Verification, implementation and harmonization of automated chemiluminescent immunoassays for MPO- and PR3-ANCA detection.

OBJECTIVES: Antineutrophil cytoplasmic antibody (ANCA) testing assists clinicians diagnose ANCA-associated vasculitis (AAV). We aimed to verify and harmonize chemiluminescent immunoassays for the detection of myeloperoxidase (MPO)- and proteinase 3 (PR3)-ANCA. METHODS: An in-house ELISA, a capture ELISA, and a chemiluminescent assay QUANTA Flash on a BIO-FLASH analyzer were used to detect MPO- and PR3-ANCA in sera from 39 patients with AAV, 55 patients with various non-AAV, and 66 patients with connective tissue diseases. The results of the assays were evaluated, and their clinical performance was assessed. The precision and linearity of the QUANTA Flash assays were determined, and likelihood ratios (LRs) for AAV at diagnosis were calculated. RESULTS: The precision and linearity of the QUANTA Flash assays were confirmed. Overall agreement between 97.5 and 98.8 % and Cohen's kappa coefficients between 0.861 and 0.947 were observed for the results of the QUANTA Flash assays and ELISAs. The diagnostic sensitivity, specificity, and ROC analysis of the assays for AAV were statistically similar (in-house ELISA 89.7 %, 95.0 %, and 0.937; capture ELISA 92.3 %, 98.3 %, and 0.939; and QUANTA Flash 89.7 %, 95.9 %, and 0.972). For the QUANTA Flash assay results, the interval-specific LRs for AAV at diagnosis were: 0-8 CU had LR 0.08, 8-29 CU had LR 1.03, 29-121 CU had LR 7.76, 121-191 CU had LR 12.4, and >191 CU had LR ∞. CONCLUSIONS: The QUANTA Flash MPO and PR3 assays provide precise and consistent results and have comparable clinical utility for AAV. The calculated LRs were consistent with published LRs, confirming the utility of LRs for harmonization of ANCA results.

Post-test diagnostic accuracy measures under tree ordering of disease classes.

The medical field commonly employs post-test measures such as predictive values and likelihood ratios to assess diagnostic accuracy. Predictive values, including positive and negative values (PPV and NPV), indicate the probability that individuals have a target health condition based on test results. On the other hand, likelihood ratios, including positive and negative ratios (LR+ and LR- respectively), compare the probability of a particular test result between the diseased and non-diseased groups. While predictive values are useful in evaluating diagnostic test accuracy in populations with varying disease prevalence, likelihood ratios provide a direct link between pre-test and post-test probabilities in specific patients. In this study, we introduce and analyze a new approach called generalized predictive values and likelihood ratios, using a tree ordering of disease classes. We evaluate the effectiveness of these methods through simulation studies and illustrate their use with real data on lung cancer.

Diagnostic accuracy of antineutrophil cytoplasmic antibodies (ANCA) in predicting relapses of ANCA-associated vasculitis: systematic review and meta-analysis.

Relapse in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is associated with significant morbidity and mortality. Utility of ANCA for prediction of relapses is still controversial. PubMed/MEDLINE, Scopus, and WebOfScience were searched, screened and confirmed for inclusion [PROSPERO No: CRD42020220308]. Studies measuring serial ANCA by ELISA or indirect immunofluorescence (IF), reporting relapses with sufficient data to calculate sensitivity and specificity were included. Diagnostic odds ratio (OR), sensitivity, specificity and likelihood ratios (LR) were synthesized using a bivariate mixed-effect regression model. Sub-group analysis included a comparison between ELISA and IIF, anti-myeloperoxidase (MPO) and -proteinase 3(PR3), and type of rise in ANCA. For meta-analysis of survival outcomes, hazard ratios were synthesized using a random-effect model. QUADAS-2 was used for assessing quality of studies, I2 statistic for heterogeneity Begg's test for publication bias. 2946 abstracts and 43 full-texts were reviewed to identify 26 eligible studies that included 2623 patients with AAV and 848 relapses. Overall heterogeneity was high [I2 = 99%] and the overall risk of bias was low to moderate. ANCA positivity by either ELISA or immunofluorescence for predicting relapse of AAV had a sensitivity of 0.70(95% CI 0.58-0.81), specificity of 0.66(0.55-0.76), positive LR of 2.1(1.6-42.7) and negative LR of 0.44(0.30-0.60). ELISA performed marginally better [OR: 5(3-7)] than IIF [OR: 4(2-9)] with similar sensitivity, specificity, PLR and NLR. The area under the curve for PR3 was 0.74(0.7-0.77), while that for MPO was not computed as the number of eligible studies was only three. In the survival analysis, the hazard ratio for relapse was 3.11(1.7-5.65). The meta-analysis shows modest accuracy of ANCA in predicting relapses of ANCA vasculitis and supports the use of serial ANCA monitoring as a biomarker for relapse.

