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Overactive bladder (OAB) and frailty are independently associated with patient burden. However, economic burden and treatment-taking behavior have not been well characterized among frail patients with OAB, which, given the varying safety and tolerability profiles of available treatments, is crucial.To assess costs, health care resource utilization, treatment-taking behavior (persistence and adherence) to OAB medication in older, frail OAB patients.This was a retrospective cohort study using international business machines MarketScan Medicare Supplemental claims data. Eligible frail patients (per Claims-based Frailty Index score) initiating mirabegron were 1:2 propensity score matched (based on age, sex, and other characteristics) with those initiating antimuscarinics and were followed up to 1 year. All-cause, per-person, per-month costs, health care encounters, persistence (median days to discontinuation assessed using Kaplan-Meier methods) and adherence (≥80% of proportion of days covered at Day 365) were compared.From 2527 patients with incident mirabegron (21%) or antimuscarinic (79%) dispensations, 516 incident mirabegron users (median age: 82 years, 64% female) were matched to 1032 incident antimuscarinic users (median age: 81 years, 62% female). Median cost was higher in mirabegron group ($1581 vs. $1197 per month); this was primarily driven by medication cost. There was no difference in medical encounters. Adherence (39.1% vs. 33.8%) and persistence (103 vs. 90 days) were higher in mirabegron users.Among frail older adults with OAB, mirabegron use was associated with higher costs and potential improvements in treatment-taking behaviors, particularly with respect to treatment adherence, versus those initiating antimuscarinics.

Educating patients about methotrexate is a core role of rheumatology nurses. We have previously reported the scoring of videoed interviews of rheumatology nurses educating patients prior to commencing methotrexate in comparison with the Calgary-Cambridge consultation model, and the qualitative analysis of the transcripts (Robinson et al. Musculoskeletal Care 2021). We were interested to investigate what could be learned from a more quantitative analysis of utterances and movements in these consultations and how they related to the qualitative interpretations.To investigate the frequency of utterances and body movements during interactions between rheumatology nurses and patients commencing methotrexate and to relate these to the qualitative interpretations of the interviews.Video-recordings of ten patients receiving methotrexate education from four different rheumatology nurses were available from the previous study. They were analysed using the Medical Interaction Process System (MIPS). This involved coding all utterances and body movements minute-by-minute by multiple inspections of the recordings. The first 10 min of each consultation was coded. The utterances and movements of the nurses and patients were compared. The thematic analysis based on the structure and content of the Calgary-Cambridge (C-C) consultation model was available from the previous study. This enabled the results from the MIPS to be compared between the interviews that scored higher on the C-C model and those scoring lower.The inter-rater reliability between 2 raters for one video was satisfactory (80-100% agreement). Numerically, giving information dominated the nurse contribution and assent by positive utterances and head nodding dominated for the patients. The results were consistent with the nurse agenda dominating the interaction with little opportunity for patient involvement. Nurses in high-scoring interviews made more illustrative gestures and fewer batonic movements while patients did the opposite. Nurses in high-scoring consultations asked more open questions, with more checking of understanding and summarising but fewer interruptions. Patients in low-scoring consultations were much more animated with head movements and illustrative gestures. Patients also checked and interrupted more.In this pilot study, the MIPS was usable and demonstrated verbal and non-verbal behaviours consistent with the qualitative assessments. It also showed some behaviours that are not intuitive but may indicate how effectively the interview was progressing. Some nurse behaviours identified that were associated with the higher scoring interviews may be useful indictors for training including making illustrative rather than batonic gestures and checking understanding. Patient behaviours, such as greater animation, were exhibited in low-scoring consultations, and could indicate that the interview was not addressing the patient perspective. Quantification of utterances and movements can be done and may give insights into the consultation process.

To understand the experience of rural Aboriginal and Torres Strait Islanders in engaging with oral health care services and programs in order to support the development of oral health services and prevention programs that better meet their needs.The study used a qualitative research design, which aims to describe participants' lived experience of engaging with oral health services and prevention programs in a rural Aboriginal and Torres Strait Islander community. Focus group discussions and in-depth interviews were conducted with 27 participants. The 15 transcribed discussions were analysed using a 6-step phenomenological process.A rural community in Queensland, Australia, with a predominantly Aboriginal population.Participants were purposively recruited from established health and community groups.System-level barriers to accessing and engaging with oral health services and prevention influence how communities manage oral health and seek treatment.The study identified 4 main themes describing the community's experience: service location and the efforts required to access oral health services; the financial burden of accessing oral health care and practising prevention; lack of confidence in oral health services; and the avoidance or delaying of accessing care for dental problems. Results confirmed a high burden of oral disease but limited attendance at an oral health facility and difficulties engaging in preventative oral health behaviours. Treatment seeking was usually instigated by the experience of pain and typically at a tertiary health facility.Aboriginal and Torres Strait Islanders in rural communities experience a high burden of oral disease but have limited engagement with oral health services. This is associated with system-level barriers to accessing and engaging with oral health services and prevention.

Background and Objective Antimuscarinics, drugs with anticholinergic properties, are frequently prescribed for overactive bladder, and anticholinergic burden is associated with adverse events. The “Polypharmacy: Use of Multiple Anticholinergic Medications in Older Adults” (Poly-ACH) measure was developed by the Pharmacy Quality Alliance and is used by the Centers for Medicare and Medicaid Services. Using the Poly-ACH measure, we assessed the prevalence of anticholinergic polypharmacy among Medicare patients in the USA with overactive bladder and determined associations between polypharmacy and medical conditions, care, and spending. Methods This was a retrospective cohort study of Medicare beneficiaries with overactive bladder (coverage period: 2006–2017). Anticholinergic polypharmacy, measured by the Poly-ACH, was defined as concurrent use of two or more anticholinergics, each with two or more prescription claims on different dates of service for ≥ 30 cumulative days. Change in annual frequency of anticholinergic polypharmacy was assessed using logistic regression. Associations between anticholinergic polypharmacy over 3 years and falls, fractures, mental status, and medical care spending were assessed with longitudinal regression models. Results In total, 226,712 patients contributed 940,201 person-years of follow-up after overactive bladder diagnosis. The share of patients meeting the Poly-ACH definition was 3.3% in 2006 and 1.7% in 2017. Women and nursing home residents had higher risks of anticholinergic polypharmacy. Having 1 year or more of positive Poly-ACH status in the 3 years prior was associated with higher rates of all outcomes. Conclusions Anticholinergic polypharmacy was uncommon among older adults with overactive bladder. Prevalence was higher among women and nursing home residents, and it was associated with negative outcomes, highlighting potential longitudinal implications of anticholinergic burden. Supplementary Information The online version contains supplementary material available at 10.1007/s40266-021-00901-2.

