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The aim of this paper is to describe and compare components of diagnostic delay (patient, primary care, referral, secondary care) for six cancers (breast, colorectal, lung, ovarian, prostate and non-Hodgkin's lymphoma), and to compare delays in patients who saw their GP prior to diagnosis with those who did not. Secondary data analysis of The National Survey of NHS Patients : Cancer was undertaken (65 192 patients). Breast cancer patients experienced the shortest total delays (mean 55.2 days), followed by lung (88.5), ovarian (90.3), non-Hodgkin's lymphoma (102.8), colorectal (125.7) and prostate (148.5). Trends were similar for all components of delay. Compared with patient and primary care delays, referral delays and secondary care delays were much shorter. Patients who saw their GP prior to diagnosis experienced considerably longer total diagnostic delays than those who did not. There were significant differences in all components of delay between the six cancers. Reducing diagnostic delays with the intention of increasing the proportion of early stage cancers may improve cancer survival in the UK, which is poorer than most other European countries. Interventions aimed at reducing patient and primary care delays need to be developed and their effect on diagnostic stage and psychological distress evaluated.

This paper aims to explore the relationship between sociodemographic factors and the components of diagnostic delay (total, patient and primary care, referral, secondary care) for these six cancers (breast, colorectal, lung, ovarian, prostate, or non-Hodgkin's lymphoma). Secondary analysis of patient-reported data from the ‘National Survey of NHS patients: Cancer’ was undertaken (65 192 patients). Data were analysed using univariate analysis and Generalised Linear Modelling. With regard to total delay, the findings from the GLM showed that for colorectal cancer, the significant factors were marital status and age, for lung and ovarian cancer none of the factors were significant, for prostate cancer the only significant factor was social class, for non-Hodgkin's lymphoma the only significant factor was age, and for breast cancer the significant factors were marital status and ethnic group. Where associations between any of the component delays were found, the direction of the association was always in the same direction (female subjects had longer delays than male subjects, younger people had longer delays than older people, single and separated/divorced people had longer delays than married people, lower social class groups had longer delays than higher social class groups, and Black and south Asian people had longer delays than white people). These findings should influence the design of interventions aimed at reducing diagnostic delays with the aim of improving morbidity, mortality, and psychological outcomes through earlier stage diagnosis.

Background Iron deficiency (ID) is common in patients with chronic kidney disease (CKD). Intravenous (IV) iron in heart failure leads to improvement in exercise capacity and improvement in quality-of-life measurements; however, data in patients with CKD are lacking. Methods The Iron and the Heart Study was a prospective double blinded randomised study in non-anaemic CKD stages 3b-5 patients with ID which investigated whether 1000 mg of IV iron (ferric derisomaltose (FDI)) could improve exercise capacity in comparison to placebo measured at 1 and 3 months post infusion. Secondary objectives included effects on haematinic profiles and haemoglobin, safety analysis and quality of life questionnaires (QoL). Results We randomly assigned 54 patients mean (SD) age for FDI ( n  = 26) 61.6 (10.1) years vs placebo ( n  = 28; 57.8 (12.9) years) and mean eGFR (33.2 (9.3) vs. 29.1 (9.6) ml/min/1.73m 2 ) at baseline, respectively. Adjusting for baseline measurements, six-minute walk test (6MWT) showed no statistically significant difference between arms at 1 month ( p  = 0.736), or 3 months ( p  = 0.741). There were non-significant increases in 6MWT from baseline to 1 and 3 months in the FDI arm. Haemoglobin (Hb) at 1 and 3 months remained stable. There were statistically significant increases in ferritin (SF) and transferrin saturation (TSAT) at 1 and 3 months ( p  < 0.001). There was a modest numerical improvement in QoL parameters. There were no adverse events attributable to IV iron. Conclusion This study demonstrated a short-term beneficial effect of FDI on exercise capacity, but it was not significant despite improvements in parameters of iron status, maintenance of Hb concentration, and numerical increases in functional capacity and quality of life scores. A larger study will be required to confirm if intravenous iron is beneficial in iron deficient non-anaemic non-dialysis CKD patients without heart failure to improve the 6MWT. Trial registration European Clinical Trials Database (EudraCT) No: 2014-004133-16 REC no: 14/YH/1209 Date First Registered: 2015-02-17 and date of end of trail 2015-05-23 Sponsor ref R1766 and Protocol No: IHI 141

