Development of a multivariable prediction model for early revision of total knee arthroplasty - The effect of including patient-reported outcome measures.

BACKGROUND: Revision TKA is a serious adverse event with substantial consequences for the patient. As revision is becoming increasingly common in patients under 65 years, the need for improved preoperative patient selection is imminently needed. Therefore, this study aimed to identify the most important factors of early revision and to develop a prediction model of early revision including assessment of the effect of incorporating data on patient-reported outcome measures (PROMs). MATERIAL AND METHODS: A cohort of 538 patients undergoing primary TKA was included. Multiple logistic regression using forward selection of variables was applied to identify the best predictors of early revision and to develop a prediction model. The model was internally validated with stratified 5-fold cross-validation. This procedure was repeated without including data on PROMs to develop a model for comparison. The models were evaluated on their discriminative capacity using area under the receiver operating characteristic curve (AUC). RESULTS: The most important factors of early revision were age (OR 0.63 [0.42, 0.95]; P = 0.03), preoperative EQ-5D (OR 0.07 [0.01, 0.51]; P = 0.01), and number of comorbidities (OR 1.01 [0.97, 1.25]; P = 0.15). The AUCs of the models with and without PROMs were 0.65 and 0.61, respectively. The difference between the AUCs was not statistically significant (P = 0.32). CONCLUSIONS: Although more work is needed in order to reach a clinically meaningful quality of the predictions, our results show that the inclusion of PROMs seems to improve the quality of the prediction model.

Do femoral fractures in adult patients with osteogenesis imperfecta imitate atypical femoral fractures? A case series.

Atypical femoral fractures (AFFs) are low-energy femoral fractures with characteristic radiological features and a suspected relation to treatment with bisphosphonate (BP) or denosumab. In osteogenesis imperfecta (OI), BP is currently the drug of choice when medical treatment is indicated. Due to bone deformities, the radiologic appearance of femoral fractures may be different in patients with OI and patients with osteoporosis. We investigated the prevalence and appearance of femoral fractures in a cohort of adult patients with confirmed OI (55 patients, age range 19-69 years, 26 women (47%) and 35 patients (64%) had received BP treatment), who attended the outpatient clinic at Aarhus University Hospital. The fractures were evaluated according to major and minor AFF criteria. In our OI cohort, we found that eight out of 55 patients had suffered a femoral fracture in adult year: five women and three men, aged 25 to 54 years. One patient had OI type I, two had OI type III, four had OI type IV, and one had OI type V. All fractures were associated with no or minimal trauma. Four patients had fractures that fulfilled the criteria of AFFs. Two of the four patients had received long-term BP treatment prior to the fracture and three patients had severe deformities of the femur. Femoral fractures in OI imitate AFFs. This suggests that bone deformity, collagen deficiencies, and alterations in mineralization of bone may cause femoral fractures that imitate AFFs even in the absence of antiresorptive treatment. Bone deformities should be monitored as part of the management of adult patients with OI. Continuous dull or aching pain in the groin or thigh should lead to radiographic examination. The radiologic appearance of femoral fractures may be different in patients with osteogenesis imperfecta (OI) and patients with osteoporosis, thus imitate atypical femoral fractures (AFF). We found that bone deformity, collagen deficiencies, and alterations in bone mineralization may cause femoral fractures that imitate AFFs even in the absence of antiresorptive treatment.

Evaluation of the iPLEX® Sample ID Plus Panel designed for the Sequenom MassARRAY® system. A SNP typing assay developed for human identification and sample tracking based on the SNPforID panel.

