Spotlight on Compounded Bioidentical Hormones.

BACKGROUND: The role of hormonal replacement therapy in menopause is under debate. The premature closure of the Women's Health Initiative (WHI) study in 2002 is still a source of concern among treating physicians. OBJECTIVES: The interest in alternatives to conventional hormone therapy has significantly increased. The adoption of personalized steroid hormone galenic preparations, formulated by compounding pharmacies, has recently spread. METHODS: In June 2023, an extensive literature search was conducted by different authors to identify relevant studies in various databases (MEDLINE, Embase, PubMed, and Cochrane). The studies that met the inclusion and exclusion criteria were further analyzed, and relevant data were extracted and analyzed for each paper. Any discrepancies between the investigators were resolved through a consensus approach. OUTCOMES: The primary outcomes observed included the clinical utility of CBHT. This study reviewed the current evidence on the utility of compounded bioidentical hormones, concluding that improving knowledge and awareness of bioidentical hormones is necessary to consider their use in clinical practice. CONCLUSION AND OUTLOOK: These formulations might provide effective options to best tailor therapies to each patient.

A highly integrated bionic hand with neural control and feedback for use in daily life.

Restoration of sensorimotor function after amputation has remained challenging because of the lack of human-machine interfaces that provide reliable control, feedback, and attachment. Here, we present the clinical implementation of a transradial neuromusculoskeletal prosthesis-a bionic hand connected directly to the user's nervous and skeletal systems. In one person with unilateral below-elbow amputation, titanium implants were placed intramedullary in the radius and ulna bones, and electromuscular constructs were created surgically by transferring the severed nerves to free muscle grafts. The native muscles, free muscle grafts, and ulnar nerve were implanted with electrodes. Percutaneous extensions from the titanium implants provided direct skeletal attachment and bidirectional communication between the implanted electrodes and a prosthetic hand. Operation of the bionic hand in daily life resulted in improved prosthetic function, reduced postamputation, and increased quality of life. Sensations elicited via direct neural stimulation were consistently perceived on the phantom hand throughout the study. To date, the patient continues using the prosthesis in daily life. The functionality of conventional artificial limbs is hindered by discomfort and limited and unreliable control. Neuromusculoskeletal interfaces can overcome these hurdles and provide the means for the everyday use of a prosthesis with reliable neural control fixated into the skeleton.

Malpractice Claims and Incident Reporting: Two Faces of the Same Coin?

Incident reporting is an important method to identify risks because learning from the reports is crucial in developing and implementing effective improvements. A medical malpractice claims analysis is an important tool in any case. Both incident reports and claims show cases of damage caused to patients, despite incident reporting comprising near misses, cases where no event occurred and no-harm events. We therefore compare the two worlds to assess whether they are similar or definitively different. From 1 January 2014 to 31 December 2021, the claims database of Policlinico Universitario A. Gemelli IRCCS collected 843 claims. From 1 January 2020 to 31 December 2021, the incident-reporting database collected 1919 events. In order to compare the two, we used IBNR calculation, usually adopted by the insurance industry to determine loss to a company and to evaluate the real number of adverse events that occurred. Indeed, the number of reported adverse events almost overlapped with the total number of events, which is indicative that incurred-but-not-reported events are practically irrelevant. The distribution of damage events reported as claims in the period from 1 January 2020 to 31 December 2021 and related to incidents that occurred in the months of the same period, grouped by quarter, was then compared with the distribution of damage events reported as adverse events and sentinel events in the same period, grouped by quarter. The analysis of the claims database showed that the claims trend is slightly decreasing. However, the analysis of the reports database showed that, in the period 2020-2021, the reports trend was increasing. In our study, the comparison of the two, malpractice claims and incident reporting, documented many differences and weak areas of overlap. Nevertheless, this contribution represents the first attempt to compare the two and new studies focusing on single types of adverse events are, therefore, desirable.

Microbiological screening tests for SARS-CoV-2 in the first hour since the hospital admission: A reliable tool for enhancing the safety of pediatric care.

