A cost analysis of treating postoperative periprosthetic femoral fractures following hip replacement surgery in a UK tertiary referral centre.

AIM: This study aims to evaluate costs associated with periprosthetic femoral fracture (PFF) treatment at a UK tertiary referral centre. METHODS: This study included 128 consecutive PFFs admitted from 02/04/2014-19/05/2020. Financial data were provided by Patient Level Information and Costing Systems. Primary outcomes were median cost and margin. Secondary outcomes were length of stay, blood transfusion, critical care, 30-day readmission, 2-year local complication, 2-year systemic complication, 2-year reoperation and 30-day mortality rates. Statistical comparisons were made between treatment type. Statistical significance was set at p<0.05. RESULTS: Across the cohort, median cost was £15,644.00 (IQR £11,031.00-£22,255.00) and median loss was £3757.50 (£599.20-£8296.20). The highest costs were ward stay (£3994.00, IQR £1,765.00-£7,013.00), theatre utilisation (£2962.00, IQR £0.00-£4,286.00) and overheads (£1705.10, IQR £896.70-£2432.20). Cost (£17,455.00 [IQR, £13,194.00-£23,308.00] versus £7697.00 [IQR £3871.00-£10,847.00], p<0.001) and loss (£4890.00 [IQR £1308.00-£10,009.00] versus £1882.00 [IQR £313.00-£3851.00], p = 0.02) were greater in the operative versus the nonoperative group. There was no difference in cost (£17,634.00 [IQR £12,965.00-£22,958.00] versus £17,399.00 [IQR £13,394.00-£23,404.00], p = 0.98) or loss (£5374.00 [IQR £1950.00-£10,143.00] versus £3860.00 [IQR -£95.50-£7601.00], p = 0.21) between the open reduction and internal fixation (ORIF) and revision groups. More patients required blood transfusion in the operative versus the nonoperative group (17 [17.9%] versus 0 [0.0%], p = 0.009). There was no difference in any clinical outcome between the ORIF and revision groups (p>0.05). CONCLUSION: PFF treatment costs are high with inadequate reimbursement from NHS tariff. Work is needed to address this disparity and reduce hospital costs. Cost should not be used to decide between ORIF and revision surgery.

Associations with baseline visual acuity in 12,414 eyes starting treatment for neovascular AMD.

AIMS: To determine baseline visual acuity before the start of treatment for neovascular age-related macular degeneration (AMD), compare median and visual acuity states between treatment sites and investigate the association of socio-demographic and clinical characteristics with baseline acuity. METHODS: Anonymised demographic and clinical data, collected as part of routine clinical care, were extracted from electronic medical records at treating National Health Service (NHS) Trusts. Analyses were restricted to eyes with baseline visual acuity recorded at treatment initiation. Associations with baseline acuity were investigated using multivariate linear regression. RESULTS: Analysis included 12,414 eyes of 9116 patients at 13 NHS Trusts. Median baseline acuity was LogMAR 0.46 (interquartile range = 0.26-0.80) and 34.5% of eyes had good acuity, defined as LogMAR ≤0.3. Baseline acuity was positively associated with second-treated eye status, younger age, lower socio-economic deprivation, independent living, and female sex. There was little evidence of association between baseline acuity and distance to the nearest treatment centre, systemic or ocular co-morbidity. Despite case-mix adjustments, there was evidence of significant variation of baseline visual acuity between sites. CONCLUSIONS: Despite access to publicly funded treatment within the NHS, variation in visual acuity at the start of neovascular AMD treatment persists. Identifying the characteristics associated with poor baseline acuity, targeted health awareness campaigns, professional education, and pathway re-design may help to improve baseline acuity, the first eye gap, and visual acuity outcomes.

Associations with visual acuity outcomes after 12 months of treatment in 9401 eyes with neovascular AMD.