Sequenom launched the first commercial SNP typing kit for human identification, named the iPLEX(®) Sample ID Plus Panel. The kit amplifies 47 of the 52 SNPs in the SNPforID panel, amelogenin and two Y-chromosome SNPs in one multiplex PCR. The SNPs were analyzed by single base extension (SBE) and Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). In this study, we evaluated the accuracy and sensitivity of the iPLEX(®) Sample ID Plus Panel by comparing the typing results of the iPLEX(®) Sample ID Plus Panel with those obtained with our ISO 17025 accredited SNPforID assay. The average call rate for duplicate typing of any one SNPs in the panel was 90.0% when the mass spectra were analyzed automatically with the MassARRAY(®) TYPER 4.0 genotyping software in real time. Two reproducible inconsistencies were observed (error rate: 0.05%) at two different SNP loci. In addition, four inconsistencies were observed once. The optimal amount of template DNA in the PCR was ≥10ng. There was a relatively high risk of allele and locus drop-outs when ≤1ng template DNA was used. We developed an R script with a stringent set of "forensic analysis parameters" based on the peak height and the signal to noise data exported from the TYPER 4.0 software. With the forensic analysis parameters, all inconsistencies were eliminated in reactions with ≥10ng DNA. However, the average call rate decreased to 69.9%. The iPLEX(®) Sample ID Plus Panel was tested on 10 degraded samples from forensic case-work. Two samples could not be typed, presumably because the samples contained PCR and SBE inhibitors. The average call rate was generally lower for degraded DNA samples and the number of inconsistencies higher than for pristine DNA. However, none of the inconsistencies were reproduced and the highest match probability for the degraded samples typed with the panel was 1.7E-9 using the stringent forensic analysis parameters. Although the relatively low sensitivity of the iPLEX(®) Sample ID Plus Panel makes it inappropriate for typing of trace samples from crime scenes, the panel may be interesting for relationship testing and for identification of e.g. samples in biobanks because of the low reagent costs, the limited hands-on time of the iPLEX(®) assay and the automatic analysis of the mass spectra.

Process-scale purification of immunoglobulin M concentrate.

An IgM concentrate was purified from Cohn fraction III. Efficiency of euglobin precipitation was shown to be controlled by pH and ionic strength. Prekallikrein activator activity in the product was insignificant. Overall yield from the octanoic acid supernate and purity of the concentrate were 66 +/- 8 (n = 16) and 50 +/- 5% (n = 16), respectively. Solvent-detergent treatment to inactivate lipid-enveloped viruses was demonstrated and implemented into the process. Process studies to control residual virucidal agents and C4a generating activity are presented.

Clinical significance of the ST-segment response and other early exercise test variables in uncomplicated vs complicated myocardial infarction.

An exercise test was performed in 455 patients in the third week after acute myocardial infarction (AMI). One hundred and seventeen (26%) of them were considered as having a complicated AMI. During a follow-up of 4.5 years their mortality was 49% vs 23% in the remaining patients with uncomplicated AMI. The survival of the patients was assessed in each clinical group in relation to various exercise variables. Exercise-induced ST-segment depression, irrespective of its degree, did not discriminate significantly between dead and living patients in any of the clinical groups. A high value of the rise of the pressure-rate product (PRP) from rest to maximal exercise (dPRP) and absence of significant exercise-induced ventricular arrhythmias identified in both clinical groups patients with a very low risk of dying. A low dPRP and/or occurrence of significant ventricular arrhythmias identified a relatively high risk in uncomplicated AMI patients and a very high risk of dying in complicated AMI subjects. The difference in the probability of survival between low-risk and high-risk patients was highly significant in each clinical group (P less than 0.0001 in uncomplicated, and less than 0.005 in complicated AMI, respectively).

Assessment of the performance of electrocardiographic computer programs with the use of a reference data base.