Validity of the Paediatric Canadian Triage Acuity Scale in a Tertiary Hospital: An Analysis of Severity Markers' Variability.

With the increasing influx of patients and frequent overcrowding, the adoption of a valid triage system, capable of distinguishing patients who need urgent care, from those who can wait safely is paramount. Hence, the aim of this study is to evaluate the validity of the Paediatric Canadian Triage and Acuity Scale (PaedCTAS) in a Portuguese tertiary hospital. Furthermore, we aim to study the performance and appropriateness of the different surrogate severity markers to validate triage. This is a retrospective study considering all visits to the hospital's Paediatric Emergency Department (PED) between 2014 and 2019. This study considers cut-offs on all triage levels for dichotomization in order to calculate validity measures e.g. sensitivity, specificity and likelihood ratios, ROC curves; using hospital admission, admission to intensive care and the use of resources as outcomes/markers of severity. Over the study period there were 0.2% visits triaged as Level 1, 5.7% as Level 2, 39.4% as Level 3, 50.5% as Level 4, 4.2% as Level 5, from a total of 452,815 PED visits. The area under ROC curve was 0.96, 0.71, 0.76, 0.78, 0.59 for the surrogate markers: "Admitted to intensive care"; "Admitted to intermediate care"; "Admitted to hospital"; "Investigations performed in the PED" and "Uses PED resources", respectively. The association found between triage levels and the surrogate markers of severity suggests that the PedCTAS is highly valid. Different surrogate outcome markers convey different degrees of severity, hence different degrees of urgency. Therefore, the cut-offs to calculate validation measures and the thresholds of such measures should be chosen accordingly.

Pairwise relatedness testing in the context of inbreeding: expectation and variance of the likelihood ratio.

In this paper we investigate various effects of inbreeding on the likelihood ratio (LR) in forensic kinship testing. The basic setup of such testing involves formulating two competing hypotheses, in the form of pedigrees, describing the relationship between the individuals. The likelihood of each hypothesis is computed given the available genetic data, and a conclusion is reached if the ratio of these exceeds some pre-determined threshold. An important aspect of this approach is that the hypotheses are usually not exhaustive: The true relationship may differ from both of the stated pedigrees. It is well known that this may introduce bias in the test results. Previous work has established formulas for the expected value and variance of the LR, given the two competing hypotheses and the true relationship. However, the proposed method only handles cases without inbreeding. In this paper we extend these results to all possible pairwise relationships. The key ingredient is formulating the hypotheses in terms of Jacquard coefficients instead of the more restricted Cotterman coefficients. While the latter describe the relatedness between outbred individuals, the more general Jacquard coefficients allow any level of inbreeding. Our approach also enables scrutiny of another frequently overlooked source of LR bias, namely background inbreeding. This ubiquitous phenomenon is usually ignored in forensic kinship computations, due to lack of adequate methods and software. By leveraging recent work on pedigrees with inbred founders, we show how background inbreeding can be modeled as a continuous variable, providing easy-to-interpret results in specific cases. For example, we show that if true siblings are subjected to a test for parent-offspring, moderate levels of background inbreeding are expected to inflate the LR by more than 50%.

