Baseline perihematomal edema, C-reactive protein, and 30-day mortality are not associated in intracerebral hemorrhage.

Background: The relationship between baseline perihematomal edema (PHE) and inflammation, and their impact on survival after intracerebral hemorrhage (ICH) are not well understood. Objective: Assess the association between baseline PHE, baseline C-reactive protein (CRP), and early death after ICH. Methods: Analysis of pooled data from multicenter ICH registries. We included patients presenting within 24 h of symptom onset, using multifactorial linear regression model to assess the association between CRP and edema extension distance (EED), and a multifactorial Cox regression model to assess the association between CRP, PHE volume and 30-day mortality. Results: We included 1,034 patients. Median age was 69 (interquartile range [IQR] 59-79), median baseline ICH volume 11.5 (IQR 4.3-28.9) mL, and median baseline CRP 2.5 (IQR 1.5-7.0) mg/L. In the multifactorial analysis [adjusting for cohort, age, sex, log-ICH volume, ICH location, intraventricular hemorrhage (IVH), statin use, glucose, and systolic blood pressure], baseline log-CRP was not associated with baseline EED: for a 50% increase in CRP the difference in expected mean EED was 0.004 cm (95%CI 0.000-0.008, p = 0.055). In a further multifactorial analysis, after adjusting for key predictors of mortality, neither a 50% increase in PHE volume nor CRP were associated with higher 30-day mortality (HR 0.97; 95%CI 0.90-1.05, p = 0.51 and HR 0.98; 95%CI 0.93-1.03, p = 0.41, respectively). Conclusion: Higher baseline CRP is not associated with higher baseline edema, which is also not associated with mortality. Edema at baseline might be driven by different pathophysiological processes with different effects on outcome.

Reported Hearing Outcome Measures Following Stereotactic Radiosurgery for Vestibular Schwannoma: A Scoping Review.

Background Evidence on hearing outcome measures when assessing hearing preservation following stereotactic radiosurgery (SRS) for adults with vestibular schwannoma (VS) has not previously been collated in a structured review. Objective The objective of the present study was to perform a scoping review of the evidence regarding the choice of hearing outcomes and other methodological characteristics following SRS for adults with VS. Methods The protocol was registered in the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) and reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses extension guidelines for scoping reviews. A systematic search of five online databases revealed 1,591 studies, 247 of which met the inclusion criteria. Results The majority of studies ( n = 213, 86%) were retrospective cohort or case series with the remainder ( n = 34, 14%) prospective cohort. Pure-tone audiometry and speech intelligibility were included in 222 (90%) and 158 (64%) studies, respectively, often summarized within a classification scheme and lacking procedural details. Fifty-nine (24%) studies included self-report measures. The median duration of follow-up, when reported, was 43 months (interquartile range: 29, 4-150). Conclusion Evidence on hearing disability after SRS for VS is based on low-quality studies which are inherently susceptible to bias. This review has highlighted an urgent need for a randomized controlled trial assessing hearing outcomes in patients with VS managed with radiosurgery or radiological observation. Similarly, consensus and coproduction of a core outcome set to determine relevant hearing and communication outcome domains is required. This will ensure that patient priorities, including communication abilities in the presence of background noise and reduced participation restrictions, are addressed.

Wellbeing After Stroke (WAterS): Feasibility Testing of a Co-developed Acceptance and Commitment Therapy Intervention to Support Psychological Adjustment After Stroke.

OBJECTIVE: Feasibility test a co-developed intervention based on Acceptance and Commitment Therapy to support psychological adjustment post-stroke, delivered by a workforce with community in-reach. DESIGN: Observational feasibility study utilising patient, carer, public involvement. SETTING: Online. UK. PARTICIPANTS: Stroke survivors with self-reported psychological distress 4 + months post-stroke. INTERVENTIONS: The co-developed Wellbeing After Stroke (WAterS) intervention includes: 9-weekly, structured, online, group sessions for stroke survivors, delivered via a training programme to upskill staff without Acceptance and Commitment Therapy experience, under Clinical Psychology supervision. MAIN MEASURES: Feasibility of recruitment and retention; data quality from candidate measures; safety. Clinical and demographic information at baseline; patient-reported outcome measures (PROMs) via online surveys (baseline, pre- and post-intervention, 3 and 6 months after intervention end) including Mood (hospital anxiety and depression scale (HADS)), Wellbeing (ONS4), Health-Related Quality of Life (EQ5D5L), Psychological Flexibility (AAQ-ABI) and Values-Based Living (VQ). RESULTS: We trained eight staff and recruited 17 stroke survivors with mild-to-moderate cognitive and communication difficulties. 12/17 (71%) joined three intervention groups with 98% attendance and no related adverse events. PROMS data were well-completed. The HADS is a possible future primary outcome (self-reported depression lower on average by 1.3 points: 8.5 pre-group to 7.1 at 3-month follow-up; 95% CI 0.4 to 3.2). CONCLUSION: The WAterS intervention warrants further research evaluation. Staff can be trained and upskilled to deliver. It appears safe and feasible to deliver online to groups, and study recruitment and data collection are feasible. Funding has been secured to further develop the intervention, considering implementation and health equality.