OBJECTIVE: To record visual acuity outcomes after 12 months of treatment for neovascular age-related macular degeneration (NvAMD), investigate variation between sites and explore associations with baseline characteristics and care processes. METHODS AND ANALYSIS: Anonymised demographic and clinical data were extracted from electronic medical records at treating National Health Service (NHS) Trusts. Associations with acuity outcomes were investigated using multivariate linear and logistic regression. RESULTS: Analysis included 9401 eyes (7686 patients) treated at 13 NHS Trusts. From baseline to month 12, median acuity improved from LogMAR 0.50 (IQR 0.30-0.80) to 0.40 (0.22-0.74) and the proportion of eyes with LogMAR ≥0.3 increased from 34.5% to 39.8%. Baseline visual acuity was the strongest predictor of visual acuity outcomes. For each LogMAR 0.1 worsening of baseline acuity, the acuity at 12 months was improved by LogMAR 0.074 (95% CI 0.073 to 0.074) and the odds of a 'poor' acuity outcome was multiplied by 1.66 (95% CI 1.61 to 1.70). Younger age, independent living status, lower socioeconomic deprivation, timely loading phase completion and higher number of injections were associated with better acuity outcomes. Despite case-mix adjustments, there was evidence of significant variation in acuity outcomes between sites. CONCLUSIONS: Even after adjustment for other variables, variation in acuity outcomes after NvAMD treatment within the NHS remains. Meaningful comparison of outcomes between different providers requires adjustment for a range of baseline characteristics, not visual acuity alone. Identifying best practice at sites with better outcomes and adapting local care processes are required to tackle this health inequality.

New Ameloblastoma Cell Lines Enable Preclinical Study of Targeted Therapies.

Ameloblastoma (AB) is an odontogenic tumor that arises from ameloblast-lineage cells. Although relatively uncommon and rarely metastatic, AB tumors are locally invasive and destructive to the jawbone and surrounding structures. Standard-of-care surgical resection often leads to disfigurement, and many tumors will locally recur, necessitating increasingly challenging surgeries. Recent genomic studies of AB have uncovered oncogenic driver mutations, including in the mitogen-activated protein kinase (MAPK) and Hedgehog signaling pathways. Medical therapies targeting those drivers would be a highly desirable alternative or addition to surgery; however, a paucity of existing AB cell lines has stymied clinical translation. To bridge this gap, here we report the establishment of 6 new AB cell lines-generated by "conditional reprogramming"-and their genomic characterization that reveals driver mutations in FGFR2, KRAS, NRAS, BRAF, PIK3CA, and SMO. Furthermore, in proof-of-principle studies, we use the new cell lines to investigate AB oncogene dependency and drug sensitivity. Among our findings, AB cells with KRAS or NRAS mutation (MAPK pathway) are exquisitely sensitive to MEK inhibition, which propels ameloblast differentiation. AB cells with activating SMO-L412F mutation (Hedgehog pathway) are insensitive to vismodegib; however, a distinct small-molecule SMO inhibitor, BMS-833923, significantly reduces both downstream Hedgehog signaling and tumor cell viability. The novel cell line resource enables preclinical studies and promises to speed the translation of new molecularly targeted therapies for the management of ameloblastoma and related odontogenic neoplasms.

Facilitators and barriers of preconception care in women with inflammatory bowel disease and rheumatic diseases: an explorative survey study in a secondary and tertiary hospital.

BACKGROUND: Preconception care (PCC) is care prior to conception to optimize parental health, and health of the future child, through biomedical and behavioral changes. Providing PCC to all women with a wish to conceive will improve perinatal health. PCC is especially important for women with a chronic disease, such as inflammatory bowel disease (IBD) and rheumatic diseases (RD). At present PCC is not part of routine care for these women. The aim of this study is to identify facilitators and barriers on a patient and professional level regarding the provision of PCC in women with IBD and RD. METHODS: An explorative survey study among women with IBD and RD, their treating physicians and obstetric professionals was performed. Patients with a wish to conceive, pregnant women or those with a recent pregnancy (< 1 year ago) visiting the outpatient clinic of a secondary and tertiary hospital and involved physicians and obstetric professionals were eligible. RESULTS: A total of 71% of the IBD patients (n = 22/31) and 35% of the RD patients (n = 20/58) received a PCC consultation. PCC consultation was considered easy to enter, short in time and patients felt comfortable. Patients (71% IBD; 62% RD) preferred a personal PCC consultation with their disease specific specialist together with an obstetrician. Patients specifically wanted to receive information about the safety of medication use and disease activity following delivery. Of the included healthcare professionals 67% (n = 31) agreed PCC was applicable to their patients. Main barrier to providing PCC was lack of time and unavailability of professionals. In total 41% (n = 16) of obstetric professionals felt they had the knowledge and skills to provide PCC compared to 33% (n = 1) and 75% (n = 3) of gastroenterologists and rheumatologists, respectively. CONCLUSION: Lack of awareness and urgency for the effectuation can be seen as important barriers for implementation of PCC. Due to the explorative nature generalisation of the results is not allowed. In the future, adaptation of the curricula of healthcare professionals by implementing interventions for pregnancy planning and preparation will generate awareness. Modelling of the impact of PCC might prove useful in resolving the lack of urgency for PCC realization.

