Annie Herbert

Incidence, predictors and clinical characteristics of orolingual angio-oedema complicating thrombolysis with tissue plasminogen activator for ischaemic stroke

Background Orolingual angio-oedema is a recognised complication of tissue plasminogen activator (tPA) for ischaemic stroke. We investigated its incidence, clinical characteristics and relationship with other factors in patients receiving tPA at a UK centre. Methods 530 consecutive patients (median age 70 years) receiving tPA treatment for confirmed ischaemic stroke were included. Cases were defined as those developing angio-oedema within 24 h of initiation of tPA. Angio-oedema was retrospectively classified as mild, moderate or severe using predefined criteria. The primary analysis was the association between prior ACE inhibitor (ACE-I) treatment and angio-oedema. Results Orolingual angio-oedema was observed in 42 patients (7.9%; 95% CI 5.5% to 10.6%), ranging from 5 to 189 min after initiation of tPA (median 65 min). 12% of the angio-oedema cases were severe (1% of all patients treated with tPA), requiring urgent advanced airway management. 172 patients (33%) were taking ACE-I. In multifactorial analyses, only prior ACE-I treatment remained a significant independent predictor of angio-oedema (odds ratio (OR) 2.3; 95% CI 1.1 to 4.7). Conclusions Angio-oedema occurs more frequently than previously reported and is associated with preceding ACE-I treatment. Angio-oedema may be delayed and progress to life-threatening airway compromise, which has implications for the assessment and delivery of thrombolysis.

Causes of death up to 10 years after admissions to hospitals for self-inflicted, drug-related or alcohol-related, or violent injury during adolescence: a retrospective, nationwide, cohort study

BACKGROUND Emergency hospital admission with adversity-related injury (ie, self-inflicted, drug-related or alcohol-related, or violent injury) affects 4% of 10-19-year-olds. Their risk of death in the decade after hospital discharge is twice as high as that of adolescents admitted to hospitals for accident-related injury. We established how cause of death varied between these groups. METHODS We did a retrospective, nationwide, cohort study comparing risks of death in five causal groups (suicide, drug-related or alcohol-related, homicide, accidental, and other causes of death) up to 10 years after hospital discharge following adversity-related (self-inflicted, drug-related or alcohol-related, or violent injury) or accident-related (for which there was no recorded adversity) injury. We included adolescents (aged 10-19 years) who were admitted as an emergency for adversity-related or accident-related injury between April 1, 1997, and March 31, 2012. We excluded adolescents who did not have their sex recorded, died during the index admission, had no valid discharge date, or were admitted with injury related to neither adversity nor accidents. We identified admissions for adversity-related or accident-related injury to the National Health Service in England with the International Classification of Diseases-10 codes in Hospital Episode Statistics data, linked to the Office for National Statistics mortality data for England, to establish cause-specific risks of death between the first day and 10 years after discharge, and to compare risks between adversity-related and accident-related index injury after adjustment for age group, socioeconomic status, and chronic conditions. FINDINGS We identified 1 080 368 adolescents (388 937 [36·0%] girls, 690 546 [63·9%] boys, and 885 [0·1%] adolescents who did not have their sex recorded). Of these adolescents, we excluded 40 549 (10·4%) girls, 56 107 (8·1%) boys, and all 885 without their sex recorded. Of the 333 009 (30·8%) adolescents admitted with adversity-related injury (181 926 [54·6%] girls and 151 083 [45·4%] boys) and 649 818 (60·2%) admitted with accident-related injury (166 462 [25·6%] girls and 483 356 [74·4%] boys), 4782 (0·5%) died in the 10 years after discharge (1312 [27·4%] girls and 3470 [72·6%] boys). Adolescents discharged after adversity-related injury had higher risks of suicide (adjusted subhazard ratio 4·54 [95% CI 3·25-6·36] for girls, and 3·15 [2·73-3·63] for boys) and of drug-related or alcohol-related death (4·71 [3·28-6·76] for girls, and 3·53 [3·04-4·09] for boys) in the next decade than they did after accident-related injury. Although we included homicides in our estimates of 10-year risks of adversity-related deaths, we did not explicitly present these risks because of small numbers and risks of statistical disclosure. There was insufficient evidence that girls discharged after adversity-related injury had increased risks of accidental deaths compared with those discharged after accident-related injury (adjusted subhazard ratio 1·21 [95% CI 0·90-1·63]), but there was evidence that this risk was increased for boys (1·26 [1·09-1·47]). There was evidence of decreased risks of other causes of death in girls (0·64 [0·53-0·77]), but not in boys (0·99 [0·84-1·17]). Risks of suicide were increased following self-inflicted injury (adjusted subhazard ratio 5·11 [95% CI 3·61-7·23] for girls, and 6·20 [5·27-7·30] for boys), drug-related or alcohol-related injury (4·55 [3·23-6·39] for girls, and 4·51 [3·89-5·24] for boys), and violent injury in boys (1·43 [1·15-1·78]) versus accident-related injury. However, the increased risk of suicide in girls following violent injury versus accident-related injury was not significantly increased (adjusted subhazard ratio 1·48 [95% CI 0·73-2·98]). Following each type of index injury, risks of suicide and risks of drug-related or alcohol-related death were increased by similar magnitudes. INTERPRETATION Risks of suicide were significantly increased after all types of adversity-related injury except for girls who had violent injury. Risks of drug-related or alcohol-related death increased by a similar magnitude. Current practice to reduce risks of harm after self-inflicted injury should be extended to drug-related or alcohol-related and violent injury in adolescence. Prevention should address the substantial risks of drug-related or alcohol-related death alongside risks of suicide. FUNDING UK Department of Health.