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

BACKGROUND: During a stimulated cycle of in vitro fertilisation or intracytoplasmic sperm injection (IVF/ICSI), women receive daily doses of gonadotropin follicle-stimulating hormone (FSH) to induce multifollicular development in the ovaries. A normal response to stimulation (e.g. retrieval of 5 to 15 oocytes) is considered desirable. Generally, the number of eggs retrieved is associated with the dose of FSH. Both hyper-response and poor response are associated with an increased chance of cycle cancellation. In hyper-response, this is due to increased risk of ovarian hyperstimulation syndrome (OHSS), while poor response cycles are cancelled because the quantity and quality of oocytes is expected to be low. Clinicians often individualise the FSH dose using patient characteristics predictive of ovarian response. Traditionally, this meant women's age, but increasingly, clinicians use various ovarian reserve tests (ORTs). These include basal FSH (bFSH), antral follicle count (AFC), and anti-Müllerian hormone (AMH). It is unclear whether individualising FSH dose improves clinical outcomes. This review updates the 2018 version. OBJECTIVES: To assess the effects of individualised gonadotropin dose selection using markers of ovarian reserve in women undergoing IVF/ICSI. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL, MEDLINE, Embase, and two trial registers in February 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared (a) different doses of FSH in women with a defined ORT profile (i.e. predicted low, normal, or high responders based on AMH, AFC, and/or bFSH) or (b) an individualised dosing strategy (based on at least one ORT measure) versus uniform dosing or a different individualised dosing algorithm. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Primary outcomes were live birth/ongoing pregnancy and severe OHSS. MAIN RESULTS: We included 26 studies, involving 8520 women (6 new studies added to 20 studies included in the previous version). We treated RCTs with multiple comparisons as separate trials for the purpose of this review. Meta-analysis was limited due to clinical heterogeneity. Evidence certainty ranged from very low to low, with the main limitations being imprecision and risk of bias associated with lack of blinding. Direct dose comparisons according to predicted response in women Due to differences in dose comparisons, caution is required when interpreting the RCTs in predicted low responders. All evidence was low or very low certainty. Effect estimates were very imprecise, and increased FSH dosing may or may not have an impact on rates of live birth/ongoing pregnancy, OHSS, and clinical pregnancy. Similarly, in predicted normal responders (10 studies, 4 comparisons), higher doses may or may not impact the probability of live birth/ongoing pregnancy (e.g. 200 versus 100 international units (IU): odds ratio (OR) 0.88, 95% confidence interval (CI) 0.57 to 1.36; I2 = 0%; 2 studies, 522 women) or clinical pregnancy. Results were imprecise, and a small benefit or harm remains possible. There were too few events for the OHSS outcome to enable inferences. In predicted high responders, lower doses may or may not affect live birth/ongoing pregnancy (OR 0.98, 95% CI 0.66 to 1.46; 1 study, 521 women), severe OHSS, and clinical pregnancy. It is also unclear whether lower doses reduce moderate or severe OHSS (Peto OR 2.31, 95% CI 0.80 to 6.67; 1 study, 521 participants). ORT-algorithm studies Eight trials compared an ORT-based algorithm to a non-ORT control group. It is unclear whether live birth/ongoing pregnancy and clinical pregnancy are increased using an ORT-based algorithm (live birth/ongoing pregnancy: OR 1.12, 95% CI 0.98 to 1.29; I2 = 30%; 7 studies, 4400 women; clinical pregnancy: OR 1.04, 95% CI 0.91 to 1.18; I2 = 18%; 7 studies, 4400 women; low-certainty evidence). However, ORT algorithms may reduce moderate or severe OHSS (Peto OR 0.60, 95% CI 0.42 to 0.84; I2 = 0%; 7 studies, 4400 women; low-certainty evidence). There was insufficient evidence to determine whether the groups differed in rates of severe OHSS (Peto OR 0.74, 95% CI 0.42 to 1.28; I2 = 0%; 5 studies, 2724 women; low-certainty evidence). Our findings suggest that if the chance of live birth with a standard starting dose is 25%, the chance with ORT-based dosing would be between 25% and 31%. If the chance of moderate or severe OHSS with a standard starting dose is 5%, the chance with ORT-based dosing would be between 2% and 5%. These results should be treated cautiously due to heterogeneity in the algorithms: some algorithms appear to be more effective than others. AUTHORS' CONCLUSIONS: We did not find that tailoring the FSH dose in any particular ORT population (low, normal, high ORT) affected live birth/ongoing pregnancy rates, but we could not rule out differences, due to sample size limitations. Low-certainty evidence suggests that it is unclear if ORT-based individualisation leads to an increase in live birth/ongoing pregnancy rates compared to a policy of giving all women 150 IU. The confidence interval is consistent with an increase of up to around six percentage points with ORT-based dosing (e.g. from 25% to 31%) or a very small decrease (< 1%). A difference of this magnitude could be important to many women. It is unclear if this is driven by improved outcomes in a particular subgroup. Further, ORT algorithms reduced the incidence of OHSS compared to standard dosing of 150 IU. However, the size of the effect is also unclear. The included studies were heterogeneous in design, which limited the interpretation of pooled estimates. It is likely that different ORT algorithms differ in their effectiveness. Current evidence does not provide a clear justification for adjusting the dose of 150 IU in poor or normal responders, especially as increased dose is associated with greater total FSH dose and cost. It is unclear whether a decreased dose in predicted high responders reduces OHSS, although this would appear to be the most likely explanation for the results.

