Medication as a risk factor for hospitalization due to heart failure and shock: a series of case-crossover studies in Swiss claims data.

PURPOSE: Heart failure is among the leading causes for hospitalization in Europe. In this study, we evaluate potential precipitating factors for hospitalization for heart failure and shock. METHODS: Using Swiss claims data (2014-2015), we evaluated the association between hospitalization for heart failure and shock, and prescription of oral potassium supplements, non-steroidal anti-inflammatory drugs (NSAIDs), and amoxicillin/clavulanic acid. We conducted case-crossover analyses, where exposure was compared for the hazard period and the primary control period (e.g., 1-30 days before hospitalization vs. 31-60 days, respectively). Conditional logistic regression was applied and subsequently adjusted for addressing potential confounding by disease progression. Sensitivity analyses were conducted and stratification for co-medication was performed. RESULTS: We identified 2185 patients hospitalized with heart failure or shock. Prescription of potassium supplements, NSAIDs, and amoxicillin/clavulanic acid was significantly associated with an increased risk for hospitalization for heart failure and shock with crude odds ratios (OR) of 2.04 for potassium (95% CI 1.24-3.36, p = 0.005, 30 days), OR 1.8 for NSAIDs (95% CI 1.39-2.33, p < 0.0001, 30 days), and OR 3.25 for amoxicillin/clavulanic acid (95% CI 2.06-5.14, p < 0.0001, 15 days), respectively. Adjustment attenuated odds ratios, while the significant positive association remained (potassium OR 1.70 (95% CI 1.01-2.86, p = 0.046), NSAIDs OR 1.50 (95% CI 1.14-1.97, p = 0.003), and amoxicillin/clavulanic acid OR 2.26 (95% CI 1.41-3.62, p = 0.001). CONCLUSION: Prescription of potassium supplements, NSAIDs, and amoxicillin/clavulanic acid is associated with increased risk for hospitalization. Underlying conditions such as pain, electrolyte imbalances, and infections are likely contributing risk factors. Physicians may use this knowledge to better identify patients at risk and adapt patient management.

Prediction of health care expenditure increase: how does pharmacotherapy contribute?

BACKGROUND: Rising health care costs are a major public health issue. Thus, accurately predicting future costs and understanding which factors contribute to increases in health care expenditures are important. The objective of this project was to predict patients healthcare costs development in the subsequent year and to identify factors contributing to this prediction, with a particular focus on the role of pharmacotherapy. METHODS: We used 2014-2015 Swiss health insurance claims data on 373'264 adult patients to classify individuals' changes in health care costs. We performed extensive feature generation and developed predictive models using logistic regression, boosted decision trees and neural networks. Based on the decision tree model, we performed a detailed feature importance analysis and subgroup analysis, with an emphasis on drug classes. RESULTS: The boosted decision tree model achieved an overall accuracy of 67.6% and an area under the curve-score of 0.74; the neural network and logistic regression models performed 0.4 and 1.9% worse, respectively. Feature engineering played a key role in capturing temporal patterns in the data. The number of features was reduced from 747 to 36 with only a 0.5% loss in the accuracy. In addition to hospitalisation and outpatient physician visits, 6 drug classes and the mode of drug administration were among the most important features. Patient subgroups with a high probability of increase (up to 88%) and decrease (up to 92%) were identified. CONCLUSIONS: Pharmacotherapy provides important information for predicting cost increases in the total population. Moreover, its relative importance increases in combination with other features, including health care utilisation.

Analysis of Drug-Drug Interactions in Swiss Claims Data Using Tizanidine and Ciprofloxacin as a Prototypical Contraindicated Combination.

