Dizziness in older patients in general practice: away from diagnostic nihilism Dros, J.

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1 UvA-DARE (Digital Academic Repository) Dizziness in older patients in general practice: away from diagnostic nihilism Dros, J. Link to publication Citation for published version (APA): Dros, J. (2013). Dizziness in older patients in general practice: away from diagnostic nihilism General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam ( Download date: 26 Feb 2019

2 Chapter 9 General discussion Jacquelien Dros

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4 Dizziness is a frequently occurring reason for encounter in general practice. It can be a great burden to older people, resulting in serious impairment in daily functioning, social isolation and falls. However, the scientific basis for diagnosis and management of dizziness is meagre, as became apparent in the Dutch College of General Practitioners practice guideline on dizziness. 1 In this thesis we aimed to provide an empirical basis for both the diagnostic evaluation and the prognosis of dizziness. We started by reviewing current knowledge on diagnostic tests used for dizziness in general practice. Many different tests have been described to diagnose diseases that may underlie dizziness, but the evidence for the validity of most tests is disappointing. We asked a panel of experts for advice on which tests they deemed feasible and worthwhile to incorporate in a diagnostic battery to be tested in a new in general practice. The tests thus selected, we applied in a cohort of 417 consecutive older patients, who consulted their general practitioner for dizziness. We then provided a second panel of clinical experts with the results of these tests and asked them to select, for each patient, those factors that contributed to the complaints of dizziness. We used broad categories since dizziness in older patients is frequently supposed to be caused by multiple failing physiological mechanisms and not by a single distinct disease. 2-5 As experts are dependent on their own clinical experience and on published research results (which appeared to be scarce), we decided not to rely solely on the opinion of experts, but to look for empirical validation as well. We included older patients with a wide range of complaints of dizziness and, using principal component analysis (PCA), looked for different profiles ( phenotypes ) of dizziness. Thus we hoped to find clues for the diagnosis of underlying diseases and medical problems or combinations thereof. A second analysis involved a comparison between the test results in older patients with and without dizziness assuming that, if no differences are found, it is unlikely that these tests are useful in diagnosing underlying causes of dizziness. Finally we analysed how impact and prognosis of dizziness vary as a function of diagnostic tests to explore factors that may be candidates for medical intervention. 191

5 Which diagnostic tests should be used to evaluate dizziness in general practice? Our systematic review of the literature (Chapter 2) shows that the evidence for the validity of commonly used diagnostic tests for dizziness in primary care is poor. Most studies of diagnostic tests for dizziness have been conducted in selected groups of patients and all included studies have, at least partially, been conducted in secondary or tertiary care settings. Furthermore, studies into the validity of frequently used tests to diagnose causes of dizziness, such as specific patient history items, pulse measurement, heart auscultation and balance or gait tests, are lacking. A meta-analysis could only be performed on two tests, the head-shaking-nystagmus test and the head-impulse test (HIT), neither of which are commonly used in general practice. In acute dizziness the HIT is the most promising, with a positive test result confirming a peripheral vestibular dysfunction and a negative test result a central lesion. In general practice, however, these findings should be interpreted with caution. Generally, to interpret the outcome of diagnostic tests properly, we need to be aware of the case-mix of conditions in the studied population as this influences test characteristics (sensitivity and specificity). 6-9 In other words, the results of our review, including mainly studies in homogeneous patient groups in secondary and tertiary care, show that no single test has documented validity for general practice. The panel of experts (Chapter 3) assessed only those tests from our review which met the crucial condition of using an appropriate reference standard likely to correctly classify the condition being studied. In addition, we searched for, and added, tests recommended by practice guidelines on dizziness, syncope or vertigo. In a structured Delphi procedure, the expert panel selected 21 out of 37 diagnostic tests (Appendix). The panel excluded sixteen diagnostic tests, although five of these are recommended by several practice guidelines on dizziness. Two diagnostic tests were included, although several guidelines question their diagnostic value and two other diagnostic tests were included, although these had never been recommended by practice guidelines on dizziness. Finally, we used these 21 tests in a standardised evaluation to dizziness in older patients in general practice. Many of these tests consist of more items, particularly those of patient history, but also for example pulse measurement, orthopaedic screening of lower extremities or the Patient Health Questionnaire (PHQ). Although recommended by the expert panel, we found that the following tests did not provide different results between patients with or without dizziness: pulse rate and rhythm measurement, orthostatic hypotension, mobility of hip/knee/ankle joints, tendon reflexes, alcohol problem (measured using PHQ), non-fasting blood glucose and anaemia based on haemoglobin level (Chapter 6 and Appendix). The lack of contrast between these test results poses questions about the extent to 192