A 53-year-old man presented to the accident and emergency department with sudden onset left-sided facial nerve palsy and a 4-day history of progressive bilateral facial swelling. There is no history of any previous medical conditions, trauma or recent travel. What is the most likely Diagnosis seen in figures 1 and 2? 1. Bell’s Palsy. 2. Stroke. 3. Vasculitis. 4. Parotid abscess. For question see page 02 Figure 1 Patient presentation with bilateral facial swellings and facial nerve palsy. Figure 2 Clinical findings when …

A (H9N2) avian influenza A viruses were first detected in Uganda in 2017 and have since established themselves in live bird markets. The aim of this study was to establish the subsequent genetic evolution of H9N2 viruses in Uganda. Cloacal samples collected from live bird market stalls in Kampala from 2017 to 2019 were screened by RT-PCR for influenza A virus and H9N2 viruses were isolated in embryonated eggs. One hundred and fifty H9N2 isolates were subjected to whole genome sequencing on the Illumina MiSeq platform. The sequence data analysis and comparison with contemporary isolates revealed that the virus was first introduced into Uganda in 2014 from ancestors in the Middle East. There has since been an increase in nucleotide substitutions and reassortments among the viruses within and between live bird markets, leading to variations in phylogeny of the different segments, although overall diversity remained low. The isolates had several mutations such as HA-Q226L and NS-I106M that enable mammalian host adaptation, NP-M105V, PB1-D3V, and M1-T215A known for increased virulence/pathogenicity and replication, and PA-E199D, NS-P42S, and M2-S31N that promote drug resistance. The PA-E199D substitution in particular confers resistance to the endonuclease inhibitor Baloxavir acid, which is one of the new anti-influenza drugs. Higher EC50 was observed in isolates with a double F105L+E199D substitution that may suggest a possible synergistic effect. These H9N2 viruses have established an endemic situation in live bird markets in Uganda because of poor biosecurity practices and therefore pose a zoonotic threat. Regular surveillance is necessary to further generate the needed evidence for effective control strategies and to minimize the threats.

Background Overactive bladder (OAB), the primary cause of urinary incontinence in nursing homes, is commonly treated with anticholinergic medications; however, the elderly population is vulnerable to the adverse effects associated with anticholinergic burden. Given the relatively high prevalence of OAB among nursing home residents, it is important to understand the magnitude of anticholinergic burden in this population. Objectives The objectives of this study were to (1) examine the prevalence of cumulative anticholinergic burden among long-stay nursing home (LSNH) residents with OAB; and (2) identify the factors associated with varying levels of cumulative anticholinergic burden. Methods This was a retrospective, cohort study using Minimum Data Set-linked Medicare claims data. Anticholinergic burden was determined based on the Anticholinergic Cognitive Burden scale and patient-specific dosing using defined daily dose. The Andersen Behavioral Model framework was used to identify the predisposing, enabling, and need factors associated with levels of anticholinergic burden. Multivariable logistic regression models were developed to determine the factors associated with levels of anticholinergic burden. Results A total of 123,308 LSNH residents with OAB were identified; 87.2% had some degree of anticholinergic burden and 27.3% had high cumulative burden. Multiple factors were associated with higher levels of burden, including younger age, female sex, and non-Hispanic White ethnicity (predisposing factors); dual eligibility, Southern geographic region, and rural residence (enabling factors); and a number of comorbidities and concomitant medications (need factors). Conclusions This study revealed a high level of anticholinergic burden among LSNH residents. Multiple factors were associated with a high level of burden. There is a need to optimize the use of anticholinergics due to their significant safety concerns in the LSNH setting. Supplementary Information The online version contains supplementary material available at 10.1007/s40266-021-00833-x.

Summary Background The WHO VISION 2020 global initiative against blindness, launched in 2000, prioritised childhood visual disability by aiming to end avoidable childhood blindness by 2020. However, progress has been hampered by the global paucity of epidemiological data concerning childhood visual disability. The British Childhood Visual Impairment and Blindness Study 2 (BCVIS2) was done to address this evidence gap. Methods BCVIS2 was a prospective UK-wide, cross-sectional, observational study to establish an inception cohort of children newly diagnosed with visual impairment. Ophthalmologists and paediatricians reported cases from 89 hospitals and community centres across the UK. We included children aged 18 years or younger who were newly diagnosed with any condition causing impaired visual acuity to a level of 0·5 logMAR or worse (worse than 6/18 Snellen) in each eye, or equivalent vision as assessed by standard qualitative measures, between Oct 1, 2015, and Nov 1, 2016. Eligible children were notified simultaneously but independently by their managing ophthalmologists and paediatricians via the two national active surveillance schemes, the British Ophthalmological Surveillance Unit and the British Paediatric Surveillance Unit. Standardised detailed demographic, socioeconomic, and clinical data about detection, management, and treatment were collected at diagnosis and 1 year later. We calculated incidence estimates and relative rates by key sociodemographic factors. We did descriptive analyses of underlying ophthalmic disorders and non-ophthalmic comorbidities. Findings 61 (7%) of 845 eligible children initially notified were ineligible at follow-up because of improved vision after treatment. Thus, the study sample comprised 784 children with permanent newly-diagnosed all-cause visual impairment, severe visual impairment, or blindness. 559 (72%) of 778 children had clinically significant non-ophthalmic impairments or conditions. 28 (4%) of 784 children died within a year after diagnosis of visual disability (all had underlying systemic disorders). Incidence of visual disability in the first year of life was 5·19 per 10 000 children (95% CI 4·71–5·72), almost ten times higher than among 1-to-4-year-olds and between 20 times and 100 times higher than in the older age groups. The overall cumulative incidence (or lifetime risk) of visual impairment, severe visual impairment, or blindness was 10·03 per 10 000 children (9·35–10·76). Incidence rates were higher for those from any ethnic minority group, the lowest quintile of socioeconomic status, and those born preterm or with low birthweight. 345 (44%) of 784 children had a single affected anatomical site. Disorders of the brain and visual pathways affected 378 (48%) of 784 children. Interpretation BCVIS2 provides a contemporary snapshot of the heterogeneity, multi-morbidity, and vulnerability associated with childhood visual disability in a high-income country. These findings could facilitate developing and delivering health care and planning of interventional research. Our findings highlight the importance of including childhood visual disability as a sentinel event and metric in global child health initiatives. Funding Fight for Sight, National Institute for Health Research, and Ulverscroft Foundation.

Objectives To describe individual views, wishes, and preferences for end of life care and to report UK anaesthetists' personal perspectives. Methods The ‘bigconversations' questionnaire was developed by modifying an existing framework for end of life discussions. An online cross-sectional survey of UK anaesthetists was then conducted using the questionnaire in January 2019. Results The bigconversations questionnaire was validated as measuring the important aspects of end of life care by an expert panel and was found to have moderate test–retest reliability. Responses were received from 760/1913 (40%) of those invited to take part. Overall, 698/760 (92%) of respondents wished to be well informed about their condition and prognosis and 518/760 (68%) wanted to be heavily involved in decision-making about their health. Meanwhile, 639/760 (84%) of respondents would choose to forego treatment aimed at prolonging life should that life be of poor quality. The desire to spend time with family was a theme which arose from the qualitative analysis. Conclusion This study provides the first systematic description of UK doctors', specifically anaesthetists', personal preferences for end of life care. Broad trends were identified: to be well informed; to avoid high-intensity medical treatments if terminally unwell; to spend remaining time with family and friends; and to be symptom-free and well cared for. However, a substantial minority expressed different, indeed opposite, opinions. This variation highlights that good quality end of life care must be driven by discussion of an individual's values, wishes, and preferences.

The cost-effectiveness of higher cost drugs (HCDs) after several failures is disputed by some purchasers of services for people with rheumatoid arthritis (RA). We were interested to explore our service experience of using HCDs beyond the third choice to document response rates and duration of treatments.Records from our multi-disciplinary team meeting (MDT) that is used to decide on the use of HCDs were used to identify all RA patients who had been exposed to four or more HCDs. Notes were scrutinised for sequence of treatments, duration and response to treatments and reasons for stopping at each choice point.From a total of 2648 RA patients in our service, 49 ( 2%) had been exposed to four or more HCDs. Response rates based on descriptive assessments for fourth to sixth choices were between 50 and 55% as well as some partial responders. There were responders and failures to all drugs at every choice point. Patients who had responded to one drug were more likely to respond to the next. Patients often responded to drugs for approximately 2 years. Only four patients had stopped looking for the next HCD.Patients often respond to late choice HCDs. There are responders and failures at each time point and they are difficult to predict. There is no justification for restricting the number of HCDs that can be tried for RA. Key Points • Less than 2% of our RA patients required 4 or more higher cost drugs. • Fourth to sixth choice drugs still worked in 50 to 55% of patients. • There is no justification for CCGs restricting the number of drugs that can be tried.

