R. Michael Benitez, MD, FACC

• Professor of Medicine
• Director, Cardiology Fellowship Program
• Division of Cardiology, University
• of Maryland School of Medicine
• Baltimore, Maryland

Trauma to the pontomesencephalic brainstema major clue to the prognosis of severe traumatic brain injury symptoms appendicitis buy prothiaden 75mg overnight delivery. The role of arousal and ``gating' systems in the neurology of impaired consciousness medicine news purchase 75 mg prothiaden mastercard. Extensive piano practicing has regionally specific effects on white matter development treatment concussion cheap 75 mg prothiaden otc. Hyperexcitability of intact neurons underlies acute development of trauma-related electrographic seizures in cats in vivo treatment croup trusted 75mg prothiaden. Thalamocortical diaschisis: single-photon emission tomographic study of cortical blood flow change after focal thalamic infarction symptoms xanax buy discount prothiaden 75mg on line. The syndrome of bilateral paramedian thalamic infarction associated with an oculogyric crisis treatment urticaria cheap prothiaden 75mg with amex. Obsessive compulsive disorder and traumatic brain injury: behavioral,cognitive,andneuroimagingfindings. Contracts, covenants and advance care planning: an empirical study of the moral obligations of patient and proxy. End-of-life decisionmaking in the hospital: current practices and future prospects. Constructing an ethical stereotaxy for severe brain injury: balancing risks, benefits and access. The ``right to die' in America: Sloganeering from Quinlan and Cruzan to Quill and Kevorkian. Twenty-five years after Quinlan: a review of the jurisprudence of death and dying. Clinical pragmatism and the care of brain damaged patients: toward a palliative neuroethics for disorders of consciousness. Functional Imaging of severely brain-injured patients-progress, challenges, and limitations. The vegetative and minimally conscious states: current knowledge and remaining questions. Affirming the right to care, preserving the right to die: disorders of consciousness and neuroethics after Schiavo. Monitoring and manipulating brain function, new neuroscience technologies and their ethical implications. Restoration of neural output from a paralyzed patient by a direct brain connection. Humanoscillatorybrain activity near 40 Hz coexists with cognitive temporal binding. This page intentionally left blank Index Page numbers followed by ``t' denote tables; those followed by ``b' denote boxes; and those followed by ``f' denote figures Abducens nerve anatomy of, 61 course of, 100 palsy of, 77, 113 paralysis of, 100 Abscess brain, 141­142, 142f, 143t cerebellar, 149­150, 150t epidural, 126­127, 144 pontine, 170f Abulia, 8 Accidental hypothermia, 259­260 Acetaminophen overdose, 245, 326 Acetic acid, 250 Acetylcholine, 208­209 Acid-base imbalances acidosis. See Alkalosis hyperventilation and, 188­191 systemic, 258­259 treatment of, 315 Acidosis lactic, 233, 250 metabolic. See Ethanol intoxication Alcoholic stupor, 242t, 243 Alcoholism, 246t Alkalosis metabolic, 191t, 191­192, 231, 258 respiratory, 189­191, 190t, 258 Alpha-ketoglutaramate, 225 Altered state of consciousness acutely, 6­7, 8t from basilar migraine, 168 chronic, 7­9, 8t descriptive terms for, 8t lateral displacement of the diencephalon and, 100 structural lesions associated with, 29­34 subacute, 7­9 Amphetamine, 242t Amyloid angiopathy, 139­140, 146 ``Amytal interview,' 298, 307­308, 327 Anemia, 325 Anemic hypoxia, 211 Anesthesia barbiturate, 205­206, 323 description of, 205­206 malignant hyperthermia associated with, 262 profound, brain death diagnosis in, 338 Aneurysms bleeding by, 129 mycotic, 140 saccular, 129 vertebrobasilar, 145, 145t Angiogenesis, 94­95 Angiography computed tomography, 78 magnetic resonance, 79, 336 Anion gap, 240 Anoxemia, 201 Anoxia, 204, 212 Anoxic-ischemic brain damage description of, 206 focal ischemia, 207­208 global ischemia, 206­207 hypoxia, 208 Antidepressants, 241, 245­246 Antidotes administration of, 315­317 types of, 317t Antifreeze. See Altered state of consciousness clouding of, 6 components of, 5 content of, 5 definition of, 5 loss of. See Drug intoxications duration of, 346, 349 history-taking, 9 hypoglycemic, 210 locked-in syndrome vs. See also Overdoses acetaminophen, 245, 326 antidepressants, 241, 245­246 antidotes for, 251t benzodiazepines, 242t, 245 evaluation of, 324 heroin, 243 list of, 242t management of, 326 opioids/opiates, 242t, 243 overview of, 240, 240t proconvulsants, 247t prognosis after, 357 sedatives, 240­241, 243­245 testing for, 240, 241t Drug withdrawal delirium, 283 Drug-induced delirium, 284 Drunkenness. See Coma scales corneal responses, 320 eye opening, 319 history-taking, 39­40, 317­318 motor responses, 320 neurologic, 9, 318­319 oculocephalic responses, 319 overview of, 38­39, 39t physical, 40 pupillary reactions, 319 respiration. See Respiration skeletal muscle tone, 320 tendon reflexes, 320 of unconscious patient, 317­320 verbal responses, 319 vestibulo-ocular responses, 65, 320 Excitatory amino acids, 114 Extradural hematoma, 309­310 Eye(s) conjugate lateral deviation, 69­70 conjugate vertical deviation, 70 nystagmoid jerks of, 71­72 opening of, 319 Eye movements in brainstem infarcts, 165t conjugate lateral deviation, 69­70 conjugate vertical deviation, 70 nonconjugate eye deviation, 70 oculocephalic stimulation of, 65 pathways for, 60f periodic alternating, 71 resting, 69 roving, 70­71 skew deviation, 70 spontaneous, 69, 69t Eyelids, 64 Falcine herniation, 100 Falx cerebri, 95­96, 96f­97f Families considerations for, 379­380 functional communication with, 380 Fat embolism, 217­218 Fatal familial insomnia, 115, 277­278 Fever, 260­261, 282­283 Flumazenil, 316 Flunitrazepam, 248 Focal continuous epilepsy, 315 Focal ischemia, 207­208 Foramen magnum, 100 Forced duction of globe, 68 Forebrain arousal of, 14 mesopontine tegmentum, 14 Index Hematoma epidural, 121­123, 143­144 subdural description of, 123­126, 124t posterior fossa, 144 Hemiparesis, 101, 106 Hemodialysis, for uremia, 229 Hemorrhage brainstem, 166­168 cerebellar. See Cerebellar hemorrhage intraventricular, 137 lobar, 136, 136f midbrain, 166t, 167 perimesencephalic, 145 pontine clinical findings of, 167t coma caused by, 167 description of, 138b, 150­151 origin of, 167 pupillary findings, 167 subarachnoid description of, 129­131, 139b grading system for, 356t outcomes after, 355­356 posterior fossa, 145 thalamic, 137, 138b, 139 into tumors, 140 Hepatic coma description of, 190, 225 prognosis for, 356­357 Hepatic encephalopathy diagnosis of, 225 hyperventilation associated with, 224 mild, 227 onset of, 224 pathology of, 224 pupillary findings in, 225 Herniation syndromes central transtentorial herniation, 101­102, 107­110 corticosteroids for, 322 falcine herniation, 100 historical view of, 97b intracranial compartments, 95­100 lateral displacement of the diencephalon, 97b, 100 Monroe-Kellie doctrine, 95 rostrocaudal brainstem deterioration, 102 tonsillar, 102, 103f­104f uncal. See also Orexin Hypoglycemia, 203­205, 234, 313 Hypomagnesemia, 258 Hyponatremia, 228­229, 237, 252f, 253­255 Hyponatremic encephalopathy, 254t Hypo-osmolar states, 253­255 Hypophosphatemia, 258 Hypothalamic ischemic lesions, 33 Hypothermia, 259­260, 315, 335 Hypothyroidism, 236­237 Hypoventilation, 191­192, 230 Hypoxia acute, 211­214 airway obstruction and, 211 anemic, 211 anoxic-ischemic brain damage caused by, 208 carbon dioxide narcosis and, 231 causes of, 210­211 cerebral malaria and, 217 cerebral venous, 211 delayed postanoxic encephalopathy after, 219 disseminated intravascular coagulation and, 217 fat embolism and, 217 histotoxic, 211 hypoxic, 211 intermittent, 215­219 ischemic, 211 multifocal cerebral ischemia and, 215­216 pupillary responses in, 59 sequelae of, 219­220 sustained, 215­219 traumatic brain injury and, 346 Hypoxic inducible factor, 212 Hypoxic-ischemic attacks, 212 Hypoxic-ischemic encephalopathy, 352­354 Hysteresis, 50­51 393 394 Index Laboratory tests blood tests, 77 computed tomography. See Computed tomography computed tomography angiography, 78 electroencephalography, 82­83 evoked potentials, 82­83 lumbar puncture. See Lumbar puncture magnetic resonance angiography, 79, 336 magnetic resonance imaging. See Central nervous system