BACKGROUND: Potential drug-drug interactions (pDDIs) are described in various case reports, but few studies have evaluated the impact of specific combinations on a population level. OBJECTIVE: To analyze the type and frequency of multiple contraindicated (X-pDDIs) and major interactions (D-pDDIs) and to subsequently assess the impact of the particular combination of tizanidine and ciprofloxacin on outpatient physician visits and hospitalizations. METHODS: Anonymized Swiss claims data from 524 797 patients in 2014-2015 were analyzed. First, frequencies of X- and D-pDDIs were calculated. Next, a retrospective cohort study was conducted among patients prescribed tizanidine and ciprofloxacin (exposed, n = 199) or tizanidine and other antibiotics (unexposed, n = 960). Hospitalizations and outpatient physician visits within 7, 14, and 30 days after initiation of antibiotic therapy were evaluated using multiple binary logistic regression and multiple linear regression. RESULTS: The relative frequencies of X- and D-pDDIs were 0.4% and 6.65%, respectively. In the cohort study, significant associations between exposure to tizanidine and ciprofloxacin and outpatient physician visits were identified for 14 and 30 days (odds ratio [OR] = 1.61 [95% CI = 1.17-2.24], P = 0.004, and OR = 1.59 [95% CI = 1.1-2.34], P = 0.016). A trend for increased risk of hospitalization was found for all evaluated time periods (OR = 1.68 [95% CI = 0.84-3.17], OR = 1.52 [95% CI = 0.63-3.33], and OR = 2.19 [95% CI = 0.88-5.02]). Conclusion and Relevance: The interaction between tizanidine and ciprofloxacin is not only relevant for individual patients, but also at the population level. Further investigation of the impact of other clinically relevant DDIs is necessary to improve patient safety and reduce avoidable health care utilization.

Two regression methods for estimation of a two-parameter Weibull distribution for reliability of dental materials.

OBJECTIVES: Comparison of estimation of the two-parameter Weibull distribution by two least squares (LS) methods with interchanged axes. Investigation of the influence of plotting positions and sample size. Derivation of 95% confidence intervals (95%CI) for Weibull parameters applicable in the context of LS estimation. Preparation of a free available Excel template for computation of point estimates and 95%CI for Weibull modulus (m) and characteristic strength (s). METHODS: Monte Carlo simulation covering a wide range of Weibull parameters and sample sizes. Mathematical derivation of formulae for computation of 95%CI according to a Menon-type approach for both m and s. Empirical proof that the practically observed coverage agrees with the nominal one of 95%. RESULTS: Relative and absolute performance of LS estimators depended on sample size, plotting positions and parameter to be estimated. For most situations they outperformed the corresponding Maximum Likelihood (ML) estimator in terms of bias, while precision was almost the same. Naïve Wald-type 95%CI based on standard errors of LS regression coefficients did not reach targeted coverage. An easy-to-apply alternative based on asymptotic standard errors (Menon 95%CI) resulted in excellent coverage. CONCLUSION: Accuracy of the LS methods for Weibull modulus and characteristic strength essentially depend on plotting position and sample size. Large sample sizes (n≥30) support a credible Weibull parameters estimation. An important complement of the point estimates of Weibull parameters is provided by the Menon 95%CI. A free available Excel template considerably facilitating computation of point and interval estimates of Weibull parameters is provided.

Peri-implantitis prevalence and treatment in implant-oriented private practices: a cross-sectional postal and Internet survey.

This survey aimed to estimate the subjective prevalence of peri-implantitis and its management in the private with and without board certified specialization. For this purpose, a cross-sectional postal and internet survey of 521 dentists, representing all members of the Swiss Society of Oral Implantology (SGI) was conducted (year 2010). The questionnaire consisted of four sections assessing 1) general information regarding the practice setting and education, 2) general questions regarding implantation profile and 3) specific questions regarding the prevalence and experience with the management of peri-implantitis. In the fourth section, therapy options of three exemplary cases were assessed. The data were separately evaluated and compared for specialists (S) and n₋specialists (N-S). A total of 253 questionnaires could be included in the present study. The results revealed that specialists placed significantly more implants than non-specialists. The subjective prevalence of cases with peri₋implantitis was 5-6 and 7-9% after 5 and 10 years, respectively. The polled dentists perceived periodontitis (N-S: 72%; S: 80%), smoking (N-S: 71; S: 77%) and bad compliance (S: 53; N-S: 61%) as the most important risk factors for peri-implantitis. Chlorhexidine was the most frequently used antiseptic agent for disinfection. A surgical approach to treat peri-implantitis was reported by more than 80% of all dentists. Specialists used significantly more resective or regenerative approaches than non-specialists.