6 which the underlying conditions contribute to dizziness or even suggest that the tests themselves may be problematic. These findings mean that these tests are unlikely to be relevant in the diagnostic evaluation of dizziness. For half of the non-discriminative tests (tendon reflexes, alcohol problem, non-fasting blood glucose and haemoglobin) the prevalence of the underlying condition tested was low and this might explain the absence of a contrast in positive test results between patients with and without dizziness. In particular, the finding that orthostatic hypotension (OH) measurement did not distinguish between patients with or without dizziness warrants further reflection. As clinicians perceive OH to be a relevant condition in patients with dizziness, a test to diagnose OH is important and several, slightly different, tests are advocated in guidelines and by experts on syncope (see Appendix) OH is diagnosed when a fall of systolic blood pressure of at least 20 mm Hg and/or a fall of diastolic blood pressure of at least 10 mm Hg within 3 min of standing or head-up tilt to at least 60 on a tilt table is recorded. 11 Relevant elements of this definition include the magnitude of the drop, time to reach the blood pressure difference defined as OH, and reproducibility of the orthostatic blood pressure drop, but each of these elements is debatable As the magnitude of the orthostatic blood pressure fall is dependent on the baseline blood pressure, experts refined the definition and suggested a reduction in systolic blood pressure of 30 instead of 20 mmhg in patients with supine hypertension in a recent update. 11 Nonetheless, this update does not overcome the problem that OH is diagnosed according to criteria and does not take into account a patients orthostatic complaints. Study of the relation between a positive test result on the OH test and orthostatic complaints is therefore still warranted. 193

7 Classification of dizziness and patients with dizziness As the complaint of dizziness refers to various sensations resulting from impairments in different organ systems simultaneously, a first step in the diagnostic management of older patients with dizziness could be to classify the patient s dizziness in categories or profiles. The current, frequently used and generally accepted classification divides dizziness into four categories: vertigo, disequilibrium, presyncope and other dizziness. This theoretical classification is based on aetiological and pathophysiological concepts. 14 Within this theoretical classification, vertigo, mainly caused by vestibular conditions, refers to a rotational or spinning sensation in which patients feel that either they, or the environment, are rotating. Presyncope, mainly caused by cardiac or vasomotor conditions, refers to a sensation of light-headedness, nearly fainting or impending loss of consciousness. Disequilibrium, mainly caused by orthopaedic, neurological or sensory problems, refers to a sensation of unsteadiness and impaired balance and gait, prominent when standing or walking. Finally, other dizziness, suggested to be mainly caused by psychiatric conditions, may include floating or swimming sensations or feelings of dissociation. Based on the information obtained through our diagnostic evaluation, a multidisciplinary panel reviewed and classified each patient independently. According to the panel, the most common category of dizziness was presyncope (69%), followed by vertigo (41%), disequilibrium (40%) and other dizziness (2%), and 44% of patients were placed in more than one category (Chapter 5). The same information from our diagnostic evaluation was used to establish an empirical classification of diagnostic dizziness profiles (Chapter 4). To generate these profiles, we used a two-step procedure which mimics the diagnostic approach in daily practice, basing the first step on demographic data and patient history and, in the second step, adding information from the physical examination and diagnostic tests. The six identified dizziness profiles have been named and were distributed among patients as followed: frailty (31%), psychiatric conditions (39%), cardiovascular constraints (49%), presyncope (43%), ear, nose and throat (ENT) (38%), and non-specific dizziness (43%). In 76% patients were placed in more than one profile. The profiles identified in both steps are quite similar, meaning that a thorough history-taking seems to be sufficient for the initial classification of dizziness. However, this finding does not indicate that additional tests should be abandoned in the diagnostic evaluation, because within a dizziness profile the additional tests may still be useful to rule in or out specific conditions. For example, within the frailty profile, an audiogram can be used to diagnose presbyacusis or within the ENT profile, the Dix-Hallpike test can be used to diagnose benign paroxysmal positional vertigo (BPPD). 194