Complications and mortality associated with olecranon fractures in the elderly: a retrospective cohort comparison from a large level one trauma centre.

Background: Olecranon fractures in the elderly have an increasing incidence. This retrospective study aims to identify the complications and survivorship of these patients. Methods: All patients >70 years old treated for an olecranon fracture at our institution were identified between 2007 and 2019. Loss of reduction and/or metalwork loosening was recorded. Also noted were wound healing problems, deep/superficial infections, and any subsequent treatment including return to surgery and/or removal of metalwork. Results: From a total of 177 cases, 28 presented with concomitant fractures (16%), half of which were hip fractures. The largest treatment group underwent tension band wiring (n = 82, 46%, mean age 80.8 yrs). Twenty-one of these suffered failure of fixation (26%), all requiring return to surgery. The second largest treatment group underwent plating (n = 50 28%, mean age 80.1 yrs). Four of these suffered failure of fixation (8%), all requiring return to surgery. Forty-four patients were treated non-operatively (25%, mean age 83.8 yrs). Two patients suffered other complications (4.5%). Overall 1 year survivorship was 0.82. Discussion: Olecranon fractures in the elderly have higher than expected 1 year mortality rates. Operative management results in high complication rates, often requiring return to surgery for metalwork problems. Significant consideration of treatment options is required in this cohort.

Association of multimorbidity and changes in health-related quality of life following myocardial infarction: a UK multicentre longitudinal patient-reported outcomes study.

BACKGROUND: Multimorbidity is prevalent for people with myocardial infarction (MI), yet previous studies investigated single-health conditions in isolation. We identified patterns of multimorbidity in MI survivors and their associations with changes in HRQoL. METHODS: In this national longitudinal cohort study, we analysed data from 9566 admissions with MI from 77 National Health Service hospitals in England between 2011 and 2015. HRQoL was measured using EuroQol 5 dimension (EQ5D) instrument and visual analogue scale (EQVAS) at hospitalisation, 6, and 12 months following MI. Latent class analysis (LCA) of pre-existing long-term health conditions at baseline was used to identify clusters of multimorbidity and associations with changes in HRQoL quantified using mixed effects regression analysis. RESULTS: Of 9566 admissions with MI (mean age of 64.1 years [SD 11.9], 7154 [75%] men), over half (5119 [53.5%] had multimorbidities. LCA identified 3 multimorbidity clusters which were severe multimorbidity (591; 6.5%) with low HRQoL at baseline (EQVAS 59.39 and EQ5D 0.62) which did not improve significantly at 6 months (EQVAS 59.92, EQ5D 0.60); moderate multimorbidity (4301; 47.6%) with medium HRQoL at baseline (EQVAS 63.08, EQ5D 0.71) and who improved at 6 months (EQVAS 71.38, EQ5D 0.76); and mild multimorbidity (4147, 45.9%) at baseline (EQVAS 64.57, EQ5D 0.75) and improved at 6 months (EQVAS 76.39, EQ5D 0.82). Patients in the severe and moderate groups were more likely to be older, women, and presented with NSTEMI. Compared with the mild group, increased multimorbidity was associated with lower EQ-VAS scores (adjusted coefficient: -5.12 [95% CI -7.04 to -3.19] and -0.98 [-1.93 to -0.04] for severe and moderate multimorbidity, respectively. The severe class was more likely than the mild class to report problems in mobility, OR 9.62 (95% confidence interval: 6.44 to 14.36), self-care 7.87 (4.78 to 12.97), activities 2.41 (1.79 to 3.26), pain 2.04 (1.50 to 2.77), and anxiety/depression 1.97 (1.42 to 2.74). CONCLUSIONS: Among MI survivors, multimorbidity clustered into three distinct patterns and was inversely associated with HRQoL. The identified multimorbidity patterns and HRQoL domains that are mostly affected may help to identify patients at risk of poor HRQoL for which clinical interventions could be beneficial to improve the HRQoL of MI survivors. TRIAL REGISTRATION: ClinicalTrials.gov NCT01808027 and NCT01819103.

