Bartley G. Cilento Jr., MD, MPH

• Assistant Professor of Surgery, Harvard Medical School
• Assistant in Urology, Children? Hospital Boston, Boston,
• Massachusetts

Ruhr-University Bochum depression symptoms forgetfulness bupropion 150mg visa, Bochum anxiety panic attack 150 mg bupropion visa, Germany; Promotes Coagulation and Infammation 2 Laboratory of Neurovascular Biology anxiety 5x5 discount bupropion on line, the Eye 1 Experimental Eye Research Institute depression and anger best 150mg bupropion, University Through Toll-Like Receptor 4 depression rehab centers discount bupropion 150mg without a prescription. Nicholas Pfahler depression lamp cheap bupropion 150 mg online, Hospital of Wenzhou Medical University, Wenzhou, 1 1 1 2 Eye Hospital, Ruhr-University Bochum, Bochum, I. Deborah Villafranca-Baughman, Oregon Health & Science University, Portland, Trust, Plymouth, United Kingdom f 4 L. Perelman School of bevacizumab monotherapy to treat Aggressive Department of Ophthalmology, University Medicine, University of Pennsylvania, Philadelphia, Posterior Retinopathy of Prematurity. Iqbal Ahmad, for Prevention of Blindness and Rehabilitation of Mezu-Ndubuisi1, 2, Y. Ophthalmology & Visual Sciences, Univ of the Visually impaired, Rome, Italy; 3Division of S. Clinical/Epidemiologic Research Vision sciences, the Hospital for Sick Children, Jennifer1, S. Israel; Endocrinology, Rambam Health Care Medicine, Kyoto, Japan Christine Sonnie, J. Optometry, Ecole dOptom de using diffusion tensor imaging in retinopathy Treated Infants with Retinopathy of 1 2 lUniv de Montreal, Montreal, Quebec, Canada 1 3 of prematurity. Taylor, 2 1 3 4 vitrectomy in stage 5 retinopathy of prematurity University, Nagasaki, Japan J. Department of in the Emergency Department of a Reference of Medicine, Shanghai Jiao Tong University, Ophthalmology, Casey Eye Institute, Oregon Hospital in Goiania. Neves Imaging, Department of Radiology, Massachusetts intravitreal injections of Conbercept versus De Melo Carneiro1, J. Chavez post-surgical pain manifesting as dry eye tomography biometer in dense cataract. Anesthesiology, Perioperative Medicine and Pain School of Science and Technology, Nagano, Japan; 2 1 4 Ravilla. Visual Sciences, University oF British Columbia, Surgery in a Hispanic population. Meredith cataracts treated surgically in Australian 1 1 2 3 6 1 2 4 3 Cystoid Macular Edema. Jeong, Mechanisms of Meibomian Gland Dysfunction 2 3, 4 1 1 1 thermodynamic features of meibum in J. Ocular Regenerative Medicine and Immunology, Ophthalmology and Vision Science, Washington 2 1 Yappert. Ophthalmology, University of Louisville, Seoul Artifcial Eye Center, Seoul National University School of Medicine, St. Chae University of Science and Technology, Pohang, 5 1 2 7 regulators of fuid hydration on the eye. The Ohio meibum according to dry eye type classifed by Ophthalmology and Anatomy/Cell Biology,Kresge State University College of Optometry, Columbus, 1 2 tear flm interferometer. The School of Optometry, Medicine, University of Southern California, ophthalmic solutions stabilize tear flm Korea (the Republic of) Lacritin, the Shed Form of Lacritin Co-Receptor Dubald, A. Yuriko University, Gwangju, Korea (the Republic of) 1, 2 3 2 4 Intraductal Probing for the Treatment of Ban, N. A induced Dry Eye Disease in Rabbits using Nantan, Kyoto, Japan; 2Ophthalmlogy, Kyoto Orlin1, M. Yukihisa School of Pharmacy, Chapman University, Irvine, Adiponectin-Derived Short Peptides and Takada, O. Ophthalmology, Yonsei University Wonju 3 Ophthalmology, Chosun University Hospital, Islands (U. Chang Gung Memorial Hospital, the First Affliated Hospital of Nanchang Universi, enhances the ocular mucin secretion in the Taoyuan, Taiwan Nanchang, China desiccation stress-mediated dry eye disease. Meri Ophthalmology, Oslo University Hospital, Oslo, Ophthalmology, Massachusetts Eye and Ear Vattulainen, T. Mary Ann Conservation Mechanisms in Cultured Sheets Stem Cell Defciency and Neovascularization. Low Vision Group / Visual Psychophysics/ cells and organ-cultured diabetic corneas for 1, 2 3 Bagherinia, A. Department Ophthalmology, University of Illinois at Chicago, Victoria, Australia; 2Bionic Eye Technologies, Inc. Huiyu Biosciences, Latrobe University, Bundoora, Victoria, Australia; 5Department of Ophthalmology, cell function in healthy and diabetic cornea. Department of Ophthalmology and Visual 1 1 University of Bonn, Bonn, Germany; 6L V Prasad Aleksandra Leszczynska, M. Stout, 3 1 1 1 1, 3 Ophthalmology and Visual Sciences, University of Department of Electrical and Electronic M. Choi, 8 1 1 1 4 Alberta, Edmonton, Alberta, Canada; Department Engineering, Jerusalem College of Technology, L. Hirota, 4 of Ophthalmology & Visual Sciences, University 2 2 3 1 Institut de la Vision, Sorbornne Universites, Paris, 12 H. Trainees, students and junior faculty will beneft from this unique opportunity to network and gain valuable information from those who have been in your shoes! This very popular program offers informal discussions over breakfast on a wide range of topics to provide personal guidance, insight and skills to help you advance your career! Topics will focus on professional development, career guidance, and best practices of interest to basic and clinical trainees and clinician-scientists. A number of the roundtable topics will be specifcally tailored to the needs of clinician-scientists. Lorie St-Amour, University of British Columbia, Vancouver, British Columbia, Canada; 6Population Health, Singapore J. Science, Friedrich-Alexander-Universitat Erlangen University, Adelaide, South Australia, Australia; Afshari. Netherlands; Ophthalmology, Radboud University and Informatics, University of Pennsylvania, 1 2 1 1 5 Bonfglio, M. Pavlou1, Seng Hospital, Singapore, Singapore; 2Department Western Australia, Perth, Western Australia, I. Osamah Saeedi1, (Centre for Vision Research), Westmead Hospital) Photoreceptor Survival in Mouse Models of B. Tsai1, and Westmead Millennium Institute, Westmead, 1 3 1 New South Wales, Australia; 7Melbourne School Retinitis Pigmentosa. Cardiff, England, United Kingdom; 2School of Biochemistry/Molecular Biology Gesualdo3, S. Connectomics, Korea Institute of Science and and Division of Preventive Ophthalmology, Guy. Bonilha complement C3 activation in models of macular Assitance Publique Hopitaux de Paris, Paris, France 1, 2 1, 3 degeneration. Shuster2, Sciences, University of Wisconsin-Madison, Department of Regenerative Medicine, Tongji Eye E. Mohamed1, 2, 1Ophthalmology and Vision Science, University potential role of age-related synuclein in the 1 S. Franziskus Hospital Munster, Munster, (the Republic of); 2 University of Ulsan College of Stepicheva1, S. Germany; 5Faculty of Medicine, University of 3 2 2, 1 1 Medicine, Ulsan, Korea (the Republic of); College S. Mukherjee, Ophthalmology, University of Pittsburgh School of Reproductive Medicine and Andrology, Wesfalian N. Aleksander Ireland, Belfast, Northern Ireland, United Institute, the Johns Hopkins University School of Tworak1, C. Department of Clinical Neuroscience, Neuroscience, Cell Biology & Anatomy, the Zhang, A. Department of Medicine Huddinge, Center for retinal pigment epithelium in the mouse. State Key Laboratory of Institutet, Stockholm, Sweden; Department of 2 2 2 1 Chrenek, J. Pham, Astronomy, Texas A&M University, College Station, Yamaguchi, Japan; 2Kyushu University School of 4 Z. Ishikawa, Biology, University of Iceland, Reykjavik, Iceland; 2, 3 1 4 mitochondrial dynamics in the retinal pigment D. Ophthalmology, Doheny Eye Clinical Neurosciences, St Erik Eye Hospital, 1 1, 2 2 epithelium. Epithelial Cells: An Alternative Metabolic Semmelweis University, Budapest, Hungary 1 1 1 Wils, J. Netherlands; Institute of Cellular and integrative 1 1 1 1 Mitochondria Depletion and Rescue by Platelet Schulz, I. Biochemistry, University Astrophysics, Optics and Electronics, Tonantzintla, Cepko1, 2, D. Ophthalmology, University of intraocular pressure in open angle glaucoma Winterbottom2, A. Andre Costa Dublin, Dublin, Ireland 3 2 2 2 University Eye Clinic, Dipartimento di Scienze Brito, R. Metz, Psychiatry, University of Illinois at Chicago, 3 3 Korea (the Republic of); Hanyang University M. New England College of 1 1 2, 3 and Behavioral Medicine, Wake Forrest University Adrienne Ng, A. Clinic, Tajimi, Japan; Topcon Corporation, Tokyo, and Applied Informatics, Nicolaus Copernicus Japan; 4Santen Pharmaceutical, Tokyo, Japan M. Ophthalmology, Massachusetts Eye and through a novel deep neural network model for Martini, M. Sciences and Public Health, University of Brescia, London, United Kingdom Yu-Chieh Ko1, 2, S. Cheng, 1, 2 1, 2 1 HsinChu, Taiwan utilizing the Glaucoma Score versus automated T. Singapore Eye Research grading of fundus photographs to detect Institute, Singapore National Eye Centre, glaucomatous eyes. Outcomes from a School-Based Vision Screening Superior to that of Retinal Nerve Fibre Layer Jihyun Kim1, 2, N. Alexandria University, Alexandria, Egypt; 3Institute affliated hospital of Fujian Medical University, Ryu Iikawa, T.

