Pessary treatment for pelvic organ prolapse and health-related quality of life: a review

Pessaries have been used to treat women with pelvic organ prolapse (POP) since the beginning of recorded history. This review aims to assess the effect of pessary treatment on the disease-specific, health-related quality of life in women with pelvic organ prolapse. After a Medline search using the Mesh term ‘pessary’ and critical appraisal, 41 articles were selected and used in this review. Pessaries are widely used to treat pelvic organ prolapse. It is minimally invasive and appears to be safe. Although there is evidence that the use of pessaries in the treatment of pelvic organ prolapse is effective in alleviating symptoms and that patient satisfaction is high, the follow-up in many published papers is short, and the use of validated urogynaecological questionnaires is limited. Comparison with surgical treatment of pelvic organ prolapse is rare and not assessed in a randomised controlled trial

State of the art and future directions in the systemic treatment of medullary thyroid cancer

PURPOSE OF REVIEW: Systemic treatment is the only therapeutic option for patients with progressive, metastatic medullary thyroid cancer (MTC). Since the discovery of the rearranged during transfection (RET) proto-oncogene (100% hereditary, 60-90% sporadic MTC), research has focused on finding effective systemic therapies to target this mutation. This review surveys recent findings. RECENT FINDINGS: Multikinase inhibitors are systemic agents targeting angiogenesis, inhibiting growth of tumor cells and cells in the tumor environment and healthy endothelium. In the phase III EXAM and ZETA trials, cabozantinib and vandetanib showed progression-free survival benefit, without evidence of prolonged overall survival. Selpercatinib and pralsetinib are kinase inhibitors with high specificity for RET; phase I and II studies showed overall response rates of 73% and 71% in first line, and 69% and 60% in second line treatment, respectively. Although resistance mechanisms to mutation-driven therapy will be a challenge in the future, phase III studies are ongoing and neo-adjuvant therapy with selpercatinib is being studied. SUMMARY: The development of selective RET-inhibitors has expanded the therapeutic arsenal to control tumor growth in progressive MTC, with fewer adverse effects than multikinase inhibitors. Future studies should confirm their effectiveness, study neo-adjuvant strategies, and tackle resistance to these inhibitors, ultimately to improve patient outcomes

Developer perspectives on the ethics of AI-driven neural implants:a qualitative study

Convergence of neural implants with artificial intelligence (AI) presents opportunities for the development of novel neural implants and improvement of existing neurotechnologies. While such technological innovation carries great promise for the restoration of neurological functions, they also raise ethical challenges. Developers of AI-driven neural implants possess valuable knowledge on the possibilities, limitations and challenges raised by these innovations; yet their perspectives are underrepresented in academic literature. This study aims to explore perspectives of developers of neurotechnology to outline ethical implications of three AI-driven neural implants: a cochlear implant, a visual neural implant, and a motor intention decoding speech-brain-computer-interface. We conducted semi-structured focus groups with developers (n = 19) of AI-driven neural implants. Respondents shared ethically relevant considerations about AI-driven neural implants that we clustered into three themes: (1) design aspects; (2) challenges in clinical trials; (3) impact on users and society. Developers considered accuracy and reliability of AI-driven neural implants conditional for users’ safety, authenticity, and mental privacy. These needs were magnified by the convergence with AI. Yet, the need for accuracy and reliability may also conflict with potential benefits of AI in terms of efficiency and complex data interpretation. We discuss strategies to mitigate these challenges.</p

Developer perspectives on the ethics of AI-driven neural implants:a qualitative study

Convergence of neural implants with artificial intelligence (AI) presents opportunities for the development of novel neural implants and improvement of existing neurotechnologies. While such technological innovation carries great promise for the restoration of neurological functions, they also raise ethical challenges. Developers of AI-driven neural implants possess valuable knowledge on the possibilities, limitations and challenges raised by these innovations; yet their perspectives are underrepresented in academic literature. This study aims to explore perspectives of developers of neurotechnology to outline ethical implications of three AI-driven neural implants: a cochlear implant, a visual neural implant, and a motor intention decoding speech-brain-computer-interface. We conducted semi-structured focus groups with developers (n = 19) of AI-driven neural implants. Respondents shared ethically relevant considerations about AI-driven neural implants that we clustered into three themes: (1) design aspects; (2) challenges in clinical trials; (3) impact on users and society. Developers considered accuracy and reliability of AI-driven neural implants conditional for users’ safety, authenticity, and mental privacy. These needs were magnified by the convergence with AI. Yet, the need for accuracy and reliability may also conflict with potential benefits of AI in terms of efficiency and complex data interpretation. We discuss strategies to mitigate these challenges.</p

