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1
Flores, Carlos A., and Xuan Chen. Average Treatment Effect Bounds with an Instrumental Variable: Theory and Practice. Singapore: Springer Singapore, 2018. http://dx.doi.org/10.1007/978-981-13-2017-0.
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Carneiro, Pedro. Evaluating marginal policy changes and the average effect of treatment for individuals at the margin. Cambridge, MA: National Bureau of Economic Research, 2009.
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3
Chen, Xuan, and Carlos A. Flores. Average Treatment Effect Bounds with an Instrumental Variable: Theory and Practice. Springer, 2019.
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4
Chen, Xuan, and Carlos A. Flores. Average Treatment Effect Bounds with an Instrumental Variable: Theory and Practice. Springer, 2018.
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5
Heidet, Laurence, Bertrand Knebelmann, and Marie Claire Gubler. Alport syndrome. Edited by Neil Turner. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0324.
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Management of Alport syndrome has in the past been expectant and supportive. Modern hearing aids have substantially improved the function of affected individuals. However, animal data and more recently observational data from Alport registries strongly suggest a protective effect of angiotensin-converting enzyme inhibitors. There is a suggestion that early commencement of treatment may slow progression substantially. These should now be recommended for all with proteinuria, and possibly even before then for those known to harbour mutations certain to cause end-stage renal failure. A very small minority develop the difficult post-transplant complication of Alport anti-glomerular basement membrane disease. This can rarely be treated successfully and leaves some patients on long-term dialysis. However, overall, patients with Alport syndrome have better than average survival and other outcomes than other patients with end-stage renal failure. Most are successfully transplanted. The question of risk to heterozygous carriers from donating kidneys to their affected relatives arises frequently. The risks may be felt acceptable in some circumstances. Additional therapies are under investigation.
6
Bedoya, Guadalupe, Luca Bittarello, Jonathan Davis, and Nikolas Mittag. Distributional Impact Analysis: Toolkit and Illustrations of Impacts Beyond the Average Treatment Effect. World Bank, Washington, DC, 2017. http://dx.doi.org/10.1596/1813-9450-8139.
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Opper, Isaac. Using Machine Learning Techniques to Improving Average Treatment Effect Estimates in Small-Scale Randomized Controlled Trials. RAND Corporation, 2020. http://dx.doi.org/10.7249/wra1004-1.
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Effects of biologically treated bleached kraft mill effluent on cold water stream productivity in experimental stream channels: Fifth progress report. New York, N.Y. (260 Madison Ave., New York 10016): National Council of the Paper Industry for Air and Stream Improvement, 1989.
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9
Petrak, Frank, and Bonnie Röhrig. Treatment of depression in type 2 diabetes. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198789284.003.0010.
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This chapter provides a brief overview of the current scientific evidence for the treatment of depression in type 2 diabetes. Considering the multiple adverse interactions between both conditions, treatment targets should always focus on diabetes-related medical outcome and improvement or remission of depression at the same time in people with diabetes. Depression can be treated with moderate to good results in depressed patients with type 2 diabetes by a variety of psychological and pharmacological interventions, with comparable results to the treatment of depressive patients without diabetes. Results regarding glycaemic control are inconsistent and indicate a low effectiveness of psychological interventions. Antidepressants demonstrated mild to moderate effect regarding better glycaemic control, but the results are still inconclusive and long-term effects are widely unknown. The chapter ends with a critical summary of methodological limitations of the research in that area and concludes with evidence-based recommendations for clinical practice.
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Thien Lim, Thien, and Hubert H. Fernandez. Parkinson Disease. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0003.
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Levodopa is the most efficacious medication to reduce motor impairment in Parkinson disease (PD). The effect of levodopa can wear off after time, which is treated by increasing the dose or shortening the inter-dose interval. Dyskinesias can be treated by a change in levodopa dosing or route of administration, such as by constant administration of levodopa as a gel through a jejunostomy tube or a change to dopamine agonists or amantadine. Non-motor signs including depression can be treated with several antidepressants. Surgical treatments including pallidotomy, thalamotomy, and deep brain stimulation (DBS) have emerged as effective therapies in selected patients with PD refractory to drug treatment.
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Najavits, Lisa M., and Melissa L. Anderson. Psychosocial Treatments for Posttraumatic Stress Disorder. Oxford University Press, 2015. http://dx.doi.org/10.1093/med:psych/9780199342211.003.0018.
