MRI, bone scintigraphy) are nonspecific. They are used to support the diagnosis, and to exclude conditions that can present similarly. Treatment is challenging and includes physical therapy, psychologic support, medication management, and minimally invasive interventions to decrease pain, to positively influence the sympathetic nervous system, and to preserve function. A multidisciplinary approach is likely to be the most beneficial.
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29

Beattie, R. Mark, Anil Dhawan, and John W.L. Puntis. Alagille syndrome. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780198569862.003.0050.

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Genetics 358Clinical features 358Differential diagnosis 359Investigations 359Management: multidisciplinary approach 360Prognosis 360Alagille syndrome is a complex multisystem disorder with a prevalence of 1:40 000–1:100 000, characterized by hepatic, cardiac, renal, and ocular involvement. At least three of the following five major criteria are required to establish the diagnosis: ...
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30

Weeber, Edwin J. Angelman Syndrome. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199744312.003.0013.

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Angelman syndrome (AS) is a devastating neurological disorder with a symptom complex that includes but is not limited to severe developmental delay, profound cognitive disruption, motor coordination defects, increased propensity for seizure with a characteristic abnormal electroencephalogram, sleep disruption, behavioral difficulties, a lack of speech, and an overall happy demeanor. Although the disorder was first described in 1965 by British pediatrician Dr. Harry Angelman, because AS is clinically characterized by a wide constellation of symptoms with varying degrees of severity, it is not readily diagnosed by clinical presentation alone and misdiagnosis has commonly occurred.
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31

Mercado, Pilar, Jamey E. Eklund, and Jennifer L. Anderson. Charge Syndrome. Edited by Kirk Lalwani, Ira Todd Cohen, Ellen Y. Choi, and Vidya T. Raman. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190685157.003.0003.

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The major diagnostic features of CHARGE syndrome include coloboma of the eyes, choanal atresia or stenosis, distinctive external ears, cranial nerve abnormalities, and absent or small semicircular canals. The mnemonic refers to coloboma of the eye, heart defects, atresia of choanae, retardation of growth and development, cenitalia hypoplasia, and ear abnormalities and deafness. There is no defined etiology, though a de novo mutation on the CHD 7 gene located on Chromosome 8 is responsible for more than 50% of CHARGE cases. The incidence of CHARGE is about 1:10,000 live births with an equal distribution between males and females. The anesthetic implications of this syndrome are many and vary with the patient’s phenotype. A potential difficult airway, congenital heart defects, choanal atresia, and cranial nerve abnormalities present the most significant issues for the anesthesiologist. A multidisciplinary team must be established early to properly care for these complex patients.
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32

Volberding, Paul, Paul Volberding, and Mark A. Jacobson. Aids Clinical Review 1990. Edited by Paul Volberding. Marcel Dekker, 1990.

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33

J, Staquet Maurice, Hemmer R, and Baert A. L. 1931-, eds. Clinical aspects of AIDS and AIDS-related complex. Oxford: Oxford University Press, 1986.

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34

(Editor), R. Norman Harden, Ralf Baron (Editor), and Wilfrid Janig (Editor), eds. Complex Regional Pain Syndrome (Progress in Pain Research and Management, V. 22). IASP Press, 2001.

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35

Janssen, Mirian C. H., and Shamima Rahman. Pyruvate Dehydrogenase Complex Deficiency. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199972135.003.0006.

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Pyruvate dehydrogenase complex (PDHc) deficiency usually first manifests at a young age and is rarely diagnosed in adulthood. The clinical picture varies from neonatal death with overwhelming lactic acidosis to a relatively benign course early in life. The three main presentations are congenital lactic acidosis, Leigh syndrome, and episodic ataxia. Treatment consists of a ketogenic diet and cofactor supplementation with thiamine. Successful therapy is rare.
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36

Grahame, Rodney, and Isobel Knight. Multidisciplinary Approach to Managing Ehlers-Danlos - Hypermobility Syndrome: Working with the Chronic Complex Patient. Kingsley Publishers, Jessica, 2013.

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37

Angie, Lewis, ed. Nursing care of the person with AIDS/ARC. Rockville, Md: Aspen Publishers, 1988.

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38

Meier, Petra M., and Thomas O. Erb. Craniosynostosis and Apert Syndrome. Edited by Kirk Lalwani, Ira Todd Cohen, Ellen Y. Choi, and Vidya T. Raman. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190685157.003.0021.

