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.

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.

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 .).

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.

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.

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.

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.

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.

Adherence to exercise referral schemes by participants - what do providers and commissioners need to know? A systematic review of barriers and facilitators.

BACKGROUND: Physical inactivity levels are rising worldwide with major implications for the health of the population and the prevalence of non-communicable diseases. Exercise referral schemes (ERS) continue to be a popular intervention utilised by healthcare practitioners to increase physical activity. We undertook a systematic review of views studies in order to inform guidance from the UK National Institute of Health and Care Excellence (NICE) on exercise referral schemes to promote physical activity. This paper reports on the participant views identified, to inform those seeking to refine schemes to increase attendance and adherence. METHODS: Fifteen databases and a wide range of websites and grey literature sources were searched systematically for publications from 1995 to June 2013. In addition, a range of supplementary methods including, a call for evidence by NICE, contacting authors, reference list checking and citation tracking were utilised to identify additional research. Studies were included where they detailed schemes for adults aged 19 years or older who were 'inactive' (i.e. they are not currently meeting UK physical activity guidelines). Study selection was conducted independently in duplicate. Quality assessment was undertaken by one reviewer and checked by a second, with 20 % of papers being considered independently in duplicate. Papers were coded in qualitative data analysis software Atlas.ti. This review was reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement). RESULTS: Evidence from 33 UK-relevant studies identified that support from providers, other attendees and family was an important facilitator of adherence and 'making exercise a habit' post programme, as was the variety and personalised nature of sessions offered. Barriers to attendance included the inconvenient timing of sessions, their cost and location. An intimidating gym atmosphere, a dislike of the music and TV and a lack of confidence in operating gym equipment were frequently reported. CONCLUSIONS: These findings provide valuable insights that commissioners and providers should consider. The main themes were consistent across a large number of studies and further research should concentrate on programmes that reflect these findings.

Anarchic hand with abnormal agency following right inferior parietal lobe damage: a case report.

Anarchic hand syndrome (AHS) is characterized by goal-directed movements performed without volitional control (agency). Different AHS subtypes have been identified; however, few studies have examined the posterior subtype. We report a case of AHS following right-hemisphere parietal damage, with left-sided somatosensory and proprioceptive impairment. Agency was examined for nonanarchic (volitional) movements performed using the anarchic hand. The patient experienced abnormal agency for movements whether motor intention and visual feedback were congruent or incongruent, but not when intention was absent (passive movement). Findings suggest a general disturbance of veridical motor awareness and agency in this case of parietal AHS.

Demonstration of uniform multicore fiber Bragg gratings.

Fiber Bragg gratings in multicore fibers have significant potential as compact and robust filters for research and commercial applications. With the aid of an innovative, flat-fielded Mach-Zehnder interferometer, we demonstrate deep (>30 dB) narrow (100 pm at 3 dB; 90 pm at 10 dB) notches in the outer 6 cores of a 7-core fiber at a constant wavelength ( ± 15 pm). This is a crucial step in the development of FBGs operating within multimode fibers that carry an arbitrary number of spatial modes.

Evidence-based decision-making in infectious diseases epidemiology, prevention and control: matching research questions to study designs and quality appraisal tools.

BACKGROUND: The Project on a Framework for Rating Evidence in Public Health (PRECEPT) was initiated and is being funded by the European Centre for Disease Prevention and Control (ECDC) to define a methodology for evaluating and grading evidence and strength of recommendations in the field of public health, with emphasis on infectious disease epidemiology, prevention and control. One of the first steps was to review existing quality appraisal tools (QATs) for individual research studies of various designs relevant to this area, using a question-based approach. METHODS: Through team discussions and expert consultations, we identified 20 relevant types of public health questions, which were grouped into six domains, i.e. characteristics of the pathogen, burden of disease, diagnosis, risk factors, intervention, and implementation of intervention. Previously published systematic reviews were used and supplemented by expert consultation to identify suitable QATs. Finally, a matrix was constructed for matching questions to study designs suitable to address them and respective QATs. Key features of each of the included QATs were then analyzed, in particular in respect to its intended use, types of questions and answers, presence/absence of a quality score, and if a validation was performed. RESULTS: In total we identified 21 QATs and 26 study designs, and matched them. Four QATs were suitable for experimental quantitative study designs, eleven for observational quantitative studies, two for qualitative studies, three for economic studies, one for diagnostic test accuracy studies, and one for animal studies. Included QATs consisted of six to 28 items. Six of the QATs had a summary quality score. Fourteen QATs had undergone at least one validation procedure. CONCLUSIONS: The results of this methodological study can be used as an inventory of potentially relevant questions, appropriate study designs and QATs for researchers and authorities engaged with evidence-based decision-making in infectious disease epidemiology, prevention and control.

