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Diagnostic data in clinical toxicology--should we use a Bayesian approach?

A number of toxidromes (toxicology syndromes) have been described for various poisonings and are promoted as a means of reaching a diagnosis in patients presenting with unknown poisonings. Many are based entirely on deductive reasoning from the known pharmacological effects of these drugs rather than on documented clinical experience. In this paper, we used our database, where we have recorded clinical signs on presentation in unselected poisonings to explore how clinical signs actually alter the odds of ingestion of different poisons. Many signs substantially altered the list of drugs likely to have been ingested. We found that the most important factor determining whether an unconscious patient had ingested a particular drug was how frequently that drug was taken generally (i.e., the a priori probability), rather than the presence of any particular physical sign. It also follows that our (or anyone else's) intuitive or deductive approach to diagnosis, derived from experience, will not necessarily be very useful at another place where predominantly different drugs are involved in poisoning. Our data were used to derive odds ratios as a measure of the strength of association of physical signs or investigations with ingested poisons. These can be used to develop simple diagnostic algorithms orflow charts to identify the most likely drugs ingested, or using more complicated programming, could also be used to calculate the precise probability of different drug-ingestion using Bayes' Theorem. The usefulness (i.e., external validity) of clinical research from other centers can also be determined.

Adolescent↗

A review of natural-rubber latex allergy in health care workers.

This brief review of natural-rubber latex (NRL) allergy in health care workers (HCWs) includes the definition of NRL allergy and data on its epidemiology, pathogenesis, diagnostic algorithm, management, long-term outcomes, economic impact, cost-effectiveness of changing facilities to a latex-free environment, and prevention. The data presented suggest that an individual with type I or type IV hypersensitivity to NRL should be able to continue to work in the workplace with careful evaluation and reasonable accommodations. Reducing exposure to latex is a safe and more economical alternative to complete removal of the individual from the place of employment. The use of low-allergen, nonpowdered NRL gloves substantially reduces airborne exposure to latex in most health care settings.

Allergens↗

Receiver operator characteristic (ROC) curves.

Receiver operator characteristic curves describe the trade-off between appropriate diagnoses of true disease and inappropriate positive diagnoses in healthy persons. ROC curves may be used to compare the accuracy of two or more tests, diagnostic algorithms, or the performance of diagnosticians.

Bacteriological Techniques↗

Ranking diagnostic protocols--a proposed process based on use of the nine-cell diagnostic decision matrix.

A process for ranking competing diagnostic protocols for a specific disease is presented. The process incorporates the basic principles of medical decision making, and provides for the consideration of equivocal test results as well as results for patients who have ill-defined or incompletely defined disease. It provides a means for developing an a priori optimization process prior to ranking competing diagnostic algorithms. Methods for transferring ranking information among populations with widely differing disease prevalences are given.

Clinical Laboratory Techniques↗

Prospective evaluation of unexplained syncope, dizziness, and falls among community-dwelling elderly adults.

BACKGROUND: Unexplained syncope, dizziness, and falls may present a difficult diagnostic challenge to primary care and emergency room physicians. The aim of this study was to evaluate a diagnostic algorithm in the assessment of a cohort of community-dwelling elderly people with symptoms of unexplained syncope, falls, or dizziness. METHODS: Fifty-four consecutive elderly patients (mean age + SD = 76.4 + 8.0 years, range 61-91) were assessed over a 12-month period. Presenting symptoms were syncope in 33 patients (61.1%), unexplained falls without loss of consciousness in 10 patients (18.5%), and dizziness without loss of consciousness in 11 (20.4%), and true vertigo in 2 patients (3.7%). Patients were assessed systematically using the algorithm, followed up until a diagnosis was made, and appropriate preventive therapy or advice given. RESULTS: Diagnoses were obtained in 41 patients (75.9%). Of the 33 patients with syncope, the cause was identified in 23 (69.7%) as follows: vasovagal in 12, arrhythmia in 5, hypotensive drugs in 3, orthostatic hypotension in 2, and major anxiety with hyperventilation in 1. The cause of syncope remained uncertain in 10 patients. Among the 10 patients with nonsyncopal falls, the cause was identified in 9 as follows: drop attacks with associated knee osteoarthritis or quadriceps muscle weakness in 3, orthostatic hypotension in 2, and single cases of cerebellar ataxia, Parkinson's disease, otologic vertigo, and vertebrobasilar insufficiency. Of 11 patients with dizziness, 4 had vasovagal syncope, 2 had orthostatic hypotension, 2 had otologic vertigo, one had carotid sinus syndrome, and the cause remained obscure in 2. Nineteen of the 41 patients (46.3%) had at least one other abnormality that was possibly contributory to their symptoms. Five of the 13 patients without a clearcut diagnosis had abnormalities of possible significance, including first-degree heart block with fascicular block in 2 patients and individual patients with severe hypertension, aortic valve disease, and vasodepressor carotid sinus hypersensitivity. CONCLUSION: A targeted, problem-oriented algorithm indicates the diagnosis in three quarters of elderly patients with unexplained syncope, falls, and dizziness.