infections opportunistic, 230 prion, 266, 277­278 subarachnoid, 131­135 treatment of, 315 Infratentorial inflammatory disorders, 169­170 Infratentorial lesions compressive, 142­143 destructive, 162­163 mass, 323­324 Infratentorial tumors, 170 Insulin, 202 Intensive care unit delirium, 283­284 Intention myoclonus, 220 Intermittent hypoxia, 215­219 Internuclear ophthalmoplegia, 63, 76 Interstitial nucleus of Cajal, 62 Intoxication. See also Prognosis factors that affect, 349 Glasgow Outcome Scale, 344, 344t mechanisms underlying, 364­365 nontraumatic coma, 347­355 Midbrain stage, of central transtentorial herniation, 107­108 Midpontine destruction, 162 Miller Fisher syndrome, 76, 170 Minimally conscious state akinetic mutism and, 360­362, 361b case study of, 362­363 cerebral metabolic rates in, 374 definition of, 8, 360 diagnostic criteria for, 360t diffusion tensor imaging of, 371f emergence from, 379 functional imaging of, 369­372 late recoveries from, 363, 375 magnetic resonance imaging of, 370f residual cognitive capacity in, 372­376 studies of, 368­372 surrogate decision making in, 379 vegetative state vs. See also Outcomes acute disseminated encephalomyelitis, 356 central nervous system infections, 356 in coma, 343­344 depressant drug poisoning, 357 etiology of injury and, 344 hepatic coma, 356­357 nontraumatic coma, 347­355 overview of, 342­343 stroke, 355 time-delimited, 377­379 traumatic brain injury. High Yield Internal Medicine Shelf Exam Review Emma Holliday Ramahi Cardiology A patient comes in with chest pain. Most common cancer is broncogenic carcinoma, but incr risk lower lobes w/ pleural for mesothelioma plaques. Exudative with high hyaluronidase Patient with kidney stones, Squamous cell carcinoma. Patient with ptosis better after 1 Lambert Eaton Syndrome from small minute of upward gaze? Roommate of the kid High protein and low glucose support bacterial in the dorms who has bacterial meningitis Rifampin!! Staph aureus seeds native valves from bacteremia Subacute Native valve endocarditis· Most common valve? Gram + aerobic branching partially acid fast · Neck or face infection w/ draining Actinomyces! Bladder/Kidney cancer until proven otherwise · "terminal hematuria" + tiny Bladder cancer or hemorrhagic cystitis (cyclophosphamide! Just hydrate ­ Stones >2cm Open or endoscopic surgical removal ­ Stones 5mm-2cm Extracorporal shock wave lithotropsy So your patient is peeing protein. Membranous- thick cap walls w/ subepi spikes · Assoc w/ heroin use and Focal-Segmental- mesangial IgM deposits. Puts at risk for Renal Vein Thrombosis Rheumatology/Dermatology A patient comes in w/ arthritis. Anterior spinal artery · Pt w/ high cholesterol presents w/ acute onset flaccid paralysis below the occlusion. Then valproate or lamotrigine · Generalized seizures begin from both hemispheres @ once. New Onset Severe Headache Things to consider: · "Worse headache of my life" Subarachnoid hemorrhage. Aminoglycosides & beta-blockers · Urinary retention, Babinski on Multiple Sclerosis. Esophageal Carcinoma Gastric Varices Squamous cell in smoker/drinkers in the If in hypovolemic shock? Stage 0 or 1 need no tx- 12 yrs till death Stage 2 tx w/ fludrabine If Anemia If Thrombocytopenia Stage 3 or 4 tx w/ steroids · Enlarged, painless, rubbery Think Lymphoma lymph nodes · Drenching night sweats, "B-symptoms" = poor prognosis along w/ fevers & 10% weight loss. Length of time patient has been under your care (years/months) Illinois Controlled Substances License Number 336. I have established a bona-fide physician-patient relationship with the qualifying patient applicant. The qualifying patient is under my care, either for his/her primary care or for his/her debilitating medical condition, as specified on this form. This bona-fide physician-patient relationship is not limited to the preparation of a written certification for the patient to use medical cannabis or a consultation simply for that purpose. I have conducted an in-person physical examination of the qualifying patient within the last 90 calendar days. I (the physician), hereby certify I am a physician duly licensed to practice medicine in the state of Illinois. The qualifying patient has the debilitating medical condition(s) specified, and the patient is under my treatment or management for the debilitating condition(s) and/or their primary care. I attest the information provided in this written certification is true and correct. Department of Veterans Affairs Disability Rating for Members of the Ready Reserve (paras 1­4c(1) and 1­4c(2)). Clarifies various waiver authorities for Officer Candidate School in-Service applicants and Warrant Officer Candidate School direct accessions (paras 1­6j and 1­6k). Army Enlisted Accessions, by changing the maximum body fat standards for males and females in the 17 ­ 20 years of age categories (tables 2­1 and 2­2). Realigns chapters into similar order as to anatomical sites and body systems (chaps 3, 4, and 5). Updates the stinging insect profiling language and policy (paras 3­3e(1) and 3­35a). Clarifies the retention standard for hearing and the Military Operational Hearing Test, such as the Speech Recognition in Noise Test (para 3­9a). Updates the psychiatric retention standards to reflect the most recent diagnoses changes in the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (para 3­33e). Supersedes Army Directive 2013­12, Implementation of Department of Defense Policy Change Concerning Chronic Adjustment Disorder (para 3­33e). Removes a section on personality and other disorders that previously rendered an individual administratively unfit (formerly para 3­35). Adds a new section on conditions and circumstances not constituting a physical disability (para 3­36). Implements Section 1177, Title 10, United States Code by requiring medical examinations in certain instances prior to administrative separations under conditions other than honorable (para 3­37a). Adds medical fitness standards for civil affairs and psychological operations initial training and retention in the military occupational specialty (paras 5­4 and 5­5). Adds initial selection and retention medical fitness standards for divers (para 5­11 and 5­12). Adds initial selection and retention medical fitness standards for Army maritime sea duty (para 5­13). Adds initial selection and retention medical fitness standards for small unmanned aircraft system operators (para 5­14). Army Reserve and Army National Guard specific issues and incorporates material in a reorganized format (throughout). This regulation applies to the Regular Army, the Army National Army internal control process. This Guard/Army National Guard of the United regulation contains internal control proviStates, and the U. It also applies to candi- identifies key internal controls that must be dates for military service. All waiver re- Guard/Army National Guard of the United quests will be endorsed by the commander States, and the U. This publication provides information on individual medical readiness elements; medical fitness standards for induction, enlistment, appointment, and retention; deployment-limiting medical conditions; and related policies and procedures. It is the responsibility of each Soldier to maintain his/her individual medical and dental readiness requirements, and report health issues that may affect their readiness to deploy or be retained to continue serving. A disability rating has no correlation to retention or fitness for duty standards. The examiners will apply the medical standards for the stated purpose and find the examinees described as follows: (1) Medically qualified. Medical examiners will report as "medically qualified" all individuals who meet the medical standards of medical fitness established for the particular purpose for which examined. No individual will be accepted on a provisional basis subject to the successful treatment or correction of a disqualifying defect. Medical fitness standards for accession, retention, or special training cannot be waived by medical examiners or by the examinee. Examinees initially reported as medically not qualified by reason of a medical condition or defect when the standards of medical fitness in chapters 2, 4, or 5 apply, may request a waiver of the medical fitness standards in accordance with the basic