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The re- cells) antibiotics in breast milk discount azitrix 100mg amex, appears in transverse section of the sulting muscle reaction is called reflex antibiotic brand names proven 100mg azitrix, the spinal cord as a butterfly configuration sur- underlying neuronal circuit is called reflex rounded by the white matter antibiotics sore throat purchase 250mg azitrix amex, substantia alba arc (D). Wedistinguishoneithersidea run directly to the motor neuron (mono- dorsal horn (posterior horn) (AB1) and a ven- synaptic reflex arc) but via interneurons that tral horn (anterior horn) (AB2). Between them lies the cen- reflex)and the multisynaptic extrinsic reflex tral intermediate substance (A3) with the (withdrawal reflex) are of clinical impor- obliterated central canal (A4). In the stretch reflex (F), the muscle is thoracicspinalcord,thelateralhorn(AB5)is briefly stretched by a tap on its tendon. The lateral posterior sulcus (A6) is results in a momentary contraction of the the site where the posterior root fibers muscle as a counter reaction. The anterior root fibers (AB8) volves only a few neurons at any level of the leave the anterior side of the spinal cord as spinal cord. The signal spreads through several tains neurons of the afferent system (B). The levels of the spinal cord and involves many anterior horn is derived from the basal plate interneurons. The lateral horn contains autonomic nerve cells of the sym- pathetic nervous system (p. The white matter is subdivided into the dorsal column, or posterior funiculus (A9), which reaches from the posterior septum (A10) to the posterior horn, the lateral column, or lateral funiculus (A11), which reaches from the posterior horn to the ante- rior root, and the ventral column, or anterior funiculus (A12), which reaches from the anterior root to the anterior fissure (A13). Reflex Arcs (C–G) The afferent fibers of the posterior root, which originate from the nerve cells of the spinal ganglion, transmit sensory signals to the posterior horn cells of the spinal cord, Kahle, Color Atlas of Human Anatomy, Vol. Gray and White Matter, Reflex Arcs 51 6 7 7 10 9 1 1 3 4 5 11 5 14 2 2 12 13 8 8 A Cross section of spinal cord B Longitudinal zones of spinal cord C Afferent fibers (ascending tracts) D Monosynaptic reflex arc E Multisynaptic reflex arc F Stretch reflex G Withdrawal reflex Kahle, Color Atlas of Human Anatomy, Vol. The somatotopic subdivi- proprius (A1), the major portion of the pos- sions do not occupy a single plane in the terior horn from which the dorsal nucleus anterior horn but are spread over a certain (Clarke’s nucleus) (A2) is set apart. The gelat- height in such a way that the neurons for inous substance (Rolando’s substance) (A3) the shoulder girdle lie at a higher level, borders dorsally on the nucleus proprius. Between posterior horn and contraction of a muscle group, there must anteriorhornliestheintermediategraymat- be simultaneous relaxation of the corre- ter (A6) and lateral to it the lateral horn (A7). This is achieved The border to the white matter between through inhibition of the corresponding posterior horn and lateral horn is diffuse anterior horn cells (D). Other interneurons mediate the spread of Lateral group of nuclei impulses over several levels, either on the! Posterolateral nucleus (A12) cending and descending fibers run in basic! Retroposterolateral nucleus (A13) bundles, fasciculi proprii (E21), which border directly on the gray matter. In general, the Central group of nuclei in the cervical spi- ascending and descending fibers reach only nal cord one or two root levels. Accessory nucleus connecting the cervical spinal cord and the lumbar spinal cord (as shown in cats and For example, in the cervical spinal cord (B), monkeys). These fibers transmit excitatory the anterior horn is subdivided somatotopi- and inhibitory impulses to anterior horn cally so that the neurons of the medial motor cells, a fact that is thought to be im- group of nuclei supply neck and back portant for coordinated movement of the muscles, intercostal, and abdominal anterior and posterior extremities during muscles (B14). About half of the posterolateral lateral nucleus supply the muscles of tract (Lissauer’s tract) (E5) consists of fibers shoulder girdle and upper arm (B15), and of the intrinsic system. Finally, the retroposterolateral nu- cleus contains particularly large motor neu- rons that supply the small finger muscles (B17).