Clinical benefit of systemic therapies for recurrent ovarian cancer-ESMO-MCBS scores

BACKGROUND: Licensed systemic treatment options for platinum-sensitive recurrent ovarian cancer are platinum-based chemotherapy and maintenance treatment with bevacizumab and poly (ADP-ribose) polymerase inhibitors. For platinum-resistant disease, several non-platinum options are available. We aimed to assess the clinical benefit of these treatments according to the European Society of Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS). MATERIALS AND METHODS: A PubMed search was carried out including all studies evaluating systemic treatment of recurrent epithelial ovarian cancer, from 1990 onwards. Randomised trials with an adequate comparator and design showing a statistically significant benefit of the study arm were independently scored by two blinded observers using the ESMO-MCBS. RESULTS: A total of 1127 papers were identified, out of which 61 reported results of randomised trials of sufficient quality. Nineteen trials showed statistically significant results and the studied treatments were graded according to ESMO-MCBS. Only three treatments showed substantial benefit (score of 4 on a scale of 1-5) according to the ESMO-MCBS: platinum-based chemotherapy with paclitaxel in the platinum-sensitive setting and the addition of bevacizumab to chemotherapy in the platinum-resistant setting. The WEE1 inhibitor adavosertib (not licensed) also scores a 4, based on a recent small phase II study. Assessment of quality-of-life data and toxicity using the ESMO-MCBS showed to be complex, which should be taken into account in using this score for clinical decision making. CONCLUSION: Only a few licensed systemic therapies for recurrent ovarian cancer show substantial clinical benefit based on ESMO-MCBS scores. Trials demonstrating overall survival benefit are sparse

Progressive neurological deficits in multiple myeloma: meningeal myelomatosis without MRI abnormalities

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Beta-blockers and glioma: a systematic review of preclinical studies and clinical results

Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was to systematically review the evidence on the effect of beta-blockers on glioma growth. A systematic literature search was performed in the PubMed, Embase, Google Scholar, Web of Science, and Cochrane Central to identify all relevant studies. Preclinical studies concerning the pharmacodynamic effects of beta-blockers on glioma growth and proliferation were included, as well as clinical studies that studied the effect of beta-blockers on patient outcomes according to PRISMA guidelines. Among the 980 citations, 10 preclinical studies and 1 clinical study were included after title/abstract and full-text screening. The following potential mechanisms were identified: reduction of glioma cell proliferation (n = 9), decrease of glioma cell migration (n = 2), increase of drug sensitivity (n = 1), induction of glioma cell death (n = 1). Beta-blockers affect glioma proliferation by inducing a brief reduction of cAMP and a temporary cell cycle arrest in vitro. Contrasting results were observed concerning glioma cell migration. The identified clinical study did not find an association between beta-blockers and survival in glioma patients. Although preclinical studies provide scarce evidence for the use of beta-blockers in glioma, they identified potential pathways for targeting glioma. Future studies are needed to clarify the effect of beta-blockers on clinical endpoints including survival outcomes in glioma patients to scrutinize the value of beta-blockers in glioma care

