Avoidability of drug-induced liver injury (DILI) in an elderly hospital cohort with cases assessed for causality by the updated RUCAM score.

BACKGROUND: Drug-induced liver injury (DILI) represents an increasing morbidity in the general population, but more so in the elderly cohort of patients. Despite this, the concept of its prevention through prospective analysis has largely remained unexamined. We evaluated the utility of recently validated adverse drug reactions (ADR) avoidability tool in a cohort of elderly patients with DILI. METHODS: We examined 38 DILI-drug pairs from n=38 patients in a prospective cohort of patients presenting with adverse drug reactions to a Weill Cornell-affiliated tertiary hospital between February 2019 and January 2020. DILI outcomes were adjudicated by the updated Roussel Uclaf Causality Assessment Method (RUCAM). Two clinical pharmacologists and two general physicians utilized the Liverpool adverse drug reactions avoidability tool (LAAT) and the modified Hallas tools to rate the preventability of DILI-drug pairs. Inter-rater, exact agreement proportions, as well as intraclass correlation coefficients were generated and expressed as ordinal outcomes. RESULTS: The cases examined for the determination of DILI avoidability had probability likelihood of "probable" or "highly probable" by the updated RUCAM scale. Examination of the 38 DILI-drug pairs (n= 38 patients) resulted in a total of 152 ordinal outcome decisions. We found about 32.3% (50/152) and 34.2% (52/152) of DILI-drug pairs were rated as "avoidable" ("probable" or "definite") by the LAAT and the modified Hallas tools respectively. The overall median Krippendorf's kappa with the LAAT was 0.61 (SE 0.12, CI 0.36, 0.85) and for modified Hallas tool was 0.53 (SE 0.18; CI 0.16, 0.89). The inter-rater correlation coefficient (ICC) for the LAAT and modified Hallas were 0.50 [0.32, 0.65] and 0.63 [0.48, 0.76] respectively. Exact pairwise agreement was present in 30/38 (IQR 29.5, 34.5), and 28/38 (IQR 27.5-35.5) of DILI-ADR pairs using the LAAT and modified Hallas tools respectively. CONCLUSION: We found a significant proportion of drug-induced liver injury adjudicated by the updated RUCAM scale in elderly hospitalized cohort of patients were avoidable with significant implication for therapeutic commissioning as well as cost effectiveness interventions in this cohort of patients.

A comparison of the direct and indirect methods of estimating skeletal height from tibial fragments in black South Africans.

The estimation of maximum bone length from its fragments is important in forensic anthropology as these length estimates can be used to estimate the total skeletal height (TSH), and thereby stature, of unknown skeletal remains. This is known as the indirect method of stature estimation. Alternatively, TSH can be estimated directly from bone fragments without first estimating maximum bone length. While regression equations for estimating maximum bone length from its fragments exist for long bones of the upper and lower limbs, these equations are population- and sex-specific and their use on populations other than the one they were derived from is not recommended. The aim of this study was therefore to develop formulae for estimating maximum tibial length from its fragments in black South Africans, which previously did not exist, and to compare the accuracies of the direct and indirect methods of estimating TSH from tibial fragments. Several measurements representing fragments were measured on the tibiae of 99 male and 99 female black South Africans, and equations estimating tibial length from these measurements were derived. Correlation coefficients of each equation were significant, and all equations estimated tibial length with moderate to high accuracy. A comparison of the standard errors of estimate (SEEs) between the direct and indirect methods of stature estimation indicate that the direct method is more accurate and should be used to estimate stature from tibial fragments when such equations exist.

Efficacy of sodium-glucose co-transporter 2 inhibitors in patients with type II diabetes: A protocol for systematic review of randomised controlled clinical trials utilising a generalised pairwise modelling methodology.