Evaluating Mixture Solution™- rapid and non-MCMC probabilistic mixture analysis.

We compare DNA mixture analysis via DNAˑVIEW® Mixture Solution™ and the current combined probability of inclusion (CPI) method of the South African Police Service (SAPS). South Africa has a high incidence of property-related crimes and sexual offences and consequently a great deal of low-template (LT-DNA) forensic DNA mixture casework and a perpetual backlog. A range of casework and laboratory-prepared sexual assault mixtures with initial male DNA amounts varying from about 2 to 200 cells were analysed to evaluate the benefits of a continuous model program. Unfortunately CPI methods are nearly useless for LT-DNA cases because of dropout-common from a mixture contribution of fewer than 20 or 30 cells. We further argue that proposed CPI elaborations to circumvent dropout lack supporting research or even explanation. Mixture Solution models mixture data as continuous rather than binary, with a mathematically coherent ("probabilistic") model which incorporates dropout and other phenomena realistically. Much more information is thereby utilised resulting in applicability to more cases (7 or fewer contributor cells suffice), stronger evidence against a suspect who is a mixture contributor and stronger evidence to absolve a non-contributor. Mixture Solution incidentally provides information which, along with rfu data, allows estimating contributions in terms of number of cells, which is a useful perspective. The method of calculation is explained.

Translation and validation of an epilepsy-screening questionnaire in three Nigerian languages.

OBJECTIVE: We describe the development, translation and validation of epilepsy-screening questionnaires in the three most popular Nigerian languages: Hausa, Igbo and Yoruba. METHODS: A 9-item epilepsy-screening questionnaire was developed by modifying previously validated English language questionnaires. Separate multilingual experts forward- and back-translated them to the three target languages. Translations were discussed with fieldworkers and community members for ethnolinguistic acceptability and comprehension. We used an unmatched affected-case versus unaffected-control design for the pilot study. Cases were people with epilepsy attending the tertiary hospitals where these languages are spoken. The controls were relatives of cases or people attending for other medical conditions. An affirmative response to any of the nine questions amounted to a positive screen for epilepsy. RESULTS: We recruited 153 (75 cases and 78 controls) people for the Hausa version, 106 (45 cases and 61 controls) for Igbo and 153 (66 cases and 87 controls) for the Yoruba. The sensitivity and specificity of the questionnaire were: Hausa (97.3% and 88.5%), Igbo (91.1% and 88.5%) and Yoruba (93.9% and 86.7%). The three versions reliably indicated epilepsy with positive predictive values of 85.9% (Hausa), 85.4% (Igbo) and 87.3% (Yoruba) and reliably excluded epilepsy with negative predictive values of 97.1% (Hausa), 93.1% (Igbo) and 95.1% (Yoruba). Positive likelihood ratios were all greater than one. CONCLUSIONS: Validated epilepsy screening questionnaires are now available for the three languages to be used for community-based epilepsy survey in Nigeria. The translation and validation process are discussed to facilitate usage and development for other languages in sub-Saharan Africa.

Diagnostic modalities to determine ventriculoperitoneal shunt malfunction: A systematic review and meta-analysis.

