Redesigned Electrodes for Improved Intraoperative Nerve Conduction Studies during the Treatment of Peripheral Nerve Injuries.

Traumatic peripheral nerve injuries (PNI), present with symptoms ranging from pain to loss of motor and sensory function. Difficulties in intraoperative visual assessment of nerve functional status necessitate intraoperative nerve conduction studies (INCSs) by neurosurgeons and neurologists to determine the presence of functioning axons in the zone of a PNI. This process, also referred to as nerve "inching", uses a set of stimulating and recording electrode hooks to lift the injured nerve from the surrounding surgical field and to determine whether an electrical stimulus can travel through the zone of injury. However, confounding electrical signal artifacts can arise from the current workflow and electrode design, particularly from the mandatory lifting of the nerve, complicating the definitive assessment of nerve function and neurosurgical treatment decision-making. The objective of this study is to describe the design process and verification testing of our group's newly designed stimulating and recording electrodes that do not require the lifting or displacement of the injured nerve during INCSs. Ergonomic in vivo analysis of the device within a porcine model demonstrated successful intraoperative manipulation of the device, while quantitative nerve action potential (NAP) signal analysis with an ex vivo simulated "inching" procedure on healthy non-human primate nerve tissue demonstrated excellent reproducible recorded NAP fidelity and the absence of NAP signal artifacts at all points of recording. Lastly, electrode pullout force testing determined maximum forces of 0.43 N, 1.57 N, and 3.61 N required to remove the device from 2 mm, 5 mm, and 1 cm nerve models, respectively, which are well within established thresholds for nerve safety. These results suggest that these new electrodes can safely and successfully perform accurate PNI assessment without the presence of artifacts, with the potential to improve the INCS standard of care while remaining compatible with currently used neurosurgical technology, infrastructure, and clinical workflows.

Unmet needs in relapsed/refractory mantle cell lymphoma (r/r MCL) post-covalent Bruton tyrosine kinase inhibitor (BTKi): a systematic literature review and meta-analysis.

To quantify the clinical unmet need of r/r MCL patients who progress on a covalent Bruton tyrosine kinase inhibitor (BTKi), we conducted a systematic review to identify studies that reported overall survival (OS), progression-free survival (PFS), or response outcomes of patients who received a chemo(immunotherapy) ± targeted agent standard therapy (STx) or brexucabtagene autoleucel (brexu-cel) in the post-BTKi setting. Twenty-six studies (23 observational; three trials) reporting outcomes from 2005 to 2022 were included. Using two-stage frequentist meta-analyses, the estimated median PFS/OS for patients treated with an STx was 7.6 months (95% CI: 3.9-14.6) and 9.1 months (95% CI: 7.3-11.3), respectively. The estimated objective response rate (ORR) was 45% (95% CI: 34-57%). For patients treated with brexu-cel, the estimated median PFS/OS was 14.9 months (95% CI: 10.5-21.0) and 32.1 months (95% CI: 25.2-41.2), with a pooled ORR of 89% (95% CI: 86-91%). Our findings highlight a significant unmet need for patients whose disease progresses on a covalent BTKi.

Unmet clinical needs in women with polycystic ovary syndrome in regard to mental health: a cross-sectional study.

