By: Christopher Whaley PhD
Increased tone is classifed as either pyramidal (upper motor neurone) or as extrapyramidal (Parkinson’s disease) arteria alveolaris inferior discount vasotec 10 mg amex. In the leg tone is best appreciated in the lying position with the legs straight by rolling the knee from side to blood pressure explanation discount vasotec generic side and on rapid fexing and extending the leg at the knee and ankle joints pulse pressure ati discount vasotec 10mg on line. Persistent clonus or more than 5 beats is always abnormal and indicates an upper motor neurone lesion blood pressure chart elderly order vasotec from india. Clonus occurs less commonly around other joints but may be present at the knee and wrist heart attack telugu buy vasotec online. In extrapyramidal disease the tone is increased and is classifed as either lead pipe or cogwheel in type. The rigidity is equally stif throughout both fexion and extension and is best appreciated by slowly fully fexing and extending the elbow and knee and by pronating and supinating the wrist. It may be increased by distracting the patient by asking him to move the contralateral limb. This is done by the examiner stabilizing the limb proximal to the joint where the movement is being tested and then passively resisting the movement. A screening test for mild loss of power in the upper limbs is the pronator test; this involves holding the arms outstretched with the hands held in supination and eyes closed. In the ambulant patient walking on the heels is also a good guide to foot drop and walking on toes to weakness of the calf muscles. Rising out of a chair or from the squat position and climbing stairs are the best tests for weakness of the quadriceps and ileopsoas. If the umbilicus moves excessively upwards in paraplegia it is called Beevor’s sign. Any signifcant weakness or impairment of joint position sense invalidates the tests for coordination. Cerebellar dysfunction is characterized by incoordination of speech, limbs and gait. The speech in cerebellar disease is dysarthric or slow and slurred with a typical scanning quality of getting stuck on the consonants. Nystagmus is a sign of cerebellar disease and is worse on looking to the side of the lesion. The fnger nose test this test is carried out with the arms fully extended horizontally by asking the patient to touch the tip of his nose with the tip of the index fnger of his right hand followed by the same with his left hand. The examiner’s index fnger should be held at arm’s length away in front of the patient ensuring that the patient has to fully stretch to touch the fnger. The frst step is asking the patient to frst hold the foot up in the air, then step two to place the heel on the other knee and slowly run it down the shin. Any wobble on reaching the target or side to side or falling of movement on sliding down the shin points to cerebellar disease on the same side. The former is known as dysdiadochokinesia and is demonstrated by rapid tapping the palmThe heel-shin test of one hand alternately with the palm and back of the other hand and then repeating on the opposite hand. In the normal person the alternate movements are smooth and regular whereas in cerebellar disease they are irregular in amplitude and timing and are jerky. Difculty judging distance or dysmetria is shown by repeatedly tapping the back of one hand with the palm of the other. The rebound phenomenon occurs in cerebellar disease where the tapped outstretched hand oscillates before coming back to rest. The gait in cerebellar disease is wide based and ataxic and worse on walking a straight line with a tendency to fall to the side of the lesion. The most common cause of absent refexes is poor technique with a clumsy or inadequate blow of target. Strike the patella tendon near its origin and watch the quadriceps for contraction William Howlett Neurology in Africa 33 Chapter 1 history and examination Chapter 1 history and examination · for the ankle refex, the knee should be fexed to 90 degrees with the leg in external rotation lying to the side and the medial malleolus pointing upwards. Hold the foot at 90 degree angle exerting gentle pressure on the toes and strike the Achilles tendon and look at the calf muscles for contraction. Gently draw a blunt key up the lateral border of the sole of the foot crossing the foot pads or metatarsal heads. In the calloused foot it may be useful to run the stimulus on the outside or lateral aspect of the foot A the biceps reflex the biceps reflex the triceps re ex the supinator re exC5,6The supinator re ex C 7 the triceps re ex C5,6 C 7 B A B the knee re ex L3,4 the knee re ex L3,4 Testing the plantar responseTesting the plantar response A A NormalNormal B Upgoing plantar response the ankle re ex B Upgoing plantar responseor Babinski sign the ankle re exS1 Testing the plantar responseTesting the plantar response S1 or Babinski sign Figure 1. The aim of the examination is to detect any loss of sensation and the pattern of loss. Tere are fve main modalities of sensation to test for, these are light touch, pin prick and temperature (superfcial) and vibration and joint position (deep). The patient should be instructed about 34 Part 1 – Clinical skills Neurological Examination examination of the limbs the test being performed and frst demonstrate the test you are using on familiar non afected places. Ten start the examination with the patient’s eyes closed by testing from a distal to proximal direction touching main dermatomes and comparing right and left sides. Testing superfcial sensation It is usually sufcient to touch each site once varying the timing and moving from an area of abnormal sensation to normal sensation. If the neurological examination is a screening examination to exclude any unsuspected sensory fndings then it’s enough to use one example of superfcial sensation (light touch) and one example of deep sensation (joint position sense) and to test on all four limbs distally. If the patient has noticed an altered sensation in any part of the body then a more detailed sensory examination is required, testing the main sensory modalities. Sensory testing begins with testing for light touch by using a wisp of cotton wool or a fnger tip being careful each time to touch or dab the skin lightly rather than to drag it across the skin. The patient is shown an upward and downward movement frst with his eyes open and told that he will be asked to identify the direction of movement once his eyes are closed. If the patient cannot identify the direction correctly then the next proximal larger joints should be tested until a joint with intact joint position sense is found. The beating fork should be frst placed on the back of terminal phalanx of the index fnger and big toe and the patient asked if he can feel the vibration. If not felt distally it must then be placed on the metacarpal phalangeal joints, wrist, elbow and shoulder in the upper limbs and the medial malleolus, tibial tuberosity in the lower limbs moving onto the anterior iliac crest, rib margin, sternum or clavicle in search of an intact vibration level. Note whether the patient is unsteady and if he is able to walk a straight line by putting one foot in front of the other. Examples are the small symmetrical steps of Parkinson’s disease and asymmetrical steps of hemiplegic gait. The main abnormal types of gaits are: hemiplegic, paraplegic, cerebellar, Parkinsonian, sensory ataxic, neuropathic and myopathic. In neurology patients the level of consciousness may range from being awake and fully conscious which is normal through confusion to altered consciousness and coma (Table 1. Teir value is that they produce objective measurement of the patient’s level of alertness (orientation) and consciousness (coma) which are important for the assessment and ongoing care of the patient. Patients with psychiatric disorders should be referred for psychiatric evaluation. Cognitive function The level of patient cooperation and insight into the illness are also important factors. This initially involves simple bedside clinical tests for attention and concentration. Tese include testing for orientation in time and place, checking the ability to repeat a set of up to 6 numbers or to count back from 20 or recite the months of the year backwards or other learned abilities. Key points · patient’s general appearance & performance · level of alertness and orientation are used to are indicators of neurological & mental health monitor the confused patient · a detailed assessment of mental