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The relationship between bone mineral density and fracture risk.

Osteoporosis is a disorder characterized by low bone density and impaired bone strength which is an important risk factor for fracture in older adults. The diagnosis of osteoporosis in postmenopausal women is now based on bone density testing by dual energy x-ray absorptiometry but not other methodologies. However, a specific but arbitrary diagnostic threshold must be distinguished from a strategy to assess fracture risk. In untreated postmenopausal women and older men, bone density is an important, but not the only, determinant for fracture risk. Combining bone density measurements with other independent and validated risk factors for fracture provides a much more accurate assessment of an individual patient's risk for fracture than does bone density alone. The most important of these other risk factors are age and prior fracture history. Clinical guidelines will move away from recommending treatment at specific T scores toward intervention thresholds based on absolute fracture risk. By basing who to treat on fracture probability, therapy can be targeted to those patients who would receive the greatest benefit.

Absorptiometry, Photon↗

An update on the diagnosis of osteoporosis.

In 1994 the World Health Organization (WHO) proposed guidelines for the diagnosis of osteoporosis based on measurement of bone mineral density. These guidelines have been widely used for epidemiologic studies, clinical research, and treatment strategies. This update reviews the recent literature that has highlighted the strengths and weaknesses of diagnostic thresholds.

Absorptiometry, Photon↗

Recurrent brief depression: a new subtype of affective disorder.

This paper presents the diagnostic criteria for a new subtype of affective disorder, recurrent brief depression (RBD). Data from a prospective longitudinal cohort of young adults from the general population of Zurich, Switzerland, showed that a substantial proportion met all of the criteria for major depression in current diagnostic systems except duration. The validity of the subtype of RBD was examined according to clinical manifestations, severity, longitudinal course, and family history. RBD was found to be similar to major depressive disorder (MDD) on most of the indicators of validity including symptomatology, association with somatic and psychiatric disorders, age at onset, family history, longitudinal course and levels of impairment, except duration of depressive episodes. This suggests that RBD constitutes a valid subtype of affective disorder. The major implications of these findings are that both recurrence and duration should be considered in developing diagnostic thresholds for depression and in assessing the severity of affective disorders.

Cohort Studies↗

Sex differences in the lifetime prevalence of depression: does varying the diagnostic criteria reduce the female/male ratio?

Most studies report the lifetime prevalence of major depressive disorder to be higher among women than men. One possible explanation is that this finding is the result of the diagnostic criteria used, in particular the inclusion of criterion symptoms associated with depressed mood. The number of criterion symptoms required for a diagnosis were varied and applied to 2163 first-degree relatives of affectively disordered probands of the NIMH Collaborative Study of the Psychobiology of Depression. Results indicated that differences between men and women in number of symptoms reported could not account for the difference in rates of depression. Women had a greater number of associated symptoms only at higher symptom levels, suggesting an excess of women only above a diagnostic threshold. Thus, findings supported a true difference in rates of major depressive disorder rather than a general trend for women to remember or report more criterion symptoms.

Adult↗

Fat plane radiological signs in wrist and elbow trauma.

With most elbow or wrist injuries, if fractures are not evident, they are probably nonexistent. But in a small percentage of cases, these signs serve to lower diagnostic thresholds. Of the four fat plane signs reviewed, the posterior fat pad sign and the navicular fat stripe seem to be more valuable than the supinator and pronator quadratus signs. However, each is useful in its own way. Although the clinical appearance of the extremity may dictate the same initial treatment whether or not a fracture is found, early identification of more subtle fractures will avoid delay of definitive treatment and provide a better estimation of healing time. None of these signs alone is completely reliable; they should be used as adjuncts in fracture diagnosis. Finally, no sign is specific to one type of fracture, although one or two types of occult fractures are most commonly identified on supplementary views when such signs are positive.

Elbow Joint↗

Reference values for SphygmoCor measurements in South Africans of African ancestry.