Accidental Falls↗

Delirium among newly admitted postacute facility patients: prevalence, symptoms, and severity.

BACKGROUND: Delirium may persist for weeks or months, and discharging elderly patients quickly from acute care facilities is not uncommon. Therefore, the adverse impact of delirium on loss of independence may occur in the postacute setting rather than in the hospital. The purpose of this study is to describe the prevalence of delirium, delirium symptoms, and severity assessed at admission to postacute facilities. METHODS: Subjects were recruited from seven Boston-area skilled nursing facilities specializing in postacute care. Assessment instruments included the Mini-Mental Status Exam, Delirium Symptom Interview, Memorial Delirium Assessment Scale, and Confusion Assessment Method (CAM) Diagnostic Algorithm. Delirium status was categorized into four groups: full, two or more symptoms, one symptom, and no delirium. Descriptive statistics were calculated and chi-square analyses and an analysis-of-variance were used to examine delirium characteristics by delirium group. RESULTS: Among 2158 subjects, approximately 16% had full CAM-defined delirium at admission to the postacute facility. In addition, nearly 13% of the subjects had two or more symptoms of delirium, approximately 40% had one delirium symptom, and 32% had no symptoms of delirium. In a comparison of the group with no symptoms of delirium with that with CAM-defined delirium, there was a significant trend toward (a) older age, (b) lower scores on the Mini-Mental Status Exam, (c) more Delirium Symptom Interview symptoms, and (d) higher Memorial Delirium Assessment Scale Scores. CONCLUSIONS: Results indicate that 16% of admissions to postacute facilities have CAM-defined delirium, and over two thirds had at least one delirium symptom. It is not known whether or not postacute staff have the training necessary to detect or manage delirium. Managing delirium may require different strategies and techniques in a postacute setting, thereby requiring further research.

Aged↗

Characteristics associated with delirium persistence among newly admitted post-acute facility patients.

BACKGROUND: Delirium is costly, common, and may persist for weeks or months. Therefore, the adverse impact of delirium on loss of independence may occur in the post-acute setting rather than in the hospital. The purpose of this study is to describe the rate of delirium persistence and identify baseline patient characteristics that are associated with delirium persistence at 1 month among newly admitted post-acute facility patients who were admitted with delirium. METHODS: Patients were recruited from 4 Boston area skilled nursing facilities specializing in post-acute care (PAC). Assessment instruments included the Confusion Assessment Method Diagnostic Algorithm, the modified Delirium Symptom Interview, the Memorial Delirium Assessment Scale (MDAS), and the Blessed Dementia Rating Scale (BDRS). Multiple logistic regression analyses were used to identify patient characteristics associated with delirium persistence (at 1 month). RESULTS: Nearly 51% of the 85 delirious patients enrolled in this study had delirium at their 1-month follow-up assessment. Four patient factors associated with delirium persistence were identified: older age (> or =85 years), severe delirium at PAC admission (MDAS score >15), prehospital cognitive impairment based on proxy report [BDRS], and the presence of all 8 modified Delirium Symptom Interview symptoms at PAC admission. Our model has very good predictive power (area under the receiver operating characteristic = 0.85). CONCLUSIONS: Delirium is persistent in the post-acute setting. If verified in further research, the risk factors found in this study could be used to identify patients who are likely to have delirium after 1 month, and may prove useful in developing and targeting interventions of care.

Aged↗

Validation of postmortem interviews to ascertain selected causes of death in children.

