Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) Guideline for difficult airway management. Part I.

The Airway Management section of the Spanish Society of Anesthesiology, Resuscitation, and Pain Therapy (SEDAR), the Spanish Society of Emergency Medicine (SEMES), and the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) present the Guide for the comprehensive management of difficult airway in adult patients. Its principles are focused on the human factors, cognitive processes for decision-making in critical situations, and optimization in the progression of strategies application to preserve adequate alveolar oxygenation in order to enhance safety and the quality of care. The document provides evidence-based recommendations, theoretical-educational tools, and implementation tools, mainly cognitive aids, applicable to airway management in the fields of anesthesiology, critical care, emergencies, and prehospital medicine. For this purpose, an extensive literature search was conducted following PRISMA-R guidelines and was analyzed using the GRADE methodology. Recommendations were formulated according to the GRADE methodology. Recommendations for sections with low-quality evidence were based on expert opinion through consensus reached via a Delphi questionnaire.

Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) Guideline for difficult airway management. Part II.

The Airway Management section of the Spanish Society of Anesthesiology, Resuscitation, and Pain Therapy (SEDAR), the Spanish Society of Emergency Medicine (SEMES), and the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) present the Guide for the comprehensive management of difficult airway in adult patients. Its principles are focused on the human factors, cognitive processes for decision-making in critical situations, and optimization in the progression of strategies application to preserve adequate alveolar oxygenation in order to enhance safety and the quality of care. The document provides evidence-based recommendations, theoretical-educational tools, and implementation tools, mainly cognitive aids, applicable to airway management in the fields of anesthesiology, critical care, emergencies, and prehospital medicine. For this purpose, an extensive literature search was conducted following PRISMA-R guidelines and was analyzed using the GRADE methodology. Recommendations were formulated according to the GRADE methodology. Recommendations for sections with low-quality evidence were based on expert opinion through consensus reached via a Delphi questionnaire.

Further evidence of misclassification of the injury deaths in South Africa: When will the barriers to accurate injury death statistics be removed?

BACKGROUND: Contrary to the World Health Organization's internationally recommended medical certificate of cause of death, the South African (SA) death notification form (DNF) does not allow for the reporting of the manner of death to permit accurate coding of external causes of injury deaths. OBJECTIVES: To describe the injury cause-of-death profile from forensic pathology records collected for the National Cause-of-Death Validation (NCoDV) Project and compare it with profiles from other sources of injury mortality data. In particular, the recording of firearm use in homicides is compared between sources. METHODS: The NCoDV Project was a cross-sectional study of deaths that occurred during a fixed period in 2017 and 2018, from a nationally representative sample of 27 health subdistricts in SA. Trained fieldworkers scanned forensic records for all deaths investigated at the forensic mortuaries serving the sampled subdistricts during the study period. Forensic practitioners reviewed the records and completed a medical certificate of cause of death for each decedent. Causes of death were coded to the International Statistical Classification of Diseases, 10th revision (ICD-10), using Iris automated coding software. Cause-specific mortality fractions for injury deaths were compared with Injury Mortality Survey 2017 (IMS 2017) and Statistics South Africa 2017 (Stats SA 2017) datasets. The cause profile for all firearm-related deaths was compared between the three datasets. RESULTS: A total of 5 315 records were available for analysis. Males accounted for 77.6% of cases, and most decedents were aged between 25 and 44 years. Homicide was the leading cause of death (34.7%), followed by transport injuries (32.6%) and suicide (14.7%). This injury cause profile was similar to IMS 2017 but differed markedly from the official statistics, which showed markedly lower proportions of these three causes (15.0%, 11.6% and 0.7%, respectively), and a much higher proportion of other unintentional causes. Investigation of firearm-related deaths revealed that most were homicides in NCoDV 2017/18 (88.5%) and IMS 2017 (93.1%), while in the Stats SA 2017 data, 98.7% of firearm deaths were classified as accidental. Approximately 7% of firearm-related deaths were suicides in NCoDV 2017/18 and IMS 2017, with only 0.3% in Stats SA 2017. CONCLUSION: The official cause-of-death data for injuries in SA in 2017 differed substantially from findings from the NCoDV 2017/18 study and IMS 2017. Accurate data sources would ensure that public health interventions are designed to reduce the high injury burden. Inclusion of the manner of death on the DNF, as is recommended internationally, is critically important to enable more accurate, reliable and valid reporting of the injury profile.

South Africa's male homicide epidemic hiding in plain sight: exploring sex differences and patterns in homicide risk in a retrospective descriptive study of postmortem investigations.