BACKGROUND: Measurements of blood pressure (BP) together with applanation tonometry at the radial and femoral arteries allow for reproducible assessments of various indexes of arterial stiffness, including peripheral (PP(p)) and central (PP(c)) pulse pressures, peripheral (AI(p)) and central (AI(c)) augmentation indexes, and aortic pulse wave velocity (PWV). In the absence of an outcome-driven and ethnicity-specific reference frame, we defined preliminary diagnostic thresholds for subjects of African descent living in Africa, using the distributional characteristics of these hemodynamic measurements. METHODS: We randomly recruited 347 subjects from a South African population of African origins. The PP(p) was the average difference between systolic and diastolic BP measured five times consecutively at one home visit. For measurement of PP(c), AI(p), AI(c), and PWV, we used a high-fidelity micromanometer interfaced with a laptop computer running the SphygmoCor software. For analyses we selected 185 subjects without hypertension, diabetes, and previous or concomitant cardiovascular disease. RESULTS: Mean age (33.5 years) was similar in 77 men and 108 women. The PP(p), PP(c), AI(p), AI(c), and PWV significantly increased with age. The 95th prediction bands of this relation at age 30 years, approximated to 70 mm Hg for PP(p), 50 mm Hg for PP(c), 100% for AI(p), 40% for AI(c), and 8.0 m/sec for PWV. The aforementioned thresholds would need adjustment by approximately 2.5 mm Hg, 4.0 mm Hg, 10%, 6%, and 1.0 m/sec, respectively, for each decade that age differs from 30 years. CONCLUSIONS: Pending validation in prospective outcome-based studies 70 mm Hg for PP(p), 50 mm Hg for PP(c), 100% for AI(p), 40% for AI(c), and 8.0 m/sec might be considered as preliminary thresholds to diagnose increased arterial stiffness in young adult subjects of African descent.

Adolescent↗

Correlation between cardiovascular disease and diabetes mellitus: current concepts.

Individuals exhibiting precursor symptoms of diabetes mellitus or reaching diagnostic thresholds for diabetes are at increased risk of death due to cardiovascular disease (CVD). Moreover, patients with diabetes alone, as well as those who have diabetes paired with established CVD, remain undertreated for cardiovascular risk factors. The clear correlation between these disease processes has led many to speculate that they share common pathogenetic processes. Recent research has made it increasingly evident that the core metabolic defects that mark diabetes, including impaired glucose tolerance, insulin resistance, and proinflammatory and prothrombotic states, lead to endothelial dysfunction and accelerate atherogenesis. Moreover, increases in sympathetic tone with diabetes are associated with changes in cardiac and vascular function that lead to hypertension, left ventricular dysfunction, and cardiac autonomic neuropathy; such changes set the stage for arrhythmia, silent infarction, and sudden death. Furthermore, diabetes-related changes in metabolic and autonomic functioning, as well as increases in inflammatory and thrombotic signaling, compromise the ability of myocardial and vascular tissue to remodel after injury and to recover and sustain functionality. Because potentiation of atherogenesis and cardiac dysfunction occurs in the presence of early diabetic symptoms as well as in the established disease, early implementation of strategies to reduce cardiovascular risk factors and to slow diabetes progression may help to improve long-term outcomes for at-risk individuals. Such interventions may include well-established treatments for hypertension and dyslipidemia, diet improvements, weight loss, and exercise as well as novel pharmacologic interventions aimed at newly identified therapeutic targets.

Arterial Occlusive Diseases↗

Glucocorticoid-induced osteoporosis.

Glucocorticoids are important drugs in the treatment of variety diseases, but long-term period use can lead to various adverse effects, including osteoporosis. Glucocorticoid-induced osteoporosis is mainly caused by inhibition of osteoblastic bone formation, which results not only in decreased bone mineral density, but reduction of bone strength by trabecular thinning in bone microstructures. The evidence suggests that daily oral glucocorticoid doses higher than 5 mg prednisolone or equivalent increase the risk of fracture within 3-6 months after the start of therapy. High-dose inhaled glucocorticoids may also increase fracture risk. The diagnostic procedures are similar to those for primary osteoporosis, but the diagnostic threshold for bone mineral density needs to be higher than that for primary osteoporosis. Treatment with vitamin D, calcitonin, sex hormone replacement, and bisphosphonates has been shown to be effective, and bisphosphonates have been demonstrated to be the most valuable drugs for glucocorticoid-induced osteoporosis. There are several lines of evidence indicating that they are effective in preventing and treating low bone mineral density and in reducing fracture risk.

Animals↗

Influence of physical exercise and relationship with biochemical variables of NT-pro-brain natriuretic peptide and ischemia modified albumin.

