In what kind of clinical situation

What distinguishes risk-based conditions from non—risk-based conditions is the lack of dysfunction present in risk-based conditions for some patients meeting the diagnostic criteria. Typically, risk-based conditions are those for which overdiagnosis is a problem.

Schwartz a equates pathology with dysfunction, which is different than suboptimal or below-average function. Type 2 diabetes, for example, becomes a disease when dysfunction is present but is still a disease for many HbA1c levels i.

Risk-based conditions show how a condition can straddle the boundary between one and another typology category B and D. When diagnostic criteria lower the threshold by which a person is considered to have a disease, more people who are not diseased may be classified as being diseased, resulting in overdiagnosis and the medicalization of normal variation.

She thinks that medium or severe hypertension in itself is probably not a dysfunction. Schwartz considers these levels dysfunctional, in contrast to mild hypertension which he considers to not involve dysfunction. Because she is correct that blood pressure is not a direct measurement of the dysfunction i. Indeed, hypertension, as well as blood glucose levels, could be indications of disease, although they are also potentially pathogenic themselves such as with glucotoxicity or when blood pressure gets really high, as pointed out by Boorse [].

Nonetheless, it is possible that there is dysfunction not only in medium or severe hypertension but even in mild hypertension. The dysfunction may just not rise to the level of clinically apparent dysfunction.

There may still be dysfunction such as at the level of the cell or molecule , that is undetectable with current clinical and diagnostic tools. But as Boorse notes, although there may be reduced functional efficiency in mild hypertension, if this is not age-excessive, then it does not count as disease on the BST. In summary, conflation of risk for disease or potential indicators of dysfunction, such as some levels of blood pressure, with dysfunction itself, can result in erroneous attribution of disease, a point to which diagnostic criteria should be sensitive if they are to accurately characterize a condition.

Risk-based conditions are only one of several types of clinical conditions possible based on the interplay among symptomaticity, dysfunction, and meeting of diagnostic criteria. Preclinical disease is another. Another clinical condition for which risk for another disease or more severe disease plays a strong part involves mild, preclinical disease states for which diagnostic criteria for the disease are not met in contrast with risk-based conditions where diagnostic criteria are met but there is no dysfunction.

These other clinical conditions are categories C and G. Dysfunction is present, but not enough to cause symptoms. Because preclinical disease creates something of a penumbral state, diagnostic criteria for some diseases explicitly incorporate symptom-based criteria, without which the person does not have the disease. However, doing so is not always advisable depending on the disease.

In myasthenia gravis, for example, symptoms are helpful in reaching a diagnosis. In fact, a myasthenia gravis specialist, because of cost and other issues, may almost never encounter a patient tested for antibodies prior to entering the clinic with suspected myasthenia gravis Prof. Joseph Bergmans, personal communication. Yet to date no consensus group has promulgated diagnostic criteria requiring symptoms for myasthenia gravis.

This makes sense for a disease like myasthenia gravis where a pathognomonic feature is present—antibody positivity—because no patients who are antibody positive will lack the disease. Regarding AD, if AD were diagnosed solely on the basis of symptoms and not neuropathology, a person presenting with AD symptoms could not fall under category C.

This is because category C involves asymptomatic people with dysfunction who do not meet diagnostic criteria for a disease. Were AD's diagnostic criteria to include laboratory evidence of AD neuropathology, however, then an asymptomatic person with AD could fall under category C if they were to not meet all the diagnostic criteria. This could happen if the person were to possess AD pathology not detectable by current technology i. Importantly, this clinically unapparent dysfunction is not the same as risk for frank dysfunction.

It could increase such risk, however, in the same way as any disease could increase the risk for another disease. This clinically unapparent dysfunction is still disease though—disease that current diagnostic tools just have not caught up with yet.

For example, years ago a person with the Huntington disease expansion still had Huntington disease even if unaware of their carrier status and not yet symptomatic. A similar situation exists for familial AD, because people with such genetic mutations are virtually guaranteed to develop dementia, the symptomatic hallmark of AD Dubois et al.

Yet AD presents an even more intriguing test case for the typology than Huntington disease. This is because most cases of AD are of the sporadic type Dubois et al. Nonetheless, recently proposed research diagnostic criteria allow for an AD diagnosis based entirely on biomarker findings Dubois et al. Although these new diagnostic criteria are intended for research, some clinicians around the world do use biomarkers as an aid to diagnosis Frisoni et al.