BACKGROUND: Ventriculoperitoneal (VP) shunt malfunction is an emergency. Timely diagnosis can be challenging because shunt malfunction often presents with symptoms mimicking other common pediatric conditions. METHODS: We performed a systematic review and meta-analysis to determine which commonly used imaging modalities; Magnetic resonance imaging (MRI), Computed Tomography (CT), X-ray Shunt series or Optic Nerve Sheath Diameter (ONSD) ultrasound, are superior in evaluating shunt malfunction. INCLUSION CRITERIA: patients less than 21 years old with symptoms of shunt malfunction. We calculated the pooled sensitivity, specificity, Likelihood Ratios (LR+, LR-) using a random-effects model. RESULTS: Eight studies were included encompassing 1906 patients with a prevalence of VP shunt malfunction of (29.3%). Shunt series: sensitivity (14%-53%), specificity (99%), LR+ (23.2), and LR- (0.47-0.87). CT scan: sensitivity (53%-100%), specificity (27%-98%), LR+ (1.34-22.87), LR- (0.37). MRI: sensitivity (57%), specificity (93%), LR+ (7.66), and LR- (0.49). ONSD: sensitivity (64%), specificity (22%-68%), LR+ (4.4-8.7), LR- (0.93). A positive shunt series, CT scan, MRI, or ONSD has a post-test probability of (23%-84%). A normal shunt series, CT scan, MRI, or ONSD results in a post-test probability of (7%-31%). A positive shunt series results in a post-test probability of 80%, which is equivalent to the post-test probability of CT scan (23-84%) and MRI (83%). CONCLUSION: Despite the low sensitivity, a positive shunt series obviates the need for further imaging studies. Prompt referral for neurosurgical intervention is recommended. A negative shunt series or any result (positive or negative) from CT, MRI, or ONSD will still require an emergent neurosurgical referral.

Concordance of 3 alternative teratogenicity assays with results from corresponding in vivo embryo-fetal development studies: Final report from the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) DruSafe working group 2.

An IQ DruSafe working group evaluated the concordance of 3 alternative teratogenicity assays (rat whole embryo culture, rWEC; zebrafish embryo culture, ZEC; and murine embryonic stem cells, mESC) with findings from rat or rabbit embryo-fetal development (EFD) studies. Data for 90 individual compounds from 9 companies were entered into a database. In vivo findings were deemed positive if malformations or embryo-fetal lethality were reported in either species. Each company used their own criteria for deciding whether the alternative assay predicted the in vivo findings. Standard concordance parameters were calculated, positive and negative predictive values (PPV and NPV) were adjusted for the aggregate portfolio prevalence of positive compounds (established by a survey of participating companies), and positive and negative likelihood ratios (LR+ and iLR-) were calculated. Of the 3 assays, only rWEC data were robustly predictive, particularly for negative predictions (NPVadj = 92%). However, both LR+ (4.92) and iLR- (4.72) were statistically significant for the rWEC assay. When analyzed separately for rats, the NPVadj and iLR-values for the rWEC assay increased to 96% and 9.75, respectively. These data suggest that a negative rWEC outcome could defer or replace a rat EFD study in certain regulatory settings.

The limitations of kinship determinations using STR data in ill-defined populations.

The likelihood ratio (LR) method is commonly used to determine kinship in civil, criminal, or forensic cases. For the past 15 years, our research group has also applied LR to ancient STR data and obtained kinship results for collections of graves or necropolises. Although we were able to reconstruct large genealogies, some pairs of individuals showed ambiguous results. Second-degree relationships, half-sibling pairs for example, were often inconsistent with detected first-degree relationships, such as parent/child or brother/sister pairs. We therefore set about providing empirical estimations of the error rates for the LR method in living populations with STR allelic diversities comparable to that of the ancient populations we had previously studied. We collected biological samples in the field in North-Eastern Siberia and West Africa and studied more than 800 pairs of STR profiles from individuals with known relationships. Because commercial STR panels were constructed for specific regions (namely Europe and North America), their allelic makeup showed a significant deficit in diversity when compared to European populations, replicating a situation often faced in ancient DNA studies. We assessed the capacity of the LR method to confirm known relationships (effectiveness) and its capacity to detect those relationships (reliability). Concerns over the effectiveness of LR determinations are mostly an issue in forensic studies, while the reliability of the detection of kinship is an issue for the study of necropolises or other large gatherings of unidentified individuals, such as disaster victims or mass graves. We show that the application of LR to both test populations highlights specific issues (both false positives and false negatives) that prevent the confirmation of second-degree kinship or even full siblingship in small populations. Up to 29% of detected full sibling relationships were either overestimated half-sibling relationships or underestimated parent-offspring relationships. The error rate for detected half-sibling relationships was even higher, reaching 41%. Only parent-offspring pairs were reliably detected or confirmed. This implies that, in populations that are small, ill-defined, or for which the STR loci analyzed are inappropriate, an examiner might not be able to distinguish a pair of full siblings from a pair of half-siblings. Furthermore, half-sibling pairs might be overlooked altogether, an issue that is exacerbated by the common confusion, in many languages and cultures, between half-siblings and full siblings. Consequently, in the study of ancient populations, human remains of unknown origins, or poorly surveyed modern populations, we recommend a conservative approach to kinship determined by LR. Next-generation sequencing data should be used when possible, but the costs and technology involved might be prohibitive. Therefore, in potentially contentious situations or cases lacking sufficient external information, uniparental markers should be analyzed: ideally, complete mitochondrial genomes and Y-chromosome haplotypes (STR, SNP, and/or sequencing).