In developing countries, diagnoses of diseases associated with deaths in children are frequently derived from retrospective maternal interviews. To determine the validity of this methodology, and to define sensitive and specific diagnostic algorithms, we compared symptoms and signs reported by mothers using structured questionnaires, with selected physician diagnoses for 164 deaths among hospitalized children on the Philippine island of Cebu. The 164 decreased children had 256 physician diagnoses of acute lower respiratory infections (ALRI) (100), diarrhoeas (92), measles (48), and neonatal tetanus cases (16). Forty-three per cent of children had multiple illnesses. An algorithm for tetanus (age at death less than or equal to 30 days with convulsion or spasm) was 100% sensitive, but specificity could not be estimated due to the small number of comparison neonatal deaths. An algorithm for measles (age greater than or equal to 120 days, with rash and fever for at least three days) had 98% sensitivity and 90% specificity. Diagnosis of ALRI was more difficult, cough and dyspnoea alone yielding 86% sensitivity but low specificity, whereas prolonged cough and dyspnoea provided 93% specificity but low sensitivity (41%). Diarrhoea diagnoses based on frequent loose or liquid stools had high sensitivity (78-84%) and specificity (79%), irrespective of whether the child died with diarrhoea alone or in combination with other illnesses. However, maternal reports of moderate/severe dehydration had low specificity. We conclude that, in this setting, verbal autopsies can diagnose major illnesses contributing to death in children with acceptable sensitivity and specificity.

Algorithms↗

Validation of the diagnosis of childhood morbidity using maternal health interviews.

The diagnosis of childhood illness by maternal health interview surveys is widely used to estimate the prevalence of childhood morbidity in developing countries. To determine the validity of interview-based diagnoses, and to define simple, sensitive and specific diagnostic algorithms, we compared symptoms and signs reported by mothers during structured interviews with physicians' diagnoses for 271 children on the Philippine island of Cebu. The 271 children had 318 physician diagnosed illnesses: 105 acute lower respiratory infections (ALRI), 121 diarrhoeas, 36 measles, 50 upper respiratory infections (URTI), 5 roseola infantums and one milaria rubria. An algorithm for measles (age greater than or equal to 120 days, rash and fever greater than or equal to 3 days and fading of rash) had a sensitivity and specificity of 94%. For ALRI an algorithm of cough, dysponea and fever had a sensitivity of 82%, but specificity was lower in comparison with URTI (58%) than with children who had no respiratory illness (79%). Inclusion of signs of respiratory distress (flaring of nostrils, intercostal retraction) raised the specificity to 83-84%, but reduced sensitivity to 68%. Diagnosis of diarrhoea based on frequent loose or liquid stools had a sensitivity of 95-97% and specificity of 80% in children with or without concomitant non-diarrhoeal illnesses. Addition of questions on numbers of stools (greater than or equal to 6 per day), and no signs of dehydration increased specificity to 95% but reduced the sensitivity to 84-86%. However, specific signs of dehydration were not well reported by the mothers.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Short stature and cardiovascular disease among men and women from two southeastern New England communities.

BACKGROUND: Short stature has been associated with an increased risk of coronary heart disease (CHD), although the reason for the association remains unclear. Data on the relation between stature and stroke is more limited. We examined the association between stature and CHD as well as between stature and stroke in men and women from two communities in southeastern New England. METHODS: Coronary heart disease and stroke events were abstracted from medical records between January 1980 and December 1991. An epidemiological diagnostic algorithm developed to measure CHD was used in the present analysis. Unadjusted relative risks (RR) and RR adjusted for age, smoking status, obesity, high-density lipoprotein (HDL) cholesterol <0.91 mmol/l, total cholesterol >6.21 mmol/l, hypertension, diabetes, education, and being foreign born were computed by gender-specific height categories separately for men (n = 2826) and women (n = 3741). RESULTS: A graded inverse association between stature and risk of CHD was observed among men which persisted after adjustment for confounders. Men >69.75 inches had an 83% lower risk of CHD compared with men < or = 65 inches. In addition, the tallest men had a 67% decreased risk of stroke compared with the shortest men. No significant relation between stature and CHD or stroke was observed among women. CONCLUSIONS: These data support the hypothesis that stature is inversely related to both risk of CHD and stroke at least among men. Factors which might explain this association remain to be determined.

Adolescent↗

BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression and rejection in a puzzling game.