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Treatments for posttraumatic stress disorder (PTSD) work better than treatment as usual; average effect sizes are in the moderate to high range. A variety of treatments have been established as effective, with no one treatment having superiority. Both present-focused and past-focused treatment models work (neither consistently outperforms the other). Areas of future development include training, dissemination, client access to care, optimal delivery modes, and mechanisms of action. Methodological issues include improving research reporting, broadening study samples, and greater use of active comparison conditions.
12
Larocca, Nicholas G. Cognitive Impairment and Mood Disturbances. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199341016.003.0018.
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This chapter presents a comprehensive review of two of the most prevalent symptoms in persons with multiple sclerosis. While cognitive impairment and mood disorders may affect at least half of the MS population, and can have a significant effect on function and quality of life, they are often under recognized and under treated. The epidemiology and most common clinical manifestations of cognitive dysfunction and mood disorders are presented, along with a detailed discussion of screening and assessment tools. Pharmacologic and behavioral treatment interventions are reviewed, with analyses of their comparative efficacy.
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Turney, Ben, and John Reynard. Medical therapy (dissolution therapy). Edited by John Reynard. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199659579.003.0024.
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Medical therapy of stone disease aims to prevent stones or dissolve existing stones. Dissolution therapy aims to dissolve stones through administration of oral agents to by direct chemolysis through renal irrigation. Since dissolution therapy may take weeks to achieve an effect, it is usually used as an adjunct to endourological treatment. Urate stones are most amenable to dissolution therapy. Stones containing any calcium have a lower chance of successful dissolution. Providing stone composition is known, irrigating chemolysis is an option for patients with large stone burdens who are unsuitable for percutaneous nephrolithotomy (PCNL). Both uric acid and cystine stones can be treated with irrigating solutions of trihydroxymethyl-aminomethan with pH 8.5–9.0, though it takes a long time to dissolve stones and oral treatment is preferred.
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Caballero-Manrique, Esther, and Carlos A. Pino. Head and Neck Cancer Pain. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190271787.003.0026.
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In the United States, there are 48,000 new cases of head and neck cancer (HNC) annually. Although HNC used to be associated mainly with smoking and drinking, it is now found in many nonsmokers and nondrinkers in their 50s due to the spread of HPV. Pain is typically present at the time of diagnosis. Treatment usually includes radiation, chemotherapy, and/or surgery, which address the mass effect and pain. Yet, patients continue to experience pain during and after treatment, because the treatment modalities can cause significant inflammation and neuropathy and can lead to central sensitization. Painful mucositis is a complication of chemotherapy and radiation treatment; it can become severe, impacting patients’ ability to speak and eat, and sometimes limiting treatment. Pain treatment for HNC is multimodal, and includes preemptive approaches to prevent neuropathy and central sensitization with antiepileptics, such as gabapentin and pregabalin. Mucositis pain is treated using a stepwise protocol.
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Kaplan, Tamara B., and Marcelo Matiello. Multiple Sclerosis. Edited by Angela O’Neal. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190609917.003.0026.
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Multiple sclerosis (MS) often affects women of childbearing age. There are many issues to consider when counseling women about their disease and treatment during this time. The Pregnancy in Multiple Sclerosis (PRIMS) study, published in 1998, is the best large-scale prospective study published to date. Based on this trial, and those that followed, it is recognized that the rate of relapse in MS decreases during pregnancy, especially during the third trimester, but there is a significant increase in relapse rate in the first three months postpartum. If relapses do occur during pregnancy, women are often treated with methylprednisolone, but this is generally avoided in the first trimester. Disease-modifying therapies (DMTs) are usually discontinued during preconception, pregnancy, and while breast-feeding. DMTs are classified under different FDA pregnancy categories based on human and animal data. Breast-feeding may influence postpartum relapse rate, but the true effect continues to be debated.
16
Simonoff, Emily. Intellectual impairment and neurogenetic disorders. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198739258.003.0025.
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Intellectual disability (ID) is a neurodevelopmental disorder commencing in early life in which both learning, typically measured with IQ tests, and adaptive functioning are impaired. Prevalence rates of ID vary widely, but converge around 3%. ID is associated with increased rates of all mental disorders but most with other neurodevelopmental disorders; hyperkinetic disorder is estimated to be increased 10-fold in ID, and rates of ADHD have been estimated to be approximately 5%. The full explanation for this association is uncertain, but shared genetic influences play an important role. Co-occurring ID should be considered when undertaking assessments for ADHD. The limited evidence base for treatment of ADHD with ID shows methylphenidate to be effective in randomized controlled trials (RCTs), but the effect sizes are about half those reported for children with average intellectual ability and with higher rates of non-serious adverse effects. No non-pharmacological interventions have been evaluated in RCTs.