Validation of a transparent decision model to rate drug interactions.

BACKGROUND: Multiple databases provide ratings of drug-drug interactions. The ratings are often based on different criteria and lack background information on the decision making process. User acceptance of rating systems could be improved by providing a transparent decision path for each category. METHODS: We rated 200 randomly selected potential drug-drug interactions by a transparent decision model developed by our team. The cases were generated from ward round observations and physicians' queries from an outpatient setting. We compared our ratings to those assigned by a senior clinical pharmacologist and by a standard interaction database, and thus validated the model. RESULTS: The decision model rated consistently with the standard database and the pharmacologist in 94 and 156 cases, respectively. In two cases the model decision required correction. Following removal of systematic model construction differences, the DM was fully consistent with other rating systems. CONCLUSION: The decision model reproducibly rates interactions and elucidates systematic differences. We propose to supply validated decision paths alongside the interaction rating to improve comprehensibility and to enable physicians to interpret the ratings in a clinical context.

Assessment of changes in vascularity and blood volume in canine sarcomas and squamous cell carcinomas during fractionated radiation therapy using quantified contrast-enhanced power Doppler ultrasonography: a preliminary study.

Radiation therapy does not only target tumour cells but also affects tumour vascularity. In the present study, changes in tumour vascularity and blood volume were investigated in five grade 1 oral fibrosarcomas, eight other sarcomas (non-oral soft tissue and bone sarcomas) and 12 squamous cell carcinomas in dogs during fractionated radiation therapy (total dose, 45-56 Gy). Contrast-enhanced power Doppler ultrasound was performed before fraction 1, 3, 6, 8, 10, 12, 14 and 15 or 16 (sarcomas) or 17 (squamous cell carcinomas). Prior to treatment, median vascularity and blood volume were significantly higher in squamous cell carcinomas (P=0.0005 and 0.001), whereas measurements did not differ between oral fibrosarcomas and other sarcomas (P=0.88 and 0.999). During the course of radiation therapy, only small, non-significant changes in vascularity and blood volume were observed in all three tumour histology groups (P=0.08 and P=0.213), whereas median tumour volume significantly decreased until the end of treatment (P=0.04 for fibrosarcomas and other sarcomas, P=0.008 for squamous cell carcinomas). It appeared that there was a proportional decrease in tumour volume, vascularity and blood volume. Doppler measurements did not predict progression free interval or survival in any of the three tumour groups (P=0.06-0.86). However, the number of tumours investigated was small and therefore, the results can only be considered preliminary.

Clinical assessment of repeated propofol-associated anesthesia in cats.

