Trends in keratinocyte skin cancer incidence, mortality and burden of disease in 33 countries between 1990 and 2017.

BACKGROUND: Keratinocyte cancers (KCs) are the most common type of cancer in the White population worldwide, with associated high healthcare costs. Understanding the epidemiological trends for KCs, namely basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs), is required to assess burden of disease, project future trends and identify strategies for addressing this pressing global health issue. OBJECTIVES: To report trends in BCC and SCC incidence, and SCC mortality and disability-adjusted life-years (DALYs). METHODS: An observational study of the Global Burden of Disease (GBD) database between 1990 and 2017 was performed. European Union countries and other selected high-income countries, including the UK and the USA, classified as having high-quality mortality data, were included. Annual age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs) and DALYs for each country were obtained from the GBD database. Trends were described using joinpoint regression analysis. RESULTS: Overall, 33 countries were included. For both BCC and SCC in 2015-2017, the highest ASIRs were observed in the USA and Australia. Males had higher ASIRs than females at the end of the observation period in all countries for SCC, and in all countries but two for BCC. In contrast, the highest ASDRs for SCC were observed in Australia and Latvia for males, and in Romania and Croatia for females. The highest DALYs for SCC for both sexes were seen in Australia and Romania. Over the observation period, there were more countries demonstrating decreasing trends in mortality than in incidence, and disparities were observed between which countries had comparatively high mortality rates and which had high incidence rates. Overall reductions in SCC DALYs were observed in 24 of 33 countries for males, and 25 countries for females. CONCLUSIONS: Over the past 27 years, although trends in SCC incidence have risen in most countries, there is evidence that mortality rates have been decreasing. Burden of disease as assessed using DALYs has decreased in the majority of countries. Future work will explore potential explanatory factors for the observed disparity in trends in SCC incidence and mortality.

Trends in prevalence, mortality, and disability-adjusted life-years relating to chronic obstructive pulmonary disease in Europe: an observational study of the global burden of disease database, 2001-2019.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is associated with significant mortality and well-defined aetiological factors. Previous reports indicate that mortality from COPD is falling worldwide. This study aims to assess the burden of COPD using prevalence, mortality, and disability-adjusted life years (DALYs) between 2001 and 2019 in 28 European countries (the European Union and the United Kingdom). METHODS: We extracted COPD data from the Global Burden of Disease database based on the International Classification of Diseases versions 10 (J41, 42, 43, 44 and 47). Age-standardised prevalence rates (ASPRs), age-standardised mortality rates (ASMRs), and DALYs were analysed for European countries by sex for each year (2001-2019) and reported per 100,000 population. We used Joinpoint regression analysis to quantify changing trends in the burden of COPD. RESULTS: In 2019, the median ASPR across Europe was 3230/100,000 for males and 2202/100,000 for females. Between 2001 and 2019, the median percentage change in ASPR was - 9.7% for males and 4.3% for females. 23/28 countries demonstrated a decrease in ASPRs in males, and 11/28 demonstrated a decrease in females. The median percentage change in ASMR between 2001 and 2019 was - 27.5% for males and - 10.4% for females. 25/28 and 19/28 countries demonstrated a decrease in ASMR in males and females, respectively. CONCLUSION: In the EU between 2001 and 2019 COPD prevalence has overall increased in females but continues to decrease in males and in some countries, female prevalence now exceeds that of males. COPD mortality in the EU has decreased overall between 2001 and 2019; however, this decrease is not universal, particularly in females, and therefore remains a substantial source of amenable mortality.

An observational epidemiological study to analyze intracerebral hemorrhage across the United States: Incidence and mortality trends from 1990 to 2017.

OBJECTIVES: Intracerebral Hemorrhage (ICH) accounts for 10% of strokes annually in the United States (US). Up-to-date trends in disease burden and regional variations remain unknown. Our study reports updated trends of ICH incidence, mortality, and mortality to incidence ratio (MIR) across the US. MATERIALS AND METHODS: Observational study to evaluate the incidence and mortality from ICH across the US. Data was obtained from Global Burden of Disease (GBD) database. Age-Standardized Incidence (ASIRs) and Death (ASDRs) Rates, as well as the Mortality- to-Incidence ratios (MIRs) for ICH in the US overall and state-wise from 1990-2017. Joinpoint regression analysis was used, with presentation of estimated annual percentage changes (EAPCs). RESULTS: Overall decrease in ASIRs, ASDRs, and MIRs in the US for both sexes. The 2017 mean ASIR was 25.67/100,000 for men and 19.17/100,000 for women, whereas mean ASDR was 13.96/100,000 for men and 11.35/100,000 for women. District of Columbia had greatest decreases in ASIR EAPCs for both men and women at -41.25% and -40.58%, respectively, and greatest decreases in ASDR EAPCs for men and women at -55.38% and -48.51%, respectively. MIR between 1990-2017 decreased in men by -12.12% and women by -7.43%. MIR increased in men from 2014-2017 (EAPC +2.2%) and in women from 2011-2017 (EAPC +1.0%). CONCLUSION: Decreasing trends in incidence, mortality, and MIR. No significant trends in mortality were found in the last 6 years of the study period. MIR worsened in males from 2014-2017 and females from 2011-2017, suggesting decreased ICH-related survival lately.

