Search

Purpose: The aim of this study is to investigate the cost-effectiveness of revision total knee arthroplasty compared to primary total knee arthroplasty in terms of cost-per-quality-adjusted life year (QALY)., Methods: Data were retrieved for all primary and revision total knee replacement (TKA) procedures performed at a tertiary Swiss hospital between 2006 and 2019. A Markov model was created to evaluate revision risk and we calculated lifetime QALY gain and lifetime procedure costs through individual EuroQol 5 dimension (EQ-5D) scores, hospital costs, national life expectancy tables and standard discounting processes. Cost-per-QALY gain was calculated for primary and revision procedures., Results: EQ-5D data were available for 1343 primary and 103 revision procedures. Significant QALY gains were seen following surgery in all cases. Similar, but significantly more QALYs were gained following primary TKA (PTKA) (5.67 ± 3.98) than following revision TKA (RTKA) (4.67 ± 4.20). Cost-per-QALY was €4686 for PTKA and €10,364 for RTKA. The highest average cost-per-QALY was seen in two-stage RTKA (€12,292), followed by one-stage RTKA (€8982)., Conclusion: RTKA results in a similar QALY gain as PTKA. The costs of achieving health gain are two to three times higher in RTKA, but both procedures are highly cost-effective., Level of Evidence: Economic level II., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Purpose: Revision total knee arthroplasty (RTKA) results in high costs with inadequately low reimbursement in different healthcare systems. Therefore, a financial analysis was performed comparing costs and reimbursements of primary total knee arthroplasty (PTKA) versus RTKA using financial and total knee arthroplasty-register data from a large tertiary hospital, the Cantonal Hospital of St. Gallen (KSSG), Switzerland., Methods: All PTKA and RTKA performed between January 2012 and September 2019 at the KSSG were included. Financial and TKA-register data for each case were collected, including detailed cost allocation, reimbursement, patients' insurance status, type and indication for surgery and length of hospital stay. RTKA was further subdivided in one-stage and two-stage RTKA. Direct hospital costs were analyzed and compared to reimbursement in both groups. Cost-coverage ratios were calculated., Results: 730 PTKA and 106 RTKA were included. The RTKA group contained 66 one-stage and 40 two-stage RTKA. Cost-coverage ratio for PTKA and RTKA showed to be 110.9% and 81.3%, respectively. Cost-coverage ratio was lower for two-stage RTKA than for one-stage RTKA with 74.1% and 92.3%, respectively., Conclusion: RTKA leads to financial deficits especially for tertiary hospitals within the Swiss healthcare system. Restructuring of the reimbursements for PTKA and RTKA should be considered in favor of RTKA. Otherwise, tertiary hospitals will face a growing financial burden with the constantly increasing annual number of RTKA procedures, predominantly performed in this type of hospitals., Level of Evidence: III., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Phospholipid-based formulations provide a key technology to formulate poorly water-soluble drugs. A recent interest has been in using phospholipids with a high content of monoacyl phosphatidylcholine (monoacyl PC) due to its ability to form mixed micelles of mono- and di-acylphospholipids upon aqueous dispersion. The present work focused on binary drug- monoacyl PC systems (at about equimolar ratio) with respect to screening of solid dispersion feasibility. It was tested whether or not a molecular rule of thumb can predict the desirable absence of drug crystallinity in the products. Subsequently, molecular simulations were performed to gain a better understanding of molecular association between drugs and monoacyl PC. Finally, the glass-forming ability (GFA) of pure drugs was considered with respect to solid dispersion formation. All products were obtained from a solvent-evaporation process and subsequent analysis of potential drug crystallinity was measured with X-ray powder diffraction and differential scanning calorimetry. Molecular simulations were making use of a Monte Carlo algorithm and molecular properties relevant for GFA were calculated. As a result, the dataset of 28 drugs confirmed an earlier proposed empirical rule that enthalpy of fusion and logP were important for solid dispersion formation, while some relevance was also evidenced for drug energies of frontal orbitals. Interestingly, the Monte Carlo simulations revealed several likely associations between drug and phospholipid rather than a well-defined single complex formation. However, drug-excipient interactions were still pivotal, since GFA of pure drug could not predict solid dispersion formation. These findings led to important molecular insights into binary solid dispersions of drug and monoacyl PC, which can guide formulators in early drug product development., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Lipid-based formulations (LBFs) represent one of the successful formulation approaches that enable oral delivery of poorly water-soluble drugs. This work presents a simple equilibrium approach based on solubility in lipids and their corresponding digestion media to estimate a maximum drug supersaturation ratio (SR max ). This value of drug concentration normalized by the solubility in the aqueous digestion phase indicates the propensity for drug precipitation. A set of 16 structurally diverse drugs was first measured for their solubility in tricaprin and tricaprylin and results were compared to an empirical model based on molecular predictors. In the next step, digestion media were either prepared by in vitro lipolysis or by assembling a composition to mimic the endpoint of digestion. It was found that drug solubility in the pure lipids mainly was related to the melting point in that increased values resulted in reduced solubility. The solubility values measured in the lipolysis media correlated well with those obtained from assembled digestion media. Interestingly, the solubilization upon digestion was typically higher when using tricaprin than tricaprylin in spite of that the latter oil (as pure excipient) generally was a more potent solvent. This work suggests that a simplified digestion screen can be used to facilitate evaluation of formulations during early development. Estimation of SR max provides an early risk assessment of drug precipitation for LBFs. The method is easily scaled down to the microtiter plate format and can be used for selecting candidate formulations that merit further evaluation in more complex and dynamic in vitro tests., (Copyright © 2016 Elsevier B.V. All rights reserved.)

