Systematic review on the frequency and quality of reporting patient and public involvement in patient safety research.

BACKGROUND: In recent years, patient and public involvement (PPI) in research has significantly increased; however, the reporting of PPI remains poor. The Guidance for Reporting Involvement of Patients and the Public (GRIPP2) was developed to enhance the quality and consistency of PPI reporting. The objective of this systematic review is to identify the frequency and quality of PPI reporting in patient safety (PS) research using the GRIPP2 checklist. METHODS: Searches were performed in Ovid MEDLINE, EMBASE, PsycINFO, and CINAHL from 2018 to December, 2023. Studies on PPI in PS research were included. We included empirical qualitative, quantitative, mixed methods, and case studies. Only articles published in peer-reviewed journals in English were included. The quality of PPI reporting was assessed using the short form of the (GRIPP2-SF) checklist. RESULTS: A total of 8561 studies were retrieved from database searches, updates, and reference checks, of which 82 met the eligibility criteria and were included in this review. Major PS topics were related to medication safety, general PS, and fall prevention. Patient representatives, advocates, patient advisory groups, patients, service users, and health consumers were the most involved. The main involvement across the studies was in commenting on or developing research materials. Only 6.1% (n = 5) of the studies reported PPI as per the GRIPP2 checklist. Regarding the quality of reporting following the GRIPP2-SF criteria, our findings show sub-optimal reporting mainly due to failures in: critically reflecting on PPI in the study; reporting the aim of PPI in the study; and reporting the extent to which PPI influenced the study overall. CONCLUSIONS: Our review shows a low frequency of PPI reporting in PS research using the GRIPP2 checklist. Furthermore, it reveals a sub-optimal quality in PPI reporting following GRIPP2-SF items. Researchers, funders, publishers, and journals need to promote consistent and transparent PPI reporting following internationally developed reporting guidelines such as the GRIPP2. Evidence-based guidelines for reporting PPI should be encouraged and supported as it helps future researchers to plan and report PPI more effectively. TRIAL REGISTRATION: The review protocol is registered with PROSPERO (CRD42023450715).

A systematic review critically appraising quantitative survey measures assessing power dynamics among multidisciplinary teams in acute care settings.

By valuing the knowledge of each discipline holistic patient-centered care can be achieved as decisions arise from expertise rather than established hierarchies. While healthcare has historically operated as a hierarchical power structure (i.e., some voices have more influence), these dynamics are rarely discussed. This review addresses this issue by appraising extant quantitative measures that assess multidisciplinary team (MDT) power dynamics. By identifying psychometrically sound measures, change agents can uncover the collective thought processes informing power structures in practice and develop strategies to mitigate power disparities. Several databases were searched. English language articles were included if they reported on quantitative measures assessing power dynamics among MDTs in acute/hospital settings. Results were synthesized using a narrative approach. In total, 6,202 search records were obtained of which 62 met the eligibility criteria. The review reveals some promising measures to assess power dynamics (e.g., Interprofessional Collaboration Scale). However, the findings also confirm several gaps in the current evidence base: 1) need for further psychometric and pragmatic testing of measures; 2) inclusion of more representative MDT samples; 3) further evaluation of unmatured power dimensions. Addressing these gaps will support the development of future interventions aimed at mitigating power imbalances and ultimately improve collaborative working within MDTs.

Impact of Metabolic Stress on BeWo Syncytiotrophoblast Function.

During placental formation, cytotrophoblasts (CTBs) fuse into multinucleate, microvilli-coated syncytiotrophoblasts (STBs), which contact maternal blood, mediating nutrient, metabolite, and gas exchange between mother and fetus, and providing a barrier against fetal infection. Trophoblasts remodel the surrounding extracellular matrix through the secretion of matrix metalloproteinases (MMPs). Maternal obesity and diabetes mellitus can negatively impact fetal development and may impair trophoblast function. We sought to model the impact of metabolic stress on STB function by examining MMP and hormone secretion. The BeWo CTB cell line was syncytialized to STB-like cells with forskolin. Cell morphology was examined by electron microscopy and immunofluorescence; phenotype was further assessed by ELISA and RT-qPCR. STBs were exposed to a metabolic stress cocktail (MetaC: 30 mM glucose, 10 nM insulin, and 0.1 mM palmitic acid). BeWo syncytialization was demonstrated by increased secretion of HCGß and progesterone, elevated syncytin gene expression (ERVW-1 and ERVFRD-1), loss of tight junctions, and increased surface microvilli. MetaC strongly suppressed syncytin gene expression (ERVW-1 and ERVFRD-1), suppressed HCGß and progesterone secretion, and altered both MMP-9 and MMP-2 production. Metabolic stress modeling diabetes and obesity altered BeWo STB hormone and MMP production in vitro.