PURPOSE: Polycystic ovary syndrome (PCOS) management has hardly been standardized until recent years. Despite the existence of a detailed, evidence-based guideline published by the European Society of Human Reproduction and Embryology (ESHRE), it remains unclear to what extent healthcare providers adhere to this guideline. Our aim is to evaluate the gynaecological medical care provided in women with PCOS, particularly in terms of mental health, from the patients' perspective. METHODS: For this cross-sectional online cohort study in women with PCOS, we designed a standardized, non-validated questionnaire covering aesthetic aspects, metabolism, menstrual cycle, reproduction, mental health, and prevention of chronic non-communicable diseases. RESULTS: Among 1879 participants, various mental health aspects were reported: body image (n = 1879), eating patterns/habits (n = 1878), and emotional well-being (n = 1874). Although nearly all women (99.7%) reported complaints on at least one session of mental health, consultation rates were low (body image 9.7%, eating patterns/habits 16.6%, emotional well-being 4.4%). Mean satisfaction with counselling on the different domains varied from moderate to fairly satisfying, with scores of 56.0 points (SD 31.7), 53.5 points (SD 32.0), and 63.7 points (SD 30.2), respectively. More complaints were associated with lower satisfaction. The overall satisfaction with the management provided by the healthcare practitioner (HCP) was low, averaging 36.5 points (SD 29.7). Consequently, most women wished for more counselling (58.9%). CONCLUSION: Women affected by PCOS are not properly managed according to ESHRE guideline in regard to mental health issues. Overall consultation rates and corresponding satisfaction with management were poor, highlighting the need for significant improvements in healthcare provision.

Pleural clinic: where thoracic ultrasound meets respiratory medicine.

Thoracic ultrasound (TUS) has become an essential procedure in respiratory medicine. Due to its intrinsic safety and versatility, it has been applied in patients affected by several respiratory diseases both in intensive care and outpatient settings. TUS can complement and often exceed stethoscope and radiological findings, especially in managing pleural diseases. We hereby aimed to describe the establishment, development, and optimization in a large, tertiary care hospital of a pleural clinic, which is dedicated to the evaluation and monitoring of patients with pleural diseases, including, among others, pleural effusion and/or thickening, pneumothorax and subpleural consolidation. The clinic was initially meant to follow outpatients undergoing medical thoracoscopy. In this scenario, TUS allowed rapid and regular assessment of these patients, promptly diagnosing recurrence of pleural effusion and other complications that could be appropriately managed. Over time, our clinic has rapidly expanded its initial indications thus becoming the place to handle more complex respiratory patients in collaboration with, among others, thoracic surgeons and oncologists. In this article, we critically describe the strengths and pitfalls of our "pleural clinic" and propose an organizational model that results from a synergy between respiratory physicians and other professionals. This model can inspire other healthcare professionals to develop a similar organization based on their local setting.

Unmet Clinical Needs in Women with Aesthetic Manifestations of Polycystic Ovary Syndrome: A Cross-Sectional Study.

Background: Polycystic ovary syndrome (PCOS) management has hardly been standardized until recent years. There is an accurate, evidence-based guideline published by the European Society of Human Reproduction and Embryology (ESHRE). However, it remains unclear to which extent, if at all, the guideline is followed by health care providers. The aim was to explore the subjectively perceived quality of gynecological medical care in women with PCOS suffering from aesthetic complaints. Materials and Methods: A nonvalidated questionnaire was constructed in a standardized manner covering the domains: aesthetic aspects, metabolism, menstrual cycle, reproduction, mental health, and prevention of chronic noncommunicable diseases. Results: A total of 1960 participants with aesthetic complaints, such as acne (66.2%), alopecia (43.9%), hirsutism (77.9%), or overweight/obesity (72.3%) were included. The percentage of women being counseled was low (acne 20.3%, alopecia 12.9%, hirsutism 17.5%, overweight/obesity 36.2%). Satisfaction with counseling was moderate (40.4-44.1 points). Many women tried at least one therapeutic method (75.9%), whereas only a few were counseled for therapy (acne 27.0%, alopecia 24.6%, hirsutism 24.0%, overweight/obesity 18.8%) with moderate satisfaction for hyperandrogenism (mean 55.1-59.5 points) and good satisfaction for overweight/obesity (mean 60.8 points). Overall satisfaction was rated with a mean of 30.5 points (standard deviation 27.1) on a scale from 0 to 100 and thus considered "not satisfied." Fewer complaints were significantly correlated with higher satisfaction. Most women wished for more counseling (80.8%), as well as more diagnostic (63.2%) and therapeutic options (70.2%). Conclusions: Women affected by PCOS are not properly managed according to the ESHRE guideline. Indeed, this guideline recommends comprehensive history and physical examination for clinical hyperandrogenism as well as holistic approaches in therapy, including education and counseling of patients. Still, overall consultation rates and satisfaction were poor.