Gynecological trials frequently exclude people based on their symptoms rather than their condition: a systematic review of Cochrane reviews and their component trials.

OBJECTIVES: To identify strategies used in recent randomized controlled trials (RCTs) and their associated Cochrane Reviews where patients with the same gynecological condition present with different symptoms but would plausibly benefit from a common intervention. STUDY DESIGN AND SETTING: We searched the Cochrane library (February 2022) for reviews in polycystic ovarian syndrome (PCOS) and endometriosis. Reviews were included if the intervention was intended to treat all condition-specific symptoms. For each trial we recorded the strategy used and the number of potentially eligible participants excluded as a direct result of the chosen strategy. For each review we recorded the numbers of RCTs and participants excluded on the basis of symptoms experienced. RESULTS: There were 89 distinct PCOS trials in 13 reviews, and 13 Endometriosis trials in 11 reviews. Most trials restricted their eligibility to participants with specific symptoms (55% PCOS, 46% endometriosis). The second most common strategy was to measure and analyze clinical outcomes that were not relevant to all participants (38% PCOS, 31% endometriosis). Reviews excluded 27% of trials in participants evaluating the same intervention in participants experiencing the same condition based on the outcomes measured in the trials. CONCLUSION: Most gynecological trials exclude patients who could benefit from treatment or measure outcomes not relevant to all participants. We introduce a taxonomy to describe trial design strategies for conditions with heterogeneous symptoms.

Phase II randomised, placebo-controlled, clinical trial of interleukin-1 receptor antagonist in intracerebral haemorrhage: BLOcking the Cytokine IL-1 in ICH (BLOC-ICH).

PURPOSE: Recombinant human interleukin-1 receptor antagonist (anakinra) is an anti-inflammatory with efficacy in animal models of stroke. We tested the effect of anakinra on perihaematomal oedema in acute intracerebral haemorrhage (ICH) and explored effects on inflammatory markers. METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled trial in patients with acute, spontaneous, supratentorial ICH between May 2019 and February 2021. Patients were randomised to 100 mg subcutaneous anakinra within 8 h of onset, followed by five, 12-hourly, 100 mg subcutaneous injections, or matched placebo. Primary outcome was oedema extension distance (OED) on a 72 h CT scan. Secondary outcomes included plasma C-reactive protein (CRP) and interleukin-6 (IL-6). FINDINGS: 25 patients (target = 80) were recruited, 14 randomised to anakinra, 11 to placebo. Mean age was 67 and 52% were male. The anakinra group had higher median baseline ICH volume (12.6 ml, interquartile range[IQR]:4.8-17.9) versus placebo (5.5 ml, IQR:2.1-10.9). Adjusting for baseline, 72 h OED was not significantly different between groups (mean difference OED anakinra vs placebo -0.05 cm, 95% confidence interval [CI]: -0.17-0.06, p = 0.336). There was no significant difference in area-under-the-curve to Day 4 for IL-6 and CRP, but a post-hoc analysis demonstrated IL-6 was 56% (95% CI: 2%-80%) lower at Day 2 with anakinra. There were 10 and 2 serious adverse events in anakinra and placebo groups, respectively, none attributed to anakinra. CONCLUSION: We describe feasibility for delivering anakinra in acute ICH and provide preliminary safety data. We lacked power to test for effects on oedema thus further trials will be required.

Does stroke-associated pneumonia play an important role on risk of in-hospital mortality associated with severe stroke? A four-way decomposition analysis of a national cohort of stroke patients.