administrative directive governing the personnel action. Upon such request, the designated administrative authority or their designees for the purpose may grant such a waiver in accordance with current directives. The Office of the Surgeon General provides guidance when necessary to the review and waiver authorities on the interpretation of the medical standards and appropriateness of medical waivers. Review and medical waiver authority for direct appointment to the Judge Advocate General Corps is the the Judge Advocate General. Medical waivers for initial enlistment or appointment, including entrance and retention in officer procurement programs, will not be granted if the applicant does not meet the retention standards of chapter 3. These standards are not all inclusive and other diseases or defects can be a cause for rejection based upon the medical judgment of the examining healthcare provider where such conditions may reasonably be expected to interfere with the successful performance of military duty or training, or limit geographical assignment. This chapter prescribes the medical conditions, physical defects, and procedures that are causes for rejection for appointment, enlistment, and induction into the U. Unless otherwise stipulated, the conditions listed in this chapter are those that would be disqualifying by virtue of current diagnosis or for which the candidate has a verified past medical history. Those individuals found medically qualified based on the medical standards of chapter 2 that were in effect prior to this publication will not be disqualified solely on the basis of the new standards. The designated waiver authorities listed in paragraph 1­6 may grant waivers for selection or continuation in the programs described in paragraph 2­2c, provided the individual meets the retention standards of chapter 3. However, the standards regarding the immune mechanism including immunodeficiencies will not be waived. This includes enlisted Soldier applicants for appointment as commissioned or warrant officers. For both men and women, height below 58 inches or over 80 inches does not meet the standard.

Eye poking is particularly concerning; it occurs more frequently among children with visual impairment medicine quizlet purchase 75 mg prothiaden overnight delivery. Stereotypic movements may occur many times during a day medicine 5 rights cheap prothiaden 75mg, lasting a few seconds to several minutes or longer medications 222 discount prothiaden 75 mg without a prescription. Frequency can vary from many occurrences in a single day to several weeks elapsing between episodes treatment 20 prothiaden 75mg without a prescription. The behaviors vary in context medicine 834 order 75mg prothiaden mastercard, occurring when the individual is engrossed in other activities medicine organizer discount prothiaden 75 mg, when excited, stressed, fatigued, or bored. For example, stereotypic movements might reduce anxiety in response to external stressors. Criterion B states that the stereotypic movements interfere with social, academic, or other activities and, in some children, may result in self-injury (or would if protective mea sures were not used). Onset of stereotypic movements is in the early developmental period (Criterion C). Criterion D states that the repetitive, stereotyped behavior in stereotypic movement disorder is not at tributable to the^physiological effects of a substance or neurological condition and is not better explained by another neurodevelopmental or mental disorder. The presence of stereotypic movements may indicate an undetected neurodevelopmental problem, espe cially in children ages 1-3 years. Complex stereotypic movements are much less common (occurring in approximately 3%-4%). Between 4% and 16°/« of individuals v^ith intellectual disability (intellectual develop mental disorder) engage in stereotypy and self-injury. Among individuals with intellectual disability living in res idential facilities, 10%-15% may have stereotypic movement disorder with self-injury. Development and Course Stereotypic movements typically begin within the first 3 years of life. Simple stereotypic move ments are common in infancy and may be involved in acquisition of motor mastery. In chil dren who develop complex motor stereotypies, approximately 80% exhibit symptoms before 24 months of age, 12% between 24 and 35 months, and 8% at 36 months or older. In most typ ically developing children, these movements resolve over time or can be suppressed. Onset of complex motor stereotypies may be in infancy or later in the developmental period. Among individuals with intellectual disability, the stereotyped, self-injurious behaviors may persist for years, even though the typography or pattern of self-injury may change. Social isolation is a risk factor for self-stimulation that may progress to stereotypic movements with repetitive self-injury. Fear may alter physiological state, resulting in increased frequency of stereotypic behaviors. Lower cognitive functioning is linked to greater risk for stereo typic behaviors and poorer response to interventions. Stereotypic movements are more fre quent among individuals with moderate-to-severe/profound intellectual disability, who by virtue of a particular syndrome. Repet itive self-injurious behavior may be a behavioral phenotype in neurogenetic syndromes. For example, in Lesch-Nyhan syndrome, there are both stereotypic dystonie movements and self mutilation of fingers, lip biting, and other forms of self-injury unless the individual is re strained, and in Rett syndrome and Cornelia de Lange syndrome, self-injury may result from the hand-to-mouth stereotypies. Culture-Related Diagnostic Issues Stereotypic movement disorder, with or without self-injury, occurs in all races and cultures. Overall cultural tolerance and attitudes toward stereotypic movement vary and must be considered. Rocking may occur in the transition from sleep to awake, a behavior that usu ally resolves with age. Complex stereotypies are less common in typically developing children and can usually be suppressed by distraction or sensory stimulation. Stereotypic movements may be a presenting symptom of autism spectrum disorder and should be considered when repetitive movements and be haviors are being evaluated. Deficits of social communication and reciprocity manifesting in autism spectrum disorder are generally absent in stereotypic movement disorder, and thus social interaction, social communication, and rigid repetitive behaviors and interests are distinguishing features. When autism spectrum disorder is present, stereotypic move ment disorder is diagnosed only when there is self-injury or when the stereotypic behav iors are sufficiently severe to become a focus of treatment. Typically, stereotypies have an earlier age at onset (before 3 years) than do tics, which have a mean age at onset of 5-7 years. They are consistent and fixed in their pattern or topography compared with tics, which are variable in their presentation. Ste reotypies may involve arms, hands, or the entire body, while tics commonly involve eyes, face, head, and shoulders. Stereotypies are more fixed, rhythmic, and prolonged in dura tion than tics, which, generally, are brief, rapid, random, and fluctuating. Trichotillomania (hair-pulling disorder) and excoria tion (skin-picking) disorder are characterized by body-focused repetitive behaviors. Furthermore, onset in tricho tillomania and excoriation disorder is not typically in the early developmental period, but rather around puberty or later. The diagnosis of stereotypic movements requires the exclusion of habits, mannerisms, paroxysmal dyskinesias, and benign he reditary chorea. A neurological history and examination are required to assess features suggestive of other disorders, such as myoclonus, dystonia, tics, and chorea. Involuntary movements associated with a neurological condition may be distinguished by their signs and symptoms. For example, repetitive, stereotypic movements in tardive dyskinesia can be distinguished by a history of chronic neuroleptic use and characteristic oral or facial dyskinesia or irregular trunk or limb movements. A diagnosis of stereotypic movement disorder is not appropriate for repet itive skin picking or scratching associated with amphetamine