Compbdt: an R program to compare two binary diagnostic tests subject to a paired design.

BACKGROUND: The comparison of the performance of two binary diagnostic tests is an important topic in Clinical Medicine. The most frequent type of sample design to compare two binary diagnostic tests is the paired design. This design consists of applying the two binary diagnostic tests to all of the individuals in a random sample, where the disease status of each individual is known through the application of a gold standard. This article presents an R program to compare parameters of two binary tests subject to a paired design. RESULTS: The "compbdt" program estimates the sensitivity and the specificity, the likelihood ratios and the predictive values of each diagnostic test applying the confidence intervals with the best asymptotic performance. The program compares the sensitivities and specificities of the two diagnostic tests simultaneously, as well as the likelihood ratios and the predictive values, applying the global hypothesis tests with the best performance in terms of type I error and power. When the global hypothesis test is significant, the causes of the significance are investigated solving the individual hypothesis tests and applying the multiple comparison method of Holm. The most optimal confidence intervals are also calculated for the difference or ratio between the respective parameters. Based on the data observed in the sample, the program also estimates the probability of making a type II error if the null hypothesis is not rejected, or estimates the power if the if the alternative hypothesis is accepted. The "compbdt" program provides all the necessary results so that the researcher can easily interpret them. The estimation of the probability of making a type II error allows the researcher to decide about the reliability of the null hypothesis when this hypothesis is not rejected. The "compbdt" program has been applied to a real example on the diagnosis of coronary artery disease. CONCLUSIONS: The "compbdt" program is one which is easy to use and allows the researcher to compare the most important parameters of two binary tests subject to a paired design. The "compbdt" program is available as supplementary material.

Approximate confidence intervals for the likelihood ratios of a binary diagnostic test in the presence of partial disease verification.

The classic parameters used to assess the accuracy of a binary diagnostic test (BDT) are sensitivity and specificity. Other parameters used to describe the performance of a BDT are likelihood ratios (LRs). The LRs depend on the sensitivity and the specificity of the diagnostic test, and they reflect how much greater the probability of a positive or negative diagnostic test result for individuals with the disease than that for the individuals without the disease. In this study, several confidence intervals are studied for the LRs of a BDT in the presence of missing data. Two confidence intervals were studied through the method of maximum likelihood and seven confidence intervals were studied by applying the multiple imputation by chained equations method. A program in R software has been written that allows us to solve the estimation problem posed. The results obtained have been applied to the two real examples.

Threshold values affect predictive accuracy of caries risk assessment.

