Vial Sharing of High-Cost Drugs to Decrease Leftovers and Costs: A Retrospective Observational Study on Patisiran Administration in Bologna, Italy.

Waste of high-cost medicines, such as orphan drugs, is a major problem in healthcare, which leads to excessive costs for treatments. The main objective of this study was to evaluate the impact of a vial-sharing strategy for patisiran, an orphan drug used for the treatment of hereditary transthyretin-mediated amyloidosis, in terms of a reduction in the discarded drug amount and cost savings. The retrospective observational study was conducted in a tertiary referral center (Emilia-Romagna, Italy), between February 2021 and November 2022. Data on drug waste were calculated as "(mg used-mg prescribed)/mg prescribed" for each session. We found a statistically significant (-9.14%, p < 0.001, 95% CI 5.87-12.41) absolute difference in mean discarded drug rates per session based on the study phase (before and after vial-sharing introduction) at the two-sample t-test. The absolute difference corresponded to a percentage decrease in the average reduction in the discarded drug rate with vial sharing of 82.96% per session. On an annual scale, the estimated cost savings was EUR 26,203.80/year for a patient with a standard body weight of 70 kg. In conclusion, we demonstrated that a patisiran vial-sharing program undoubtedly offsets some of the high costs associated with this treatment. We suggest that this easy-to-introduce and cost-effective approach can be applied to the administration of other high-cost drugs.

Generative deep learning applied to biomechanics: A new augmentation technique for motion capture datasets.

Deep learning biomechanical models perform optimally when trained with large datasets, however these can be challenging to collect in gait labs, while limited augmentation techniques are available. This study presents a data augmentation approach based on generative adversarial networks which generate synthetic motion capture (mocap) datasets of marker trajectories and ground reaction forces (GRFs). The proposed architecture, called adversarial autoencoder, consists of an encoder compressing mocap data to a latent vector, a decoder reconstructing the mocap data from the latent vector and a discriminator distinguishing random vectors from encoded latent vectors. Direct kinematics (DK) and inverse kinematics (IK) joint angles, GRFs, and inverse dynamics (ID) joint moments calculated for real and synthetic trials were compared using statistical parametric mapping to assure realistic data generation and select optimal architectural hyperparameters based on percentage average differences across the gait cycle length. We observed negligible differences for DK computed joint angles and GRFs, but not for inverse methods (IK: 29.2%, ID: 35.5%). When the same architecture was trained also including the joint angles calculated by IK, we found no significant differences in the kinematics and GRFs, and improvements in joint moments estimation (ID: 25.7%). Finally, we showed that our data augmentation approach improved the accuracy of joint kinematics (up to 23%, 0.8°) and vertical GRFs (11%) predicted by standard neural networks using a single simulated pelvic inertial measurement unit. These findings suggest that predictive deep learning models can benefit from the synthetic datasets produced with the proposed technique.

Multidimensional Impact of Mediterranean Diet on IBD Patients.

BACKGROUND & AIMS: Malnutrition with the accumulation of fat tissue and nonalcoholic fatty liver disease (NAFLD) are conditions associated with inflammatory bowel disease (IBD). Visceral fat and NAFLD-related liver dysfunction can both worsen intestinal inflammation. Because the Mediterranean diet (Md) has been shown to ameliorate both obesity and NAFLD, the aim of this study was to analyze the impact of Md on the nutritional state, liver steatosis, clinical disease activity, and quality of life (QoL) in IBD patients. METHODS: Patients with IBD, both Crohn's disease (CD) and ulcerative colitis (UC), followed Md for 6 months. Their body mass index (BMI), body tissue composition, liver steatosis and function, serum lipid profile, clinical disease activity, and inflammatory biomarkers (C-reactive protein and fecal calprotectin) were collected at baseline (T0) and compared with those obtained after 6 months (T180) to evaluate the impact of Md. RESULTS: One hundred forty-two IBD patients, 84 UC and 58 CD, followed Md for 6 months. At T180, diet-adherent CD and UC improved BMI (UC -0.42, P = 0.002; CD -0.48, P = 0.032) and waist circumference (UC -1.25 cm, P = 0.037; CD -1.37 cm, P = 0.041). Additionally, the number of patients affected by liver steatosis of any grade was significantly reduced in both groups (UC T0 31 of 84 [36.9%] vs T180 18 of 84 [21.4%], P = 0.0016; CD T0 27 of 58 [46.6%] vs T180 18 of 58 [31.0%], P < 0.001) after dietary intervention. Finally, after 6 months of the diet, fewer UC and CD patients with stable therapy had active disease (UC T0 14 of 59 [23.7%] vs T180 4 of 59 [6.8%], P = 0.004; CD T0 9 of 51 [17.6%] vs T180 2 of 51 [3.0%], P = 0.011) and elevated inflammatory biomarkers. Mediterranean diet improved QoL in both UC and CD, but neither serum lipid profile nor liver function were modified by the diet. CONCLUSIONS: A significant reduction of malnutrition-related parameters and liver steatosis was observed in both CD and UC patients after short-term dietary intervention based on the adoption of Md, and this was associated with a spontaneous improvement of disease activity and inflammatory markers.