There is a growing interest in drug-phospholipid complexes and similar formulations that are mostly solid dispersions with high drug load. This study aims to explore the feasibility of such phospholipid-based solid dispersions as well as to characterize them. A particular aim was to compare monoacyl phosphatidylcholine (PC) with the diacyl excipient. The solid dispersions were manufactured using a solvent evaporation technique and characterized by means of differential scanning calorimetry and X-ray diffractometry. Density functional theory was used to calculate molecular frontier orbitals of the different compounds. Finally, the dissolution properties were analyzed in a flow-through cell by means of UV imaging. It was found that the ability to form solid dispersions with the phospholipids containing amorphous or solubilized drug (at equimolar ratio with the lipid) was dependent on the drug's frontier orbital energy, the enthalpy of fusion, as well as the log P value. In a subsequent dissolution study, UV imaging revealed pronounced surface swelling of the solid dispersions. Only the monoacyl PC was found to substantially enhance in vitro dissolution compared to pure drug. The gained understanding will support a future development of solid drug dispersions using phospholipids as matrix components., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A focal uterine adenomyosis is described in two bitches. In both cases, the uterus showed knobbly enlargements of 4 to 8 cm in diameter, which resulted in distinct clinical symptoms. Other pathological changes of the uterus were not present. One bitch was presented because of a history of vaginal discharge of several months' duration. Radiographs, as well as ultrasonography, revealed a soft tissue lesion at the cervix. The other bitch showed a marked reduction in its general condition and a sudden onset of a tense abdomen. Radiologically, a lesion of soft tissue opacity was observed in the mid-abdomen and was seen to originate from the left uterine horn during exploratory laparotomy. A torsion of the lesion was present, which explained the clinical signs in this second case.

It is still controversial whether a bitch should be spayed before or after the first oestrus. It would be desirable to spay bitches at an age that would minimize the side effects of neutering. With regard to the risk of mammary tumours, early spaying must be recommended because the incidence of tumours is reduced considerably. The aim of the present study was to determine whether early spaying also reduces the risk of urinary incontinence. The owners of 206 bitches that had been spayed before their first oestrus and for at least 3 years were questioned on the occurrence of urinary incontinence as a result of spaying. At the time of the enquiry the average age of the bitches was 6.5 years, and the average age at the time of surgery was 7.1 months. Urinary incontinence after spaying occurred in 9.7% of bitches. This incidence is approximately half that of spaying after the first oestrus. Urinary incontinence affected 12.5% of bitches that were of a large body weight (> 20 kg body weight) and 5.1% of bitches that were of a small body weight (< 20 kg body weight). The surgical procedure (ovariectomy versus ovariohysterectomy) had no influence on the incidence, or on the period between spaying and the occurrence of urinary incontinence. Urinary incontinence occurred on average at 2 years and 10 months after surgery and occurred each day, while the animals were awake or during sleep. However, compared with late spaying the clinical signs of urinary incontinence were more distinct after early spaying.