Sentinel node biopsy for diagnosis of lymph node involvement in endometrial cancer.

BACKGROUND: Pelvic lymphadenectomy provides prognostic information for those diagnosed with endometrial (womb) cancer and provides information that may influence decisions regarding adjuvant treatment. However, studies have not shown a therapeutic benefit, and lymphadenectomy causes significant morbidity. The technique of sentinel lymph node biopsy (SLNB), allows the first draining node from a cancer to be identified and examined histologically for involvement with cancer cells. SLNB is commonly used in other cancers, including breast and vulval cancer. Different tracers, including colloid labelled with radioactive technetium-99, blue dyes, e.g. patent or methylene blue, and near infra-red fluorescent dyes, e.g. indocyanine green (ICG), have been used singly or in combination for detection of sentinel lymph nodes (SLN). OBJECTIVES: To assess the diagnostic accuracy of sentinel lymph node biopsy (SLNB) in the identification of pelvic lymph node involvement in women with endometrial cancer, presumed to be at an early stage prior to surgery, including consideration of the detection rate. SEARCH METHODS: We searched MEDLINE (1946 to July 2019), Embase (1974 to July 2019) and the relevant Cochrane trial registers. SELECTION CRITERIA: We included studies that evaluated the diagnostic accuracy of tracers for SLN assessment (involving the identification of a SLN plus histological examination) against a reference standard of histological examination of removed pelvic +/- para-aortic lymph nodes following systematic pelvic +/- para-aortic lymphadenectomy (PLND/PPALND) in women with endometrial cancer, where there were sufficient data for the construction of two-by-two tables. DATA COLLECTION AND ANALYSIS: Two review authors (a combination of HN, JM, NW, RG, and WH) independently screened titles and abstracts for relevance, classified studies for inclusion/exclusion and extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We calculated the detection rate as the arithmetic mean of the total number of SLNs detected out of the total number of women included in the included studies with the woman as the unit of analysis, used univariate meta-analytical methods to estimate pooled sensitivity estimates, and summarised the results using GRADE. MAIN RESULTS: The search revealed 6259 unique records after removal of duplicates. After screening 232 studies in full text, we found 73 potentially includable records (for 52 studies), although we were only able to extract 2x2 table data for 33 studies, including 2237 women (46 records) for inclusion in the review, despite writing to trial authors for additional information. We found 11 studies that analysed results for blue dye alone, four studies for technetium-99m alone, 12 studies that used a combination of blue dye and technetium-99m, nine studies that used indocyanine green (ICG) and near infra-red immunofluorescence, and one study that used a combination of ICG and technetium-99m. Overall, the methodological reporting in most of the studies was poor, which resulted in a very large proportion of 'unclear risk of bias' ratings. Overall, the mean SLN detection rate was 86.9% (95% CI 82.9% to 90.8%; 2237 women; 33 studies; moderate-certainty evidence). In studies that reported bilateral detection the mean rate was 65.4% (95% CI 57.8% to 73.0%) . When considered according to which tracer was used, the SLN detection rate ranged from 77.8% (95% CI 70.0% to 85.6%) for blue dye alone (559 women; 11 studies; low-certainty evidence) to 100% for ICG and technetium-99m (32 women; 1 study; very low-certainty evidence). The rates of positive lymph nodes ranged from 5.2% to 34.4% with a mean of 20.1% (95% CI 17.7% to 22.3%). The pooled sensitivity of SLNB was 91.8% (95% CI 86.5% to 95.1%; total 2237 women, of whom 409 had SLN involvement; moderate-certainty evidence). The sensitivity for of SLNB for the different tracers were: blue dye alone 95.2% (95% CI 77.2% to 99.2%; 559 women; 11 studies; low-certainty evidence); Technetium-99m alone 90.5% (95% CI 67.7% to 97.7%; 257 women; 4 studies; low-certainty evidence); technetium-99m and blue dye 91.9% (95% CI 74.4% to 97.8%; 548 women; 12 studies; low-certainty evidence); ICG alone 92.5% (95% CI 81.8% to 97.1%; 953 women; 9 studies; moderate-certainty evidence); ICG and blue dye 90.5% (95% CI 63.2.6% to 98.1%; 215 women; 2 studies; low-certainty evidence); and ICG and technetium-99m 100% (95% CI 63% to 100%; 32 women; 1 study; very low-certainty evidence). Meta-regression analyses found that the sensitivities did not differ between the different tracers used, between studies with a majority of women with FIGO stage 1A versus 1B or above; between studies assessing the pelvic lymph node basin alone versus the pelvic and para-aortic lymph node basin; or between studies that used subserosal alone versus subserosal and cervical injection. It should be noted that a false-positive result cannot occur, as the histological examination of the SLN is unchanged by the results from any additional nodes removed at systematic lymphadenectomy. AUTHORS' CONCLUSIONS: The diagnostic test accuracy for SLNB using either ICG alone or a combination of a dye (blue or ICG) and technetium-99m is probably good, with high sensitivity, where a SLN could be detected. Detection rates with ICG or a combination of dye (ICG or blue) and technetium-99m may be higher. The value of a SLNB approach in a treatment pathway, over adjuvant treatment decisions based on uterine factors and molecular profiling, requires examination in a high-quality intervention study.