intoxication or abuse. Comorbidity Stereotypic movement disorder may occur as a primary diagnosis or secondary to another disorder. For example, stereotypies are a common manifestation of a variety of neurogenetic disorders, such as Lesch-Nyhan syndrome, Rett syndrome, fragile X syndrome, Cornelia de Lange syndrome, and Smith-Magenis syndrome. When stereotypic move ment disorder co-occurs with another medical condition, both should be coded. Both multiple motor and one or more vocal tics have been present at some time during the illness, although not necessarily concurrently. The tics may wax and wane in frequency but have persisted for more than 1 year since first tic onset. Single or multiple motor or vocal tics have been present during the illness, but not both motor and vocal. Diagnosis for any tic disorder is based on the presence of motor and/or vocal tics (Criterion A), duration of tic symptoms (Criterion B), age at onset (Criterion C), and ab sence of any known cause such as another medical condition or substance use (Criterion D). An individual may have various tic symptoms over time, but at any point in time, the tic rep ertoire recurs in a characteristic fashion. Although tics can include almost any muscle group or vocalization, certain tic symptoms, such as eye blinking or throat clearing, are common across patient populations. Tics are generally experienced as involuntary but can be vol untarily suppressed for varying lengths of time. Simple vocal tics include throat clearing, sniffing, and grunting often caused by contraction of the diaphragm or muscles of the oropharynx. Importantly, coprolalia is an abrupt, sharp bark or grunt utterance and lacks the prosody of similar inappropriate speech observed in human interactions. The presence of motor and/or vocal tics varies across the four tic disorders (Criterion A). For other specified or un specified tic disorders, the movement disorder symptoms are best characterized as tics but are atypical in presentation or age at onset, or have a known etiology. For an individual with motor and/or vocal tics of less than 1 year since first tic onset, a provisional tic disorder diagnosis can be considered. There is no duration specification for other specified and unspecified tic disorders. Tic disorders typically begin in the prepubertal period, with an average age at onset between 4 and 6 years, and with the incidence of new-onset tic disorders decreasing in the teen years. New onset of tic symptoms in adulthood is exceedingly rare and is often associated with expo sures to drugs. Although tic onset is uncommon in teenagers and adults, it is not uncommon for adolescents and adults to present for an initial diagnostic assessment and, when carefully evaluated, provide a history of milder symptoms dating back to child hood. New-onset abnormal movements suggestive of tics outside of the usual age range should result in evaluation for other movement disorders or for specific etiologies. Tic symptoms cannot be attributable to the physiological effects of a substance or an other medical condition (Criterion D). When there is strong evidence from the history, physical examination, and/or laboratory results to suggest a plausible, proximal, and probable cause for a tic disorder, a diagnosis of other specified tic disorder should be used. Similarly, a previ ous diagnosis of persistent (chronic) motor or vocal tic disorder negates a diagnosis of provisional tic disorder or other specified or unspecified tic disorder (Criterion E). Males are more commonly affected than females, with the ratio varying from 2:1 to 4:1. A national survey in the United States estimated 3 per 1,000 for the prevalence of clinically identified cases. The frequency of identified cases was lower among African Americans and Hispanic Americans, which may be related to differences in access to care. Peak severity occurs between ages 10 and 12 years, with a decline in severity during adolescence. A small percentage of individuals will have persis tently severe or worsening symptoms in adulthood. Tics wax and wane in severity and change in affected muscle groups and vocalizations over time. As children get older, they begin to report their tics being associated with a premonitory urge-a somatic sensation that precedes the tic-and a feeling of tension reduction follow ing the expression of the tic. Tics associated with a premonitory urge may be experienced as not completely 'involuntary" in that the urge and the tic can be resisted. Tics are worsened by anxiety, excitement, and exhaustion and are better during calm, focused activities. Individuals may have fewer tics when engaged in schoolwork or tasks at work than when relaxing at home after school or in the evening. Observing a gesture or sound in another person may result in an indi vidual with a tic disorder making a similar gesture or sound, which may be incorrectly perceived by others as purposeful. This can be a particular problem when the individual is interacting with authority figures. Obstetrical complications, older paternal age, lower birth weight, and maternal smoking during pregnancy are as sociated with worse tic severity. Culture-Related Diagnostic Issues Tic disorders do not appear to vary in clinical characteristics, course, or etiology by race, ethnicity, and culture. However, race, ethnicity, and culture may impact how tic disorders are perceived and managed in the family and community, as well as influencing patterns of help seeking, and choices of treatment. Gender-Related Diagnostic Issues Males are more commonly affected than females, but there are no gender differences in the kinds of tics, age at onset, or course. Women with persistent tic disorders may be more likely to experience anxiety and depression. Functional Consequences of Tic Disorders Many individuals with mild to moderate tic severity experience no distress or impairment in functioning and may even be unaware of their tics. Individuals with more severe symp toms generally have more impairment in daily living, but even individuals with moderate or even severe tic disorders may function well. Less commonly, tics dis rupt functioning in daily activities and result in social isolation, interpersonal conflict, peer victimization, inability to work or to go to school, and lower quality of life. Differential Diagnosis Abnormal movements that may accompany other medical conditions and stereotypic movement disorder. Motor stereotypies are defined as involuntary rhythmic, repetitive, predictable movements that appear purposeful but serve no obvious adaptive function or purpose and stop with distraction. Examples include repetitive hand waving/rotating, arm flapping, and finger wiggling. Chorea represents rapid, random, continual, abrupt, irregular, unpredictable, nonstereotyped actions that are usually bilateral and affect all parts of the body. The timing, direction, and distribution of movements vary from mo ment to moment, and movements usually worsen during attempted voluntary action. Dys tonia is the simultaneous sustained contracture of both agonist and antagonist muscles, resulting in a distorted posture or movement of parts of the body. Dystonie postures are of ten triggered by attempts at voluntary movements and are not seen during sleep. Paroxysmal dyskinesias usually oc cur as dystonie or choreoathetoid movements that are precipitated by voluntary move ment or exertion and less commonly arise from normal background activity. Myoclonus is characterized by a sudden unidirectional movement that is often nonrhythmic. Myoclonus is differentiated from tics by its rapidity, lack of suppressibility, and absence of a premon itory urge. Clues favoring an obsessive-compulsive behavior in clude a cognitive-based drive. Impulse-control problems and other repetitive be haviors, including persistent hair pulling, skin picking, and nail biting, appear more goal directed and complex than tics. The obsessive-compulsive symptoms observed in tic disorder tend to be characterized by more aggressive symmetry and order symptoms and poorer response to pharmacotherapy with selective serotonin reuptake inhibitors. Individuals with tic disorders can also have other movement disorders and other mental disorders, such as depressive, bipolar, or substance use disorders.

