Whom to treat? The contribution of vertebral X-rays to risk-based algorithms for fracture prediction. Results from the European Prospective Osteoporosis Study

Introduction Vertebral fracture is a strong risk factor for future spine and hip fractures; yet recent data suggest that only 5–20% of subjects with a spine fracture are identified in primary care. We aimed to develop easily applicable algorithms predicting a high risk of future spine fracture in men and women over 50 years of age.Methods Data was analysed from 5,561 men and women aged 50+ years participating in the European Prospective Osteoporosis Study (EPOS). Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. These were evaluated by an experienced radiologist. The risk of a new (incident) vertebral fracture was modelled as a function of age, number of prevalent vertebral fractures, height loss, sex and other fracture history reported by the subject, including limb fractures occurring between X-rays. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of models.Results In a negative binomial regression model without baseline X-ray data, the risk of incident vertebral fracture significantly increased with age [RR 1.74, 95% CI (1.44, 2.10) per decade], height loss [1.08 (1.04, 1.12) per cm decrease], female sex [1.48 (1.05, 2.09)], and recalled fracture history; [1.65 (1.15, 2.38) to 3.03 (1.66, 5.54)] according to fracture site. Baseline radiological assessment of prevalent vertebral fracture significantly improved the areas subtended by ROC curves from 0.71 (0.67, 0.74) to 0.74 (0.70, 0.77) P=0.013 for predicting 1+ incident fracture; and from 0.74 (0.67, 0.81) to 0.83 (0.76, 0.90) P=0.001 for 2+ incident fractures. Age, sex and height loss remained independently predictive. The relative risk of a new vertebral fracture increased with the number of prevalent vertebral fractures present from 3.08 (2.10, 4.52) for 1 fracture to 9.36 (5.72, 15.32) for 3+. At a specificity of 90%, the model including X-ray data improved the sensitivity for predicting 2+ and 1+ incident fractures by 6 and 4 fold respectively compared with random guessing. At 75% specificity the improvements were 3.2 and 2.4 fold respectively. With the modelling restricted to the subjects who had BMD measurements (n=2,409), the AUC for predicting 1+ vs. 0 incident vertebral fractures improved from 0.72 (0.66, 0.79) to 0.76 (0.71, 0.82) upon adding femoral neck BMD (P=0.010).Conclusion We conclude that for those with existing vertebral fractures, an accurately read spine X-ray will form a central component in future algorithms for targeting treatment, especially to the most vulnerable. The sensitivity of this approach to identifying vertebral fracture cases requiring anti-osteoporosis treatment, even when X-rays are ordered highly selectively, exceeds by a large margin the current standard of practice as recorded anywhere in the world.This work was presented in part at the 30th European Symposium on Calcified Tissues, 8–12 May 2003, Rome, Italy.A.J. Silman and J. Reeve are the EU Grant holders and Project Leaders.     

Clinical experience of the pharmacological treatment algorithm for major depression in advanced cancer patients: preliminary study

INTRODUCTION : Treatment of major depression in advanced cancer patients is often difficult because of their special characteristics. METHOD : The authors developed a treatment algorithm for major depression in advanced cancer patients and report on their clinical experience using it. The applicability, tolerability, and clinical efficacy of the algorithm were evaluated in 95 advanced cancer patients with major depression. RESULTS : The algorithm was not suitable for seven patients and was not used correctly in 14 cases. It was correctly applied to 74 patients (77%), 23 of whom dropped out for cancer-related reasons (deterioration of physical condition, transfer to other hospitals, cancer death). As for tolerability, 22 patients (43%) of the 51 dropped out of the antidepressant treatment regimen because of delirium due to deterioration of their physical condition, adverse effects of the antidepressant, etc. In the 29 cases that could be followed up, clinical efficacy was evaluated for 4 weeks, and improvement was observed in 22 cases (76%). CONCLUSION : These preliminary findings suggest that use of the algorithm may be feasible, but that it requires some alterations to manage major depression in advanced cancer patients. (Int J Psych Clin Pract 2002; 6: 83-89)     

