Paediatric tibial shaft fractures: an instructional review for the FRCS exam.

This instructional review presents the literature and guidelines relevant to the classification, management and prognosis of paediatric tibial shaft fractures at a level appropriate for the FRCS exit examination in Trauma and Orthopaedic surgery.

Paediatric distal radius fractures: an instructional review for the FRCS examination.

An instructional review of the literature and guidelines relevant for the classification, management and prognosis of paediatric distal radius fractures. Aimed at the knowledge level required for the trauma and orthopaedic FRCS examination.

Risk factors for perioperative blood transfusions after urogenital fistula repair in Uganda: a retrospective cohort study.

OBJECTIVE: To determine the incidence of and risk factors for perioperative blood transfusions after urogenital fistula repairs in Uganda. DESIGN: A retrospective cohort study. SETTING: A community hospital in Masaka, Uganda. POPULATION: Women who underwent fistula repair at the Kitovu Hospital between 2013 and 2019. METHODS: Retrospective review of demographics and clinical perioperative characteristics of patients surgically treated for urogenital fistula. Patient characteristics were compared between those who did and those who did not require a blood transfusion. MAIN OUTCOME MEASURES: Need for perioperative blood transfusion and risk factors. RESULTS: A total of 546 patients treated for urogenital fistulas were included in this study. The median age was 31.1 ± 13.2 years. A vaginal surgical approach was used in the majority of patients (84.6%). Complications occurred in 3.5% of surgical repairs, and the incidence of blood transfusions was 6.2%. In multivariable analyses, for each gram per deciliter (g/dl) increase in preoperative haemoglobin, the odds of blood transfusion decreased by approximately 28% (adjusted OR 0.72, 95% CI 0.59-0.86). Women who had their fistula repaired abdominally were 3.4 times more likely to require transfusions (95% CI 1.40-8.08). CONCLUSIONS: The incidence of blood transfusions among urogenital fistula repairs in our population is twice that of developed nations. An abdominal surgical approach to urogenital fistula is a significant risk factor for perioperative blood transfusions. The timing of the repair may warrant further study. TWEETABLE ABSTRACT: One of the first studies to look at blood transfusion risk factors after fistula repair in a low-resource setting.

First results from five multidisciplinary diagnostic centre (MDC) projects for non-specific but concerning symptoms, possibly indicative of cancer.

BACKGROUND: Patients with non-specific symptoms often experience longer times to diagnosis and poorer clinical outcomes than those with site-specific symptoms. This paper reports initial results from five multidisciplinary diagnostic centre (MDC) projects in England, piloting rapid referral for patients with non-specific symptoms. METHODS: The evaluation covered MDC activity from 1st December 2016 to 31st July 2018, with projects using a common dataset. Logistical regression analyses were conducted, with a diagnosis of any cancer as the dependent variable. Exploratory analysis was conducted on presenting symptoms and diagnoses of cancer, and on comparisons within these groupings. RESULTS: In total, 2961 patients were referred into the MDCs and 241 cancers were diagnosed. The pathway detected cancers across a broad range of tumour sites, including several rare and less common cancers. An association between patient age and cancer was identified (p < 0.001). GP 'clinical suspicion' was identified as a strong predictor of cancer (p = 0.006), with a reduced association with cancer observed in patients with higher numbers of GP consultation before referral (p = 0.008). CONCLUSIONS: The MDC model diagnoses cancer in patients with non-specific symptoms, with a conversion rate of 8%, demonstrating the diagnostic potential of a non-site-specific symptomatic referral pathway.

Impact of choice of volumetry software and nodule management guidelines on recall rates in lung cancer screening.