OBJECTIVE: To evaluate effects of thresholds on estimates of predictive accuracy of methods for caries risk assessment. MATERIAL AND METHODS: Adolescents, aged 12 visiting two dental clinics, were examined by visual/tactile examination and bitewing radiography at baseline and after one year. Three methods for caries risk assessment were applied: previous caries experience, dentists' risk assessment according to set criteria (presence or absence of caries lesion) and acid tolerance of dental biofilm. The measure for validity (the reference standard) comprised caries lesion progression at 1 year. Predictive accuracy estimates were calculated for several thresholds. RESULTS: Accuracy estimates changed with threshold values of the methods and the reference standard. Patient spectrum differed between the clinics, which resulted in different accuracy estimates for the two samples. Generally, negative predictive values were high while positive ones were low indicating that these methods were more efficient in finding individuals who are at low risk of developing caries lesions than those with increased risk. CONCLUSIONS: As thresholds and patient spectrum affected predictive accuracy, it may be difficult to design a universal model with set thresholds for caries risk assessment. Foremost, a model should consider the level of aspiration for prediction and clinical decisions that will be made based on the risk assessment in the actual clinical setting.

Interpreting Evidence of Torture.

The Istanbul Protocol provides a scheme for giving evidence of signs of torture. This scheme does not conform with the principles of logical inference, revolving as it does round the concept of 'consistency'. The shortcomings of the Protocol are explained using the evidence given in the recent case of KV(Sri Lanka) and the logical approach to such evidence explained.

The forensic value of X-linked markers in mixed-male DNA analysis.

Autosomal genetic markers and Y chromosome markers have been widely applied in analysis of mixed stains at crime scenes by forensic scientists. However, true genotype combinations are often difficult to distinguish using autosomal markers when similar amounts of DNA are contributed by multiple donors. In addition, specific individuals cannot be determined by Y chromosomal markers because male relatives share the same Y chromosome. X-linked markers, possessing characteristics somewhere intermediate between autosomes and the Y chromosome, are less universally applied in criminal casework. In this paper, X markers are proposed to apply to male mixtures because their true genes can be more easily and accurately recognized than the decision of the genotypes of AS markers. In this study, an actual two-man mixed stain from a forensic case file and simulated male-mixed DNA were examined simultaneously with the X markers and autosomal markers. Finally, the actual mixture was separated successfully by the X markers, although it was unresolved by AS-STRs, and the separation ratio of the simulated mixture was much higher using Chr X tools than with AS methods. We believe X-linked markers provide significant advantages in individual discrimination of male mixtures that should be further applied to forensic work.

Sense and sensibility: on the diagnostic value of control chart rules for detection of shifts in time series data.

BACKGROUND: The aim of this study was to quantify and compare the diagnostic value of The Western Electric (WE) statistical process control (SPC) chart rules and the Anhoej rules for detection of non-random variation in time series data in order to make recommendations for their application in practice. METHODS: SPC charts are point-and-line graphs showing a measure over time and employing statistical tests for identification of non-random variation. In this study we used simulated time series data with and without non-random variation introduced as shifts in process centre over time. The primary outcome was likelihood ratios of combined tests. Likelihood ratios are useful measures of a test's ability to discriminate between the true presence or absence of a specific condition. RESULTS: With short data series (10 data points), the WE rules 1-4 combined and the Anhoej rules alone or combined with WE rule 1 perform well for identifying or excluding persistent shifts in the order of 2 SD. For longer data series, the Anhoej rules alone or in combination with the WE rule 1 seem to perform slightly better than the WE rules combined. However, the choice of which and how many rules to apply in a given situation should be made deliberately depending on the specific purpose of the SPC analysis and the number of available data points. CONCLUSIONS: Based on these results and our own practical experience, we suggest a stepwise approach to SPC analysis: Start with a run chart using the Anhoej rules and with the median as process centre. If, and only if, the process shows random variation at the desired level, apply the 3-sigma rule in addition to the Anhoej rules using the mean as process centre.

Relationship inference based on DNA mixtures.