COVID-19 community assessment hubs in Ireland: A study of staff and patient perceptions of their value.

BACKGROUND: Critical care bed capacity per capita in Ireland is among the lowest in Europe. The COVID-19 pandemic has put additional strain on an over-stretched healthcare system. COVID-19 community assessment hubs (CAHs) were established to prevent unnecessary admission to acute hospitals and to reduce infection spread. OBJECTIVE: The aim of this study was to assess the effectiveness and acceptability of CAHs and identify how the service might be improved or adapted for possible future use. DESIGN: This was a mixed methods study, incorporating co-design with clinical stakeholders. Data collection was via an online survey and semistructured telephone interviews with staff and patients conducted between January and May 2021. SETTING AND PARTICIPANTS: Thirty-one patients completed the survey and nine were interviewed. Twenty interviews were conducted with staff. RESULTS: The findings suggest that the CAH model was successful in providing a dedicated pathway for assessing patients with COVID-19 symptoms, whilst mitigating the risk of infection. Patients were particularly positive about the timely, comprehensive and holistic care they received, as well as the accessibility of the clinics and the friendly attitudes of the staff. Staff welcomed the training and clinical protocols which contributed to their feelings of safety and competency in delivering care to this cohort of patients. They also highlighted the benefits of working in a multidisciplinary environment. Both staff and patients felt that the hubs could be repurposed for alternative use, including the treatment of chronic diseases. DISCUSSION: This study describes staff and patients' experiences of these hubs. An unexpected outcome of this study is its demonstration of the true value of effective multidisciplinary working, not only for the staff who were deployed to this service but also for the patients in receipt of care in these hubs. CONCLUSION: This multidisciplinary patient-centred service may provide a useful model for the delivery of other services currently delivered in hospital settings. PATIENT OR PUBLIC CONTRIBUTION: An earlier phase of this study involved interviews with COVID-19-positive patients on a remote monitoring programme. The data informed this phase. Several of the authors had worked in the CAHs and provided valuable input into the design of the staff and patient interviews.

Exploring healthcare staff narratives to gain an in-depth understanding of changing multidisciplinary team power dynamics during the COVID-19 pandemic.

BACKGROUND: Multidisciplinary teams (MDTs) are integral to healthcare provision. However, healthcare has historically adopted a hierarchical power structure meaning some voices within the MDT have more influence than others. While power dynamics can influence interprofessional communication and care coordination, the field's understanding of these power structures during the COVID-19 pandemic is limited. METHODS: Adopting a narrative inquiry methodology, this research addresses this knowledge gap and provides an in-depth understanding of MDT power dynamics during COVID-19. Using semi-structured interviews (n = 35) and inductive thematic analysis, this research explores staff perspectives of changing power dynamics in MDTs during the pandemic response. RESULTS: An in-depth analysis generated three overarching themes: (1) Healthcare: a deeply embedded hierarchy reveals that while a hierarchical culture prevails within the Irish health system, staff perceptions of influence in MDTs and 'real' experiences of autonomy differ significantly. (2) Team characteristics: the influence of team structure on MDT power dynamics highlights the impact of organisational structures (e.g., staff rotations) and local processes (e.g., MDT meeting structure) on collaborative practice. (3) Ongoing effort to stimulate true collaboration underscores the importance of ongoing interprofessional education to support collaborative care. CONCLUSION: By offering a greater understanding of MDT power dynamics throughout the COVID-19 pandemic, this research supports the development of more appropriate strategies to promote the provision of interprofessional care in practice.

A resilient workforce: patient safety and the workforce response to a cyber-attack on the ICT systems of the national health service in Ireland.