PURPOSE: Appropriate lung nodule management is essential to minimizing unnecessary patient recall in lung cancer screening. Two European guidelines provide differing recommendations in that participants with nodules ≥100 mm3 or ≥80 mm3 respectively should be recalled, at baseline. Nodule size estimation is known to vary between volumetry software packages (VSPs). The aim of this study was to examine the impact of choice of VSP on participant recall rates, when applying different European nodule management guidelines. An additional aim was to compare recall rates between 7 VSPs and manual diameter measurements. METHODS: 156 small-sized lung nodules (50-150 mm3) from the UK Lung Screening trial were measured using 7 different VSPs (VSP1-7) and also using manual diameter. The type of VSP used in the NELSON study (VSP1), on which European nodule management guidelines are based, provided the reference standard. Nodule size was compared using Bland Altman, and recall rates by Mcnemar's test. RESULTS: Compared to the reference standard, a 100 mm3 threshold for recall, resulted in no difference in recall rates only for VSP 5 & 7. Using an 80mm3 threshold resulted in no difference in recall rates for VSP2 & 6. Recall rates were significantly higher for VSP 4 regardless of threshold and when using manual diameter measurements. CONCLUSIONS: Appropriate nodule size thresholds for recall in screening depend on the type of volumetry software used. The results highlight the importance of benchmarking of volumetry packages.

Final Results of the Prospective FH02 Mammographic Surveillance Study of Women Aged 35-39 at Increased Familial Risk of Breast Cancer.

BACKGROUND: Many women who are at increased risk of breast cancer due to a mother or sister diagnosed with breast cancer aged under 40 do not currently qualify for surveillance before 40 years of age. There are almost no available data to assess whether mammography screening aged 35-39 years would be effective in this group, in terms of detection of breast cancer at an early stage or cost effective. METHODS: A cohort screening study (FH02) with annual mammography was devised for women aged 35-39 to assess the sensitivity and screening performance and potential survival of women with identified tumours. FINDINGS: 2899 women were recruited from 12/2006-12/2015. These women underwent 12,086 annual screening mammograms and were followed for 13,365.8 years. A total of 55 breast cancers in 54 women occurred during the study period (one bilateral) with 50 cancers (49 women) (15 CIS) adherent to the screening. Eighty percent (28/35) of invasive cancers were ≤ 2 cm and 80% also lymph node negative. Invasive cancers diagnosed in FH02 were significantly smaller than the comparable (POSH-unscreened prospective) study group (45% (131/293) ≤ 2 cm in POSH vs 80% (28/35) in FH02 p < 0.0001), and were less likely to be lymph-node positive (54% (158/290, 3 unknown) in POSH vs 20% (7/35) in FH02: p = 0.0002. Projected and actual survival were also better than POSH. Overall radiation dose was not higher than in an older screened population at mean dose on study per standard sized breast of 1.5 mGy. INTERPRETATION: Mammography screening aged 35-39 years detects breast cancer at an early stage and is likely to be as effective in reducing mortality as in women at increased breast cancer risk aged 40-49 years.

Towards evidence-based follow-up intervals for breast cancer survivors: Estimates of the preclinical detectable phase of contralateral second breast cancer.

PURPOSE: Follow-up schemes in breast cancer survivors are predominantly consensus-based. To determine evidence-based follow-up intervals, estimates of sensitivity of the screening test(s) and duration of the preclinical detectable phase (PCDP) are key. We estimated the sensitivity and the duration of the PCDP of clinical breast examination (CBE) and mammography for the detection of contralateral second breast cancers (CBC) in breast cancer survivors. METHODS: Women with a CBC (N = 589) diagnosed in Florence between 1980 and 2005 were included. Test sensitivity and the duration of PCDP were estimated using a simple exponential model of PCDP duration. Analyses were stratified by follow-up period (0-5 vs. >5 years after primary diagnosis) and age at CBC diagnosis (<50 vs. ≥50 years). RESULTS: For CBE, test sensitivity was 55% and the duration of the PCDP 16 months. Mammography sensitivity was 91% and duration of the PCDP 35 months. Stratified analyses showed a higher test sensitivity for CBE for women aged <50 (70% vs. 51%). No difference in the duration of PCDP of CBE was found. For mammography, test sensitivity and the duration of the PCDP were higher for women with longer follow-up and in older women. CONCLUSIONS: Poor test sensitivity for CBE with a shorter duration of the PCDP compared with mammography were observed. Mammography had high test sensitivity and the potential to detect CBCs early. The estimated duration of the PCDP (35 months) was considerably longer than the recommended follow-up interval (12 months). Future studies are needed to determine whether a longer follow-up interval is appropriate.

The impact of mammography screening programmes on incidence of advanced breast cancer in Europe: a literature review.