Median arcuate ligament syndrome.

BACKGROUND: Median arcuate ligament syndrome (MALS) describes the clinical presentation associated with direct compression of the celiac artery by the median arcuate ligament. The poorly understood pathophysiologic mechanism, variable symptom severity, and unpredictable response to treatment make MALS a controversial diagnosis. METHODS: This review summarizes the literature pertaining to the pathophysiologic mechanism, presentation, diagnosis, and management of MALS. A suggested diagnostic workup and treatment algorithm are presented. RESULTS: Individuals with MALS present with signs and symptoms of foregut ischemia, including exercise-induced or postprandial epigastric pain, nausea, vomiting, and weight loss. Consideration of MALS in patients' diagnostic workup is typically delayed. Currently, no group consensus agreement as to the diagnostic criteria for MALS exists; duplex ultrasound, angiography, and gastric exercise tonometry are used in different combinations and with varying diagnostic values throughout the literature. Surgical management involves decompression of the median arcuate ligament's constriction of the celiac artery; robotic, laparoscopic, endoscopic retroperitoneal, and open surgical intervention can provide effective symptom relief, but long-term follow-up data (>5 years) are lacking. Patients treated nonoperatively appear to have worse outcomes. CONCLUSIONS: MALS is an important clinical entity with significant impact on affected individuals. Presenting symptoms, patient demographics, and radiologic signs are generally consistent, as is the short-to medium-term (<5 years) response to surgical intervention. Future prospective studies should directly compare long-term symptomatic and quality of life outcomes after nonoperative management with outcomes after open, laparoscopic, endoscopic retroperitoneal, and robotic celiac artery decompression to enable the development of evidence-based guidelines for the management of MALS.

Editor's Choice - Trends in Lower Extremity Amputation Incidence in European Union 15+ Countries 1990-2017.

OBJECTIVE: Lower extremity amputation (LEA) carries significant mortality, morbidity, and health economic burden. In the Western world, it most commonly results from complications of peripheral arterial occlusive disease (PAOD) or diabetic foot disease. The incidence of PAOD has declined in Europe, the United States, and parts of Australasia. The present study aimed to assess trends in LEA incidence in European Union (EU15+) countries for the years 1990-2017. METHODS: This was an observational study using data obtained from the 2017 Global Burden of Disease (GBD) Study. Age standardised incidence rates (ASIRs) for LEA (stratified into toe amputation, and LEA proximal to toes) were extracted from the GBD Results Tool (http://ghdx.healthdata.org/gbd-results-tool) for EU15+ countries for each of the years 1990-2017. Trends were analysed using Joinpoint regression analysis. RESULTS: Between 1990 and 2017, variable trends in the incidence of LEA were observed in EU15+ countries. For LEAs proximal to toes, increasing trends were observed in six of 19 countries and decreasing trends in nine of 19 countries, with four countries showing varying trends between sexes. For toe amputation, increasing trends were observed in eight of 19 countries and decreasing trends in eight of 19 countries for both sexes, with three countries showing varying trends between sexes. Australia had the highest ASIRs for both sexes in all LEAs at all time points, with steadily increasing trends. The USA observed the greatest reduction in all LEAs in both sexes over the time period analysed (LEAs proximal to toes: female patients -22.93%, male patients -29.76%; toe amputation: female patients -29.93%, male patients -32.67%). The greatest overall increase in incidence was observed in Australia. CONCLUSION: Variable trends in LEA incidence were observed across EU15+ countries. These trends do not reflect previously observed reductions in incidence of PAOD over the same time period.