This means some AD-diagnosed people could fall under category B or D, depending upon whether biological dysfunction is present. The implications of this are discussed next.

AD offers an example of how the typology can help understand factors important for research, treatment, diagnosis, and nosology. First, to know whether there is a theoretical disease present per the BST it is necessary to know the population distribution of the functional efficiency of a physiological part or process in a reference class Boorse, Taking the elderly as a reference class, the pathophysiological hallmarks of AD, whether at the symptomatic or presymptomatic stage, would only count as theoretical disease if they are not commonly found in the appropriate reference class.

For the purposes of this discussion I will assume this to be true, although given the high prevalence of AD pathology in individuals aged greater than 80 years Jack et al. AD was therefore a syndrome collection of symptoms. The presence of AD neuropathology was simply presumed Jack et al. Although autopsy can confirm an AD diagnosis, this is rarely done now given the availability of in vivo biomarkers previously validated against postmortem AD pathology.

Moreover, biomarker-based diagnostic criteria have recently been proposed for AD, enabling diagnosis independent of clinical symptoms, such as in the predementia phases. Brain biopsy is rarely performed to diagnose AD because it has low diagnostic yield—not only because it is too difficult and risky not least of which from general-anesthesia sequelae but because it is not sensitive and specific enough Venneti et al.

In the last few years, with the advent of more sensitive biomarkers specifically, those based on cerebrospinal fluid analysis and imaging, such as fluorodeoxyglucose positron emission tomography , a tension has sprung up between the clinical diagnostic criteria and newly promulgated research-based diagnostic criteria.

These criteria viewed AD no longer as a syndrome but rather as a clinical—biomarker entity. However, a new preclinical stage was defined that could be diagnosed mostly or entirely on the basis of biomarkers though in contrast to MCI and dementia such diagnoses were to be used for research purposes only as biomarkers continued to develop [ Jack et al. With the recognition that early treatment, even before clinical onset, could result in a greater chance to arrest the disease than with later treatment Langbaum et al.

This tension is borne out in different recommendations for research diagnostic criteria promulgated by AD research groups, such as the research framework of the NIA-AA Jack et al. The latest NIA-AA framework defines AD as a biological entity, solely by its pathophysiology as evidenced by biomarkers, without consideration of symptoms Jack et al.

This allows for a biomarker-based diagnosis in asymptomatic people. A publication Dubois et al. These developments in diagnostic criteria do more than change how AD is identified—they go to the heart of how AD is defined. Is AD a syndrome, a distinct type of neuropathology, or both? The distinction between a condition's diagnostic criteria and the definition of a condition is an important one, one the typology brings into sharp relief.

This is by virtue of the symptomatology and dysfunction factors, because whereas a condition's definition may in some cases coincide with current diagnostic criteria, this is not always so.

These cases of contested definitions such as with AD offer philosophically interesting and ethically important tests of whether biological dysfunction is more important than symptoms for defining a disease. Yet this can be problematic because AD pathophysiological processes do not always lead to dementia. In the terms of the typology, positive cases of AD i. Instead, they would be risk states. Although there are some benefits to separating the pathological features from the clinical features Jack et al.

Indeed, reconceptualizing AD as solely a biological entity privileges a disease approach instead of an illness approach. It could even result in a worry-type illness state characterized by anxiety over the putative certainty of developing dementia, compounded by the negative societal consequences of being labeled as having AD. By contrast, there could be benefits to conceiving AD solely as a biological entity. As mentioned, category C allows for a biomarker-based diagnosis of AD.

If an AD diagnosis depended on clinical symptoms, then a large number of asymptomatic people who have the pathophysiological defects of AD might not be considered for treatment because they would not be diagnosed.

This is particularly important given that the window for affecting the pathogenesis of AD via treatment may exist years before symptoms become apparent. Applied to the clinic, there are risks with this approach to diagnosis and treatment, however. This is especially true when the line between physiological and pathological changes is difficult to distinguish. For example, in cardiomyopathy, technological advances have resulted in identification of asymptomatic, nonhypertrophic, genotype-positive people.