Coughing mood disorder pills purchase bupropion 150mg online, particularly at night depression glass definition history cheap bupropion 150 mg without prescription, may be have great difficulty lying at because the contents of their caused by the early stages of pulmonary congestion and be abdomen tend to push upwards on to the diaphragm when a sign of impending left heart failure anxiety rash symptoms discount bupropion 150 mg with mastercard. A useful line of questioning while taking can also be a symptom either of asthma or of gastrointesti the history can be to ask the patient what happens if they nal re ux depression symptoms how long 150 mg bupropion. Patients with true orthopnoea tend to wake up distressed because of breath Palpitation(s) (cardiac arrhythmias) lessness depression brochure buy 150 mg bupropion, but other patients may simply continue to sleep in Patients usually perceive cardiac arrhythmias (E Chapters a atter position than the one they started the night in depression symptoms dysthymia buy genuine bupropion on line. This this dramatic symptom must be sought in taking the car can be one of the most difficult areas in which to obtain diovascular history and distinguished, if possible, from a precise history. They old method of asking the patient to tap out the rhythm on frequently go to the window because they believe that they the desk or on their knee is extremely helpful. Frequently can improve the situation by inhaling fresh air which they patients, when asked to do so, say they are unable to repro believe contains with more oxygen. Clearly this is not true, duce the arrhythmia but if they have a demonstration from but the effect of standing up dramatically reduces venous the examining doctor of the possibilities then they soon get return and thereby reduces right heart output and relieves the idea and are able to do this. The intermittent breathing that is usually the result of a low Although the patient may describe the classical sudden start cardiac output is really a physical sign. The patient is usually obese and may be plethoric and their chronic emotional stress of all types. The doctor must try to main complaint is of somnolence during the day and they distinguish whether an arrhythmia is regular or irregular and may develop heart failure as a complication. The Patient usually silent Grunting and involuntary noises patient was reassured, but developed a similar but more Pallor + + Often cyanosed and suffused with prolonged episode while playing football a few months (particularly in tonic phase) later. Afterwards: usually tired Afterwards: confusion common and a but not confused with feeling of being hungover and also possible Lesson fairly quick recovery residual paralysis Always use careful questioning to establish precipitat ing factors. Attempt to test when precipitating factors are present and continue testing until you have caught this can be extremely difficult, both for the patient and for an episode. There may also be asso unexplained lightheadedness or syncope (E Chapter 26) ciated nausea. Cardiovascular presyncope does not usually or chest pain, it is important to question the patient as to have a rotational element, although the patient may still whether or not there is an associated palpitation, which could describe a symptom as dizziness which is really a feeling of represent an arrhythmia which is causing the problem. If the Perhaps the commonest symptoms are those due to ven patient does not notice that the room is revolving, and if tricular or atrial ectopic beats. Patients variously describe they feel as though they are close to losing consciousness, the sensation as the heart skipping a beat or stumbling then the problem is more likely to be cardiovascular. In a patient who Some patients who describe palpitation are in fact complains of blacking out, it is very important to estab describing a normal cardiac rhythm. Some be made more forceful because of anxiety or for no obvi patients may say they are blacking out, when in fact they ous reason and the patient then perceives an acceleration simply feel very distant from surrounding events. Sinus tachycardia is usu feelings of with being disembodied but remaining fully con ally relatively slow compared with a true tachyarrhythmia, scious is often associated with anxiety or other psychologi often at a rate of about 110 beats per minute. Another area in which confusion occurs is cardia usually builds up over a matter of some minutes when the patient says they have lost consciousness when and then goes off slowly and does not have a sudden onset. If the patient remembers hitting the ground this prominent if the patient is lying in bed on their left side; potential differential diagnosis has to be considered. Similarly are a particular group of patients whose legs simply give a slow regular thumping or heavy beat may occasionally way on them and there is no cardiovascular cause for this. In addition to trying to elicit the Occasionally patients may give a history of collapsing symptoms that may distinguish between a cardiovascular with syncope and then coming round after a short period and a cerebrovascular cause, it is also necessary to estab and being aware of a rapid tachycardia. This may be because lish the circumstances under which an episode of syncope whatever caused the syncope also produced a tachycardia. This information may be helpful in making a diag However, more often it is because the sudden drop in car nosis, particularly when the episodes occur as a result of diac output caused by the tachycardia and an unprepared either fear, emotion, prolonged standing, micturition, def dilated peripheral circulation causes a severe fall in blood ecation, etc. Then protective constrictive re exes known to lead to a high level of vagal tone and lead on to raise the blood pressure despite the continuing tachycardia vasovagal syncope. They frequently occur in young patients without any other illness, although problems with voiding, i. Oedema and ascites micturition and defecation syncope, are much more likely Although oedema and ascites are physical signs, they are to occur in the elderly. It is most striking when a patient has If the patient describes injury associated with syncope a successful treatment and suddenly realizes how tired they then this usually denotes a lack of warning and suggests were before. If it occurs intermittently it may have a de a signi cant underlying problem and a sudden onset. A nite underlying cause although this may be difficult to track warning favours a neurological cause, particularly if this down (E Box 1. This should Less common cardiological symptoms not be confused with a brief period of presyncope prior to a true syncopal episode. Following an episode of cardio Vomiting vascular syncope, patients may feel tired, but do not usu Patients in the early stage of an acute myocardial infarction ally feel particularly unwell, whereas patients who have may vomit profusely. It may be difficult to be sure whether experienced a convulsion often feel extremely unwell for the stress and dehydration of the vomiting precipitates the a long period of time with headache, lethargy, and what infarction, or vice versa [11, 12]. She decided that she must go to the racing he suddenly and unexpectedly ran out of energy lavatory, stands, and starts to walk to the door but loses and became tired. When he did so the symptoms usually resolved within a few minutes and he felt normal again. Holter monitoring during a the arrhythmia initially causes a moderate fall in cardiac cycle race showed that this loss of energy was due to the output but while she is sitting the circulation can com sudden occurrence of atrial utter with 1:1 conduction. As soon as she stands up the gravitational effect this has been cured by ablation and he is now racing on the circulation reduces the cardiac output further and successfully again. This is not good prac common in atrial brillation (Chapter 29), and paroxys tice and must be resisted. The patient who wants to go home It is particularly common in patients who have severe tri cuspid regurgitation. In addition to this, venous back pres the patient in the emergency room who feels perfectly well sure into the liver stretches the liver capsule and causes at the time when their history is taken but has presented with discomfort. This is because the atrium contracts at the same condition progresses, appropriate therapy, including early time as the ventricle, i. It is no Unusual noises in the chest disgrace to admit a patient for one night, decide the diagno A very unusual but striking symptom is when the patient sis is not myocardial ischaemia, and send the patient home. This ease which requires immediate treatment if the patient is to is very rare, but may indicate a mechanical fault with the survive. In such patients it is important to look for ancil valve with a component sticking. For example, a patient who has a massive sticks the noises generated by the valve cease. These observations may have been made in the There is a high potential for harm if a serious cardiovas ambulance bringing the patient to hospital. It is therefore cular diagnosis is missed and if a patient who is either in crucial in any acute patient to obtain a history from the the clinic or emergency department is then sent home with relatives and ambulance staff, and also information from out further investigation. Again it is the associated symptoms that act Cardiovascular exam Comments as the telltale for a serious underlying condition. This Hands Splinters/peripheral cyanosis