Violence, self-harm and drug or alcohol misuse in adolescents admitted to hospitals in England for injury: a retrospective cohort study

Objectives Of adolescents in the general population in England, we aimed to determine (1) the proportion that has an emergency admission to hospital for injury related to adversity (violence, self-harm or drug or alcohol misuse) and (2) the risk of recurrent emergency admissions for injury in adolescents admitted with adversity-related injury compared with those admitted with accident-related injury only. Design We used longitudinally linked administrative hospital data (Hospital Episode Statistics) to identify participants aged 10–19 years with emergency admissions for injury (including day cases lasting more than 4 h) in England in 1998–2011. We used the Office for National Statistics mid-year estimates for population denominators. Results Approximately 4.3% (n=141 248) of adolescents in the general population (n=3 254 046) had one or more emergency admissions for adversity-related injury (girls 4.6%, boys 4.1%), accounting for 50% of all emergency admissions for injury in girls and 29.1% in boys. Admissions for self-harm or drug or alcohol misuse commonly occurred in the same girls and boys. Recurrent emergency admissions for injury were more common in adolescents with adversity-related injury (girls 17.3%, boys 16.5%) than in those with accident-related injury only (girls 4.7%, boys 7.4%), particularly for adolescents with adversity-related injury related to multiple types of adversity (girls 21.1%, boys 24.2%). Conclusions Hospital-based interventions should be developed to reduce the risk of future injury in adolescents admitted for adversity-related injury.

Hearing Impairment and Incident Dementia: Findings from the English Longitudinal Study of Ageing

To determine whether hearing loss is associated with incident physician‐diagnosed dementia in a representative sample.

10-y risks of death and emergency re-admission in adolescents hospitalised with violent, drug- or alcohol-related, or self-inflicted injury: a population-based cohort study