Responses to burn injury vary; cystoscope cutaneous superficial ureterostomyureters invasive urosto- my bag ileal conduit radical cystectomy ileum urinary diversion Continent urinary diversions ureterosigmoidostomy chronic pyelonephritis 494 CHAPTER 18 MANAGED CARE AND CHRONIC ILLNESS AND DISABILITY plans that deliver specific services to a viders are employees of the organization antibiotics for uti toddler generic 500 mg azitrix otc. This model provides the HMO with more HMOs are managed care organizations control over services rendered antibiotic resistance and natural selection order azitrix 250mg line. Consequently antibiotics used for urinary tract infections 250mg azitrix mastercard, routine practices form partnerships or corpora- medical checks and health promotion ac- tions. If the individual Health care providers in the group are travels outside the service area, coverage then responsible for paying employees, is only guaranteed for life-threatening paying for hospital care, and paying for emergencies. HMOs are combined with traditional in- The ( demnity plans in which physicians are re- ) enables individual physicians to be imbursed for services provided or in associated with an HMO without being which individuals covered in the plan are under a direct contract or being a direct reimbursed for money spent for services. Physicians This type of plan provides individuals in the IPA model can deliver services to in- with the option at each “point of service” dividuals who are in the specific HMO to choose a provider covered under the plan and those who are not in the plan. Precise definitions of managed care are are a predetermined difficult because the concept is shaped by group of health care providers who have market forces and thus is continually be- agreed to follow specific practice guide- ing modified. Although initially imple- lines and accept a specified amount for mented as a cost-containment strategy, services. Identi- clinics, hospitals, or other facilities to pro- fying appropriate treatment, including the vide care. The is dividuals in a group, regardless of the a system in which the organization owns amount of care actually delivered. The the facilities in which enrolled individu- is the negotiated rate per indi- als receive services, and health care pro- vidual enrolled for a specified period. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording and/or otherwise, without the prior written permission of the publishers. First published in 2002 by BMJ Books, BMA House,Tavistock Square, London WC1H 9JR www. At the same time, this process has revealed the need for a more extensive and more valid evidence base as input for EBM. Accordingly, investigators have been encouraged to intensify the production and innovation of clinical knowledge, and clinical research has become more successful in seeing its results implemented in practice more completely in a shorter period. In developing the evidence base of clinical management it has come forward that, even 3 decades after Archie Cochrane wrote the words cited above, the methodology of diagnostic research lags far behind that of research into the effectiveness of treatment. This is the more challenging because making an adequate diagnostic process is a prime requirement for appropriate clinical decision making, including prognostic assessment and the selection of the most effective treatment options. In view of this apparent need for further methodological development of the evidence base of clinical diagnosis, this book was initiated. The aim is ix Contents Contributors vii Preface ix 1 General introduction: evaluation of 1 diagnostic procedures J ANDRÉ KNOTTNERUS and CHRIS VAN WEEL 2 The architecture of diagnostic research 19 DAVID L SACKETT and R BRIAN HAYNES 3 Assessment of the accuracy of diagnostic tests: 39 the cross-sectional study J ANDRÉ KNOTTNERUS and JEAN W MURIS 4 Diagnostic testing and prognosis: the randomised 61 controlled trial in diagnostic research JEROEN G LIJMER and PATRICK M BOSSUYT 5 The diagnostic before–after study to assess 81 clinical impact J ANDRÉ KNOTTNERUS,GEERT-JAN DINANT and ONNO P VAN SCHAYCK 6 Designing studies to ensure that estimates of test 95 accuracy will travel LES M IRWIG,PATRICK M BOSSUYT,PAUL P GLASZIOU, CONSTANTINE GATSONIS and JEROEN G LIJMER 7 Analysis of data on the accuracy of diagnostic tests 117 J DIK F HABBEMA,RENÉ EIJKEMANS,PIETA KRIJNEN and J ANDRÉ KNOTTNERUS 8 Guidelines for conducting systematic reviews of 145 studies evaluating the accuracy of diagnostic tests WALTER L DEVILLÉ and FRANK BUNTINX v THE EVIDENCE BASE OF CLINICAL DIAGNOSIS 9 Diagnostic decision support: contributions from 167 medical informatics JOHAN VAN DER LEI and JAN H VAN BEMMEL 10 Clinical problem solving and diagnostic 179 decision making: a selective review of the cognitive research literature ARTHUR S ELSTEIN and ALAN SCHWARTZ 11 Improving test ordering and diagnostic 197 cost effectiveness in clinical practice – bridging the gap between clinical research and routine health care RON AG WINKENS and GEERT-JAN DINANT 12 Epilogue: overview of evaluation strategy 209 and challenges J ANDRÉ KNOTTNERUS Index 217 vi Contributors Jan H van Bemmel Department of Medical Informatics, Erasmus University Rotterdam, The Netherlands Patrick M Bossuyt Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam, The Netherlands Frank Buntinx Department of General Practice, Catholic University Leuven, Belgium Walter L Devillé Institute for Research in Extramural Medicine,Vrije Universiteit, Amsterdam, The