Such individuals are at risk of being overdiagnosed because they are unlikely to become symptomatic or have deadly arrhythmias Quarta et al. With respect to AD, diagnosis not dependent upon clinical symptoms is also subject to overdiagnosis if there are people with the pathophysiological defects who do not go on to develop AD symptoms.

This could happen if the pathophysiological defects are normal signs of aging or if abnormal AD biomarkers are also present in old age, which in fact they are Vinters, Indeed, Alexopoulous and Kurz think there is practical validity in defining preclinical states of AD, such as by its effect on protective behaviors across the lifespan.

Moreover, the pathology associated with AD has been shown to not be due to aging-related mechanisms Nelson et al. These findings highlight that the pathophysiological deficits of AD can begin well ahead of clinical symptoms. While clinical dementia may sometimes be simply a product of normal aging, the dementia of AD is not. Several studies have shown that there are significant AD brain lesions in people at early stages of clinical cognitive symptoms reviewed in Vinters, The reason recent trials of AD therapies may have failed is because only symptomatic patients were enrolled, thus excluding the chance to arrest the disease by addressing the pathophysiological defects in their incipient stages when therapy might have been more effective Lyon, ; Langbaum et al.

How then should AD, or any other disease, be defined? Defined according to the BST on the basis of biological dysfunction, only biomarker-assessed neuropathology is needed for an AD diagnosis. But this does not mean that all diseases need to be recognized by clinical medicine Tresker, However, each disease presents its own set of considerations, which militates against cookie-cutter solutions.

Although whether a disease involves readily identifiable pathological signs might help, on its own this is insufficient to guide the setting of diagnostic criteria i. What is also needed is the use of normative considerations to dictate what criteria are used Tresker, As shown with AD, understanding a condition's place in the typology may sensitize one to whether it may be possible to diagnose well before symptoms appear.

For example, the beta-cell dysfunction and insulin resistance of type 2 diabetes have been hypothesized to exist years before glucose levels become elevated Kahn, Type 2 diabetes and other conditions can also stress the line between disease and risk. For example, Vickers, Basch, and Kattan propose unambiguous lesions as distinguishing disease from risk.

They give the example of a torn aorta. However, this should not be taken to mean that type 2 diabetes could not have unambiguous lesions. In the case of a torn aorta the lesion is at the level of the organ. With type 2 diabetes unambiguous lesions could be at the level of the cell or lower. Other risk states, listed roughly in order of likelihood of resulting in dementia, include an asymptomatic person with some biomarker evidence of AD pathology, to such a person with more biomarker evidence, to a patient in the prodromal stage without biomarker evidence, to a prodromal patient with biomarker evidence, to a person with presymptomatic AD i.

The nature of the biomarker evidence results in different amounts of risk Jack et al. A key difference between the NIA-AA research framework and the IWG criteria is that whereas the former views asymptomatic but AD-biomarker—positive people as at risk for developing AD symptoms , the latter views these people as being at risk for developing AD Jack et al. Jack et al. The key to differentiating when conditions such as AD should be viewed as risk instead of disease may be the confidence with which diagnostic methods can unequivocally identify if and when the asymptomatic cases will turn into symptomatic cases and the prodromal cases will turn into manifest cases e.

High confidence might call for viewing as disease whereas low confidence might call for viewing as risk. However, this is easier said than done and the typology cannot directly help in this regard. A direct consequence of the BST's conception of disease is its ability to distinguish cases where there is a disparity between the diagnostic criteria for a disease and the dysfunction putatively underlying the disease.

Recognition of this can contribute to robust research programs that lead to revised diagnostic criteria for diseases. It can also affect nosology, leading to the splitting of one disease into many, or the unification of previously unrelated diseases e. The result can be earlier diagnosis and more timely, effective interventions. As technology advances, the ability to probe into the pathophysiological defects of many diseases may improve, such that they can be treated, even if asymptomatic and representing just mild dysfunction.

Such proactive intervention well ahead of when a person becomes symptomatic may also make it possible to modify the disease process and hopefully avert the development of the disease, or mitigate certain aspects of its presentation. This is now true for rheumatoid arthritis, for which disease-modifying drugs are available. For other diseases, such as atherosclerosis and type 2 diabetes, early lifestyle interventions exercise, diet have been shown to prevent their development or progression.