BACKGROUND: Recent systematic reviews have evaluated the efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT2) inhibitors (SGLT2I) in improving glycaemic control and mortality in patients with type II diabetes mellitus. None have incorporated the most recent study or utilized the generalized pairwise modeling methodology network meta-analysis (NMA), as well as a novel bias risk assessment approach. METHODS: We propose to conduct literature search of all randomized controlled clinical trials published in English language evaluating the efficacy of (SGLT2I) versus placebo or usual standard of care from the inception of following databases to September 30, 2019: Controlled Clinical Trials Cochrane Controlled Trials Register (CCTR), Cochrane Database of Systematic Reviews (CDSR), EMBASE, Database of Abstracts of Reviews of Effectiveness (DARE), PubMed. Two reviewers will independently search these databases to identify studies that satisfy pre-specified eligibility criteria. Study bias risk assessment amongst other methodology quality evaluation of the studies will be carried out using a novel risk bias assessment tool. RESULTS: We anticipate that the result of this review will provide additional insight into the ranking of the efficacy of various (SGLT2I) in type II diabetic patients especially as it relates to mortality, glycemic control, and body weight reduction. CONCLUSION: The result of this review will be useful informing therapeutic decisions by policy makers with regards to commissioning of diabetic care.Prospero registration number: CRD42019139708.

Using tibial fragments to reconstruct the total skeletal height of black South Africans.

Stature is an important component of the biological profile of unknown skeletal remains and regression equations for estimating stature have been derived for a number of bones. However, bones are rarely recovered intact in both forensic and archaeological cases, and regression formulae for fragmentary remains have therefore been developed. These equations are, however, both sex- and population-specific, and while formulae exist for many populations, those using fragmentary tibiae do not exist for black South Africans. The aim of this study was therefore to establish regression equations for estimating total skeletal height (TSH), and thereby stature, from tibial fragments in a black South African population. A sample of 99 male and 99 female black South African skeletons were obtained from the Raymond A. Dart Collection of Human Skeletons and the TSH of each skeleton was calculated using the anatomical method. Eleven additional measurements representing tibial fragments were taken on each tibia, and both uni- and multivariate equations were established for estimating TSH from these fragments. All tibial variables were significantly, positively correlated with TSH, and equation correlations ranged between 0.41 and 0.91. The range of standard errors of estimate for the derived sex-specific (3.43-5.06 cm) and sex-pooled (3.44-5.94 cm) multivariate equations were slightly larger than those reported for intact tibiae in black (2.78-3.06 cm) and white (2.59-3.16 cm) South Africans. All uni- and multivariate-equations estimated TSH with moderate to high accuracy, which indicates that in the absence of intact tibiae, the equations presented in this study can be used to give accurate estimates of TSH, and thereby stature, for black South Africans.

Plasma cell leukaemia and HIV co-infection: profile of patients and experience at Universitas Academic Hospital in Bloemfontein, South Africa.

Plasma cell leukaemia (PCL) is a rare condition with high mortality. HIV-positive patients have a propensity to develop malignancy; however, the occurrence of PCL with HIV infection in South Africa has not been documented. We describe patients with PCL in Universitas Hospital in Bloemfontein, South Africa, and report two new cases of HIV infection concurrent with PCL. A retrospective case series of PCL patients (2006-2012) seen at our Clinical Haematology unit is reported. Patient files were used to obtain information. The median age of patients (n = 9) was 51 years, and 66.7 % of cases were of African ethnicity. The condition was equally distributed between genders. Two patients were HIV positive. Both received combination antiretroviral therapy. The diagnosis of PCL was usually made as an incidental finding, subsequently confirmed on bone marrow aspirate and trephine. Deranged haematological and biochemical parameters, including severe anaemia, hypoalbuminaemia, and hyper-cellular bone marrow, were observed. Only one patient improved markedly on treatment, and remains alive at the time of writing. PCL shows poor response to treatment and predominates among Africans. The small sample size made it difficult to determine whether co-infection with HIV was a coincidental finding or the two diseases are pathophysiologically linked.

New soft tissue correction factors for stature estimation: results from magnetic resonance imaging.