Netherlands Geert-Jan Dinant Department of General Practice, University of Maastricht, The Netherlands René Eijkemans Center for Clinical Decision Sciences, Department of Public Health, Erasmus University Rotterdam, The Netherlands Arthur S Elstein Department of Medical Education, University of Illinois College of Medicine, Chicago, Illinois, USA Constantine Gatsonis Center for Statistical Sciences, Brown University, Providence, Rhode Island, USA Paul P Glasziou Department of Social and Preventive Medicine, University of Queensland Medical School, Australia J Dik F Habbema Center for Clinical Decision Sciences, Department of Public Health, Erasmus Medical Center Rotterdam, The Netherlands vii THE EVIDENCE BASE OF CLINICAL DIAGNOSIS R Brian Haynes Clinical Epidemiology and Biostatistics, McMaster University Medical Centre, Hamilton, Ontario, Canada Les M Irwig Department of Public Health and Community Medicine, University of Sydney, Australia J André Knottnerus Netherlands School of Primary Care Research, University of Maastricht, The Netherlands Pieta Krijnen Center for Clinical Decision Sciences, Department of Public Health, Erasmus Medical Center Rotterdam, The Netherlands Johan van der Lei Department of Medical Informatics, Erasmus University Rotterdam, The Netherlands Jeroen G Lijmer Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam, The Netherlands Jean W Muris Department of General Practice, University of Maastricht, The Netherlands David L Sackett Trout Research and Education Centre at Irish Lake, Markdale, Ontario, Canada Onno P van Schayck Institute for Extramural and Transmural Health Care, University of Maastricht, The Netherlands Alan Schwartz Department of Medical Education, University of Illinois College of Medicine, Chicago, Illinois, USA Chris van Weel Department of General Practice and Social Medicine, Institute for Evidence-Based Practice, University of Nijmegen, The Netherlands Ron AG Winkens Transmural and Diagnostic Centre, Academic Hospital Maastricht, The Netherlands viii THE EVIDENCE BASE OF CLINICAL DIAGNOSIS to provide a comprehensive framework for (future) investigators who want to do diagnostic research, and for clinicians, practitioners and students who are interested to learn more about principles, and about relevant methodological options and pitfalls. Clearly, not all topics relevant for diagnostic research could be covered, nor could the selected subjects be dealt with in all detail. For those who wish to know more, the references in the chapters can be a useful guide. In preparing the work, the contributors were able to profit from the experience and insights collected and reported by many leading clinical researchers in the field. What are the key objectives, the challenges, and the corresponding options for study design? What should the architecture of diagnostic research look like to provide us with an appropriate research strategy, yielding the clinical information we are looking for, with a minimum burden for study patients and an efficient use of resources?

In recent years computed tomography distinguished from insufficiency fractures bacteria 2 discount 250mg azitrix visa, which occur (CT) and isotope bone scanning have been superseded due to normal stress on weakened bone infection under root canal buy azitrix 500mg on-line. The latter are not by magnetic resonance (MR) imaging for demonstrating infrequently noted in the talus and may be confused with most osseous and soft-tissue abnormalities antibiotic brands buy generic azitrix 500mg. MR images depict a arthrographic techniques produce additional informa- hypointense fracture line or lines that may extend to the tion in the assessment of capsular recesses and carti- cortex and the accompanying bone-marrow edema. Ultrasound (US) can be alternatively used for soft- Occasionally, early periosteal callous formation can also tissue assessment. The lack of Traumatic Osseous Abnormalities periosteal reaction in fractures of the hindfoot and tarsal bones makes the diagnosis even more difficult. In those Occult Fractures, Stress Fractures, Bone Bruises and instances, the extent of T1 signal alterations is a useful Stress Reaction guideline in differentiating the above three entities. In bone bruises and stress reaction, the T1 signal alterations Conventional radiography remains the primary diagnos- are subtle or non-existent, while fractures depict more tic method for evaluating bony lesions. However, MR significant signal alterations on both T1 and fluid-sensi- imaging, because of its ability to demonstrate bone-mar- tive sequences. Metatarsal stress fracture can also be dis- row edema, has become a reliable technique for diagnos- tinguished from stress reaction by the presence of a pe- ing occult fractures that are not seen on plain radi- riosteal reaction, which is not usually seen in stress reac- ographs. Stress reaction particularly related to abnormal bio- scintigraphy; however, this modality is nonspecific, espe- mechanics may be asymptomatic and may involve multi- cially when dealing with the small bones of the feet, and ple bones. Isolated periosteal or adjacent soft-tissues ede- fails to demonstrate anatomic detail. Occult fractures of ma without T1-weighted changes are other clues to the the foot and ankle occur most frequently in the talus, cal- presence of stress reaction. They are most commonly seen on the contralat- sent, a fracture line appears on T1-weighted images as a eral side of the ankle, in the medial talus, tibia and cal- linear line of low signal intensity traversing the