BACKGROUND: Observational studies have reported conflicting results on the impact of mammography service screening programmes on the advanced breast cancer rate (ABCR), a correlation that was firmly established in randomized controlled trials. We reviewed and summarized studies of the effect of service screening programmes in the European Union on ABCR and discussed their limitations. METHODS: The PubMed database was searched for English language studies published between 01-01-2000 and 01-06-2018. After inspection of titles and abstracts, 220 of the 8644 potentially eligible papers were considered relevant. Their abstracts were reviewed by groups of two authors using predefined criteria. Fifty studies were selected for full paper review, and 22 of these were eligible. A theoretical framework for their review was developed. Review was performed using a ten-point checklist of the methodological caveats in the analysis of studies of ABCR and a standardised assessment form designed to extract quantitative and qualitative information. RESULTS: Most of the evaluable studies support a reduction in ABCR following the introduction of screening. However, all studies were challenged by issues of design and analysis which could at least potentially cause bias, and showed considerable variation in the estimated effect. Problems were observed in duration of follow-up time, availability of reliable reference ABCR, definition of advanced stage, temporal variation in the proportion of unknown-stage cancers, and statistical approach. CONCLUSIONS: We conclude that much of the current controversy on the impact of service screening programmes on ABCR is due to observational data that were gathered and/or analysed with methodological approaches which could not capture stage effects in full. Future research on this important early indicator of screening effectiveness should focus on establishing consensus in the correct methodology.

Clopidogrel, prasugrel or ticagrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

BACKGROUND: Guidelines recommend prasugrel or ticagrelor instead of clopidogrel in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary interventions (PCI). AIM: We sought to describe the trends in uptake of the newer agents and analyse the clinical characteristics and short-term outcomes of patients treated with clopidogrel, prasugrel or ticagrelor. METHODS: We analysed the temporal trends of antiplatelet use since the availability of prasugrel (2009-2013) in patients with ACS from the Melbourne Interventional Group registry. To assess clinical characteristics and outcomes, we included 1850 patients from 2012 to 2013, corresponding to the time all three agents were available. The primary outcome was major adverse cardiovascular events (MACE). The safety end-point was in-hospital bleeding. RESULTS: For the period of 2009-2013, the majority of patients were treated with clopidogrel (72%) compared with prasugrel (14%) or ticagrelor (14%). There was a clear trend towards ticagrelor by the end of 2013. Patients treated with clopidogrel were more likely to present with non-ST-elevation ACS, be older, and have more comorbidities. There was no difference in unadjusted 30-day mortality (0.9 vs 0.5 vs 1.0%, P = 0.76), myocardial infarction (2 vs 1 vs 2%, P = 0.52) or MACE (3 vs 3 vs 4%, P = 0.57) between the three agents. There was no difference in in-hospital bleeding (3 vs 2 vs 2%, P = 0.64). CONCLUSION: Prasugrel and ticagrelor are increasingly used in ACS patients treated with PCI, predominantly in a younger cohort with less comorbidity. Although antiplatelet therapy should still be individualised based on the thrombotic and bleeding risk, our study highlights the safety of the new P2Y12 inhibitors in contemporary Australian practice.

UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening.

BACKGROUND: Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial. METHODS: The pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction. RESULTS: 247 354 individuals aged 50-75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm(3) or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm(3) at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569). CONCLUSIONS: The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective-this needs to be confirmed using data on observed lung cancer mortality reduction. TRIAL REGISTRATION: ISRCTN 78513845.

CT screening for lung cancer: Is the evidence strong enough?

The prevailing questions at this time in both the public mind and the clinical establishment is, do we have sufficient evidence to implement lung cancer Computed Tomography (CT) screening in Europe? If not, what is outstanding? This review addresses the twelve major areas, which are critical to any decision to implement CT screening and where we need to assess whether we have sufficient evidence to proceed to a recommendation for implementation in Europe. The readiness level of these twelve categories in 2015 have been with colour coded, where green indicates we have sufficient evidence, amber is borderline evidence and red requires further evidence. Recruitment from the 'Hard to Reach' community still remains at red, while mortality data, cost effectiveness and screening interval are all categorised as amber. The integration of smoking cessation into CT screening programmes is still considered to be category amber. The US Preventive Services Task Force have recommended that CT screening is implemented in the USA utilising the NLST criteria, apart from continuing screening to 80 years of age. The cost effectiveness of the NLST was calculated to be $81,000/QALY, however, its well recognised that the costs of medical care in the USA, is far higher than that of Europe. Medicare have agreed to cover the cost of screening but have stipulated a number of stringent requirements for inclusion. To date we do not have good CT screening mortality data available in Europe and eagerly await the publication of the NELSON trial data in 2016 and then the pooled UKLS and NELSON data thereafter. However in the meantime we should start planning for implementation in Europe, especially in the areas of the radiological service provision and accreditation, as well as identifying novel mechanisms to recruit from the hardest to reach communities.