Background: South Africa has homicide rates six times the global average, predominantly among men, but little is known about male victims. As part of the country's first ever study of male homicide we compared 2017 male and female victim profiles for selected covariates, against global averages and previous estimates for 2009. Methods: We conducted a retrospective descriptive study of routine data collected through postmortem investigations, calculating age-standardised mortality rates for manner of death by age, sex and province and male-to-female incidence rate ratios with 95% confidence intervals. We then used generalised linear models and linear regression models to assess the association between sex and victim characteristics including age and mechanism of injury (guns, stabs and blunt force) within and between years. Findings: 87% of 19,477 homicides in 2017 were males, equating to seven male deaths for every female, with sharp force and firearm discharge the most common external causes. Rates were higher among males than females at all ages, and up to eight times higher among males aged 15-44 years. Provincial rates varied overall and by sex, with the highest comparative risk for men vs. women in the Western Cape Province (11.4 males for every 1 female). Male homicides peaked during December and were highest on weekends, underscoring the prominent role of alcohol as a risk factor. Significantly more males tested positive for alcohol than females. Interpretation: The massive, disproportionate and enduring homicide risk borne by adult South African men highlights the negligible prevention response. Only through challenging the normative perception of male invulnerability can we begin to address the enormous burden of violence impacting men. There is an urgent need to address the insidious effect of such societal norms alongside implementing structural interventions to overcome the root causes of poverty and inequality and better control alcohol and firearms. Funding: South African Medical Research Council and Ford Foundation.

Patient-Centered Outcomes in a Randomized Trial Investigating a Multimodal Prevention Program After Transient Ischemic Attack or Minor Stroke: The INSPiRE-TMS Trial.

BACKGROUND: The INSPiRE-TMS trial (Intensified Secondary Prevention Intending a Reduction of Recurrent Events in Transient Ischemic Attack and Minor Stroke Patients) investigated effects of a multicomponent support program in patients with nondisabling stroke or transient ischemic attack. Although secondary prevention targets were achieved more frequently in the intensified care group, no significant differences were seen in rates of recurrent major vascular events. Here, we present the effects on prespecified patient-centered outcomes. METHODS: In a multicenter trial, we randomized patients with modifiable risk factors either to the intensified or conventional care alone program. Intensified care was provided by stroke specialists and used feedback and motivational interviewing strategies (≥8 outpatient visits over 2 years) aiming to improve adherence to secondary prevention targets. We measured physical fitness, disability, cognitive function and health-related quality of life by stair-climbing test, modified Rankin Scale, Montreal Cognitive Assessment, and European Quality of Life 5 Dimension 3 Level during the first 3 years of follow-up. RESULTS: Of 2072 patients (mean age: 67.4years, 34% female) assessed for the primary outcome, patient-centered outcomes were collected in 1,771 patients (877 intensified versus 894 conventional care group). Physical fitness improved more in the intensified care group (mean between-group difference in power (Watt): 24.5 after 1 year (95% CI, 5.5-43.5); 36.1 after 2 years (95% CI, 13.1-59.7) and 29.6 (95% CI, 2.0-57.3 after 3 years). At 1 year, there was a significant shift in ordinal regression analysis of modified Rankin Scale in favor of the intensified care group (common odds ratio, 1.23 [95% CI, 1.03-1.47]) but not after 2 (odds ratio, 1.17 [95% CI, 0.96-1.41]) or 3 years (odds ratio, 1.16 [95% CI, 0.95-1.43]) of follow-up. However, Montreal Cognitive Assessment and European Quality of Life 5 Dimension scores showed no improvement in the intensified intervention arm after 1, 2, or 3 years of follow-up. CONCLUSIONS: Patients of the intensified care program group had slightly better results for physical fitness and modified Rankin Scale after 1 year, but none of the other patient-centered outcomes was significantly improved. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01586702.

Opioid Use After Nephrectomy for Kidney Cancer in Ontario: A Population-Based Study.