Introduction/purpose: Since a significant proportion of SARS-CoV-2 infections occur within healthcare facilities, a multidisciplinary approach is required for careful and timely assessment of the risk of infection in asymptomatic patients or those whose COVID-19 diagnosis has not yet been made. The aim of this study was to investigate whether an adaptative model based on microbiological testing can represent a valid risk management strategy. Material and methods: We collected data from the risk management unit database of a 1,550-bed tertiary hospital (Fondazione Policlinico Gemelli IRCCS, Rome, Italy) concerning pediatric admissions to the Emergency Department (ED) from 1 March 2020 to 31 December 2021. The study period was subdivided in period A and period B according to the technique used for the microbiological screening, respectively reverse-transcription polymerase chain reaction (RT-PCR) and antigen-detection test. Results: In Period A, 426 children (mean age: 6 years) underwent microbiological screening at the ED. The total number of molecular tests performed was 463. 459/463 tested negative at the molecular test. In Period B, 887 children (mean age: 6 years) underwent microbiological screening in the ED. The total number of molecular tests performed was 1,154. 1,117/1,154 tested negative at the molecular test. Neither in Period A nor in Period B hospital-acquired SARS-CoV-2 infections were reported. Discussion and conclusion: Despite high volumes, no cases of hospital-acquired SARS-CoV-2 infection have been reported. SARS-CoV-2 antigen-based tests can be used as a first-line option as they provide rapid results compared to RT-PCR, reducing the risk of infection in ED waiting rooms.

Real-World Clinical Outcomes and Replacement Factor VIII Consumption in Patients with Haemophilia A in Italy: A Comparison between Prophylaxis Pre and Post Octocog Alfa (BAY 81-8973).

(1) Background: new generations of rFVIII products offered the possibility to improve personalized therapeutic approaches, reducing the number of infusions or increasing the protection against bleeding risk. The aim of this study was to assess the effectiveness of prophylaxis with BAY 81-8973 (octocog alfa, Kovaltry®, Bayer Pharma AG) in the real-world setting and its impact on FVIII consumption compared to previous standard half-life treatments. (2) Methods: a retrospective observational study was conducted in five Italian Haemophilia Centers. Patients with haemophilia A under prophylactic treatment with BAY 81-8973 for at least one year, and previously on prophylaxis with a different product were included in the study. Annual bleeding rate (ABR) and annual FVIII consumption were compared. (3) Results: forty-four patients were included in the study. After switching to BAY 81-8973, ABR was significantly reduced (1.76 vs. 0.23; p = 0.015), the percentage of patients with zero bleeds increased from 54.6% to 84.1% (p = 0.003), and the overall FVIII consumption decreased by 25,542 (-7.2%, p = 0.046) IU per patient-year. Patients treated every 3 days or 2 times per week increased from 0% to 27.3%. (4) Conclusion: our results suggest that prophylaxis with BAY 81-8973 can improve clinical outcomes and reduce FVIII consumption, in the real-world practice, compared with the previous prophylaxis regimen with standard half-life products.

Efficiency measures of emergency departments: an Italian systematic literature review.

Life expectancy globally increased in the last decades: the number of people aged 65 or older is consequently projected to grow, and healthcare demand will increase as well. In the recent years, the number of patients visiting the hospital emergency departments (EDs) rocked in almost all countries of the world. These departments are crucial in all healthcare systems and play a critical role in providing an efficient assistance to all patients. A systematic literature review covering PubMed, Scopus and the Cochrane Library was performed from 2009 to 2019. Of the 718 references found in the literature research, more than 25 studies were included in the current review. Different predictors were associated with the quality of EDs care, which may help to define and implement preventive strategies in the near future. There is no harmonisation in efficiency measurements reflecting the performance in the ED setting. The identification of consistent measures of efficiency is crucial to build an evidence base for future initiatives. The aim of this study is to review the literature on the problems encountered in the efficiency of EDs around the world in order to identify an organisational model or guidelines that can be implemented in EDs to fill inefficiencies and ensure access optimal treatment both in terms of resources and timing. This review will support policy makers to improve the quality of health facilities, and, consequently of the entire healthcare systems.

Real-Life Clinical Data of Cabozantinib for Unresectable Hepatocellular Carcinoma.