Differentiation of Cannabis subspecies by THCA synthase gene analysis using RFLP

Cannabis sativa subspecies, known as industrial hemp (C. sativa sativa) and marijuana (C. sativa indica) show no evident morphological distinctions, but they contain different levels of psychoactive Δ-9-tetrahidrocanabinol (THC), with considerably higher concentration in marijuana than in hemp. C. sativa subspecies differ in sequence of tetrahydrocannabinolic acid (THCA) synthase gene, responsible for THC production, and only one active copy of the gene, distinctive for marijuana, is capable of producing THC in concentration more then 0,3% in dried plants, usually punishable by the law.Twenty different samples of marijuana that contain THC in concentration more then 0,3% and three varieties of industrial hemp were analyzed for presence of an active copy of THCA synthase gene using in-house developed restriction fragment length polymorphism (RFLP) method All twenty samples of marijuana were positive for the active copy of THCA synthase gene, 16 of them heterozygous. All three varieties of industrial hemp were homozygous for inactive copy.An algorithm for the fast and accurate forensic analysis of samples suspected to be marijuana was constructed, answering the question if an analyzed sample is capable of producing THC in concentrations higher than 0.3%.     

Understanding Hispanic Patient Satisfaction with Telehealth During COVID-19

BackgroundRecent studies have described the use of telehealth for pediatric surgical care during the COVID-19 pandemic. We aimed to evaluate equity in telehealth use by comparing rates of utilization and satisfaction with pediatric surgical telemedicine among Hispanic patients.MethodsWe conducted a retrospective cohort study of patients seen by a surgical subspecialty provider in the outpatient setting at a quaternary pediatric hospital between April 1 and June 30, 2020. Patients evaluated in the same three-month period in 2019 were analyzed as a historic control. Differences in Family Experience Survey (FES) responses based on race and ethnicity and preferred language of care were assessed using univariable and multivariable generalized linear modeling.ResultsThe pandemic cohort included fewer patients of Hispanic ethnicity and fewer Spanish-speakers. After controlling for visit type, comparison of Spanish-speaking and English-speaking patients revealed that Spanish-speaking families had significantly lower scores for FES items that evaluated healthcare provider explaining (IRR 0.74, 95% CI: 0.61–0.90), listening (IRR 0.76, 95% CI: 0.63–0.92), and time spent with the family (IRR 0.73, 95% CI: 0.60–0.89). There were no differences in FES responses based on insurance status or degree of medical complexity.ConclusionsTelehealth services were less commonly used among Hispanic and Spanish-speaking patients. Language may differentially affect family satisfaction with healthcare and telehealth solutions. Strategies to mitigate these inequities are needed and may include strengthening interpreter services and providing language-concordant care.Level of evidenceLevel IV.     

An algorithm accounting for plating efficiency in estimating spontaneous mutation rates

An algorithm is described for calculating the probability distribution of the number of mutant colonies arising in a Luria-Delbrück fluctuation experiment subject to a plating efficiency of less than 100%. A table is constructed to facilitate the estimation of spontaneous mutation rates taking into account the plating efficiency.     

Evaluation of gene expression profile of keratinocytes in response to JP-8 jet fuel

The skin is the principal barrier against any environmental insult. Therefore, there is a high risk for a large number of military and civilian personnel exposed to jet fuel JP-8 to suffer percutaneous absorption of this fuel. This paper reports the use of cDNA microarray to identify the gene expression profile in normal human epidermal keratinocytes exposed to JP-8 for 24-h and 7-day periods. The effects of JP-8 exposure on keratinocytes at these two different periods induced a set of genes with altered expression in response to this type of insult. Microarray data were visualized using a novel algorithm based on simple statistical analyses to reduce data dimensionality and identify subsets of discriminant genes. Predictive neural networks were built using a multiplayer perceptron to carry out a proper classification task in microarray data in the untreated versus JP-8-treated samples. The pattern of expressions in response to JP-8 provides evidences that detoxificant-related and cell growth regulator genes with the most variability in the level of expression may be useful genetic markers in adverse health effects of personnel exposed to JP-8. The approaches in our analysis provide a simple, safe, novel, and effective method that is reliable in identifying and analyzing gene expression in samples treated with JP-8 or over potential toxic agents. Gene expression data from these studies can be used to build accurate predictive models that separate different molecular profiles. The data establish the use and effectiveness of these approaches for future prospective studies.     