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Leys, Didier, Charlotte Cordonnier, and Valeria Caso. Stroke. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199687039.003.0067.
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Stroke is a major public health issue. Many are treatable in the acute stage, provided patients are admitted soon enough. The overall incidence of stroke in Western countries is approximately 2400 per year per million inhabitants, and 80% are due to cerebral ischaemia. The prevalence is approximately 12 000 per million inhabitants. Stroke is associated with increased long-term mortality, handicap, cognitive and behavioural impairments, recurrence, and an increased risk of other types of vascular events. It is of major interest to take the heterogeneity of stroke into account, because of differences in the acute management, secondary prevention, and outcomes, according to the subtype and cause of stroke. In all types of stroke, early epileptic seizures, delirium, increased intracranial pressure, and non-specific complications are frequent. In ischaemic strokes, specific complications, such as malignant infarcts, spontaneous haemorrhagic transformation, early recurrence, and a new ischaemic event in another vascular territory, are frequent. In haemorrhagic strokes, the major complication is the subsequent increased volume of bleeding. There is strong evidence that stroke patients should be treated in dedicated stroke units; each time 24 patients are treated in a stroke unit, instead of a conventional ward, one death and one dependence are prevented. This effect does not depend on age, severity, and the stroke subtype. For this reason, stroke unit care is the cornerstone of the treatment of stroke, aiming at the detection and management of life-threatening emergencies, stabilization of most physiological parameters, and prevention of early complications. In ischaemic strokes, besides this general management, specific therapies include intravenous recombinant tissue plasminogen activator, given as soon as possible and before 4.5 hours, otherwise aspirin 300 mg, immediately or after 24 hours in case of thrombolysis, and, in a few patients, decompressive surgery. In intracerebral haemorrhages, blood pressure lowering and haemostatic therapy, when needed, are the two targets, but surgery does not seem effective to reduce death and disability.
18
Leys, Didier, Charlotte Cordonnier, and Valeria Caso. Stroke. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199687039.003.0067_update_001.
Full textAbstract:
Stroke is a major public health issue. Many are treatable in the acute stage, provided patients are admitted soon enough. The overall incidence of stroke in Western countries is approximately 2400 per year per million inhabitants, and 80% are due to cerebral ischaemia. The prevalence is approximately 12 000 per million inhabitants. Stroke is associated with increased long-term mortality, handicap, cognitive and behavioural impairments, recurrence, and an increased risk of other types of vascular events. It is of major interest to take the heterogeneity of stroke into account, because of differences in the acute management, secondary prevention, and outcomes, according to the subtype and cause of stroke. In all types of stroke, early epileptic seizures, delirium, increased intracranial pressure, and non-specific complications are frequent. In ischaemic strokes, specific complications, such as malignant infarcts, spontaneous haemorrhagic transformation, early recurrence, and a new ischaemic event in another vascular territory, are frequent. In haemorrhagic strokes, the major complication is the subsequent increased volume of bleeding. There is strong evidence that stroke patients should be treated in dedicated stroke units; each time 24 patients are treated in a stroke unit, instead of a conventional ward, one death and one dependence are prevented. This effect does not depend on age, severity, and the stroke subtype. For this reason, stroke unit care is the cornerstone of the treatment of stroke, aiming at the detection and management of life-threatening emergencies, stabilization of most physiological parameters, and prevention of early complications. In ischaemic strokes, besides this general management, specific therapies include intravenous recombinant tissue plasminogen activator, given as soon as possible and before 4.5 hours, otherwise aspirin 300 mg, immediately or after 24 hours in case of thrombolysis, and, in a few patients, decompressive surgery. In intracerebral haemorrhages, blood pressure lowering and haemostatic therapy, when needed, are the two targets, but surgery does not seem effective to reduce death and disability.
19
Leys, Didier, Charlotte Cordonnier, and Valeria Caso. Stroke. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199687039.003.0067_update_002.