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No significant changes were observed in injury rates during games or practices over the 16-year study period treatment of shingles cheap 75 mg prothiaden amex. Regardless of whether injuries occurred in practices or games symptoms bipolar disorder buy 75 mg prothiaden, more than one-half of all injuries reported across the 15 sports examined during the study period were to the lower extremity crohns medications 6mp order prothiaden 75 mg without prescription. Specifically medicine look up drugs buy 75mg prothiaden visa, joint injuries have been a primary concern treatment jaundice purchase prothiaden 75 mg, as it is well documented that these injuries can lead to chronic instability and increase the risk of osteoarthritis and degenerative joint disease asthma medications 7 letters cheap prothiaden 75mg without prescription. This observation was confirmed in a follow-up study that examined data from 1990 through 2002. They also noted that non-contact injuries occurred more frequently on artificial turf surfaces (44. The average annual rate of ankle sprain injury during the 16-year study period examined was 0. They also examined the annual injury rates for ankle sprains among males and females participating in these sports combined between 1988 and 2004 and reported that injury rates remained constant during the 16-year study period. Recurrent shoulder instability has also been associated with the increased risk of osteoarthritis in the shoulder. Surgical reconstruction is common following shoulder instability in young athletes. Injury rates for shoulder Copyright © 2014 by the United States Bone and Joint Initiative. Just over half (53%) of the shoulder instability events documented during the study period were first-time instability events, with the remaining injuries being recurrent instability events (47%). The majority of shoulder instability events were due to contact with another athlete (68%) and other contact (20%). Arendt E, Dick R: Knee injury patterns among men and women in collegiate basketball and soccer. They also reported that the prevalence of joint-related health concerns was significantly higher in older former athletes when compared to younger former athletes. Specifically, former athletes reported poorer scores on the physical function, depression, fatigue, sleep disturbances, and pain interference scales. The authors also noted that former collegiate athletes reported significantly more major injuries, chronic injuries, daily limitations, and physical activity limitations when compared to non-athletes. Decreased health-related quality of life in former college athletes may also contribute to greater daily activity and physical activity limitations when compared to non-athletes and may lead to significant chronic health comorbidities. Further research is needed to determine which factors contribute to the poorer health-related quality of life outcomes observed among former collegiate athletes in these studies. Injury-related musculoskeletal conditions include conditions such as Achilles tendinitis (code 726. With the exception of the Relative Burden analysis, a 60-day "unique hospitalization/outpatient rule" was used in this analysis in order to reduce the effect of follow-up injury visits and potential overestimation of frequencies and rates. Department of Health and Human Services, Centers for Disease Control and Prevention, Centers for Medicaid and Medicare Services. Conclusions and recommendations of the DoD injury surveillance and prevention work group. Summary Data: Military Injuries In 2012, there were approximately 370 injury-related deaths, 5,000 injury-related hospitalizations (3,000 acute injuries and 2,000 injury-related musculoskeletal conditions), and 661,000 injury-related outpatient visits (245,000 acute injuries and 415,000 injury-related musculoskeletal conditions). As illustrated by these data, however, there are far more injury-related hospitalizations and outpatient visits than deaths. These nonfatal outcomes result in significant losses in duty time and manpower for the Army. Injuries were the leading cause of medical encounters and affected more individuals than all other medical conditions, including mental health disorders. During this period, more than half the injury visits were due to lower extremity overuse injuries. The top three reasons for hospitalization were mental disorders (27%), pregnancyrelated issues (17%), and injuries and injury-related musculoskeletal conditions (12%). A total of 2,511,276 unique outpatient visits were made by active duty Army personnel. Injuries and injury-related musculoskeletal conditions were responsible for 26%, or more than 660,000, of visits. Two types of analytical injury matrices are available to further describe acute injuries and injury-related musculoskeletal conditions: (1) the Barell Injury Diagnosis matrix1 and (2) the injury-related musculoskeletal conditions matrix. Leading specific reasons for hospitalizations included fractures of the lower leg and/or ankle (13 %), facial fracture (6%), and fracture of the foot/toes (3%). Comparing all body regions, the lower extremity accounted for 30%, the upper extremity for 19%, and the head for 16%. Within the head region, traumatic brain injury, including skull fracture, accounted for 15%, and other specified head injuries accounted for less than 1%. Leading specific reasons for outpatient visits included Copyright © 2014 by the United States Bone and Joint Initiative. The most common types of injury-related musculoskeletal conditions leading to hospital admission were joint derangement (58%), followed by inflammation and pain due to overuse (23%). The vertebral column (including spine/back) was the most affected by injury-related musculoskeletal conditions (63%), followed by lower extremities (25%) and upper extremities (10%). Most outpatient visits for injury-related musculoskeletal Copyright © 2014 by the United States Bone and Joint Initiative. Lower extremities (44%) was the body region most often treated on an outpatient basis, followed by the vertebral column (including spine/back) at (34%), and upper extremities at 19%. The leading specific injury-related musculoskeletal conditions requiring outpatient treatment were inflammation and pain (overuse) to the knee and/or lower leg (20%), inflammation and pain (overuse) to the lumbar spine (18%), inflammation and pain (overuse) to the ankle and/or foot (14%), and inflammation and pain (overuse) to the shoulder (12%). A total of 6% of unintentional injury hospitalizations were due to sports and another 6% were due to heat injury. The top nine causes of unintentional injuries accounted for nearly three-fourths of hospitalizations (74%). The leading causes of unintentional injury outpatient visits in 2012 were attributed to overexertion (27%), falls (16%), and injuries due to soldiers being struck by or against objects or other people (16%). Over the past three decades, contributions to Army injury prevention have been made in each of these areas, including the establishment of deployment injury surveillance capabilities2 and implementation of a data-driven process to define Army injury prevention priorities. Collaborations with academia and other government organizations will aid in identifying modifiable causes, risk factors, and effective prevention strategies. Fostering existing and new partnerships between Army leadership, public health, safety, research, health promotion, and other communities will be critical for the success of military injury prevention activities. Given the magnitude and severity of the problem of injuries, effective injury prevention will make a significant contribution to the health and productivity of soldiers and the Army. Acknowledgements: Military Injuries the material presented here is adapted from the following sources: Esther Dada-Laseinde, Michelle Canham-Chervak, Bruce H. Army Public Health Command (Provisional), 5158 Blackhawk Rd, Aberdeen Proving Ground, Maryland 21010-5403. Army Institute of Public Health, Epidemiology and Disease Surveillance Portfolio, Injury Prevention Program. Advancing age, those 75 years and older, account for the largest share of these patients, with a rate of 3. Fractures are the primary injury type among older patients hospitalized or seen in an emergency department. The rate of death due to a fall is the cause of more than 63% of unintentional injury deaths in persons age 85 years and older. After the age of 65, the proportion of hospital discharge patients with a musculoskeletal injury who are transferred to a skilled nursing, intermediate care, or other long-term care facility is more than one in two. Watkins-Castillo, PhD Between the years 1996-1998 and 2009-2011, the number of persons in the population reporting a musculoskeletal injury rose only slightly, from 23. Ambulatory health care visits for musculoskeletal injuries rose by 85% between the years 1996-1998 and 2009-2011, from 54 million to 99 million visits. However, physician office visits continue to account for the largest share of treatment visits. Hospital discharges for musculoskeletal injuries remain a very small proportion of overall treatment visits, indicating that most musculoskeletal injuries are not serious enough to require hospitalization. Prescription medications for musculoskeletal injuries nearly doubled over the time frame, jumping from 201 million prescriptions to 397 million between 1996-1998 and 2009-2011, an increase of 97%. At an average cost of $2,648 per person in 2009-2011, an increase of 80% from 1996-1998, ambulatory