is a particularly difficult area in which to establish a diag Face/eyes Pallor, cyanosis, jaundice nosis, but if a patient with a mechanical valve notices the Ocular fundi Diabetic and hypertensive changes, clicks have stopped or changed in character the diagnosis of endocarditis a malfunctioning valve must be seriously considered. Time because very high pressures even in an out-patient environment often make a Normal < 4cm above sternal Left usually more reliable than right full examination impractical. It is important to understanding the relevance Chest of both the presence and the absence of particular clinical Inspect Scars, deformity, movement signs. If necessary assess sounds effect of: a quiet, warm, comfortable environment with good light Position ing, although clinical circumstances often dictate the need Respiration to perform an examination under suboptimal conditions. Examination begins before the patient is settled on an examination couch and valuable insights can be gained Camm-Chap-01. Xanthelasma Hyperlipidaemia Often occur as normal There are many clinical signs that might be elicited dur (E. Although a median ster Tremor Hyperthyroidism Alcohol withdrawal notomy scar can relate to many types of cardiac surgery it Drug induced may also indicate other past mediastinal problems. A left thoracot pulsations regurgitation omy scar may indicate aortic surgery, particularly previous Rash and Vasculitis, Very non-speci c but surgery for coarctation of the aorta, and a right thoracotomy petechiae endocarditis, extremely helpful. Always look at the legs rheumatic fever Often associated with and arms for scars indicating that a vascular conduit has been arthralgia or arthropathy harvested, strongly suggesting a previous coronary artery Uncommon signs bypass graft. Chest scars may be due to previous lung surgery Finger clubbing Infective endocarditis Also in lung cancer and (and toes) Cyanotic congenital other lung disease which may shift the mediastinum and with it the heart, mak heart disease ing interpretation of physical signs more difficult. In patients with cardiomegaly Facial Down, Turner, A variety of congenital dysmorphism Noonan syndromes chromosomal since early childhood the chest wall may bulge out over the abnormalities enlarged heart. The character of the pulse is a valuable sign but must C usually be assessed using a central pulse and the carotid is usually best although the brachial may be helpful. One exception is the collapsing pulse of severe aortic regurgita tion which, although detected at the carotid, is often best appreciated by palpating the radial pulse with the arm raised above the head when the pulse acquires a very sharp D tapping quality. There is a time delay to peak systolic pres fairly rapid upstroke of the pulse to its peak, then a more gradual descent sure which gets later as stenosis gets worse and the pulse which includes an impalpable with dicrotic notch created as a result of aortic volume also falls. Often associated with combined aortic stenosis and regurgitation, it tion a 100mmHg gradient across the aortic valve still leaves is characterized by twin peaks (percussion wave and tidal wave) separated by a mid-systolic dip. The typical slow rising pulse can be mimicked by local disease in the carotid and hard sclerotic vessels which amplify the pulse pressure and checking both carotids may clarify the situation. This is because these patients are often elderly with resulting from severe aortic regurgitation (E Chapter 21). These pulse char acteristics also occur in any situation when there is a large volume systolic leak from the central circulation. The pulse in these conditions has some similarities to the collapsing pulse but there are subtle Figure 1. The upstroke and particularly the downstroke linear haemorrhagic lesions at the distal nail bed. Illustration of the aortic pressure waveform in aortic stenosis and aortic regurgitation compared to the simultaneous left ventricular pressure. In aortic stenosis the aortic pressure rises slowly to its peak in late systole 100 and there is a signi cant systolic pressure difference between the aorta and left ventricle. There are two peaks (percussion wave and from the pulmonary circulation is reduced and the output tidal wave) separated by a mid-systolic dip. Inspiration also pulls pulse is rare but very striking when it is encountered in the heart down and the globular shape of the heart becomes clinical practice. The sign is elicited and measured by slowly de at due to asthma, the very striking swings in intrathoracic ing the blood pressure cuff while listening to the blood pres pressure also produce pulsus paradoxus [20]. The physi this is when there are alternate strong and weak pulses in ological mechanism is complicated but the main effect is a basically regular pulse. Aortic pressure waveform demonstrating variation in pulse amplitude with respiration, the pressure decreasing with inspiration Insp Insp Insp (insp). As well as there results from transmission of the pulsation from the inter being a weak and strong pulse as in pulsus alternans, there nal jugular vein to the skin surface, and it is the pulsation is also an irregularity in the underlying pulse rhythm which rather than the vein itself that is visible. If all foot pulses (dorsalis pedis and posterior tibial on the liver may accentuate it further. The with hepatojugular on both sides) are strong and present it is very unlikely that re ex (sometimes stated as with re ux) does not in our experi that patient will be suffering from coarctation, particularly if ence generally contribute anything else further to the exam they have a normal blood pressure. In the presence of hyper ination although some authorities believe it to be helpful in tension the femoral pulses must be examined to exclude diagnosing heart failure [24]. Pulsation from the carotid artery can be the radial arteries at about the same time as they are approxi transmitted to the surface and has to be distinguished from mately the same distance from the heart. The carotid there is severe obstruction at the site of coarctation the blood pulse is usually a single wave. This has the disadvantage that an inaccuracy in Right ventricular infarction the previous blood pressure may be perpetuated, and the Pulmonary hypertension blood pressure may have changed in the time between the Hypervolaemia two examinations. Tricuspid regurgitation With the progressively more obese population it is impor Reduced right ventricular compliance tant to use a large cuff on big arms, otherwise there is an Pericardial constriction/tamponade overestimation of blood pressure levels [21]. Right atrial pressure trace in tricuspid pid valve towards the apex as a result of longitudinal shorten regurgitation illustrating the early, accentuated, and dominant with v wave. This can also occur in some other clinical situations such as right ventricular infarction [26]. Cannon waves can also some times occur as a result of a ventricular ectopic beat that closes the tricuspid valve but is not electrically conducted Figure 1. Regular cannon waves occur in systole causing descent of the tricuspid valve towards the apex as a result of ventricular tachycardia with intact retrograde conduction longitudinal shortening of the ventricle with systolic contraction. Auscultation Apical impulse (apex beat) the lowest and most lateral position on the chest wall where this still remains an important aspect of the clinical cardio a cardiac impulse can be felt is known as the apex beat. This with the almost universal availability of echocardiography can be confusing as sometimes the most laterally felt impulse in the developed world. The apical impulse or apex beat often not difficult to time in the cardiac cycle but if there is usually located in the fth intercostal space at the level of, is doubt, palpation of the carotid pulse is extremely useful. Chest deformity, Systolic events tend to occur at the same time as the carotid lung disease, and obesity all reduce the intensity of the apex pulse since as there is only a short distance between the beat or render it impalpable. In these situations, rotating aortic valve and the carotid artery, the systolic pulse wave the patient to a left lateral decubitus position tips the heart in the carotid artery occurs only a matter of milliseconds towards the chest wall and makes the apex beat easier to feel. Abnormalities of the apical impulse the most common abnormalities of the apex impulse are Normal heart sounds as follows: S 1 and S2 are usually the only heart sounds heard on aus cultation of a normal heart (E. Clinically the apical impulse may be displaced to the left and have a this splitting is usually narrow and is difficult to hear unless more diffuse heaving nature. This is usually when there is there is right bundle branch block which accentuates this volume overload. If the patient S 2 results from closure of the aortic and pulmonary valves has an audible gallop rhythm this can sometimes also be (A2 and P2) [31], and is also normally split, the dominant aor palpated with a hand placed over the cardiac apex [27, 28]. This splitting is usually accen Mitral stenosis (E Chapter 21) produces a particularly tuated by inspiration when right heart lling is increased and characteristic cardiac apical impulse.