Cumulative exposure to one or more anticholinergic medications (“anticholinergic burden”) is associated with an increased risk of adverse outcomes, particularly among older individuals. Mirabegron, an oral selective β3-adrenergic receptor agonist, has demonstrated efficacy in managing the symptoms of overactive bladder without contributing to anticholinergic burden. However, it is not known whether the favorable safety profile of mirabegron relative to antimuscarinics varies with increasing age among a patient population who may have a high anticholinergic burden. The primary objective of this study was to indirectly compare the safety and efficacy profile of mirabegron relative to antimuscarinics in older adults with overactive bladder. A systematic literature review was conducted to identify randomized controlled trials that reported safety and efficacy endpoints among patients aged ≥ 65 years. Identified randomized controlled trials were subsequently synthesized via a network meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines in designing, performing, and reporting the literature review were followed. In line with current best practices, the network meta-analysis was conducted using a Bayesian approach and according to the overall general guidance for evidence synthesis developed by the National Institute for Health and Care Excellence decision support unit. Estimates of relative safety were assessed via the odds ratio and estimates of relative efficacy were assessed via means and credible intervals. A total of 3078 abstracts, 300 of which underwent full-text screening, were identified using the search criteria. Twenty articles reporting on 21 randomized controlled trials were eligible for data extraction and synthesis. Following review, five safety and five efficacy endpoints were considered for inclusion in the network meta-analysis. Regarding findings typical of anticholinergic exposure in older adults, mirabegron was not associated with an increased odds of dry mouth (odds ratio 95% credible interval 0.76 [0.26–2.37]) or constipation (1.08 [0.39–3.02]) relative to placebo, whereas antimuscarinics were strongly associated with these events (odds ratio range 3.78–7.85 and 2.12–4.66, respectively). In this older population, mirabegron was associated with a similar odds of experiencing adverse event-related treatment discontinuations relative to placebo (0.99 [0.57–1.70]), while the odds of experiencing an adverse event-related treatment discontinuation for antimuscarinics had a range of 1.14–3.03 (in most cases, the association was mild). No increased odds of experiencing overall treatment-emergent adverse events was observed for mirabegron or antimuscarinics (odds ratio range 1.25–1.55), apart from fesoterodine (2.23 [1.37–3.37]). Finally, a similar treatment effect was observed across all efficacy endpoints between mirabegron and antimuscarinics in this older population. This study indicates that the safety and efficacy profile of mirabegron remains favorable compared with antimuscarinics among older adults. This includes safety outcomes typically associated with anticholinergic burden, which were less frequently observed in patients treated with mirabegron.

Background The aim of the project was to identify risk factors associated with visual progression and treatment indications in pediatric patients with neurofibromatosis type 1 associated optic pathway glioma (NF1-OPG). Methods A multidisciplinary expert group consisting of ophthalmologists, pediatric neuro-oncologists, neurofibromatosis specialists, and neuro-radiologists involved in therapy trials assembled a cohort of children with NF1-OPG from 6 European countries with complete clinical, imaging, and visual outcome datasets. Using methods developed during a consensus workshop, visual and imaging data were reviewed by the expert team and analyzed to identify associations between factors at diagnosis with visual and imaging outcomes. Results Eighty-three patients (37 males, 46 females, mean age 5.1 ± 2.6 y; 1–13.1 y) registered in the European treatment trial SIOP LGG-2004 (recruited 2004–2012) were included. They were either observed or treated (at diagnosis/after follow-up). In multivariable analysis, factors present at diagnosis associated with adverse visual outcomes included: multiple visual signs and symptoms (adjusted odds ratio [adjOR]: 8.33; 95% CI: 1.9–36.45), abnormal visual behavior (adjOR: 4.15; 95% CI: 1.20–14.34), new onset of visual symptoms (adjOR: 4.04; 95% CI: 1.26–12.95), and optic atrophy (adjOR: 3.73; 95% CI: 1.13–12.53). Squint, posterior visual pathway tumor involvement, and bilateral pathway tumor involvement showed borderline significance. Treatment appeared to reduce tumor size but improved vision in only 10/45 treated patients. Children with visual deterioration after primary observation are more likely to improve with treatment than children treated at diagnosis. Conclusions The analysis identified the importance of symptomatology, optic atrophy, and history of vision loss as predictive factors for poor visual outcomes in children with NF1-OPG.

Aims To characterize the epidemiology and treatment patterns of adult men (≥40 years) diagnosed with, or treated for, overactive bladder (OAB) and/or benign prostatic hyperplasia (BPH). Methods This retrospective observational study used data extracted from the IBM MarketScan Commercial Claims and Encounters database and the Medicare Supplemental Coordination of Benefits database. Men with BPH and/or OAB were identified and observed to assess treatment and diagnostic patterns. Results Within the entire study sample (N = 462 400), BPH diagnosis (61.5%) and BPH treatment (73.7%) were more common than the corresponding values for OAB (25.8% and 7.0%, respectively). Notably, among diagnosed individuals, the dispensation of a corresponding treatment was more likely in individuals diagnosed with BPH (183 672 out of 284 416 = 64.6%) compared with OAB (16 468 out of 119 236 = 13.8%). Among newly diagnosed and/or treated patients (n = 196 576), only 60.3% received treatment. Among treated patients, most experienced only a single type of treatment (93.4%), 6.6% went on to receive a secondary treatment and 3.5% a tertiary. The most common primary treatment was alpha‐blocker monotherapy (76.9%) followed by tadalafil monotherapy (16.4%). Among those untreated at first diagnosis, the median time between diagnosis and treatment initiation was 128 days. Conclusions Diagnosis and management of OAB among males are challenging given the inherent overlap in symptoms observed with BPH. Unsurprisingly, we found that BPH is diagnosed and treated more frequently than OAB; but the differences between diagnosis and treatment patterns for the two conditions highlight the potential undertreatment of OAB and misdirection of therapy for men with a combination of voiding and storage symptoms.

Cutaneous and renal glomerular vasculopathy (CRGV) has been recognized as a potentially life-threatening condition of dogs in the UK since 2012, although there was a single (non-azotaemic) case reported in the UK in 2000. Prior to that, CRGV was recognized in the 1980s in southern USA as a disease affecting solely racing greyhounds (which gave rise to the colloquial name of 'Alabama rot'). CRGV manifests as ulcerative skin lesions, generally sparing the dorsum. It is variably associated with systemic signs including anaemia, thrombocytopenia and acute kidney injury, which, when it develops, is often severe and fatal. CRGV is characterized histopathologically as a thrombotic microangiopathy. To date in the UK, more than 230 dogs of varying breed and age have been humanely destroyed and histopathologically confirmed to be suffering from CRGV. The aetiology remains unknown, but the seasonal distribution (highest case incidence November-May each year) suggests that environmental or climatic factors may play a role in disease development. Further research to determine the aetiology and improve ante-mortem diagnostic testing, therapeutic options and preventive strategies is urgently needed.

Leptomeningeal malignancy complicates childhood cancers, including leukaemias, brain tumours, and solid tumours. In leukaemia, such malignancy is thought to invade leptomeninges via the vascular route. In brain tumours, dissemination from the primary tumour, before or after surgery, via CSF pathways is assumed; however, evidence exists to support the vascular route of dissemination. Success in treating leptomeningeal malignancy represents a rate-limiting step to cure, which has been successfully overcome in leukaemia with intensified systemic therapy combined with intra-CSF therapy, which replaced cranial radiotherapy for many patients. This de-escalated CNS-directed therapy is still associated with some neurotoxicity. The balanced benefit justifies exploration of ways to further de-escalate CNS-directed therapy. For primary brain tumours, standard therapy is craniospinal radiotherapy, but attendant risk of acute and delayed brain injury and endocrine deficiencies compounds post-radiation impairment of spinal growth. Alternative ways of treating leptomeninges by intensifying drug therapy delivered to CSF are being investigated—preliminary evidence suggests improved outcomes. This Review seeks to describe methods of intra-CSF drug delivery and drugs in use, and consider how the technique could be modified and additional drugs might be selected for this route of administration.