bony tra- caneus, and are related to an impaction injury. Acute frac- may also be associated with bone bruises in the talar tures often present with increased signal intensity adja- neck, talar head and navicular, possibly related to talar ro- 40 Z. The ipsilateral bone bruises tend to since premature secondary degenerative arthritis is more be subtler and smaller in size than the contralateral ones. Plain films may depict the osteochondral lesions but may be seen up to a year following the injury. The possi- are less sensitive than CT and MRI, especially for de- bility of chronic instability with repetitive impaction in- tecting grade I lesions. Plain films also cannot easily dif- juries should be raised when the bruises do not resolve ferentiate the grades because of the inability to visualize quickly. It is recommended that resumption of any sports the overlying articular cartilage. CT is less sensitive than activity should be delayed for 4-6 weeks due to the po- MRI for detecting early lesions and for assessing the ar- tential development of a complete fracture; however, the ticular cartilage. The subchondral bone, however, may be treatment of bone bruises in the ankle has not yet been better assessed with CT than with MR imaging. MR imaging is the optimal modality to assess the pres- ence, size and exact location of the lesion as well as the Osteochondral Talar Lesions integrity of the overlying cartilage, the degree of attach- ment, displacement and viability of the osteochondral Osteochondral lesions of the talar dome, formerly called fragment, and the location of loose bodies in the joint osteochondritis dissecans, osteochondral fractures or ta- space. MR diagnosis of fragment stability has relied on lar transchondral fractures, occur in 6. A low signal intensity rim at the laceration of the articular cartilage and fracture of the un- interface between the normal bone and the osteochondral derlying subchondral microtrabeculae. Talar osteochon- fragment is consistent with healing and stability, while a dral fractures commonly occur in the medial or lateral high signal intensity interface on fat-suppressed post-in- corners of the dome, although central lesions have been tra-articular contrast T1-weighted images indicates a also sporadically described.

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Obviously antimicrobial finish discount azitrix 250mg with mastercard, radioiodine abla- rotroph sensitivity to thyrotropin-releasing hormone tion or surgical removal of the thyroid gland also causes (TRH) infection gum purchase 500mg azitrix with amex. Consequently bacteria synonym purchase genuine azitrix on line, when the circulating concentration thyroid hormone deficiency. Hypothyroidism is the dis- of free thyroid hormones is high, thyrotrophs are relatively ease state that results from thyroid hormone deficiency. The resulting fall of TSH levels in the blood re- of most tissues in the body. As described earlier, a defi- duces the rate of thyroid hormone release from the follicu- ciency of thyroid hormones at birth that is not treated lar cells in the thyroid. When the free thyroid hormone during the first few months of postnatal life causes irre- level falls in the blood, however, the negative-feedback ef- versible mental retardation. Thyroid hormone deficiency fect of T3 on thyrotrophs is reduced, and the rate of TSH later in life also influences the function of the nervous sys- secretion increases. For example, all cognitive functions, including the thyroid gland to secrete thyroid hormones at a greater speech and memory, are slowed and body movements rate. These changes can usually be reversed to changes in gene expression in these cells. The physiological actions of the thyroid hormones de- Metabolism is also reduced in thyroid hormone-defi- scribed above are summarized in Table 33. Basal metabolic rate is reduced, resulting in impaired body heat production. Vasoconstriction occurs in the skin as a compensatory mechanism to conserve body THYROID HORMONE DEFICIENCY AND heat. Food in- take is reduced, and the synthetic and degradative EXCESS IN ADULTS processes of intermediary metabolism are slowed. In severe A deficiency or an excess of thyroid hormones produces hypothyroidism, a substance consisting of hyaluronic acid characteristic changes in the body. These changes result and chondroitin sulfate complexed with protein is de- from dysregulation of nervous system function and altered posited in the extracellular spaces of the skin, causing wa- metabolism. This effect gives a puffy ap- pearance to the face, hands, and feet called myxedema. All of the above disorders can be normalized with thyroid hor- Thyroid Hormone Deficiency Causes Nervous mone therapy. For example, iodide deficiency may result in a re- Nervous and Other Disorders duction in thyroid hormone production. Autoimmune dis- eases, such as Hashimoto’s disease, impair thyroid hor- The most common cause of excessive thyroid hormone mone synthesis (see Clinical Focus Box 33. Other causes production in humans is Graves’ disease, an autoimmune CHAPTER 33 The Thyroid Gland 605 CLINICAL FOCUS BOX 33. The disease is occur when an individual’s immune system fails to recog- also observed in patients known to have Graves’ disease. This usually triggers both increased immune system function following the suppres- humoral and cellular immune responses. Of these women, about 50% have opposite effects on thyroid function are Hashimoto’s dis- transient thyrotoxicosis alone, 25% have transient hy- ease and Graves’ disease.