Surgical approach significantly affects the complication rates associated with total hip arthroplasty.

AIMS: A variety of surgical approaches are used for total hip arthroplasty (THA), all with reported advantages and disadvantages. A number of common complications can occur following THA regardless of the approach used. The purpose of this study was to compare five commonly used surgical approaches with respect to the incidence of surgery-related complications. PATIENTS AND METHODS: The electronic medical records of all patients who underwent primary elective THA at a single large-volume arthroplasty centre, between 2011 and 2016, with at least two years of follow-up, were reviewed. After exclusion, 3574 consecutive patients were included in the study. There were 1571 men (44.0%) and 2003 women (56.0%). Their mean age and body mass index (BMI) was 63.0 years (sd 11.8) and 29.1 kg/m2 (sd 6.1), respectively. Data gathered included the age of the patient, BMI, the American Society of Anesthesiologists (ASA) score, estimated blood loss (EBL), length of stay (LOS), operating time, the presence of intra- or postoperative complications, type of complication, and the surgical approach. The approaches used during the study were posterior, anterior, direct lateral, anterolateral, and the northern approach. The complications that were recorded included prolonged wound drainage without infection, superficial infection, deep infection, dislocation, aseptic loosening, and periprosthetic fracture. Finally, the need for re-operation was recorded. Means were compared using analysis of variance (ANOVA) and Student's t-tests where appropriate and proportions were compared using the chi-squared test. RESULTS: A total of 248 patients had 263 complications related to the surgery, with an incidence of 6.94%. The anterior approach had the highest incidence of complications (8.5% (113/1329)) and the posterior approach had the lowest, at 5.85% (97/1657; p = 0.006). Most complications were due to deep infection (22.8%), periprosthetic fracture (22.4%), and prolonged wound drainage (21.3%). The rate of dislocation was 0.84% (14/1657) with the posterior approach and 1.28% (17/1329) with the anterior approach (p = 0.32). CONCLUSION: Overall, THA has a relatively low complication rate. However, the surgical approach plays a role in the incidence of complications. We found that the posterior approach had a significantly lower overall complication rate compared with the anterior approach, with an equal dislocation rate. Periprosthetic fracture and surgical site infection contributed most to the early complication rates. Cite this article: Bone Joint J 2019;101-B:646-651.

Can some early revision total hip arthroplasties be avoided?

AIMS: Studying the indications for revision total hip arthroplasty (THA) may enable surgeons to change their practice during the initial procedure, thereby reducing the need for revision surgery. The aim of this study was to identify and describe the potentially avoidable indications for revision THA within five years of the initial procedure. PATIENTS AND METHODS: A retrospective review of 117 patients (73 women, 44 men; mean age 61.5 years (27 to 88)) who met the inclusion criteria was conducted. Three adult reconstruction surgeons independently reviewed the radiographs and medical records, and they classified the revision THAs into two categories: potentially avoidable and unavoidable. Baseline demographics, perioperative details, and quality outcomes up to the last follow-up were recorded. RESULTS: A total of 60 revision THAs (51.3%) were deemed potentially avoidable and 57 (48.7%) were deemed unavoidable. The following were identified as avoidable factors: suboptimal positioning of the acetabular component (29; 48%), intraoperative fracture or a fracture missed on an intraoperative radiograph (20; 33%), early (less than two weeks) aseptic loosening (seven; 11.7%), and symptomatic leg length discrepancy of > 1 cm (four; 6.7%). CONCLUSION: A surprisingly large proportion of acute revision THAs are potentially avoidable. Surgeons must carefully evaluate the indications for revision THAs in their practice and identify new methods to address these issues. Cite this article: Bone Joint J 2019;101-B(6 Supple B):97-103.

2019 Frank Stinchfield Award: A comparison of prosthetic joint infection rates between direct anterior and non-anterior approach total hip arthroplasty.

