Multidisciplinary consensus guideline for the diagnosis and management of spontaneous intracranial hypotension.

BACKGROUND: We aimed to create a multidisciplinary consensus clinical guideline for best practice in the diagnosis, investigation and management of spontaneous intracranial hypotension (SIH) due to cerebrospinal fluid leak based on current evidence and consensus from a multidisciplinary specialist interest group (SIG). METHODS: A 29-member SIG was established, with members from neurology, neuroradiology, anaesthetics, neurosurgery and patient representatives. The scope and purpose of the guideline were agreed by the SIG by consensus. The SIG then developed guideline statements for a series of question topics using a modified Delphi process. This process was supported by a systematic literature review, surveys of patients and healthcare professionals and review by several international experts on SIH. RESULTS: SIH and its differential diagnoses should be considered in any patient presenting with orthostatic headache. First-line imaging should be MRI of the brain with contrast and the whole spine. First-line treatment is non-targeted epidural blood patch (EBP), which should be performed as early as possible. We provide criteria for performing myelography depending on the spine MRI result and response to EBP, and we outline principles of treatments. Recommendations for conservative management, symptomatic treatment of headache and management of complications of SIH are also provided. CONCLUSIONS: This multidisciplinary consensus clinical guideline has the potential to increase awareness of SIH among healthcare professionals, produce greater consistency in care, improve diagnostic accuracy, promote effective investigations and treatments and reduce disability attributable to SIH.

CATALYST: challenging antibiotic allergy status.

OBJECTIVES: To develop a transferable process, CATALYST (challenging antibiotic allergystatus), to assess and challenge penicillin allergy status of inpatients within an NHS Foundation Hospital. METHODS: A multidisciplinary team (MDT) steering group reviewed existing literature and protocols enabling penicillin allergy assessment, challenge and de-labelling. Using this, they identified five key steps forming the basis of CATALYST: clinical assessment of the nature of allergy; inclusion/exclusion criteria; consent; direct oral penicillin challenge; and removal of allergy label. A pharmacist-led pilot was conducted to assess the process, during which a continuous PDSA (plan-do-study-act) cycle was observed. This included formally auditing endpoint data such as accuracy of allergy status in medical records post-intervention. RESULTS: CATALYST was successfully developed with key resources produced to support clinicians. It was piloted in 304 patients, with 172 patients excluded and 132 successful allergy challenges. There was one incident of an adverse event (acute kidney injury) in the 132 successful patients, which occurred as a delayed reaction following 22 days of penicillin therapy. Only 64% of permanent records (held by GP) were appropriately updated when audited at the end of the pilot. CONCLUSIONS: CATALYST is a transferable process to facilitate safe assessment, challenge and removal of spurious penicillin allergy labels. Handover between care sectors forms a key element of allergy removal to ensure all records are updated and work is needed to ensure this process is done effectively.

The Early Care Model for Initiation of Perinatal Care: "I Actually Felt Listened To".

Early access to prenatal care is a crucial component in reducing poor perinatal outcomes. Institutional barriers such as insurance enrollment, clinic wait times, and systemic racism dramatically influence perinatal care engagement. The Early Care model seeks to address these barriers through a collaborative care model with licensed midwives and certified nurse-midwives. In contrast to traditional models of prenatal care in which the first visit is deferred until gestational age allows for a dating ultrasound, the Early Care model allows for care to be initiated at any gestation. Patients are offered accessible telehealth early pregnancy appointments for thorough assessment of clinical and social needs to better meet each person's unique and diverse experiences. Patients can receive timely referrals for emergent clinical and social needs, as well as education about all care options. This model promotes improved outcomes and decreased disparities, as well as broader awareness of midwifery care. This article provides an overview of the Early Care model experience.

Potential of commercial SiN MPW platforms for developing mid/high-resolution integrated photonic spectrographs for astronomy.

Integrated photonic spectrographs offer an avenue to extreme miniaturization of astronomical instruments, which would greatly benefit extremely large telescopes and future space missions. These devices first require optimization for astronomical applications, which includes design, fabrication, and field testing. Given the high costs of photonic fabrication, multi-project wafer (MPW) silicon nitride (SiN) offerings, where a user purchases a portion of a wafer, provide a convenient and affordable avenue to develop this technology. In this work, we study the potential of two commonly used SiN waveguide geometries by MPW foundries, i.e., square and rectangular profiles, to determine how they affect the performance of mid/high-resolution arrayed waveguide grating (AWG) spectrometers around 1.5 µm. Specifically, we present results from detailed simulations on the mode sizes, shapes, and polarization properties, and on the impact of phase errors on the throughput and cross talk as well as some laboratory results of coupling and propagation losses. From the MPW run tolerances and our phase-error study, we estimate that an AWG with R ∼10,000 can be developed with the MPW runs, and even greater resolving power is achievable with more reliable, dedicated fabrication runs. Depending on the fabrication and design optimizations, it is possible to achieve throughputs ∼60% using the SiN platform. Thus, we show that SiN MPW offerings are highly promising and will play a key role in integrated photonic spectrograph developments for astronomy.