state & higher · Glasgow Coma Scale is used to monitor level cerebral function is done when the history of consciousness in the semi or unconscious indicates patient 38 Part 1 – Clinical skills Neurological Examination ConsCiousness Other neurological signs · Signs of meningism · Superfcial refexes · Frontal lobe release signs · Straight leg raising test Signs of meningism Tese signs are found in patients with meningitis, subarachnoid haemorrhage and other causes of meningism. The head should be supported by placing your hands under the patient’s occiput until the weight of the head is carried in the hands indicating the patient has relaxed. In the normal person the neck fexes easily without resistance with the chin usually reaching the chest. Neck stifness is present when the neck is rigid or resists any attempt to passively fex the neck. This is elicited by passively attempting to straighten the leg after fexing both the thigh and knee to an angle of greater than 90 degrees. In meningitis this is met by pain and resistance in the lumbar area as a result of stretching of infamed nerve roots. However they occur more frequently and are usually exaggerated in frontal lobe disorders and other difuse mainly cortical neurological disorders. Snout refex this is elicited by pressing or tapping on the closed lips in the midline with a patella hammer or closed knuckle. In positive cases this elicits a puckering of the lips (orbicularis oris) and occasionally a contraction of the chin (mentalis muscle). Grasp refex Place your fngers in the palm of the patient’s hand and stroke it gently whilst pulling your hand away. The abdominal refexes may also be absent in obese persons and after pregnancy and after abdominal surgery. Abdominal refex Test by stroking lightly with the sharp end of the patella hammer in each of the four quadrants of the abdomen from the outside in a diagonal or horizontal approach. Harrison Michael, Neurological Skills, A guide to examination and management in Neurology. Details concerning localization and the cranial nerves neuromuscular junction are outlined in Chapter 12. The motor tract begins in the frontal lobe, descends via the corona radiata on the same side to become the internal capsule. The main clinical disorders causing these signs spinal cord are peripheral neuropathies, mononeuropathies and anterior horn cell cranial nerve palsies. It is important to note that loss of power is common to both and therefore does not help to distinguish between them, and that these signs may not all be present in any one individual patient. The peripheral nerves transmitting these sensations enter via enter the posterior roots of the spinal cord and ascend in the dorsal columns to the lower end of the medulla, where they synapse. They then cross the midline and ascend to reach the thalamus, from where a further relay goes to the sensory cortex in the parietal lobe of the brain on the same side. Tese enter the posterior spinal cord ascend a few segments, and then cross the midline to ascend in the anterolateral spinothalamic tract via second order neurones to the ipsilateral thalamus, and fnally to the parietal lobe on the same side. The main sensory symptoms arising from disorders of the spinothalamic tract are pain and dysaesthesia. The main sensory sites of clinical interest are at the level of peripheral nerves, spinal cord and brain. Frontal lobe Parietal lobe hemiparesis sensory impairment expressive dysphasia (dominant) receptive dysphasia (dominant) social disinhibition apraxia sensory inattention urinary incontinence contralateral lower homonymous quadrantanopia Temporal lobe Occipital lobe receptive dysphasia (dominant) contralateral homonymous hemianopia memory loss contralateral upper homonymous quadrantanopia Figure 2. Personality changes with features of social disinhibition and urinary incontinence may also occur. They have an inability to recognise familiar shapes, textures and numbers and an impairment of fne touch when tested on the opposite hand on either side. Lesions involving the non dominant hemisphere result in a lack of visuo-spatial awareness with hemi neglect of the opposite side of the body. This can result in an inability to dress or wash on the William Howlett Neurology in Africa 51 Chapter 2 loCalization afected side. Seizures originating in the temporal lobe may begin with a characteristic hallucinatory prodrome of smell, taste, vision, hearing or emotion.
Seek Evidence has accumulated that advice from the Department of Human antibiotics may not always be indicated Services blood pressure ranges and pulse purchase vasotec 10 mg on-line. The current version of Therapeutic guidelines: Additional sources of information antibiotics (Therapeutic Guidelines • Passmore prehypertension chart buy vasotec 10mg amex, J blood pressure form 5 mg vasotec for sale, Kelpie pulse pressure 74 purchase vasotec with amex, L & Carapetis blood pressure chart europe purchase 5mg vasotec mastercard, J Limited) should be consulted prior to 2003, ‘Surveillance for invasive group A treatment. People with skin lesions should be excluded from food handling until infection has resolved. These notified in writing within five days of indeterminate duration, in the absence include Treponema pallidum particle diagnosis. To maintain involvement and neurosyphilis is and give no indication of current confidentiality, only the name code (first present. A questionnaire is sent to the stillbirth, premature delivery and becoming more commonly used for diagnosing doctor to collect additional perinatal death. These assays information on the case that is essential generalised systemic disease in a live have a high specificity and sensitivity. Method of diagnosis detection of IgM antibodies to Medical practitioners have a statutory Syphilis can be diagnosed by the Treponema pallidum is a useful assay obligation under the Children and Young demonstration of spirochaetes in the for the diagnosis of congenital syphilis. This results in biological subspecies pallidum is the infective unreliable on mucous membrane lesions false positives. The incubation period is from ten days to Period of communicability For primary syphilis, all persons having three months and is usually three weeks. A case is considered sexually infectious sexual contact with the index case during Public health significance until the end of the early latent period the three months preceding onset should and occurrence which is approximately two years after be evaluated. National management guidelines for • Centers for Disease Control and sexually transmissible infections, Prevention 2002, ‘Sexually transmitted. Many tissues asymptomatic, but the larval stage of Period of communicability and organs may be infected by the larval T. Adult tapeworms may which may be manifest as headaches, communities in many parts of the world. Humans are infected by ingestion of raw or undercooked beef Specific serological tests are available to infected with cysticerci bovis, the larval support the clinical diagnosis of stage of T. Meat should be routinely inspected for Additional sources of information evidence of taeniasis at slaughter. Case fatality rates vary from 10–90% and Infectious agent are highest in infants and the elderly. Intravenous drug use is an independent Clostridium tetani, the tetanus bacillus is risk factor for tetanus in the absence of Method of diagnosis the causative agent. Spores can usually be found detectable in serum samples but may produce an exotoxin that reaches the wherever there is contamination with result from waning past immunisation. Depending on the incubation period is usually three to Spores may be introduced through severity, muscle rigidity usually affects 21 days although it may range from one contaminated puncture wounds, most parts of the body and is associated day to several months depending upon lacerations, burns or contaminated with hyperreflexia. Tetanus rarely follows surgical and occurrence involve most body muscles procedures today. Primary adequate airway and to control muscle immunisation for children begins at two spasm months of age and requires three doses • case investigation to determine the of tetanus toxoid-containing vaccine at circumstances of injury two-monthly intervals. The use of tetanus toxoid in the management of wounds, with or without tetanus immunoglobulin, is determined by considering the vaccination history of the person and the nature of the wound. The blue book: Guidelines forthe control of infectious diseases 227 