A Methodological Assessment of Diabetic Foot Syndrome Clinical Practice Guidelines.

OBJECTIVE: Diabetic foot syndrome (DFS) contributes to significant morbidity in diabetic patients. Diagnostic and therapeutic approaches to DFS may be summarised in clinical practice guidelines (CPGs) to aid clinical practice but may only benefit patients if the CPG is of high quality. This study determines the methodological quality of DFS CPGs using a validated assessment tool to identify CPGs adequate for use in clinical practice. METHODS: Medline, EMBASE, and CPG databases were searched to 31 May 2019. Reference lists were also searched. Full text English evidence based DFS CPGs were included. CPGs based on expert consensus, guideline summaries, or those only available if purchased were excluded. Four reviewers independently assessed methodological quality using the Appraisal of Guidelines for Research and Evaluation II instrument. An overall guideline assessment scaled score of ≥80% was considered to be of adequate quality to recommend use. RESULTS: Sixteen CPGs were identified. Good inter-reviewer reliability (ICC 0.985, 95% CI 0.980-0.989) was achieved. Poor scores were noted in domains 2 (stakeholder involvement), 5 (applicability), and 6 (editorial independence). Significant methodological heterogeneity was observed in all domains with the most noted in domain 6 (mean scaled score 43.2 ± 32.1%). Four CPGs achieved overall assessment scores of ≥80%. CONCLUSION: Four CPGs were considered to be adequate for clinical practice based on methodological quality. However, elements of methodological quality were still lacking, and all CPGs had areas for improvement, potentially through increased multidisciplinary team involvement and trial application of recommendations. Methodological rigour may be improved using structured approaches with validated CPG creation tools in the future. Future work should also assess recommendation accuracy using available validated assessment tools.

A Systematic Review of the Impact of Foot Care Education on Self Efficacy and Self Care in Patients With Diabetes.

OBJECTIVE: This review aims to assess the evidence supporting the impact of patient foot care education on self efficacy, self care behaviour, and self care knowledge in individuals with diabetes. METHODS: This systematic review was registered prospectively on the PROSPERO database (CRD42019106171). Ovid EMBASE and MEDLINE databases were searched from 1946 to the end of March 2019, using search terms related to the domains diabetic foot, patient education, self efficacy, self care behaviour, and self care knowledge. All included studies were prospective, randomised controlled trials that assessed foot care education interventions in individuals with diabetes and recorded an outcome related to self efficacy, self care behaviour, and/or self care knowledge. RESULTS: Thirteen randomised controlled trials were included, reporting on a total of 3948 individuals. The risk of bias was high or unclear in 11 of the 13 included studies, and low in two studies. Both the education interventions delivered, and the outcome assessment tools used were heterogenous across included studies: meta-analysis was therefore not performed. Eight of 11 studies identified significantly better foot self care behaviour scores in individuals randomised to education compared with controls. Self efficacy scores were significantly better in education groups in four of five studies reporting this primary outcome. Foot care knowledge was significantly better in intervention vs. control in three of seven studies. In general, studies assessing secondary endpoints including quality of life and ulcer/amputation incidence tended not to identify significant clinical improvements. CONCLUSION: The available evidence is of inadequate quality to reliably conclude that foot care education has a positive impact on foot self care behaviour and self efficacy in individuals with diabetes. Quality data supporting accompanying benefits on quality of life or ulcer/amputation incidence are also lacking and should be considered as an important outcome measure in future studies.

Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer.