INTRODUCTION: Cabozantinib has been approved by the European Medicine Agency (EMA) for hepatocellular carcinoma (HCC) previously treated with sorafenib. Cabozantinib is also being tested in combination with immune checkpoint inhibitors in the frontline setting. Real-life clinical data of cabozantinib for HCC are still lacking. Moreover, the prognostic factors for HCC treated with cabozantinib have not been investigated. METHODS: We evaluated clinical data and outcome of HCC patients who received cabozantinib in the legal context of named patient use in Italy. RESULTS: Ninety-six patients from 15 centres received cabozantinib. All patients had preserved liver function (Child-Pugh A), mostly with an advanced HCC (77.1%) in a third-line setting (75.0%). The prevalence of performance status (PS) > 0, macrovascular invasion (MVI), extrahepatic spread, and alpha-fetoprotein (AFP) >400 ng/mL was 50.0, 30.2, 67.7, and 44.8%, respectively. Median overall survival (OS) and progression-free survival were 12.1 (95% confidence interval 9.4-14.8) and 5.1 (3.3-6.9) months, respectively. Most common treatment-related adverse events (AEs) were fatigue (67.7%), diarrhoea (54.2%), anorexia (45.8%), HFSR (43.8%), weight loss (24.0%), and hypertension (24.0%). Most common treatment-related Grade 3-4 AEs were fatigue (6.3%), HFSR (6.3%), and increased aminotransferases (6.3%). MVI, ECOG-PS > 0, and AFP >400 ng/mL predicted a worse OS. Discontinuation for intolerance and no new extrahepatic lesions at the progression were associated with better outcomes. CONCLUSIONS: In a real-life Western scenario (mostly in a third-line setting), cabozantinib efficacy and safety data were comparable with those reported in its registration trial. Data regarding the prognostic factors might help in patient selection and design of clinical trials.

Feasibility of generating 90 Hz vibrations in remote implanted magnets.

Limb amputation not only reduces the motor abilities of an individual, but also destroys afferent channels that convey essential sensory information to the brain. Significant efforts have been made in the area of upper limb prosthetics to restore sensory feedback, through the stimulation of residual sensory elements. Most of the past research focused on the replacement of tactile functions. On the other hand, the difficulties in eliciting proprioceptive sensations using either haptic or (neural) electrical stimulation, has limited researchers to rely on sensory substitution. Here we propose the myokinetic stimulation interface, that aims at restoring natural proprioceptive sensations by exploiting the so-called tendon illusion, elicited through the vibration of magnets implanted inside residual muscles. We present a prototype which exploits 12 electromagnetic coils to vibrate up to four magnets implanted in a forearm mockup. The results demonstrated that it is possible to generate highly directional and frequency-selective vibrations. The system proved capable of activating a single magnet, out of many. Hence, this interface constitutes a promising approach to restore naturally perceived proprioception after an amputation. Indeed, by implanting several magnets in independent muscles, it would be possible to restore proprioceptive sensations perceived as coming from single digits.

Proprioceptive Augmentation With Illusory Kinaesthetic Sensation in Stroke Patients Improves Movement Quality in an Active Upper Limb Reach-and-Point Task.

Stroke patients often have difficulty completing motor tasks even after substantive rehabilitation. Poor recovery of motor function can often be linked to stroke-induced damage to motor pathways. However, stroke damage in pathways that impact effective integration of sensory feedback with motor control may represent an unappreciated obstacle to smooth motor coordination. In this study we investigated the effects of augmenting movement proprioception during a reaching task in six stroke patients as a proof of concept. We used a wearable neurorobotic proprioceptive feedback system to induce illusory kinaesthetic sensation by vibrating participants' upper arm muscles over active limb movements. Participants were instructed to extend their elbow to reach-and-point to targets of differing sizes at various distances, while illusion-inducing vibration (90 Hz), sham vibration (25 Hz), or no vibration was applied to the distal tendons of either their biceps brachii or their triceps brachii. To assess the impact of augmented kinaesthetic feedback on motor function we compared the results of vibrating the biceps or triceps during arm extension in the affected arm of stroke patients and able-bodied participants. We quantified performance across conditions and participants by tracking limb/hand kinematics with motion capture, and through Fitts' law analysis of reaching target acquisition. Kinematic analyses revealed that injecting 90 Hz illusory kinaesthetic sensation into the actively contracting (agonist) triceps muscle during reaching increased movement smoothness, movement directness, and elbow extension. Conversely, injecting 90 Hz illusory kinaesthetic sensation into the antagonistic biceps during reaching negatively impacted those same parameters. The Fitts' law analyses reflected similar effects with a trend toward increased throughput with triceps vibration during reaching. Across all analyses, able-bodied participants were largely unresponsive to illusory vibrational augmentation. These findings provide evidence that vibration-induced movement illusions delivered to the primary agonist muscle involved in active movement may be integrated into rehabilitative approaches to help promote functional motor recovery in stroke patients.

Localization accuracy of multiple magnets in a myokinetic control interface.