We review BK-virus nephropathy (BKN) as a new complication that increasingly affects renal allografts and causes dysfunction. Since starting in 1996, we have seen 11 cases. Currently, the prevalence of BKN is 3% in our graft biopsies. The diagnosis can only be made histologically. The virus affects tubular epithelial cells that show characteristic intranuclear inclusion bodies. The major reason for impaired graft function and a possible way for viral particles to gain access to the blood via peritubular capillaries is necrosis of infected epithelial cells. BK-virus DNA in the plasma, which can be detected by PCR, is closely associated with nephropathy. BK-virus does not stimulate tubular MHC-class II expression as judged by immunofluorescence double labelling. The inflammatory response is inconsistent and the frequency of rejection episodes is not increased during disease. Clinical manifestation of viral nephropathy evolves in several stages. (i) Initial, asymptomatic and reversible activation of the virus, judged by the presence of inclusion bearing cells in the urine. (ii) High dose immunosuppressive drug regimens, often including tacrolimus. (iii) Tubular injury and viraemia as additional promoting conditions. BKN nephropathy was associated with graft loss in 45% of our patients. The remaining patients with persistent viral nephropathy showed renal dysfunction (serum creatinine levels on average 150% above baseline readings). Currently, no established antiviral therapy is available. We discuss attempts to lower immunosuppression as a means to control viral replication. We propose a diagnostic algorithm for screening and monitoring the disease.

Animals↗

Bacterial pneumonia in adult populations with human immunodeficiency virus (HIV) infection.

Recurrent bacterial pneumonia was recently added to the definition of the acquired immunodeficiency syndrome (AIDS), based on the observation that bacterial pneumonia rates have been increased in human immunodeficiency virus (HIV)-infected persons and are indicative of immunosuppression in this population. Nonetheless, risk factors for bacterial pneumonia among HIV-infected persons remain largely uninvestigated. Identification of risk factors that may be associated with bacterial pneumonia can guide development of future interventions and further clarify target groups for such interventions. From a methodological viewpoint, diagnostic algorithms need to be further standardized to provide comparable estimates of disease incidence. Epidemiologic studies will also need to address the effectiveness of chemoprophylaxis and vaccine interventions in HIV-infected populations. Since clinical trials will not be feasible for testing efficacy of interventions that are already recommended, observational data will be critically important in guiding clinical practice.

AIDS-Related Opportunistic Infections↗

Screening for peripheral arterial disease: the sensitivity, specificity, and predictive value of noninvasive tests in a defined population.

Large vessel peripheral arterial disease (LV-PAD) is a common condition that causes significant morbidity and disability. The authors evaluated the individual components of a comprehensive noninvasive vascular examination to identify the most sensitive and specific measurements for diagnosing LV-PAD. This cohort, initially screened between 1979 and 1981 in Rancho Bernardo, California, included 421 normal subjects and 63 subjects with LV-PAD. Segmental blood pressure ratios and flow velocities by Doppler ultrasound were used to define cases of LV-PAD. The sensitivity, specificity, positive predictive value, and negative predictive value of each individual component of the diagnostic algorithm were determined. Overall, measurements of posterior tibial flow showed the highest sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy. In addition, an absent or non-recordable posterior tibial peak forward flow, occurring in 96% of all limbs with isolated posterior tibial disease, or an ankle ratio < or = 0.8 considered in parallel yielded a test with sensitivity of 89%, specificity of 99%, positive predictive value of 90%, negative predictive value of 99%, and overall accuracy of 98%. These results indicate that the vast majority of LV-PAD cases can be detected with a single measurement using a handheld Doppler flowmeter employed at the ankle.

Adult↗

Protean manifestations of neonatal hyperinsulinism.

Endogenous hyperinsulinism is the leading cause of persistent hypoglycemia in children under one year of age. Classically, the symptoms of neonatal hypoglycemia have been referable to central nervous system dysfunction, with seizures described in nearly all patients. Our experience with eight neonates emphasizes the protean manifestations of this disease. One patient presented with a maternal history of diuretic use, and developed asymptomatic hyperinsulinism documented by provocative testing. The hyperinsulinism cleared after two weeks of medical therapy. This transient hyperinsulinism may have been secondary to use of a thiazide-type diuretic. A second patient presented, as a neonate, with a large abdominal mass but no seizure activity. Exploratory laparotomy revealed an 11 x 5 x 3 cm pancreatic tumor, which required splenectomy, 60% gastrectomy and duodenectomy for removal. Histologic examination demonstrated an insulin-secreting hamartoma. A third patient died suddenly without prior symptoms, and was found to have striking nesidioblastosis on pathologic examination. One infant presented with absence of the abdominal musculature (prune belly syndrome) and features of the Beck-with-Wiedeman syndrome, as well as profound hypoglycemia. Only three patients had seizures, and an additional patient had jitteriness. Pathologic diagnoses were: nesidioblastosis (n = 2); islet cell hyperplasia (n = 1); adenoma (n = 1); hamartoma (n = 1); transient hyperinsulinism (n = 1). One patient's pancreas showed areas of nesidioblastosis, islet cell hyperplasia, and a discrete adenoma in the region of the common bile duct. Careful diagnostic testing is essential in these patients, inasmuch as hypoglycemia is poorly tolerated by neonates and infants. Using the diagnostic algorithm presented here, all patients' endogenous hyperinsulinism was documented quickly and efficiently. Recognition of the broad spectrum of symptoms with which these patients may present is essential if serious neurologic sequelae are to be avoided.