Full textAbstract:
Stroke is a major public health issue. Many are treatable in the acute stage, provided patients are admitted soon enough. The overall incidence of stroke in Western countries is approximately 2400 per year per million inhabitants, and 80% are due to cerebral ischaemia. The prevalence is approximately 12 000 per million inhabitants. Stroke is associated with increased long-term mortality, handicap, cognitive and behavioural impairments, recurrence, and an increased risk of other types of vascular events. It is of major interest to take the heterogeneity of stroke into account, because of differences in the acute management, secondary prevention, and outcomes, according to the subtype and cause of stroke. In all types of stroke, early epileptic seizures, delirium, increased intracranial pressure, and non-specific complications are frequent. In ischaemic strokes, specific complications, such as malignant infarcts, spontaneous haemorrhagic transformation, early recurrence, and a new ischaemic event in another vascular territory, are frequent. In haemorrhagic strokes, the major complication is the subsequent increased volume of bleeding. There is strong evidence that stroke patients should be treated in dedicated stroke units; each time 24 patients are treated in a stroke unit, instead of a conventional ward, one death and one dependence are prevented. This effect does not depend on age, severity, and the stroke subtype. For this reason, stroke unit care is the cornerstone of the treatment of stroke, aiming at the detection and management of life-threatening emergencies, stabilization of most physiological parameters, and prevention of early complications. In ischaemic strokes, besides this general management, specific therapies include intravenous recombinant tissue plasminogen activator, given as soon as possible and before 4.5 hours, mechanical thrombectomy in case of proximal occlusion (middle cerebral artery, intracranial internal carotid artery, basilar artery), on top of thrombolysis in the absence of contraindication or alone otherwise, aspirin 300 mg, immediately or after 24 hours in case of thrombolysis, and, in a few patients, decompressive surgery. In intracerebral haemorrhages, blood pressure lowering and haemostatic therapy, when needed, are the two targets, while surgery does not seem effective to reduce death and disability.
20
Gilchrist, Francis J., and Alex Horsley. Management of respiratory exacerbations. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780198702948.003.0005.
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Cystic fibrosis lung disease is characterized by chronic infection, inflammation and a progressive loss of lung function. Patients are also affected by recurrent episodes of increased respiratory symptoms, called exacerbations which have a detrimental effect on quality of life, the rate of lung function decline, and mortality. Early diagnosis and treatment is vital. Diagnosis relies on a combination of symptoms, examination findings, the results of laboratory tests, and lung function. Antibiotics are the mainstay of treatment but airway clearance, nutrition, and glucose homeostasis must also be optimized. Mild exacerbations are usually treated with oral antibiotics and more severe exacerbations with intravenous antibiotics. The choice of antibiotic is guided by the patient’s chronic pulmonary infections, the in-vitro antibiotic sensitivities, known antibiotic allergies, and the previous response to treatment. In patients with chronic Pseudomonas aeruginosa infection, antibiotic monotherapy is thought to increase the risk of resistance and treatment with 2 antibiotics is therefore suggested (usually a β-lactam and an aminoglycoside). Although there is a lack of evidence on the duration of treatment, most patients receive around 14 days. This can be altered according to the time taken for symptoms and lung function to return to pre-exacerbation levels. If patients are carefully selected and receive appropriate monitoring, home intravenous antibiotics can be as effective as in-patient treatment. They are also associated with decreased disruption to patients / family life, decreased risk of cross infection and decreased costs.
21
Heijstek, Marloes, Mario Abinun, and Nico Wulffraat. Vaccination in immunocompromised children. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0095.
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Can immunocompromised children be safely and effectively vaccinated? This chapter discusses the recommendations from the European League Against Rheumatism (EULAR) for the immunization of immunocompromised patients. Patients with rheumatic or autoinflammatory diseases treated with high-dose glucocorticoids, high-dose disease-modifying anti-rheumatic drugs (DMARDs), or biologicals are considered immunocompromised. Safe and effective vaccination is crucial in these patients, given their increased risk of infection. Safe vaccination implies that vaccination has no effect on disease activity and has only mild adverse effects. Effective vaccination denotes that patients are protected against infections after immunization. Particularly in severely immunosuppressed patients, concerns arise on the safety of (live-attenuated) vaccines and on the detrimental effect of immunosuppressive treatment on the immunogenicity of vaccines. Overall, vaccinations do not increase disease activity and do not cause severe adverse events. Although non-live vaccines are safe, it is recommended to withhold live-attenuated vaccines in patients on high-dose immunosuppressive drugs and biologicals. However, booster vaccinations can be considered when essential. Generally, immunogenicity of vaccines is good with some exceptions: responses are reduced in patients on high-dose glucocorticoids and rituximab; methotrexate reduces responses to (pneumococcal) polysaccharide vaccines; and anti-tumour necrosis factor alpha (TNFα) may lower vaccine-induced antibody concentrations. Offering vaccination before immunosuppressive drugs and/or measuring antibodies after immunization is recommended.
22
Heijstek, Marloes, Mario Abinun, and Nico Wulffraat. Vaccination in immunocompromised children. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199642489.003.0095_update_003.