BACKGROUND: In May 2021, the Irish public health service was the target of a cyber-attack. The response by the health service resulted in the widespread removal of access to ICT systems. While services including radiology, diagnostics, maternity, and oncology were prioritised for reinstatement, recovery efforts continued for over four months. This study describes the response of health service staff to the loss of ICT systems, and the risk mitigation measures introduced to safely continue health services. The resilience displayed by frontline staff whose rapid and innovative response ensured continuity of safe patient care is explored. METHODS: To gain an in-depth understanding of staff experiences of the cyber-attack, eight focus groups (n = 36) were conducted. Participants from a diverse range of health services were recruited, including staff from radiology, pathology/laboratories, radiotherapy, maternity, primary care dental services, health and wellbeing, COVID testing, older person's care, and disability services. Thematic Analysis was applied to the data to identify key themes. RESULTS: The impact of the cyber-attack varied across services depending on the type of care being offered, the reliance on IT systems, and the extent of local IT support. Staff stepped-up to the challenges and quickly developed and implemented innovative solutions, exhibiting great resilience, teamwork and adaptability, with a sharp focus on ensuring patient safety. The cyber-attack resulted in a flattening of the healthcare hierarchy, with shared decision-making at local levels leading to an empowered frontline workforce. However, participants in this study felt the stress placed on staff by the attack was more severe than the cumulative effect of the COVID-19 pandemic. CONCLUSIONS: Limited contingencies within the health system IT infrastructure - what we call a lack of system resilience - was compensated for by a resilient workforce. Within the context of the prevailing COVID-19 pandemic, this was an enormous burden on a dedicated workforce. The adverse impact of this attack may have long-term and far-reaching consequences for staff wellbeing. Design and investment in a resilient health system must be prioritised.

HYPHAEdelity: a quantitative image analysis tool for assessing peripheral whole colony filamentation.

The yeast Saccharomyces cerevisiae, also known as brewer's yeast, can undergo a reversible stress-responsive transition from individual ellipsoidal cells to chains of elongated cells in response to nitrogen- or carbon starvation. Whole colony morphology is frequently used to evaluate phenotypic switching response; however, quantifying two-dimensional top-down images requires each pixel to be characterized as belonging to the colony or background. While feasible for a small number of colonies, this labor-intensive assessment process is impracticable for larger datasets. The software tool HYPHAEdelity has been developed to semi-automate the assessment of two-dimensional whole colony images and quantify the magnitude of peripheral whole colony yeast filamentation using image analysis tools intrinsic to the OpenCV Python library. The software application functions by determining the total area of filamentous growth, referred to as the f-measure, by subtracting the area of the inner colony boundary from the outer-boundary area associated with hyphal projections. The HYPHAEdelity application was validated against automated and manually pixel-counted two-dimensional top-down images of S. cerevisiae colonies exhibiting varying degrees of filamentation. HYPHAEdelity's f-measure results were comparable to areas determined through a manual pixel enumeration method and found to be more accurate than other whole colony filamentation software solutions.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

BACKGROUND: Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with ongoing transmission (WHO 2020). The World Health Organization (WHO) estimated that, in 2019, approximately 229 million cases of malaria occurred worldwide, with 94% occurring in the WHO's African region (WHO 2020). Of these malaria cases, an estimated 409,000 deaths occurred globally, with 67% occurring in children under five years of age (WHO 2020). Malaria also negatively impacts the health of women during pregnancy, childbirth, and the postnatal period (WHO 2020). Sulfadoxine/pyrimethamine (SP), an antifolate antimalarial, has been widely used across sub-Saharan Africa as the first-line treatment for uncomplicated malaria sTo examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure?Criteria for considering studies for this review Types of studies Inclusion criteria Randomized controlled trials (RCTs) Quasi-RCTs with randomization at the individual or cluster level conducted in malaria-endemic areas (areas with ongoing, local malaria transmission, including areas approaching elimination, as listed in the World Malaria Report 2020) (WHO 2020) Exclusion criteria Ecological studies Observational studies In vivo/in vitro studies Economic studies Systematic literature reviews and meta-analyses (relevant systematic literature reviews and meta-analyses will be excluded but flagged for grey literature screening) Types of participants Inclusion criteria Individuals of any age or gender, living in a malaria endemic area, who are taking antifolate antimalarial medications (inclu

Persistent bacteremia and psoas abscess caused by a lethal toxin-deficient Paeniclostridiumsordellii.