Osteomalacia is a condition where bone mineralisation is impaired by lack of vitamin D. It more commonly affects darker skinned individuals in the UK, especially if they wear occlusive clothing. Lifestyle changes and Vitamin D supplementation are recommended for those people most at risk through these factors, but such advice is not commonly followed. This indicates an educational need for information on osteomalacia and its treatment. Using a previously developed Mind-Map on osteomalacia, a layered and interactive" PowerPoint" style presentation was developed, using hyperlinks. The "basic" layer was translated into Urdu and validated by Urdu speaking professionals. The translation was accurate and meaningful and the tool was well received by representatives of the community. The tool was used to educate a group of 10 community leaders from the Urdu community in Stourbridge, UK. Knowledge about osteomalacia was tested in these people, before and after the education, and increased from an average of 14 to 25 points (p < 0.05). Qualitative feedback gained was very positive. Conclusion: An interactive educational tool for Osteomalacia was developed and translated into Urdu. Use of the tool resulted in increased knowledge about osteomalacia.

Background Management of unresectable pediatric low-grade glioma and glioneuronal tumor (LGG/LGGNT) is controversial. There are no validated prognostic features to guide use of radiation therapy (RT). Our study aimed to identify negative prognostic features in patients treated with RT using clinicopathologic and molecular data and validate these findings in an external dataset. Methods Children with non-metastatic, biopsy-proven unresectable LGG/LGGNT treated with RT at a single institution between 1997 and 2017 were identified. Recursive partitioning analysis (RPA) was used to stratify patients into low- and high-risk prognostic groups based on overall survival (OS). CNS9702 data were used for validation. Results One hundred and fifty patients met inclusion criteria. Median follow-up was 11.4 years. RPA yielded low- and high-risk groups with 10-year OS of 95.6% versus 76.4% (95% CI: 88.7%–98.4% vs 59.3%–87.1%, P = 0.003), respectively. These risk groups were validated using CNS9702 dataset (n = 48) (4-year OS: low-risk vs high-risk: 100% vs 64%, P < 0.001). High-risk tumors included diffuse astrocytoma or location within thalamus/midbrain. Low-risk tumors included pilocytic astrocytoma/ganglioglioma located outside of the thalamus/midbrain. In the subgroup with known BRAF status (n = 49), risk stratification remained prognostic independently of BRAF alteration (V600E or fusion). Within the high-risk group, delayed RT, defined as RT after at least one line of chemotherapy, was associated with a further decrement in overall survival (P = 0.021). Conclusion A high-risk subgroup of patients, defined by diffuse astrocytoma histology or midbrain/thalamus tumor location, have suboptimal long-term survival and might benefit from timely use of RT. These results require validation.

Optic Pathway Glioma (OPG) is a relatively common brain tumour in childhood; however, there is scarce understanding of neuropsychological sequelae in these survivors. In this study, 12 children with diagnosis of OPG before 6 years of age received a comprehensive standardised assessment of visual perception, general intelligence and academic achievement, using adjustments to visual materials of the tests, to examine the extent of concurrent impairment in these functional domains. Information about vision, clinical and socio-demographic factors were extracted from medical records to assess the associations of neuropsychological outcomes with clinical and socio-demographic factors. Children with OPG exhibited high within-patient variability and moderate group-level impairment compared to test norms. Visual perception was the most impaired domain, while scholastic progression was age-appropriate overall. For cognition, core verbal and visuo-spatial reasoning skills were intact, whereas deficits were found in working memory and processing speed. Visual function was associated with tasks that rely on visual input. Children with OPG are at moderate risk of neuropsychological impairment, especially for visual perception and cognitive proficiency. Future research should elucidate further the relative contribution of vision loss and neurofibromatosis type 1 co-diagnosis within a large sample.

IntroductionChildhood cancer is diagnosed in 400 000 children and young people (CYP) aged 0–19 years worldwide annually. In the UK, a child’s cumulative cancer risk increases from 1 in 4690 from birth to aged 1, to 1 in 470 by age 15. Once diagnosed, access to treatments offers survival to adulthood for over 80%. Tumour diagnoses are at a later stage and mortality is higher when compared with those in other parts of Europe. This means higher risk, more intensive therapies for a cure. Some CYPs are known to experience delays to diagnosis which may further contribute to poor outcomes. This study aims to understand the current pathway of childhood cancer referrals and diagnosis and quantify diagnostic intervals in the UK.Methods and analysisThis is a prospective multicentre observational study including all tertiary childhood cancer treatment centres in the UK. CYP (0–18 years) with a new diagnosis of cancer over the study period will be invited to participate. Data will be collected at initial diagnosis and 5 years after diagnosis. Data will include demographic details, clinical symptoms, tumour location, stage and clinical risk group. In addition, key diagnostic dates and referral routes will be collected to calculate the diagnostic intervals. At 5 years’ follow-up, data will be collected on refractory disease, relapse and 1-year and 5-year survival. Population characteristics will be presented with descriptive analyses with further analyses stratified by age, geographical region and cancer type. Associations between diagnostic intervals/delay and risk factors will be explored using multiple regression and logistic regression.EthicsThe study has favourable opinion from the York and Humber, Leeds West REC (19/YH/0416).DisseminationResults will be presented at academic conferences, published in peer-reviewed journals and disseminated through public messaging in collaboration with our charity partners through a national awareness campaign (ChildCancerSmart).Study registrationresearchregistry.com (researchregistry5313).

This article discusses the joint guidance from the Faculty of Intensive Care Medicine and Centre for Perioperative Care, which provides recommendations for establishing and delivering enhanced perioperative care services.

BackgroundThe COVID-19 pandemic led to changes in patterns of presentation to emergency departments. Child health professionals were concerned that this could contribute to the delayed diagnosis of life-threatening conditions, including childhood cancer (CC) and type 1 diabetes (T1DM). Our multicentre, UK-based service evaluation assessed diagnostic intervals and disease severity for these conditions.MethodsWe collected presentation route, timing and disease severity for children with newly diagnosed CC in three principal treatment centres and T1DM in four centres between 1 January and 31 July 2020 and the corresponding period in 2019. Total diagnostic interval (TDI), patient interval (PI), system interval (SI) and disease severity across different time periods were compared.ResultsFor CCs and T1DM, the route to diagnosis and severity of illness at presentation were unchanged across all time periods. Diagnostic intervals for CCs during lockdown were comparable to that in 2019 (TDI 4.6, PI 1.1 and SI 2.1 weeks), except for an increased PI in January–March 2020 (median 2.7 weeks). Diagnostic intervals for T1DM during lockdown were similar to that in 2019 (TDI 16 vs 15 and PI 14 vs 14 days), except for an increased PI in January–March 2020 (median 21 days).ConclusionsThere is no evidence of diagnostic delay or increased illness severity for CC or T1DM, during the first phase of the pandemic across the participating centres. This provides reassuring data for children and families with these life-changing conditions.