BACKGROUND: Severe strokes and stroke-associated pneumonia (SAP) have long been associated with poorer patient health outcomes, for example, in-hospital mortality. However, it is unclear what role SAP plays in the risk of in-hospital mortality associated with a severe stroke at admission. METHODS: Using the Sentinel Stroke National Audit Program data on stroke admissions (2013-2018) in England and Wales, we modeled the "total" effect for severe stroke on risk of in-hospital mortality. Through four-way decomposition methodology, we broke down the "total" observed risk into four components. The direct "severity on outcome only" effect, the pure indirect effect of severity mediated via SAP only, the interaction between severity and SAP when mediation is not present, and when mediation via SAP is present. RESULTS: Of 339,139 stroke patients included, 9.4% had SAP and 15.6% died in hospital. Of SAP patients, 45% died versus 12% of non-SAP patients. The risk ratio for in-hospital mortality associated with severe versus mild/moderate stroke (i.e. total effect) was 4.72 (95% confidence interval: 4.60-4.85). Of this, 43%-increased risk was due to additive SAP interaction, this increased to 50% for "very severe" stroke. The remaining excess relative risk was due to the direct severity on outcome effect only, that is, there was no evidence here for a mediation effect via SAP. CONCLUSION: SAP was associated with a higher mortality in severe stroke patients. Prioritizing SAP prevention in severe stroke patients may improve in-hospital survival. Our results suggest that in severe stroke patients avoiding SAP might result in an up to 43% reduction in mortality.

Early mobilisation is associated with lower subacute blood pressure and variability in ICH: A retrospective cohort study✰.

BACKGROUND: Very early rehabilitation after stroke appears to worsen outcome, particularly in intracerebral haemorrhage (ICH). Plausible mechanisms include increased mean blood pressure (BP) and BP variability. AIMS: To test associations between early mobilisation, subacute BP and survival, in observational data of ICH patients during routine clinical care. METHODS: We collected demographic, clinical and imaging data from 1372 consecutive spontaneous ICH patients admitted between 2 June 2013 and 28 September 2018. Time to first mobilisation (defined as walking, standing, or sitting out-of-bed) was extracted from electronic records. We evaluated associations between early mobilisation (within 24 h of onset) and both subacute BP and death by 30 days using multifactorial linear and logistic regression analyses respectively. RESULTS: Mobilisation at 24 h was not associated with increased odds of death by 30 days when adjusting for key prognostic factors (OR 0.4, 95% CI 0.2 to 1.1, p = 0.07). Mobilisation at 24 h was independently associated with both lower mean systolic BP (-4.5 mmHg, 95% CI -7.5 to -1.5 mmHg, p = 0.003) and lower diastolic BP variability (-1.3 mmHg, 95% CI -2.4 to -0.2 mg, p = 0.02) during the first 72 h after admission. CONCLUSIONS: Adjusted analysis in this observational dataset did not find an association between early mobilisation and death by 30 days. We found early mobilisation at 24 h to be independently associated with lower mean systolic BP and lower diastolic BP variability over 72 h. Further work is needed to establish mechanisms for the possible detrimental effect of early mobilisation in ICH.

Molecular biomarkers predicting newly detected atrial fibrillation after ischaemic stroke or TIA: A systematic review.

Background: Several molecular biomarkers are available that predict newly detected atrial fibrillation (NDAF). We aimed to identify such biomarkers that predict NDAF after an Ischaemic stroke (IS)/Transient Ischaemic Attack (TIA) and evaluate their performance. Methods: A systematic review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies of patients with IS, TIA, or both, who underwent ECG monitoring for ⩾24 h, which reported molecular biomarkers and frequency of NDAF after electronic searches of multiple databases were included. Results: Twenty-one studies (76% IS, 24% IS and TIA) involving 4640 patients were included. Twelve biomarkers were identified, with cardiac biomarkers evaluated in the majority (75%) of patients. Performance measures were inconsistently reported. Among cohorts selecting high-risk individuals (12 studies), the most studied biomarkers were N-Terminal-Pro Brain Natriuretic Peptide (NT-ProBNP, five studies; C-statistics reported by three studies, 0.69-0.88) and Brain Natriuretic Peptide (BNP, two studies; C-statistics reported in two studies, 0.68-0.77). Among unselected cohorts (nine studies), the most studied biomarker was BNP (six studies; C-statistics reported in five studies, 0.75-0.88). Only BNP was externally validated (two studies) but using different thresholds to categorise risk of NDAF. Conclusion: Cardiac biomarkers appear to have modest to good discrimination for predicting NDAF, although most analyses were limited by small, heterogeneous study populations. Their clinical utility should be explored further, and this review supports the need to assess the role of molecular biomarkers in large prospective studies with standardised selection criteria, definition of clinically significant NDAF and laboratory assays.

Increased Circulating Chemokines and Macrophage Recruitment in Growing Vestibular Schwannomas.