Factors associated with non-essential workplace attendance during the COVID-19 pandemic in the UK in early 2021: evidence from cross-sectional surveys.

OBJECTIVES: Working from home where possible is important in reducing the spread of COVID-19. In early 2021, a quarter of people in England who believed they could work entirely from home reported attending their workplace. To inform interventions to reduce this, this study examined associated factors. STUDY DESIGN: Data from the ongoing COVID-19 Rapid Survey of Adherence to Interventions and Responses survey series of nationally representative samples of people in the UK aged 16+ years in January-February 2021 were used. METHODS: The study sample was 1422 respondents who reported that they could work completely from home. The outcome measure was self-reported workplace attendance at least once during the preceding week. Factors of interest were analysed in three blocks: 1) sociodemographic variables, 2) variables relating to respondents' circumstances and 3) psychological variables. RESULTS: 26.8% (95% confidence interval [CI] = 24.5%-29.1%) of respondents reported having attended their workplace at least once in the preceding week. Sociodemographic variables and living circumstances significantly independently predicted non-essential workplace attendance: male gender (odds ratio [OR] = 1.85, 95% CI = 1.33-2.58); dependent children in the household (OR = 1.65, 95% CI = 1.17-2.32); financial hardship (OR = 1.14, 95% CI = 1.08-1.21); lower socio-economic grade (C2DE; OR = 1.65, 95% CI = 1.19-2.53); working in sectors such as health or social care (OR = 4.18, 95% CI = 2.56-6.81), education and childcare (OR = 2.45, 95% CI = 1.45-4.14) and key public service (OR = 3.78, 95% CI = 1.83-7.81) and having been vaccinated (OR = 2.08, 95% CI = 1.33-3.24). CONCLUSIONS: Non-essential workplace attendance in the UK in early 2021 during the COVID-19 pandemic was significantly independently associated with a range of sociodemographic variables and personal circumstances. Having been vaccinated, financial hardship, socio-economic grade C2DE, having a dependent child at home and working in certain key sectors were associated with higher likelihood of workplace attendance.

"Strong Teeth": an early-phase study to assess the feasibility of an oral health intervention delivered by dental teams to parents of young children.

BACKGROUND: Tooth decay (caries) is a significant health burden in young children. There is strong evidence for the benefits of establishing appropriate home-based oral health behaviours in early childhood. Dental teams are well placed to provide this information and there is clear advice on what oral health information should be given to parents. However, research has shown that there is limited guidance, training and resources on how dental teams should deliver this advice. "Strong Teeth" is a complex oral health intervention, using evidence-based resources and training underpinned by behaviour change psychology, to support behaviour change conversations in dental practice. This early phase evaluation aims to assess the feasibility of this intervention, prior to a full-scale trial. METHODS: The study recruited 15 parents of children aged 0-2-years-old and 21 parents of children aged 3-5 years old, from five NHS dental practices across West Yorkshire. Participant demographics, self-reported brushing behaviours, dietary habits, a dental examination and three objective measures of toothbrushing were collected in a home-setting at baseline, then at 2-weeks and 2-months post-intervention. Recruitment, retention and intervention delivery were analysed as key process outcomes. Brushing habits were compared to national toothbrushing guidelines - the Delivering Better Oral Health toolkit (Public Health England). RESULTS: Strong Teeth was feasible to deliver in a General Dental Practice setting in 94% of cases. Feasibility of recruitment (37%) exceeded progression criterion, however retention of participants (75%) was below the progression criterion for the 0-2 age group. More than half of children recruited aged 3-5-years had caries experience (52%). Total compliance to toothbrushing guidance at baseline was low (28%) and increased after the intervention (52%), an improvement that was statistically significant. Dietary habits remained largely unchanged. Plaque scores significantly decreased in the 3-5-year-olds and toothbrushing duration increased in all age groups. CONCLUSION: "Strong Teeth" intervention delivery and data collection in the home setting was feasible. There was a positive indication of impact on reported toothbrushing behaviours. Some amendments to study design, particularly relating to the inclusion of the 0-2-year-old group, should be considered before progression to a full trial. Trial registration ISRCTN Register: ISRCTN10709150. Registered retrospectively 24/7/2019.