From April 2018 to October 2019, we continued active surveillance for influenza viruses in Bangladeshi live poultry markets (LPMs) and in Tanguar Haor, a wetland region of Bangladesh where domestic ducks have frequent contact with migratory birds. The predominant virus subtypes circulating in the LPMs were low pathogenic avian influenza (LPAI) H9N2 and clade 2.3.2.1a highly pathogenic avian influenza (HPAI) H5N1 viruses of the H5N1-R1 genotype, like those found in previous years. Viruses of the H5N1-R2 genotype, which were previously reported as co-circulating with H5N1-R1 genotype viruses in LPM, were not detected. In addition to H9N2 viruses, which were primarily found in chicken and quail, H2N2, H3N8 and H11N3 LPAI viruses were detected in LPMs, exclusively in ducks. Viruses in domestic ducks and/or wild birds in Tanguar Haor were more diverse, with H1N1, H4N6, H7N1, H7N3, H7N4, H7N6, H8N4, H10N3, H10N4 and H11N3 detected. Phylogenetic analyses of these LPAI viruses suggested that some were new to Bangladesh (H2N2, H7N6, H8N4, H10N3 and H10N4), likely introduced by migratory birds of the Central Asian flyway. Our results show a complex dynamic of viral evolution and diversity in Bangladesh based on factors such as host populations and geography. The LPM environment was characterised by maintenance of viruses with demonstrated zoonotic potential and H5N1 genotype turnover. The wetland environment was characterised by greater viral gene pool diversity but a lower overall influenza virus detection rate. The genetic similarity of H11N3 viruses in both environments demonstrates that LPM and wetlands are connected despite their having distinct influenza ecologies.

PURPOSE The structural relationship between benign prostate hyperplasia (BPH) and prostate cancer (Pca) is controversial. The purpose of our study was to examine the association between quantitative prostate compositional metrics by magnetic resonance imaging (MRI) and Pca. METHODS We identified 405 patients who underwent prostate MRI and biopsy and/or prostatectomy from January 2019 to January 2021 at our institution. Segmentation volumetric methods were used to assess central gland (CG) and peripheral zone (PZ) volume. PZ mean thickness and mean apparent diffusion coefficient (ADC), marker of underlying histologic components, were measured. Multivariable logistic regression was performed with outcomes of ≥Grade Group (GG) 2 Pca and for multifocal disease. RESULTS On multivariable analysis, higher CG volumes were at lower odds of ≥GG2 disease (n = 227) (OR: 0.97, 95% CI 0.96-0.98, p

Prostate volume and PSA density (PSAd) are important in the risk stratification of suspected prostate cancer (Pca). PI-RADS v2.1 allows for determining volume via segmentation or ellipsoid calculation. The purpose of our study was to compare ellipsoid and segmentation volume calculation methods and evaluate if PSAd diagnostic performance is altered.We retrospectively assessed 397 patients (mean age/standard deviation: 63.7/7.4 years) who underwent MRI and prostate biopsy or prostatectomy, with Pca classified by Gleason ≥3 + 4 and ≥4 + 4 disease. Prostate total volumes were determined with ellipsoid calculations (TVe) and with semi-automated segmentation (TVs), along with inter-rater reliability with intraclass correlation coefficient (ICC). PSAd was calculated for TVe and TVs and ROC curves were created to compare performance for Gleason ≥3 + 4 and ≥4 + 4 disease.TVe was significantly higher than TVs (p 0.0001), with mean TVe = 55.4 mL and TVs = 51.0 mL. ROC area under the curve for PSAd derived with TVe (0.63, 95%CI:0.59-0.68) and TVs (0.64, 95%CI:0.59-0.68) showed no significant difference for Gleason ≥3 + 4 disease (p = 0.45), but PSAd derived with TVs (0.63, 95%CI: 0.58-0.68) significantly outperformed TVe (0.61, 95%CI: 0.57-0.67) for Gleason ≥4 + 4 disease (p = 0.02). Both methods demonstrated excellent inter-rater reliability with TVe with ICC of 0.93(95%CI: 0.92-0.94) and TVs with ICC of 0.98(95%CI: 0.98-0.99).Traditional ellipsoid measurements tend to overestimate total prostate volume compared to segmentation, but both methods demonstrate similar diagnostic performance of derived PSA density for PI-RADS clinically significant disease. For higher grade disease, PSAd derived from segmentation volumes demonstrates statistically significant superior performance. Both methods are viable, but segmentation volume is potentially better.

BACKGROUND: Brain tumours are the most common solid tumours in childhood. Half of these tumours occur in the posterior fossa, where surgical removal is complicated by the risk of cerebellar mutism syndrome, of which postoperative speech impairment (POSI) is a cardinal symptom, in up to 25% of patients. The surgical approach to midline tumours, mostly undertaken by transvermian or telovelar routes, has been proposed to influence the risk of POSI. We aimed to investigate the risk of developing POSI, the time course of its resolution, and its association with surgical approach and other clinical factors. METHODS: In this observational prospective multicentre cohort study, we included children (aged

Background This study examines vector density, the prevailing knowledge, awareness, attitudes and practice (KAAP) of community members regarding dengue disease and their willingness to pay (WTP) for vector control in Dhaka, Bangladesh. Methods A population-based, cross-sectional study design was followed: (i) an entomological survey was carried out in 727 randomly selected households in 12 wards, representing four urban ecological zones and (ii) a survey of 330 household heads was conducted to study their KAAP. The χ2 test and multinomial logistic regression (MLR) were applied to investigate factors associated with WTP and other variables. Results The Stegomyia indices significantly vary among the urban zones, revealing that the paved and built areas with concentrated public/commercial services have the highest mosquito density. Most respondents (93.9%) knew about dengue and its severity (90.3%); however, many of them were unaware (79.3%) about the types of mosquitoes causing dengue. MLR modelling reveals that average spending per month for mosquito control, household income and knowledge about the effects of land use and seasonality on dengue were significantly associated with the WTP for controlling the dengue vector. Conclusions Concerted efforts should be made to increase awareness about dengue transmission and develop community-based sustainable dengue vector control programmes involving both the public and private sectors.

OBJECTIVE To compare the efficacy and safety of mirabegron and onabotulinumtoxinA in the management of treatment-experienced patients with overactive bladder. METHODS The network meta-analysis was based on evidence from a systematic literature review of randomized controlled trials and a post-hoc analysis of treatment-experienced subpopulations from mirabegron studies. RESULTS Nineteen trials described in 21 publications were included. CONCLUSION Overall, compared to mirabegron, there was some evidence that onabotulinumtoxinA was associated with improved outcomes, including reductions in the number of micturitions in a 24-hour period, and the number of incontinence episodes. However, mirabegron was associated with a lower risk of urinary tract infections compared with onabotulinumtoxinA.

Introduction The objective was to identify the most commonly used patient-reported outcome (PRO) instruments for overactive bladder (OAB), determine which are the most useful for measuring burden in OAB and characterize the findings of recent studies that have employed PRO instruments to assess OAB symptoms and the effects of treatment. Methods A systematic search of OAB literature published between January 2006 and November 2017 using Medline/PubMed and EMBASE databases. Results Of 3425 abstracts and 500 full-text articles reviewed, 58 studies (both clinical trials and observational studies) were included in the review. The most commonly used PRO instruments were the OAB Questionnaire (OAB-q; 64%), followed by the King’s Health Questionnaire (KHQ; 31%) and the Patient Perception of Bladder Condition (PCBC; 21%). Synthesis of data from studies using the OAB-q showed that OAB treatment with antimuscarinics, mirabegron and onabotulinumtoxinA all improve health-related quality of life (HRQoL) and symptoms beyond the benefits observed with placebo. The OAB-q could detect dose–response relationships in some studies and demonstrated there were no significant differences across therapies from different drug classes. Conclusion The HRQoL burden of OAB and response to treatment can be reliably measured by PRO instruments, and the OAB-q is the most commonly used instrument in OAB, particularly in clinical trials of OAB interventions. These data will be useful to provide benchmarks of burden levels for PRO scores obtained among those on contemporary therapies for comparison with outcomes from patients managed with emerging treatments. Funding Astellas Pharma Global Development, Inc. Electronic supplementary material The online version of this article (10.1007/s12325-019-0880-8) contains supplementary material, which is available to authorized users.

