广西少数民族地区不同文化程度人群国际HIV相关性痴呆量表诊断界值的探索性研究

目的 以简易智能量表(MMSE)为金标准,确定国际HIV相关性痴呆量表(IHDS)在广西少数民族地区不同文化程度人群中的诊断界值,并评价IHDS在相应界值下的真实性和可靠性.方法 从广西少数民族地区筛选出血清阳性的HIV感染者200例,对每名感染者采用随机、同期、盲法测试MMSE和IHDS;以MMSE测试结果为金标准,通过ROC曲线确定IHDS在少数民族地区不同文化程度人群中的HIV相关性痴呆诊断界值,并评价特定界值下IHDS的灵敏度、特异度及内部一致性系数.结果 当不考虑感染者的文化程度差异时,少数民族地区人群的IHDS诊断界值为8.25,此时IHDS的灵敏度为0.925、特异度为0.731、Kappa为0.477 (P＜ 0.001).当考虑感染者的文化程度差异时,不同文化程度人群的IHDS诊断界值有所不同:中学或以上文化人群的IHDS诊断界值为8.25,此时灵敏度为0.917、特异度为0.895、Kappa为0.722(P＜0.001);小学文化人群的IHDS诊断界值为7.25,灵敏度为0.875、特异度为0.661、Kappa为0.372 (P＜0.001).结论 广西少数民族地区人群的IHDS诊断界值低于国际推荐的诊断界值水平(IHDS≤10分);在该地区运用IHDS筛查HIV相关性痴呆时,应根据当地HIV感染者的文化程度差异制订出适用于不同文化层次HIV感染者的IHDS诊断界值.     

Testing for publication bias in diagnostic meta‐analysis: a simulation study

The present study investigates the performance of several statistical tests to detect publication bias in diagnostic meta‐analysis by means of simulation. While bivariate models should be used to pool data from primary studies in diagnostic meta‐analysis, univariate measures of diagnostic accuracy are preferable for the purpose of detecting publication bias. In contrast to earlier research, which focused solely on the diagnostic odds ratio or its logarithm ( ln ω), the tests are combined with four different univariate measures of diagnostic accuracy. For each combination of test and univariate measure, both type I error rate and statistical power are examined under diverse conditions. The results indicate that tests based on linear regression or rank correlation cannot be recommended in diagnostic meta‐analysis, because type I error rates are either inflated or power is too low, irrespective of the applied univariate measure. In contrast, the combination of trim and fill and ln ω has non‐inflated or only slightly inflated type I error rates and medium to high power, even under extreme circumstances (at least when the number of studies per meta‐analysis is large enough). Therefore, we recommend the application of trim and fill combined with ln ω to detect funnel plot asymmetry in diagnostic meta‐analysis. Copyright © 2014 John Wiley & Sons, Ltd.     

Local diagnostic reference levels for angiographic and fluoroscopic procedures: Australian practice

Although diagnostic and interventional fluoroscopic procedures are amongst the highest dose examinations performed in radiology, these procedures currently lack established national diagnostic reference levels (DRLs) in Australia. In this absence, local diagnostic reference levels (LDRLs) are proposed for a wide range of diagnostic and interventional angiographic and fluoroscopic procedures based upon data collected from 11,000 examinations, performed over a 2.5 year period at a major Australian public, teaching hospital. Each procedure type assessed included a minimum of 50 cases. LDRLs were defined for each procedure in terms of the 75th percentile of the dose area product and median fluoroscopic times have also been provided. The detailed categories of procedures used in this study may inform the Australian Radiation Protection and Nuclear Safety Agency when establishing national DRLs for angiographic and fluoroscopic procedures. Until national DRLs for these complex procedures are available, these LDRLs may provide guidance to other institutions on achievable dose levels.     

Neurogenic switching: a hypothesis for a mechanism for shifting the site of inflammation in allergy and chemical sensitivity.