BACKGROUND: There is evidence that macrophage infiltration in the tumor microenvironment promotes vestibular schwannoma (VS) growth. Efficacy of bevacizumab in NF2-associated VS demonstrates the value of therapies targeting the microvascular tumor microenvironment, and tumor-associated macrophages (TAMs) may represent another druggable target. OBJECTIVE: To characterize the relationship between growth, TAM infiltration, and circulating monocyte chemokines in a large cohort of patients with VS. METHODS: Immunostaining for Iba1 (macrophages), CD31 (endothelium), and fibrinogen (permeability) was performed on 101 growing and 19 static sporadic VS. The concentrations of monocyte-specific chemokines were measured in the plasma of 50 patients with growing VS and 25 patients with static VS. RESULTS: The Iba1 + cell count was significantly higher in growing as compared with static VS (592 vs 226/×20 HPF, P =<0.001). Similarly, the CD31 + % surface area was higher in growing VS (2.19% vs 1.32%, P = .01). There was a positive correlation between TAM infiltration and VS growth rate, which persisted after controlling for the effect of tumor volume (aR2 = 0.263, P =<0.001). The plasma concentrations of several monocytic chemokines were higher in patients with growing rather than static VS. CONCLUSION: There is a strong positive correlation between TAM infiltration and volumetric growth of VS, and this relationship is independent of tumor size. There is a colinear relationship between TAM infiltration and tumor vascularity, implying that inflammation and angiogenesis are interlinked in VS. Chemokines known to induce monocyte chemotaxis are found in higher concentrations in patients with growing VS, suggestive of a potential pathophysiological mechanism.

Do Stroke Care Processes Modify Clinical Outcomes in Patients with Stroke-Associated Pneumonia? A Registry Cohort Study in England and Wales.

INTRODUCTION: It is not known whether modern stroke unit care reduces the impact of stroke complications, such as stroke-associated pneumonia (SAP), on clinical outcomes. We investigated the relationship between SAP and clinical outcomes, adjusting for the confounding effects of stroke care processes and their timing. METHODS: The Sentinel Stroke National Audit Programme provided patient data for all confirmed strokes between April 2013 and December 2018. SAP was defined as new antibiotic initiation for suspected pneumonia within the first 7 days from stroke admission. We compared outcomes after SAP versus non-SAP in appropriate multilevel mixed models. Each model was adjusted for patient and clinical characteristics, as well as markers of stroke care and their timing within the first 72 h. The appropriate effect estimates and corresponding 95% confidence intervals (CIs) were reported. RESULTS: Of 201,778 patients, SAP was present in 14.2%. After adjustment for timing of acute stroke care processes and clinical characteristics, adverse outcomes remained for SAP versus non-SAP patients. In these adjusted analyses, patients with SAP maintained an increased risk of longer length of in-hospital stay (IRR of 1.27; 95% CI: 1.25, 1.30), increased odds of worse functional outcome at discharge (OR of 2.9; 95% CI: 2.9, 3.0), and increased risk of in-hospital mortality (HR of 1.78; 95% CI: 1.74, 1.82). CONCLUSION: We show for the first time that SAP remains associated with worse clinical outcomes, even after adjusting for processes of acute stroke care and their timing. These findings highlight the importance of continued research efforts aimed at preventing SAP.

A study of prisms and therapy in attention loss after stroke (SPATIAL): A feasibility randomised controlled trial.

OBJECTIVE: Investigate feasibility and acceptability of prism adaptation training for people with inattention (spatial neglect), early after stroke, during usual care. DESIGN: Phase II feasibility randomised controlled trial with 3:1 stratified allocation to standard occupational therapy with or without intervention, and nested process evaluation. SETTING: Ten hospital sites providing in-patient stroke services. PARTICIPANTS: Screened positive for inattention more than one-week post-stroke; informal carers. Occupational therapists participated in qualitative interviews. INTERVENTION: Adjunctive prism adaptation training at the start of standard occupational therapy sessions for three weeks. MAIN MEASURES: Feasibility measures included recruitment and retention rates, intervention fidelity and attrition. Outcomes collected at baseline, 3 weeks and 12 weeks tested measures including Nottingham Extended Activities of Daily Living Scale. Acceptability was explored through qualitative interviews and structured questions. RESULTS: Eighty (31%) patients were eligible, 57 (71%) consented, 54 randomised (40:13, +1 exclusion) and 39 (74%) completed 12-week outcomes. Treatment fidelity was good: participants received median eight intervention sessions (IQR: 5, 12) lasting 4.7 min (IQR: 4.1, 5.0). All six serious adverse events were unrelated. There was no signal that patients allocated to intervention did better than controls. Twenty five of 35 recruited carers provided outcomes with excellent data completeness. Therapists, patients and carers found prism adaptation training acceptable. CONCLUSIONS: It is feasible and acceptable to conduct a high-quality definitive trial of prism adaptation training within occupational therapy early after stroke in usual care setting, but difficult to justify given no sign of benefit over standard occupational therapy. CLINICAL TRIAL REGISTRATION: https://www.isrctn.com/ Ref ISRCTN88395268.

Feasibility study of mobile phone photography as a possible outcome measure of systemic sclerosis-related digital lesions.