8 With the classification according to dizziness profiles we were able to classify 88% of the patients. Fifty patients (12%) could be placed in one profile and diagnosing underlying causes of their dizziness may be relatively easy using a few diagnostic tests. The finding that patients are often placed in more than one dizziness profile (76%) corroborates the concept of dizziness as a multifactorial problem. For these patients the classification according profiles can make a first selection of diagnostic domains, and although more diagnostic tests will be necessary to find underlying causes as when a patient is classified into one profile, these tests can be directed and will be less than in a total work-up. Theoretical concepts and empirical classification When comparing the six dizziness profiles with the four dizziness categories, the following similarities can be seen: the ENT profile in the absence of the non-specific dizziness profile, consisting of mainly non-ent elements like the absence of head movement as a provoking circumstance and a negative Dix- Hallpike test, resembles vertigo. The Frailty profile, although this term represents a far broader concept, includes not only impaired stability at rest and abnormal functional mobility, but also characteristics such as living in a residential home and using hearing and walking aids, resembles disequilibrium. The combined profiles cardiovascular constraints and presyncope resemble presyncope, and the psychiatric conditions profile, although more specific, for example with anxiety and/or depressive disorder (history and presence) and the use of psychotropic drugs, resembles other dizziness. Thus, the newly established profiles provide empirical ground for the existing theoretical classification. Next, with this empirically classification and the theoretical concepts of dizziness we can make the following distribution into dizziness categories. Approximately 69% of the patients dizziness can be classified as presyncope ( cardiovascular constraints and/or presyncope profiles). Fourteen per cent of cases of dizziness can be classified as vertigo (the ENT profile combined with the absence of the non-specific dizziness profile) and defining vertigo less strictly (based on the ENT profile only), 38% of patients can be classified. Next, disequilibrium (the frailty profile) was found in 31% and other dizziness (the psychiatric conditions profile) occurred in 39% of patients with dizziness. Compared to the classification in categories assigned by the panel, with presyncope 69%, vertigo 41%, disequilibrium 40% and other dizziness 2%, this was the only category with a markedly different classification. This notable discrepancy might mean that the multidisciplinary panel, was too focussed on the more well-defined categories of presyncope, vertigo and disequilibrium as they were asked to be as explicit as possible. The 2% other dizziness found by the panel is also less than might be expected from the literature (16-17%). 15,16 It might also mean that the dizziness 195