Toxoplasmosis Victorian statutory requirement Serological results require careful Reservoir Notification and school exclusion are not interpretation and should preferably be the main host in Australia is the required. They sheep, goats, rodents, cattle, swine, with other symptoms of muscle pain, are common in autoimmune disease. This occurs more commonly in Dormant infection persists for life and muscle and brain. Tissue cysts remain can reactivate in the immunosuppressed Testing paired sera taken two weeks viable for long periods. In early Toxoplasmosis occurs worldwide in particularly kittens, or other animals. Transplacental Toxoplasmosis acquired after birth severe complications for the foetus. Infection later in Tissue cysts in meat remain infective for Cats should only be fed with dry, canned pregnancy results in a higher infection as long as the meat is edible and under or boiled food and should be discouraged rate but generally less severe disease. Where infection of the immunosuppressive therapy, in particular mother is confirmed, treatment is Control of case for haematological malignancies, or indicated. Work exclusion: exclusions apply to food • typhoid fever is usually 8–14 days but handlers and some health care workers Susceptibility and resistance this depends on the infective dose and (see below). Outbreaks occur in areas with Vaccination is not routinely Clinical features poor sanitation and inadequate sewerage recommended, except for travellers who Typhoid fever (enteric fever) is a systems. Approximately 30–35 cases of will be exposed to potentially septicaemic illness characterised initially enteric fever occur in Victoria each year. A combination hepatitis A and typhoid Method of diagnosis Mode of transmission injectable vaccine is also available. All Diagnosis is made by culture of typhoid or Salmonella is transmitted by formulations are equally effective. A history of travel to an about personal hygiene, especially they should be advised to cease work until endemic area is usually found. If there is no history of travel, local the Department arranges the collection sources of infection are investigated to Control of case and testing of weekly faecal specimens identify further cases, asymptomatic Hospitalisation is usually required for for S. Food preparation, the Department will ciprofloxacin, ceftriaxone, handlers and workers in high risk determine the appropriate management chloramphenicol, amoxycillin or co professions are generally excluded from of the workplace on an individual basis. Faecal screening is generally consumption Therapeutic guidelines: antibiotic arranged for: • reviewing the integrity of waste and (Therapeutic Guidelines Limited). Fever is usually the incubation period is two to eight meat or mince, is a source of infection. Implicated food should be Committee on Gastrointestinal Avoid ingestion of inadequately cooked destroyed and contaminated water Infections 2000, ‘Guidelines for the meat and meat products, unpasteurised sources treated. Explosive outbreaks have considered infectious until at least 48 adenoviruses are the infective agents. If so, report to Local Government environmental health officers or the Department’s Communicable Diseases Section so that outbreak investigation and control can occur. Control of environment the ability of norovirus to survive relatively high levels of chlorine and varying temperatures (from freezing to 60°C) means rigorous attention to clean up procedures and personal and home hygiene is essential in preventing further transmission. The blue book: Guidelines forthe control of infectious diseases 235 Viral haemorrhagic fevers Victorian statutory requirement infections are complicated by massive • Marburg virus is usually three to nine Viral haemorrhagic fever (Group A haemorrhage and multi-organ failure. Public health significance rate of 1% of infected cases but 25% of and occurrence School exclusion: until medical hospitalised cases. Appropriate specimens Dengue haemorrhagic fever and yellow are: and treatment is commenced as early as fever are discussed elsewhere. Other the incubation period varies according to the reservoir for Lassa fever virus is a symptoms include retrosternal chest pain, the causative agent: rodent known as the multimammate rat cough, abdominal pain, diarrhoea, of the genus Mastomys spp. Severe (range 1–12 days) animals such as sheep, goats and cattle 236 the blue book: Guidelines forthe control of infectious diseases may act as amplifying hosts. Period of communicability All patients should be cared for at the Communicability of viral haemorrhagic hospital where they are first seen (if the natural reservoir of Ebola virus fevers depends on the infective agent: possible), or transferred to the Victorian remains unknown. Intravenous ribavirin may be useful for treatment purposes; a stock of this drug • Crimean-Congo haemorrhagic fever Mode of transmission is maintained at a number of tertiary virus communicability is unknown. Virus has with these materials, or through cuts or precautions should be instituted been isolated in seminal fluid 60 days sores. Abstinence from sexual also been reported through any decisions concerning patient’s intercourse is advised until genital fluids contaminated needles and syringes. The blue book: Guidelines forthe control of infectious diseases 237 Post-mortem is discouraged. A contact is a discouraged from travel during their Ribavirin may be prescribed as post person who has been exposed to an period of surveillance. These disinfection measures may apply Close contacts are defined as those to the patient’s place of residence and living with the patient, nursing and other environments where the patient hugging the patient, or handling the has spent a significant period of time patient’s laboratory specimens. If the while symptomatic, such as aircraft and diagnosis is confirmed, close contacts hotel rooms. Method of diagnosis in the preceding six days and no history of the diagnosis is based on the presence vaccination with yellow fever vaccine in the School exclusion is not applicable. Sometimes the infection specimen confirmed by neutralisation and of South America and Central Africa. Vaccine providers in kilometre radius, with an effective Humans have no essential role in Victoria must be accredited with the insecticide to eliminate vectors. Control of case destroyed, emptied or sprayed within this In Victoria suspected or confirmed cases area. Mode of transmission that require inpatient treatment should Contacts of the patient who have not Yellow fever is transmitted via infected be referred to the Victorian Infectious previously been immunised should be mosquitoes. Mosquitoes become Diseases Service at the Royal Melbourne offered yellow fever vaccine. This is unexplained deaths possibly consistent transmission has not been documented. During this period Therefore, the case should be protected they are required to notify the Chief Susceptibility and resistance from exposure to mosquitoes for greater Quarantine Medical Officer if suffering Mild infections are common in endemic than five days after onset of infection. International measures Yellow fever must be notified to the World Health Organization under the International Health Regulations (1969). In some instances a single case animals from others in such places and will constitute such an unusual under such conditions as to prevent or communicable disease occurrence. Categories of from an infected person or species to a fomes (plural fomites) isolation include: susceptible host, either directly or An object such as a book, wooden indirectly. High level disinfection Disease or condition that is required by refers to the inactivation of all incubation period law to be notified to the State health microorganisms except some bacterial the time interval between initial contact department. Such reservoir of infectious agents precautions involve the use of safe work Any person, animal, or substance in practices and protective barriers, and the which an infectious agent normally lives safe disposal of body substances and and multiplies in such a manner that it soiled material. The blue book: Guidelines forthe control of infectious diseases 247 Appendix 3: Standard and additional precautions General Standard precautions should be Standard precautions for infection Infection control and prevention uses a implemented at all times particularly control in health care settings consist of risk management approach to minimise when patients are undergoing