Full textAbstract:
Can immunocompromised children be safely and effectively vaccinated? This chapter discusses the recommendations from the European League Against Rheumatism (EULAR) for the immunization of immunocompromised patients. Patients with rheumatic or autoinflammatory diseases treated with high-dose glucocorticoids, high-dose disease-modifying antirheumatic drugs (DMARDs), or biologicals are considered immunocompromised. Safe and effective vaccination is crucial in these patients, given their increased risk of infection. Safe vaccination implies that vaccination has no effect on disease activity and has only mild adverse effects. Effective vaccination denotes that patients are protected against infections after immunization. Particularly in severely immunosuppressed patients, concerns arise on the safety of (live-attenuated) vaccines and on the detrimental effect of immunosuppressive treatment on the immunogenicity of vaccines. Overall, vaccinations do not increase disease activity and do not cause severe adverse events. It is recommended to withhold live-attenuated vaccines in patients on high-dose immunosuppressive drugs and biologicals, but booster vaccinations can be considered when essential. Generally, immunogenicity of vaccines is good with some exceptions: responses are reduced in patients on high-dose glucocorticoids and rituximab; methotrexate reduces responses to (pneumococcal) polysaccharide vaccines; and tumour necrosis factor alpha (TNFα) may lower vaccine-induced antibody concentrations and may cause accelerated waning of immunity. Offering vaccination before immunosuppressive drugs and/or measuring antibodies after immunization is recommended.
23
Misra, V. Peter, and Santiago Catania. EMG-guided botulinum toxin therapy. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199688395.003.0026.
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This chapter explains the mechanism by which botulinum neurotoxin (BoNT) causes its neuromuscular paralytic effects, and reviews the developments that led these effects to be harnessed therapeutically. It specifically focuses upon the conditions of dystonia and spasticity. Within the spectrum of these diseases, it discusses those situations where BoNT injections are the treatment of choice. The very accurate targeting of BoNT into specific muscles in many situations is both desirable and crucial in some situations BoNT’s therapeutic neuroparalytic effect may need to be restricted to a single muscle fascicle.. In some cases, an inaccurately placed injection may be associated with unacceptable side effects. In order to achieve accuracy of BoNT injection delivery, intramuscular injections of BoNT aided by electromyography (EMG) guidance allows the very accurate targeting of specific muscles. The practical aspects related to the preparation of BoNT for injection and the methodology and techniques for injecting using EMG guidance are discussed. The importance of good anatomical knowledge and the relevant EMG techniques to target individual muscles are highlighted and applied to injection of muscles in different body areas. Finally, certain diagnostic neurophysiological tests, which may be useful for the management of some neurological conditions that are treated by BoNT are briefly discussed.
24
Arroyo, Vicente, Mónica Guevara, and Javier Fernández. Renal failure in cirrhosis. Edited by Norbert Lameire. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0247.
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A major event in liver cirrhosis is the development of a progressive deterioration of circulatory function due to splanchnic arterial vasodilation and impairment in cardiac function. This feature determines a homeostatic activation of the renin–angiotensin–aldosterone system, sympathetic nervous system, and antidiuretic hormone. The splanchnic microcirculation is resistant to the vasoconstrictor effect of these systems. Therefore, the homeostasis of arterial pressure in cirrhosis occurs in the extrasplanchnic, mainly renal circulation. The activation of these systems produces renal fluid retention, which accumulates as ascites, and water retention and dilutional hyponatraemia. In the latest phase of cirrhosis, when circulatory dysfunction is severe, renal vasoconstriction is intense and patients develop type 2 hepatorenal syndrome (HRS) and refractory ascites.Type 1 HRS is an acute and rapidly progressive renal failure that occurs in the setting of a precipitating event, commonly an infection. Patients with type 1 HRS also present with rapid deterioration of liver function (encephalopathy, jaundice) and relative adrenal insufficiency. The mechanism of this multiorgan failure is an acute deterioration in circulatory function due to both an accentuation of arterial vasodilation and of cardiac dysfunction.There is no specific test for the diagnosis of HRS. The most accepted diagnostic criteria are those proposed by the International Ascites Club which are based on the exclusion of other types of renal failure. The course of renal failure following treatment of the precipitating event of HRS is another important diagnostic feature.The treatment of choice of tense ascites in cirrhosis is paracentesis associated with intravenous albumin infusion. Moderate sodium restriction and diuretics (spironolactone alone or associated with furosemide) are subsequently given to prevent re-accumulation of ascites. Diuretics are the treatment of choice in patients with moderate ascites. Patients with type 2 HRS and refractory ascites (not responding to diuretics) could be treated by frequent paracentesis or by the insertion of a transjugular intrahepatic portosystemic shunt (TIPS).Terlipressin plus albumin is the treatment of choice in type 1 HRS