OBJECTIVE: To compare the odds of early and prolonged post-operative opioid use in patients undergoing minimally invasive surgery (MIS) vs open surgery for nephrectomy. METHODS: For opioid-naïve patients in Ontario who underwent nephrectomy for kidney cancer (1994-2017, n = 7900), post-discharge opioid use was determined by prescriptions in the Ontario Drug Benefit database (age ≥65 years) and the Narcotics Monitoring System (all patients from 2012). Early opioid use was defined as ≥1 prescription 1-90 days after surgery. Two separate definitions of prolonged opioid use were examined: (1) prescription(s) for ≥60 days during post-operative days 90-365; (2) ≥1 prescriptions between both of: 1-90 days AND 91-180 days after surgery. Predictors of opioid use were assessed using multivariable generalized estimating equation logistic regression, accounting for surgeon clustering. RESULTS: Overall, 67.4% of patients received early opioid prescriptions; however, prolonged use was low, ranging from 1.6 to 4.4% of patients depending on the definition. In multivariable analysis, open nephrectomy was associated with higher odds of early opioid use compared to MIS nephrectomy (Odds Ratio [OR] 1.36, 95% Confidence Interval [CI] 1.19-1.55). Surgery type was not significantly associated with prolonged opioid use for either definition (OR 1.22, CI 0.79-1.89 and OR 1.06, CI 0.83-1.35). CONCLUSIONS: In this population-level study of patients undergoing nephrectomy for kidney cancer, patients who received open surgery were at increased odds of receiving early post-operative opioids compared to MIS. Prolonged opioid use was low overall and was not significantly with associated with type of surgery.

Local recommendations for death scene investigation of sudden unexpected death in infants (SUDI) based on prospective observations.

BACKGROUND: The analyses of death scenes of sudden unexpected death in infants (SUDI) form an integral part of postmortem investigations. However, previous research has suggested that death scene investigation in SUDI cases is inconsistent and limited in South Africa. OBJECTIVES: To suggest realistic and feasible improvements for SUDI scene investigation by means of prospective observation. METHODS: Ten SUDI cases were followed up from death scene until autopsy and detailed observations were made using a semi-structured checklist. Data were analysed in conjunction with published data from the same mortuary to suggest realistic improvements. RESULTS: In all observed cases, the infant was moved prior to the arrival of forensic pathology officers; yet, reconstruction of the events leading to death were never demonstrated with a doll. The use of photography varied, with a median of 15 (standard deviation 6.5) photographs taken at each scene. However, critical photographs, such as those of medication, were often omitted. Furthermore, medicine was not collected from any scene. The use of documentation was inconsistent, where the intended longitudinal use was achieved in only 2 of 10 cases. Forms were inadequately filled in, due to the sensitivity or lack of understanding of various questions, rendering the forms incomplete. CONCLUSIONS: Training of specialised staff should therefore focus on five areas: doll re-enactment, photography, handling of medicine, accurate use of relevant documentation and use of a glossary. The implementation of these recommendations is deemed to be feasible in a resource-scarce mortuary setting and could assist other mortuaries in the development of locally relevant strategies.

Factors Associated with Discontinuation of Active Surveillance among Men with Low-Risk Prostate Cancer: A Population-Based Study.

PURPOSE: The purpose of this study was to describe the uptake, discontinuation and variation of active surveillance (AS) by provider and patient level characteristics. MATERIALS AND METHODS: This observational, population-based study used linked administrative databases and pathology reports to identify all men diagnosed with Gleason score ≤6 prostate cancer (PC) between January 1, 2008 and December 31, 2014 in Ontario, Canada. The Cochran-Armitage test was used for AS trend over time. Treatment-free survival was estimated using cumulative incidence function. Factors associated with discontinuation of AS were evaluated using Cox proportional hazard models. RESULTS: Active surveillance was the initial management strategy for 8,541 cases (51%). Use of AS significantly increased from 38% in 2008 to 69% in 2014 (p=0.001). Men on AS were significantly older (64 years, SD 8.0) than those on initial treatment (62 years, SD 7.7; p=0.001). After a median followup of 48 months, 4,337 (51%) patients had discontinued AS. Treatment-free survival for AS patients at 1, 3, and 5 years were 85%, 58% and 52%, respectively. Median time to definitive treatment after initial AS was 16 months (IQR 11-25 months). Factors associated with AS discontinuation were younger age at diagnosis, year of diagnosis, higher comorbidities, treatment at academic center, treatment by physician and institution in the highest volume tertile, and adverse cancer-specific characteristics (higher prostate specific antigen [PSA], higher number of positive cores and higher percentage of core involvement at diagnosis). CONCLUSIONS: Although the uptake of AS significantly increased over time, there has been a relatively high rate of discontinuation over 5 years. Factors associated with transition to definitive treatment were younger age, care provided by higher volume physicians and institutions, higher PSA and greater PC volume at diagnosis. These results may help guide policy making, developing quality indicators, and developing targeted continued education for physician and patients embarking on AS to establish realistic expectations.

Real-World Practice Patterns and Predictors of Continuous versus Intermittent Androgen Deprivation Therapy Use for Prostate Cancer in Older Men.