In stature reconstruction using Fully's method, it is essential that a soft tissue correction factor be added to skeletal height in order to obtain an estimate of living stature. While some anthropologists consider Fully's method to be the most reliable for stature estimation, others consider it to be inadequate as it seems to be underestimating living stature, possibly due to an error in the magnitude of Fully's soft tissue factors. A recent study by Raxter and co-workers revised Fully's technique and also presented a new "universally applicable" soft tissue correction factor. The present study examines the reliability of soft tissue correction factors of Fully and Raxter et al. on a living sample of indigenous South African males. The current study is based on data collected from 28 indigenous South African (ISA) male volunteers. Standing height of each subject was measured using a stadiometer. Fully's method was used in the calculation of total skeletal height from a full body MRI scan of each subject. Subsequent analyses of the acquired data revealed that the previously derived soft tissue correction factors are not applicable to the studied sample, and why they are not applicable. The correction factors of Fully and Raxter et al. both significantly underestimate living stature in a living sample of indigenous South African males. Consequently, a new correction factor was calculated based on the prediction of living stature from TSH using regression analysis.

An assessment of the accuracy of discriminant function equations for sex determination of the femur and tibia from a South African population.

The purpose of this study is to test the accuracy of seven discriminant function equations that have been derived by Steyn and Isçan for sex determination using measurements of the femur and tibia of South Africans of European descent (SAED). While the validity of some of the discriminant functions has been assessed by the authors who derived them, no previous independent study has been carried out to assess the accuracy of these equations. These equations have not been tested on skeletons located outside of the Gauteng province. A suite of measurements were taken on 272 femora and 256 tibiae obtained from four South African skeletal collections. The validity of each of the previously published equations for the femur was confirmed. However, two functions of the tibia showed low accuracy rates, most likely due to difficulties in recording the distal epiphyseal breadth measurement, and thus were found to be poor assessors of sex.

Fragmentary femora: evaluation of the accuracy of the direct and indirect methods in stature reconstruction.

Selected measurements of the femur have been used in the derivation of regression equations for stature estimation in several populations. Various studies have indicated that stature can be estimated from fragmentary bones by either the direct or the indirect method. The direct method allows for the estimation of stature directly from individual or combination of measurements of fragments of the femur. However, the indirect method consists of two steps. An initial step which involves the estimation of maximum length of the femur from measurements of its fragments is followed by stature estimation from the estimated maximum length of the femur. While Steele noted that the indirect method provides a relatively more precise estimate of stature, none of the subsequent studies on stature reconstruction has addressed the issue of accuracy of the two methods. The current study utilized 120 complete skeletons obtained from the Raymond A. Dart Collection of Human Skeletons. Total skeletal height for each of the skeletons (TSH(Fully)) was calculated using the Fully's method. Measurements of fragments of the femur acquired from the current study were substituted into each of the previously derived equations for Indigenous South Africans (ISA) and South Africans of European Descent (SAED) in order to obtain an estimate of the skeletal height (TSH(Est)). Analyses were carried out separately for each group. An assessment of the differences between the estimated skeletal height (TSH(Est)) and the obtained skeletal height using the Fully's method (TSH(Fully)) was performed using the paired t test. While no significant difference was observed between TSH(Fully) and TSH(Est) for all equations (except one) used in the direct estimation of skeletal height, a number of indirect equations significantly overestimated TSH(Fully). These observations indicate that the direct method is more accurate than the indirect method. Since it is also less complicated, it is therefore the preferred of the two methods contrary to earlier recommendation made by Steele.

The skull and humerus in the determination of sex: reliability of discriminant function equations.