This eversion technique is required to remove for eign bodies or lost contact lenses from the superior fornix or to clean the conjunctiva of lime particles in a chemical injury with lime depression test kit cheap 150 mg bupropion with mastercard. Examination of the upper eyelid and superior fornix (full eversion with retractor) depression cherry bupropion 150mg without prescription. In contrast to simple eversion mood disorder icd 9 code cheap bupropion 150 mg with amex, this procedure allows examination of the superior fornix in addition to the palpebral conjunctiva anxiety relief techniques order cheap bupropion on-line. In these cases ventilatory depression definition generic 150 mg bupropion with mastercard, the spasm should first be eliminated by instilling a topical anesthetic such as oxy buprocaine hydrochloride eyedrops depression chemical imbalance buy generic bupropion 150mg online. Epithelial defects, which are also very painful, will take on an intense green color after application of fluorescein dye; corneal infiltrates and scars are grayish white. Sensitivity is evaluated bilaterally to detect possible differences in the reaction of both eyes. The examiner holds the upper eyelid to prevent reflexive closing and touches the cornea anteriorly. Decreased sensitivity can provide information about trigeminal or facial neuropathy, or may be a sign of a viral infection of the cornea. The patient looks straight ahead while the examiner holds the upper eyelid and touches the cornea anteriorly. In a cham ber of normal depth, the iris can be well illuminated by a lateral light source. The pupillary dilation should be avoided in patients with shallow ante rior chambers because of the risk of precipitating a glaucoma attack. Dilation of the pupil with a mydriatic is contraindicated in patients with a shallow anterior chamber due to the risk of precipitating angle closure glaucoma. Direct illumination will produce a red reflection of the fundus if the lens is clear and gray shadows if lens opacities are present. The examiner then illuminates the eye laterally with a focused light held as close to the eye as possible and inspects the eye through a +14 diopter loupe (see. This examination permits better evaluation of changes in the conjunctiva, cornea, and anterior chamber. With severe opacification of the lens, a gray coloration will be vis ible in the pupillary plane. Each vascular structure should be of uni form diameter, and there should be no vascular constriction where vessels overlap. Younger patients will have a foveal and macular light reflex, and the retina will have a reddish color (see. The examiner moves an object such as a pen, cotton swab, or finger from the periphery toward the midline in all four quadrants (in the superior and infe rior nasal fields and superior and inferior temporal fields). A patient with a normal field of vision will see the object at the same time as the examiner; a patient with an abnormal or restricted field of vision will see the object later than the examiner. It can be used to diagnose a severely restricted field of vision such as homonymous hemianopsia or quadrant anopsia. The examiner moves a pen from the periphery toward the midline in all four quadrants in the nasal and temporal fields and in the superior and inferior fields. Slight increases in intraocular pressure such as occur in chronic glau coma will not be palpable. One drop or strip of ointment approximately 1cm long should be administered laterally to the inferior conjunctival sac. To avoid injury to the eye, drops should be administered with the patient supine. Eye ointment should not be administered following ocular trauma as this may complicate subsequent examination or surgery. Dilation of the pupils with a mydriatic in unconscious patients should be avoided as this complicates neurologic examination. A sterile swab or commercially available bandage (two oval layers of bandage material with a layer cotton between them) may be used. Strong mechanical, optical, and acoustic stimuli (such as a foreign body, blinding light, or sudden loud noise) automatically elicit an eye closing reflex. Structure of the eyelids: the eyelids consist of superficial and deep layers. The tarsal muscle is supplied by the sympathetic nervous system and regulates the width of the palpebral fissure. High sympathetic tone contracts the tarsal muscle and widens the palpebral fissure; low sympathetic tone relaxes the tarsal muscle and narrows the palpebral fissure. Every time the eye blinks, it acts like a windshield wiper and uniformly distributes glandular secretions and tears over the conjunctiva and cornea. Orbicularis oculi muscle Orbital septum Orbital fat Levator palpebrae muscle Accessory lacrimal gland Superior M. Thedeeplayerconsists of the tarsal plate, tarsal muscle, palpebral conjunctiva, and meibomian glands. Their function is to prevent the escape of tear fluid past the margins of the eyelids. On the upper eyelid, approximately 150 eyelashes are arranged in three or four rows; on the lower eyelid there are about 75 in two rows. Like the eyebrows, the eyelashes help prevent dust and sweat from entering the eye. The orbital septum is located between the tarsal plate and the margin of the orbit. It is a membranous sheet of connective tissue attached to the margin of the orbit that retains the orbital fat. Bilateral inspection of the eyelids includes the following aspects: O Eyelid position: Normally the margins of the eyelids are in contact with the eyeball and the puncta are submerged in the lacus lacrimalis. O Width of the palpebral fissure: When the eye is open and looking straight ahead, the upper lid should cover the superior margin of the cornea by about 2mm. Occasionally a thin strip of sclera will be visible between the cornea and the margin of the lower lid. Varying widths of the gaps between the eyelids may be a sign of protrusion of the eyeball, enophthal mos, or eyeballs of varying size (Table 2. O Skin of the eyelid: the skin of the eyelid is thin with only a slight amount of subcutaneous fatty tissue. Allergic reaction and inflammation can rapidly cause extensive edema and swelling. In older patients, the skin of the upper eyelid may become increasingly flaccid (cutis laxa senilis). Occa sionally it can even hang down over the eyelashes and restrict the field of vision (dermatochalasis or blepharochalasis). The normal palpebral conjunctiva is smooth