Background Approximately one quarter of people with an intellectual disability (PwID) have epilepsy of whom nearly three-quarters are pharmaco-resistant. There are higher reported neuropsychiatric side-effects to anti-seizure medication (ASM) in this group. Levetiracetam (LEV) is a first-line ASM with a stronger association with neuropsychiatric symptoms for PwID than other ASMs. Brivaracetam (BRV) is a newer ASM. Recent studies suggest a beneficial effect of swapping people who experience neuropsychiatric events with LEV to BRV. However, there is limited evidence of this for PwID. This evaluation analyses real world outcomes of LEV to BRV swap for PwID compared to those without ID. Methods We performed a multicentre, retrospective review of clinical records. Demographic, clinical characteristics and reported adverse events of patients switched from LEV to BRV (2016–2020) were recorded at 3 months pre and 6- and 12-month post-BRV initiation. Outcomes were compared between PwID and those without and summarised using cross-tabulations and logistic regression models. A Bonferroni correction was applied. Results Of 77 participants, 46 had ID and 52% had a past psychiatric illness. 71% participants switched overnight from LEV to BRV. Seizure reduction of > 50% was seen in 40% patients. Psychiatric illness history was predictive of having neuropsychiatric side-effects with LEV but not BRV ( p  = 0.001). There was no significant difference for any primary outcomes between PwID versus without ID. Conclusions Switching from LEV to BRV appears as well tolerated and efficacious in PwID as those without ID with over 90% still on BRV after 12 months.

Purpose To determine the effect of oral acetazolamide on lowering the peak and duration of intraocular pressure (IOP) rise in glaucoma and glaucoma suspect patients, following intravitreal injection of ranibizumab for neovascular age-related macular degeneration. Methods The study was an open-label, parallel, randomised, controlled trial (EudraCT Number: 2010-023037-35). Twenty-four glaucoma or glaucoma suspect patients received either 500 mg acetazolamide or no treatment 60–90 min before 0.5 mg ranibizumab. The primary outcome measure was the difference in IOP immediately after injection (T0) and 5, 10, and 30 min following injection. ANCOVA was used to compare groups, adjusting for baseline IOP. The study was powered to detect a 9-mm Hg difference at T0. Results The IOP at T0 was 2.3 mm Hg higher in the non-treated group (mean 44.5 mm Hg, range (19–86 mm Hg)) compared with the treated group (mean 42.2 mm Hg, range (25–58 mm Hg)), but was not statistically significant after adjusting for baseline IOP ( P =0.440). At 30 min, IOP was 4.9 mm Hg higher in the non-treated group (mean 20.6 mm Hg, range (11–46 mm Hg)) compared with the treated group (mean 15.7 mm Hg, range (8–21 mm Hg)). This was statistically significant after adjusting for baseline IOP ( P =0.013). Conclusions Although the primary end points were not reached, 500 mg oral acetazolamide, 60–90 min before intravitreal injection, results in a statistically significant reduction in IOP at 3O min post injection. Prophylactic treatment may be considered as an option to minimise neuro-retinal rim damage in high-risk glaucoma patients who are most vulnerable to IOP spikes and undergoing repeated intravitreal injections of ranibizumab.

Background Hip fracture is a procedure with high mortality and complication rates, and there exists a group especially at risk of these outcomes identified by their Nottingham Hip Fracture Score (NHFS). Meta-analysis suggests a possible benefit to this patient group from intravascular volume optimisation. We investigated whether intraoperative fluid and blood pressure optimisation improved complications in this group. Methods Patients with a NHFS ≥ 5 were enrolled into this multicentre observer-blinded randomised control trial. Patients were allocated to either standard care or a combination of fluid optimisation and blood pressure control using a non-invasive system. The primary outcome was the number of patients with one or more complications in each group. Secondary outcomes included hospital length of stay (LOS), incidence of hypotension and fluid and vasopressor usage. Results Forty-six percent of patients in the intervention group suffered one or more complications compared to the 51% in the control group (OR 0.82 (95% CI 0.49–1.36)). Per-protocol analysis improved the OR to 0.73 (95% CI 0.43–1.24). Median LOS was the same between both groups; however, the mean LOS on a per-protocol analysis was longer in the control group compared to the intervention group (23.2 (18.0) days vs. 18.5 (16.5), p  = 0.047). Conclusions Haemodynamic optimisation including blood pressure management in high-risk patients undergoing repair of a hip fracture did not result in a statistically significant reduction in complications; however, a potential reduction in length of stay was seen. Trial registration A randomised trial of non-invasive cardiac output monitoring to guide haemodynamic optimisation in high risk patients undergoing urgent surgical repair of proximal femoral fractures (ClearNOF trial NCT02382185 ).