The impact of penicillin allergy de-labelling on the WHO AWaRe antibiotic categories: a retrospective cohort study.

BACKGROUND: The WHO's AWaRe classification categorizes antibiotics into three stewardship groups: Access, Watch and Reserve. The Access group includes antibiotics with lower resistance potential than antibiotics in the other two groups. The UK five-year AMR strategy has set targets for reducing non-Access antibiotic use. The majority of penicillins are in the Access group and therefore patients with a penicillin allergy record are likely to receive more non-Access antibiotics. This study aimed to quantify the impact of penicillin allergy records on non-Access antibiotic prescribing and to estimate potential reductions in non-Access antibiotic use through penicillin allergy de-labelling. METHODS: Inpatients of a 750-patient-bed UK district general hospital in England prescribed antibiotics between 1st April 2018 and 31st March 2019 were included. Variables included: age, sex, co-morbidity, infection treated, antibiotic usage, hospital length of stay, penicillin allergy status. Multivariable logistic regression was used to explore the association between patient characteristics and their receipt of antibiotics in the Access and non-Access groups. RESULTS: A total of 67,059 antibiotic prescriptions for 23,356 inpatients were analysed. Penicillin allergy records were present in 14.3% of hospital admissions. Patients with a penicillin allergy record were around four times more likely (odds ratio = 4.7) to receive an antibiotic from the non-Access groups (i.e. Reserve and Watch groups). We estimate de-labelling 50% of hospital inpatients with a penicillin allergy record could reduce non-Access antibiotic use by 5.8% and total antibiotic use by 0.86%. CONCLUSION: Penicillin allergy records are associated with non-Access antibiotic prescribing. Penicillin allergy de-labelling has potential to reduce non-Access antibiotic use.

Modeling human peri-implantation placental development and function†.

It is very difficult to gain a better understanding of the events in human pregnancy that occur during and just after implantation because such pregnancies are not yet clinically detectable. Animal models of human placentation are inadequate. In vitro models that utilize immortalized cell lines and cells derived from trophoblast cancers have multiple limitations. Primary cell and tissue cultures often have limited lifespans and cannot be obtained from the peri-implantation period. We present here two contemporary models of human peri-implantation placental development: extended blastocyst culture and stem-cell derived trophoblast culture. We discuss current research efforts that employ these models and how such models might be used in the future to study the "black box" stage of human pregnancy.

Survivorship of fixed vs mobile bearing unicompartmental knee replacement: A systematic review and meta-analysis of sixty-four studies and National Joint Registries.

BACKGROUND: Unicompartmental knee replacement (UKR) prostheses can use fixed (FB) or mobile bearing (MB) constructs. We compared survivorship and failure modes of both designs. METHODS: The inclusion criteria were studies published between 2005 and 2020 with minimum average follow-up of five years reporting the survival and/or number of revisions of specific designs in medial and lateral UKRs. Pooled rate of revision per 100 patient years (PTIR) was estimated using a random effects model. RESULTS: Seventy cohorts of 17,405 UKRs with weighted mean follow-up of 7.3 years (0.1-29.4 years) were included. A total of 170,923 UKRs were identified in registry reports at a weighted mean implant survival time of 15.4 years. PTIR in MB UKR versus FB UKR was similar [1.45 vs 1.40, (p = 0.8)]. In cohort studies, the overall PTIR for MB was also similar to FB [1.03 vs 0.78, (p = 0.1)]. For medial UKR, the PTIR for MB was marginally greater but not significantly different to FB [0.96 vs 0.81, (p = 0.3)], whilst for lateral UKR, the PTIR for MB was significantly worse than for FB [2.20 vs 0.72, (p < 0.01)]. Polyethylene wear is more common in FB implants, whilst MB implants are revised more often for bearing dislocation. CONCLUSIONS: Overall implant survival in mid- to long-term studies is similar for MB versus FB medial UKRs. MB have a four-fold higher risk of revision in comparison to FB when used for lateral UKR.