Background Hospitalisation for adversity-related injury (violent, drug/alcohol-related, or self-inflicted injury) has been described as a “teachable moment”, when intervention may reduce risks of further harm. Which adolescents are likely to benefit most from intervention strongly depends on their long-term risks of harm. We compared 10-y risks of mortality and re-admission after adversity-related injury with risks after accident-related injury. Methods and Findings We analysed National Health Service admissions data for England (1 April 1997–31 March 2012) for 10–19 y olds with emergency admissions for adversity-related injury (violent, drug/alcohol-related, or self-inflicted injury; n = 333,009) or for accident-related injury (n = 649,818). We used Kaplan–Meier estimates and Cox regression to estimate and compare 10-y post-discharge risks of death and emergency re-admission. Among adolescents discharged after adversity-related injury, one in 137 girls and one in 64 boys died within 10 y, and 54.2% of girls and 40.5% of boys had an emergency re-admission, with rates being highest for 18–19 y olds. Risks of death were higher than in adolescents discharged after accident-related injury (girls: age-adjusted hazard ratio 1.61, 95% CI 1.43–1.82; boys: 2.13, 95% CI 1.98–2.29), as were risks of re-admission (girls: 1.76, 95% CI 1.74–1.79; boys: 1.41, 95% CI 1.39–1.43). Risks of death and re-admission were increased after all combinations of violent, drug/alcohol-related, and self-inflicted injury, but particularly after any drug/alcohol-related or self-inflicted injury (i.e., with/without violent injury), for which age-adjusted hazard ratios for death in boys ranged from 1.67 to 5.35, compared with 1.25 following violent injury alone (girls: 1.09 to 3.25, compared with 1.27). The main limitation of the study was under-recording of adversity-related injuries and misclassification of these cases as accident-related injuries. This misclassification would attenuate the relative risks of death and re-admission for adversity-related compared with accident-related injury. Conclusions Adolescents discharged after an admission for violent, drug/alcohol-related, or self-inflicted injury have increased risks of subsequent harm up to a decade later. Introduction of preventive strategies for reducing subsequent harm after admission should be considered for all types of adversity-related injury, particularly for older adolescents.

Precision, accuracy and added value of central pressure measurement.

The interest in measurement of central pressure is a hot subject at the present time. Indeed, as the geometry of the arterial tree and its mechanical properties are altering the pressure generated by the left ventricle, this has important consequences for measurement of blood pressure. The conventional site of blood pressure measurement is the upper arm. Blood pressure measured at the brachial artery site does not represent accurately the pressure applied on organs suffering from increased blood pressure, such as the brain, the kidney and the left ventricle. Because of anatomical proximity (for left ventricle), and because the kidney and the brain have torrential blood flow exposing them directly to the pulsatility of central pressure, it is believed that pressure measured centrally, that is close to the root of the aorta may be more relevant in terms of associated risk. The main difficulty with central pressure is that it is not accessible by direct measurement outside the catheterization room but it is rather estimated from peripheral waveforms. Although there is compelling evidence for added predicted risk for aortic stiffness (measured by carotid to femoral pulse wave velocity) [1–3], evidence is scarcer for central pressure, likely because central pressure is estimated, not directly measured [4]. This is the principal interest of the article from Kips et al. in the present issue of the Journal of Hypertension, which carefully investigates the systematic differences between two popular devices estimating central pressure, the SphygmoCor system, first introduced in the market and making use of a transfer function to synthesize aortic pressure from radial tonometry, and the Omron HEM 9000 AI, which uses intelligent multisensor radial tonometry to extract central pressure from the late systolic peak (using a dedicated algorithm and an additional linear equation) [5]. The authors chose to compare these two devices to calibrate carotid waveforms obtained from carotid tonometry. This choice was a pragmatic one, as there is no noninvasive gold standard and as invasive

Time-trends in rates of hospital admission of adolescents for violent, self-inflicted or drug/alcohol-related injury in England and Scotland, 2005-11: population-based analysis

Background Incidence of emergency admissions for violent injury in 10- to 18-year olds decreased in England and Scotland between 2005 and 2011, but more steeply in Scotland. To generate hypotheses about causes of these differences, we determined whether trends were consistent across admissions for three common types of adversity-related injury (violent, self-inflicted and drug/alcohol-related). Methods Emergency admissions to NHS hospitals were captured using Hospital Episode Statistics and Scottish Morbidity Records. Adversity-related injury was defined using ICD-10 codes. Analyses were stratified by sex/age groups (10-12, 13-15 and 16-18 years) and adjusted for background trends in admissions for injury. Results During 2005-11, rates declined in all sex/age groups in Scotland (reductions adjusted for background trends ranged from -22.0 to -103.7/100 000) and in girls and boys aged <16 years in England (adjusted reductions -12.0 to -49.9/100 000). However, these rates increased in England for both sexes aged 16-18 years (adjusted increases, girls 71.8/100 000; boys 28.0/100 000). However, throughout 2005-11 overall rates remained relatively similar in England and Scotland for both sexes aged <16 years, and remained higher in Scotland for both sexes aged 16-18 years. Conclusions A greater decline in the rates of emergency admissions for adversity-related injury for adolescents in Scotland compared with England could signal more effective policies in Scotland for reducing violence, self-harm, or drug/alcohol misuse, particularly for 16 to 18-year olds.