and shiny without any scar strictures or papilliform projections. Colobomas are rare defects resulting from a reduction malformation (defective closure of the optic cup). Diagnostic considerations: the disorder is often accompanied by additional deformities such as dermoid cysts or a microphthalmos. Depending on the extent of the coloboma, desiccation symptoms on the conjunctiva and cornea with incipient ulceration may arise from the lack of regular and uniform moisten ing of the conjunctiva and cornea. Treatment: Defects are closed by direct approximation or plastic surgery with a skin flap. The nasal bridge becomes more pro nounced as the child grows, and most epicanthal folds disappear by the age of four. Blepharophimosis is a rare disorder that is either congenital or acquired (for example, from scar contracture or aging). As long as the center of the pupil remains unobstructed despite the decreased size of the palpebral fissure, surgical enlargement of the palpebral fissure (by canthotomy or plastic surgery) has a purely cosmetic purpose. Usually, the partial or total fusion between the upper and lower eyelids will be bilateral, and the palpebral fissure will be partially or completely occluded as a result. The following forms are differentiated according to their origin (see also Etiology): O Congenital ptosis. The disorder is usually hereditary and is primarily auto somal dominant as opposed to recessive. The cause is frequently aplasia in the core of the oculomotor nerve (neurogenic) that supplies the levator palpe brae muscle; less frequently it is attributable to an underdeveloped levator palpebrae muscle (myogenic). The drooping of the upper eyelid may be unilateral (usually a sign of a neurogenic cause) or bilateral (usually a sign of a myogenic cause). A characteristic feature of the unilateral form is that the patient attempts to increase the palpebral fissure by frowning (contracting the frontalis muscle). The skin of the upper eyelid is smooth and thin; the supe rior palpebral furrow is absent or ill-defined. A typical symptom is lid lag in which the upper eyelid does not move when the patient glances down. This important distinguishing symptom excludes acquired ptosis in differential diag nosis. In about 3% of all cases, congenital ptosis is associated with epicanthal folds and blepharophimosis (Waardenburg syndrome). Congenital ptosis can occur in varying degrees of severity and may be com plicated by the presence of additional eyelid and ocular muscle disorders such as strabismus. Congenital ptosis in which the upper eyelid droops over the center of the pupil always involves an increased risk of amblyopia. Often there will be other signs of palsy in the area supplied by the oculomotor nerve. In external oculomotor palsy, only the extraocular muscles are affected (mydriasis will not be present), whereas in complete oculomotor palsy, the inner ciliary muscle and the sphincter pupillae muscle are also affected (internal oph thalmoplegia with loss of accommodation, mydriasis, and complete loss of pupillary light reflexes). Rapidly opening and closing the eyelids provokes ptosis in myasthenia gravis and simplifies the diagnosis. Treatment: O Congenital ptosis: this involves surgical retraction of the upper eyelid. As palsies often resolve spontaneously, the patient should be observed before resorting to surgical intervention. Conservative treatment with special eyeglasses may be suffi cient even in irreversible cases. Because of the risk of overcorrecting or undercorrecting the disorder, several operations may be necessary. Prognosis and complications: Prompt surgical intervention in congenital ptosis can prevent amblyopia. Surgical overcorrection of the ptosis can lead to desiccation of the conjunctiva and cornea with ulceration as a result of incomplete closure of the eyelids. The margin of the eyelid and eyelashes or even the outer skin of the eyelid are in contact with the globe instead of only the conjunctiva. The following forms are differ entiated according to their origin (see Etiology): O Congenital entropion. Epidemiology: Congenital entropion occurs frequently among Asians but is rare among people of European descent, in whom the spastic and cicatricial forms are more commonly encountered (see also Chap. Etiology: O Congenital entropion: this results from fleshy thickening of the skin and orbicularis oculi muscle near the margin of the eyelid. The frontalis suspen sion technique may employ autogenous fascia lata or plastic suture. O Cicatricial entropion: this form of entropion is frequently the result of postinfectious or post-traumatic tarsal contracture (such as trachoma; burns and chemical injuries). Symptoms and diagnostic considerations (see also etiology): Constant rubbing of the eyelashes against the eyeball (trichiasis) represents a per manent foreign-body irritation of the conjunctiva which causes a blepharo spasm (p. Treatment: O Congenital entropion: To the extent that any treatment is required, it con sists of measured, semicircular resection of skin and orbicularis oculi muscle tissue that can be supplemented by everting sutures where indi cated. O Spastic entropion: Surgical management must be tailored to the specific situation. Usually treatment combines several techniques such as shorten ing the eyelid horizontally combined with weakening or diverting the pre tarsal fibers of the orbicularis oculi muscle and shortening the skin verti cally. O Cicatricial entropion: the surgical management of this form is identical to that of spastic entropion. An adhesive bandage may be applied to increase tension on the eyelid for temporary relief of symptoms prior to surgery. Prognosis and complications: Congenital entropion is usually asymptomatic and often resolves within the first few months of life. O Spastic entropion: the prognosis is favorable with prompt surgical inter vention, although the disorder may recur. Left untreated, spastic entropion entails a risk of damage to the corneal epithelium with superin fection which may progress to the complete clinical syndrome of a serpigi nous corneal ulcer (see p. O Cicatricial entropion: the prognosis is favorable with prompt surgical intervention. The following forms are differentiated according to their origin (see also Etiology): O Congenital ectropion. Epidemiology: Senile ectropion is the most prevalent form; the paralytic and cicatricial forms occur less frequently.