Neurogenic switching is proposed as a hypothesis for a mechanism by which a stimulus at one site can lead to inflammation at a distant site. Neurogenic inflammation occurs when substance P and other neuropeptides released from sensory neurons produce an inflammatory response, whereas immunogenic inflammation results from the binding of antigen to antibody or leukocyte receptors. There is a crossover mechanism between these two forms of inflammation. Neurogenic switching is proposed to result when a sensory impulse from a site of activation is rerouted via the central nervous system to a distant location to produce neurogenic inflammation at the second location. Neurogenic switching is a possible explanation for systemic anaphylaxis, in which inoculation of the skin or gut with antigen produces systemic symptoms involving the respiratory and circulatory systems, and an experimental model of anaphylaxis is consistent with this hypothesis. Food-allergy-iducing asthma, urticaria, arthritis, and fibromyalgia are other possible examples of neurogenic switching. Neurogenic switching provides a mechanism to explain how allergens, infectious agents, irritants, and possibly emotional stress can exacerbate conditions such as migraine, asthma, and arthritis. Because neurogenic inflammation is known to be triggered by chemical exposures, it may play a role in the sick building syndrome and the multiple chemical sensitivity syndrome. Thus neurogenic switching would explain how the respiratory irritants lead to symptoms at other sites in these disorders.     

On sample size for sensitivity and specificity in prospective diagnostic accuracy studies

The design of a study of disease screening tests may be based on hypothesis tests for the sensitivity and specificity of the tests. The case-control study requires knowledge of the disease status of patients at the time of enrollment. This may not be possible in a prospective setting, when the gold standard is obtained subsequent to the initial screening and the number of diseased individuals is random and can not be fixed by design. Several ad hoc procedures for determining the total sample size are commonly used by practitioners, for example, the prevalence inflation method. The properties of these methods are not well understood. We develop a formal method for sample size and power calculations based on the unconditional power properties of the test statistics. The approach provides novel insights into the behaviour of the commonly used methods. We find that the ad hoc prevalence inflation method may serve as a useful approximation to our rigorous framework for sample size determination in the prospective set-up. The design of a large population-based study of mammography for breast cancer screening illustrates the key issues.     

Estimation of adult patient doses for common diagnostic X-ray examinations in Wad-madani,Sudan: derivation of local diagnostic reference levels

The objectives of this study were to estimate patient dose in some common diagnostic X-ray examinations. Radiation doses were estimated for 307 patients in six public hospitals comprising 7 X-ray units in Wad-madani, Sudan. Entrance surface air kerma (ESAK) was estimated in a three step protocol: First, X-ray unit output Y(d) was measured at a distance, d for different peak tube voltages and tube loadings (mAs). Next, incident air kerma (K_i) was calculated from Y(d) using inverse square law combined with patient exposure factors. ESAK was calculated from K_i using backscatter factor, B. Mean ESAK values are comparable to those reported in other countries and are below reference dose levels. The estimated mean ESAK values are: 0.3, 2.2, 2.2, 2.9, 2.8, 3.1, and 7.5 mGy for chest PA, Skull AP/PA, Skull LAT, Abdomen, Pelvis AP, Lumbar Spine AP and Lumbar Spine LAT examinations, respectively. The results are used for dose optimization, and to propose local diagnostic reference levels.     

Foot-and-mouth disease non-structural protein serology in cattle: use of a Bayesian framework to estimate diagnostic sensitivity and specificity of six ELISA tests and true prevalence in the field