Toolkit for emerging technologies in laboratory medicine.

An emerging technology (ET) for laboratory medicine can be defined as an analytical method (including biomarkers) or device (software, applications, and algorithms) that by its stage of development, translation into broad routine clinical practice, or geographical adoption and implementation has the potential to add value to clinical diagnostics. Considering the laboratory medicine-specific definition, this document examines eight key tools, encompassing clinical, analytical, operational, and financial aspects, used throughout the life cycle of ET implementation. The tools provide a systematic approach starting with identifying the unmet need or identifying opportunities for improvement (Tool 1), forecasting (Tool 2), technology readiness assessment (Tool 3), health technology assessment (Tool 4), organizational impact map (Tool 5), change management (Tool 6), total pathway to method evaluation checklist (Tool 7), and green procurement (Tool 8). Whilst there are differences in clinical priorities between different settings, the use of this set of tools will help support the overall quality and sustainability of the emerging technology implementation.

Meeting Challenges of Pediatric Drug Delivery: The Potential of Orally Fast Disintegrating Tablets for Infants and Children.

A majority of therapeutics are not available as suitable dosage forms for administration to pediatric patients. The first part of this review provides an overview of clinical and technological challenges and opportunities in the development of child-friendly dosage forms such as taste masking, tablet size, flexibility of dose administration, excipient safety and acceptability. In this context, developmental pharmacology, rapid onset of action in pediatric emergency situations, regulatory and socioeconomic aspects are also reviewed and illustrated with clinical case studies. The second part of this work discusses the example of Orally Dispersible Tablets (ODTs) as a child-friendly drug delivery strategy. Inorganic particulate drug carriers can thereby be used as multifunctional excipients offering a potential solution to address unique medical needs in infants and children while maintaining a favorable excipient safety and acceptability profile in these vulnerable patient populations.

Reducing the number of unnecessary laboratory tests within hospital through the use of educational interventions.

BACKGROUND: The growing number of laboratory investigation requests is placing an increased burden upon NHS resources. Around a quarter of all tests are unnecessary repeats, and almost a third have no impact on patient management. Doctors recognise that tests should only be performed when clinically indicated, but a culture persists of undertaking unnecessary repeat investigations. METHODS: A cohort study was undertaken at a district general hospital to observe the impact of introducing educational interventions in the form of a poster and a series of educational lectures, encouraging clinicians to consider whether an investigation was clinically indicated. Data was collected from nine different sites across the hospital run by different medical teams regarding the number of tests undertaken and the impact on patient care. RESULTS: Data from over 13,000 tests and over 2000 patients was analysed from nine different sites across the hospital. There was a significant reduction (33%, p = 0.0001) in the number of blood tests performed. This reduction in testing saved £7006 over the course of 1 month, in addition to other benefits. There was a reduction in testing in eight out of the nine sites in which the study was undertaken, demonstrating good generalisability of results. There was no significant increase in length of admission or mortality. CONCLUSION: Educational interventions to doctors have a significant and safe impact in reducing the number of unnecessary investigations, providing cost saving benefits to the NHS.

Plasma supply in the United States.

This descriptive article summarizes the current state of source plasma collection in the United States. It follows the trend of collections over the past several years, ending at 2019, and also includes the number of source plasma collection centers. Usage and distribution of the plasma is also discussed, along with a brief summary of donor compensation policies in the United States.

Practical guide for identifying unmet clinical needs for biomarkers.