AIMS: We studied the impact of direct anterior (DA) versus non-anterior (NA) surgical approaches on prosthetic joint infection (PJI), and examined the impact of new perioperative protocols on PJI rates following all surgical approaches at a single institution. PATIENTS AND METHODS: A total of 6086 consecutive patients undergoing primary total hip arthroplasty (THA) at a single institution between 2013 and 2016 were retrospectively evaluated. Data obtained from electronic patient medical records included age, sex, body mass index (BMI), medical comorbidities, surgical approach, and presence of deep PJI. There were 3053 male patients (50.1%) and 3033 female patients (49.9%). The mean age and BMI of the entire cohort was 62.7 years (18 to 102, sd 12.3) and 28.8 kg/m2 (13.3 to 57.6, sd 6.1), respectively. Infection rates were calculated yearly for the DA and NA approach groups. Covariates were assessed and used in multivariate analysis to calculate adjusted odds ratios (ORs) for risk of development of PJI with DA compared with NA approaches. In order to determine the effect of adopting a set of infection prevention protocols on PJI, we calculated ORs for PJI comparing patients undergoing THA for two distinct time periods: 2013 to 2014 and 2015 to 2016. These periods corresponded to before and after we implemented a set of perioperative infection protocols. RESULTS: There were 1985 patients in the DA group and 4101 patients in the NA group. The overall rate of PJI at our institution during the study period was 0.82% (50/6086) and decreased from 0.96% (12/1245) in 2013 to 0.53% (10/1870) in 2016. There were 24 deep PJIs in the DA group (1.22%) and 26 deep PJIs in the NA group (0.63%; p = 0.023). After multivariate analysis, the DA approach was 2.2 times more likely to result in PJI than the NA approach (OR 2.2 (95% confidence interval 1.1 to 3.9); p = 0.006) for the overall study period. CONCLUSION: We found a higher rate of PJI in DA versus NA approaches. Infection prevention protocols such as use of aspirin, dilute povidone-iodine lavage, vancomycin powder, and Gram-negative coverage may have been positively associated with diminished PJI rates observed for all approaches over time. Cite this article: Bone Joint J 2019;101-B(6 Supple B):2-8.

C5aR antagonist inhibits occurrence and progression of complement C5a induced inflammatory response of microglial cells through activating p38MAPK and ERK1/2 signaling pathway.

OBJECTIVE: To discuss the effect of complement C52 (C5a) and complement C5a receptor (C5aR) antagonists on inflammatory status of mouse microglial cells. MATERIALS AND METHODS: Primary culture was performed on mouse microglial cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to detect effect of C5a and C5aR antagonists on vitality of microglial cells. The effect of C5a and C5aR antagonists on mRNA expression of p38MAPK and ERK1/2 was determined using quantitative PCR (qPCR). Enzyme linked immunosorbent assay (ELISA) was used to measure expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in cells. RESULTS: According to quantitative fluorescent PCR, relative expression of p38MAPK and ERK1/2 mRNA in C5a antagonist treatment group was significantly higher compared to normal group and C5a+C5aR antagonist treatment group (p<0.05). However, the relative expression of the C5a+C5aR antagonist treatment group was significantly lower compared to that of the normal group (p<0.05). Expression of Iba1, p-p38MAPK and p-ERK1/2 proteins in C5a antagonist treatment group was significantly higher than normal group, in C5a+C5aR antagonist treatment group was lower than C5a antagonist treatment group (p<0.05). There were significant differences for IL-6 and TNF-α levels among 5 groups (p<0.05). Expression of cytokines was the highest in 100 nM C5a antagonist treatments and lowest in normal group. CONCLUSIONS: Complement C5a upregulated expression of inflammatory factors in mouse microglial cells, while C5aR antagonist inhibited occurrence and progression of inflammatory status. This was achieved by affecting transcriptional and translational processes of different factors in p38MAPK and ERK1/2 signaling pathway.

[Diagnosis of a case with Williams-Beuren syndrome with nephrocalcinosis using chromosome microarray analysis].