Risk Factors for Revision of Polished Taper-Slip Cemented Stems for Periprosthetic Femoral Fracture After Primary Total Hip Replacement: A Registry-Based Cohort Study from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

BACKGROUND: Total hip replacement (THR) with a cemented polished taper-slip (PTS) femoral stem has excellent long-term results but is associated with a higher postoperative periprosthetic femoral fracture (PFF) risk compared with composite beam stems. This study aimed to identify risk factors associated with PFF revision following THR with PTS stems. METHODS: In a retrospective cohort study, 299,019 primary THRs using PTS stems from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) were included, with a median follow-up of 5.2 years (interquartile range [IQR], 3.1 to 8.2 years). The adjusted hazard ratio (HR) of PFF revision was estimated for each variable using multivariable Cox survival regression analysis. RESULTS: Of 299,019 THR cases, 1,055 underwent revision for PFF at a median time of 3.1 years (IQR, 1.0 to 6.1 years). The mean age (and standard deviation) was 72 ± 9.7 years, 64.3% (192,365 patients) were female, and 82.6% (247,126 patients) had an American Society of Anesthesiologists (ASA) class of 1 or 2. Variables associated with increased PFF were increasing age (HR, 1.02 per year), intraoperative fracture (HR, 2.57 [95% confidence interval (CI), 1.42 to 4.66]), ovaloid (HR, 1.96 [95% CI, 1.22 to 3.16]) and round cross-sectional shapes (HR, 9.58 [95% CI, 2.29 to 40.12]), increasing stem offset (HR, 1.07 per millimeter), increasing head size (HR, 1.04 per millimeter), THR performed from 2012 to 2016 (HR, 1.45 [95% CI, 1.18 to 1.78]), cobalt-chromium stem material (HR, 6.7 [95% CI, 3.0 to 15.4]), and cobalt-chromium stems with low-viscosity cement (HR, 22.88 [95% CI, 9.90 to 52.85]). Variables associated with a decreased risk of PFF revision were female sex (HR, 0.52 [95% CI, 0.45 to 0.59]), increasing stem length (HR, 0.97 per millimeter), and a ceramic-on-polyethylene bearing (HR, 0.55 [95% CI, 0.36 to 0.85]). CONCLUSIONS: Increased risk of PFF revision was associated with PTS stems that are short, have high offset, are used with large femoral heads, are made of cobalt-chromium, or have ovaloid or round cross-sectional shapes. Large increases in PFF risk were associated with cobalt-chromium stems used with low-viscosity cement. Further study is required to confirm causation. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Increased Discontinuation Rates of Anti-TNF Therapy in Elderly Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: There is paucity of data on safety and efficacy of anti-tumour necrosis factor [TNF] in elderly inflammatory bowel disease [IBD] patients. We aimed to compare the long-term treatment failure rates and safety of a first anti-TNF agent in IBD patients between different age groups [<40 years/40-59 years/≥60 years]. METHODS: IBD patients who started a first anti-TNF agent were identified through IBDREAM, a multicentre prospective IBD registry. Competing risk regression was used to study treatment failure, defined as time to drug discontinuation due to adverse events [AEs] or lack of effectiveness, with discontinuation due to remission as a competing risk. RESULTS: A total of 895 IBD patients were included; 546 started anti-TNF at age <40 [61.0%], 268 at age 40-59 [29.9%], and 81 at age ≥60 [9.1%]. Treatment failure rate was higher in the two older groups (subhazard rate [SHR] age ≥60 1.46, SHR age 40-59 1.21; p = 0.03). The SHR in the elderly [>60] was 1.52 for discontinuation due to AEs and 1.11 for lack of effectiveness. Concomitant thiopurine use was associated with a lower treatment failure rate (SHR 0.78, 95% confidence interval [CI] 0.62-0.98, p = 0.031). Serious adverse event [SAE] rate, as well as serious infection rate, were significantly higher in elderly IBD patients [61.2 versus 16.0 and 12.4 per 1000 patient-years, respectively] whereas the malignancy rate was low in all age groups. CONCLUSIONS: Elderly IBD patients starting a first anti-TNF agent showed higher treatment failure rates, but concomitant thiopurine use at baseline was associated with lower failure rates. Elderly IBD patients demonstrated higher rates of SAEs and serious infections.

A calcar collar is protective against early periprosthetic femoral fracture around cementless femoral components in primary total hip arthroplasty: a registry study with biomechanical validation.