Sex determination plays a crucial role in the identification of human remains as it narrows the possibility for identification by 50%. The purpose of this study is to test the validity of five discriminant function equations, with accuracies of 80% and higher, that have been derived by Steyn and Iscan [M. Steyn, M.Y. Iscan, Sexual dimorphism in the crania and mandibles of South African Whites, Forensic Sci. Int. 98 (1998) 9-16; M. Steyn, M.Y. Iscan, Osteometric variation in the humerus: sexual dimorphism in South Africans, Forensic Sci. Int. 106 (1999) 77-85] for the skull and humerus of South Africans of European Descent (SAED). These equations were tested on different regional populations of SAED within South Africa. While the validity of some of the discriminant functions has been assessed by the authors who derived them, no other previous independent study has been carried out to assess the reliability of these equations. In addition, these equations have not been tested on skeletons located outside the Gauteng province. The study sample consisted of 230 skulls and 264 humeri of SAED obtained from four South African skeletal collections: Raymond A. Dart Collection of Human Skeletons (Johannesburg); Pretoria Bone Collection; Cape Town Skeletal Collection; and the Osteology Archive Student Collection (Stellenbosch). A total of 14 measurements (12 cranial and 2 humeral) were taken on these skeletal elements. The observed accuracies from the present study (72.0-95.5%), with the exception of one sample's accuracy, compared well with the original classification rates (80.2-92.5%) for most of the functions thereby confirming the validity of the discriminant function equations for sex determination for the skull and humerus of SAED, for SAED in all regions of South Africa.

Metatarsals in the estimation of stature in South Africans.

To date, only one study has investigated the potential of metatarsals in the estimation of stature for forensic purposes. The morphology of these bones from clinical and paleontological perspectives is well researched in different parts of the world including South Africa. The present study aimed at assessing the usefulness of metatarsals of South Africans in the estimation of stature. For this study, 226 complete skeletons obtained from the Raymond A. Dart Collection were used in the formulation of univariate and multivariate regression equations from six linear measurements of metatarsals. The standard error of estimate for these equations was lower than that obtained for fragments of long bones and other skeletal elements studied so far for stature estimation in South Africans with the exception of intact long bones. Therefore, regression equations presented in this study can provide a reliable estimate of stature in cases where intact long bones are not available for forensic analysis.

Stature reconstruction using fragmentary femora in South Africans of European descent.

It is well documented that the intact femur has the highest correlation with stature and as such has been widely used in the derivation of regression equations for stature estimation. As intact femur is not always present for analyses in forensic cases, it has become necessary to derive regression equations for the estimation of stature from fragments of this bone. Few studies have presented regression equations for stature estimation from fragments of the femur. Because these equations are population specific, it was the aim of this study to derive similar equations for estimation of stature and maximum length of femur from measurements of the femur of South Africans of European descent. A sample of 50 male and 50 female complete skeletons were obtained from the Raymond A. Dart Collection of Human Skeletons. Total skeletal height for each of the skeletons was calculated using the Fully's method. Six variables were measured on each femur which included the vertical neck diameter, upper breadth of femur, epicondylar breadth, bicondylar breadth, lateral condyle length, and medial condyle length. Regression equations for the estimation of stature are presented. The range of standard error of estimate for these equations (3.71-5.31) was slightly higher than those obtained for intact long bones (2.13-3.79). It is therefore suggested that in the absence of intact femur, regression equations derived from the present study can provide a reliable estimate of adult stature.

Estimation of stature using fragmentary femora in indigenous South Africans.

Intact long bones of the upper and lower extremities have been used in the derivation of regression equations for the estimation of stature in different population groups. These bones are sometimes presented to forensic anthropologists in different states of fragmentation thereby making the derived equations unusable. This has necessitated the need to assess the usefulness of measurements of fragments of long bones (e.g., femur) in the estimation of stature. While few studies have reported such equations, which are population and sex specific, it was the aim of this study to derive equations based on measurements of commonly preserved fragments of the femur for the indigenous South African population group. A total of 100 complete skeletons, equally distributed by sex, were obtained from the Raymond A. Dart collection of human skeletons. Stature was estimated for each of the skeleton using the Fully's method (Fully in Ann Med Leg 35:266-273, 1956). Regression equation for the estimation of stature and maximum length of the femur were derived from six measurements of the femur. The standard error of estimate for regression equations for stature estimation (3.72-4.38) was slightly higher than that presented for intact femur. This study confirms the usefulness of fragments of the femur of indigenous South Africans in the estimation of stature.

Discriminating sex in South African blacks using patella dimensions.