The diagnostic performance of six foot-and-mouth disease (FMD) assays for detection of antibodies to the non-structural proteins (NSP) of the FMD virus (FMDV) was estimated using a Bayesian analysis on field sera from cattle of unknown infection status originating from post-FMDV outbreak situations in Israel and Zimbabwe. Estimations of the disease prevalence in both populations were also obtained. The diagnostic sensitivity estimates did not differ between both field studies, although overall Bayesian estimates were markedly higher than those previously reported based on sera from comparable experimentally infected (vaccinated) cattle populations. All NSP-based assays demonstrated a lower diagnostic specificity when applied to the Zimbabwean sera compared to both published specificities and similar Bayesian specificity estimates derived for the Israeli dataset. In Israel, the disease prevalence was estimated at 23.9% (95% credibility interval: 19.5-28.8%), whereas 65.4% (59.0-72.5%) was found in Zimbabwe. The need for reliable diagnostic test performance estimates and the benefits of Bayesian analysis in obtaining them are also addressed.     

Accounting for within-patient correlation in assessing relative sensitivity of an adjunctive diagnostic test: application to lung cancer

We address the comparison of results between two diagnostic tests applied multiple times to the same subjects. The estimand of interest is the sensitivity of the combined test (primary and adjunct) relative to a primary test. Analytical methods are first described that assume independence between the multiple observations within a subject. In order to account for the within-subject correlation introduced by the multiple measurements, analytical approaches for correlated, categorical response data are described. In the discussion of these methods, we pay particular attention to the presence of a structural zero which results from the decision rule for the combination of diagnostic tests. In a simulation study, we compare the finite sample performances of all analytical approaches in terms of confidence interval coverage rates and median lengths. Our methods are cast in the context of a diagnostic bronchoscopy technology for the detection of lung cancer.     

Cause-of-death statements in Ceylon: A study in levels of diagnostic reporting*

The author presents a critical discussion of the current system of registration of deaths in Ceylon, pointing out the difficulties inherent in collecting and analysing data relating to causes of death in a country where many of the cause-of-death statements are made by lay registars whose knowledge of modern medical terminology is slight or non-existent. He suggests various ways in which the present system might be improved, stressing particularly the need for continuous scrutiny of the Sinhalese or Tamil terms commonly used in reporting causes of death in rural areas and for the preparation of simple instructions to lay registrars regarding a system of priorities to be followed in selecting the symptoms to report as a result of interrogation of the relatives notifying the death.     

Testing taste sensitivity and aversion in very young children: development of a procedure

Taste perception in 45 3- to 6-year-old children was tested using procedures specifically designed for this age group. Detection thresholds for sucrose and urea were measured by a staircase method and aversion to urea was assessed hedonically, using drawings of facial expressions. All children understood the task and could perform the necessary actions. A subgroup of 20 children participated in a second measurement after a mean interval of 9.5 days: there was a satisfactory degree of stability between the sessions. However, a third measurement, on a subgroup of 13 children after a somewhat longer interval, showed a marked drop in the stability of the urea thresholds. This drop was thought to arise from a decrease in the children's motivation, leading to increased distractibility. Mean threshold estimates were 31 mmol/l for sucrose detection, 59 mmol/l for urea detection and 134 mmol/l for urea aversion, but some children were extremely sensitive to the taste of urea. The findings show that it is possible to study taste perception in very young children if their age is taken into consideration in developing the test procedure. Valid data can be obtained if the procedures are short, easy to understand and intrinsically motivating.     

Radiation dose in interventional cardiology procedures: urgent need for monitoring dose and establishing diagnostic reference levels

The use of fluoroscopy in interventional cardiology procedures may expose patients to levels of radiation that manifest in unintended outcomes. Such outcomes may include skin injury and cancer. Currently, there is limited understanding of the magnitude of dose administered in an individual procedure. Canada does not have a formal policy for monitoring and recording the radiation dose administered to patients. This article reviews existing American, European and international policies for both monitoring administered radiation dose and patient follow-up. As a subsequent focus, this article presents the process for setting benchmarks for optimizing administered dose in the Hamilton Health Sciences Heart Investigation Unit.     

Children with moderately elevated blood lead levels: a role for other diagnostic tests?