Nursing home-acquired pneumonia: an emergency department treatment algorithm

SUMMARY

Nursing home-acquired pneumonia (NHAP) is a leading cause of morbidity, hospitalization, and mortality among older nursing home residents. Too often, these patients are erroneously grouped with cases of community-acquired and hospital-acquired pneumonia. Yet, they differ in terms of most common pathogens, significant underlying disease, impaired functional and cognitive status, and poor nutrition. The NHAP emergency department treatment algorithm presented here shows that an important decision for initial care in the emergency department (ED) is whether the patient should return to the nursing home. This decision often is based on the facility's ability to administer parenteral antibiotics, and care for co-morbidities and complications. Cephalosporins are the foundation of initial treatment of NHAP in the ED, and are combined with other antibiotics in anticipation of the most likely pathogens and treatment variables discussed here. It is hoped the NHAP treatment algorithm will contribute to improved outcomes.     

Effective estimation and computer control of minimum tumours temperature during conductive interstitial hyperthermia

The goal of heat therapy in the treatment of malignant disease is to raise the temperature of all neoplastic tissue to a cytotoxic temperature for a predetermined period of time. This seemingly simple task has proved difficult in vivo in part because of non-uniform power absorption and in part because of non-homogeneous and time-varying tumour blood flow. We have addressed this difficulty first by utilizing the conceptually simple technique of conductive interstitial hyperthermia, in which the tumour is warmed by multiple, electrically heated catheters, and second by implementing on-line control of minimum tumour temperatures near each catheter, estimated on the basis of the steady-state ratio of catheter power to catheter temperature rise. This report presents an analysis of the accuracy, precision, and stability of the on-line minimum temperature estimation/control technique for 22 patients who received 31 separate courses of conductive interstitial hyperthermia for the treatment of malignant brain tumours, and in whom temperature was monitored independently by 12–16 independent sensors per patient. In all patients the technique was found to accurately and precisely estimate and control the local minimum temperatures. Comparison of measured and estimated temperatures revealed a mean difference of 0.0°0.4°C for those sensors within 1.0 mm of the expected location for minimum temperatures. This technique therefore offers an attractive method for controlling hyperthermia therapy-even in the presence of time varying local blood flow.     

An unbiased glucose clamp method using a variable insulin infusion: its application in diabetic adolescents

A simple, unbiased insulin-varying glucose clamp program is described. The aim of the program was to utilize a continuously updated array of data to predict insulin requirements for normoglycaemia. In assessing Type 1 diabetes the quantity of insulin required for maintenance of basal euglycaemia can be more clinically informative than other clamp methods. We present a method which uses an iterative computer program to predict changes in insulin infusion rate required for glucose clamping. After initial parameter estimation, the program uses no fixed algorithm but makes predictions according to previous blood glucose responses to infusion rates. The program has flexible data entry, graphic display, and running statistics including mean infusion data, mean glucose levels, and their respective standard deviations. Data for 26 consecutive overnight clamp studies have been analysed. The median coefficient of variation of glucose values at the end of the clamp was 4.1% (range 1.4-12.0%). The mean bias during the last 2 h was 0.20 +/- 0.24 mmol l-1. Cross-correlation showed that insulin had its maximal effect on the rate of decline of glucose after 15 min, and the nadir of glucose occurred 45 min after a change in insulin infusion rate.