Magnetic localizers have been widely investigated in the biomedical field, especially for intra-body applications, because they don't require a free line-of-sight between the implanted magnets and the magnetic field sensors. However, while researchers have focused on narrow and specific aspects of the localization problem, no one has comprehensively searched for general design rules for accurately localizing multiple magnetic objectives. In this study, we sought to systematically analyse the effects of remanent magnetization, number of sensors, and geometrical configuration (i.e. distance among magnets-Linter-MM-and between magnets and sensors-LMM-sensor) on the accuracy of the localizer in order to unveil the basic principles of the localization problem. Specifically, through simulations validated with a physical system, we observed that the accuracy of the localization was mainly affected by a specific angle ([Formula: see text] = tan-1(Linter-MM / LMM-sensor)), descriptive of the system geometry. In particular, while tracking nine magnets, errors below ~ 1 mm (10% of the length of the simulated trajectory) and around 9° were obtained if θ ≥ ~ 31°. The latter proved a general rule across all tested conditions, also when the number of magnets was doubled. Our results are interesting for a whole range of biomedical engineering applications exploiting multiple-magnets tracking, such as human-machine interfaces, capsule endoscopy, ventriculostomy interventions, and endovascular catheter navigation.

Urinary incontinence in women: state of the art and medical treatment.

INTRODUCTION: Urinary incontinence, the involuntary loss of urine, is a common condition that affects approximately 50% of adult women. This condition increases with age, affecting 10% to 20% of all women and up to 77% of elderly women residing in nursing homes. EVIDENCE ACQUISITION: Systematic data search performed using PubMed/MEDLINE database up to July 20, 2020. Focus was only for English language publications of original studies on urinary incontinence. EVIDENCE SYNTHESIS: Given the basis of published evidence and the consensus of European experts, this study provides an updated overview on clinical applications and surgical procedures of urinary incontinence. CONCLUSIONS: Urinary incontinence is an underestimated health problem. Patients need an overview of their health condition through a detailed anamnestic collection and physical examination to identify the type of incontinence and offer the best treatment.

Stability and in vivo safety of gold, titanium nitride and parylene C coatings on NdFeB magnets implanted in muscles towards a new generation of myokinetic prosthetic limbs.

Rare earth magnets are the elective choice when high magnetic field density is required and they are particularly intriguing for inclusion in implantable devices. A safe implantation of NdFeB magnets in muscles would enable the control of limb prostheses using a myokinetic interface i.e., direct control of artificial limb movements by means of magnetic tracking of residual muscle contractions. However, myokinetic prosthesis control is prevented by NdFeB magnets poor biocompatibility, at present. Here we investigated three biocompatible materials as NdFeB magnet coating candidates, namely gold, titanium nitride and parylene C, which have not been analyzed in a systematic way for this purpose, so far. In vitro testing in a tissue-mimicking environment and upon contact with C2C12 myoblasts enabled assessment of the superiority of parylene C coated magnets in terms of corrosion prevention and lack of cytotoxicity. In addition, parylene C coated magnets implanted in rabbit muscles for 28 days confirmed, both locally and systemically, their biocompatibility, with a lack of irritation and toxicity associated with the implant. These findings pave the way towards the development of implantable devices based on permanent magnets and of a new generation of limb prostheses.

Intracortical Microstimulation Feedback Improves Grasp Force Accuracy in a Human Using a Brain-Computer Interface.

After a spinal cord injury, a person may grasp objects using a brain-computer interface (BCI) to control a robot arm. However, most BCIs do not restore somatosensory percepts that would enable someone to sense grasp force. Intracortical microstimulation (ICMS) in the somatosensory cortex can evoke tactile sensations and may therefore offer a viable solution to provide grasp force feedback. We investigated whether a bidirectional BCI could improve grasp force control over a BCI using only visual feedback. When evaluating the error of the applied force during a force matching task, we found that ICMS feedback improved overall applied grasp force accuracy.

The Myokinetic Control Interface: How Many Magnets Can be Implanted in an Amputated Forearm? Evidence From a Simulated Environment.

We recently introduced the concept of a new human-machine interface (the myokinetic control interface) to control hand prostheses. The interface tracks muscle contractions via permanent magnets implanted in the muscles and magnetic field sensors hosted in the prosthetic socket. Previously we showed the feasibility of localizing several magnets in non-realistic workspaces. Here, aided by a 3D CAD model of the forearm, we computed the localization accuracy simulated for three different below-elbow amputation levels, following general guidelines identified in early work. To this aim we first identified the number of magnets that could fit and be tracked in a proximal (T1), middle (T2) and distal (T3) representative amputation, starting from 18, 20 and 23 eligible muscles, respectively. Then we ran a localization algorithm to estimate the poses of the magnets based on the sensor readings. A sensor selection strategy (from an initial grid of 840 sensors) was also implemented to optimize the computational cost of the localization process. Results showed that the localizer was able to accurately track up to 11 (T1), 13 (T2) and 19 (T3) magnetic markers (MMs) with an array of 154, 205 and 260 sensors, respectively. Localization errors lower than 7% the trajectory travelled by the magnets during muscle contraction were always achieved. This work not only answers the question: "how many magnets could be implanted in a forearm and successfully tracked with a the myokinetic control approach?", but also provides interesting insights for a wide range of bioengineering applications exploiting magnetic tracking.