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Apert syndrome is a complex, progressive multisystem condition of the craniosynostosis spectrum originating from a fibroblast growth factor receptor disorder. Multidisciplinary treatment teams may include craniofacial surgery, neurosurgery, otolaryngology, ophthalmology, oro-maxillofacial surgery, and pediatric intensive care. Secondary to midface hypoplasia, children often present with a compromised airway and have a high incidence of sleep disorders. Anesthetic considerations include difficult airway assessment, the presence of obstructive sleep apnea syndrome, and increased intracranial pressure. Extensive remodeling procedures can be associated with massive hemorrhage (e.g., venous sinus bleeding) and venous air embolism. Transfusion-related complications include coagulopathy, metabolic derangements, and primarily noninfectious hazards such as transfusion-related acute lung injury and transfusion-related immunomodulation. Multimodal blood management should focus on a combination of appropriate surgical techniques and blood conservation, along with guidance from point-of-care testing (including coagulation).
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39

Castle, David J., Peter F. Buckley, and Fiona P. Gaughran. The metabolic syndrome in schizophrenia. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198811688.003.0003.

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The metabolic syndrome (MS) is a constellation of risk factors including increased waist circumference, high blood pressure, and elevated fasting glucose and triglycerides in conjunction with low levels of high-density lipoprotein. MS is associated with an elevated risk of adverse cardiovascular and other events. The general population rate of MS is increasing, but people with schizophrenia have markedly elevated rates compared to people without a mental illness. Reasons for this excess are complex, but certain antipsychotic agents can exacerbate risk and due care needs to be taken in prescribing such medications, with awareness of longitudinal risk. Treatment needs to be provided following established guidelines, to address aspects of MS should they occur.
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40

1953-, Korvick Joyce A., and Benson Constance A. 1953-, eds. Mycobacterium avium-- complex infection: Progress in research and treatment. New York: Marcel Dekker, 1996.

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41

Publications, ICON Health. Complex Regional Pain Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. ICON Health Publications, 2004.

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42

Korkeila, Maarit, Bengt Lindholm, and Peter Stenvinkel. The obese patient (metabolic syndrome). Edited by Giuseppe Remuzzi. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0168.

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Overweight and obesity cause pathophysiological changes in renal function and increase the risk for chronic kidney disease in otherwise healthy subjects. This should not be a surprise as the risk factors for metabolic syndrome largely overlap with those for chronic kidney disease. Intentional weight loss has beneficial effects on risk factors, but long term effects are less clear. Bariatric surgery does seem to achieve rapid benefits on blood pressure and proteinuria as well as on other aspects of metabolic syndrome, but its long term implications for kidney function are less clear cut as there may be an increased risk of nephrolithiasis, and possibly AKI and other complications.Obesity in haemodialysis patients is one of those paradoxical examples of reverse epidemiology where a factor associated with negative outcomes in the general population is associated with better outcomes in dialysis patients. The same is true for high blood cholesterol values. Interpretation is complicated by complex competing outcomes and confounders.
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43

Korvick. Mycobacterium Avium-complex Infection (Lung Biology in Health and Disease). Informa Healthcare, 1995.

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44

Ortiz, Julian Arias, Raphaël Favory, and Jean-Louis Vincent. Infection, sepsis, and multiorgan dysfunction syndrome. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199687039.003.0072.

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Sepsis is the main cause of multiple organ failure and remains a concern because of the associated high morbidity and mortality. In recent years, important advances have been made in the understanding of the pathophysiology of sepsis. Sepsis and septic shock are the end result of complex interactions between infecting organisms and various elements of the host response. A key feature of the common sequence of organ failure is dysfunction of the cardiovascular system, including microcirculatory elements. Outcome improvement in sepsis is based on recognizing the process early and instituting effective therapies. The time window for intervention is relatively short, and treatment must promptly control the source of infection, restore haemodynamic homoeostasis, and support failing organ systems.
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45

Favory, Raphaël, and Jean-Louis Vincent. Infection, sepsis, and multiorgan dysfunction syndrome. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199687039.003.0072_update_001.

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Sepsis is the main cause of multiple organ failure and remains a concern because of the associated high morbidity and mortality. In recent years, important advances have been made in the understanding of the pathophysiology of sepsis. Sepsis and septic shock are the end result of complex interactions between infecting organisms and various elements of the host response. A key feature of the common sequence of organ failure is dysfunction of the cardiovascular system, including microcirculatory elements. Outcome improvement in sepsis is based on recognizing the process early and instituting effective therapies. The time window for intervention is relatively short, and treatment must promptly control the source of infection, restore haemodynamic homoeostasis, and support failing organ systems.
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46

Favory, Raphaël, and Jean-Louis Vincent. Infection, sepsis, and multiorgan dysfunction syndrome. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199687039.003.0072_update_002.

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Sepsis is the main cause of multiple organ failure and remains a concern because of the associated high morbidity and mortality. In recent years, important advances have been made in the understanding of the pathophysiology of sepsis. Sepsis and septic shock are the end result of complex interactions between infecting organisms and various elements of the host response. A key feature of the common sequence of organ failure is dysfunction of the cardiovascular system, including microcirculatory elements. Outcome improvement in sepsis is based on recognizing the process early and instituting effective therapies. The time window for intervention is relatively short, and treatment must promptly control the source of infection, restore haemodynamic homoeostasis, and support failing organ systems.
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47

Favory, Raphaël, and Jean-Louis Vincent. Infection, sepsis, and multiorgan dysfunction syndrome. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199687039.003.0072_update_003.