KCa3.1 K+ Channel Expression and Function in Human Bronchial Epithelial Cells.

The KCa3.1 K+ channel has been proposed as a novel target for pulmonary diseases such as asthma and pulmonary fibrosis. It is expressed in epithelia but its expression and function in primary human bronchial epithelial cells (HBECs) has not been described. Due to its proposed roles in the regulation of cell proliferation, migration, and epithelial fluid secretion, inhibiting this channel might have either beneficial or adverse effects on HBEC function. The aim of this study was to assess whether primary HBECs express the KCa3.1 channel and its role in HBEC function. Primary HBECs from the airways of healthy and asthmatic subjects, SV-transformed BEAS-2B cells and the neoplastic H292 epithelial cell line were studied. Primary HBECs, BEAS-2B and H292 cells expressed KCa3.1 mRNA and protein, and robust KCa3.1 ion currents. KCa3.1 protein expression was increased in asthmatic compared to healthy airway epithelium in situ, and KCa3.1 currents were larger in asthmatic compared to healthy HBECs cultured in vitro. Selective KCa3.1 blockers (TRAM-34, ICA-17043) had no effect on epithelial cell proliferation, wound closure, ciliary beat frequency, or mucus secretion. However, several features of TGFß1-dependent epithelial-mesenchymal transition (EMT) were inhibited by KCa3.1 blockade. Treatment with KCa3.1 blockers is likely to be safe with respect to airway epithelial biology, and may potentially inhibit airway remodelling through the inhibition of EMT.

Overdiagnosis associated with breast cancer screening: A simulation study to compare lead-time adjustment methods.

OBJECTIVE: Estimating overdiagnosis associated with breast cancer screening may use annual incidence rates of cancer. We simulated populations invited to screening programmes to assess two lead-time adjustment methods. METHODS: Overdiagnosis estimates were computed using the compensatory drop method, which considered the decrease in incidence of cancers among older age groups no longer offered screening, and the method based on the decrease in incidence of late-stage cancers. RESULTS: The true value of overdiagnosis was 0% in all the data sets simulated. The compensatory drop method yielded an overdiagnosis estimate of -0.1% (95% credibility interval -0.5% to 0.5%) when participation rates among the population and risk of cancers were constant. However, if participation rates increased with calendar year as well as risk of cancer with birth cohorts, the overdiagnosis estimated was 11.0% (10.5-11.6%). Using the method based on the incidence of early- and late-stage cancers, overdiagnosis estimates were 8.9% (8.5-9.3%) and 17.6% (17.4-17.9%) when participation rates and risks of cancer were constant or increased with time, respectively. CONCLUSION: Adjustment for lead time based on the compensatory drop method is accurate only when participation rates and risks of cancer remain constant, whereas the adjustment method based on the incidence of early- and late-stage cancers results in overestimating overdiagnosis regardless of stability of participation rates and breast cancer risk.

Likely effect of adding flexible sigmoidoscopy to the English NHS Bowel Cancer Screening Programme: impact on colorectal cancer cases and deaths.