Online Grasp Force Estimation From the Transient EMG.

Myoelectric upper limb prostheses are controlled using information from the electrical activity of residual muscles (i.e. the electromyogram, EMG). EMG patterns at the onset of a contraction (transient phase) have shown predictive information about upcoming grasps. However, decoding this information for the estimation of the grasp force was so far overlooked. In a previous offline study, we proved that the transient phase of the EMG indeed contains information about the grasp force and determined the best algorithm to extract this information. Here we translated those findings into an online platform to be tested with both non-amputees and amputees. The platform was tested during a pick and lift task (tri-digital grasp) with light objects (200 g - 1 kg), for which fine control of the grasp force is more important. Results show that, during this task, it is possible to estimate the target grasp force with an absolute error of 2.06 (1.32) % and 2.04 (0.49) % the maximum voluntary force for non-amputee and amputees, respectively, using information from the transient phase of the EMG. This approach would allow for a biomimetic regulation of the grasp force of a prosthetic hand. Indeed, the users could contract their muscles only once before the grasp begins with no need to modulate the grasp force for the whole duration of the grasp, as required with continuous classifiers. These results pave the way to fast, intuitive and robust myoelectric controllers of limb prostheses.

Neural feedback strategies to improve grasping coordination in neuromusculoskeletal prostheses.

Conventional prosthetic arms suffer from poor controllability and lack of sensory feedback. Owing to the absence of tactile sensory information, prosthetic users must rely on incidental visual and auditory cues. In this study, we investigated the effect of providing tactile perception on motor coordination during routine grasping and grasping under uncertainty. Three transhumeral amputees were implanted with an osseointegrated percutaneous implant system for direct skeletal attachment and bidirectional communication with implanted neuromuscular electrodes. This neuromusculoskeletal prosthesis is a novel concept of artificial limb replacement that allows to extract control signals from electrodes implanted on viable muscle tissue, and to stimulate severed afferent nerve fibers to provide somatosensory feedback. Subjects received tactile feedback using three biologically inspired stimulation paradigms while performing a pick and lift test. The grasped object was instrumented to record grasping and lifting forces and its weight was either constant or unexpectedly changed in between trials. The results were also compared to the no-feedback control condition. Our findings confirm, in line with the neuroscientific literature, that somatosensory feedback is necessary for motor coordination during grasping. Our results also indicate that feedback is more relevant under uncertainty, and its effectiveness can be influenced by the selected neuromodulation paradigm and arguably also the prior experience of the prosthesis user.

Indications and timing for tracheostomy in patients with SARS CoV2-related.

BACKGROUND: The indications and timing for tracheostomy in patients with SARS CoV2-related are controversial. PURPOSE: In a recent issue published in the European Archives of Otorhinolaryngology, Mattioli et al. published a short communication about tracheostomy timing in patients with COVID-19 (Coronavirus Disease 2019); they reported that the tracheostomy could allow early Intensive Care Units discharge and, in the context of prolonged Invasive Mechanical Ventilation, should be suggested within 7 and 14 days to avoid potential tracheal damages. In this Letter to the Editor we would like to present our experience with tracheostomy in a Hub Covid Hospital. METHODS: 8 patients underwent open tracheostomy in case of intubation prolonged over 14 days, bronchopulmonary overlap infections, and patients undergoing weaning. They were followed up and the number and timing of death were recorded. RESULTS: Two patients died after tracheostomy; the median time between tracheostomy and death was 3 days. A negative prognostic trend was observed for a shorter duration of intubation. CONCLUSION: In our experience, tracheostomy does not seem to influence the clinical course and prognosis of the disease, in the face of possible risks of contagion for healthcare workers. The indication for tracheostomy in COVID-19 patients should be carefully evaluated and reserved for selected patients. Although it is not possible to define an optimal timing, it is our opinion that tracheostomy in a stable or clinically improved COVID-19 patient should not be proposed before the 20th day after orotracheal intubation.