OBJECTIVE: To assess the effects of repeated episodes of propofol-associated anesthesia on quality of recovery from anesthesia, clinical status, and erythrocyte physiology in cats. DESIGN: Original study. ANIMALS: 37 cats undergoing short-duration anesthesia for radiotherapy. PROCEDURES: Twice daily on 5 consecutive days, 13 cats with squamous cell carcinoma of the nasal planum (group 1) underwent anesthesia: first via administration of propofol or a midazolam (0.2 mg/kg [0.09 mg/lb])-propofol combination and then via administration of ketamine and midazolam each day (latter data were not analyzed). During a 19-day period, 24 cats with vaccine associated sarcoma (group 2) were anesthetized 12 times with propofol or a midazolam-propofol combination. Anesthesia was maintained with propofol in both groups. Hematologic analysis was performed before, during, and on completion of radiotherapy; changes in Hct and hemoglobin concentration between groups were compared. RESULTS: Mean duration of anesthesia was 8.1 minutes (range, 5 to 20 minutes); no adverse events were detected during recovery. Total dose of propofol administered did not differ between groups 1 (6.34 mg/kg [2.88 mg/lb]) and 2 (4.71 mg/kg [2.14 mg/lb]). Midazolam administration decreased the propofol dose by 26%. Overall decreases from baseline in Hct and hemoglobin concentration were not significantly different between the 2 groups, nor clinically important; however, compared with baseline, values in group 2 were significantly lower after 6 and 12 anesthetic episodes for both protocols. Heinz bodies were identified in low numbers in both groups during radiotherapy. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that repeated propofol-associated short-duration anesthesia does not lead to clinically relevant hematologic changes in cats undergoing short-duration radiotherapy.

Evaluation of quantified contrast-enhanced color and power Doppler ultrasonography for the assessment of vascularity and perfusion of naturally occurring tumors in dogs.

OBJECTIVE: To investigate subjective and computerized methods of evaluation of color Doppler (CD) and power Doppler (PD) ultrasonographic images (obtained before and after administration of contrast medium) for quantitative assessment of vascularity and perfusion of various naturally occurring tumors in dogs. SAMPLE POPULATION: 34 tumors in 34 dogs. PROCEDURE: Tumors in dogs were examined via CD and PD ultrasonography before and after i.v. injection of a microbubble contrast agent (pre- and postcontrast examinations, respectively). Images were digitized for subjective assessment of vessel density and vascular pattern and computer-aided assessment of parameters of vascularity (fractional area [FA]) and perfusion (color-weighted FA [CWFA] and mean color-weighted FA [CWFA] and mean color level). RESULTS: With both analysis methods, more vessels were identified in precontrast PD ultrasonographic images than in precontrast CD ultrasonographic images. Moreover, compared with values for precontrast PD ultrasonography, FA, CWFA, and mean color level were higher for postcontrast PD ultrasonography. In postcontrast images, there was a significant association between vessel densities determined through subjective and computerized assessments. Although sample size was small, vascularity of squamous cell carcinomas was significantly greater than that of other tumor types. Ten of the 19 softer than issue that sarcomas had low vessel density with minor contrast enhancement. With increasing gross tumor volume, FA and CWFA decreased for all Doppler ultrasonographic methods. CONCLUSIONS AND CLINICAL RELEVANCE: Higher values of the ultrasonographic parameters representing vascularity and perfusion of tumors in dogs were determined via PD ultrasonography after administration of contrast medium than via PD or CD ultrasonography without administration of contrast medium.

Assessment of a radiotherapy patient immobilization device using single plane port radiographs and a remote computed tomography scanner.

Radiation treatment requires a precise procedure for interfraction repositioning of the patient. The purpose of this study was to determine the accuracy of our fixation device in treatment position and to evaluate the setup accuracy with two different methods. The positioning data of 19 canine patients with tumors in the head region (oral, nasal, cerebral) treated with photon or proton irradiation were included in this study. The patients were immobilized by means of an individualized fixation device. Focus was set upon interfraction displacement with systematic and random components. In one method, treatment position was evaluated using single plane port radiographs and megavoltage x-rays. In the other method, two orthogonal CT-topograms were acquired to evaluate the precision of positioning of the patient in the immobilization device. Systematic and random displacements were calculated and presented as mean values with corresponding 95% confidence intervals. In spite of a difference between both methods, the positioning seemed to be accurate within the expected range. It seems that a safety margin of 3.7 mm would be enough for both methods to take into account systematic and random position variability in the fixation device, thereby preventing geometric inaccuracies of treatment delivery. The reported immobilization protocol provides accurate patient immobilization for photon and conformal proton radiation therapy.