9 profile psychiatric conditions does not adequately match the category other dizziness and should be interpreted as a more distinct profile. The 39% found for the psychiatric profile is quite high, meaning that psychiatric conditions are important in older patients with dizziness, at least in this population. Furthermore, the classification according to dizziness profiles, based on readily available information collected during a consultation and from the (electronic) medical record, is less dependent on the subjective description by the patient that is required to classify a patient s dizziness into one of the four categories. Especially older patients may benefit from this new approach as they experience more difficulties in communicating dizziness symptoms: due to the multifactorial nature of their dizziness, they can suffer from a combination of several dizziness sensations, which hinders this classification. Finally, with both the classification according to dizziness profiles and the panel assignment, patients are often placed in more than one dizziness profile (76%) or category (44%). This finding corroborates the concept of dizziness as a multifactorial problem. Impact and prognosis of dizziness in older primary care patients Despite the need to gain more insight into the prognosis of dizziness, few prospective studies have investigated dizziness-related impairment and the course of dizziness in primary care patients, and none of these have provided information on older patients In our on the impact of dizziness (Chapter 7), two out of three older patients presenting with dizziness to a GP experienced a moderate or severe impact on everyday life due to dizziness. We found six simple indicators to identify which patients suffer most from their dizziness: certain features of dizziness symptoms (chronic dizziness (onset at least six months ago), frequency (at least daily) and duration of dizziness ( 1 minute)), having an anxiety and/ or depressive disorder, the use of sedative drugs (mainly benzodiazepines) and impaired functional mobility. In our on the functional prognosis of dizziness (Chapter 8), two out of three patients experienced less impairment six months after inclusion compared to baseline. Nearly one out of three patients still experienced relevant impairment and one in ten had a substantial increase in impairment. Seven factors predicted an unfavourable course: chronic dizziness (onset at baseline at least six months ago), standing still as a dizziness-provoking circumstance, trouble with walking and/or (almost) falling as associated symptom, poly-pharmacy, absence of diabetes, having an anxiety and/or depressive disorder and impaired functional mobility. In conclusion, using this relatively simple risk prediction model, clinical management might be more effective if treatment is focused on those factors that 196

10 can be influenced, such as anxiety and depression, poly-pharmacy, and functional mobility. Clearly, future research is needed to determine whether interventions in these domains are effective in reducing dizziness-related impairment. How this fits in with existing knowledge on the prognosis of dizziness? Poly-pharmacy and the absence of diabetes as prognostic factors in dizziness have not previously been reported. Given the frequently described relationship between dizziness and use of drugs 5;20-25 it is not surprising that poly-pharmacy appeared to be a predictor of the persistent impact of dizziness. The finding that the absence of diabetes predicts a poor outcome is not obvious and may be a coincidence. One explanation might be that patients with diabetes consult a general practice more often, compared to patients without diabetes. In that sense, diabetes may be a marker for attentive medical care, while not having diabetes may increase the chance of receiving less medical attention. As a result, patients without diabetes may have more severe dizziness at the time of presentation. Another notable aspect in our is that the risk factors identified for an unfavourable course of dizziness are similar to those for falling. A recent systematic review 26 identified previous falls; strength, gait, and balance impairments; and the use of fall risk increasing drugs (FRID) as the strongest risk factors for falling among community-dwelling older persons. The use of drugs is an ambiguous, and therefore complex, risk factor for falling and for persistent dizziness. For example, conditions such as heart failure or hypertension and anxiety or depression may increase both dizziness and fall risk in older patients, but so may the drugs used to treat them. Furthermore, as with the risk of falling, the risk of an unfavourable course of dizziness increases with the number of drugs used. 20;25;26 This seems to be particularly true for the use of FRID, like psychoactive drugs (anxiolytics/ hypnotics, antipsychotics, and antidepressants), antihypertensives and antiarrhythmics. In terms of falling, intervening on single risk factors has shown to be effective only for balance training, cataract surgery, and medication reduction Intervening on multiple risk factors has shown to be the most effective strategy in reducing the rate of falling in older persons, both in community as in emergency care settings. 28;31 This multi intervention approach might also be valid for the management of dizziness. Methodological issues Inconsistencies in PCA clustering In the on diagnostic dizziness profiles (Chapter 4), we used principal component analysis (PCA), a technique used to summarize a large number of 197