We present a case of persistent bacteremia and psoas abscess from Paeniclostridium sordellii without severe symptoms or the classically associated toxic shock syndrome. Further laboratory evaluation demonstrated that the Paeniclostridium sordellii isolate lacked the lethal toxin gene and there was no cytotoxicity to exposed Vero cells.

Critical assessment of the current indicator for antenatal iron-containing supplementation coverage: Insights from a mixed-methods study.

Daily consumption of iron-containing supplements is recommended for all pregnant women but there is no approved global standard indicator for assessing supplementation coverage. Furthermore, the validity of commonly used coverage indicators for iron-containing supplement consumption is questionable. The WHO-UNICEF Technical Expert Advisory Group on Nutrition Monitoring, and partners, have systematically worked to identify a feasible and valid indicator of iron-containing supplement coverage for reporting by countries. In 2019, we conducted key informant interviews with respondents in eight countries, fielded an online survey (in three languages using SurveyMonkey) to which 142 nutrition professionals from 52 countries responded, and used Demographic and Health Surveys (DHS) data from four countries to assess determinants of the quality of iron-containing supplement coverage data. Less than half (45%) of online survey respondents were satisfied with the current methods for collecting iron-containing supplement coverage data in their context. Recommended changes by study respondents include recall period <5 years, adding questions about counselling, including other beneficiary groups, and assessing supply chain functionality. The DHS analysis suggested an association between time since pregnancy and data quality. Data heaping on multiples of 30 was observed in 40%-75% of data. There is a clear demand for a revised indicator and measurement guidance for coverage of iron-containing supplementation during pregnancy. Future research should continue the development and validation of a global indicator, to more precisely validate the quality of recall data, including the distinction between distribution and consumption using various question formulations.

Antibacterial and Anti-biofilm Activity of the Human Breast Milk Glycoprotein Lactoferrin against Group B Streptococcus.

Group B Streptococcus (GBS) is an encapsulated Gram-positive human pathogen that causes invasive infections in pregnant hosts and neonates, as well as immunocompromised individuals. Colonization of the human host requires the ability to adhere to mucosal surfaces and circumnavigate the nutritional challenges and antimicrobial defenses associated with the innate immune response. Biofilm formation is a critical process to facilitate GBS survival and establishment of a replicative niche in the vertebrate host. Previous work has shown that the host responds to GBS infection by producing the innate antimicrobial glycoprotein lactoferrin, which has been implicated in repressing bacterial growth and biofilm formation. Additionally, lactoferrin is highly abundant in human breast milk and could serve a protective role against invasive microbial pathogens. This study demonstrates that human breast milk lactoferrin has antimicrobial and anti-biofilm activity against GBS and inhibits its adherence to human gestational membranes. Together, these results indicate that human milk lactoferrin could be used as a prebiotic chemotherapeutic strategy to limit the impact of bacterial adherence and biofilm formation on GBS-associated disease outcomes.

Phase I clinical trial of temozolomide and methoxyamine (TRC-102), an inhibitor of base excision repair, in patients with advanced solid tumors.

Temozolomide (TMZ) generates DNA adducts that are repaired by direct DNA and base excision repair mechanisms. Methoxyamine (MX, TRC-102) potentiates TMZ activity by binding to apurinic and apyrimidinic (AP) sites after removal of N3-methyladenine and N7-methylguanine, inhibiting site recognition of AP endonuclease. We conducted a phase I trial to determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of intravenous MX when given with oral TMZ. Patients with advanced solid tumors and progression on standard treatment were enrolled to a standard 3 + 3 dose escalation trial assessing escalating doses of TMZ and MX. Tumor response was assessed per RECIST and adverse events (AEs) by CTCAEv3. Pharmacokinetics (PK) of MX and COMET assays on peripheral blood mononuclear cells were performed. 38 patients were enrolled-median age 59.5 years (38-76), mean number of cycles 2.9 [1-13]. No DLTs were observed. Cycle 1 grade 3 AEs included fatigue, lymphopenia, anemia, INR, leukopenia, neutropenia, allergic reaction, constipation, psychosis and paranoia. Cycle 2-13 grade 4 AEs included thrombocytopenia and confusion. A partial response was seen in 1 patient with a pancreatic neuroendocrine tumor (PNET) and six additional patients, each with different tumor types, demonstrated prolonged stable disease. MX PK was linear with dose and was not affected by concomitant TMZ. TMZ 200 mg/m2 daily × 5 may be safely administered with MX 150 mg/m2 intravenously once on day 1 with minimal toxicity. Further studies assessing this drug combination in select tumor types where temozolomide has activity may be warranted.