care accounted for 34% of per person direct cost in 2009-2011. While the share of mean perperson cost for inpatient care dropped from 35% to 27% between 1996-1998 and 20092011, the mean cost rose from $1,367 to $1,928, an increase of 26%. At the same time, the average per person cost for prescriptions rose from $427 to $1,314, in 2011 dollars, an increase of 161%. Incremental direct per-person costs, those costs most likely attributable to a musculoskeletal injury, rose from $1,213 to $1,913, in 2011 dollars, an increase of 58%. Watkins-Castillo, PhD Indirect costs associated with lost wages for those aged 18 to 64 years are not calculated for persons with a musculoskeletal injury. However, musculoskeletal injuries are a primary cause of lost work days by persons in the labor force. In addition to the cost of medical care for these injuries, the cost of lost wages and the potential for long-term impairment negatively impacting worker productivity are enormous. Fractures Trunk and Multiple Site Fractures Fracture of rib(s), sternum, larynx, and trachea: 807 Fracture of pelvis: 808 Ill-defined fractures of bones of trunk: 809 Multiple fractures involving both upper limbs and upper limb with rib(s) and sternum: 819 Multiple fractures involving both lower limbs, lower with upper limb, and lower limb(s) with rib(s) and sternum: 828 Fracture of unspecified bones: 829 Upper Limb Fractures Fracture of clavicle: 810 Fracture of scapula: 811 Fracture of humerus: 812 Fracture of radius and ulna: 813 Fracture of carpal bone(s): 814 Fracture of metacarpal bone(s): 815 Fracture of one or more phalanges of hand: 816 Multiple fractures of hand bones: 817 Ill-defined fractures of upper limb: 818 Multiple fractures involving both upper limbs and upper limb Copyright © 2014 by the United States Bone and Joint Initiative. National Ambulatory Medical Care Survey, 2006; National Hospital Ambulatory Medical Care Survey, Emergency Room Visits, 2006; National Hospital Ambulatory Medical Visits, Outpatient Department Visits, 2006 [7] Defined as spinal cord, vertebral column, torso, upper extremity, lower extremity injuries. National Ambulatory Medical Care Survey, 2006; National Hospital Ambulatory Medical Care Survey, Emergency Room Visits, 2006; National Hospital Ambulatory Medical Visits, Outpatient Department Visits, 2006 [10] Source: Source: Centers for Disease Control. Population [6] Sex Male Female % of Total Male Female 59% 34% 54% 58% 44% 50% 57% Total Number Hospital Discharges for Musculoskeletal Injuries (in 000s) 1,144. Population [6] Total Number of Emergency Department Visits for Musculoskeletal Injuries (in 000s) 3,964. Population [6] Total Number of Outpatient Department Visits for Musculoskeletal Injuries (in 000s) 1,256. Population [6] Sex Male Female % of Total Male Female 51% 45% 44% 46% 38% 52% 47% Total Number of Physician Visits for Musculoskeletal Injuries (in 000s) 11,948. Population [6] Total Number of Physician Visits for Musculoskeletal Injuries (in 000s) 11,948. Burden of Musculoskeletal Diseases in the United States, Third Edition Fractures Dislocations Sprains and Strains Contusions Open Wounds All Other Musculoskeletal Injuries Total All Musculoskeletal Traumatic Injuries 50,540 81% 27,042 72% 4,867 79% Physician Emergency Office Department Visits [2] Visits [3] 11,948. Total visits may be lower than sum of diagnoses due to multiple diagnoses per patient. Population [4] Sex Male Female % of Total Male Female Total Number of Hospital Discharges for Musculoskeletal Injuries (in 000s) 1,095. There is the potential for multiple diagnoses per person which is not accounted for. Population [4] Total Number of Emergency Department Visits for Musculoskeletal Injuries (in 000s) 4,044. Fracture of Upper Limb Fracture of Lower Limb Fracture of Hip/Upper Leg (Femur) Fracture of Lower Leg (Tibia/Fibula) Fracture of Ankle/Foot/Toes Fracture of Upper Arm (Humerus) Fracture of Lower Arm (Radius/Ulna) Wrist/Hand/Fingers Description Copyright © 2014 by the United States Bone and Joint Initiative. Burden of Musculoskeletal Diseases in the United States, Third Edition * Estimate does not meet standards for reliability. Burden of Musculoskeletal Diseases in the United States, Third Edition Cause of Injury Falls Struck By/Against Overexertion Motor Vehicle Occupant Cut/Pierce Bicyclist Injury Total All Causes [1] Age adjusted to 2000 standard population. Burden of Musculoskeletal Diseases in the United States, Third Edition <18 years Fractures Dislocations Sprains and strains Contusion Open Wound Other Musculoskeletal Injury All Musculoskeletal Injuries 18 to 44 years Fractures Dislocations Sprains and strains Contusion Open Wound Other Musculoskeletal Injury All Musculoskeletal Injuries 45 to 64 years Fractures Dislocations Sprains and strains Contusion Open Wound Other Musculoskeletal Injury All Musculoskeletal Injuries 65 to 74 years Fractures Dislocations Sprains and strains Contusion Open Wound Other Musculoskeletal Injury All Musculoskeletal Injuries page 376 Table 6A. Burden of Musculoskeletal Diseases in the United States, Third Edition <18 years Fractures Dislocations Sprains and strains Contusion Open Wound Other Musculoskeletal Injury All Musculoskeletal Injuries 18 to 44 years Fractures Dislocations Sprains and strains Contusion Open Wound Other Musculoskeletal Injury All Musculoskeletal Injuries 45 to 64 years Fractures Dislocations Sprains and strains Contusion Open Wound Other Musculoskeletal Injury All Musculoskeletal Injuries 65 to 74 years Fractures Dislocations Sprains and strains Contusion Open Wound Other Musculoskeletal Injury All Musculoskeletal Injuries page 378 Table 6A. Department of Labor, Bureau of Labor Statistics, Injuries, Illnesses and Fatalities Program: Case and Demographic Characteristics for Work-related Injuries and Illnesses Involving Days Away from Work. Number, percent, and incidence rate of nonfatal occupational injuries and illnesses involving days away from work by selected worker and case characteristics and musculoskeletal disorders, All United States, private industry, 2006 and 2007". Source (2000-2010): "Supplemental Table 6: Number, percent distribution, and median days away from work for nonfatal occupational injuries and illnesses involving days away from work by selected worker and case characteristics and musculoskeletal disorders, (2000 thru 2010)". Half the cases involved more days and half involved less days than a specified median. Department of Labor, Bureau of Labor Statistics, Survey of Occupational Injuries and Illnesses. Department of Labor, Bureau of Labor Statistics, Injuries, Illnesses and Fatalities Program: "Case and Demographic Characteristics for Work-related Injuries and Illnesses Involving Days Away from Work. Source (2008-2010): "Supplemental Table 6: Number, percent distribution, and median days away from work for nonfatal occupational injuries and illnesses involving days away from work by selected worker and case characteristics and musculoskeletal disorders, (2008 - 2010"). Source: "Table R45: Number of nonfatal occupational injuries and illnesses involving days away from work by nature of injury or illness and age of worker, private industry, 2011". Burden of Musculoskeletal Diseases in the United States, Third Edition Fitness Training [6] (Average N injuries treated) Upper extremity Lower extremity Trunk Head Playground Equipment [8] (Average N injuries treated) Upper extremity Lower extremity Trunk Head Skating [9] (Average N injuries treated) Upper extremity Lower extremity Trunk Head * Does not meet standards for reliability. Postseason sample sizes are much smaller (and have a higher variability) than preseason and in season sample sizes because only a small percentage of schools participated in the postseason tournaments in any sport and not all of those were a part of the Injury Surveillance System sample. Numbers do not always sum to totals because of missing division or season information. Epidemiology of Collegiate Injuries for 15 Sports: Summary and Recommendations for Injury Prevention Initiatives. Army Active Duty Incident Hospitalizations, 2012 Diagnosis Fracture Dislocation Internal Crush Burns Nerves Sprains /Strains Open Wound Amputations Blood Vessel Contusion/ Superficial Systemwide & Late Unspec Effects Total % By Body Region Copyright © 2014 by the United States Bone and Joint Initiative. Army Active Duty Incident Outpatient Visits, 2012 Diagnosis Fracture Dislocation Internal Crush Burns Nerves Sprains /Strains Open Wound Amputations Blood Vessel Contusion/ Superficial Systemwide & Late Unspec Effects Total % By Body Region Copyright © 2014 by the United States Bone and Joint Initiative. Army Active Duty IncidentHospitalizations, 2012 Diagnosis Inflammation and Pain (Overuse) Joint Derangement Dislocation 0 0 0 0 0 357 53 603 1 42 Total 245 13 465 0 11 91 40 56 0 5 0 0 0 0 0 0 0 0 0 0 Stress Fracture 21 0 82 1 26 Joint Derangement with Neurological Involvement Sprains/ Strains/ Rupture % By Body Region Copyright © 2014 by the United States Bone and Joint Initiative. Army Active Duty Incident Outpatient Visits, 2012 Diagnosis Inflammation and Pain (Overuse) Joint Derangement Dislocation 0 0 0 0 0 26,955 5,722 89,594 3,594 13,617 Total 2,610 459 10,701 0 1,430 3,460 5,263 2,428 0 252 0 0 0 0 101 0 0 0 0 0 Stress Fracture 20,885 0 76,465 3,594 11,834 Joint Derangement with Neurological Involvement Sprains/ Strains/ Rupture % By Body Region Copyright © 2014 by the United States Bone and Joint Initiative. Unfortunately, there is significantly less information regarding the burden of these conditions in young patients.