invasive the following work practices: or prevent the transmission of infection. Health procedures, including appropriate use principles and practice are based on the services that offer these procedures of skin disinfectants mode of transmission of an infectious should provide detailed protocols for • personal hygiene practices, particularly agent. They include good hygiene that should be applied in a health care chlorhexidine (0. The blue book: Guidelines forthe control of infectious diseases 249 Outline of requirements for specified categories of additional precautions Requirement Additional precautions by transmission route Airborne Droplet Contact Gloves Nil Nil For all manual contact with patient, associated devices and immediate environmental surfaces Impermeable apron/gown Nil Nil When health care worker’s clothing is in substantial contact with the patient, items in contact with the patient, and their immediate environment Respirator or mask. Goggles/face-shields Protect face if splash likely Protect face if splash likely Protect face if splash likely Special handling of equipment As per standard precautions As per standard precautions Single use or reprocess before reuse on next patient (includes all equipment in contact with patient) Single room Yes Yes If possible, or cohort with patient or or with the same infection (eg Cohort patients with Cohort patients methicillin-resistant Staphylococcus same infection. Masks, eye protection, gloves are removed, after significant faceshields patient contact such as contact with or • Change gloves between tasks and Wear a mask and eye protection or a physical examination, emptying procedures on the same patient after faceshield to protect mucous drainage bags, undertaking contact with material that may contain membranes of the eyes, nose and venepuncture or delivery of an a high concentration of mouth: injection or going to the toilet. See • Victorian Department of Human Appendix 6 for cleaning and waste Services 2000, Sure protection against disposal. Emergency Department at the nearest fluids the exposed person should have a hospital.
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Recommendations for use in elderly patients have generally suggested maintaining relatively low serum levels pulse pressure with exercise order generic vasotec online, as levels above may be associated with an increased risk of side-effects (Young 1996) pre hypertension natural cure vasotec 10 mg fast delivery. Carbamazepine is a potent inducer of cytochrome P450 2D6 and is highly protein-bound hypertension food discount vasotec 10 mg with visa, making it a significant concern for potential drug inter actions (Janicak 1993) pulse pressure is calculated by order vasotec mastercard. Medications commonly used in the elderly arteria arcuata purchase 10mg vasotec mastercard, including calcium channel blockers, erythromycin, cimetidine and fluoxetine, can increase plasma levels of carbamazepine, while carbamazepine can decrease plasma concentrations and half-lives of warfarin, theophylline, haloperidol and alprazolam. Despite the concerns about tolerability and the potential for drug interactions, a recent study of carbamazepine for the treatment of agitated, frail, demented patients suggests it can be well tolerated in the elderly (Tariot et al. In one case report the anticonvulsant gabapentin was used successfully to treat an elderly female with bipolar disorder intolerant of lithium and valproate (Sheldon et al. Elderly patients were also included in two recent case series utilizing gabapentin (Ghaemi et al. While response by age was not noted, in one of these studies, which included 22 mixed aged patients, the oldest subject, an 82-year-old patient, was the only subject who discontinued treatment early because of inadequate response (an increase of hypomanic and agitated symptoms) (Cabras et al. In a single case report, lamotrigine was added to divalproex to successfully treat an elderly rapid cycling bipolar patient (Kusumakar and Yatham 1997). Some elderly patients were also treated in an open-label study of lamotrigine in treatment-refractory bipolar patients (Calabrese et al. There is a single case report of a 66-year-old manic patient treated successfully with a calcium channel blocker, verapamil (Gash et al. Neuroleptics and benzodiazepines are commonly used as adjuncts in the treatment of elderly bipolars (Sajatovic et al. Elderly patients are particularly susceptible to side-effects from typical neuroleptics such as anticholinergic effects, orthostatic hypotension and extrapyramidal symp toms, including a dramatically higher incidence of tardive dyskinesia com pared with younger patients (Naranjo et al. As a result there is some suggestion that clinicians are more cautious with their use, and fewer elderly patients are discharged on these medications (Broadhead and Jacoby 1990). The atypical neuroleptics such as risperidone, olanzapine and quetia pine are better tolerated in the elderly and cause much less extrapyramidal symptoms including tardive dyskinesia (Jeste et al. Given emerging data suggesting they also have anti-manic and mood-stabilizing effects (Tohen et al. Diagnosis and classification of affective disorders: new insights from clinical and laboratory approaches. Manic and depressive symptoms in the elderly: their relation ships to treatment outcome, cognition and motor symptoms. Clinical experience with gabapentin in patients with bipolar or schizoaffective disorder: results of an open-label study. Efficacy of lithium vs valproate in the treatment of mania in the elderly: a retrospective study. Ageing and affective disorders: the age at first onset of affective disorders in Scotland, 1966–1978. Case report: efficacy of verapamil in an elderly patient with mania unresponsive to neuroleptics. Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorders. Algorithm for patient management of acute manic states: lithium, valproate, or carbamazepine A retrospective chart review of lithium side effects in a geriatric outpatient population. The relevance of clinical pharmacokinetics and therapeutic drug moni toring: anticonvulsants, mood stabilizers and antipsychotics. Lower incidence of tardive dyskinesia in risperidone compared with haloperidol in older patients. Incidence of silent lacunar lesions in normal adults and its relation to cerebral blood flow and risk factors. Die temperamente in der familien der monopolaren und bipolaren phasischen psychosen. Manic depressive illness: a comparative study of patients with and without a family history. The incidence and onset-age of hospitalized bipolar affective disorder in Finland. Classification of affective disorders – the primary–secondary, the endogenous reactive and the neurotic-psychotic. Ten-year use of hospital-based services by geriatric veterans with schizophrenia and bipolar disorder. Halstead-Reitan Category Test in bipolar and unipolar affective disorders: Relationship to age and phase of illness. Neurotic and psychotic forms of depressive illness: evidence from age-incidence in a national sample. The specificity of cerebral blood flow changes in patients with frontal lobe dementia. Structural neuroimaging and mood disorders: recent findings, implications for classification, and future directions. Discontinuation of mainte nance treatment in bipolar disorder: risks and implications. Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. Outcome in mania: a four year prospective follow-up study utilizing survival analysis. The adverse effect profile and efficacy of divalproex sodium compared with valproic acid: a pharmacoepidemiology study. This chapter will focus on significant moments in the development of the concepts of the temperament/personality of manic and bipolar patients, concepts which have changed considerably since they were first described nearly 2000 years ago. Some caution is necessary in dealing with these concepts: the meanings of basic terms such as melancholia and mania have changed considerably in the course of two millennia; the meaning of any association that may have been described, as for example between the melancholic and the sanguine temperaments and melancholia and mania will not necessarily correspond to present-day concepts; lastly, we cannot be certain – despite our assumptions – that the authors have been describing the same phenomena. As regards the sources of this chapter, for the nineteenth and twentieth centuries the original French, German and English texts were used; access to the Greek and Latin sources was through the English translations. Angst (eds), Bipolar Disorders: 100 years after manic-depressive insanity, 175–199. Angst For reasons of space this review could not take into account the full extent of modern research and theories on the personality of bipolar patients; it concentrates on the developments that currently appear to be the most significant and most promising. For more exhaustive accounts of developments in the field, the reader is referred to the reviews of von Zerssen (1993, 1996 and 1999b) on personality and affective or functional disorders in general. Gale n derived nine temperaments from the four humours; in the ideal personality, the complementary characteristics of warm-cool and dry-moist were exquisitely balanced. In the remaining four types, one pair of qualities dominated the comple mentary pair, for example, warm and moist dominated cool and dry. These latter fourwere the temperamental categories Galen called melancholic, sanguine, choleric, and phlegmatic. Health consists in a harmony of these ele ments, and excess or defect in one or more of these qualities produces disease" (p. From a modern perspective, Greenwood (1943), cited in Sharpe 1964, notes that for Galen every human temperament could be represented by a point in a plane the position of which was determined by its coordinates. As Greenwood stresses "Galen did not, of course, express this geometrically but verbally and verbosely". As Kagan observes, in the nineteenth century the term character – a much more static concept – was used to describe the distinctive behavioural styles, while temperament referred to the variation in emotional reactivity. Today, temperament conventionally refers to stable behavioural and emotional reac Temperament and personality types 177 tions that appear early and are influenced in part by genetic constitution (Kagan et al. More specifi cally, Aretaeus taught that mental disease had its origins in the head or abdomen and that both melancholy and mania were different expressions of the same malady: "it appears to me that melancholy is the commencement and a part of mania" (transl. Aretaeus departed from humoural theory, however, favouring instead descriptive terms: "Those prone to the disease are such as are naturally passionate, irritable, of active habits, of an easy, disposition, joyous, puerile: likewise those whose disposition inclines to the opposite condition, namely, such as are sluggish, sorrowful, slow to learn, but patient in labour, and who when they learn anything soon forget it; those likewise are more prone to melancholy who have formerly been in a mad condition" (trans. Aretaeus may be seen to presage contemporary continuum theories of personality (Stone 1992, p. Esquirol described manic patients as being highly sensitive, lively, irritable, angry, enthusiastic and risk-taking, and some as suffering from sleep problems, somnambulism, hysterical fits and epileptic convul sions. The ancient concepts were also still alive in Kahlbaum (1878), who considered that the melancholic temperament could be compared to melan cholia and the sanguine to mania (p. Griesinger believed in general Temperament and personality types 179 (unspecific) constitutional factors predisposing to mental disorder, namely irritable weakness (pp. Griesinger distin guished between emotional disorders (Gemuthsleiden),melancholia, mania and depression on the one hand and madness (Wahnsinn) (p. Circular insanity (bipolar disorder) and cyclothymia the modern classification of mood disorders emerged a century and a half ago with Jean-Pierre Falret (1851) who created (folie circulaire) bipolar disorder and with Baillarger 1854 (folie a double forme), both marking the beginning of a promising development. They continued to live the life of the community, or the family, without needing to be treated as sick. Such cases were considered to represent the mildest and most frequently overlooked phase of folie circulaire (Jeliffe p. Hecker (1898) described them as cyclothymics following the classification of Kahlbaum (1882). The contribution of Kahlbaum (1863) to modern psychiatric classification was decisive, because of his distinction between remitting and non-remitting forms of mood disorders. In France cyclothymia received much attention from Deny (1908, 1909) and his pupil Kahn (1909); they extended the term to cover not only the 180 J. The milder forms of cyclothymia were described as being almost normal psychological conditions (Kahn 1909, pp. Ballet (1902) had gone even further, hypothesizing that circularity might be a characteristic of the normal functioning of the nervous system, which was merely magnified and amplified during periods of pathological change. In the twentieth century the term cyclothymia has been used in three ways: (1) for manic-depressive disorder (Schneider 1967, Weitbrecht 1968); (2) for mild grades of manic-depressive disorders; and (3) for constitutional features and personalities, characteristic of bipolars. As a consequence of the conceptual diagnostic changes introduced by Kraepelin, systematic research on the temperament or personality of patients suffering from bipolar disorder was delayed for 60 years. In fact, in his empirical Temperament and personality types 181 approach Kraepelin came very close to distinguishing between mania, depression and bipolar subgroups. He found that 53% of patients with a cyclothmic disposition belonged to the combined group and 64. Kraepelin did not believe that the depressed group had any special nosologi cal status, because one-third of those with a depressive disposition were diagnosed as falling into the manic or combined groups. However, given the estimated expected values (which were not available to Kraepelin), one could also assume heterogeneity. It is worth pointing out that Kraepelin never used the term temperament, either in its ancient or its modern sense, in this context. He also stressed the existence of fundamental states (Grundzustande),which often (37%, p. In view of the many and various types of transition, Kraepelin concluded that these distinctions were artificial and arbitrary (p.
Examination of the nose and ears for *Not all patients were examined for each nding blood pressure medication used for opiate withdrawal vasotec 10 mg fast delivery. Measurement of beta-trace protein in the 90 acquired acute bacterial meningitis admitted to blood pressure chart 13 year old buy vasotec uk blood and discharge uid is more accurate blood pressure medication you can drink alcohol order vasotec 10mg overnight delivery. Clinically blood pressure vinegar vasotec 10mg overnight delivery, such children rigidity pre hypertension emedicine buy 10mg vasotec overnight delivery, and alteration of mental status was rapidly lose consciousness and develop hyper present in only 44% of patients in a large series pnea disproportionate to the degree of fever. Focalneu the pupils dilate, at rst moderately and then rologic signs were present in one-third and in widely, then x, and the child develops decer cluded cranial nerve palsies, aphasia, and hemi ebrate motor signs. Both acute and chronic stupor or coma in which there may be focal meningitis may be characterized only by leth neurologic signs but little evidence of severe argy, stupor, or coma in the absence of the systemic illness or stiff neck. Aspergillus meningitis, which is typically error is readily avoided by accurate spinal seen only in patients who have been immune uid examinations. Some observers believe that the of these cases is primarily due to the immuno diagnostic value warrants the small but de nite logic processes concerned with the infection risk. Many patients with either supratento evaluation of nuchal rigidity even in patients rial or infratentorial mass lesions tolerate lum who are stuporous. Finally, even in the ab 12 g/day in divided doses every 4 to 6 hours), sence of a mass lesion, obliteration of the peri or cefepime (4 to 6 g/day in divided doses mesencephalic cisterns or descent of the ton every 8 to 12 hours); vancomycin should be sils below the foramen magnum is a major risk added until the results of antimicrobial sus factor for the development of herniation after a ceptibility testing are known. In such cases, lumbar punc tients and those who are immune suppressed, ture should be deferred until hyperosmolar L. Re role, and ampicillin should be added to those gardless of which approach is taken, it is crit drugs. Meropenem may turn out to be an at ical for the diagnostic evaluation not to prevent