Chlorthalidone↗

Labeling revisited: diagnoses in disguise?

The study examines 125 labels central to nursology used by practicing nurses to describe patients. Each nurse described the response pattern identified by each label, organizing and prioritizing its characteristics to produce a diagnostic algorithm. After work-peer affirmation of the chart's accuracy, the response pattern was renamed as a "syndrome." Predominant characteristics of each syndrome were analyzed. Nurses developed treatment protocols that they believed would reduce, control or "cure" defining characteristics. Field testing of these protocols demonstrated that conditions identified by labels (which normally lead to nurse avoidance) could be effectively treated when approached proactively. Some syndromes involved response patterns related to medical diagnosis or treatment, specific units in the hospital or the health care system itself. Nursology also includes less-than-ideal responses to circumstances that threaten personal well-being.

Algorithms↗

Technetium-99m pertechnetate and gallium-67 imaging in salivary gland disease.

Thirty-two patients with salivary gland tumors or sialadenitis were studied with Tc-99m pertechnetate and Ga-67 imaging and, in some instances, sialography. The diagnostic algorithm presented allows the correct categorization of the salivary gland pathology in the vast majority of patients. The patients were studied serially with Tc-99m pertechnetate, Ga-67 and in certain situations sialography (or CT-sialography). Use of the algorithm can distinguish benign salivary tumors from malignant tumors and malignant tumors from inflammatory disease. The limitations and pitfalls of interpretation are discussed.

Adult↗

The Diagnostic Interview Schedule for Children-Revised Version (DISC-R): III. Concurrent criterion validity.

OBJECTIVE: To examine the concurrent criterion validity of the Revised Diagnostic Interview Schedule for Children (DISC-R), a structured lay-administered instrument designed for use in community studies, under conditions designed to provide strict controls for information and method variance. METHOD: The DISC-R was compared with a semistructured clinical interview that covered a similar information base as the DISC-R, used standardized ratings to record symptom information, and, similar to the DISC-R, was scored by DSM-III-R-based computerized diagnostic algorithms. Subjects were 74 child and adolescent clinic attendees and their adult custodians. RESULTS: Overall, moderate levels of agreement were found between DISC-R and clinician-generated diagnoses; these findings were tempered, however, by the fact that the validation interview was less reliable than the DISC-R. CONCLUSIONS: Although these findings provide preliminary support for the use of the DISC-R, they cast some doubt on the adequacy of clinician-generated diagnoses as validation criteria and suggest that alternate approaches to the assessment of validation should be pursued.

Adolescent↗

Impaired but undiagnosed.

OBJECTIVE: To investigate the prevalence and outcomes of individuals with psychosocial impairment not meeting DSM-III-R criteria for any of 29 well-defined disorders and to suggest operational definitions for not otherwise specified (NOS) diagnoses and V codes. METHODS: Two-stage general population sampling resulted in 1,015 youths aged 9, 11, and 13 years being interviewed in the first wave of the Great Smoky Mountains Study. They were reinterviewed 1 year later using the Child and Adolescent Psychiatric Assessment. RESULTS: The weighted prevalence of sibling relational problems was found to be 1.4%. That of parent-child relational problems was 3.6% and that of relational problems NOS was 0.6%. The overall rate of symptomatic impairment was 9.4%. Across a variety of "caseness measures," those with symptomatic impairment proved to be more disturbed than those without either a diagnosis or impairment, and as disturbed as those with a diagnosis but without impairment. CONCLUSION: Children and adolescents who do not meet DSM-III-R criteria for any well-defined disorder but who have symptoms associated with psychosocial impairment should be regarded as suffering from a psychiatric disorder. It is suggested that researchers adopt this definition for the many NOS diagnoses included in the DSM nosology and implement it in their research diagnostic algorithms.

Adolescent↗