The protein arginine methyltransferase 5 (PRMT5) methylates a variety of proteins involved in splicing, multiple signal transduction pathways, epigenetic control of gene expression, and mechanisms leading to protein expression required for cellular proliferation. Dysregulation of PRMT5 is associated with clinical features of several cancers, including lymphomas, lung cancer, and breast cancer. Here, we describe the characterization of JNJ-64619178, a novel, selective, and potent PRMT5 inhibitor, currently in clinical trials for patients with advanced solid tumors, non-Hodgkin's lymphoma, and lower-risk myelodysplastic syndrome. JNJ-64619178 demonstrated a prolonged inhibition of PRMT5 and potent antiproliferative activity in subsets of cancer cell lines derived from various histologies, including lung, breast, pancreatic, and hematological malignancies. In primary acute myelogenous leukemia samples, the presence of splicing factor mutations correlated with a higher ex vivo sensitivity to JNJ-64619178. Furthermore, the potent and unique mechanism of inhibition of JNJ-64619178, combined with highly optimized pharmacological properties, led to efficient tumor growth inhibition and regression in several xenograft models in vivo, with once-daily or intermittent oral-dosing schedules. An increase in splicing burden was observed upon JNJ-64619178 treatment. Overall, these observations support the continued clinical evaluation of JNJ-64619178 in patients with aberrant PRMT5 activity-driven tumors. ispartof: MOLECULAR CANCER THERAPEUTICS vol:20 issue:12 pages:2317-2328 ispartof: location:United States status: published

It is a misconception that cancer is rare in children and young people (CYP, aged

Background\ud Prior to commencing Methotrexate patients routinely attend an education consultation with a rheumatology nurse. The purpose of the consultation is to discuss the patients’ expectations and concerns related to commencing Methotrexate, the benefits of treatment, potential side effects and monitoring requirements. The aim of this study was to use video analysis to assess the structure, content and mode of delivery of the consultation.\ud Methods\ud Video-recordings of ten patient-nurse consultations, involving four specialist rheumatology nurses were analysed and transcribed. The consultations were compared with the Calgary Cambridge consultation model. Transcripts were thematically analysed. Data were quantitatively assessed for verbal and non-verbal behaviours.\ud Findings\ud Assessment of the video data using the CC model demonstrated good structure, content and flow of the consultation, influenced by the use of an information leaflet. Consultations generally consisted of communication from nurse to patient rather than a dialogue; the nurse spoke for 69% – 86% of the time; clarification of the patient’s understanding of the information did not take place in any of the consultations. Thematic analysis also showed that the nurse agenda dominated and that the nurse was aware of “overloading” the patient with information. Cues from the patients to discuss items of importance were often missed.\ud Conclusion\ud Video analysis can be used to identify aspects of the consultation that work well and those areas of the consultation that could be improved with specific training.

The accurate evaluation of perioperative risk is crucial to facilitate the shared decision-making process. Surgical outcome risk tool (SORT) has been developed to provide enhanced and more feasible identification of high-risk surgical patients. Nonetheless, SORT has not been validated for patients with colorectal cancer undergoing surgery. Our aim was to determine whether SORT can accurately predict mortality after surgery for colorectal cancer and to compare it with traditional risk models.526 patients undergoing surgery performed by a colorectal surgical team in a single Greek tertiary hospital (2011-2019) were included. Five risk models were evaluated: (1) SORT, (2) Physiology and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM), (3) Portsmouth POSSUM (P-POSSUM), (4) Colorectal POSSUM (CR-POSSUM), and (5) the Association of Great Britain and Ireland (ACPGBI) score. Model accuracy was assessed by observed to expected (O:E) ratios, and area under Receiver Operating Characteristic curve (AUC).Ten patients (1.9%) died within 30 days of surgery. SORT was associated with an excellent level of discrimination [AUC:0.81 (95% CI:0.68-0.94); p = 0.001] and provided the best performing calibration of all models in the entire dataset analysis (H-L:2.82; p = 0.83). Nonetheless, SORT underestimated mortality. SORT model demonstrated excellent discrimination and calibration predicting perioperative mortality in patients undergoing (1) open surgery, (2) emergency/acute surgery, and (3) in cases with colon-located cancer.SORT is an easily adopted risk-assessment tool, associated with enhanced accuracy, that could be implemented in the perioperative pathway of patients undergoing surgery for colorectal cancer.

Aims Quality indicators (QIs) are tools to improve the delivery of evidence-base medicine. In 2017, the European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC) developed a set of QIs for acute myocardial infarction (AMI), which have been evaluated at national and international levels and across different populations. However, an update of these QIs is needed in light of the accumulated experience and the changes in the supporting evidence. Methods and results The ESC methodology for the QI development was used to update the 2017 ACVC QIs. We identified key domains of AMI care, conducted a literature review, developed a list of candidate QIs, and used a modified Delphi method to select the final set of indicators. The same seven domains of AMI care identified by the 2017 Study Group were retained for this update. For each domain, main and secondary QIs were developed reflecting the essential and complementary aspects of care, respectively. Overall, 26 QIs are proposed in this document, compared to 20 in the 2017 set. New QIs are proposed in this document (e.g. the centre use of high-sensitivity troponin), some were retained or modified (e.g. the in-hospital risk assessment), and others were retired in accordance with the changes in evidence [e.g. the proportion of patients with non-ST segment elevation myocardial infarction (NSTEMI) treated with fondaparinux] and the feasibility assessments (e.g. the proportion of patients with NSTEMI whom risk assessment is performed using the GRACE and CRUSADE risk scores). Conclusion Updated QIs for the management of AMI were developed according to contemporary knowledge and accumulated experience. These QIs may be applied to evaluate and improve the quality of AMI care.

Background Two million non-emergency surgeries are being cancelled globally every week due to the COVID-19 pandemic, which will have a major impact on patients and healthcare systems. Methods During the peak of the pandemic in the United Kingdom, we set up a multicentre cancer network amongst 14 National Health Service institutions, performing urological, thoracic, gynaecological and general surgical urgent and cancer operations at a central COVID-19 cold site. This is a cohort study of 500 consecutive patients undergoing surgery in this network. The primary outcome was 30-day mortality from COVID-19. Secondary outcomes included all-cause mortality and post-operative complications at 30-days. Results 500 patients underwent surgery with median age 62.5 (IQR 51–71). 65% were male, 60% had a known diagnosis of cancer and 61% of surgeries were considered complex or major. No patient died from COVID-19 at 30-days. 30-day all-cause mortality was 3/500 (1%). 10 (2%) patients were diagnosed with COVID-19, 4 (1%) with confirmed laboratory diagnosis and 6 (1%) with probable COVID-19. 33/500 (7%) of patients developed Clavien-Dindo grade 3 or higher complications, with 1/33 (3%) occurring in a patient with COVID-19. Conclusion It is safe to continue cancer and urgent surgery during the COVID-19 pandemic with appropriate service reconfiguration., Highlights • Priority surgeries are being cancelled every week due to the COVID-19 pandemic. • A multicentre surgical referral network was set up as part of an NHS England approach to continuing safe surgery • The referral network consisted of 14 NHS trusts and surgery was performed at a single COVID-19 ‘cold site’. • After 500 surgeries performed, there was a 0% 30-day mortality from COVID-19. • It is safe to continue cancer and priority surgery during the COVID-19 pandemic with appropriate service reconfiguration.