To allow an exchange of measurements and criteria between different electrocardiographic (ECG) computer programs, an international cooperative project has been initiated aimed at standardization of computer-derived ECG measurements. To this end an ECG reference library of 250 ECGs with selected abnormalities was established and a comprehensive reviewing scheme was devised for the visual determination of the onsets and offsets of P, QRS, and T waves. This task was performed by a group of cardiologists on highly amplified, selected complexes from the library of ECGs. With use of a modified Delphi approach, individual outlying point estimates were eliminated in four successive rounds. In this way final referee estimates were obtained that proved to be highly reproducible and precise. This reference data base was used to study measurement results obtained with nine vectorcardiographic and 10 standard 12-lead ECG analysis programs. The medians of program determinations of P, QRS, and T wave onsets and offsets were close to the final referee estimates. However, an important variability could be demonstrated between measurements from individual programs and mean differences from the referee estimates amounted to 10 msec for QRS for certain programs. In addition, the variances of all programs with respect to the referee point estimates were variable. Some programs proved to be more accurate and stable when the data from high- vs low-noise recordings were analyzed. Average Q wave durations calculated from ECGs for which programs agreed on the presence of a Q or QS wave differed by more than 8 msec in several program-to-program comparisons. Such differences may have important consequences with respect to diagnostic performance. Various factors that might explain these differences have been determined. The present study demonstrates that to allow an exchange of results and diagnostic criteria between different ECG computer programs, definitions, minimum wave requirements, and measurement procedures urgently need to be standardized.

Post-myocardial infarction exercise testing: clinical significance of a left ventricular function index and ventricular arrhythmias. A prospective study.

A predischarge exercise test was performed in a prospective series of 187 patients, less than 70 years old, with acute myocardial infarction. A survival analysis confirmed previous retrospective findings of a significantly increased long-term mortality in patients with a low increase in the pressure-rate-product (PRP) and/or with major exercise-induced arrhythmias. ST segment depression was without prognostic significance. By a graduated, quantitative re-evaluation of the significance of exercise-induced ventricular arrhythmias, an appropriate, significantly discriminating cutoff point for the frequency of solitary ventricular premature beats (VPBs) was found at two or more VPBs/min. Repetitive VPBs had an equal significance. The probability of 4.5-year survival in patients with these arrhythmias and a low increase in PRP was 0.49 vs. 0.85 in patients with less frequent arrhythmias and with a high increase in PRP (p less than 10(-6)).

Prognostic significance of the ST-segment response during exercise test shortly after acute myocardial infarction. Comparison with other exercise variables.

An exercise test was made in 317 patients in the third week after acute myocardial infarction. The following types of exercise associated ST-segment responses were registered in patients less than 70-years-old. I: no ST-deviation (33.6%), II: ST-depression (42.9%), III: ST-elevation (13.4%) and IV: inconclusive ST-response (10.1%). The 5-year mortality was significantly lower in group III than in groups II and IV. Group IV had a significantly higher 5-year mortality than all the other groups. Patients with ST-depression had an increased late mortality compared to that of the patients without ST-deviation, but the total mortality did not differ between these two groups. A highly increased risk of dying was found in groups I, II and IV in patients with exercise associated major ventricular arrhythmias and/or with a small increase of the pressure-rate-product (PRP) during exercise. Patients without arrhythmias and with a high increase of the PRP had a low mortality rate irrespective of their ST-response. In the older patients (70-years-old or more) the ST-response was of no prognostic value at all. The ST-segment response was thus generally of limited value in the prognostic management of the present patients. Their survival was mainly determined by the other exercise variables-the magnitude of an exercise index of left ventricular function and the occurrence of ventricular arrhythmias.

Haemolysis and hyposideraemia in patients with Lillehei-Kaster prosthetic heart valves: a long-term follow-up.

Forty-four patients with mitral and/or aortic Lillehei-Kaster valvular prostheses were evaluated with regard to haemolysis, hyposideraemia and anaemia, with median intervals of 0.4 years and 7.0 years after the operation. At the first study the majority of patients presented slight to moderate haemolysis; 7 per cent showed hyposideraemia, while none had overt anaemia. At the long-term follow-up the incidence and degree of haemolysis had increased slightly; hyposideraemia was present in 16 per cent, while only one patient had developed anaemia. The modest increase of haemolysis could be accounted for, at least in part, by the development of paravalvular regurgitation or additional valvular disease. It is concluded that the Lillehei-Kaster prostheses are less traumatic to the red cells than earlier types of synthetic prostheses. Apparently, iron medication is indicated only in the minority of patients who develop hyposideraemia and a low normal or decreased haemoglobin value.