If pain always occurs at a site other then peri umbilical the possibility of other organ system pathology depression definition causes discount bupropion uk. Classic features are periodic acute self Treatment limiting febrile episodes with peritonitis anxiety prayer generic 150mg bupropion with visa, pleuritis depression definition illness generic 150mg bupropion with mastercard, syno Colchicine is effective beck depression test inventory generic bupropion 150 mg on line. Diagnostic Criteria Site Periodic attacks of peritonitis (rarely pleuritis) occurring Abdomen or chest anxiety 2 year old 150 mg bupropion otc. Self-limiting and associated with fever depression test bdi discount bupropion 150mg line, leucocytosis, and occasional System rash. Onset: abdominal pain Code (peritoneal) most frequent presenting feature, varies in 434. Chest wall tenderness may be marked Definition during attack, and transient pleural effusion may occur. Characterized by recurrent attacks of abdominal pain, Attacks occur with varying frequency. Associated Symptoms Erysipelas-like erythema over the cutaneous aspects of System thighs, legs, or dorsa of feet. Arthralgias or acute arthri Unknown; vasospasm in the autonomic diencephalic this involving mainly large joints such as knees or ankles. Precipitants such as exercise, emotional stress, Site menstruation, fatty food, and cold exposure have been Abdomen. Relief obtained only from strong analgesics, though colchicine may diminish frequency of attacks. Main Features Prevalence: unknown; but uncommon in contrast to Laboratory Findings common or classical migraine. Aura: pro dromal symptoms may occur such as listlessness, mood Complications disturbance, yawning or, rarely, typical aura of common Amyloidosis is the commonest cause of death and is migraine. Its occurrence is highly variable ally epigastric or periumbilical; a diffuse burning or ach depending on race and geography. When it does occur ing increasing in severity lasting several hours but death is usually before age 40. Definition Signs Inherited disturbance of porphyrin metabolism not asso Skin may show vasodilation; nonspecific fever has been ciated with photosensitivity, with attacks of abdominal recorded. Course Tends to become less frequent with age and usually dis Main Features appears when personal conflicts resolve. Attacks may be precipi teria tated by (a) a wide variety of drugs, hormones; or (b) Recurrent attacks of vomiting and/or abdominal pain metabolic and nutritional factors (dieting, low carbohy occurring either as a migraine equivalent or associated drate intake). Associated Symptoms Neurological symptoms and signs are variable but may Differential Diagnosis include peripheral neuritis (motor), autonomic, brain Gallstones; peptic ulcer, porphyria, irritable gut stem, cranial nerve, and cerebral dysfunction. Social and Physical Disabilities Pain often results in frequent admissions to hospital. Definition Essential Features A rare hereditary disorder of porphyria metabolism Acute intermittent abdominal colic without photosensi characterized by acute attacks of abdominal pain, neuro tivity, with or without neuropsychiatric associated symp psychiatric manifestations, and photocutaneous lesions. Differential Diagnosis Main Features Peptic ulcer, gallstones, appendicitis, diverticulitis, irri Prevalence: unknown. First reported in Dutch descen Code dants in South Africa where incidence is 3 in 1000 Afri 404. Onset: usually in third decade, with cutaneous photosensitivity being initial feature. Permanent neuropathic Very rare; only a few families described; autosomal change can occur. Similar but milder disturbance; acute attacks often Pathology precipitated by drugs. X9d Chronic abdominal pain and depression: epidemiologic find ings in the United States Hispanic Health and Nutrition Ex amination Survey, Pain, 49 (1992) 77-85. It is Definition mostly found in young women, between 20 and 30 years Mittelschmerz, also called midcycle pain, occurs as re of age. Symptoms: usually presents as a recurrent pain current pain episodes at the time of ovulation. It presents around the date of ovula Female internal genital organs; in an ovary, a tube, or tion as a severe pain in an iliac fossa, lasting some 20 to the uterus. It may be accompanied by symptoms and signs of intraperitoneal Site bleeding: anemia, abdominal meteorism, diaphragmatic Either unilateral or bilateral in the lower abdomen. Time Course: the be felt always in the same iliac fossa, or alternately on severe form recurs only rarely; it may be followed by the one side or the other, or in the whole lower abdomen. Definition Dysmenorrhea is called secondary if a structural anom Signs aly is found that is probably responsible for the pain or In the less severe form, there are no signs, or only ten when the pain seems to have a psychological origin. When the severe form is System accompanied by intraperitoneal bleeding, there are signs Genital system. The pain is more often unilateral than in the pri Complications mary variety, especially when the causal condition is None in the less severe forms. In the severe forms there unilateral, as for example in some cases of endometrio may be massive intraperitoneal hemorrhage; as in these sis. Main Features these resemble primary dysmenorrhea, but the pain of Pathology ten lasts longer. Possible causes include maturation of Main Causes the follicle or ovulation itself or contractions of the tubal the main causes of secondary dysmenorrhea are: endo wall in a case of hydrosalpinx, or an increase in the basal metriosis, adenomyosis, submucous fibroids, and vari tone of the myometrial contractions around the time of ous causes of obstructive dysmenorrhea, as described ovulation. In more severe forms with intraperitoneal bleeding, a laparotomy may be necessary. The most frequent symptom is pain, which may present Diagnostic Criteria and Differential Diagnosis as dysmenorrhea or as premenstrual pain with menstrual the essential feature is recurrence at the time of ovula exacerbation, or continuous pain with or without men tion. The menstrual pain may last the the periovulatory period by means of the basal body whole duration of the menstrual period and sometimes temperature, which will show a shift toward a premen even one day after its end. Severe cases with right-sided location of endometriosis, refer to the section on Endometriosis may erroneously be taken for appendicitis. Main Features: hemorrhage, the time of occurrence will differentiate clinical diagnosis is difficult, so diagnosis has generally severe Mittelschmerz from ectopic pregnancy or rupture to await microscopic examination of a hysterectomy of a corpus luteum cyst, but blood transfusion and lapa specimen. The prevalence varies greatly, depending on rotomy will be indicated in both cases. The most common symp Reference toms are menorrhagia or metrorrhagia and dysmenor Renaer, M. Page 165 Associated Symptoms: adenomyosis frequently causes blood in the vagina will manifest itself by distention of infertility. Signs: the uterus is either symmetrically or the vagina with the hymen bulging at the introitus and asymmetrically enlarged and firm, and there are gener the posterior wall of the vagina bulging into the rectum. Usual Course: the uterine volume enlarges cause an asymmetrical enlargement of the uterus. The progressively over the years but rarely grows larger than distended blind half of a double vagina will bulge into a 14-week gestation. Pathology: Various con ing disappear at menopause but, owing to the severity of genital anomalies may cause secondary dysmenorrhea, symptoms, most patients have to undergo a hysterec. Pathol double uterus one half of which does not communicate ogy: adenomyosis is diagnosed only when endometrial with the vagina, or a uterus duplex bicollis, one half of glands are found at least one low-power microscopic which opens into a blind half of a double vagina. The nests of quired forms may be due to adhesions in the cervical endometrial tissue are generally surrounded by a prolif canal after amputation of the cervix or conization or eration of fibrous tissue. In the lower part of the uterine cavity, for example, in an adenomyosis no nodules are found; the uterus varies in Asherman syndrome. An early unilateral dysmenorrhea, contrast medium may suggest adenomyosis if, in a pa combined with the presence of an asymmetrical mass in tient with dysmenorrhea and menorrhagia, the uterine the lower abdomen or in the vagina is suggestive of an cavity has an irregular shape and if small diverticula are asymmetric malfusion deformity. If dysmenorrhea or teria: if the uterine size is only slightly enlarged, hys cryptomenorrhea appear after an amputation of the cer terography may detect a submucous fibroid or a fibroid vix or an electrocoagulation or a conization of the cer polyp. A circular or polycyclic filling defect is then vix, or after a curettage performed for retained products found that generally deforms the uterine cavity, whereas of conception, the diagnosis is easy and the condition a mucous polyp does not. A laparotomy will rarely be required menorrhea is called obstructive when obstruction of the to divide the adhesions under visual control. In congenital forms the pain mostly the frequency of such dysmenorrhea has been exagger begins a few months after menarche, as it starts only ated. The diagnosis of dysmenorrhea of psychological when enough blood has been retained to distend the va origin should be accepted only where no organic cause gina or the uterus. When there is an atresia of the hymen, can be found and when psychopathologic evaluation there is dysmenorrhea with cryptomenorrhea as the men reveals neurotic behavior or other psychopathological strual blood is retained in the vagina. X4 With adenomyosis or fibrosis double uteri are frequently accompanied by absence or 765. X6b With acquired obstruction tend the vagina and the uterus and give rise to a retro 765. X9a Psychological, tension grade menstruation, which, after a few months, may 765. Social and Physical Disability Third degree dysmenorrhea is the cause of periodic ab Definition sence from work or school in many teenagers and young Dysmenorrhea, or