Nonalcoholic fatty liver disease in patients with inflammatory bowel disease: Beyond the natural history.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a frequently reported condition in patients with inflammatory bowel disease (IBD). Both intestinal inflammation and metabolic factors are believed to contribute to the pathogenesis of IBD-associated NAFLD. AIM: To evaluate the prevalence of steatosis and liver fibrosis (LF) in a cohort of IBD patients and the identification of metabolic- and IBD-related risk factors for NAFLD and LF. METHODS: IBD patients were consecutively enrolled from December 2016 to January 2018. Demographic, anthropometric and biochemical data were collected so as eating habits. Abdominal ultrasound and transient elastography were performed to evaluate the presence of NAFLD and LF respectively. RESULTS: A total of 178 consecutive patients were enrolled and included in the analysis (95 Ulcerative colitis, 83 Crohn's disease). NAFLD was detected by imaging in 72 (40.4%) patients. Comparison between patients with and without NAFLD showed no significant differences in terms of IBD severity, disease duration, location/extension, use of IBD-related medications (i.e., steroids, anti-TNFs, and immunomodulators) and surgery. NAFLD was significantly associated with the presence of metabolic syndrome [MetS; odds ratio (OR): 4.13, P = 0.001] and obesity defined by body mass index (OR: 9.21, P = 0.0002). IBD patients with NAFLD showed higher caloric intake and lipid consumption than those without NAFLD, regardless disease activity. At the multivariate analysis, male sex, advanced age and high lipid consumption were independent risk factors for the development of NAFLD. An increased liver stiffness was detected in 21 patients (16%) and the presence of MetS was the only relevant factor associated to LF (OR: 3.40, P = 0.01). CONCLUSION: In this study, we demonstrate that risk factors for NAFLD and LF in the IBD population do not differ from those in the general population.

An engineering approach towards a more discrete and efficient urinary drainage system.

Modern urinary catheter-to-leg-bag systems suffer from a number of shortcomings. Drainage tubing of current urinary leg bags is perceived as unnecessarily bulky compared to the indwelling catheters to which it is connected, and catheter designs are prone to the formation of biofilms, leading ultimately to encrustation and blocking. We used analytical and experimental engineering methodologies, aligned with current international (International Standards Organisation) and European standards, to optimise drainage tube size and flow efficiency and characterise tube kinking behaviour. Using computational fluid dynamics, we studied the influence of modern Foley catheter design on urodynamics and explored its potential influence on biofilm formation and encrustation. Results indicate that tubing diameters could be reduced by 40%-50% and still satisfy current International Standards Organisation flow rate standards for leg bags; this might also reduce the likelihood of tube kinking. The computational study showed how current catheter design may promote the development of lower velocity recirculating flows and high shear in proximity of regions known to be affected by bacterial adhesion and biofilm formation. If confirmed, these findings will give manufacturers greater flexibility to develop less obtrusive and more encrustation-resistant products for end users.

Gastric paraganglioma: case report and review of the literature.

Very few cases of gastric paragangliomas have been reported in the literature to date. We report a rare case of parietal gastric paraganglioma fortuitously detected during intraoperative exploration. A 82-years-old woman presented to our emergency room for abdominal pain. On physical examination abdomen was painful on palpation and Blumberg's sign was present. The laboratory exams showed a neutrophilia in absence of leukocytosis. Acute appendicitis was suspected and a laparoscopy was performed. At exploration, the vermiform appendix was normal while a lumpy, hard-fibrous and white-pinkish extraluminal lesion of the anterior wall of the gastric body near the greater curvature of about 2 cm in diameter was present. Laparoscopic resection of the gastric lesion was performed. The patient was discharged in good condition in the fourth postoperative day. Pathologic examination revealed a gangliocitic paraganglioma. The patient is alive and well without evidence of relapse 6 months after surgery. Gastric paraganglioma is a very rare tumor and its diagnosis is very difficult. Surgical excision is the treatment of choice which can be performed successfully with laparoscopy.

Bayesian sensitivity analysis of a 1D vascular model with Gaussian process emulators.