A systematic review of contextual factors relating to smokeless tobacco use among South Asian users in England.

INTRODUCTION: Certain types of smokeless tobacco (ST) are popular among some people of South Asian origin in England; however, little is known about the contextual factors surrounding use in this population. This systematic review explores the factors associated with ST use among people of South Asian origin in England. METHODS: An iterative search strategy in targeted databases and grey literature sources was conducted in the summer of 2011. Data extractions and quality assessments were completed and verified by two reviewers, and results were presented as a narrative. RESULTS: A total of 2,968 references were screened by two reviewers who agreed on the inclusion of 14 studies. ST use is more prevalent among older participants who may have started chewing in India; however, the evidence suggests that some younger English-born South Asians are using ST as well. Reasons for chewing included the use of these products in times of stress, boredom or simply to relax. Traditional health messages and prior held beliefs may lead them to chew these products because of misconceptions about their health benefits, since very few people were aware of the health risks. Many expressed a desire to quit, however found it difficult to go without ST. CONCLUSION: This review examines the complex factors that underpin and influence ST use among South Asians in England with the potential of informing targeted interventions and health policy.

The cost-effectiveness of public health interventions.

BACKGROUND: The need to make best use of limited resources in the English National Health Service is now greater than ever. This paper contributes to this endeavour by synthesizing data from cost-effectiveness evidence produced to support the development of public health guidance at the National Institute of Health and Clinical Excellence (NICE). No comprehensive list of cost-effectiveness estimates for public health interventions has previously been published in England. METHODS: Cost-effectiveness estimates using English cost data were collected and analysed from 21 (of 26) economic analyses underpinning public health guidance published by NICE between 2006 and 2010. RESULTS: Two hundred base-case cost-effectiveness estimates were analysed, 15% were cost saving (i.e. the intervention was more effective and cheaper than comparator). Eighty-five per cent were cost-effective at a threshold of £20,000 per quality-adjusted life year and 89% at the higher threshold of £30,000. A further 5.5% were above £30,000 and 5.5% of the interventions were dominated (i.e. the intervention was more costly and less effective than comparator). CONCLUSIONS: The majority of public health interventions assessed are highly cost-effective. The next challenge is to provide commissioners with a framework that allows information from economic analyses to be combined with other criteria that supports making better investment decisions at a local level.

HIV diagnoses and missed opportunities. Results of the British HIV Association (BHIVA) National Audit 2010.

The late diagnosis of HIV in patients across the UK is an increasing problem. Here, we report on a retrospective case-notes audit carried out to assess the impact of the 2008 UK HIV testing guidelines on clinical practice and identify missed opportunities for HIV testing. The audit was carried out in 2010 and focussed on patients with newly diagnosed HIV at centres providing adult HIV services across the UK. Data were collected on 1,112 patients, of whom 52.2% were found to have a late HIV diagnosis as defined as a CD4 T lymphocyte count of <350 cells/mm3. Most patients (62.6%) were diagnosed in traditional settings, with a significant increase in those diagnosed with HIV in non-traditional settings (33%) compared with the 2003 audit (18.5%) (p<0.001). The most frequent indicator conditions that patients had experienced were chronic diarrhoea or weight loss, sexually transmitted infection, blood dyscrasia or lymphadenopathy. A quarter of patients were identified as having had a missed opportunity for earlier diagnosis. Based on our results, we suggest that HIV testing needs to continue to expand across clinical settings to reduce the number of patients living with undiagnosed HIV infection.

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.

Hexabundles: imaging fiber arrays for low-light astronomical applications.

We demonstrate a novel imaging fiber bundle ("hexabundle") that is suitable for low-light applications in astronomy. The most successful survey instruments at optical-infrared wavelengths use hundreds to thousands of multimode fibers fed to one or more spectrographs. Since most celestial sources are spatially extended on the celestial sphere, a hexabundle provides spectroscopic information at many distinct locations across the source. We discuss two varieties of hexabundles: (i) lightly fused, closely packed, circular cores; (ii) heavily fused non-circular cores with higher fill fractions. In both cases, we find the important result that the cladding can be reduced to ~2 µm over the short fuse length, well below the conventional ~10λ thickness employed more generally, with a consequent gain in fill factor. Over the coming decade, it is to be expected that fiber-based instruments will be upgraded with hexabundles in order to increase the spatial multiplex capability by two or more orders of magnitude.