BACKGROUND: Epithelial ovarian cancer presents at an advanced stage in the majority of women. These women require surgery and chemotherapy for optimal treatment. Conventional treatment has been to perform surgery first and then give chemotherapy. However, there may be advantages to using chemotherapy before surgery. OBJECTIVES: To assess whether there is an advantage to treating women with advanced epithelial ovarian cancer with chemotherapy before debulking surgery (neoadjuvant chemotherapy (NACT)) compared with conventional treatment where chemotherapy follows debulking surgery (primary debulking surgery (PDS)). SEARCH METHODS: We searched the following databases on 11 February 2019: CENTRAL, Embase via Ovid, MEDLINE (Silver Platter/Ovid), PDQ and MetaRegister. We also checked the reference lists of relevant papers that were identified to search for further studies. The main investigators of relevant trials were contacted for further information. SELECTION CRITERIA: Randomised controlled trials (RCTs) of women with advanced epithelial ovarian cancer (Federation of International Gynaecologists and Obstetricians (FIGO) stage III/IV) who were randomly allocated to treatment groups that compared platinum-based chemotherapy before cytoreductive surgery with platinum-based chemotherapy following cytoreductive surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias in each included trial. MAIN RESULTS: We found 1952 potential titles, with a most recent search date of February 2019, of which five RCTs of varying quality and size met the inclusion criteria. These studies assessed a total of 1713 women with stage IIIc/IV ovarian cancer randomised to NACT followed by interval debulking surgery (IDS) or PDS followed by chemotherapy. We pooled results of the three studies where data were available and found little or no difference with regard to overall survival (OS) (1521 women; hazard ratio (HR) 1.06; 95% confidence interval (CI) 0.94 to 1.19, I2 = 0%; moderate-certainty evidence) or progression-free survival in four trials where we were able to pool data (1631 women; HR 1.02; 95% CI 0.92 to 1.13, I2 = 0%; moderate-certainty evidence). Adverse events, surgical morbidity and quality of life (QoL) outcomes were poorly and incompletely reported across studies. There may be clinically meaningful differences in favour of NACT compared to PDS with regard to serious adverse effects (SAE grade 3+). These data suggest that NACT may reduce the risk of need for blood transfusion (risk ratio (RR) 0.80; 95% CI 0.64 to 0.99; four studies,1085 women; low-certainty evidence), venous thromboembolism (RR 0.28; 95% CI 0.09 to 0.90; four studies, 1490 women; low-certainty evidence), infection (RR 0.30; 95% CI 0.16 to 0.56; four studies, 1490 women; moderate-certainty evidence), compared to PDS. NACT probably reduces the need for stoma formation (RR 0.43, 95% CI 0.26 to 0.72; two studies, 581 women; moderate-certainty evidence) and bowel resection (RR 0.49, 95% CI 0.26 to 0.92; three studies, 1213 women; moderate-certainty evidence), as well as reducing postoperative mortality (RR 0.18; 95% CI 0.06 to 0.54:five studies, 1571 women; moderate-certainty evidence). QoL on the EORTC QLQ-C30 scale produced inconsistent and imprecise results in two studies (MD -1.34, 95% CI -2.36 to -0.32; participants = 307; very low-certainty evidence) and use of the QLQC-30 and QLQC-Ov28 in another study (MD 7.60, 95% CI 1.89 to 13.31; participants = 217; very low-certainty evidence) meant that little could be inferred. AUTHORS' CONCLUSIONS: The available moderate-certainty evidence suggests there is little or no difference in primary survival outcomes between PDS and NACT. NACT may reduce the risk of serious adverse events, especially those around the time of surgery, and the need for bowel resection and stoma formation. These data will inform women and clinicians and allow treatment to be tailored to the person, taking into account surgical resectability, age, histology, stage and performance status. Data from an unpublished study and ongoing studies are awaited.

Multicentre collaborative cohort study of the use of Kirschner wires for the management of supracondylar fractures in children.

PURPOSE: Supracondylar fractures of the humerus cause significant morbidity in children. Nerve damage and loss of fracture reduction are common recognised complications in patients with this injury. Uncertainty surrounds the optimal Kirschner wire configuration and diameter for closed reduction and pinning of these fractures. This study describes current practice and examined the association between wire configuration or diameter and outcomes (clinical and radiological) in the operative management of paediatric supracondylar fractures. METHODS: Children presenting with Gartland II or III supracondylar fractures at five hospitals in south-west England were eligible for inclusion. Collaborators scrutinised paper and electronic case notes. Outcome measures were maintenance of reduction and iatrogenic nerve injury. RESULTS: Altogether 209 patients were eligible for inclusion: 15.7% had a documented neurological deficit at presentation; 3.9% who were neurologically intact at presentation sustained a new deficit caused by treatment and 13.4% experienced a clinically significant loss of reduction following fixation. Maintenance of reduction was significantly better in patients treated specifically with crossed ×3 Kirschner wire configuration compared to all other configurations. The incidence of iatrogenic nerve injury was not significantly different between groups treated with different wire configurations. CONCLUSION: We present a large multicentre cohort study showing that crossed ×3 Kirschner wires are associated with better maintenance of reduction than crossed ×2 or lateral entry wires. Greater numbers would be required to properly investigate nerve injury relating to operative management of supracondylar fractures. We found significant variations in practice and compliance with the British Orthopaedic Association Standard for Trauma (BOAST) 11 guidelines.

Epidermal growth factor receptor blockers for the treatment of ovarian cancer.