tractive candidate for monotherapy in elderly the immediate drawing of blood cultures, fol patients. In a setting where Rocky Mountain lowed by administration of appropriate anti spotted fever or ehrlichiosis are possible in biotics. A Whether corticosteroids should be used is normal or low pressure raises the question of controversial. Adjuvant dexamethasone is re whether there has already been partial herni commended for children and adults with hae ation of the cerebellar tonsils. The cell count mophilus meningitis or pneumococcal menin and protein are elevated, and glucose may be gitis but is not currently recommended for depressed or normal. Meningeal enhancement usually does not Hence, we have included this class of lesions occur until several days after the onset of in with compressive processes. Cortical infarction, which may be due to in ammation and occlusion either of pene trating arteries or cortical veins, also tends to Intracerebral Hemorrhage occur late. In contrast, gion include those into the basal ganglia, inter despite their differing pathophysiology, the nal capsule, and thalamus. Hemorrhages into signs and symptoms of primary intracerebral the pons and cerebellum are discussed in the hemorrhages are due to the compressive ef section on infratentorial hemorrhages. Chung fects of the hematoma, and thus are more alike and colleagues divided patients with striato than different, depending more on location capsular hemorrhages into six groups with vary 100 than on the underlying pathologic process. These Spontaneous supratentorial intracerebral hem included posterolateral (33%), affecting pri orrhages are therefore usually classi ed as lo marily the posterior portion of the putamen; bar or deep, with the latter sometimes extend massive (24%), involving the entire striatal ing intraventricularly. As compared tween the external capsule and insular cortex; to deeper hemorrhages, patients with lobar anterior (11%), involving the caudate nucleus; hemorrhages are older, less likely to be male, middle (7%), involving the globus pallidus in and less likely to be hypertensive. Severe head the middle portion of the medial putamen; and ache is a characteristic of lobar hemorrhages. About half the pa in anterior and posterior medial lesions, but tients have a decreased level of conscious was impaired in about one-third of patients Figure 4–6. She took 325 mg aspirin at home on the advice of her primary care doctor because she suspected a stroke. He presented with headache, left-sided weakness and sensory loss, and some left-sided inattention. About half the patients the treatment of intraventricular hemor with posterolateral lesions were drowsy, but rhage is aimed at controlling intracranial pres not comatose, as were about one-half the pa sure. Ventricular drainage may help, but the tients with the lateral lesions who rarely be catheter often becomes occluded by the blood. Hemiparesis is common in the treatment of an intracerebral hemor posterolateral and massive lesions. Early surgery to evacu icits are relatively frequent in posterior and ate the hematoma has not been associated with 105 medial lesions. However, treatment with tients with all of the lesions save the massive hemostatic drugs, such as recombinant factor ones, where the fatality rate is about 50%. Most patients but may be ‘‘wrong way’’ in those with pos who have relatively small lesions and do not terolateral and massive lesions. Herniation should be treated vigorously ter) and by location (posterolateral, anterolat in patients with relatively small hematomas be eral, medial, and dorsal; Figure 4–6B). These include rupture of a deep ce (the lower eye on the side of the lesion); gaze rebral endartery, amyloid angiopathy, mycotic preference, which may either be toward or aneurysm, arteriovenous malformation, or hem away (wrong-way eyes) from the side of the orrhage into a tumor, and each requires a dif lesion; loss of vertical gaze; and miotic pupils. Sensory and motor differentiate clinically between acute cerebral disturbances depend on the site and size of the vascular lesions potentially causing stupor or 101 lesion. The blood vessels that are most likely primary or result from extension of an intra to hemorrhage are the same ones that cause cerebral hemorrhage. Pri perforating arteries, which give rise to thalamic mary intraventricular hemorrhages can result hemorrhages; the midline perforating arteries from vascular anomalies within the ventricle, of the pons, which give rise to pontine hemor surgical procedures, or bleeding abnormali rhages; and the penetrating branches of the 104 ties. Clinical ndings include sudden onset cerebellar long circumferential arteries, which of headache and vomiting sometimes followed cause cerebellar hemorrhages. If the hemorrhage nds with the rst two, which cause supratentorial its way into the subarachnoid space, nuchal masses, in this section, and the latter two in the rigidity occurs. Hemorrhage into are characteristic of the part of the brain that the ventricle from a primary intracerebral hem is injured. Obtundation from the start or within hours, progressing to stupor in 12 to 24 hours, coma usually in 36 to 96 hours. Conjugate gaze paresis to side of motor weakness; contralateral oculovestibulars can be sup pressed for 12 hours or so. Contralateral hemiplegia, usually with extensor plantar response and paratonia ipsilateral to lesion. Sudden-onset headache, followed by more or less rap idly evolving aphasia, hemiparesis to hemiplegia, conjugate ocular deviation away from hemiparesis. Pupils small and reactive, or ipsilateral Horner’s with excessive contralateral sweating, or stupor to coma and bilateral motor signs within hours of onset. Clinical picture similar to frontoparietal hemorrhage but seizures rare, vomiting frequent, eyes characteristically deviated down and laterally to either side. Bilateral thalamic infarction in the paramedian regions Sudden onset of coma, akinetic mutism, hypersomnolence or altered mental status may accompany bland infarcts of the paramedian thalamus arising bilaterally as a result of a ‘‘top of the basilar’’ syndrome or a branch occlusion of a thalamope duncular artery (Percheron’s artery) providing vascular supply to both thalami and often the tegmental mesencephalon. Sudden onset of coma or speechlessness, pinpoint pupils, ophthal moplegia with absent or impaired oculovestibular responses, quadriplegia, irreg ular breathing, hyperthermia. Acute and rapid onset and worsening within hours of occipital headache, nausea and vomiting, dizziness or vertigo, unstead iness, dysarthria, and drowsiness. Small and reactive pupils, nystagmus or hori zontal gaze paralysis toward the side of the lesion. Midline and ipsilateral ataxia, (continued) 138 Speci c Causes of Structural Coma 139 ipsilateral peripheral facial palsy, and contralateral extensor plantar response. Vertigo, ataxia, nausea, dull headache, nystagmus, dysarthria, ipsilateral dysmetria; 24 to 96 hours later: drowsiness, miosis, ipsilateral gaze paresis and facial paresis, worsening ataxia, extensor plantar responses. Acute subarachnoid hemorrhage Awake at onset, sometimes hypertensive, sudden headache, often followed within minutes by unconsciousness. Subhyaloid hemorrhages, hemiparesis or aphasia may or may not be present, hemisensory changes rare. Thalamic hemorrhage may pres infarctions in postmortem examination of the 109 ent with sensory phenomena, but often the brain. He found an eosinophilic degenera hemorrhage compresses ascending arousal tion of the wall of small penetrating arteries in systems early so that loss of consciousness is the region of the infarct and proposed that this 101 the primary presentation. Given 102 to dorsal midbrain compression or injury the fact that such vessels typically take off at (seepage110),withsomecombinationofforced a right angle from large cerebral arteries, one downgaze and convergence (‘‘peering at the might expect high sheering forces at the vessel tip of the nose’’), xed pupils, and retractory origin, so that high blood pressure or other ath nystagmus. Another neuro-ophthalmologic pre erosclerotic risk factors might cause earlier or sentation of thalamic hemorrhage was descri more severe damage. Whereas frontal lobe insults usually result in End artery hemorrhages typically produce a deviation of the eyes toward the side of the le large hematoma with considerable local tissue sion. Because much of the of space), after thalamic hemorrhage (or occa clinical appearance is due to the mass