One-dimensional models of the cardiovascular system can capture the physics of pulse waves but involve many parameters. Since these may vary among individuals, patient-specific models are difficult to construct. Sensitivity analysis can be used to rank model parameters by their effect on outputs and to quantify how uncertainty in parameters influences output uncertainty. This type of analysis is often conducted with a Monte Carlo method, where large numbers of model runs are used to assess input-output relations. The aim of this study was to demonstrate the computational efficiency of variance-based sensitivity analysis of 1D vascular models using Gaussian process emulators, compared to a standard Monte Carlo approach. The methodology was tested on four vascular networks of increasing complexity to analyse its scalability. The computational time needed to perform the sensitivity analysis with an emulator was reduced by the 99.96% compared to a Monte Carlo approach. Despite the reduced computational time, sensitivity indices obtained using the two approaches were comparable. The scalability study showed that the number of mechanistic simulations needed to train a Gaussian process for sensitivity analysis was of the order O(d), rather than O(d×103) needed for Monte Carlo analysis (where d is the number of parameters in the model). The efficiency of this approach, combined with capacity to estimate the impact of uncertain parameters on model outputs, will enable development of patient-specific models of the vascular system, and has the potential to produce results with clinical relevance.

Skeletal fragility definition.

Strategies to reduce fracture risk must be based on the understanding of the mechanisms that underline the increased incidence of fractures with age and with bone diseases that reduce bone stock. There is evidence that in addition to bone minerals density, other factors influence bone strength. This study reviews the biomechanical aspects of age-related fractures, including the interacting roles of traumatic loading and bone strength, and the factors that determine the resistances of bones to fracture. Although low bone mineral density (BMD) is among the strongest risk factors for fracture, a number of clinical studies have demonstrated the limitations of bone mineral density measurements in assessing fracture risk and monitoring the response to therapy. These observations have brought renewed attention to the broader array of factors that influence skeletal fragility, including bone size, shape, micro-architecture and bone quality. Bone fragility can be defined by biomechanical parameters, including ultimate force, ultimate displacement and energy absorption. Many osteoporosis treatments build bone mass but also change tissue quality. Antiresorptive therapies, such as bisphosphonates, substantially reduce bone turnover, impairing micro-damage repair and causing increased bone mineralization, which can increase the brittleness of bone. Anabolic therapies, such as teriparatide, increase bone turnover and porosity, which offset some of the positive effects on bone strength. Osteoporosis therapies may also affect bone architecture by causing the redistribution of bone structure. Restructuring of bone during treatment may change bone fragility, even in the absence of drug effects on BMD.

Gray-scale and color Doppler sonographic findings in a case of mesenteric Castleman's disease incidentally detected in a patient with Graves' disease.

We report a case of localized Castleman's disease of mesentery, studied with sonography, that was incidentally detected as an abdominal mass in a patient with Graves' disease. Its lymphatic nature and mesenteric origin was indicated preoperatively on the basis of gray-scale and color Doppler sonographic features.

Correlation of computerized gray-scale sonographic findings with thyroid function and thyroid autoimmune activity in patients with Hashimoto's thyroiditis.

PURPOSE: The objective of this study was to retrospectively assess whether computerized gray-scale sonography can allow objective measurement of thyroid echogenicity in patients with Hashimoto's thyroiditis (HT) at various functional stages of the disease. METHODS: Of the 77 patients with HT who were included in our study, 28 had been euthyroid, 20 had had subclinical hypothyroidism, and 29 had had clinical hypothyroidism. Of those with clinical hypothyroidism, 6 had been untreated and 23 had been receiving L-thyroxine substitution therapy. Fifty volunteers without thyroid disease served as a control group. Thyroid echogenicity was evaluated by computerized gray-scale sonography as mean tissue density (MTD) +/- standard deviation; the echogenicity of the prethyroid muscles served as a control of the system variability. RESULTS: The MTD was significantly lower for the patients with HT (15.9 +/- 4) than for the control subjects (24.3 +/- 3; p < 0.05). Moreover, a significant difference was found between the MTD values of euthyroid patients with HT (18.9 +/- 3.4) and hypothyroid patients with HT analyzed either as a group (14.3 +/- 3.8) or separately for subclinical hypothyroidism (14.9 +/- 3.8) and clinical hypothyroidism (13.9 +/- 3.7; p < 0.05). The lowest MTD was found in patients with untreated clinical hypothyroidism (11.1 +/- 4.3), with a significant difference (p < 0.05) compared to all other groups of patients. Untreated patients with clinical hypothyroidism also showed the highest mean anti-thyroid peroxidase autoantibody levels (1,286 +/- 177 IU/ml versus 570 +/- 489 IU/ml for L-thyroxine-treated patients; p < 0.05), although no correlation between the MTD values and anti-thyroid peroxidase autoantibody levels was found in any group of patients. CONCLUSIONS: Computerized gray-scale sonography provides an objective measure of thyroid hypoechogenicity, which correlates well to the clinical stages of HT. Use of this modality may prove beneficial in the diagnosis and follow-up of patients with HT.