Seeking celestial positronium with an OH-suppressed diffraction-limited spectrograph.

Celestially, positronium (Ps) has been observed only through gamma-ray emission produced by its annihilation. However, in its triplet state, a Ps atom has a mean lifetime long enough for electronic transitions to occur between quantum states. This produces a recombination spectrum observable in principle at near IR wavelengths, where angular resolution greatly exceeding that of the gamma-ray observations is possible. However, the background in the near IR is dominated by extremely bright atmospheric hydroxyl (OH) emission lines. In this paper, we present the design of a diffraction-limited spectroscopic system using novel photonic components-a photonic lantern, OH fiber Bragg grating filters, and a photonic TIGER 2D pseudo-slit-to observe the Ps Balmer alpha line at 1.3122 µm for the first time, to our knowledge.

Astrophotonics: introduction to the feature issue.

Astrophotonics is an emerging field that focuses on the development of photonic components for astronomical instrumentation. With ongoing advancements, astrophotonic solutions are already becoming an integral part of existing instruments. A recent example is the €60M ESO GRAVITY instrument at the Very Large Telescope Interferometer, Chile, that makes heavy use of photonic components. We envisage far-reaching applications in future astronomical instruments, especially those intended for the new generation of extremely large telescopes and in space. With continued improvements in extreme adaptive optics, the case becomes increasingly compelling. The joint issue of JOSA B and Applied Optics features more than 20 state-of-the-art papers in diverse areas of astrophotonics. This introduction provides a summary of the papers that cover several important topics, such as photonic lanterns, beam combiners and interferometry, spectrographs, OH suppression, and coronagraphy.

Optimizing photonic ring-resonator filters for OH-suppressed near-infrared astronomy.

Near-infrared wavelength observations are crucial for understanding numerous fields of astrophysics, such as supernova cosmology and positronium annihilation detection. However, current ground-based observations suffer from an enormous background due to OH emission in the upper atmosphere. One promising way to solve this problem is to use ring-resonator filters to suppress OH emission lines. In this work, we discuss our optimization of ring-resonator filter performance from five perspectives: resonance wavelength matching, polarization-independent operation, low insertion loss, low-loss coupling to astronomical instruments, and broadband operation. In the end, we discuss next steps needed for reliable supernova and positronium observations, thus providing a roadmap for future advances in near-infrared astronomy.

The effect of testosterone on ovulatory function in transmasculine individuals.

BACKGROUND: An estimated 1.4 million persons in the United States identify as transgender or nonbinary, signifying that their gender identity does not correspond with their assigned sex at birth. Individuals assigned female at birth may seek gender-affirming hormone therapy with testosterone. No studies have directly examined ovulatory function in transmasculine individuals using injectable testosterone. OBJECTIVES: Our primary objective was to determine the effect of testosterone on ovulatory suppression in transmasculine individuals. Secondary objectives were to determine predictors of ovulation in transmasculine individuals on testosterone, and to assess the effect of testosterone on antimüllerian hormone. MATERIALS AND METHODS: This prospective observational study recruited participants from a community clinic that provides gender-affirming hormone therapy. Enrolled individuals were assigned female at birth and were currently using or seeking to initiate masculinizing therapy with injectable testosterone esters (transmasculine individuals). Over a 12-week study period, participants collected daily urine samples for pregnanediol-3-glucoronide testing and completed daily electronic bleeding diaries. We assessed monthly serum mid-dosing interval testosterone, estradiol and sex hormone binding globulin, and antimüllerian hormone values at baseline and study end. Ovulation was defined as pregnanediol-3-glucoronide greater than 5 µg/mL for 3 consecutive days. The primary outcome was the proportion of participants who ovulated during the study period. We examined predictors of ovulation such as age, length of time on testosterone, serum testosterone levels, body mass index, and bleeding pattern. RESULTS: From July to November 2018, we enrolled 32 individuals; 20 completed the study (14 continuing testosterone users, 6 new users). Median age was 23 years (range 18-37 years). Bleeding or spotting during the study period was noted by 41% of participants (13/32). Among continuing users, median testosterone therapy duration was 11 months (range 1-60 months). A single ovulation was observed out of a total of 61 combined months of testosterone use; however, several transient rises in pregnanediol-3-glucoronide followed by bleeding episodes were suggestive of 7 dysfunctional ovulatory cycles among 7 individuals. There was no difference in antimüllerian hormone from baseline to 12 weeks between participants initiating testosterone and continuing users of testosterone. We did not have the power to examine our intended predictors given the low numbers of ovulatory events, but found that longer time on testosterone and presence of vaginal bleeding over 12 weeks were associated with transient rises in pregnanediol-3-glucoronide. CONCLUSION: This study suggests that testosterone rapidly induces hypothalamic-pituitary-gonadal suppression, resulting in anovulation in a proportion of new users. Importantly, these data also suggest that some long-term testosterone users break through the hormonal suppression and experience an ovulatory event, thereby raising concerns pertaining to the need for contraception in transmasculine individuals engaged in sexual intercourse with sperm-producing partners. Given the small number of overall participants, this work is hypothesis generating. Larger studies are needed to confirm and to clarify these findings.