Today, there exists a number of tools for solving kinship cases. But what happens when information comes from a mixture? DNA mixtures are in general rarely seen in kinship cases, but in a case presented to the Norwegian Institute of Public Health, sample DNA was obtained after a rape case that resulted in an unwanted pregnancy and abortion. The only available DNA from the fetus came in form of a mixture with the mother, and it was of interest to find the father of the fetus. The mother (the victim), however, refused to give her reference data and so commonly used methods for paternity testing were no longer applicable. As this case illustrates, kinship cases involving mixtures and missing reference profiles do occur and make the use of existing methods rather inconvenient. We here present statistical methods that may handle general relationship inference based on DNA mixtures. The basic idea is that likelihood calculations for mixtures can be decomposed into a series of kinship problems. This formulation of the problem facilitates the use of kinship software. We present the freely available R package relMix which extends on the R version of Familias. Complicating factors like mutations, silent alleles, and θ-correction are then easily handled for quite general family relationships, and are included in the statistical methods we develop in this paper. The methods and their implementations are exemplified on the data from the rape case.

The likelihood ratio as a random variable for linked markers in kinship analysis.

The likelihood ratio is the fundamental quantity that summarizes the evidence in forensic cases. Therefore, it is important to understand the theoretical properties of this statistic. This paper is the last in a series of three, and the first to study linked markers. We show that for all non-inbred pairwise kinship comparisons, the expected likelihood ratio in favor of a type of relatedness depends on the allele frequencies only via the number of alleles, also for linked markers, and also if the true relationship is another one than is tested for by the likelihood ratio. Exact expressions for the expectation and variance are derived for all these cases. Furthermore, we show that the expected likelihood ratio is a non-increasing function if the recombination rate increases between 0 and 0.5 when the actual relationship is the one investigated by the LR. Besides being of theoretical interest, exact expressions such as obtained here can be used for software validation as they allow to verify the correctness up to arbitrary precision. The paper also presents results and advice of practical importance. For example, we argue that the logarithm of the likelihood ratio behaves in a fundamentally different way than the likelihood ratio itself in terms of expectation and variance, in agreement with its interpretation as weight of evidence. Equipped with the results presented and freely available software, one may check calculations and software and also do power calculations.

Utility of features of the patient's history in the diagnosis of atraumatic shoulder pain: a systematic review.

BACKGROUND: Whereas physical examination tests for shoulder disorders have numeric values that describe the utility of the test and its effect on the probability of having a diagnosis, this information is lacking for elements of the history. The purpose of this study was to conduct a systematic review of the literature to determine numeric data (sensitivity, specificity, predictive values, and likelihood or odds ratios) for elements of the history with regard to diagnoses in patients with chronic atraumatic shoulder pain. METHODS: We performed a systematic review to extract information from the existing literature regarding the numeric utility of different features of the patient history as they pertain to chronic atraumatic shoulder pain. Data sources were MEDLINE through PubMed (1946-January 2012) and EMBASE through Ovid (1980-January 2012). RESULTS: Twenty-one studies met inclusion criteria. A diagnosis of rotator cuff tear was more likely with a history of hypercholesterolemia, having a relative with rotator cuff disease, excessive lifting, above-shoulder work, hand-held vibration work, or age older than 60 years. Acromioclavicular arthritis was more likely in weightlifters. Glenohumeral arthritis was more likely if the patient has a history of prior dislocation, age >75 years, or a diagnosis of knee osteoarthritis. Adhesive capsulitis was more likely with a history of diabetes or thyroid disorder. Posterior labral tear was more likely in football players. CONCLUSIONS: The numeric values for the utility of these history features will help establish numeric probabilities for diagnoses in patients with shoulder pain.

Posterior distributions for likelihood ratios in forensic science.

Evaluation of evidence in forensic science is discussed using posterior distributions for likelihood ratios. Instead of eliminating the uncertainty by integrating (Bayes factor) or by conditioning on parameter values, uncertainty in the likelihood ratio is retained by parameter uncertainty derived from posterior distributions. A posterior distribution for a likelihood ratio can be summarised by the median and credible intervals. Using the posterior mean of the distribution is not recommended. An analysis of forensic data for body height estimation is undertaken. The posterior likelihood approach has been criticised both theoretically and with respect to applicability. This paper addresses the latter and illustrates an interesting application area.