effect, sionally deep intraparenchymal hemorrhage which eventually is resorbed, the patient may 108 that damages the same pathways) there may initially to be much more neurologically im be a paresis of gaze toward the side of the lesion paired than would be caused by a comparably (see Chapter 3). The reason of beta-amyloid peptide in the walls of cerebral for the predilection of this class of artery for blood vessels. Because amyloid deposits identify the arteries that had caused lacunar occur along blood vessels as they penetrate the 140 Plum and Posner’s Diagnosis of Stupor and Coma cerebral cortex, the hemorrhages are typically mediate death than are saccular aneurysms, lobar. The arteries that hemorrhage tend harder to treat and bleeding may recur multi to be small vessels, which seal spontaneously, ple times with gradually worsening outcome. Acute epilepsy, or by causing a vascular steal from onset of focal hemispheric signs and a head surrounding brain. As tion without hemorrhage have about a 2% to with end artery hemorrhages, the severity of 4% per year chance of bleeding, but those that the initial presentation often is misleading, and have previously bled have a much higher risk. Hemorrhage into a tumor typically occurs in Mycotic aneurysms are typically seen in the the setting of a patient with known metasta setting of a patient who has subacute bacterial tic cancer. A brain lodge in small penetrating arteries in the higherpercentage ofmetastatic melanoma, thy white matter just deep to the cerebral cortex. These aneurysms, common than these tumors that it is the sin which may be visualized on cerebral angiog gle most common cause of hemorrhage into 121 raphy, may be multiple. Primary brain tumors, particularly be multiple mycotic aneurysms, and to elimi oligodendrogliomas, may also present with a nate an arteriovenous malformation or saccular hemorrhage into the tumor. Because it is often aneurysm as the source, an angiogram is gener dif cult to see contrast enhancement of the ally necessary. They range from small cavernous angiomas to large arteriovenous mal formations that are life threatening. The abnormal vessels in these malfor vade the brain, resulting in impairment of con 121,122 mations are thin-walled, low-pressure and low sciousness. Certain prin may cause coma if they hemorrhage and have ciples apply broadly across these classes of a tendency to rebleed. Radiosurgery may also Gliomas include both astrocytic tumors and 122 reduce the risk of hemorrhage, but can cause oligodendrogliomas. Speci c Causes of Structural Coma 141 They more often present as seizures than as tients with lung cancer may have long-term 124 mass lesions. Astrocytomas typically present survival and even apparent cure has been re either with seizures or as a mass lesion, with ported after removal of a single brain metas headache and increased intracranial pressure. Pa In other cases, the patients may present with tients with brain tumors frequently suffer focal or multifocal signs of cerebral dysfunction. Small, surgically inaccessible metas of necrosis or hemorrhage and formation of tases can be treated by stereotactic radio 128 cystic components. Surpris ingly, primary brainstem astrocytomas, which Brain Abscess and Granuloma are typically seen in adolescents and young adults, cause mainly impairment of cranial A wide range of microorganisms, including motor nerves while leaving sensory function viruses, bacteria, fungi, and parasites, can in and consciousness intact until very late in the vade the brain parenchyma, producing an acute course. The tumors invade the brain much like tiguous organ (paranasal sinus, middle ear). They often occur along the Most bacterial brain abscesses occur in the ventricular surfaces and may in ltrate along cerebral hemispheres, particularly in the fron white matter tracts.
No statistical differences between radiation modalities were seen in Kaplan-Meier assessment of either overall or progression-free survival at two years hypertension jnc 7 buy 5 mg vasotec with amex. Patients in both groups were followed for a median of 24 months; dose was >50 GyE or Gy in approximately 75% of patients blood pressure form discount 10 mg vasotec fast delivery. While statistical testing was not performed blood pressure medication vision changes order vasotec 5 mg free shipping, rates of local tumor control and the proportion of patients experiencing reductions in tumor volume were nearly identical between groups blood pressure 24 cheapest vasotec. No statistically-significant differences between groups were observed in three-year actuarial estimates of local control arrhythmia recognition chart discount vasotec 5 mg otc, progression-free survival, or overall survival. Ocular Tumors In comparison to other cancer types, the evidence base for ocular tumors was relatively substantial. Three of the cohort studies were all fair-quality and involved comparisons to surgical enucleation in patients with uveal melanoma at single centers (Mosci, 2012; Bellman, 2010; Seddon, 1990). Metastasis-free survival also did not differ in Cox regression adjusting for age, sex, and tumor thickness. Prostate Cancer the largest evidence base available was for prostate cancer (10 studies). Overall QoL, general health status, and treatment-related symptom scales were employed. Five-year estimates of disease-free survival (using biochemical failure definitions) did not statistically differ between groups. Statistical changes were assessed within (but not between) each cohort immediately following treatment as well as at 12 and 24 months of follow-up, and were also assessed for whether the change was considered “clinically meaningful” (>0. Statistically-significant differences between treatment groups were observed for many baseline characteristics, only some of which were adjusted for in multivariate analyses. In Kaplan-Meier analysis of outcomes adjusting for differential follow-up between treatment groups, therapeutic modality had no statistically-significant effects on stabilization of visual acuity (p=0. Rates did not numerically differ between treatment groups, although these were not tested statistically. In the radiation-only group, two of four patients died of disease at 4-5 years of follow-up; the other two were alive with disease at last follow-up. The other patient was free of local progression and metastases as of 9 years of follow-up. Patients receiving radiation alone reported numerically lower rates of abnormal bowel or bladder function as well as difficulty ambulating in comparison to those receiving combination therapy, but rates were not statistically tested. No differences in the rate of gastrointestinal complications were observed for any treatment comparison. Nearly all outcome and toxicity measures were reported for the entire cohort only. Two comparative studies were identified with comparative information on radiation-related harms. The combination therapy group had a significantly lower rate of secondary enucleation (p=0. Three additional studies involved retrospective comparisons using available databases. No other statistical differences were noted in genitourinary morbidity, erectile dysfunction, hip fracture, or use of additional cancer therapy. However, in Cox proportional hazards regression adjusting for between-group differences, no effect of radiation modality on outcomes was observed, including retinopathy (p=0. In other comparative studies, clinical characteristics, including prior therapy received, had no effect on treatment outcomes (Brown, 2013; Tokuuye, 2004). Tumor Characteristics the impact of tumor characteristics on estimates of treatment effect was measured in six comparative studies. No differences were observed among those with well or moderately-differentiated tumors. In the more recent study, five different fractionation schemes were compared in 82 men with stage T1-T3 prostate cancer, with total doses ranging from 35-60 GyE (Kim, 2013); patients were followed for a median of approximately 3. Five of the 16 studies focused attention on the operating costs, reimbursement, and/or viability of proton treatment centers for multiple types of cancer, and are summarized at the end of this section. The base case involved a 65 year-old cohort with head and neck cancers of all stages. Effects of therapy included both overall and disease-related mortality as well as adverse events such as pneumonitis and esophagitis. Costs included those of treatment (currently abroad, as the Netherlands has no proton facilities), the