BACKGROUND: The diagnostic approach and the clinical management of patients presenting with suspected acute coronary syndrome or cardiac dysfunction are as yet challenging. Although ischemia modified albumin (IMA) and natriuretic peptides were recently proposed for detection of myocardial ischemia and cardiac dysfunction, little information is available on preanalytical and metabolic sources of variability of these markers. METHODS: To establish the influence of a regular endurance training and the relationship with conventional biochemical variables, NT-pro-brain natriuretic peptide (NT-proBNP) and IMA were assayed, along with cardiac troponin T (cTnT), lactate dehydrogenase (LDH), creatine kinase (CK), creatinine and albumin, in 35 sedentary healthy individuals and 50 male professional road cyclists, 12-24 h following the last demanding training session. RESULTS: Athletes displayed higher values of both LDH (299+/-61 vs. 257+/-36 U/l, P=0.002) and CK (184+/-123 vs. 115+/-74 U/l, P=0.011), and slightly lower concentrations of creatinine (82+/-12 vs. 87+/-9 micromol/l, P=0.044). No athlete or sedentary control displayed cTnT concentrations exceeding the lower sensitivity limit of the assay. As compared to the sedentary controls, main IMA concentration was increased in athletes (100+/-13 vs. 94+/-6 KU/l, P=0.035), whereas that of NT-proBNP appeared significantly decreased (2.8+/-1.6 vs. 4.3+/-34, P=0.005). The percentage of subjects displaying values exceeding the upper reference limit for the IMA assay was significantly different between athletes and sedentary controls (50% vs. 7%; P<0.001). Pearson correlation analysis revealed an inverse association between IMA and albumin in both athletes (r=-0.640; P<0.001) and sedentary controls (r=-0.583; P=0.001). CONCLUSIONS: Results of our investigation indicate that a demanding and regular aerobic training regimen, though able to trigger skeletal muscle sufferance, is not associated with any biochemical sign of severe and irreversible chronic cardiac involvement. Moreover, we suggest the adoption of specific IMA diagnostic thresholds following patients' stratification according to serum albumin concentration and physical activity.

Adult↗

Diastolic heart failure. Paroxysmal or chronic?

Heart failure with preserved systolic function is considered by some to be synonymous with diastolic heart failure (DHF). Although recent epidemiological studies have suggested that DHF constitutes 30-50% of all patients with heart failure, many cardiologists dealing with ambulant heart failure patients on a daily basis find that the vast majority of heart failure patients have systolic dysfunction. What could be the reasons for this? Referral bias and varying diagnostic thresholds and interpretation of results could be one important reason. Heart failure with preserved systolic function comprises a heterogeneous group of conditions: whilst some patients may truly have DHF, others may have heart failure due to subtle systolic dysfunction (noted on tissue Doppler imaging of the left ventricular long axis). Other patients actually have pulmonary disease, obesity or ischaemic heart disease, and have their symptoms attributed to 'diastolic heart failure' on the basis of 'abnormal' mitral diastolic flow indices that may, in fact, simply reflect aging. True DHF may be much less prevalent than suggested. A further possibility is that heart failure in patients with diastolic dysfunction might be paroxysmal rather than chronic. This group of patients may present predominantly to acute units like accident and emergency, coronary care units and intensive care units and are, therefore unlikely to figure prominently in the usual outpatient population of chronic systolic left ventricular dysfunction.

Acute Disease↗

A brief review of the use and utility of growth hormone stimulation testing in the NCGS: do we need to do provocative GH testing?

True growth hormone deficiency (GHD) in childhood, while rare, has major clinical consequences. GHD is often associated with other pituitary hormone deficiencies, so these children may require multiple hormonal replacement and close clinical follow-up to optimize their outcome. Growth hormone stimulation testing (GHST), as currently conducted, is not a reliable diagnostic tool. Both changes in growth hormone assay methodologies and increases in the diagnostic threshold contribute to the incorrect labeling of a substantial proportion of normal children as having idiopathic GHD. Fortunately, newer imaging technologies and laboratory tests form a more rational basis to diagnose true GHD. The use of GHST among GH-naive subjects (<20 years of age) enrolled in the National Cooperative Growth Study has declined over the past two decades, from a high of 89% between 1987 and 1989 to only 52% in 2002. Given that GH stimulation testing does not meaningfully aid in distinguishing those few children with true growth hormone deficiency from the much more common short normal child and that alternatives are now available, it is time to discontinue the routine use of GHST in children.

Body Height↗

Impact of atrial fibrillation on the diagnostic performance of B-type natriuretic peptide concentration in dyspneic patients: an analysis from the breathing not properly multinational study.