This number includes Lactobacillus strains not explicitly used as a probiotic agent but included in the product medicine grand rounds cheap 75mg prothiaden visa, for example as a starter culture for yogurt sewage treatment buy discount prothiaden 75mg. Streptococcus strains were included in 15 percent of studies; this number includes studies investigating Streptococcus strains explicitly as probiotic agents as well as other uses such as part of a yogurt starter culture symptoms 0f kidney stones 75 mg prothiaden overnight delivery. Enterococcus strains were investigated in 16 studies only (5 percent of included studies) medicine hat jobs generic prothiaden 75mg fast delivery. Preparations containing Bacillus strains were investigated in 10 studies (3 percent) medicine yeast infection cheap prothiaden 75mg. With regard to direct comparisons of genera across the included controlled studies medicine 3605 purchase 75 mg prothiaden with mastercard, only very few studies were identified that directly compared the effects of two different genera within the study. Cui (2004) compared Bacillus coagulans and Bifidobacterium longum in the treatment of acute and chronic diarrhea and reported that body weight, body temperature, respiratory rate, heart rate, blood pressure, routine blood tests, and liver and renal function were within normal limits after treatment, and no adverse reactions were found. De Simone (2001) compared a commercial product containing Streptococcus thermophilus, Bifidobacterium strains, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus casei, Lactobacillus delbrueckii bulgaricus, and Streptococcus faecium to a product containing Enterococcus faecium in the treatment of irritable bowel syndrome and found no significant changes in blood counts and chemistry in the groups. Margreiter (2006) compared a Lactobacillus gasseri and Bifidobacterium longum intervention with Enterococcus faecium and reported no lab abnormalities in either group. There was one case each of epistaxis, unstable angina, and chest pain due to anxiety, but the group was not specified. Probiotic studies often used Lactobacillus strains in combination with other genera, but we also identified a substantial number of studies using exclusively Lactobacillus strains. The identified case studies describing harms potentially associated with this genus are described in Key Question 1. Using the alternative measure, the number of incidences per group, the relative risk was 0. To explore the nature of adverse events experienced in Lactobacillus exclusive trials, we differentiated gastrointestinal complaints, infections and infestations, and all other reported adverse events. We also investigated the genus Lactobacillus as a factor in a metaregression comparing studies that used Lactobacillus strains (alone or in combination) with interventions that did not. The relative risk ratio across studies did not indicate that the Lactobacillus genus was associated 60 with a statistically significantly increased risk of adverse events compared to other genera based on the number of participants with adverse events (relative risk ratio 1. This result was confirmed by the alternative measure of adverse event incidences (relative risk ratio 1. Probiotic studies often used Bifidobacterium strains in combination with other genera, and we also identified a few studies using exclusively Bifidobacterium organisms. The identified case study describing harms potentially associated with this genus is described in Key Question 1. Using the alternative measure, the number of adverse event incidences, the relative risk was 0. To explore the nature of adverse events experienced in exclusively Bifidobacterium trials, we differentiated gastrointestinal complaints, infections and infestations, and all other reported adverse events. We also investigated the genus Bifidobacterium as a factor in a metaregression comparing studies that used Bifidobacterium strains (alone or in combination) with interventions that did not. The relative risk ratio across studies did not indicate that the Bifidobacterium genus was associated with an increased or reduced risk of adverse events compared to other genera, based on the number of participants with adverse events (relative risk ratio 1. We identified a number of case studies describing harms potentially associated with this genus; details are reported in the response to Key Question 1. Using the alternative measure, the number of adverse event incidences per treatment group, the relative risk was 1. The relative risk ratio across studies did not indicate that the Saccharomyces genus was associated with a statistically significantly increased risk of adverse events compared to other genera, based on the number of participants with adverse events (relative risk ratio 1. The results of the individual studies are reported in the Evidence Table C4, Results. We also investigated the genus Streptococcus as a factor in a metaregression comparing studies that used Streptococcus strains (alone or in combination) with interventions that did not. The relative risk ratio across studies did not indicate that the Streptococcus genus was associated with an increased or reduced risk of adverse events compared to other genera, based on the number of participants with adverse events (relative risk ratio 1. However, the result using the alternative measure of adverse event incidences indicated that intervention participants were at a greater risk of adverse events compared to other genera (relative risk ratio 1. We also investigated the genus Enterococcus as a factor in a metaregression comparing studies that used Enterococcus strains (alone or in combination) with interventions that did not. The relative risk ratio across studies did not indicate that the Enterococcus genus was associated 64 with a statistically significantly increased or reduced risk of adverse events compared to other genera, based on the number of participants with adverse events (relative risk ratio 0. This finding was confirmed by the alternative measure of adverse event incidences (relative risk ratio 0. We included the study described by La Rosa (2003), although the study originally described the investigated organism as Lactobacillus coagulans. The relative risk for intervention participants exposed to Bacillus organisms to experience an adverse event was 0. The pooled number of adverse incidences could not be computed, as only two studies reported the number of individual adverse event incidences for both treatment groups. The only other study that investigated a Bacillus intervention (Cui, 2004) found no adverse reactions in either the Bacillus coagulans group or the control group receiving Bifidobacterium longum. We also investigated the genus Bacillus as a factor in a metaregression comparing studies that used Bacillus strains (alone or in combination) with interventions that did not. The relative risk ratio across studies did not indicate that the Bacillus genus was associated with a statistically significantly different risk of adverse events compared to other genera, based on the number of participants with adverse events (relative risk ratio 0. This result was confirmed by the alternative measure of adverse event incidences (relative risk ratio 0. The indirect comparison of genera across studies did not indicate genera-specific safety results, with the exception of Streptococcus interventions: a metaregression based on the number of adverse incidences indicated a different risk ratio for participant and control group participants compared to other genera. However, this result was not confirmed based on the alternative measure, the number of participants with adverse events; the risk difference between intervention 65 and control groups was not statistically significantly different; and only few studies were identified overall that used other genera than Lactobacillus and Bifidobacterium alone or in combination. Finally, direct comparisons within studies are needed to answer this Key Question with confidence. The strains have not been used in research studies, which may indicate less use in clinical practice. Given the potentially unreliable identification of species actually used in the intervention studies, the large number of blends, the differences in dosing, the absence of direct comparisons, and the unsystematic assessment of adverse events across studies, it appears infeasible to draw conclusions regarding species-specific safety in interventions studies. Gracheva (1999) reported one incident of abdominal pain in a group given Bifidobacterium bifidum forte to treat acute intestinal infections, chronic diseases of the gastrointestinal tract, and viral hepatitis B (the participant withdrew) but no incidence in another Bifidobacterium bifidum treatment group. Krasse (2005) compared 2 Lactobacillus reuteri strains (both of human origin but not named) and reported that 1/20 participants in one of the groups experienced increased bowel movement. Some included studies compared groups consuming a yogurt product enriched with probiotic organisms to a control group consuming ordinary yogurt, and the results are documented in the evidence tables, but other comparisons of probiotic species were not found. No other studies made direct comparisons between probiotic products or compared mixtures of genera, species, or strains that would allow insight into the differential adverse event rates of individual species or individual strains. Based on the extremely limited number of studies that directly compared adverse events between probiotic organisms of different species or strains, it is not possible to draw any conclusions regarding the comparative safety of species or strains. Few studies employed a single species or strain; few studies characterized or verified the exact strain used; and given that microbial strains also mutate relatively quickly, the potential for attributing a particular event to a particular strain, let alone comparing events attributed to particular strains, is limited. In many