Objective: To explore the clinical phenotypes and the genetic cause for a boy with unexplained growth retardation, nephrocalcinosis, auditory anomalies and multi-organ/system developmental disorders. Method: Routine G-banding and chromosome microarray analysis were applied to a child with unexplained growth retardation, nephrocalcinosis, auditory anomalies and multi-organ/system developmental disorders treated in the Department of Pediatrics of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in September 2015 and his parents to conduct the chromosomal karyotype analysis and the whole genome scanning. Deleted genes were searched in the Decipher and NCBI databases, and their relationships with the clinical phenotypes were analyzed. Result: A six-month-old boy was refered to us because of unexplained growth retardation and feeding intolerance.The affected child presented with abnormal manifestation such as special face, umbilical hernia, growth retardation, hypothyroidism, congenital heart disease, right ear sensorineural deafness, hypercalcemia and nephrocalcinosis. The child's karyotype was 46, XY, 16qh+ , and his parents' karyotypes were normal. Chromosome microarray analysis revealed a 1 436 kb deletion on the 7q11.23(72701098_74136633) region of the child. This region included 23 protein-coding genes, which were reported to be corresponding to Williams-Beuren syndrome and its certain clinical phenotypes. His parents' results of chromosome microarray analysis were normal. Conclusion: A boy with characteristic manifestation of Williams-Beuren syndrome and rare nephrocalcinosis was diagnosed using chromosome microarray analysis. The deletion on the 7q11.23 might be related to the clinical phenotypes of Williams-Beuren syndrome, yet further studies are needed.

Robust parameter extraction for decision support using multimodal intensive care data.

Digital information flow within the intensive care unit (ICU) continues to grow, with advances in technology and computational biology. Recent developments in the integration and archiving of these data have resulted in new opportunities for data analysis and clinical feedback. New problems associated with ICU databases have also arisen. ICU data are high-dimensional, often sparse, asynchronous and irregularly sampled, as well as being non-stationary, noisy and subject to frequent exogenous perturbations by clinical staff. Relationships between different physiological parameters are usually nonlinear (except within restricted ranges), and the equipment used to measure the observables is often inherently error-prone and biased. The prior probabilities associated with an individual's genetics, pre-existing conditions, lifestyle and ongoing medical treatment all affect prediction and classification accuracy. In this paper, we describe some of the key problems and associated methods that hold promise for robust parameter extraction and data fusion for use in clinical decision support in the ICU.

Medical informatics: reasoning methods.

The progress of medical informatics has been characterized by the development of a wide range of reasoning methods. These reasoning methods are based on organizing principles that make use of the various relations existing in medical domains: associations, probabilities, causality, functional relationships, temporal relations, locality, similarity, and clinical practice. Some, such as those based on associations and probabilities have been developed to the point where there are off-the-shelf tools available for the researcher to develop new decision support tools. Others such as temporal relations require more effort to use effectively. Even so, we have learned the importance of a separate explicit representation of the domain knowledge and have considerable experience and an impressive armamentarium with which to face the new milieu provided by the Internet.

New approaches to measuring the performance of programs that generate differential diagnoses using ROC curves and other metrics.

INTRODUCTION: Evaluation of computer programs which generate multiple diagnoses can be hampered by a lack of effective, well recognized performance metrics. We have developed a method to calculate mean sensitivity and specificity for multiple diagnoses and generate ROC curves. METHODS: Data came from a clinical evaluation of the Heart Disease Program (HDP). Sensitivity, specificity, positive and negative predictive value (PPV, NPV) were calculated for each diagnosis type in the study. A weighted mean of overall sensitivity and specificity was derived and used to create an ROC curve. Alternative metrics Comprehensiveness and Relevance were calculated for each case and compared to the other measures. RESULTS: Weighted mean sensitivity closely matched Comprehensiveness and mean PPV matched Relevance. Plotting the Physician's sensitivity and specificity on the ROC curve showed that their discrimination was similar to the HDP but sensitivity was significantly lower. CONCLUSIONS: These metrics give a clear picture of a program's diagnostic performance and allow straightforward comparison between different programs and different studies.