Objective: Clinical trials assessing systemic sclerosis (SSc)-related digital ulcers have been hampered by a lack of reliable outcome measures of healing. Our objective was to assess the feasibility of patients collecting high-quality mobile phone images of their digital lesions as a first step in developing a smartphone-based outcome measure. Methods: Patients with SSc-related digital (finger) lesions photographed one or more lesions each day for 30 days using their smartphone and uploaded the images to a secure Dropbox folder. Image quality was assessed using six criteria: blurriness, shadow, uniformity of lighting, dot location, dot angle and central positioning of the lesion. Patients completed a feedback questionnaire. Results: Twelve patients returned 332 photographs of 18 lesions. Each patient sent a median of 29.5 photographs [interquartile range (IQR) 15-33.5], with a median of 15 photographs per lesion (IQR 6-32). Twenty-two photographs were duplicates. Of the remaining 310 images, 256 (77%) were sufficiently in focus; 268 (81%) had some shadow; lighting was even in 56 (17%); dot location was acceptable in 233 (70%); dot angle was ideal in 107 (32%); and the lesion was centred in 255 (77%). Patient feedback suggested that 6 of 10 would be willing to record images daily in future studies, and 9 of 10 at least one to three times per week. Conclusion: Taking smartphone photographs of digital lesions was feasible for most patients, with most lesions in focus and central in the image. These promising results will inform the next research phase (to develop a smartphone monitoring application incorporating photographs and symptom tracking).

Does PGT-A improve assisted reproduction treatment success rates: what can the UK Register data tell us?

PURPOSE: To show how naïve analyses of aggregated UK ART Register data held by the Human Fertilisation and Embryology Authority to estimate the effects of PGT-A can be severely misleading and to indicate how it may be possible to do a more credible analysis. Given the limitations of the Register, we consider the extent to which such an analysis has the potential to answer questions about the real-world effectiveness of PGT-A. METHODS: We utilise the publicly available Register datasets and construct logistic regression models for live birth events (LBE) which adjust for confounding. We compare all PGT-A cycles to control groups of cycles that could have had PGT-A, excluding cycles that did not progress to having embryos for biopsy. RESULTS: The primary model gives an odds ratio for LBE of 0.82 (95% CI 0.68-1.00) suggesting PGT-A may be detrimental rather than beneficial. However, due to limitations in the availability of important variables in the public dataset, this cannot be considered a definitive estimate. We outline the steps required to enable a credible analysis of the Register data. CONCLUSION: If we compare like with like groups, we obtain estimates of the effect of PGT-A that suggest an overall modest reduction in treatment success rates. These are in direct contrast to an invalid comparison of crude success rates. A detailed analysis of a fuller dataset is warranted, but it remains to be demonstrated whether the UK Register data can provide useful estimates of the impact of PGT-A when used as a treatment add-on.

Nailfold capillaroscopy: a survey of current UK practice and 'next steps' to increase uptake among rheumatologists.

OBJECTIVES: To identify barriers to the use of nailfold capillaroscopy as a diagnostic tool for patients presenting with Raynaud's phenomenon in UK rheumatology centres and to obtain rheumatologists' views on a proposed internet-based standardized system for clinical reporting of nailfold capillaroscopy images. METHODS: An online survey was developed using expert opinion from clinicians, scientists and health service researchers. The survey was piloted and sent to UK-based rheumatologists using established electronic mailing lists between October 2020 and March 2021. Survey data were analysed using descriptive statistics. RESULTS: A total of 104 rheumatologists representing rheumatology centres across the UK responded to the survey. Wide variations in terms of workloads and practices were described. Thirty-four (33%) respondents reported using nailfold capillaroscopy only at their own centre, 33 (32%) referred to other centres, 9 (9%) did both and 28 (27%) did not use capillaroscopy at all. Of the 43 respondents using capillaroscopy on site, 25 (58%) used either a dermatoscope or universal serial bus microscope and 9 (21%) used videocapillaroscopy. Among the 61 respondents not undertaking capillaroscopy on site, barriers included lack of equipment (85%), lack of experience in acquiring images (69%) and lack of expertise in interpreting images (67%). Sixty-six respondents (63%) expressed interest in an internet-based, standardized automated system for reporting images. CONCLUSION: Most UK rheumatologists currently do not perform nailfold capillaroscopy on site. An internet-based nailfold capillaroscopy system for use with low-cost microscopes as well as with videocapillaroscopy could help increase uptake of capillaroscopy and thereby facilitate early diagnosis of SSc across the UK.

The Timing of Stroke Care Processes and Development of Stroke Associated Pneumonia: A National Registry Cohort Study.