A Survey of Midwives' Attitudes Toward Men in Midwifery.

INTRODUCTION: The midwifery profession in the United States demonstrates a significant lack of diversity. The critical need to address the lack of racial and ethnic diversity in the midwifery workforce is well recognized; little attention, however, has been given to gender diversity. This study focused on gender diversity within midwifery, specifically with regard to men who are midwives. Nearly 99% of midwives in the United States are women. No research has previously explored the attitudes of the predominantly female midwifery workforce toward its male members. METHODS: An invitation to an internet survey was sent to the American College of Nurse-Midwives (ACNM) membership. Quantitative and open-ended questions assessed attitudes toward and experiences with male midwives, whether members thought men belong in the profession, whether gender impacts quality of care, if ACNM should facilitate gender diversification, and whether exposure to male midwives impacts attitudes toward gender diversification. Data analysis of qualitative responses used a qualitative description methodology to identify common themes. RESULTS: Six thousand, nine hundred sixty-five surveys were distributed, and 864 participants completed the survey. Respondents reported beliefs that men belong in midwifery (71.4%), that gender does not affect quality of care (74%), and that ACNM should support gender diversity (72%). Respondents' perspectives revealed 3 dichotomous themes pertaining to the core nature of midwifery and how men fit within the profession: 1) inclusion versus exclusion, 2) empowerment versus protection, and 3) sharing with versus taking from. Often, the same respondent expressed both aspects of the dichotomy simultaneously. DISCUSSION: This study contributes new information about midwives' attitudes and beliefs toward gender diversity in midwifery in the United States. The values of professionalism, tradition, feminism, protection, and diversification inform participant responses. Findings support efforts toward gender diversification and have implications for implementation in education and practice.

Oral versus intravenous antibiotics for bone and joint infections: the OVIVA non-inferiority RCT.

BACKGROUND: Management of bone and joint infection commonly includes 4-6 weeks of intravenous (IV) antibiotics, but there is little evidence to suggest that oral (PO) therapy results in worse outcomes. OBJECTIVE: To determine whether or not PO antibiotics are non-inferior to IV antibiotics in treating bone and joint infection. DESIGN: Parallel-group, randomised (1 : 1), open-label, non-inferiority trial. The non-inferiority margin was 7.5%. SETTING: Twenty-six NHS hospitals. PARTICIPANTS: Adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least 6 weeks of antibiotics, and who had received ≤ 7 days of IV therapy from definitive surgery (or start of planned curative treatment in patients managed non-operatively). INTERVENTIONS: Participants were centrally computer-randomised to PO or IV antibiotics to complete the first 6 weeks of therapy. Follow-on PO therapy was permitted in either arm. MAIN OUTCOME MEASURE: The primary outcome was the proportion of participants experiencing treatment failure within 1 year. An associated cost-effectiveness evaluation assessed health resource use and quality-of-life data. RESULTS: Out of 1054 participants (527 in each arm), end-point data were available for 1015 (96.30%) participants. Treatment failure was identified in 141 out of 1015 (13.89%) participants: 74 out of 506 (14.62%) and 67 out of 509 (13.16%) of those participants randomised to IV and PO therapy, respectively. In the intention-to-treat analysis, using multiple imputation to include all participants, the imputed risk difference between PO and IV therapy for definitive treatment failure was -1.38% (90% confidence interval -4.94% to 2.19%), thus meeting the non-inferiority criterion. A complete-case analysis, a per-protocol analysis and sensitivity analyses for missing data each confirmed this result. With the exception of IV catheter complications [49/523 (9.37%) in the IV arm vs. 5/523 (0.96%) in the PO arm)], there was no significant difference between the two arms in the incidence of serious adverse events. PO therapy was highly cost-effective, yielding a saving of £2740 per patient without any significant difference in quality-adjusted life-years between the two arms of the trial. LIMITATIONS: The OVIVA (Oral Versus IntraVenous Antibiotics) trial was an open-label trial, but bias was limited by assessing all potential end points by a blinded adjudication committee. The population was heterogenous, which facilitated generalisability but limited the statistical power of subgroup analyses. Participants were only followed up for 1 year so differences in late recurrence cannot be excluded. CONCLUSIONS: PO antibiotic therapy is non-inferior to IV therapy when used during the first 6 weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within 1 year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy. FUTURE WORK: Further work is required to define the optimal total duration of therapy for bone and joint infection in the context of specific surgical interventions. Currently, wide variation in clinical practice suggests significant redundancy that likely contributes to the excess and unnecessary use of antibiotics. TRIAL REGISTRATION: Current Controlled Trials ISRCTN91566927. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 38. See the NIHR Journals Library website for further project information.