11 variables by a small number of components, that is associated variables forming a distinct pattern or profile. Although the PCA-generated components are easily interpretable, the clustering of some variables leads to important inconsistencies. For example, the use of fall risk-increasing drugs (FRID) belongs to the cardiovascular constraints profile, but not to the frailty profile; the dizzinessassociated symptom tinnitus/decay in hearing belongs to the presyncope profile, but not to the ENT profile; and the duration of dizziness attacks shorter than one hour does not feature in the ENT profile. These inconsistencies are all due to the use of the PCA method: some expected cross-loadings do not appear in our population or are too low for our definition of cross loading ( or 0.35). Coming back to one of the examples mentioned above, the loading of tinnitus/decay in hearing is 0.42 in the presyncope profile, 0.25 in the ENT profile and almost zero in the 4 other components or profiles. In our opinion, this highlights two points. Firstly, the empirically-established components actually represent different distinct presentations or profiles of dizziness and, secondly, dizziness in older patients often fits in several dizziness profiles. To reflect on another example of inconsistency, namely FRID clustering in the cardiovascular constraints profile, but not in the frailty profile: it would be more likely for FRID to be placed in the cardiovascular constraints profile than that of frailty as patients in the former will certainly use many blood pressure-decreasing drugs (with dizziness as potential adverse effect), while the frailty profile covers a wide range of disabilities. Furthermore, as one in five patients fits in both the profiles frailty and cardiovascular constraints, from a patient level it is more consistent. As a solution to some of the inconsistencies associated with the PCA method, the use of other loadings is suggested, for example >0.5 is sometimes used as convention. With higher loadings, the threshold to cluster in a component will increase and consequently each component will consist of fewer variables. However, this will make the content of components less informative and together with the fact that it does not change the number of components, we do not believe it to be an adequate solution. As PCA is known to depend considerably on the sample (size) used, it would be interesting to validate our findings in another (larger) sample of older primary care patients with dizziness, applying the same diagnostic test protocol. Prognostic potential or just ineffective treatment? The aim of prognostic research is to predict the course of diseases so that patients and physicians can learn about the future, and to enable physicians to guide management, with respect to patients perspective. In our prospective cohort, we have ensured consecutiveness of patients (to avoid selection bias) and a specific spectrum of patients (older patients presenting with dizziness 198

12 in general practice). Furthermore, to carry out a comprehensive assessment of candidate predictors we used information collected in clinical practice, including demographic data, history, physical examination and diagnostic tests and we measured the outcome (unfavourable course of dizziness-related impairment) as accurately as possible, allowing a reasonable time for this outcome to develop (six months). Additionally, there was no selective loss to follow-up. Nonetheless, we have not assessed treatment by GPs or specialists during the six months of follow-up while that might be of importance for the outcome. As treatment was left at the discretion of the treating physicians we assume that our results reflect the prognosis of dizziness in a usual care setting. During follow-up some patients may have recovered because of medical or non-medical interventions. In terms of the course of dizziness-related impairment, we only know that less complex problems, such as viral causes or acute ear problems, were already filtered out at inclusion and that two out of three dizzy patients had experienced dizziness complaints for more than six months at inclusion. Our analyses explored the areas in which there is room for improvement. Clinical management may improve if physicians are able to select patients with an unfavourable course of dizziness by using predictors such as poly-pharmacy, anxiety and depression, and functional mobility. Thus, in our opinion, rather than reflecting ineffective treatment, the results of our prognostic offer recommendations to improve treatment. Recommendations for future research Diagnostic tests evaluating dizziness in general practice As the results of our review of the literature show, evidence to support the diagnostic process in general practice is scarce and studies on the accuracy of diagnostic tests used in patients with dizziness were only conducted in highly selected homogeneous groups of patients (Chapter 2). As patients with dizziness are mainly seen and managed in general practice, frequently used and recommended diagnostic tests should be validated in patients in general practice. Therefore, additional research into these tests is warranted. In particular, diagnostic accuracy studies are needed into history-taking, confirmed as an important diagnostic tool in our studies (Chapter 4 and 5), and into the examination in the fields of mobility, ENT and psychiatry, for example the measurement of peripheral neuropathy with the monofilament test, the Dix- Hallpike test, and tests to diagnose an anxiety and/or major depressive disorder (Chapter 6, 7 and 8). The appropriate patients to be included in such studies are those presenting to a GP with complaints of dizziness. Dizziness profiles may subsequently be used as an initial pre-selection step for these studies. For example, patients with an ENT-profile and without a non-specific dizziness 199