In this study we examined potential limitations of relying exclusively on blood lead (BPb) levels to evaluate children with moderately elevated BPb levels (1.21-2.12 micromol/l, or 25-44 microg/dl).We tested the following hypotheses: 1) such children without elevated erythrocyte protoporphyrin (EP) levels (>=0.62 micromol/l or >/= 35 microg/dl) are unlikely to respond to a chelating agent with a brisk urinary Pb diuresis; 2) those with elevated EP levels, but low hematologic indices consistent with iron deficiency, are also unlikely to respond to a chelating agent with a robust urinary Pb diuresis; and 3) those with elevated EP levels and iron sufficiency are more likely to respond to a chelating agent. To test these hypotheses, we performed retrospective analyses of the relationships between EP concentrations, hematologic indices, and urinary Pb excretion ratios (uPbr) in moderately Pb-poisoned children undergoing the CaNa2EDTA lead mobilization test (Pb-MT). Data from 122 children were available. Urinary Pb excretion was limited in children with an EP <0.62 micromol/l (<35 microg/dl); only 5% (1/21) of Pb-MTs were positive (uPbr >=0.6). In children with an EP >=0.62 micromol/l, low hematologic indices, such as a mean corpuscular hemoglobin (MCH) <23 pg, were associated with relatively little Pb excretion (0/14 positive Pb-MTs). In contrast, 32% (28/87) of Pb-MTs were positive in children with an EP >/= 0.62 micromol/l and iron sufficiency (p<0.01 by chi-square comparison between groups with EP >/= 0.62 micromol/l and either MCH <23 pg or MCH >/= 23 pg). We conclude that only a minority of moderately Pb-poisoned children will demonstrate enhanced urinary Pb excretion in response to chelation therapy. Some of the predicted nonresponders can be readily identified by adding the EP and complete blood count to the panel of tests performed.     

Test-retest reproducibility of the relative dose response for vitamin A status in Guatemalan adults: issues of diagnostic sensitivity

The relative dose response (RDR) test has been used as a functional measure of whole-body stores of vitamin A in humans. We have examined the reproducibility of the RDR procedure in a population of Guatemalan adult subjects who would be expected to show a moderate prevalence of hypovitaminosis A. Fifty-one subjects were administered a standard RDR test, and the plasma samples were analyzed for retinol, tocopherol, retinol binding protein (RBP) and prealbumin (PAL). Thirty-four of the subjects underwent repeat RDR tests 7 d later. Plasma levels in fasted subjects were as follows: retinol, 1.35 +/- 0.30 mumol/L; RBP, 37.8 +/- 7.7 mg/L; PAL, 187.0 +/- 39.0 mg/L; and tocopherol, 16.6 +/- 6.2 mumol/L. RDRs ranged from -35.2% to +63.1%, with a mean of 2.6 +/- 10.4%. Overall, we observed poor within-subject reproducibility of the RDR procedure whether expressed numerically or by diagnostic classification. Moreover, in contrast to previous studies in children, we observed fewer positive RDR tests than would be expected for the population studied. Nevertheless, the mean RDR was inversely proportional to fasting retinol levels, thus confirming the validity of the biological basis of the RDR procedure in humans. Because of high intra-individual variability with this test, investigators should be cautious when using the RDR procedure in serial studies to monitor the efficacy of therapeutic interventions or subject compliance to dietary regimens.     

Pyrimethamine sensitivity in Plasmodium falciparum: determination in vitro by a modified 48-hour test

Four strains of Plasmodium falciparum recently isolated in culture were assessed in vitro for their response to pyrimethamine. A simple modified 48-hour test was used, which showed two strains to be sensitive to the drug in vitro, while the other two were resistant at a very high level. In the two strains for which relevant clinical information was available the in vivo response to pyrimethamine was corroborated by the in vitro findings. This modified 48-hour test is thus useful for determining patterns of drug sensitivity in laboratory-adapted strains, and would be a valuable asset if found to be equally applicable under field conditions.