studies, the form of the probiotic organism was not described, as can be seen in the Evidence Table C2, Intervention. We identified 10 studies that compared adverse events between forms of organisms, but these were comparisons of viable and heat-killed strains rather than comparisons between active and lyophilized forms. The direct comparisons did not indicate that adverse events were restricted to or more common in viable preparations. Alberda (2007) compared viable probiotic strains (Lactobacillus, Bifidobacterium, Streptococcus strains) with bacterial sonicates and reported one case of bowel obstruction and one congestive heart failure death in the viable treatment group. There was one death due to respiratory failure in the sonicates group and one myocardial infarction in the placebo groups. No cases of Lactobacillus induced sepsis occurred in this group of critically ill patients. Horvat (2010) reported one mild wound infection with secretion in the heat-killed group of a synbiotic intervention containing Lactobacillus, Pediococcus, and Leuconostoc strains. The study was prematurely terminated due to complaints 67 of adverse gastrointestinal symptoms in the heat-killed group. Merenstein (2009) reported one incidence of emesis in the active and one incidence of constipation in the heat-killed group. Rampengan (2010) compared a live and a heat-killed Lactobacillus preparation and reported four versus three adverse events (respiratory or bowel symptoms) in the respective groups. Rayes (2002) compared active and heat-killed Lactobacillus plantarum 299 strains and found 6/31 abdominal side effects in the active group, 11/31 in the heat-killed group and 8/32 in the not enriched enteral nutrition formula group in liver transplant recipients. In a study on patients with major abdominal surgery, Rayes (2002) reported three incidences of abdominal distention, four of abdominal cramps, and zero of diarrhea in the active Lactobacillus plantarum 299 group compared to six, five, and zero events in the heat-killed group; the corresponding control group incidences were four, six, and zero. Tsuchiya (2004) compared a synbiotic with (presumably) active Lactobacillus and Bifidobacterium strains with a similar heat-killed preparation and found no overt clinical or biochemical adverse side effects, but "a few" of the irritable bowel syndrome participants presented initially with transient diarrhea-like symptoms (group unclear). Xiao (2003) compared lyophilized and heat-killed Lactobacillus acidophilus to an active strain and found three cases of vomiting in the active group compared to one case in the heat-killed group. There was one case of constipation and one case of insomnia in the heat-killed group. In particular, the description of "active" may have been used interchangeably with "viable" rather than explicitly differentiating active and lyophilized forms. Very few studies indicated that they independently tested the content of the preparation given to participants, either for contaminants or for the viability of the included organisms at the time of the intervention. The Evidence Table C4, Results lists the organisms that constituted the intervention for easy reference. Overall, 60 percent of the included studies investigated the effect of only one genus believed to have probiotic properties, while 40 percent investigated the effect of a mixture of organisms, for example using a product that contained Lactobacillus and Bifidobacterium strains. Only two studies were identified that compared a single probiotic with a mixture of probiotic organisms directly. As described previously, De Simone (2001) compared a commercial product including several Streptococcus, Bifidobacterium, and Lactobacillus strains to treatment with Enterococcus faecium and found no significant changes in blood counts and chemistry across groups. Margreiter (2006) compared results of Lactobacillus gasseri plus Bifidobacterium longum treatment with the results of a group receiving Enterococcus faecium and reported no adverse events or clinically relevant abnormalities in laboratory characteristics. One other study (Metts, 2003) randomized participants to vaginal suppositories of Lactobacillus acidophilus, suppositories and oral capsules containing Lactobacillus and Bifidobacterium strains, and placebo; one participant in the oral and vaginal suppository group and one in the placebo group reported vaginal discharge. Kim (2006) compared interventions with 5, 6, and 12 probiotic species and reported that one participant with pre-existing hypertension had elevated blood pressure, loose stool, diarrhea, and dehydration in the 12-species treatment group, one participant 68 each in the 5- and the 6-species groups reported loose stool, diarrhea, and worsening of gastrointestinal symptoms. In the absence of further direct comparisons, we compared the included trials indirectly in subgroup analyses and a metaregression. Single Probiotic Strain Interventions A stratified analysis for studies using only one probiotic strain indicated a somewhat reduced, although not statistically significant, relative risk of adverse events compared to control (0. The corresponding risk difference between intervention and control group participants was -0. Using the alternative measure, the number of adverse event incidences showed a similar result, a relative risk of 0. Both types of intervention showed no statistically significantly increased risk of adverse events compared to control; however, results appeared to favor single-strain interventions compared to interventions including multiple probiotic strains. Meta-Regression: Single Versus Multiple Probiotics To find out whether the risk for adverse events was significantly different between these two kinds of interventions, we conducted a meta-regression. The metaregression did not indicate a statistically significant difference for the risk of adverse events between single and multiple strain interventions (relative risk ratio 0. A number of studies were identified that investigated a synbiotic product; that is containing a probiotic as well as a prebiotic, or explicitly gave probiotic organisms together with prebiotics. Some studies were identified that compared the effects of probiotics and synbiotics directly. Satokari (2001) and also Alander (2001) reported one incident of gastrointestinal symptoms and one participant not completing the study in the prebiotic treatment group (galacto oligosaccharide), and no adverse events in the probiotic group or the group consuming probiotics and prebiotics (as described in the response to Key Question 1f). Chouraqui (2008) reported 7/70 adverse event incidences in a group receiving Bifidobacterium longum, Lactobacillus rhamnosus, and galacto-oligosaccharide; 4/74 incidences in a second group receiving Bifidobacterium longum, Lactobacillus paracasei, and prebiotics; 11/70 incidences in the probiotics group; and 7/70 in a control group (for event details see Evidence Table C4, Results). De Preter (2006) compared Saccharomyces boulardii [cerevisiae], lactulose, and placebo in various sequences and reported that "some" participants experienced flatulence in the lactulose and placebo phases. Fujimori (2009) reported no adverse events related to blood counts, liver enzymes, total protein, albumin, total cholesterol, triacylglycerol, serum urea nitrogen, creatinine, and electrolytes across groups receiving probiotic organisms (Bifidobacterium longum), prebiotics (psylium), or synbiotics (both preparations). Ishikawa (2005) reported the deaths of two participants who died from colorectal cancer in a probiotic group during a 4-year study on prevention of colorectal tumors compared to one death from colorectal cancer in the group that consumed probiotics and wheat bran biscuits; in addition, one participant in this group died from cerebral hemorrhage, and one reported peritonitis, but no lung cancer death occurred in either group. Tomoda (1991) reported no changes in blood chemistry in treatment groups receiving a Bifidobacterium intervention with or without lactulose. Underwood (2009) reported four cases of necrotizing enterocolitis, six infections, and three cases of feeding intolerance in the probiotics group compared to one, two, and zero incidences of the same outcome in the synbiotic group. Worthley (2009) reported that 11/18 participants in the synbiotic group reported excessive flatus compared to 5/19 in the probiotic group. In the absence of further direct comparisons we investigated differences between probiotics and synbiotics in subgroup analyses and a metaregression. Meta-Regression: Probiotics Versus Synbiotics To establish whether the results seen in probiotics only and synbiotics studies differ statistically significantly, a metaregression was undertaken. Summary and Strength of Evidence Key Question 3 What is the evidence that harms of Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and Bacillus differ by product and delivery characteristics? Volume: Varied across questions Risk of bias: Medium the evidence to answer this Key Question stem from a variety of study designs and quality. Consistency: Inconsistent Very few studies overall were identified that directly compared delivery characteristics. Indirect comparisons showed only trends in replications rather than confirming exact results. Precision: Imprecise the majority of included studies used small or moderate sample sizes and although some large studies were included, these were not designed to monitor adverse events. Overall, the identified evidence is insufficient to answer the Key Question with confidence. Stratified analyses by probiotic genus identified a large number of studies exclusively using Lactobacillus strains; about a dozen studies on Bifidobacterium entered stratified analyses; and there were a small number of exclusive Saccharomyces interventions. However, there were very few studies using Streptococcus, Enterococcus, and Bacillus strains exclusively, and only some studies using these genera in combination with other genera.