A government purchaser perspective: TennCare--strengthening the safety net.

BACKGROUND: On January 1, 1994, in response to escalating Medicaid costs, the State of Tennessee implemented TennCare, a statewide managed health care system for three population groups: Medicaid eligibles, uninsurable individuals, and people who lacked access to insurance through their place of employment. METHODS: Under the TennCare program, the State contracts with ten managed care organizations to provide a comprehensive benefit package to each enrollee. Preventive services are exempt from copayment or deductible requirements. Each patient is assigned to a primary care provider who is responsible for assuring that the enrollee receives preventive services. RESULTS: More than 400,000 previously uninsured and uninsurable persons now receive health care coverage through the TennCare program. An extensive quality assurance program monitors managed care organization service delivery, with particular emphasis on prevention and access. Effective case management, combined with an enrollment cap, have enabled the program to grow at a predictable rate, without exceeding the annual rate of growth of state revenues. CONCLUSIONS: The TennCare program has been successful in using the savings experienced during the shift from a fee-for-service to a managed care Medicaid program to expand coverage to previously uninsured populations.

Differential diagnoses of the heart disease program have better sensitivity than resident physicians.

We describe a prospective clinical evaluation of a computer program to assist with the diagnosis of heart disease. The Heart Disease Program (HDP) is a large diagnostic program covering most areas of heart disease and some related areas of general medicine. The program's output is a set of differential diagnoses with explanations and it can be deployed in a clinical setting using a web interface. A framework for assessing the complex diagnostic summaries generated by the HDP was developed and the program's diagnostic accuracy in a clinical setting was assessed. The diagnoses used for comparison came from the physician entering the case, a "gold standard" assigned by review of patient charts and investigations, and the opinions of expert cardiologists. The data collection, methods of comparison, example analyses and results on 114 cases are presented here. The HDP had a significantly higher sensitivity for both the gold standard (60%) and the cardiologist's diagnoses (58%) than the physicians did (39%, 34%). These findings were consistent in the 2 collection cohorts and for the more serious diagnoses alone. The significance of these findings and the many challenges in comparing these different diagnoses and minimizing bias are discussed.

Using classification tree and logistic regression methods to diagnose myocardial infarction.

Early and accurate diagnosis of myocardial infarction (MI) in patients who present to the Emergency Room (ER) complaining of chest pain is an important problem in emergency medicine. A number of decision aids have been developed to assist with this problem but have not achieved general use. Machine learning techniques, including classification tree and logistic regression (LR) methods, have the potential to create simple but accurate decision aids. Both a classification tree (FT Tree) and an LR model (FT LR) have been developed to predict the probability that a patient with chest pain is having an MI based solely upon data available at time of presentation to the ER. Training data came from a data set collected in Edinburgh, Scotland. Each model was then tested on a separate Edinburgh data set, as well as on a data set from a different hospital in Sheffield, England. Previously published models, the Goldman classification tree[1] and Kennedy LR equation[2], were evaluated on the same test data sets. On the Edinburgh test set, results showed that the FT Tree, FT LR, and Kennedy LR performed equally well, with ROC curve areas of 94.04%, 94.28%, and 94.30%, respectively, while the Goldman Tree's performance was significantly poorer, with an area of 84.03%. The difference in ROC areas between the first three models and the Goldman model is significant beyond the 0.0001 level. On the Sheffield test set, results showed that the FT Tree, FT LR, and Kennedy LR ROC areas were not significantly different (p > = 0.17), while the FT Tree again outperformed the Goldman Tree (p = 0.006). Unlike previous work[3], this study indicates that classification trees, which have certain advantages over LR models, may perform as well as LR models in the diagnosis of patients with MI.

Reasoning requirements for diagnosis of heart disease.