Early exercise test vs. clinical parameters in the long-term prognostic management after myocardial infarction.

An early exercise test was performed in 317 patients with acute myocardial infarction (AMI). The long-term prognosis was assessed after an average follow-up of 5.7 years. The patients with a small increase in the pressure rate product from rest to maximal exercise and/or wih major ventricular arrhythmias constituted a general prognostic high-risk group. The survival was analyzed further applying the above mentioned exercise parameters in the following clinical subgroups: I) patients with clinical heart failure during hospitalization and/or previous myocardial infarction, II) patients with anterior AMI, III) patients with inferior or indefinite AMI. Within each clinical group there was a highly significant difference in survival between the exercise-determined high-risk and low-risk patients. The exercise parameters were more sensitive and more specific prognostic determinators than the clinical variables. The most striking difference was found in patients with clinical heart failure and/or previous infarction. In this group the exercise-determined high-risk patients had a probability of 5-year survival of 0.238 vs. 0.909 in the corresponding low-risk patients (p less than 0.0005).

Temporal relationship between cardiac performance and myocardial uptake of dl-propranolol in man.

1. The temporal relationship between the myocardial arteriovenous difference of plasma propranolol concentration and heart rate and left ventricular dp/dt maximum was examined for 30 min after intravenous administration of 10mg (0.04 mmol) dl-propranolol in nine patients with ischaemic heart disease. 2. Very large positive myocardial a.v. differences of propranolol within the first 5 min became negative after 5 min, indicating a rapid, avid uptake with subsequent release of propranolol from the heart. 3. The heart rate and left ventricular dp/dt maximum increased 1 min after propranolol administration and did not change after the fifth min of the observation period. 4. The data suggest that a large number of unspecific binding sites for propranolol are present in the heart in addition to the specific beta-receptors.

DC-conversion of atrial fibrillation after mitral valve operation. An analysis of the long-term results.

In a prospective study comprising 43 patients with atrial fibrillation after mitral valve surgery, an evaluation was made of the prognostic significance of clinical, radiological, haemodynamic and operative factors for the maintenance of sinus rhythm after DC-conversion. Atrial fibrillation with a duration of less than 12 months proved to be the only single factor of significance for sustained sinus rhythm after 12 months and it is suggested as a simple clinical criterion for selection of patients for DC-conversion after mitral valve operation.

Spironolactone-induced changes in digoxin kinetics.

Plasma clearance, volumes of distribution, and renal and extrarenal clearances of digoxin were calculated from plasma digoxin concentrations and urinary excretion of digoxin after intravenous injection of digoxin in 8 subjects. The investigation was repeated in the same subjects during long-term treatment with spironolactone. Increased plasma concentration of digoxin was detected during spironolactone treatment. Calculated plasma and renal clearances of digoxin and the volumes of distribution decreased statistically significant. Near maximal capacity for the tubular secretion of digoxin was found when normal digoxin dosage was used. It is suggested that unless spironolactone decreases the myocardial sensitivity for digoxin, the loading dose as well as the maintenance dose of digoxin should be reduced during treatment with spironolactone.

Long-term ECG monitoring in suspected Adams-Stokes disease.

Long-term ECG recording techniques have facilitated the diagnosis in atypical cases of Adams-Stockes syndrome. In the use of ambulatory ECG monitoring, new and mainly technical problems have been arisen. In 200 ECG recordings on cassette tape, 78% was considered sufficient for an accurate diagnosis. More than 50% of the unsuccessful recordings were unreadable due to electrode problems. The use of ambulatory monitoring demands that electrode fixation and placement be handled carefully and that the mechanical and electronic equipment be serviced frequently. Patients with third-degree atrioventricular block and syncopes of fainting spells run a high risk of sudden death. It is therefore not recommended to use ambulatory monitoring techniques on these patients.