AIMS: The aim of this study was to estimate the 90-day risk of revision for periprosthetic femoral fracture associated with design features of cementless femoral stems, and to investigate the effect of a collar on this risk using a biomechanical in vitro model. MATERIALS AND METHODS: A total of 337 647 primary total hip arthroplasties (THAs) from the United Kingdom National Joint Registry (NJR) were included in a multivariable survival and regression analysis to identify the adjusted hazard of revision for periprosthetic fracture following primary THA using a cementless stem. The effect of a collar in cementless THA on this risk was evaluated in an in vitro model using paired fresh frozen cadaveric femora. RESULTS: The prevalence of early revision for periprosthetic fracture was 0.34% (1180/337 647) and 44.0% (520/1180) occurred within 90 days of surgery. Implant risk factors included: collarless stem, non-grit-blasted finish, and triple-tapered design. In the in vitro model, a medial calcar collar consistently improved the stability and resistance to fracture. CONCLUSION: Analysis of features of stem design in registry data is a useful method of identifying implant characteristics that affect the risk of early periprosthetic fracture around a cementless femoral stem. A collar on the calcar reduced the risk of an early periprosthetic fracture and this was confirmed by biomechanical testing. This approach may be useful in the analysis of other uncommon modes of failure after THA. Cite this article: Bone Joint J 2019;101-B:779-786.

'Warning: allergic to penicillin': association between penicillin allergy status in 2.3 million NHS general practice electronic health records, antibiotic prescribing and health outcomes.

BACKGROUND: The prevalence of reported penicillin allergy (PenA) and the impact these records have on health outcomes in the UK general population are unknown. Without such data, justifying and planning enhanced allergy services is challenging. OBJECTIVES: To determine: (i) prevalence of PenA records; (ii) patient characteristics associated with PenA records; and (iii) impact of PenA records on antibiotic prescribing/health outcomes in primary care. METHODS: We carried out cross-sectional/retrospective cohort studies using patient-level data from electronic health records. Cohort study: exact matching across confounders identified as affecting PenA records. Setting: English NHS general practices between 1 April 2013 and 31 March 2014. Participants: 2.3 million adult patients. Outcome measures: prevalence of PenA, antibiotic prescribing, mortality, MRSA infection/colonization and Clostridioides difficile infection. RESULTS: PenA prevalence was 5.9% (IQR = 3.8%-8.2%). PenA records were more common in older people, females and those with a comorbidity, and were affected by GP practice. Antibiotic prescribing varied significantly: penicillins were prescribed less frequently in those with a PenA record [relative risk (RR)  = 0.15], and macrolides (RR = 4.03), tetracyclines (RR = 1.91) nitrofurantoin (RR = 1.09), trimethoprim (RR = 1.04), cephalosporins (RR = 2.05), quinolones (RR = 2.10), clindamycin (RR = 5.47) and total number of prescriptions were increased in patients with a PenA record. Risk of re-prescription of a new antibiotic class within 28 days (RR = 1.32), MRSA infection/colonization (RR = 1.90) and death during the year subsequent to 1 April 2013 (RR = 1.08) increased in those with PenA records. CONCLUSIONS: PenA records are common in the general population and associated with increased/altered antibiotic prescribing and worse health outcomes. We estimate that incorrect PenA records affect 2.7 million people in England. Establishing true PenA status (e.g. oral challenge testing) would allow more people to be prescribed first-line antibiotics, potentially improving health outcomes.

Prospective observational cohort study of the association between antiplatelet therapy, bleeding and thrombosis in patients with coronary stents undergoing noncardiac surgery.

BACKGROUND: The perioperative management of antiplatelet therapy in noncardiac surgery patients who have undergone previous percutaneous coronary intervention (PCI) remains a dilemma. Continuing dual antiplatelet therapy (DAPT) may carry a risk of bleeding, while stopping antiplatelet therapy may increase the risk of perioperative major adverse cardiovascular events (MACE). METHODS: Occurrence of Bleeding and Thrombosis during Antiplatelet Therapy In Non-Cardiac Surgery (OBTAIN) was an international prospective multicentre cohort study of perioperative antiplatelet treatment, MACE, and serious bleeding in noncardiac surgery. The incidences of MACE and bleeding were compared in patients receiving DAPT, monotherapy, and no antiplatelet therapy before surgery. Unadjusted risk ratios were calculated taking monotherapy as the baseline. The adjusted risks of bleeding and MACE were compared in patients receiving monotherapy and DAPT using propensity score matching. RESULTS: A total of 917 patients were recruited and 847 were eligible for inclusion. Ninety-six patients received no antiplatelet therapy, 526 received monotherapy with aspirin, and 225 received DAPT. Thirty-two patients suffered MACE and 22 had bleeding. The unadjusted risk ratio for MACE in patients receiving DAPT compared with monotherapy was 1.9 (0.93-3.88), P=0.08. There was no difference in MACE between no antiplatelet treatment and monotherapy 1.03 (0.31-3.46), P=0.96. Bleeding was more frequent with DAPT 6.55 (2.3-17.96) P=0.0002. In a propensity matched analysis of 177 patients who received DAPT and 177 monotherapy patients, the risk ratio for MACE with DAPT was 1.83 (0.69-4.85), P=0.32. The risk of bleeding was significantly greater in the DAPT group 4.00 (1.15-13.93), P=0.031. CONCLUSIONS: OBTAIN showed an increased risk of bleeding with DAPT and found no evidence for protective effects of DAPT from perioperative MACE in patients who have undergone previous PCI.