Over the past dozen years, the Heart Disease Program (HDP) has been developed to assist physicians in reasoning about cardiovascular disorders. Driven by several evaluations, the inference mechanism has progressed from a logic based model, to a Bayesian Probability Network (BPN) and finally a pseudo-Bayesian network with temporal and severity reasoning. Though aspects of cardiovascular reasoning are handled well by BPNs, temporal reasoning, homeostatic feedback mechanisms and effects of disease severities require additional inference strategies. This article discusses how these reasoning problems are handled, and deals with closely linked issues in building the user interface to collect detailed cardiovascular data and provide clear explanations of diagnoses.

Characterization of a soluble stable human cytomegalovirus protease and inhibition by M-site peptide mimics.

The human cytomegalovirus (HCMV) protease is a potential target for antiviral chemotherapeutics; however, autoprocessing at internal sites, particularly at positions 143 and 209, hinders the production of large quantities of stable enzyme for either screening or structural studies. Using peptides encompassing the sequence of the natural M-site substrate (P5-P5', GVVNA/SCRLA), we previously demonstrated that substitution of glycine for valine at the P3 position in the substrate abrogates processing by the recombinant protease in vitro. We now demonstrate that introduction of the V-to-G substitution in the P3 positions of the two major internal processing sites, positions 143 and 209, in the mature HCMV protease renders the enzyme stable to autoprocessing. When expressed in Escherichia coli, the doubly substituted protease was produced almost exclusively as the 30-kDa full-length protein. The full-length V141G, V207G (V-to-G changes at positions 141 and 207) protease was purified as a soluble protein by a simple two-step procedure, ammonium sulfate precipitation followed by DEAE ion-exchange chromatography, resulting in 10 to 15 mg of greater than 95% pure enzyme per liter. The stabilized enzyme was characterized kinetically and was indistinguishable from the wild-type recombinant protease, exhibiting Km and catalytic constant values of 0.578 mM and 13.18/min, respectively, for the maturation site (M-site) peptide substrate, GVVNASCRLARR (underlined residues indicate additions to or substitutions from peptides derived from the wild-type substrate). This enzyme was also used to perform inhibition studies with a series of truncated and/or substituted maturation site peptides. Short nonsubstrate M-site-derived peptides were demonstrated to be competitive inhibitors of cleavage in vitro, and these analyses defined amino acids VVNA, P4 through P1 in the substrate, as the minimal substrate binding and recognition sequence for the HCMV protease.

Web interface for the Heart Disease Program.

The task of making a large complex diagnostic program available to a broad audience of physicians has become more feasible with the ubiquitous accessibility of the client-server architecture of the World Wide Web. This paper describes the design and implementation of a Web interface for the Heart Disease Program (HDP). The client-server architecture imposes a number of requirements on the program. The graphical capabilities of the Web enable a number of enhancements to the program but also cause some limitations. Our initial experience with physicians using the HDP through the Web interface has been positive and we are now conducting an evaluation of the HDP using this form of access.

A comparison of performance of mathematical predictive methods for medical diagnosis: identifying acute cardiac ischemia among emergency department patients.

BACKGROUND: There is increasing interest in mathematical methods for the prediction of medical outcomes. Three methods have attracted particular attention: logistic regression, classification trees (such as ID3 and CART), and neural networks. To compare their relative performance, we used a large clinical database to develop and compare models using these methods. METHODS: Each modeling method was used to generate predictive instruments for acute cardiac ischemia (which includes acute myocardial infarction and unstable angina pectoris), using prospectivel-collected clinical data on 5773 patients, who presented over a two year period to six hospitals' emergency departments with chest pain or symptoms suggesting acute ischemia. This data set was then split into training (n = 3453) and test (n = 2320) sets. Of 200 available variables, modeling was restricted to those available within the first 10 minutes of emergency department care (history, physical exam, and electrocardiogram). RESULTS: When the number of variables was limited to eight, representing a practical number for input in the real-time clinical setting, the logistic regression's receiver-operating characteristic (ROC) curve area, as a measure of diagnostic performance, was 0.887; the classification tree model's ROC curve area was 0.858, and the neural network's ROC curve area was 0.902. When the number of variables used by a model was not limited, the logistic regression's ROC area was 0.905, the classification tree model's 0.861, and the neural network's 0.923. Among these models the neural networks had noticeably poorer calibration. When the outputs from each of these unrestricted models were presented to each of the other methods as an additional independent variable, the ROC areas of the new "hybrid" models were not significantly better than the original unlimited models (ROC areas 0.858 to 0.920). CONCLUSIONS: Logistic regression, classification tree, and neural network models all can provide excellent predictive performance of medical outcomes for clinical decision aids and policy models. Their ultimate limitations seem due to the availability of the information in data (a "data barrier") rather than their respective intrinsic properties. Choices between these methods would seem to be most appropriately based on the needs of the specific application, rather than on the premise that any one of these methods is intrinsically more powerful.