Treatment of bone and joint infection usually requires a long course of antibiotics. Doctors usually give these by injection through a vein (intravenously) for the first 4­6 weeks, rather than by mouth (orally). Although intravenous (IV) administration is more expensive and less convenient for patients, most doctors believe that it is more effective. However, there is little evidence to support this. The OVIVA (Oral Versus IntraVenous Antibiotics) trial set out to challenge this assumption. A total of 1054 patients from 26 UK hospitals were randomly allocated to receive the first 6 weeks of antibiotic therapy either intravenously or orally. Irrespective of the route of administration, the choice of antibiotic was left to an infection specialist so as to ensure that the most appropriate antibiotics were given. Patients were followed up for 1 year. Thirty-nine participants were lost to follow-up. Among the remaining 1015 participants, treatment failure occurred in 14.6% of those treated intravenously and 13.2% of those treated with PO antibiotics. This difference could easily have occurred by chance. Even if it was not by chance, the difference does not suggest that PO therapy is associated with worse outcomes than IV therapy and is too small to conclude that PO therapy is better than IV therapy. Participants in the IV group stayed in hospital longer and 10% of them had complications related to the IV line used for administering the antibiotics. In addition, their treatment was, overall, more expensive. We conclude that PO antibiotic therapy has no disadvantages for the early management of bone and joint infection. It is also cheaper and associated with fewer complications.

Midwifery Care for Transfeminine Individuals.

This article focuses on the provision of gender-affirming care and preventive care for transfeminine individuals-those assigned male at birth who identify as female or on the feminine spectrum. To meet the learning needs of health care providers less familiar with gender-affirming care, this article begins with an overview of gender identity concepts. Initiation and management of feminizing gender-affirming hormone therapy is then covered in detail, including common gender-affirming medications and their adverse effects, diagnostic criteria, psychosocial evaluation, initial physical examination and laboratory work, and recommendations for follow-up visits and laboratory monitoring. Lastly, the article briefly reviews health care of transfeminine individuals before and after surgical gender-affirming interventions and details best practices for transfeminine preventive care.

Oral versus Intravenous Antibiotics for Bone and Joint Infection.

BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).

Risky decision-making and affective features of impulse control disorders in Parkinson's disease.

Impulse control disorders (ICDs) in Parkinson's disease (PD) are considered dopaminergic treatment side effects. Cognitive and affective factors may increase the risk of ICD in PD. The aim is to investigate risky decision-making and associated cognitive processes in PD patients with ICDs within a four-stage conceptual framework. Relationship between ICDs and affective factors was explored. Thirteen PD patients with ICD (ICD+), 12 PD patients without ICD (ICD-), and 17 healthy controls were recruited. Overall risky decision-making and negative feedback effect were examined with the Balloon Analogue Risk Task (BART). A cognitive battery dissected decision-making processes according to the four-stage conceptual framework. Affective and motivational factors were measured. ANOVA showed no effect of group on overall risky decision-making. However, there was a group × feedback interaction [F (2, 39) = 3.31, p = 0.047]. ICD+, unlike ICD- and healthy controls, failed to reduce risky behaviour following negative feedback. A main effect of group was found for anxiety and depression [F(2, 38) = 8.31, p = 0.001], with higher symptoms in ICD+ vs. healthy controls. Groups did not differ in cognitive outcomes or affective and motivational metrics. ICD+ may show relatively preserved cognitive function, but reduced sensitivity to negative feedback during risky decision-making and higher symptoms of depression and anxiety.