A systematic review exploring the impact of focal leader behaviours on health care team performance.

AIM: The aim of this study is to understand how the behaviour of focal leaders impacts health care team performance and effectiveness. BACKGROUND: Despite recent shifts towards more collectivistic leadership approaches, hierarchical structures that emphasize the role of an individual focal leader (i.e., the formal appointed leader) are still the norm in health care. Our understanding of the effect of focal leader behaviours on health care team performance remains unclear. EVALUATION: A systematic review was conducted. Five electronic databases were searched using key terms. One thousand forty-seven records were retrieved. Data extraction, quality appraisal and narrative synthesis were conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. KEY ISSUES: Fifty papers met the criteria for inclusion, were reviewed and synthesized under the following categories: task-focused leadership, directive leadership, empowering leadership and relational focused leadership. CONCLUSIONS: Categories are discussed in relation to team performance outcomes, safety specific outcomes, individual-level outcomes and outcomes related to interpersonal dynamics. Emerging themes are explored to examine and reflect on how leadership is enacted in health care, to catalogue best practices and to cascade these leadership practices broadly. IMPLICATIONS FOR NURSING MANAGEMENT: Empowering and relational leadership styles were associated with positive outcomes for nursing team performance. This underscores the importance of training and encouraging nursing leaders to engage in more collaborative leadership behaviours.

A qualitative evaluation of participants' experiences of using co-design to develop a collective leadership educational intervention for health-care teams.

INTRODUCTION: Co-design involves stakeholders as design partners to ensure a better fit to user needs. Many benefits of involving stakeholders in design processes have been proposed; however, few studies have evaluated participants' experience of co-design in the development of educational interventions. As part of a larger study, health-care professionals, researchers and patients co-designed a collective leadership intervention for health-care teams. This study evaluated their experiences of the co-design process. METHODS: Semi-structured interviews were conducted with individuals (n = 10) who took part in the co-design workshops. Interviews were audio-recorded, transcribed verbatim and analysed thematically. RESULTS: Four key themes were identified from the data: (a) Managing expectations in an open-ended process; (b) Establishing a positive team climate; (c) Focusing on frustrations-challenging but informative; and (d) Achieving a genuine co-design partnership. CONCLUSIONS: The development of a positive team climate is essential to the co-design process. Organizers should focus on building strong working relationships from the beginning to enable open discussion. Organizers of co-design should be conscious of establishing and maintaining a genuine partnership where participants are involved as equal partners and co-creators. This can be done through the continuous use of feedback to allow participants to influence the workshop directions, and through limiting researcher domination. Lastly, co-design can be daunting, but organizers can positively impact participants' experience by acknowledging the emergent nature of the process in order to reduce participant apprehension, thereby limiting the barriers to participation.

The micropolitics of implementation; a qualitative study exploring the impact of power, authority, and influence when implementing change in healthcare teams.

BACKGROUND: Healthcare organisations are complex social entities, comprising of multiple stakeholders with differing priorities, roles, and expectations about how care should be delivered. To reach agreement among these diverse interest groups and achieve safe, cost-effective patient care, healthcare staff must navigate the micropolitical context of the health service. Micropolitics in this study refers to the use of power, authority, and influence to affect team goals, vision, and decision-making processes. Although these concepts are influential when cultivating change, there is a dearth of literature examining the mechanisms through which micropolitics influences implementation processes among teams. This paper addresses this gap by exploring the role of power, authority, and influence when implementing a collective leadership intervention in two multidisciplinary healthcare teams. METHODS: The multiple case study design adopted employed a triangulation of qualitative research methods. Over thirty hours of observations (Case A = 16, Case B = 15) and twenty-five interviews (Case A = 13, Case B = 12) were completed. An in-depth thematic analysis of the data using an inductive coding approach was completed to understand the mechanisms through which contextual factors influenced implementation success. A context coding framework was also employed throughout implementation to succinctly collate the data into a visual display and to provide a high-level overview of implementation effect (i.e. the positive, neutral, or negative impact of contextual determinants on implementation). RESULTS: The findings emphasised that implementing change in healthcare teams is an inherently political process influenced by prevailing power structures. Two key themes were generated which revealed the dynamic role of these concepts throughout implementation: 1) Exerting hierarchical influence for implementation; and 2) Traditional power structures constraining implementation. Gaining support across multiple levels of leadership was influential to implementation success as the influence exercised by these individuals persuaded follower engagement. However, the historical dynamics of each team determined how this influence was exerted and perceived, which negatively impacted some participants' experiences of the implementation process. CONCLUSION: To date, micropolitics has received scant attention in implementation science literature. This study introduces the micropolitical concepts of power, authority and influence as essential contextual determinants and outlines the mechanisms through which these concepts influence implementation processes.