Funder: Samantha Dickson Brain Tumour Trust; doi: http://dx.doi.org/10.13039/501100000394, Purpose: Posterior fossa brain tumours (PFT) and their treatment in young children are often associated with subsequent cognitive impairment. However, reported follow-up periods rarely exceed 10 years. This study reports very long-term cognitive consequences of surviving an early childhood PFT. Methods: 62 adult survivors of a PFT, ascertained from a national register, diagnosed before 5 years of age, and a sibling control, received a single IQ assessment an average of 32 years (range 18–53) after initial diagnosis, using the Weschler Abbreviated Scale of Intelligence. Regression models were fitted to survivor–sibling pair differences on verbal and performance IQ (VIQ and PIQ) scores to investigate whether increasing time between PFT diagnosis and follow-up IQ assessment contributed to survivor–sibling IQ differences. Results: At follow-up, survivors had, on average, VIQ 15 points and PIQ 19 points lower than their siblings. There was no significant effect of time since diagnosis on survivor–sibling VIQ difference. Survivors who received radiotherapy showed no significant effect of time since diagnosis on survivor–sibling PIQ difference. Survivors who did not receive radiotherapy demonstrated a trend for it to reduce. Conclusions: VIQ and PIQ deficits persist in adulthood, suggesting the effect of a fixed injury imposing on cognitive development, rather than an ongoing pathological process. Implications for cancer survivors: The findings will help parents and others supporting survivors of an early life PFT to identify and plan for possible cognitive outcomes, and highlight the importance of early interventions to optimize cognitive function during the developmental period.

Effective treatment of diffuse intrinsic pontine glioma (DIPG) remains a formidable challenge due to inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies. The BBB can be overcome by directly infusing drugs into pons using method of convection-enhanced delivery (CED). We describe our clinical experience and what we have learned about the safety and feasibility of treating DIPG with intermittent CED of carboplatin and sodium valproate to the pons through the Renishaw Drug Delivery System (RDDS).Retrospective review (2017-2020) of children with DIPG, who following radiotherapy, received compassionate treatment commencing 3.3-10 months post-diagnosis (median 4.9 months). They received up to 7 cycles of 3-6 weekly pontine infusions of carboplatin (0.12-0.18 mg/ml) and sodium valproate (14.4-28.8 mg/ml).13 children 3-19 years (mean 6.9 years) were treated. There were no surgical complications. With the exception of infusion channels blocking in one device, there were no adverse device effects. Two patients developed persistent 6th nerve palsies, which led to drug concentration reduction in the combination therapy. Subsequently infusion/ drug-related toxicities were transient. Tumour was controlled in pons in 10/13 patients. Median progression-free survival (PFS) was 13.0 months, while median overall survival (OS) was 15.3 months.Use of the RDDS was safe and well tolerated in all 13 patients. Treatment improved control of pontine disease resulting in longer PFS and OS and merits further evaluation in a clinical trial.

Extragonadal non-gestational choriocarcinoma is a rare but well-described phenomenon occurring in patients with midline germ cell tumors. Choriocarcinoma (ChC) is an aggressive neoplasm usually developing in women as a rare complication of pregnancy. In male patients ChC occurs in the testes, usually as a component of mixed germ cell tumors. Very few patients develop extragonadal choriocarcinoma with the tumor occurring in midline locations, such as the mediastinum, retroperitoneum, and central nervous system (mostly pineal gland). Non-midline choriocarcinoma can occur in the lung, gastrointestinal tract, and breast, sometimes blended with another primary malignancy. A midline choriocarcinoma manifesting as a head and neck malignancy is exceptional. During an evaluation of multiple enlarged cervical lymph nodes suspected to be lymphoma in a 72-year-old man, a core biopsy was taken from one of the left neck lymph nodes which histologically showed a necrotic malignancy with strong diffuse pancytokeratin staining. After an initial interpretation of metastatic carcinoma, further samples were taken from both tonsils and from a right level 5 neck lymph node. Histologically, all samples contained the same tumor, showing profound pleomorphism and multinucleated syncytial-type giant cells. A panel of immunohistochemistry studies were performed, including β-human chorionic gonadotropin, with positive findings leading to a diagnosis of extragonadal non-gestational choriocarcinoma.

Objective The aim of the study was to determine whether perforated appendicitis rates in children were influenced by the Coronavirus disease 2019 (COVID-19) surge. Background Disruption of care pathways during a public health crisis may prevent children from obtaining prompt assessment for surgical conditions. Progression of appendicitis to perforation is influenced by timeliness of presentation. In the context of state-mandated controls and public wariness of hospitals, we investigated the impact of the COVID-19 outbreak on perforated appendicitis in children. Study design We conducted an analysis of all children presenting to 3 hospital sites with acute appendicitis between March 1 and May 7, 2020, corresponding with the peak COVID-19 outbreak in the New York City region. Control variables were collected from the same institutions for the preceding 5 years. The primary outcome measure was appendiceal perforation. Results Fifty-five children presented with acute appendicitis over 10 weeks. Compared to a 5-year control cohort of 1291 patients, we observed a higher perforation rate (45% vs 27%, odds ratio 2.23, 95% confidence interval 1.29-3.85, P = 0.005) and longer mean duration of symptoms in children with perforations (71 ± 39 vs 47 ± 27 h, P = 0.001) during the COVID-19 period. There were no differences in perforation rates (55% vs 59%, P = 0.99) or median length of stay (1.0 vs 3.0 days, P = 0.58) among children screening positive or negative for SARS-CoV-2. Conclusions Children in the epicenter of the COVID-19 outbreak demonstrated higher rates of perforated appendicitis compared to historical controls. Preoperative detection of SARS-CoV-2 was not associated with inferior outcomes. Although children likely avoid much of the morbidity directly linked to COVID-19, disruption to local healthcare delivery systems may negatively impact other aspects of pediatric surgical disease.

Purpose The purpose of this study is to elucidate the chest imaging findings of suspected COVID-19 patients presenting to the emergency department and the relationship with their demographics and RT-PCR testing results. Methods Patients presenting to the ED between March 12 and March 28, 2020, with symptoms suspicious for COVID-19 and subsequent CXR and/or CT exam were selected. Patients imaged for other reasons with findings suspicious for COVID-19 were also included. Demographics, laboratory test results, and history were extracted from the medical record. Descriptive statistics were used to explore the relationship between imaging and these factors. Results A total of 227 patients from the emergency department were analyzed (224 CXRs and 25 CTs). Of the 192 patients with COVID-19 results, 173 (90.1%) had COVID-19 RT-PCR (+). Abnormal imaging (CXR, 85.7% and/or CT, 100%) was noted in 155 (89.6%) of COVID-19 RT-PCR (+) cases. The most common imaging findings were mixed airspace/interstitial opacities (39.8%) on CXR and peripheral GGOs on CT (92%). The most common demographic were African Americans (76.8%). Furthermore, 97.1% of African Americans were RT-PCR (+) compared to 65.8% of Caucasians. Conclusion We found a similar spectrum of thoracic imaging findings in COVID-19 patients as previous studies. The most common demographic were African Americans (76.8%). Furthermore, 97.1% of African Americans were RT-PCR (+) compared to 65.8% of Caucasians. Both CT and CXR can accurately identify COVID-19 pneumonitis in 89.6% of RT-PCR (+) cases, 89.5% of false negatives, and 72.7% of cases with no RT-PCR result. Electronic supplementary material The online version of this article (10.1007/s10140-020-01787-0) contains supplementary material, which is available to authorized users.