BACKGROUND: This is an update of a previously published version of the review (Issue 10, 2011).Epithelial ovarian cancer (EOC) is the seventh most common cause of cancer death among women worldwide. Treatment consists of a combination of surgical debulking and platinum-based chemotherapy. Between 55% and 75% of women who respond to first-line therapy experience relapse within two years. Second-line chemotherapy is palliative and aims to reduce symptoms and prolong survival. Improved understanding about the molecular basis of EOC has led to the development of novel agents, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and anti-EGFR antibodies. OBJECTIVES: To compare the effectiveness and harmful effects of interventions that target the epidermal growth factor receptor in the treatment of epithelial ovarian cancer (EOC). SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL; 2010, Issue 4), MEDLINE, and Embase up to October 2010. We also searched registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies, and we contacted experts in the field. This update includes further searches up to September 2017. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing anti-EGFR agents with or without conventional chemotherapy versus conventional chemotherapy alone or no treatment in women with histologically proven EOC. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data, assessed risk of bias, and performed GRADE assessment. MAIN RESULTS: From 6105 references obtained through the literature search and an additional 15 references derived from grey literature searches, we identified seven RCTs that met our inclusion criteria and included 1725 participants. Trial results show that after first-line chemotherapy is provided, maintenance treatment with erlotinib (EGFR tyrosine kinase inhibitor (TKI)) probably makes little or no difference in overall survival (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.81 to 1.20; one study; 835 participants; low-certainty evidence) and may make little or no difference in progression-free survival (HR 1.05, 95% CI 0.90 to 1.23; one study; 835 participants; very low-certainty evidence). Less than 50% of participants provided quality of life data, and study authors reported these results incompletely. The certainty of evidence is very low, but treatment may reduce quality of life compared to observation.Treatment with an EGFR TKI (vandetanib) for women with relapsed EOC may make little or no difference in overall survival (HR 1.25, 95% CI 0.80 to 1.95; one study; 129 participants; low-certainty evidence) and may make little or no difference in progression-free survival (HR 0.99, 95% CI 0.69 to 1.42; one study; 129 participants; very low-certainty evidence). In treating patients with relapse, giving EGFR TKI may slightly increase some toxicities, such as severe rash (risk ratio (RR) 13.63, 95% CI 0.78 to 236.87; one study; 125 participants; very low-certainty evidence). Quality of life data were not available for meta-analysis.Anti-EGFR antibody treatment in relapsed EOC may or may not make a difference to overall survival (HR 0.93, 95% CI 0.74 to 1.18; four studies; 658 participants; moderate-certainty evidence) and may or may not have any effect on progression-free survival (HR 0.90, 95% CI 0.70 to 1.16; four studies; 658 participants; low-certainty evidence). Anti-EGFR antibody treatment may or may not increase side effects, including severe nausea and/or vomiting (RR 1.27, 95% CI 0.56 to 2.89; three studies; 503 participants; low-certainty evidence), severe fatigue (RR 1.06, 95% CI 0.66 to 1.73; I² = 0%; four studies; 652 participants; low-certainty evidence), and hypokalaemia (RR 2.01, 95% CI 0.80 to 5.06; I² = 0%; three studies; 522 participants; low-certainty evidence). Severe diarrhoea rates were heterogeneous across studies (RR 2.87, 95% CI 0.59 to 13.89; four studies; 652 participants; low-certainty evidence), and subgroup analysis revealed that severe diarrhoea was more likely with pertuzumab (RR 6.37, 95% CI 1.89 to 21.45; I² = 0%; three studies; 432 participants; low-certainty evidence) than with seribantumab treatment (RR 0.38, 95% CI 0.07 to 2.23; I² = 0%; one study; 220 participants; very low-certainty evidence). Quality of life data were incompletely reported, and we were unable to combine them in a meta-analysis. AUTHORS' CONCLUSIONS: Current evidence suggests that an anti-EGFR single-agent biological treatment (EGFR TKI or anti-EGFR antibody) makes little or no difference to survival, either as maintenance treatment after first-line chemotherapy or in association with chemotherapy in recurrent cancer. Anti-EGFR therapy may increase some side effects and may or may not reduce quality of life.

Temporal Analysis of the Incidence, Mortality and Disability-Adjusted Life Years of Benign Gallbladder and Biliary Diseases in High-Income Nations, 1990-2019.