Associations between diagnostic pathways and care experience in colorectal cancer: evidence from patient-reported data

Objective To examine how different pathways to diagnosis of colorectal cancer may be associated with the experience of subsequent care. Design Patient survey linked to information on diagnostic route. English patients with colorectal cancer (analysis sample n=6837) who responded to a patient survey soon after their hospital treatment. Main outcome measures Odds Ratios and adjusted proportions of negative evaluation of key aspects of care for colorectal cancer, including the experience of shared decision-making about treatment, specialist nursing and care coordination, by diagnostic route (ie, screening detection, emergency presentation, urgent and elective general practitioner referral). Results For 14 of 18 questions, there was evidence (p≤0.02) for variation in patient experience by diagnostic route, with 6–31 percentage point differences between routes in adjusted proportions of negative experience. Emergency presenters were more likely to report a negative experience for most questions, including those about adequacy of information about their diagnosis and sufficient explanation before operations. Screen-detected patients were least likely to report negative experiences except for support from primary care. Patients diagnosed through elective primary care referrals were most likely to report worse experience for questions for which overall variation by route was generally small. Conclusions Screening-detected patients tend to report the best and emergency presenters the worst experience of subsequent care. Improvement efforts can target care integration for screening-detected patients and provision of information about the diagnosis and treatment of emergency presenters.

Diagnostic timeliness in adolescents and young adults with cancer: a cross-sectional analysis of the BRIGHTLIGHT cohort

Summary Background Adolescents and young adults (AYAs) are thought to experience prolonged intervals to cancer diagnosis, but evidence quantifying this hypothesis and identifying high-risk patient subgroups is insufficient. We aimed to investigate diagnostic timeliness in a cohort of AYAs with incident cancers and to identify factors associated with variation in timeliness. Methods We did a cross-sectional analysis of the BRIGHTLIGHT cohort, which included AYAs aged 12–24 years recruited within an average of 6 months from new primary cancer diagnosis from 96 National Health Service hospitals across England between July 1, 2012, and April 30, 2015. Participants completed structured, face-to-face interviews to provide information on their diagnostic experience (eg, month and year of symptom onset, number of consultations before referral to specialist care); demographic information was extracted from case report forms and date of diagnosis and cancer type from the national cancer registry. We analysed these data to assess patient interval (time from symptom onset to first presentation to a general practitioner [GP] or emergency department), the number of prereferral GP consultations, and the symptom onset-to-diagnosis interval (time from symptom onset to diagnosis) by patient characteristic and cancer site, and examined associations using multivariable regression models. Findings Of 1114 participants recruited to the BRIGHTLIGHT cohort, 830 completed a face-to-face interview. Among participants with available information, 204 (27%) of 748 had a patient interval of more than a month and 242 (35%) of 701 consulting a general practitioner had three or more prereferral consultations. The median symptom onset-to-diagnosis interval was 62 days (IQR 29–153). Compared with male AYAs, female AYAs were more likely to have three or more consultations (adjusted odds ratio [OR] 1·6 [95% CI 1·1–2·3], p=0·0093) and longer median symptom onset-to-diagnosis intervals (adjusted median interval longer by 24 days [95% CI 11–37], p=0·0005). Patients with lymphoma or bone tumours (adjusted OR 1·2 [95% CI 0·6–2·1] compared with lymphoma) were most likely to have three or more consultations and those with melanoma least likely (0·2 [0·1–0·7] compared with lymphoma). The adjusted median symptom onset-to-diagnosis intervals were longest in AYAs with bone tumours (51 days [95% CI 29–73] longer than for lymphoma) and shortest in those with leukaemia (33 days [17–49] shorter than for lymphoma). Interpretation The findings provide a benchmark for diagnostic timeliness in young people with cancer and help to identify subgroups at higher risk of a prolonged diagnostic journey. Further research is needed to understand reasons for these findings and to prioritise and stratify early diagnosis initiatives for AYAs. Funding National Institute for Health Research, Teenage Cancer Trust, and Cancer Research UK.

Vision Impairment and Risk of Dementia: Findings from the English Longitudinal Study of Ageing: Findings from the English Longitudinal Study of Ageing

To determine whether vision impairment is independently associated cross‐sectionally and longitudinally with dementia.