Guiding cities under increased droughts: The limits to sustainable urban futures

Climate change is likely to increase droughts. The vulnerability of cities to droughts is increasing worldwide. Policy responses from cities to droughts lack consideration of long-term climatic and socio-economic scenarios, and focus on short-term emergency actions that disregard sustainability in the connected regional and river basin systems. We aim to explore the dynamics of the water-energy-land nexus in urban systems suffering increased climate change-related droughts, and their implications for sustainability. We complement a case study with a literature review providing cross-regional insights, and detail pervasive knowledge, policy and ambition gaps in the interaction between cities and droughts. We show that water availability with low emissions, without compromising ecosystems and with low costs to society, poses a local-scale limit to sustainable urban growth, a new concept delineating the limits to growth in cities. We conclude that urban and river basin planners need to institutionalize transparency and cross-sectoral integration in multi-sector partnerships, to consider long-term land use planning together with water and energy, and to apply integrated climate services to cities. Our study reveals the importance of including land, water and energy in long-term urban planning, and to connect them with the county, region, river basin and global scales. © 2021 The Author(s)The authors would like to express their gratitude for limited contributions, comments and discussions that helped to improve the manuscript to Muhamad Bahri, Jörg Cortekar, Mirabela Marin, Serban Octavian Davidescu, Iñaki Torres Cobián, and to two anonymous reviewers that helped to substantially improve the manuscript. Valuable feedback obtained in two conference sessions co‑lead by some of the authors (at Adaptation Futures 2018 in Cape Town, and at the 4th European Climate Change Adaptation conference, in Lisbon in 2019) is acknowledged. The authors acknowledge financial support from the project CLISWELN funded by ERA4CS. ERA4CS is an ERA-NET initiated by JPI Climate, and CLISWELN is funded by BMBF (DE), UEFISCDI (RO), BMBWF and FFG (AT), and MINECO (ES), with co-funding from the European Union (Grant 690462 ). This paper and the content included in it do not represent the opinion of the European Union, and the European Union is not responsible for any use that might be made of its content. Marta OlazabalThe authors would like to express their gratitude for limited contributions, comments and discussions that helped to improve the manuscript to Muhamad Bahri, Jörg Cortekar, Mirabela Marin, Serban Octavian Davidescu, Iñaki Torres Cobián, and to two anonymous reviewers that helped to substantially improve the manuscript. Valuable feedback obtained in two conference sessions co‑lead by some of the authors (at Adaptation Futures 2018 in Cape Town, and at the 4th European Climate Change Adaptation conference, in Lisbon in 2019) is acknowledged. The authors acknowledge financial support from the project CLISWELN funded by ERA4CS. ERA4CS is an ERA-NET initiated by JPI Climate, and CLISWELN is funded by BMBF (DE), UEFISCDI (RO), BMBWF and FFG (AT), and MINECO (ES), with co-funding from the European Union (Grant 690462 ). This paper and the content included in it do not represent the opinion of the European Union, and the European Union is not responsible for any use that might be made of its content. Marta Olazaba

Upscaling urban recycled water schemes : An analysis of the presence of required governance conditions in the city of Sabadell (Spain)

Cleaning wastewater and using it again for secondary purposes is a measure to address water scarcity in urban areas. However, upscaling of recycled water schemes is challenging, and little is known about the governance conditions which are required for this. This paper addresses this knowledge gap. Based on a review of governance literature we suggest that five governance conditions are necessary for a successful upscaling of recycled water schemes: (1) policy leadership, (2) policy coordination, (3) availability of financial resources, (4) awareness of a problem, and (5) the presence of a public forum. We applied these concepts in a case study on the upscaling of a recycled water scheme in Sabadell, Spain. We reviewed policy documents, conducted a set of 21 semi-structured interviews, and attended two policy meetings about the subject. Our results suggest that Sabadell meets the required conditions for upscaling reused water to a certain extent. However, a public forum is not well-developed. We discuss the implications of this and conclude with some suggestions for future research and some lessons for other cities that plan to upscale their recycled water schemes

Diagnostics and treatment delay in primary central nervous system lymphoma:What the neurosurgeon should know

Purpose: The gold standard for diagnostics in primary central nervous system lymphoma (PCNSL) is histopathological diagnosis after stereotactic biopsy. Yet, PCNSL has a multidisciplinary diagnostic work up, which associated with diagnostic delay and could result in treatment delay. This article offers recommendations to neurosurgeons involved in clinical decision-making regarding (novel) diagnostics and care for patients with PCNSL with the aim to improve uniformity and timeliness of the diagnostic process for patients with PCNSL. Methods: We present a mini review to discuss the role of stereotactic biopsy in the context of novel developments in diagnostics for PCNSL, as well as the role for cytoreductive surgery. Results: Cerebrospinal fluid-based diagnostics are supplementary and cannot replace stereotactic biopsy-based diagnostics. Conclusion: Histopathological diagnosis after stereotactic biopsy of the brain remains the gold standard for diagnosis. Additional diagnostics should not be a cause of diagnostic delay. There is currently no sufficient evidence supporting cytoreductive surgery in PCNSL, with recent studies showing contradictive data and suboptimal study designs.</p