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Sepsis is the main cause of multiple organ failure and remains a concern because of the associated high morbidity and mortality. In recent years, important advances have been made in the understanding of the pathophysiology of sepsis. Sepsis and septic shock are the end result of complex interactions between infecting organisms and various elements of the host response. A key feature of the common sequence of organ failure is dysfunction of the cardiovascular system, including microcirculatory elements. Outcome improvement in sepsis is based on recognizing the process early and instituting effective therapies. The time window for intervention is relatively short, and treatment must promptly control the source of infection, restore haemodynamic homoeostasis, and support failing organ systems.
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48

Price, Elizabeth J., and Anwar R. Tappuni, eds. Oxford Textbook of Sjögren's Syndrome. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198806684.001.0001.

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The Oxford Textbook of Sjögren’s Syndrome is an authoritative textbook, rich with valuable illustrations and figures, providing a practical guide to diagnosing and managing all aspects of this condition. Sjögren’s syndrome is a chronic, immune-mediated condition typically presenting in women in their fifth or sixth decade. With increased awareness and improvement in diagnostic tests, younger women and occasionally men are now being diagnosed with this condition. Frequently, Sjögren’s syndrome occurs in association with other autoimmune diseases, usually rheumatoid arthritis, systemic lupus erythematosus, or scleroderma. The hallmark of this condition is dryness of the eyes and mouth, but many patients have systemic effects that can be debilitating, including fatigue, peripheral neuropathy, and lung damage. It has potentially serious long-term complications, including a higher risk of developing lymphoma and foetal congenital heart block. Diagnosis of the condition can be challenging as the presenting symptoms are variable. Management of the condition can be complex as the course of the disease is unpredictable and the available therapy is mainly symptomatic, with no known cure as yet. Experts in the condition from around the world have contributed to this book to provide the most up-to-date information on pathophysiology, classification criteria, diagnostic tests, systemic manifestations of the disease, and emerging therapeutic options. The publication of this book coincides with a period of increased interest in Sjögren’s within the scientific, medical, and pharmacological worlds.
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49

Anderson, Leslie K., Stuart B. Murray, and Walter H. Kaye, eds. Clinical Handbook of Complex and Atypical Eating Disorders. Oxford University Press, 2017. http://dx.doi.org/10.1093/med-psych/9780190630409.001.0001.

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The aim of this book is to collate what is known about an array of complicating factors for patients with eating disorders, serving as an accessible introduction to each of the comorbidities and symptom presentations highlighted in the volume. The Handbook of Complex and Atypical Eating Disorders presents the available data about atypical and complex ED, in addition to what is known about treatment approaches. The first section contains chapters on the treatment of eating disorders with various psychiatric comorbidities, including trauma, borderline personality disorder, substance use, suicidality, anxiety disorders, and autism spectrum disorders, which may greatly complicate the application of standard treatment approaches. The second section contains chapters exploring treatment of eating disorders with atypical symptom presentations which (i) are not located as a specific diagnostic category in diagnostic criteria for ED’s, (ii) centrally feature ED pathology, and (iii) have emerging data suggesting the distinct nature of the syndrome, including purging disorder, muscle dysmorphia, night eating syndrome, and anorexia with a history of obesity. The final section has chapters which focus on how to adapt eating disorder treatment for atypical populations typically neglected in controlled treatment trials: LGBT, pediatric, male, ethnically diverse, and older adults.
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50

Ware, Lorraine B. Pathophysiology of acute respiratory distress syndrome. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0108.

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The acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure characterized by the acute onset of non-cardiogenic pulmonary oedema due to increased lung endothelial and alveolar epithelial permeability. Common predisposing clinical conditions include sepsis, pneumonia, severe traumatic injury, and aspiration of gastric contents. Environmental factors, such as alcohol abuse and cigarette smoke exposure may increase the risk of developing ARDS in those at risk. Pathologically, ARDS is characterized by diffuse alveolar damage with neutrophilic alveolitis, haemorrhage, hyaline membrane formation, and pulmonary oedema. A variety of cellular and molecular mechanisms contribute to the pathophysiology of ARDS, including exuberant inflammation, neutrophil recruitment and activation, oxidant injury, endothelial activation and injury, lung epithelial injury and/or necrosis, and activation of coagulation in the airspace. Mechanical ventilation can exacerbate lung inflammation and injury, particularly if delivered with high tidal volumes and/or pressures. Resolution of ARDS is complex and requires coordinated activation of multiple resolution pathways that include alveolar epithelial repair, clearance of pulmonary oedema through active ion transport, apoptosis, and clearance of intra-alveolar neutrophils, resolution of inflammation and fibrinolysis of fibrin-rich hyaline membranes. In some patients, activation of profibrotic pathways leads to significant lung fibrosis with resultant prolonged respiratory failure and failure of resolution.
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