Feasibility of a randomized single-blind crossover trial to assess the effects of the second-generation slow-release dopamine agonists pramipexole and ropinirole on cued recall memory in idiopathic mild or moderate Parkinson's disease without cognitive impairment.

BACKGROUND: The aim was to assess the feasibility of a single-centre, single-blind, randomized, crossover design to explore the effects of two slow-release dopamine agonists, ropinirole and pramipexole, on cued recall in Parkinson's disease. As the design required a switch from the prescribed agonist (pramipexole-to-ropinirole, or ropinirole-to-pramipexole), the primary objectives were to (a) examine the efficacy of processes and procedures used to manage symptoms during the washout period and (b) to use cued recall estimates to inform a power calculation for a definitive trial. Secondary objectives were to assess consent and missing data rates, acceptability of clinical support for the OFF sessions, experience of the OFF sessions and of agonist switching, barriers-to-participation for patients and informal caregivers. METHODS: Patients were randomized in a 1:1 ratio to two treatment arms and stabilized on each agonist for 6 weeks. The arms differed only in the sequence in which the agonists were administered. Cued recall was assessed ON medication and, following a washout period resulting in 93.75% agonist elimination, OFF medication. RESULTS: A total of 220 patients were screened: 145 were excluded and 75 invitations to participate were sent to eligible patients. Fifty-three patients declined, 22 consented and 16 completed the study. There were no serious adverse events, and rates of non-serious adverse events were equivalent between the agonists. Using the largest standard deviation (SD) of the ON-OFF difference cued recall score (inflated by ~25% to give a conservative estimate of the SD in a definitive trial) and assuming an effect of at least 10% of the observed range of OFF medication cued recall scores for either agonist to be clinically important, a main trial requires a sample size of just under 150 patients. The consent and missing data rates were 29 and 27% respectively. The washout period and the preparation for the OFF sessions were acceptable, and the sessions were manageable. The experience of switching was also manageable. Barriers to participation included concerns about disease stability, side effects, research process, carer workload and accessibility of the information sheet. CONCLUSIONS: This study presented challenges to recruitment both in design and execution, and while it was a major aim of the study to assess this, evaluation of these challenges provided the opportunity to explore how they could be overcome for future studies. TRIAL REGISTRATION: EudraCT 2012-000801-64.

PRECEPT: an evidence assessment framework for infectious disease epidemiology, prevention and control.

Decisions in public health should be based on the best available evidence, reviewed and appraised using a rigorous and transparent methodology. The Project on a Framework for Rating Evidence in Public Health (PRECEPT) defined a methodology for evaluating and grading evidence in infectious disease epidemiology, prevention and control that takes different domains and question types into consideration. The methodology rates evidence in four domains: disease burden, risk factors, diagnostics and intervention. The framework guiding it has four steps going from overarching questions to an evidence statement. In step 1, approaches for identifying relevant key areas and developing specific questions to guide systematic evidence searches are described. In step 2, methodological guidance for conducting systematic reviews is provided; 15 study quality appraisal tools are proposed and an algorithm is given for matching a given study design with a tool. In step 3, a standardised evidence-grading scheme using the Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) methodology is provided, whereby findings are documented in evidence profiles. Step 4 consists of preparing a narrative evidence summary. Users of this framework should be able to evaluate and grade scientific evidence from the four domains in a transparent and reproducible way.

Writing Bragg Gratings in Multicore Fibers.

Fiber Bragg gratings in multicore fibers can be used as compact and robust filters in astronomical and other research and commercial applications. Strong suppression at a single wavelength requires that all cores have matching transmission profiles. These gratings cannot be inscribed using the same method as for single-core fibers because the curved surface of the cladding acts as a lens, focusing the incoming UV laser beam and causing variations in exposure between cores. Therefore we use an additional optical element to ensure that the beam shape does not change while passing through the cross-section of the multicore fiber. This consists of a glass capillary tube which has been polished flat on one side, which is then placed over the section of the fiber to be inscribed. The laser beam enters the fiber through the flat surface of the capillary tube and hence maintains its original dimensions. This paper demonstrates the improvements in core-to-core uniformity for a 7-core fiber using this method. The technique can be generalized to larger multicore fibers.