clinical trial vs. Results were sensitive to a number of parameters, including treatment costs abroad and costs of suboptimal treatment. Clinical effectiveness and impact on mortality were assumed to be equivalent across all three groups. A total of 1,042 patients were treated with other radiation modalities, receiving nearly 20,000 treatment fractions. Applying this payment level to all 110 patients would result in a total of approximately $3. We judged the net health benefit to be “Comparable” (equivalent net health benefit) in several other cancers, including liver, lung, and prostate cancer, as well as hemangiomas. These studies will never produce evidence as persuasive as randomized comparisons because of concerns regarding selection and other biases, and administrative databases lack the clinical detail necessary to create rigorously-designed observational datasets. The continued growth of electronic health records from integrated health systems may allow for the creation of more detailed clinical and economic comparisons in large, well-matched patient groups receiving alternative radiation modalities. Among the treatment options for cancer, radiation therapy is commonly employed; an estimated 50% of patients receive radiation therapy at some point during the course of their illness (Delaney, 2005). Objectives and Methods the objective of this review was to appraise the comparative clinical effectiveness and comparative value of proton beam therapy in a variety of cancers and noncancerous conditions. To support this appraisal we report the results of a systematic review of published randomized controlled trials, comparative observational studies, and case series on clinical effectiveness and potential harms, as well as any published studies examining the costs and/or cost-effectiveness of proton beam therapy. Background Protons are positively-charged subatomic particles that have been in clinical use as a form of external beam radiotherapy for over 60 years. Compared to the photon X-ray energy used in conventional radiotherapy, proton beams have physical attributes that are potentially appealing. In contrast, photons deliver radiation across tissue depths on the way toward the target tumor and beyond, as depicted in Figure 1 below. The goal of any external beam radiotherapy is to deliver sufficient radiation to the target tumor while mitigating the effects on adjacent normal tissue. This so-called “exit” dose is absent for protons, as tissue beyond the point of peak energy deposition receives little to no radiation (Kjellberg, 1962). In addition, proton beam therapy was advocated for many pediatric tumors because even lower-dose irradiation of normal tissue in pediatric patients can result in pronounced acute and long-term toxicity (Thorp, 2010). The construction of cyclotrons at the heart of proton beam facilities is very expensive ($150-$200 million for a multiple gantry facility); accordingly, as recently as 10 years ago there were fewer than 5 proton beam facilities in the United States (Jarosek, 2012). As depicted in Figure 2 below, there are now 14 operating proton centers in the U. One is the use of “hypofractionation”, a process of delivering higher-dose fractions of radiation that has the potential to reduce the frequency of radiation delivery and shorten the overall treatment course (Nguyen, 2007). Another is the construction of compact, single-gantry proton facilities that have been estimated to cut the construction cost of a proton facility to the range of $15-$25 million. Some commentators believe that lower construction costs will reduce the debt incurred by medical institutions and therefore lead to the ability to reduce the price charged to payers for each treatment course (Smith, 2009). Some concerns have been raised about the hypothetical advantages of the radiation deposition for proton beams. Due to the growth in popularity of proton beam therapy as well as concerns regarding its use in certain patient populations, there is interest in understanding the clinical benefits, potential harms, and costs associated with proton beam therapy relative to treatment alternatives in multiple types of cancer as well as certain noncancerous conditions. Note: L&I and Medicaid reported no Proton Beam Therapy in the 2009-2012 timeframe. The prostate patients (all red patterned areas above) were between 63 and 79 years old. Proton Beam Therapy: What Patients Can Expect Following an initial consultation with the treatment team, patients are then scheduled for a pretreatment planning and simulation session. Proton treatments themselves are typically delivered in daily fractions (Monday through Friday). Each treatment session may take 15-60 minutes, depending on the type and location of the tumor. The total duration of the treatment course also will vary by type and location of the tumor, and may last up to 8 weeks. Clinical Guidelines and Training Standards Major guideline statements as well as competency and/or accreditation standards regarding proton beam therapy can be found in the sections that follow below. More comparative studies are necessary to evaluate the outcomes between the different modalities, with identification of the appropriate therapy for different kinds of cancer. Clinical and technical training programs focused on proton therapy are offered for radiation oncologists, medical physicists, dosimetrists, radiation therapists and other support staff. Local Therapies for Unresectable Primary Hepatocellular Carcinoma (2013). Local Nonsurgical Therapies for Stage I and Symptomatic Obstructive Non-Small-Cell Lung Cancer (2013). Future clinical comparative studies are necessary to determine appropriate localized therapy in this patient population. Comparative Effectiveness and Safety of Radiotherapy Treatments for Head and Neck Cancer (2010). Further research regarding treatment planning and therapy delivery to inform treatment protocols is also necessary. Its role as a therapeutic option for localized prostate cancer remains uncertain with respect to safety, efficacy and improvement in patient outcomes. Ongoing Clinical Studies Information on ongoing clinical studies that have been submitted to the U. National Institutes of Health’s registry of publicly and privately-supported studies ( We focused on randomized controlled trials comparing proton beam therapy alone to an alternate treatment modality with a projected study enrollment of more than 50 patients. We concentrated on trials evaluating the various conditions that are the focal point of this review, and excluded comparative studies of carbon ion therapy, as this treatment modality is not currently available in the U. Methods Objectives the primary objectives of the systematic review were to: Evaluate and compare the published evidence on the impact of proton beam therapy relative to other radiotherapy modalities and non-radiation treatment alternatives on survival, control of cancerous and noncancerous tumors, health-related quality of life, and other patient outcomes for populations with both primary and recurrent disease; Evaluate and compare the harms of proton beam therapy and treatment alternatives, including generalized effects. A total of 19 categories (16 cancer types, three types of noncancerous tumors) of disease were selected for this review (see “Patient Populations” on page 27). We do recognize and make explicit mention, however, of clinical areas in which simulation studies are likely to remain the cornerstone of evidence, given logistical and ethical challenges posed by conducting clinical trials in these areas. One notable exception to this rule was the use of modeling to answer questions of cost and/or cost-effectiveness, as clinical outcomes in these studies were typically derived from actual clinical outcome data from other published studies. In addition, because the risk of secondary malignancy is felt to be of great interest because of its link to radiation of normal tissues, these outcomes were abstracted when reported. Analytic Framework the analytic framework for this review is shown in the Figure on the following page. Some studies are randomized or observational comparisons focused directly on survival, tumor control, health-related quality of life, and long-term harms, while in other studies a series of conceptual links must be made between intermediate effectiveness measures. The condition categories of interest are listed below, and included 16 cancer types and three types of noncancerous conditions as listed in Table 1 below.