13 profile can be selected for a of the Dix-Hallpike test, while patients with a psychiatric dizziness profile could be selected for a of a diagnostic test for anxiety and/or major depressive disorders. This pre-selection is in line with clinical practice, where, for example, a GP will not perform the Dix-Hallpike test if head movements do not provoke a patients dizziness. Furthermore, as it is expected that three out of four patients will be classified into more than one dizziness profile, patients could be selected for more diagnostic studies. This would prevent too much selection of the patients with dizziness and respects the multifactorial nature of dizziness. Validation of dizziness profiles Our empirical classification of dizziness in clinically plausible profiles, with frailty, psychiatric conditions, cardiovascular constraints, presyncope, ENT, and non-specific dizziness, might serve as a first step in the diagnostic work-up of older patients with dizziness (Chapter 4). Before implementing this classification, validation in other groups of older patients presenting with dizziness in general practice is mandatory. Therefore other older patients with dizziness should be tested using similar tests to those in our standardised evaluation. The test results should also be analysed using a technique that summarizes a large number of variables according to a small number of components, where associated variables form a distinct pattern or profile, such as PCA or another kind of clustering analysis techniques. If future dizziness profiles overlap with the established profiles, the validity of these profiles will be strengthened. Differences, on the other hand, should lead to adjustment of the profiles, following international discussion to consolidate agreement. Once the dizziness profiles have been validated, older patients can be classified according these profiles as a first step in the diagnostic strategy. Within these profiles, it will be easier for an attending GP to decide whether and which further diagnostic steps to take. From a prospective to a prediction model for dizziness In our prospective cohort we have been the first to investigate the course of dizziness and dizziness-related impairment in older patients in general practice (Chapter 8). In this we found seven predictors for an unfavourable course. Although there is some evidence for several of these predictors (chronic dizziness, anxiety disorder, impaired mobility and the use of drugs), future research is needed to estimate the predictive value of these and possibly other predictors. Validation must be performed in older patients presenting with dizziness in general practice and, for optimal generalisation, preferably in other countries. The simple sum score (based on counting the number of predictors 200

14 present in a particular patient) and presented as prediction model, could be further developed to a robust prediction model. Multiple intervention trial? Based on our findings and in line with others 5;24;32;33, we believe that it would be interesting to reduce dizziness-related impairment and maybe dizziness itself by influencing treatable associated factors, such as the use of drugs, psychiatric disorders, hearing and/or mobility disabilities. However, future research is needed to ascertain whether and which interventions in these domains are effective in reducing the burden of dizziness in older patients. A multi-intervention randomised controlled trial, with interventions including medication reduction, non-drug treatment of anxiety/depressive disorders, hearing aids, and exercise and physical therapy to optimise mobility, is worthwhile. Implications for clinical practice Although comprehensive clinical guidance is not yet available, we offer general practitioners the outline of a functional approach to overcome diagnostic and therapeutic nihilism in the management of dizziness in older patients. In older patients presenting with dizziness life-threatening conditions are rare, mainly acute (like arrhythmia, stroke or intoxication) and almost never present with dizziness as a stand-alone symptom. In patients presenting with acute vertigo, nausea, vomiting and gait problems, indicating an acute vestibular syndrome, the HIT can discriminate between benign peripheral (such as vestibular neuritis) and central vestibular dysfunction (such as TIA or stroke). A positive test result increases the probability of peripheral vestibular dysfunction and a negative test result suggests a central lesion. Our results confirm that most older patients present with chronic dizziness (persistent and recurrent for more than six months) Firstly, with our profiles GPs can classify a patients dizziness and this allows GPs to taper the diagnostic process rather than performing a complete diagnostic work-up for dizziness. GPs might then, pending research on which tests are indicated, be able to sort out underlying conditions contributing to dizziness and, if possible, treat these conditions. Secondly, using the same easily obtainable clinical information and without knowing precisely the cause(s) of a patients dizziness, GPs can identify older patients with the poorest prognosis, in other words those who will suffer most in the future. In this group in particular, it might be most effective to reduce impairment with interventions focussing on modifiable factors influencing dizziness, such as mobility, hearing, anxiety and depression, and the use of drugs (especially FRID). 201