For diseases in which there are neither cures nor effective treatments, such as Huntington disease, the value of knowing in advance whether one has the disease may be less than for diseases in which therapeutic interventions are available.

Nonetheless, in Huntington disease detectable pathophysiological changes are present one to two decades prior to clinical diagnosis Paulsen et al. Research trials aimed at preventive therapeutics can thus still benefit from this lag between the beginning of pathophysiology and the appearance of symptoms. The existence of risk-based conditions—category B—which in some cases medicalize individual variation, could lead to less diagnosis of disease if recognized as not involving dysfunction , whereas for category C diseases it could lead to more diagnosis if diagnostic criteria are changed to allow for laboratory evidence of pathology.

Understanding the nature of the categories could provide a conceptual toolkit for nosology and the setting of diagnostic criteria. This can lead to approaches that are directly relevant to patients. For example, patients falling within certain categories could be provided direct indicators of disease rather than treating risk factors for disease.

Similarly, measurement of intima-media thickness affected both physician and patient behaviors, leading to better treatment behaviors Korcarz et al. Making visible direct indicators of disease can in a way turn a sign into a symptom i. As a classificatory system, the typology has several beneficial features: it is simple, containing only eight categories; exhausts the conditions clinicians encounter; has mutually exclusive categories; is flexible, able to accommodate new conditions and diseases; and is compatible with and can be integrated with other classification systems, such as the International Statistical Classification of Diseases and Related Health Problems ICD.

There are, however, some limitations. Although the typology can be conceptualized as a framework to help medical researchers, philosophers, bioethicists, and others think through considerations surrounding risk, disease, and the classification of medical conditions, the typology might only make explicit approaches that are already utilized, such as direct application of the notion of risk to classify a condition as a disease or not. The typology has not been empirically tested for its usefulness.

Furthermore, the typology is silent on etiology, although it is fully compatible with classification systems that rely on etiology. Ultimately, a key argument of this paper and one for which a typology is not even needed , is that normative considerations—although absent on the conception of disease used here—do guide how disease is recognized in clinical practice.

Here the typology may be useful by showing how normative considerations determine whether biological dysfunction or symptoms are more important for a condition's diagnostic criteria. Tensions between the relative importance of the typology's factors for a given condition can result in category reassignment, which can have enormous implications for how a condition is diagnosed, reimbursed by insurance, and viewed by patients.

This is especially true when clinicians, patients, or researchers hold implicit biases against certain categories with respect to how conditions falling under those categories should be managed as a class. But you may need more tests to find out which specific fungal infection you have. Learn more about laboratory tests, reference ranges, and understanding results. If you are diagnosed with a bacterial infection, you will probably be prescribed antibiotics. It's important to take your medicine as prescribed, even if your symptoms are mild.

This can prevent your infection from getting worse and causing serious complications. The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health. Gram Stain. What is a Gram stain? The two categories cause different types of infections: Gram-positive infections include methicillin-resistant Staphylococcus aureus MRSA , strep infections , and toxic shock.

Gram-negative infections include salmonella , pneumonia , urinary tract infections , and gonorrhea. Other names: Gram's stain. What is it used for? Why do I need a Gram stain? What happens during a Gram stain? Wound sample: A provider will use a special swab to collect a sample from the site of your wound. Blood test: A provider will take a sample of blood from a vein in your arm.

Urine test: You will provide a sterile sample of urine in a cup, as instructed by your health care provider. Throat culture: Your health care provider will insert a special swab into your mouth to take a sample from the back of the throat and tonsils.

Your health care provider will ask you to cough up sputum into a special cup, or a special swab may be used to take a sample from your nose.

Will I need to do anything to prepare for the test? You don't need any special preparations for a Gram stain. Are there any risks to the test? There is no risk to having a swab, sputum, or urine test. What do the results mean? New faces of an old pathogen: emergence and spread of multidrug-resistant Streptococcus pneumoniae.

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Combination of flucloxacillin and gentamicin inhibits toxic shock syndrome toxin 1 production by Staphylococcus aureus in both logarithmic and stationary phases of growth. Clindamycin in the treatment of streptococcal and staphylococcal toxic shock syndromes. Issue Section:. Download all slides. Comments 0. Add comment Close comment form modal. I agree to the terms and conditions. You must accept the terms and conditions. Add comment Cancel.

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