A barrier to routine preoperative frailty assessment is the large number of frailty instruments described. Previous systematic reviews estimate the association of frailty with outcomes, but none have evaluated outcomes at the individual instrument level or specific to clinical assessment of frailty, which must combine accuracy with feasibility to support clinical practice.The authors conducted a preregistered systematic review (CRD42019107551) of studies prospectively applying a frailty instrument in a clinical setting before surgery. Medline, Excerpta Medica Database, Cochrane Library and the Comprehensive Index to Nursing and Allied Health Literature, and Cochrane databases were searched using a peer-reviewed strategy. All stages of the review were completed in duplicate. The primary outcome was mortality and secondary outcomes reflected routinely collected and patient-centered measures; feasibility measures were also collected. Effect estimates were pooled using random-effects models or narratively synthesized. Risk of bias was assessed.Seventy studies were included; 45 contributed to meta-analyses. Frailty was defined using 35 different instruments; five were meta-analyzed, with the Fried Phenotype having the largest number of studies. Most strongly associated with: mortality and nonfavorable discharge was the Clinical Frailty Scale (odds ratio, 4.89; 95% CI, 1.83 to 13.05 and odds ratio, 6.31; 95% CI, 4.00 to 9.94, respectively); complications was associated with the Edmonton Frail Scale (odds ratio, 2.93; 95% CI, 1.52 to 5.65); and delirium was associated with the Frailty Phenotype (odds ratio, 3.79; 95% CI, 1.75 to 8.22). The Clinical Frailty Scale had the highest reported measures of feasibility.Clinicians should consider accuracy and feasibility when choosing a frailty instrument. Strong evidence in both domains support the Clinical Frailty Scale, while the Fried Phenotype may require a trade-off of accuracy with lower feasibility.

Introduction Urinary symptoms are associated with an increased risk of falls, but few studies have focused on patients with overactive bladder (OAB). This study aimed to synthesize estimates of the risk of falls and fractures in patients with OAB. Methods Medline, EMBASE, the Cumulative Index to Nursing and Allied Health Literature, and Scopus were systematically searched for observational studies that focused on patients with OAB. When available, data from a non-OAB comparison sample were included. Double independent review and data extraction were performed. Falls and fractures data were summarized by unadjusted and adjusted risks, and percent attributable risk (PAR) of falls and fractures associated with OAB. Results Fifteen studies were included in the analyses. The proportion of patients with OAB experiencing at least one fall over a year ranged from 18.9% to 50.0%, and the proportion of patients with OAB experiencing recurrent or serious falls ranged from 10.2% to 56.0%. In studies that included a non-OAB comparison sample, a higher risk of falls was observed in patients with OAB compared to those without. A significantly increased (1.3- to 2.3-fold) adjusted OAB-associated risk of falls was reported, while unadjusted PARs for OAB associated falls ranged from 3.7% to 15.5%. Risk was higher among women and those 65 years of age or older. While analysis of fractures showed elevated point estimates, most studies were underpowered to detect a statistically significant difference between groups. Conclusions Evidence from the published literature clearly demonstrates the importance of OAB and its symptoms as risk factors for falls and fractures. Funding Astellas. Electronic supplementary material The online version of this article (10.1007/s12325-018-0796-8) contains supplementary material, which is available to authorized users.

Objectives\ud Methotrexate is commonly used to treat patients with inflammatory arthritis. A key role of a rheumatology nurse is to educate patients on how to take this drug safely prior to the commencement of treatment. The objective of the present study was to explore the experiences of rheumatology nurses conducting this role, focusing on the content of the consultation and training received to perform the role.\ud \ud Methods\ud A qualitative phenomenological approach was used. Six semi‐structured interviews were performed with nurses from two hospitals who regularly counsel patients prior to starting methotrexate. The interviews were thematically analysed by two researchers and themes extracted.\ud \ud Results\ud Four main themes were identified: (a) using written information to structure the content of the consultation; (b) patients have different information needs; (c) time pressures; and (d) training and evolution of practice. All participants described a lack of confidence when they first started counselling patients commencing methotrexate, with a wide variation in training. Participants reported that patients required different information depending on whether they were commencing this agent on its own or in combination with other drugs. All participants experienced some time pressure.\ud \ud Conclusions\ud Participants reported that the majority of the consultation focused on conveying information, with little opportunity for patient interaction and questions. We suggest that there is a clear need for further exploration of these consultations, to identify possible training needs. Participants also used standard written information to guide both the structure and content of the consultation limiting patients’; opportunities to ask questions.

It is unknown which respiratory muscles are mainly activated by respiratory muscle training. This study evaluated Inspiratory Pressure Threshold Loading (IPTL), Inspiratory Flow Resistive Loading (IFRL) and Voluntary Isocapnic Hyperpnea (VIH) with regard to electromyographic (EMG) activation of the sternocleidomastoid muscle (SCM), parasternal muscles (PARA) and the diaphragm (DIA) in randomized order. Surface EMG were analyzed at the end of each training session and normalized using the peak EMG recorded during maximum inspiratory maneuvers (Sniff nasal pressure: SnPna, maximal inspiratory mouth occlusion pressure: PImax). 41 healthy participants were included. Maximal activation was achieved for SCM by SnPna; the PImax activated predominantly PARA and DIA. Activations of SCM and PARA were higher in IPTL and VIH than for IFRL (p

A 61-year-old man presented to the ENT emergency clinic with a history of unilateral facial nerve palsy occurring shortly after each dose of the Pfizer-BioNTech COVID-19 vaccine. The first episode developed 5 hours after administration of the first dose and the second 2 days after administration of the second dose. Investigations at initial presentation to the emergency department were unremarkable, and the patient was diagnosed with Bell’s palsy on both occasions. We describe the first case of Bell’s palsy occurring after each dose of any UK-approved COVID-19 vaccine. Single episodes of unilateral facial nerve palsies have been reported in clinical trials and in subsequent case reports. There has been no evidence, however, of an episode after each dose. We also describe the earliest onset of symptoms from timing of administration of the vaccine, further suggesting the Bell’s palsy was associated with the vaccine.

To compare healthcare costs and resource utilization in patients with overactive bladder (OAB) in the US who switch from mirabegron to onabotulinumtoxinA (onabotA) with those who persist on mirabegron.A retrospective observational claims analysis of the OptumHealth Administrative Claims database conducted between April 1, 2012 and September 30, 2015 used medical and pharmacy claims to identify patients with at least one OAB diagnosis who switched from mirabegron to onabotA (onabotA group) or persisted on mirabegron for at least 180 days (mirabegron persisters). Propensity score weighting was used to balance baseline characteristics that were associated with increased healthcare expenditures across treatment groups. Multivariate analyses assessed the impact of switching and persistence on all-cause and OAB-related healthcare costs and resource utilization in the year following each patient's index date.In total, 449 patients were included in this study: 54 patients were included in the onabotA group, and 395 patients were included in the mirabegron persister group. Compared with the mirabegron persister patients, the onabotA patients observed significantly higher OAB-related total costs ($5,504 vs $1,772, p .001), OAB-related medical costs ($5,033 vs $351, p .001), sacral neuromodulation costs ($865 vs $60, p = .017), and outpatient costs ($17,385 vs $9,035, p = .009), and more OAB-related medical visits (6.0 vs 1.9, p .001). OnabotA patients had lower OAB-related prescription costs ($470 vs $1,421, p .001) and fewer OAB-related pharmacy claims (1.6 vs 5.0, p .001). There were no significant differences in all-cause total medical or prescription costs.This study was a retrospective analysis using claims data that only included patients with commercial health coverage or Medicare supplemental coverage. Accuracy of the diagnosis codes and the generalizability of the results to other OAB populations are limited. The study was not designed to determine the impact of OAB treatments on the economic outcomes examined.OAB patients who persisted on mirabegron treatment for at least 180 days had lower OAB-related healthcare costs and resource utilization compared with those who switched to onabotA.