OBJECTIVES: This study was designed to assess the diagnostic performance of B-type natriuretic peptide (BNP) in the diagnosis of acute congestive heart failure (CHF) in patients with permanent/paroxysmal atrial fibrillation (AF) presenting with acute dyspnea. BACKGROUND: It is unknown to what extent AF affects the diagnostic performance of BNP in patients presenting with acute dyspnea. METHODS: We studied 1,431 patients drawn from a cohort of patients (n = 1,586) with acute dyspnea who had BNP levels measured on arrival. Patients were prospectively classified according to the presence or absence of permanent/paroxysmal AF. RESULTS: In total, 292 patients had permanent/paroxysmal AF. In patients without HF, permanent/paroxysmal AF was associated with significantly higher BNP levels (p = 0.001). Conversely, in patients with HF, BNP levels did not differ significantly between patients with and without AF (p = 0.533). A BNP cutoff value of 100 pg/ml had a specificity of 40% and 79% for the diagnosis of acute HF in patients with and without AF, respectively. The areas under the receiver-operating characteristic curves were 0.84 (95% confidence interval 0.78 to 0.89) and 0.91 (95% confidence interval 0.89 to 0.93) for patients with and without AF, respectively. CONCLUSIONS: In patients without, but not in those with HF, the presence of AF is associated with higher circulating BNP levels, suggesting that a higher diagnostic threshold should be used in patients with AF.

Acute Disease↗

The role of the external genitalia score (EGS) in evaluation of disorders of sex development.

OBJECTIVE: To investigate the utility of the External Genitalia Score (EGS) in the diagnosis of disorders of sex development (DSD) and decision-making regarding gender assignment in affected patients. METHODS: A retrospective cohort study was conducted, enrolling 114 DSD patients aged <2 years (88 reared as males, 26 reared as females) treated at our hospital between April 2005 and June 2023, alongside 40 hypospadias patients aged <2 years who underwent surgery at our institution from January to July 2023. Demographic data (age) and EGS assessments of external genitalia were collected for all participants. Statistical analyses included independent samples t-tests, Mann-Whitney U tests and Receiver Operating Characteristic (ROC) curve analysis. Specifically, EGS scores were compared between the hypospadias group and the male-reared subgroup of the DSD cohort; additionally, EGS scores were contrasted between male-reared and female-reared DSD subgroups. RESULTS: The mean age was 20.3 months in the hypospadias group, 17.9 months in the male-reared DSD group, and 18.8 months in the female-reared DSD group. EGS ranged from 5.5 to 11.5 (median 10.5) in the hypospadias group and from 1 to 12 (median 4.75) in the DSD group. ROC curve analysis was performed to compare EGS scores between the hypospadias group and the male-reared DSD subgroup. The optimal diagnostic threshold was determined by maximizing the Youden index (sensitivity + specificity - 1), which balances sensitivity and specificity. A cut-off value of &#x2264;8.50 was identified as indicative of DSD; clinically, patients with an EGS score <9 should be prioritized for DSD screening. Further comparison between male-reared and female-reared DSD subgroups yielded a threshold of 4.00. Clinically, an EGS score &#x2264;4 may suggest a preference for female gender assignment. DISCUSSION: The EGS scale is a reliable, valid, and clinically feasible tool for characterizing external genitalia in DSD patients. An EGS score of 9 can serve as an indicator for initiating detailed sex development evaluation in hypospadias patients. While gender assignment in DSD is a complex, multifactorial process, EGS scores showed a significant association with the sex of rearing in our cohort. In settings where major determinants are balanced, EGS may serve as an adjunctive descriptive parameter rather than a standalone decision-making tool.

Humans↗

Gender differences in blood velocities across carotid stenoses.

OBJECTIVES: Carotid duplex scanning is the standard test for documenting carotid disease. Carotid endarterectomy effectively reduces stroke in selected patients with carotid artery disease. Data from large national randomized trials suggest that the benefits of CEA may be gender dependent. Because many diagnoses are made and treatment is based on the results of carotid duplex ultrasound scanning alone, it is important to determine whether different diagnostic thresholds should be used in men and women. The purpose of this study was 2-fold: to examine whether there is an overall gender difference in carotid velocity at similar arteriographic stenoses, and to determine whether there are significant differences at clinically relevant thresholds of disease. METHODS: A database of 938 carotid arteriogram entries was established prospectively, with accompanying measurements of peak systolic velocity (PSV) and end-diastolic velocity (EDV). The percent of internal carotid artery stenosis seen on arteriograms was calculated according to criteria from the North American Symptomatic Carotid Endarterectomy Trial. Analyses were made in 536 carotid arteries in men and 402 carotid arteries in women. In addition, the single most diseased artery per patient was analyzed by gender. PSV and EDV were averaged for data subsets according to 10% intervals of internal carotid artery stenoses. Velocity for each interval was compared between men and women with the Student t test. Receiver operator characteristic curves were developed to define optimal duplex criteria for 60% and 70% stenosis. RESULTS: For all intervals, PSV and EDV averaged 9% and 6% higher, respectively, in women than in men. Significant gender differences existed between PSV and EDV for 60% and 70% stenosis (P = .03). When a single vessel per patient was analyzed these observations persisted, but lost significance for PSV at 60% stenosis (P = .18). Receiver operator characteristic curves at 90% sensitivity demonstrated that optimal PSV for 60% stenosis was 160 cm/s and 180 cm/s, and for 70% stenosis was 185 cm/s and 202 cm/s, in male and female patients, respectively. CONCLUSIONS: Women have higher carotid blood flow velocity than men do. Gender differences exist, and are notably different at clinically relevant thresholds for intervention. These data indicate that different criteria should be used for interpreting carotid velocity profiles in women than in men, and have potentially important implications for patient care.