The development and evaluation of novel biomarkers and testing strategies requires a close examination of existing clinical pathways, including mapping of current pathways and identifying areas of unmet need. This approach enables early recognition of analytical and clinical performance criteria to guide evaluation studies, in a cyclical and iterative manner, all the time keeping the clinical pathway and patient health outcomes as the key drivers in the process. The Test Evaluation Working Group of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM TE-WG) https://www.eflm.eu/site/page/a/1158 has published a conceptual framework of the test evaluation cycle which is driven by the clinical pathway, inherent to which is the test purpose and role within the pathway that are defined by clinical need. To supplement this framework, the EFLM TE-WG has also published an interactive checklist for identifying unmet clinical needs for new biomarkers; a practical tool that laboratories, clinicians, researchers and industry can equally use in a consistent manner when new tests are developed and before they are released to the market. It is hoped that these practical tools will provide consistent and appropriate terminology in this diverse field and offer a platform that facilitates greater consultation and collaboration between all stakeholders. The checklist should assist the work of all colleagues involved in the discovery of novel biomarkers and implementation of new medical tests. The tool is aligned with the IOM recommendations and the FDA and CE regulating body's requirements.

Transcranial Near-Infrared Laser Therapy for Stroke: How to Recover from Futility in the NEST-3 Clinical Trial.

Development of drugs and devices for the treatment of stroke is not exempt from current translational research standards, which include Stroke Treatment Academic Industry Roundtable (STAIR) criteria and RIGOR guidelines. Near-infrared laser therapy (NILT) was developed to treat stroke in an era when STAIR criteria were not adhered to, thus NILT was not optimized in multiple species, nor was it optimized for efficacy across barriers in translational animal models before proceeding to expensive and extensive clinical trials. Moreover, the majority of rodent studies did not adhere to RIGOR guidelines. This ultimately led to failure in the NeuroThera Effectiveness and Safety Trial-3. Because NILT remains a promising therapeutic approach to treat stroke, we designed a systematic study to determine laser light penetration profiles across the skull of four different species with increasing skull thickness: mouse, rat, rabbit, and human.Our study demonstrates that NILT differentially penetrates the skulls. There is especially extensive attenuation of light energy penetration across the human calvaria, compared with animal skulls, which suggests that the power density setting used in stroke clinical trials may not have optimally stimulated neuroprotection and repair pathways. The results of our study suggest that NILT cannot be sufficiently optimized in "small" animals and directly translated to humans because of significant variances of skull thickness and penetration characteristics across species. NILT neuroprotection should be further studied using a research design that endeavors to incorporate human skull characteristics (thickness) into the development plan to increase the probability of success in stroke victims.

Unmet clinical need in autoimmune liver diseases.

Despite recent advances in understanding and treatment, there remain significant areas of unmet clinical need in each of the autoimmune liver diseases (AILDs). The evolving research landscape and emerging large patient cohorts are creating unique opportunities to translate science into new therapies and care pathways, with the potential to significantly improve the lives of AILD patients. However, the areas of unmet need represent real challenges, which need to be addressed, if this vision is to be realised. This review describes the areas of unmet need in AILD in adults relating to diagnostic and prognostic assessment, primary therapy, symptom management, trial design and delivery, and structured care delivery, with the aim of focusing future research prioritisation.

Identifying and addressing unmet clinical needs in Ph-neg classical myeloproliferative neoplasms: a consensus-based SIE, SIES, GITMO position paper.

This article presents the results of group discussion among experts from SIE, SIES and GITMO societies aimed at highlighting unmet challenges in the management of Ph-neg myeloproliferative neoplasms (MPNs). The issues analyzed were: diagnosis of prefibrotic myelofibrosis; diagnosis of Ph-neg MPNs in the setting of splanchnic vein thrombosis (SVT); management of low-risk PV and low-risk ET patients with JAK2V617F mutation; molecular biomarkers in the prognostic evaluation of myelofibrosis (MF); ruxolitinib therapy in low-risk MF; therapy in patients with SVT-associated Ph-neg MPN; indications of splenectomy in MF. For each of these issues, proposals for advancement in clinical research were addressed.