Susceptibilities of human immunodeficiency virus type 1 enzyme and viral variants expressing multiple resistance-engendering amino acid substitutions to reserve transcriptase inhibitors.

To evaluate the potential that multiply resistant human immunodeficiency virus type 1 variants may arise during combination nucleoside and nonnucleoside reverse transcriptase inhibitor therapy, we constructed a series of mutant reverse transcriptase enzymes and viruses that coexpressed various combinations of resistance-associated amino acid substitutions. Substitutions at residues 100 (Leu-->Ile) and 181 (Tyr-->Cys), which mediate resistance to the nonnucleosides, suppressed resistance to 3'-azido-3'-deoxythymidine (AZT) when coexpressed with AZT-specific substitutions. However, a number of viral variants that exhibited significantly reduced susceptibilities to both classes of inhibitors were constructed.

Peptide substrate cleavage specificity of the human cytomegalovirus protease.

The human cytomegalovirus UL80 gene encodes an 80-kDa precursor polyprotein whose N-terminal 256-amino acid domain is a protease. This enzyme cleaves a specific peptide bond that results in its own release from the precursor, as well as a peptide bond near the C terminus of the viral assembly protein. The latter cleavage is apparently required for encapsidation of the viral genomic DNA and maturation of the viral capsid. A series of peptide substrates, representing the assembly protein cleavage site, was used to study the enzyme's substrate requirements and specificity. It was found that efficient cleavage minimally required the amino acid residues spanning the P4 to P4' positions. Substitution at any of these residues adversely affected the reaction. Conservation of the hydrophobic residues at P3 and P4 was essential. In addition, cleavage of a peptide representing the protease domain release site was reduced almost 100-fold relative to cleavage of the assembly protein maturation site peptide substrate.

Evaluation of a new method for cardiovascular reasoning.

OBJECTIVE: Evaluate the accuracy of the detailed diagnostic reasoning of the Heart Failure Program incorporating a new mechanism to handle temporal relationships and severity constraints. DESIGN: Tools were developed to summarize diagnoses and automatically generate evaluation forms. Five expert cardiologists were asked to review the reasoning of the program, with two analyzing each case. Cases were gathered retrospectively for diversity and difficulty and 26 randomly selected cases were evaluated. The underlying issues were identified and classified. RESULTS: Both reviewers rated the first diagnosis correct in 25% of the cases and at least one rated it wrong in 10%. Analyzing the detailed reasoning, 137 issues were raised, about 5.3 per case. Of these, 53% were possible concerns raised by one reviewer. Of the 5.3 issues per case, 2.5 were attributable to controversies, misunderstandings, or mistakes; 1 was due to the overly simplistic representation of the summaries; and 1.8 were issues related to the program. CONCLUSION: Overall, the program is capable of providing high-quality detailed diagnostic hypotheses for complex cardiovascular cases. The results highlight several issues: 1) the difficulty of effectively summarizing hypotheses, 2) the nature of a physician's causal explanation, and 3) some problems in evaluating detailed diagnostic reasoning. The mistakes the program made imply that some additional refinement is needed but that the reasoning mechanisms developed can support the appropriate reasoning. The appropriate next step is a prospective evaluation addressing the program's usefulness.