Adult↗

Liability to substance use disorders: 2. A measurement approach.

Liabilities to complex disorders, discussed in the accompanying paper, present difficulties in measurement related to the arbitrariness of diagnostic threshold definitions and problems with discrimination between trait values, especially within the 'normal' individuals. The inability to quantitatively estimate the risk for a disorder, such as substance use disorders (SUD), is an obstacle for studying etiological (e.g. genetic) mechanisms and developing efficient prevention and treatment measures. Based on the concept of common liability to SUD, this paper delineates an application of the longitudinal family/high-risk design and item response theory to the development of a continuous index of liability. The method has been tested in both simulation study and empirical data. The approach described affords the opportunity to quantitatively estimate the risk for SUD at an early age and before any drug exposure. This method is also applicable to measuring liabilities to other complex disorders, especially those with relatively late onset.

Algorithms↗

A rapid method for mass screening for parkinsonism.

Epidemiology studies of parkinsonism employ a variety of techniques for unbiased sampling of populations. No current method permits mass screening of all subjects in a population for parkinsonism by movement disorders specialists. We developed and piloted a new approach to facilitate accurate and efficient screening of large populations for diagnosis of parkinsonism and provide data on sensitivity and specificity. We evaluated 2081 welders referred for medical-legal screening. Subjects were video taped using a standardized protocol, and videos were rated on the Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3). A "video rater" viewed video tapes and entered ratings through a web-based database. An "in-person" examiner performed a UPDRS3 examination in a randomly selected subgroup of 48 workers drawn from the 2081. We developed quantitative diagnostic criteria for parkinsonism that established minimum diagnostic thresholds based upon UPDRS3 scores and compared these criteria with diagnosis by an in-person examiner. Specificity of these criteria compared to in-person examination was 91-100% but sensitivity was 56%. A threshold UPDRS3 score greater than nine provided 100% sensitivity and 81% specificity. Liberal criteria identified 266 (13.1%) subjects with probable parkinsonism and 220 (10.8%) subjects with definite parkinsonism. Conservative criteria identified 260 (12.8%) with probable parkinsonism and 122 (6%) with definite parkinsonism. Our screening method permits rapid assessment of parkinsonian signs. An absolute UPDRS3 score greater than nine provided the best combination of sensitivity and specificity for the diagnosis of parkinsonism, while quantitative exam-based criteria for cardinal parkinsonian signs maximized specificity. Parkinsonism as diagnosed by our criteria was common in this group of welders.

Female↗

Prevalence of depression in congestive heart failure.

Patients with congestive heart failure had higher scores than control subjects using a case-finding instrument for depression; such patients also were more likely to exceed the diagnostic threshold for depression with this instrument. Identification and treatment of depressed CHF patients may significantly improve level of functioning in these patients.

Adult↗

Impaired growth and risk of fetal death: is the tenth percentile the appropriate standard?

OBJECTIVE: Our purpose was to determine whether the 10th percentile of birth weight for gestational age is appropriate to identify fetuses at risk of death associated with impaired growth. STUDY DESIGN: All live births recorded in Virginia from Jan. 1, 1991, through Dec. 31, 1993, were examined. Percentile growth curves were constructed, and fetal, neonatal, and perinatal mortality rates were calculated for births within various percentile intervals. RESULTS: Significantly elevated fetal mortality was found for birth weights through the 15th percentile. The odds ratio for fetal mortality relative to the baseline for births < or = 5th percentile was 5.6, for the 5th through the 10th percentile 2.8, and for the 10th through the 15th percentile 1.9. These were all significant. CONCLUSION: Fetuses with birth weights between the 10th and 15th percentiles are at a significantly increased risk for fetal death. Therefore the use of the 15th percentile as a diagnostic threshold for the identification of the fetus at increased risk associated with impaired growth is recommended.

Birth Weight↗