Objective: The aim of this observational study was to analyze trends in the incidence, mortality, and disability-adjusted life years (DALYs) of benign gallbladder and biliary diseases across high-income countries between 1990 and 2019. Background: Benign gallbladder and biliary diseases place a substantial burden on healthcare systems in high-income countries. Accurate characterization of the disease burden may help optimize healthcare policy and resource distribution. Materials and methods: Age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and DALYs data for gallbladder and biliary diseases in males and females were extracted from the 2019 Global Burden of Disease (GBD) study. A mortality-incidence index (MII) was also calculated. Joinpoint regression analysis was performed. Results: The median ASIRs across the European Union 15+ countries in 2019 were 758/100,000 for females and 282/100,000 for males. Between 1990 and 2019 the median percentage change in ASIR was +2.49% for females and +1.07% for males. The median ASMRs in 2019 were 1.22/100,000 for females and 1.49/100,000 for males with a median percentage change over the observation period of -21.93% and -23.01%, respectively. In 2019, the median DALYs was 65/100,000 for females and 37/100,000 among males, with comparable percentage decreases over the observation period of -21.27% and -19.23%, respectively. Conclusions: International variation in lifestyle factors, diagnostic and management strategies likely account for national and sex disparities. This study highlights the importance of ongoing clinical efforts to optimize treatment pathways for gallbladder and biliary diseases, particularly in the provision of emergency surgical services and efforts to address population risk factors.

Trends in the incidence of rib and sternal fractures: A nationwide study of the global burden of disease database, 1990-2019.

INTRODUCTION: Fractures of the ribs and sternum are associated with significant morbidity and mortality. Characterization of the injury burden across England is necessary to inform and evaluate developments in trauma care and infrastructure, however is yet to be comprehensively undertaken. Therefore, the aim of this study was to describe trends in the incidence of sternal and rib fractures across England between 1990 and 2019. MATERIALS AND METHODS: Age-standardised incidence rates (ASIRs) for rib and sternal fractures in males and females were extracted from the 2019 Global Burden of Disease (GBD) study by all causes, falls and road traffic collisions for 9 sub-regions of England. Temporal trends within the study period were analysed using Joinpoint regression analysis. RESULTS: The overall ASIRs in England in 2019 were 30.34/100,000 and 46.02/100,000 for females and males, respectively. Between 1990 and 2019, the estimated overall percentage change across England was +0.20 % among females and -7.05 % among males. A statistically significant increase in ASIR was observed in all 9 sub-regions of England among females from 2014-2019 (p<0.001). Among males, a statistically significant increase in ASIR was observed in 7 of the 9 regions from 2014-2019 (p<0.001) and in the remaining 2 regions from 2015-2019 (p<0.001). DISCUSSION: Increasing ASIRs of rib and sternal fractures were observed among females and decreasing ASIRs among males, with overall ASIRs higher among males. Developments in trauma infrastructure and associated variations in diagnostic and management strategies over the observation period likely contribute to changes in the national injury burden. The findings are suggestive of the importance of ongoing financial investment in trauma infrastructure and of clear clinical guidelines to manage an increasing national injury burden.

Structural validation of the Manchester-Oxford Foot Questionnaire for use in foot and ankle surgery.

Aims: The Manchester-Oxford Foot Questionnaire (MOxFQ) is an anatomically specific patient-reported outcome measure (PROM) currently used to assess a wide variety of foot and ankle pathology. It consists of 16 items across three subscales measuring distinct but related traits: walking/standing ability, pain, and social interaction. It is the most used foot and ankle PROM in the UK. Initial MOxFQ validation involved analysis of 100 individuals undergoing hallux valgus surgery. This project aimed to establish whether an individual's response to the MOxFQ varies with anatomical region of disease (measurement invariance), and to explore structural validity of the factor structure (subscale items) of the MOxFQ. Methods: This was a single-centre, prospective cohort study involving 6,637 patients (mean age 52 years (SD 17.79)) presenting with a wide range of foot and ankle pathologies between January 2013 and December 2021. To assess whether the MOxFQ responses vary by anatomical region of foot and ankle disease, we performed multigroup confirmatory factor analysis. To assess the structural validity of the subscale items, exploratory and confirmatory factor analyses were performed. Results: Measurement invariance by pathology was confirmed, suggesting the same model can be used across all foot and ankle anatomical regions. Exploratory factor analysis demonstrated a two- to three-factor model, and suggested that item 13 (inability to carry out work/everyday activities) and item 14 (inability to undertake social/recreational activities) loaded more positively onto the "walking/standing" subscale than their original "social interaction" subscale. Conclusion: This large cohort study supports the current widespread use of the MOxFQ across a broad range of foot and ankle pathologies. Our analyses found indications that could support alterations to the original factor structure (items 13 and 14 might be moved from the "social interaction" to the "walking/standing" subscale). However, this requires further work to confirm.

A Qualitative Study of Patients' Lived Experiences of Free Tissue Transfer for Diabetic Foot Disease.