Introduction: Timely stroke care can result in significant improvements in stroke recovery. However, little is known about how stroke care processes relate to complications such as the development of stroke associated pneumonia (SAP). Here we investigated associations between stroke care processes, their timing and development of SAP. Methods: We obtained patient-level data from the Sentinel Stroke National Audit Programme for all confirmed strokes between 1st April 2013 and 31st December 2018. SAP was identified if new antibiotic initiation for pneumonia occurred within the first 7 days of admission. Time to key stroke care processes in the pre-hospital, hyperacute and acute phase were investigated. A mixed effects logistic regression model estimated the association between SAP [Odds ratios (OR) with 95% CI] and each process of care after controlling for pre-determined confounders such as age, stroke severity and comorbidities. Results: SAP was identified in 8.5% of 413,133 patients in 169 stroke units. A long time to arrival at a stroke unit after symptom onset or time last seen well [OR (95% CI) = 1.29 (1.23-1.35)], from admission to assessment by a stroke specialist [1.10 (1.06-1.14)] and from admission to assessment by a physiotherapist [1.16 (1.12-1.21)] were all independently associated with SAP. Short door to needle times were associated with lower odds of SAP [0.90 (0.83-0.97)]. Conclusion: Times from stroke onset and admission to certain key stroke care processes were associated with SAP. Understanding how timing of these care processes relate to SAP may enable development of preventive interventions to reduce antibiotic use and improve clinical outcomes.

Investigating the association between inpatient stroke therapy and disability, destination on discharge, length of stay and mortality: a prospective cohort study using the Sentinel Stroke National Audit Programme.

OBJECTIVE: 'More is better' is a recognised mantra within stroke therapy, however, this has been developed in patients receiving long term rehabilitation. We investigated the relationship between amount of therapy received (from therapists and psychologists) and key patient outcomes during inpatient care. DESIGN: A secondary analysis of data from a prospective cohort study was performed. Multilevel mixed models adjusting for measured confounders (eg, severity), explored the relationship between therapy dose (average minutes per day of stay) and outcomes (disability, length of stay, home at discharge and mortality). Therapy was explored using simple linear terms and flexible natural cubic splines to allow for more complex relationships. SETTING: Data from the Sentinel Stroke National Audit Programme, covering England, Wales and Northern Ireland between July 2013 and July 2015 contained 94 905 adults with a stroke and still an inpatient after 72 hours. These patients received 92% (physiotherapy), 88% (occupational therapy), 57% (speech and language therapy) and 5% (clinical psychology), respectively. RESULTS: The average amount of therapy, for individual and 'any' therapy combined per day of stay was low. Overall, 41% were discharged with an 'independent' modified Rankin Scale (≤2), 14% died, 44% were discharged home, and the median length of stay was 16 days. We observed complex relationships between amount of therapy received and outcomes. An additional minute of 'any' therapy, occupational therapy, speech and language therapy and clinical psychology was associated with improved outcomes. Conversely, more physiotherapy was also associated with lower mortality and shorter length of stay, but also lower independence and discharge home. CONCLUSIONS: Our findings suggest for stroke inpatients requiring therapy, 'More is better' may be overly simplistic. Strong limitations associated with analysis of routine data restrict further robust investigation of the therapy-response relationship. Robust prospective work is urgently needed to further investigate the relationships observed here.

Protocol for developing a core outcome set for male infertility research: an international consensus development study.

STUDY QUESTION: We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research. WHAT IS KNOWN ALREADY: Research into male infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform clinical practice for numerous reasons. These may include complex issues, such as variation in outcome measures and outcome reporting bias, as well as failure to consider the perspectives of men and their partners with lived experience of fertility problems. Previously, the Core Outcome Measure for Infertility Trials (COMMIT) initiative, an international consortium of researchers, healthcare professionals and people with fertility problems, has developed a core outcome set for general infertility research. Now, a bespoke core outcome set for male infertility is required to address the unique challenges pertinent to male infertility research. STUDY DESIGN SIZE DURATION: Stakeholders, including healthcare professionals, allied healthcare professionals, scientists, researchers and people with fertility problems, will be invited to participate. Formal consensus science methods will be used, including the modified Delphi method, modified Nominal Group Technique and the National Institutes of Health's consensus development conference. PARTICIPANTS/MATERIALS SETTING METHODS: An international steering group, including the relevant stakeholders outlined above, has been established to guide the development of this core outcome set. Possible core outcomes will be identified by undertaking a systematic review of randomized controlled trials evaluating potential treatments for male factor infertility. These outcomes will be entered into a modified Delphi method. Repeated reflection and re-scoring should promote convergence towards consensus outcomes, which will be prioritized during a consensus development meeting to identify a final core outcome set. We will establish standardized definitions and recommend high-quality measurement instruments for individual core outcomes. STUDY FUNDING/COMPETING INTERESTS: This work has been supported by the Urology Foundation small project award, 2021. C.L.R.B. is the recipient of a BMGF grant and received consultancy fees from Exscentia and Exceed sperm testing, paid to the University of Dundee and speaking fees or honoraria paid personally by Ferring, Copper Surgical and RBMO. S.B. received royalties from Cambridge University Press, Speaker honoraria for Obstetrical and Gynaecological Society of Singapore, Merk SMART Masterclass and Merk FERRING Forum, paid to the University of Aberdeen. Payment for leadership roles within NHS Grampian, previously paid to self, now paid to University of Aberdeen. An Honorarium is received as Editor in Chief of Human Reproduction Open. M.L.E. is an advisor to the companies Hannah and Ro. B.W.M. received an investigator grant from the NHMRC, No: GNT1176437 is a paid consultant for ObsEva and has received research funding from Ferring and Merck. R.R.H. received royalties from Elsevier for a book, consultancy fees from Glyciome, and presentation fees from GryNumber Health and Aytu Bioscience. Aytu Bioscience also funded MiOXYS systems and sensors. Attendance at Fertility 2020 and Roadshow South Africa by Ralf Henkel was funded by LogixX Pharma Ltd. R.R.H. is also Editor in Chief of Andrologia and has been an employee of LogixX Pharma Ltd. since 2020. M.S.K. is an associate editor with Human Reproduction Open. K.Mc.E. received an honoraria for lectures from Bayer and Pharmasure in 2019 and payment for an ESHRE grant review in 2019. His attendance at ESHRE 2019 and AUA 2019 was sponsored by Pharmasure and Bayer, respectively. The remaining authors declare no competing interests. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586. TRIAL REGISTRATION DATE: N/A. DATE OF FIRST PATIENT'S ENROLMENT: N/A.