15 Appendix Diagnostic tests and characteristics used to evaluate dizziness in general practice Diagnostic Tests SR* GL** Delphi Panel Delphi int Test battery Case Control Profiles Prognostic DEMOGRAPHIC Age Sex Ethnicity Living in residential home Living alone Level of education PATIENT HISTORY Present dizziness symptoms (1) Lifestyle Smoking Alcohol intake (2) Medication (3) Poly-pharmacy Cardiovascular drugs Psychotropic drugs Antivertigo drugs Fall risk-increasing drugs (FRID) Medical history (4) Cardiovascular Hypertension Ischaemic heart disease Arrhythmia Locomotor Orthopaedic disorder Use of walking aid Neurologic CVA or TIA Vestibular/auditory ENT disease Use of hearing aid Visual Cataract and/or macular degeneration Use of glasses

16 Diagnostic Tests SR* GL** Delphi Panel Delphi int Test battery Case Control Profiles Prognostic Psychic Anxiety and/or depressive disorder Often unexplained complaints Other Thyroid dysfunction Diabetes * PHYSICAL EXAMINATION Cardiovascular System Pulse measurement (5) Pulse rate Pulse rhythm Blood pressure (6) Orthostatic hypotension (7) Orthostatic hypotension test Orthostatic test Alternative orthostatic test Auscultation of the heart (8) Auscultation of the carotids Screening for heart failure Locomotor system Orthopaedic screening of lower extremities (9) Instability at rest Impaired walking (without walking aid) Mobility hip/knee/ankle joints Toe and heel gait One-leg stance test Tandem gait (10) Performance-oriented mobility assessment Berg Balance Scale Timed up-and-go test Neurological System Neurological screening examination Tendon reflexes (11) Achilles tendon reflex Plantar reflex Peripheral neuropathy using monofilament ǂ (12)

17 Table Appendix, continued Diagnostic Tests SR* GL** Delphi Panel Delphi int Test battery Case Control Profiles Prognostic Vestibular System Dizziness questionnaires Otoscopy (13) Dix-Hallpike manoeuvre (14) Side-lying Head-shaking nystagmus test Head Impulse test (HIT) Head heave test Vibration-induced nystagmus Cold mini caloric test High-frequency oscillopsia test Hyperventilation-induced nystagmus test Positional nystagmus test Remaining Tests Visual acuity (15) Examination of the neck ADDITIONAL TESTS Cardiovascular System Electrocardiogram (16) Carotid sinus massage ECG-monitoring (17) Laboratory Tests Erythrocyte sedimentation rate Haemoglobin # (18) Non-fasting blood glucose # (19) Serum potassium level Serum sodium level Thyroid function Psychiatric Testing Psychiatric screening examination Patient Health Questionnaire ǂ (20) Somatoform disorder Anxiety and/or major depressive disorder Major depressive disorder Anxiety disorder Alcohol problem

18 Diagnostic Tests SR* GL** Delphi Panel Delphi int Test battery Case Control Profiles Prognostic Vestibular System Audiometry (21) Whispered voice test : included/recommended/significant; 0: excluded/not recommended/not significant; *SR: systematic review; **GL: practice guidelines on dizziness, syncope or vertigo; (1) (21): corresponds with the 21 diagnostic tests used in the test battery. All tests/characteristics included in the test battery were analysed in the profiles. All tests/ characteristics included except the dizziness characteristics were analysed in the case control. Only tests with no difference in results between patients with and without dizziness are presented; : test excluded by the panel although recommended by practice guidelines; 1 : idem as &, but finally included by us with consensus from the panel; ǂ: test in test battery not recommended by any practice guidelines on dizziness, syncope or vertigo; #test in test battery although guidelines question the value. 205

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