painful menstruation, refers to epi women. Pathophysiology Primary dysmenorrhea is found at the end of an ovula System tory cycle; it has also been reported in women taking Female internal genital organs; either the uterus or both oral contraceptives. Several authors have found ele radiate towards the sacro-gluteal zone in the lower back, vated prostaglandin concentrations in endometrium and i. It sometimes radiates into Although the exact mechanism of primary dysmenorrhea the anterior and superior aspect of one or both thighs. If the pain has a with an increased production (or perhaps increased re lower abdominal location, which is usually symmetrical, tention) of prostaglandins, which leads to increased, or and if no structural anomaly is found on clinical exami dysrhythmic, myometrial contractions, sensitization of nation, the dysmenorrhea is termed primary. Cases with nerve terminals to prostaglandins, and ischemia of the structural organic anomalies are classified as secondary uterine wall. Prevalence: between 5 and 10% of all girls in their late Treatment teens and early 20s suffer from severe, mostly primary, Mild and moderate cases are best treated by analgesics. In In severe cases the pain can be prevented by cyclic es one study, 72% of women aged 19 years had some dys troprogestogens, or the pain may, when it appears, be menorrhea. Pain Quality: the pain is generally colicky; in Differential Diagnosis about one-fourth of all cases the pain is continuous. In From conditions causing secondary dysmenorrhea, tensity: the pain may be mild. Third degree or incapacitating dysmenorrhea has ity of the internal female genital organs. Du tions have shown that in about 10% of cases with a ration: in most cases the pain starts a few hours or half a negative clinical examination, laparoscopic visualization day before the beginning of the blood flow, and usually of the internal genitalia may detect endometriotic le lasts less than one day. Associated Features With third degree primary dysmenorrhea there may be Code nausea, vomiting and/or diarrhea. X7b Usual Course Reference Primary dysmenorrhea may disappear spontaneously Andersch, B. The Lower abdominal pain due to foci of ectopic endo ectopic tissue may grow on the surface of the perito metrium located outside the uterus (endometriosis ex neum or it may become buried in a fibrous capsule. The pain may start as secondary dysmenorrhea; it may later become premenstrual as well as menstrual, or Site may become continuous. The pain due to endometriotic the pain may be located in one or in both iliac fossae or foci is usually alleviated by pregnancy. Subocclusion or Prevalence: the frequency with which endometriosis is occlusion of the small or the large intestine is possible found depends on the circumstances in which it is but infrequent. It was found in 15 and 20% of two different se in an ovary may cause an acute abdominal emergency ries of laparoscopies, but, on the other hand, it was due to irritation of the peritoneum by the old blood flow found in 50% of a large series of laparotomies. The ectopic foci Pathogenesis are located either in the pouch of Douglas or on the ova Retrograde menstruation, i. This seems to be the rather seldom they infiltrate the bladder wall or the wall pathogenetic mechanism in most cases of endometriosis. Age of Onset: It used to be thought that However, it does not explain all the possible locations of endometriosis usually develops in the late twenties or in the foci. Tiny fragments of menstrual endometrium may the thirties, but since more laparoscopies have been per be carried away by lymphatics and, more rarely, by formed on younger patients it has been found rather fre veins of the endometrium. Symptoms: In Diagnostic Criteria some 30 to 40% of patients with endometriosis there are the history and the findings on clinical examination will no complaints except perhaps infertility. When any doubt re symptom of endometriosis is pain; it may manifest itself mains, a therapeutic trial with cyclic estroprogestogens as dysmenorrhea, as premenstrual pain with menstrual will alleviate the pain in 8 of 10 cases. Lesions located in the inspection of the pelvic cavity has been used rather fre pouch of Douglas may provoke firm adhesions between quently in recent years to verify the diagnosis and to the anterior wall of the rectum and the posterior vaginal evaluate the extent of the lesions. Acute pain episodes in wall; this location may cause pain on defecation during the right iliac fossa due to endometriosis may be mis menstruation. Recurrent episodes of lower ab fixed uterine retroversion due to endometriotic adhe dominal pain, tenderness, and a slight fever may sions frequently cause deep dyspareunia. Endometriotic erroneously be taken for recurrent pelvic inflammatory foci that penetrate into or through the bladder wall may disease. Treatment Treatment of endometriosis will be hormonal or surgical Signs or combined. It will vary depending on age of the pa On pelvic examination a fixed painful retroversion may tient, stage of the disease, and the main presenting prob be found, or tender, enlarged, adherent adnexa on one or lem-pain or infertility or both. Small, tender nodular lesions, which are fre consists of cyclic estroprogestogens or in the continuous quently palpated either in a sacro-uterine ligament or on daily administration of oral progestogens, for example, the posterior surface of the uterus, are almost pathogno Lynestrenol or norethisterone acetate. During recent years excellent results have been obtained by the con tinuous oral administration of Danazol, a strong antigo Page 168 nadotropin and mild androgenic drug. In these circumstances treatment with broad will, depending on the indication and the stage of the spectrum antibiotics and local heat is indicated.

These should be interpreted as an aspiration or statement of action from the government and not as a measure of efectiveness or quality of implementation of programmes or objectives karst depression definition order generic bupropion line. The searches for government policies depression pain order bupropion 150 mg otc, health policy reports and published studies were conducted in English only bipolar depression vs clinical depression generic 150mg bupropion, so some relevant documents could have been omitted great depression usa definition cheap 150 mg bupropion visa. To provide a more nuanced picture of the local situation anxiety lump in throat order discount bupropion online, we conducted a survey of patient organisations for fve selected disease areas in each of the countries included in this study mood disorder lectures order genuine bupropion line. As patient advocacy groups have started to emerge only fairly recently in some countries, it proved difcult to identify independent, formally established patient organisations for all therapy areas. In these cases, the survey targeted patient groups within broader organisations or alliances that include other stakeholders, such as healthcare professionals or researchers. Therefore, some of the survey responses may represent the views of health professionals, rather than patients. Moreover, the respondents from patient organisations do not necessarily have frst-hand experience of living with certain conditions, which may further infuence the results. Many concerns are likely to be similar for patients living with diferent health conditions, such as being able to access help when needed. However, some concerns, such as the ability to drive, or freedom from stigma, may be pertinent to particular conditions. Based on the following criteria, we selected the areas marked in red for our health conditions focus: 1. A role for shared decision-making: We selected conditions that are chronic in nature, where quality of life is paramount, and that have complex therapy needs with trade-ofs in treatment; i. We chose not to include cancer and cardiovascular diseases, as these are already relatively well studied. Suggested inequitable access: Conditions in which some patients have inequitable access are more likely to have patient advocacy groups with a strong voice. Suggested neglected condition: As with access, neglected conditions will ofer us the opportunity to speak with active patient advocacy groups. Other considerations relevant to the project: We also considered other factors, such as the impact of conditions on other people. In relation to mental health, we decided to focus on common conditions such as depression and anxiety. These two conditions are burdensome and provide similar challenges, including having them acknowledged by the medical profession and the array of choices in relation to treatment options (choice of antidepressant and drug vs talking therapies). For healthy ageing, we decided to focus on bone health, including osteoporosis, fractures and falls. Again, these conditions result in a large burden on patients, which is added to by challenges around the identifcation and acknowledgement of the condition, and low adherence to medication. Mental health (with a focus on common mental health disorders, such as mild to moderate depression and anxiety) 2. Healthy ageing (with a focus on bone health, including osteoporosis, fractures and falls) 5. Health Technology Assessment or similar mechanisms for evaluation of health technologies) 1 = Existing mechanisms for introduction of innovative health technologies in the country. Health Technology Assessment or similar mechanisms for evaluation of health technologies) Source: the Economist Intelligence Unit Methodology: Desk research Domain 3: Delivery 3. If something is typical practice, even if not quite yet universal, we ask that you answer yes. Strategic planning, and incentives, monitoring and evaluation of patient-centred care Yes No Dont know My country has a strategic plan for patient-centred care My country has a bill or statement of patients rights My country has national quality standards for monitoring the implementation of patient centred care My country uses value-based payment systems as incentives for implementation of patient centred care (for example payment systems focused on patient outcomes) Healthcare professionals are