Variation of stroke-associated pneumonia in stroke units across England and Wales: A registry-based cohort study.

BACKGROUND: Pneumonia is common in stroke patients and is associated with worse clinical outcomes. Prevalence of stroke-associated pneumonia varies between studies, and reasons for this variation remain unclear. We aimed to describe the variation of observed stroke-associated pneumonia in England and Wales and explore the influence of patient baseline characteristics on this variation. METHODS: Patient data were obtained from the Sentinel Stroke National Audit Programme for all confirmed strokes between 1 April 2013 and 31 December 2018. Stroke-associated pneumonia was defined by new antibiotic initiation for pneumonia within the first seven days of admission. The probability of stroke-associated pneumonia occurrence within stroke units was estimated and compared using a multilevel mixed model with and without adjustment for patient-level characteristics at admission. RESULTS: Of the 413,133 patients included, median National Institutes of Health Stroke Scale was 4 (IQR: 2-10) and 42.3% were aged over 80 years. Stroke-associated pneumonia was identified in 8.5% of patients. The median within stroke unit stroke-associated pneumonia prevalence was 8.5% (IQR: 6.1-11.5%) with a maximum of 21.4%. The mean and variance of the predicted stroke-associated pneumonia probability across stroke units decreased from 0.08 (0.68) to 0.05 (0.63) when adjusting for patient admission characteristics. This difference in the variance suggests that clinical characteristics account for 5% of the observed variation in stroke-associated pneumonia between units. CONCLUSIONS: Patient-level clinical characteristics contributed minimally to the observed variation of stroke-associated pneumonia between stroke units. Additional explanations for the observed variation in stroke-associated pneumonia need to be explored which could reduce variation in antibiotic use for stroke patients.

Use of risk scores for predicting new atrial fibrillation after ischemic stroke or transient ischemic attack-A systematic review.

BACKGROUND: Newly detected atrial fibrillation (NDAF) following an ischemic stroke or transient ischemic attack is often paroxysmal in nature. While challenging to detect, extended electrocardiographic (ECG) monitoring is often used to identify NDAF which has resource implications. Prognostic risk scores have been derived which may stratify the risk of NDAF and inform patient selection for ECG monitoring approaches after ischemic stroke/transient ischemic attack. AIM: The overall aim was to identify risk scores that were derived and/or validated to predict NDAF after ischemic stroke/transient ischemic attack and evaluate their performance. SUMMARY OF REVIEW: A systematic literature review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, with application of the Quality Assessment of Diagnostic Accuracy-2 tool. Published studies, which derived and validated clinical risk scores in patients with ischemic stroke/transient ischemic attack, or externally validated an existing score to predict NDAF after ischemic stroke/transient ischemic attack, were considered and independently screened by two reviewers. Twenty-one studies involving 23 separate cohorts were analyzed from which 17 integer-based risk scores were identified. The overall frequency of NDAF was 9.7% (95% confidence intervals 8%-11.5%; I2 = 98%). The performance of the scores varied widely among derivation and validation cohorts (area under the receiver operating characteristic curve (AUC) 0.54-0.94); scores derived from stroke cohorts (12 scores) appeared to perform better (AUC 0.7-0.94) than those derived from non-stroke cohorts (five scores; AUC 0.53-0.79). The scores also varied considerably in their complexity, ascertainment, component variables, participant characteristics, outcome definition, and ease of application limiting their generalizability and utility. CONCLUSION: Overall, the risk scores identified performed variably in their discriminative ability and the utility of these scores to predict NDAF in clinical practice remains uncertain. Further studies are required using larger prospective cohorts and randomized control trials to evaluate the usefulness of such scores for clinical decision making and preventative intervention.