For many years, sex determination has been carried out on skeletal remains to identify individuals in forensic cases and to assess populations in archaeological cases. Since it has been shown that not all bones are found in a forensic case, discriminant function equations should be derived for all bones of the body to assist in sex determination. Numerous studies have shown the usefulness of bones of the lower extremity (e.g. femur, tibia) in sex determination using discriminant function analysis, but the use of patella measurements has not been extensively investigated for this purpose. It is therefore the aim of this study to derive discriminant function equations for sex determination from measurements of the patella of South African blacks as represented in the Raymond A. Dart Collection of Human Skeletons. A total sample of 120 (60 male, 60 female) patellae were measured using six measurements. The Statistical Product and Service Solutions (SPSS) program was used to derive the equations. Stepwise and direct analyses were performed with the highest rate of classification of 85% thereby making the patella useful for sex determination. Thus, the proposed equations derived from this study should be used with caution and only on the South African black population group.

On the non-equivalence of documented cadaver lengths to living stature estimates based on Fully's method on bones in the Raymond A. Dart Collection.

Regression equations for stature estimation have been derived from documented cadaver lengths available as part of the demographic information in the catalogue of skeletonised remains in different collections around the world. The Raymond A. Dart Collection is one such collection, but the reliability of documented cadaver lengths in it has been previously questioned. The aim of this study was to compare these lengths with estimated living stature using Fully's anatomical method. Living stature was estimated with this method from a total of 156 complete skeletons obtained from the Collection. These heights were then compared with the documented cadaver lengths. It was observed that the documented cadaver lengths were significantly higher than the estimated living stature using Fully's method.

Sexual dimorphism of the calcaneus of South African blacks.

Forensic anthropology is a rapidly growing field in South Africa and skeletal biologists are often called upon by the police to assist in personal identification from skeletal remains, which are recovered in suspected cases of homicide and suicide and in mass disaster. Measurements of the calcaneus have been shown to be sexually dimorphic in South African whites. Since the validity of discriminant function equations in sex determination is population specific, the aim of the present study was to derive similar equations for the calcanei of the South African blacks. The bones that were used in this study were obtained from the Raymond A. Dart Collection of Human Skeletons, School of Anatomical Sciences, University of the Witwatersrand, Johannesburg. One hundred and sixteen (116) intact and non-pathological calcanei, consisting of 58 males and 58 females and belonging to individuals whose age at death ranged between 22 and 75 years, were selected by the simple random sampling technique. The measured variables included the maximum length, the load arm length, the dorsal articular facet length, the body height, the maximum height, the cuboidal facet height, the middle breadth, the dorsal articular facet breadth and the maximum breadth. Discriminant function analyses were done using the Statistical Product and Service Solutions (SPSS) program. All measured parameters of the calcaneus showed significant sexual differences. Length measurements were found to be the most sexually dimorphic. Combinations of variables provided better estimate of sex (79%-86%) than individual variables (64%-79%).

Sex determination from the talus of South african whites by discriminant function analysis.

The field of forensic anthropology involves the building of an antemortem profile of an individual from skeletal remains. This includes sex and race determination and age and stature estimation. Since most bones that are conventionally used for sex determination are often recovered either in a fragmented or incomplete state, it has become necessary to use denser bones that are often recovered intact, eg, the patella, calcaneus, and talus. Thus the aim of this study is to assess the sex-determining ability of each of the measurements of the talus and derive discriminant function equations for sex determination in the South African white population. Sixty male and 60 female tali of South African whites obtained from the Raymond A. Dart Collection of Human Skeletons were used. Nine measurements were taken on each talus. Descriptive statistics and discriminant function analysis were performed on the acquired data. The basic statistics showed that all measurements were sexually dimorphic. Univariate, stepwise, and direct discriminant function equations were generated for use in sex determination. The level of average accuracy of sex classification was 80% to 82% for the univariate method, 85% to 88% for the stepwise method, and 81% to 86% for the direct method. It is concluded that the talus of South African whites is useful for sex determination.