Background: Free tissue transfer (FTT) for reconstruction of diabetic foot disease (DFD) is an emerging field to preserve the lower limb within this patient group. The design of future quantitative research and clinical services in this area must consider the needs, expectations and concerns of patients. This qualitative study explores patient experiences of FTT for reconstruction of DFD. Methods: Semistructured interviews were conducted to explore patients' lived experiences of FTT for DFD. A purposive sampling strategy identified six patients who underwent FTT for recalcitrant DFD between September 2019 and December 2021 in a single center in the United Kingdom. Results: Three experiential themes emerged. Theme 1: "negative lived experiences of living with DFD" included frustration with the chronic management of nonhealing ulcers and fear regarding limb amputation. Theme 2: "surgery related concerns" included fears of reconstructive failure and subsequent amputation, as well as foot cosmesis and donor-site morbidity. Theme 3: "positive lived experiences following reconstruction" included the positive impact the reconstruction had on their overall life and diabetic control. All patients would repeat the process to obtain their current results. Conclusions: This qualitative study provides first-hand insight into the lived experience of FTT for DFD, exploring both the negative and positive experiences and reasons for these. We found that FTT for DFD can be positively life-changing for affected individuals.

Trends in the mortality, incidence and disability-adjusted life-years of appendicitis in EU15+ countries: an observational study of the Global Burden of Disease Database, 1990-2019.

BACKGROUND: Appendicitis places a substantial burden on healthcare systems, with acute appendicitis alone being the most common abdominal surgical emergency worldwide. Further characterisation of the disease burden in EU15+ countries may help optimise the distribution of healthcare resources. The aim of this observational study was to assess the trends in mortality, incidence and disability-adjusted life-years (DALYs) of appendicitis across European Union (EU) 15+ countries between the years 1990 and 2019, Supplemental Digital Content 3, http://links.lww.com/JS9/A589 . MATERIALS AND METHODS: Age-standardised mortality rates (ASMRs), age-standardised incidence rates (ASIRs) and DALYs data for appendicitis in males and females were extracted from the 2019 Global Burden of Disease (GBD) study. Temporal trends within the study period were analysed using Joinpoint regression analysis. RESULTS: The median ASMRs across EU15+ countries in 2019 were 0.08/100 000 and 0.13/100 000 for females and males, respectively. Between 1990 and 2019 the median percentage change in ASMR was -52.12% for females and -53.18% in males. The median ASIRs in 2019 for females and males were 251/100 000 and 278/100 000, respectively, with a median percentage change of +7.22% for females and +3.78% for males during the observation period. Decreasing trends in DALYs were observed over the 30-year study period, with median percentage changes of -23.57% and -33.81% for females and males, respectively, Supplemental Digital Content 3, http://links.lww.com/JS9/A589 . CONCLUSION: Overall, a general trend of decreasing appendicitis ASMRs and DALYs was observed across EU15+ countries, despite small overall increases in appendicitis ASIRs, Supplemental Digital Content 3, http://links.lww.com/JS9/A589 . Variations in both diagnostic and management strategies over the study period are likely contributory to the changing trends.

Trends in neck of femur fracture incidence in EU15+ Countries from 1990-2017.

BACKGROUND: Neck of femur fractures (NOFF) pose significant socio-economic costs to society with a high degree of morbidity and mortality. Its incidence rate has been collated within the Global Burden of Disease (GBD) database; however, to date, no comparison across countries has been reported. METHODS: NOFF age-standardised incidence rates (ASIR) per 100,000 population were extracted from the GBD database for European Union (EU) 15+ countries over the period 1990 to 2017. Joinpoint regression analysis of the data identified trends in ASIR and associated estimated annual percentage changes (EAPC). These were analysed by specified timeframe, country and gender. RESULTS: Of the 19 EU15+ countries, 11 (58%) had overall increases in NOFF ASIRs in 2017 compared to 1990. The median ASIRs were 240/100,000 and 322/100,000 for males and females, respectively, in 1990. By 2017, this had increased to 259/100,000 and 325/100,000, respectively. Females consistently had relatively higher NOFF ASIRs with a median gender fracture gap of 62/100,000 in 2017. Males had a higher percentage change in increasing ASIRs, with a smaller percentage change in decreasing ASIRs for all included countries. The highest national ASIRs was observed in Australia, followed by Finland and Belgium. Conversely the Mediterranean countries demonstrated the lowest ASIRs, closely followed by the USA. CONCLUSION: Despite significant advances in primary and secondary hip fracture prevention strategies over the 28-year study period, significant increases in NOFF ASIRs among most EU15+ countries were observed, especially with respect to gender.