Background Interventions designed to support children with a diagnosis of Autism Spectrum Conditions (ASC) can be time consuming, needing involvement of outside experts. Social Stories™ are a highly personalised intervention aiming to give children with ASC social information or describing an otherwise difficult situation or skill. This can be delivered daily by staff in education settings. Studies examining Social Story™ use have yielded mostly positive results but have largely been single case studies with a lack of randomised controlled trials (RCTs). Despite this numerous schools are utilising Social Stories™, and a fully powered RCT is timely. Methods A multi-site pragmatic cluster RCT comparing care as usual with Social Stories™ and care as usual. This study will recruit 278 participants (aged 4–11) with a clinical diagnosis of ASC, currently attending primary school in the North of England. Approximately 278 school based staff will be recruited to provide school based information about participating children with approximately 140 recruited to deliver the intervention. The study will be cluster randomised by school. Potential participants will be screened for eligibility prior to giving informed consent. Follow up data will be collected at 6 weeks and 6 months post randomisation and will assess changes in participants’ social responsiveness, goal based outcomes, social and emotional health. The primary outcome measure is the Social Responsiveness Scale Second Edition (SRS-2) completed by school based staff at 6 months. Approvals have been obtained from the University of York’s Research Governance Committee, Research Ethics Committee and the Health Research Authority. Study results will be submitted for publication in peer-reviewed journals and disseminated to participating families, educational staff, local authority representatives, community groups and Patient and Participant Involvement representatives. Suggestions will be made to NICE about treatment evidence dependent on findings. Discussion This study addresses a much used but currently under researched intervention and results will inform school based support for primary school children with a diagnosis of ASC. Trial registration The trial is registered on the ISRCTN registry (registration number: ISRCTN11634810 ). The trial was retrospectively registered on 23rd April 2019.

A public health campaign on laryngeal cancer was conducted in 2011 in the Humber and Yorkshire Coast Cancer Network. This study evaluated its subsequent impact (if any) upon the stage of laryngeal cancer at presentation. Cases of laryngeal cancer diagnosed in the Humber and Yorkshire Coast Cancer Network from January 2009 to July 2014 were identified from cancer registries and were dichotomised into early (tumour stage T1-2) and late (T3-4) disease. Statistical analysis using segmented regression analysis of interrupted time series data was performed. There were no statistically significant changes in laryngeal cancer cases immediately after the intervention for both early (p = 0.191) and late (p = 0.680) stage disease. There were also no significant changes to monthly detection rates in both groups on follow up. Findings of the first public health campaign on laryngeal cancer in the UK are described. Such processes are complex; the implications for future study are discussed.

Summary Aim To systematically review evidence and perform a meta‐analysis of the efficacy of intra‐articular (IA) injections of Hylan G‐F 20 for the treatment of painful osteoarthritis (OA) of the knee. Methods Systematic review of the Embase and PubMed databases up to July 2013 of randomised placebo‐controlled trials studying the effect of Hylan G‐F 20 in patients with painful knee OA, with a meta‐analysis of trials reporting visual analogue scores (VAS) for weight‐bearing pain in the knees of patients followed up for a minimum of 6 months. Results Six placebo‐controlled randomised trials were identified on systematic review of which two studies met criteria for inclusion in the meta‐analysis. Meta‐analysis demonstrated that at 6‐month follow up, there was no significant difference between Hylan G‐F 20 and control in terms of reduction in VAS for weight bearing pain. (Mean Difference – 12.96 (95% CI: −35.48, 9.56). Z tests used to test for overall effect showed that the difference between the two groups was not significant (p = 0.26). Discussion A significant placebo effect exists for patients receiving IA injections for the treatment of painful knee OA. The withdrawal of fluid from the affected knee prior to any injectable therapy may itself have additional benefits which in isolation have not been studied. This may form the basis of future research. The authors’ acknowledge that although limited conclusions can be drawn from the results of this study, the meta‐analysis presented has not been performed previously and will further contribute to the knowledge on this subject. Conclusion Although Hylan G‐F 20 may produce improvement in VAS scores for weight‐bearing pain at 6‐month follow up in OA knees treated with it, patients should be informed that this may be equivalent to that seen with control treatments.

Antibiotic prophylaxis with cefuroxime can reduce the incidence of deep wound infection (DWI) in hip-fracture surgery, but may increase the risk of C. difficile infection (CDI). An alternative is gentamicin with beta-lactam for which a question exists around clinical effectiveness and safety, given the gentamicin-associated nephrotoxicity particularly in the elderly and narrower sensitivity spectrum. We compared 744 consecutive patients (group I—cefuroxime) with 756 in group II (gentamicin + flucloxacillin) who were well matched. There were 4 cases of CDI in the cefuroxime prophylaxis, whereas none in flucloxacillin plus gentamicin (group II). There was a statistically significant ( p  = 0.036) increased DWI rate in group II (2.5 %) as compared to group I (1.1 %). However, after controlling for age, gender, ASA grade, surgeon grade, implant type and type of anaesthesia, there was no statistically significant difference between the two groups ( p  = 0.146). 8.5 % of group I and 16.5 % of group II developed AKI post-operatively ( p  = 0.023); however, 79 % of group I and 80 % of in group II had complete resolution of AKI prior to their discharge. Further, a significant increase in inpatient deaths ( p  = 0.057) in group II was observed, but not at 30 days ( p  = 0.378).