trained in the principles of patient-centred care Healthcare professionals receive sufcient support with regard to stress, workload management and other job pressures 2. Personalised care, patient involvement in their own care Yes No Dont know Health professionals take a personalised approach to patient care, according to patients values and preferences Co-morbidities are taken into account when determining patient care options There arenationalpolicies for shared decision-making There areregional. Patient advocacy groups, patient empowerment Yes No Dont know For the patient group my organisation represents, my country has independent patient organisations with transparent funding Patient organisations are involved in policy development. Please answer from the point of view of the patients that your organisation represents. Each domain has six statements; please select the three most important statements for each domain. Patient experience Factors relating to how convenient care is for patients, in terms of admission and referral process, timing of tests, and timely and sufcient time spent with a courteous and helpful healthcare professional. Well-organised admission and referral process Care professionals are interested in what the patient has to say Patient is treated with courtesy and respect at all stages of the admission process Patient does not have to wait a long time to see the care professional they need Patients feel they have sufcient time with care professional. Shared decision-making Factors relating to how transparent relationships are between patients and providers, and whether there is opportunity and support for genuine shared decision-making and co-ownership of care plans. Patients are provided with options for care Patients are invited to be partners in decision-making about their care options Patients are fully informed about side-efects of treatment Family/friends can participate in discussions with care professionals Patients are allowed to review doctors notes and/or lab results High-quality information (in multiple formats) is ofered to patients 7. Inclusiveness and support Factors relating to how inclusive care providers are in terms of ensuring that all patients have equal access to quality care, regardless of issues such as age, language, gender, ethnicity or socio-economic background. Outcomes that matter to patients Factors relating to how focused healthcare professionals are in terms of ensuring that outcomes of the greatest importance to the patient are measured and used as criteria of success. Patients are ofered advice on prevention as well as cure Patients have a say in the outcomes used to measure efectiveness of treatment Patients are given advice about remaining healthy in future Patients feel that their emotional needs are being addressed Care professionals are interested in how a condition impacts upon patients lives Care professionals use validated patient reported outcome measures whenever possible 9. Most important domains the above questions have explored what is most important within certain domains of care. Wed now like you to rank which of the above fve domains of care are most important for your patients. Patient experience Shared decision-making Inclusiveness and support Outcomes that matter to patients Technology to improve accessibility and convenience Part C 11. Very Reasonably Not Not at Dont well well very all know well Patients are involved in the creation of their care plan, and throughout the care process Health services are designed to address patients clinical needs and support them to maintain their own health and wellbeing between clinical appointments Health policy mandates that clinical, emotionaland social support are all provided to patients People with long-term conditions are enabled to manage their own health in their day-to-day lives 12. Please indicate which of the following tools (if any) are used by care services in your country to monitor the application of patient-centred care. Please provide an example, from your country, of what you consider to be a best practice example of the application or monitoring of patient-centred care in any disease area (not just your own area of focus). The Economist Intelligence Unit Global Access to Healthcare Index 2017 [Internet]. Evaluating the quality of shared decision making during the patient-carer encounter: a systematic review of tools. A new drive for primary care in Europe: Rethinking the assessment tools and methodologies: Report of the expert group on health systems performance assessment [Internet]. Shared decision making in 2017: International accomplishments in policy, research and implementation. International variations in primary care physician consultation time: a systematic review of 67 countries. A Comparison of Patient-Centered Care in Pharmacy Curricula in the United States and Europe. Person centred care in Europe: a cross-country comparison of health system performance, strategies and structures. Atlas of eHealth country profiles 2015: the use of eHealth in support of universal health coverage. The fndings and views expressed in the report do not necessarily refect the views of the sponsor. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. There can be no guarantee that the investigational or approved products described in this presentation will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. Neither can there be any guarantee that the acquisition described in this presentation will be completed, or that it will be completed as currently proposed, or at any particular time. There can be no guarantee that Novartis or any potential products that would be obtained with Endocyte will achieve any particular future financial results, or that Novartis will be able to realize any potential strategic benefits or opportunities as a result of the proposed acquisition. Novartis is providing the information in this presentation as of this date and does not undertake any obligation to update any forward looking statementsas a result of new information, future events or otherwise. Until closing, Endocyte will continue to operate as a separate and independent company. Clinical trials of tropifexor in combination with Allergan and Pfizer compounds in accordance with collaboration agreements with those companies. Access Principles apply to how we research, develop and commercialize globally (though the focus of this slide is specifically R&D) 2. Psoriatic arthritis head-to-head study versus adalimumab Combination abbreviations: 5. Ankylosing spondylitis head-to-head study versus adalimumab tmx tamoxifen New indication 7. Diffuse large B-cell lymphoma 2 14 Chemotherapy-induced neutropenia and Chemotherapy-induced neutropenia and 2. Programs are not yet finalized markets as appropriate 47 Novartis R&D and investor update November 5, 2018 Value and pricing in life-long rare disease treatment 10-year drug cost vs. Inotersen and Patisiran for Hereditary Transthyretin Amyloidosis: Effectiveness and Value. The fitted regression model for the trend line is: y=63723x + 3E+06, with an R-squared value asReport 041618. Percentage of patients in later lines of therapies was calculated based on the treatment rate of the previous line. The acquisition of Endocyte is subject to customary closing conditions, including receipt of regulatory approvals and Endocyte stockholders approval. For presentation in response to an unsolicited request for medical information subject to local approval. Trends in stage distribution for patients with non-small cell lung cancer: A National Cancer Database survey. Non-small cell lung cancer: epidemiology, riskf actors, treatment, and survivorship. Fulvestrant given on Day 1 and Day 15 of the first 28-day cycle, then Day 1 of subsequent 28-day cycles. Patients receiving hydroxyurea or erythropoietin were included if prescribed for the preceding 6 months and dose was stable for at least 3 months. Domingo C et al; the prostaglandin D2 receptor 2 pathway in asthma: a key player in airway inflammation. Lancet Respir Med 2016;4:699-707 (225 mg bid, wk12) 104 Novartis R&D and investor update November 5, 2018 Fevipiprant development: targeting biologic efficacy with oral simplicity Exacerbation reduction % reduction over 52 weeks Administration Fevipiprant1 30 50 Targeted efficacy profile Benralizumab2 28 51 Mepolizumab3 42 53 Reslizumab4 50 59 Dupilumab5 67 46 1. At Week 48, the majority of patients (56% and 51%) were maintained on q12w injection interval in Hawk and Harrier respectively with remaining patients on q8w regimen (key secondary endpoints); greater than 75% of these patients continued on q12w dosing up to Week 96. The natural history of multiple sclerosis: a geographically based study 9: observations on the progressive phase of the disease. Gd enhancing T1 lesions; New or enlarging T2 lesions; Brain volume loss; Serum neurofilaments (NfL). Siponimod 2 mg is the current therapeutically relevant dose for multiple sclerosis. Siponimod 2 mg is the current therapeutically relevant dose for multiple sclerosis *p<0. Workand activityimpairment were assessed by the general health version of the WorkProductivity and Activity Impairment questionnaire. Corrona Report: Real-World Data From the Corrona Psoriasis Registry June 15, 2018. Data cut-off 31-08-2018, Novartis Pharmaceuticals Q3 2018 Financial Report dated October 2018 2. Screening Dose-blind treatment Follow-up month -1 to Day 0 12 months Fingolimod 0. In addition, for Research and Assessment by red, flaky patches on the patients with PsA are at an increased of Psoriasis and Psoriatic skin. Psoriatic Arthritis (PsA) is a form of chronic inflammatory arthritis associated with psoriasis, a skin condition characterised by red, flaky patches on the skin PsA occurs in approximately 30% of patients with psoriasis and develops on average 10 years after the onset of skin symptoms 1 What are the symptoms The exact causes of PsA are unclear; however, it is likely to be caused by a How is it diagnosed Patients with greater psoriatic skin involvement are at an increased Psoriatic nail dystrophy observed on current 1 risk of developing PsA in their lifetime 2.

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