HMGA2 is regulated by LIN28 and BRCA1 in human placental cells.

The chromatin associated transcription factor HMGA2 is a downstream target of let-7 miRNAs and binds to chromatin to regulate gene expression. Inhibition of let-7 miRNAs by RNA-binding proteins LIN28A and LIN28B is necessary during early embryogenesis to ensure stable expression of HMGA2. In addition to LIN28, HMGA2 is regulated by a BRCA1/ZNF350/CtIP repressor complex. In normal tissues, the BRCA1/ZNF350/CtIP complex binds to the HMGA2 promoter to prevent transcription. However, in many cancers the oncomiR miR-182 targets BRCA1, preventing BRCA1 translation and allowing for increased HMGA2. Little is known about the regulation of HMGA2 during early placental development; therefore, we hypothesized that both LIN28 and BRCA1 can regulate HMGA2 in placental cells. Using siRNA and CRISPR gene editing techniques, we found that knockdowns of both LIN28A and LIN28B increase HMGA2 levels in ACH-3P cells. These cells also demonstrated deficiencies in cell differentiation, seemingly differentiating solely towards the syncytiotrophoblast sublineage, secreting higher amounts of hCG, and displaying upregulated ERVW-1. Additionally, we found that a knockout of both LIN28A and LIN28B caused a significant increase of miR-182 and a decrease in BRCA1 allowing HMGA2 mRNA levels to increase and protein levels to remain the same. Using chromatin immunoprecipitation, we saw binding of the BRCA1 repressor complex to HMGA2. We also saw a decrease in binding to HMGA2's promoter in the LIN28A/B knockout cells. These findings suggest a novel role for BRCA1 during early human placental development.

Impact of penicillin allergy records on carbapenem prescribing: an observational retrospective cohort study.

Penicillin allergy labels have been associated with second-line antibiotic prescribing. This study measured the impact of penicillin allergy labels on meropenem prescribing. Rates of meropenem prescribing were compared between patients with a penicillin allergy record and patients without such a record. Potential confounders were also collected (i.e. age, sex and co-morbidities). Of the 21,272 patients with no penicillin allergy, 225 (1.06%) were prescribed meropenem, whereas of the 3443 patients with penicillin allergy, 240 (6.97%) were prescribed meropenem. Meropenem prescribing is associated with a patient's penicillin allergy record. Given that many penicillin allergy records are incorrect, addressing spurious penicillin allergy labels may reduce meropenem prescribing.

Less absorbed solar energy and more internal heat for Jupiter.

The radiant energy budget and internal heat are fundamental properties of giant planets, but precise determination of these properties remains a challenge. Here, we report measurements of Jupiter's radiant energy budget and internal heat based on Cassini multi-instrument observations. Our findings reveal that Jupiter's Bond albedo and internal heat, 0.503 ± 0.012 and 7.485 ± 0.160 W m-2 respectively, are significantly larger than 0.343 ± 0.032 and 5.444 ± 0.425 Wm-2, the previous best estimates. The new results help constrain and improve the current evolutionary theories and models for Jupiter. Furthermore, the significant wavelength dependency of Jupiter's albedo implies that the radiant energy budgets and internal heat of the other giant planets in our solar system should be re-examined. Finally, the data sets of Jupiter's characteristics of reflective solar spectral irradiance provide an observational basis for the models of giant exoplanets.