BACKGROUND: From 2013, once-only flexible sigmoidoscopy (FS) at age 55 is being phased into the England National Health Service Bowel Cancer Screening Programme (NHSBCSP), augmenting biennial guaiac faecal occult blood testing (gFOBT) at ages 60-74. Here, we project the impact of this change on colorectal cancer (CRC) cases and deaths prevented in England by mid-2030. METHODS: We simulated the life-course of English residents reaching age 55 from 2013 onwards. Model inputs included population numbers, invitation rates and CRC incidence and mortality rates. The impact of gFOBT and FS alone on CRC incidence and mortality were derived from published trials, assuming an uptake of 50% for FS and 57% for gFOBT. For FS plus gFOBT, we assumed the gFOBT effect to be 75% of the gFOBT alone impact. RESULTS: By mid-2030, 8.5 million individuals will have been invited for once-only FS screening. Adding FS to gFOBT screening is estimated to prevent an extra 9627 (-10%) cases and 2207 (-12%) deaths by mid-2030. If FS uptake is 38% or 71%, respectively, an extra 7379 (-8%) or 13 689 (-15%) cases and 1691 (-9%) or 3154 (-17%) deaths will be prevented by mid-2030. CONCLUSIONS: Adding once-only FS at age 55 to the NHSBCSP will prevent ∼10,000 CRC cases and ∼2000 CRC deaths by mid-2030 if FS uptake is 50%. In 2030, one cancer was estimated to be prevented per 150 FS screening episodes, and one death prevented per 900 FS screening episodes. The actual reductions will depend on the FS invitation schedule and uptake rates.

The impact of national cancer awareness campaigns for bowel and lung cancer symptoms on sociodemographic inequalities in immediate key symptom awareness and GP attendances.

BACKGROUND: National campaigns focusing on key symptoms of bowel and lung cancer ran in England in 2012, targeting men and women over the age of 50 years, from lower socioeconomic groups. METHODS: Data from awareness surveys undertaken with samples of the target audience (n=1245/1140 pre-/post-bowel campaign and n=1412/1246 pre-/post-lung campaign) and Read-code data extracted from a selection general practitioner (GP) practices (n=355 for bowel and n=486 for lung) were analysed by population subgroups. RESULTS: Unprompted symptom awareness: There were no significant differences in the magnitude of shift in ABC1 vs C2DE groups for either campaign. For the bowel campaign, there was a significantly greater increase in awareness of blood in stools in the age group 75+ years compared with the 55-74 age group, and of looser stools in men compared with women. Prompted symptom awareness: Endorsement of 'blood in poo' remained stable, overall and across different population subgroups. Men showed a significantly greater increase in endorsement of 'looser poo' as a definite warning sign of bowel cancer than women. There were no significant differences across subgroups in endorsement of a 3-week cough as a definite warning sign of lung cancer. GP attendances: Overall, there were significant increases in attendances for symptoms directly linked to the campaigns, with the largest percentage increase seen in the 50-59 age group. For the bowel campaign, the increase was significantly greater for men and for practices in the most-deprived quintile, whereas for lung the increase was significantly greater for practices in the least-deprived quintile. CONCLUSIONS: The national bowel and lung campaigns reached their target audience and have also influenced younger and more affluent groups. Differences in impact within the target audience were also seen. There would seem to be no unduly concerning widening in inequalities, but further analyses of the equality of impact across population subgroups is warranted.

A telephone reminder intervention to improve breast screening information and access.

OBJECTIVES: In the UK, women aged 50-70 are offered breast cancer screening every three years. Screening participation rates in London have been particularly low. Low rates have been associated with low socio-economic status, and some ethnic groups have been observed to be underserved by cancer screening. This paper reports on a telephone reminder intervention in London Newham, an area of high deprivation and ethnic diversity. STUDY DESIGN: Observational study of planned intervention. METHODS: Women invited for breast screening were telephoned to confirm receipt of the invitation letter, remind invitees of their upcoming appointment, and to provide further information. Aggregate data at general practice level on invitation to and attendance at breast screening and on numbers reached by telephone were analysed by logistic regression. RESULTS: For the 29 participating GP practices (10,928 invitees) overall uptake in 2010 was higher compared to the previous screening round in 2007 (67% vs. 51%; p < 0.001). On average 59% of invitees were reached by the reminder calls. A 10% increase in women reached resulted in an 8% increase in the odds of women attending their screening appointment (95% CI: 5%-11%), after adjusting for 2007 attendance rates. Practices with a higher proportion of South Asian women were associated with a larger uptake adjusted for 2007 uptake and population reached by the telephone intervention, (4% increase in odds of attendance per 10% increase in South Asian population, CI 1%-7%, p = 0.003) while practices with a higher proportion of black women were associated with a smaller uptake similarly adjusted. (11% decrease in odds of attendance per 10% increase in black population, CI 9%-16%, p < 0.001). CONCLUSIONS: A language- and culture-sensitive programme of reminder calls substantially improved breast cancer screening uptake.