A Nonhemolytic Group B Streptococcus Strain Exhibits Hypervirulence.

Group B streptococci (GBS) are Gram-positive bacteria that are a leading cause of neonatal infections. Most invasive isolates are ß-hemolytic, and hemolytic activity is critical for GBS virulence. Although nonhemolytic GBS strains are occasionally isolated, they are often thought to be virulence attenuated. In this study, we show that a nonhemolytic GBS strain (GB37) isolated from a septic neonate exhibits hypervirulence. Substitution of tryptophan to leucine (W297L) in the sensor histidine kinase CovS results in constitutive kinase signaling, leading to decreased hemolysis and increased activity of the GBS hyaluronidase, HylB. These results describe how nonpigmented and nonhemolytic GBS strains can exhibit hypervirulence.

Immune checkpoint-mediated myositis and myasthenia gravis: A case report and review of evaluation and management.

BACKGROUND: We present a case of myositis and possible overlapping neuromuscular junction disorder following treatment with nivolumab for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). METHODS: We report a 75-year-old man with recurrent stage IVA, T1N2cM0 oral cavity HNSCC treated with weight-dosed nivolumab who presented three weeks later with severe fatigue, generalized weakness, and bilateral ptosis. Evaluation demonstrated elevated creatine kinase and myopathic motor units on electromyography, supporting a diagnosis of an underlying muscle disease. Elevated serum acetylcholine receptor binding antibodies raised the possibility of concurrent myasthenia gravis. RESULTS: He received corticosteroids and plasmapheresis without improvement in muscle weakness. His course was complicated by bacteremia, cardiac arrest, and concerns for recurrent malignancy. Following a two-month hospital stay, he was made comfort care and died. CONCLUSIONS: With increasing usage of checkpoint inhibitors in HNSCC, clinicians must be aware of and vigilant for associated rare but serious adverse events.

Staphylococcus aureus Infection of Human Gestational Membranes Induces Bacterial Biofilm Formation and Host Production of Cytokines.

Staphylococcus aureus, a metabolically flexible gram-positive pathogen, causes infections in a variety of tissues. Recent evidence implicates S. aureus as an emerging cause of chorioamnionitis and premature rupture of membranes, which are associated with preterm birth and neonatal disease. We demonstrate here that S. aureus infects and forms biofilms on the choriodecidual surface of explanted human gestational membranes. Concomitantly, S. aureus elicits the production of proinflammatory cytokines, which could ultimately perturb maternal-fetal tolerance during pregnancy. Therefore, targeting the immunological response to S. aureus infection during pregnancy could attenuate disease among infected individuals, especially in the context of antibiotic resistance.

NCCN Guidelines Insights: Central Nervous System Cancers, Version 1.2017.

For many years, the diagnosis and classification of gliomas have been based on histology. Although studies including large populations of patients demonstrated the prognostic value of histologic phenotype, variability in outcomes within histologic groups limited the utility of this system. Nonetheless, histology was the only proven and widely accessible tool available at the time, thus it was used for clinical trial entry criteria, and therefore determined the recommended treatment options. Research to identify molecular changes that underlie glioma progression has led to the discovery of molecular features that have greater diagnostic and prognostic value than histology. Analyses of these molecular markers across populations from randomized clinical trials have shown that some of these markers are also predictive of response to specific types of treatment, which has prompted significant changes to the recommended treatment options for grade III (anaplastic) gliomas.