PURPOSE: Phase-III randomized control trial evidence suggests intermittent androgen deprivation therapy (IADT) is not significantly inferior to continuous androgen deprivation therapy (ADT) for patients with prostate cancer (PC). However, clinical practice and guidelines differ in their recommendations. We evaluate real-world utilization and practice patterns of IADT. MATERIALS AND METHODS: Ontario men ≥65 years of age with PC who initiated ADT for ≥3 months were identified (1997-2017). Lapses in ADT ≥6 months (initial gap) and ≥3 months (subsequent gaps) were used to classify IADT. Neoadjuvant/adjuvant therapy was excluded. Disease stage adjustment was completed for patients with likely metastatic disease based on de novo presentation with ADT. Patient and physician predictors of IADT were analyzed using multivariable logistic regression. RESULTS: We identified 8,544 patients with 1,715 having previously received local therapy. Among all patients, 16.4% received IADT. This ranged from 11.4%-24.8% across health-planning regions and increased to 26.6% in those with previous local therapy. Mean followup was 8.3 years. Patients with prior local therapy (OR 1.85, 95% CI 1.59-2.17, p <0.001) and those in the highest income quintile (OR 1.32, 95% CI 1.08-1.60, p=0.005) had increased odds of receiving IADT. Radiation oncologists were more likely to use IADT than urologists (OR 1.99, 95% CI 1.59-2.50, p <0.001), as were physicians with more experience (≥10 years in practice: OR 1.44, 95% CI 1.11-1.88, p=0.007). In specialty-stratified analyses, case volume was significantly associated with IADT for radiation oncologists (highest quartile: OR 1.73, 95% CI 1.14-2.62, p=0.009). CONCLUSIONS: IADT remains underutilized for patients with PC who ≥65 years of age with only 1 in 4 to 1 in 6 eligible patients receiving this form of care. Clinical, sociodemographic and physician characteristics play an important role in treatment selection.

Can Male Mice Develop Preference Towards Gentle Stroking by an Experimenter?

Gentle stroking, a type of affective touch that holds hedonic and rewarding value, is critical to our daily inter-individual communication. This positive socio-emotional aspect of touch is conveyed through a subclass of C afferents known as C-Tactile fibers in humans with an analogous system in rodents proposed. Here, we describe a novel tactile conditioned place preference paradigm using mice and demonstrate that gentle stroking by an experimenter is rewarding. In order to investigate the relationship between tactile preference and innate sociability, mice were subjected to the classic three-chambered test of social approach, where mice displayed significant preference towards the experimenter's hand. These findings suggest that gentle stroking evoked by an experimenter can play an important role in reward and preference and establish an affiliative relationship between mice and humans. Future research can potentially use this model to examine fiber type involvement and elucidate the significance of these findings for activation of the reward system.

Long-term use of 5-alpha-reductase inhibitors is safe and effective in men on active surveillance for prostate cancer.

BACKGROUND: Although 5-alpha-reductase inhibitors (5ARIs) have been shown to benefit men with prostate cancer (PCa) on active surveillance (AS), their long-term safety remains controversial. Our objective is to describe the long-term association of 5ARI use with PCa progression in men on AS. MATERIALS/SUBJECTS AND METHODS: The cohort of men with low-risk PCa was derived from a prospectively maintained AS database at the Princess Margaret (1995-2016). Pathologic, grade, and volume progression were the primary end points. Kaplan-Meier time-to-event analysis was performed and Cox proportional hazards regression was used to determine predictors of progression where 5ARI exposure was analyzed as a time-dependent variable. Patients who came off AS prior to any progression events were censored at that time. RESULTS: The cohort included 288 men with median follow-up of 82 months (interquartile range: 37-120 months). Among non-5ARI users (n = 203); 114 men (56.2%) experienced pathologic progression compared with 24 men (28.2%) in the 5ARI group (n = 85), (p < 0.001). Grade and volume progression were higher in the non-5ARI group compared with the 5ARI group (n = 82; 40.4% vs. n = 19; 22.4% respectively, p = 0.003 for grade progression; n = 87; 43.1% and n = 15; 17.7%, respectively for volume progression p < 0.001). Lack of 5ARI use was independently positively associated with pathologic progression (HR: 2.65; CI: 1.65-4.24), grade progression (HR: 2.75; CI: 1.49-5.06), and volume progression (HR: 3.15; CI: 1.78-5.56). The frequency of progression to high-grade (Grade Group 4-5) tumors was not significantly different between the groups. CONCLUSIONS: Use of 5ARIs diminished both grade and volume progression without an increased risk of developing Grade Groups 4-5 disease.

Higher levels of social and material deprivation are associated with higher rates of influenza-like illness-related emergency department visits: Edmonton, Alberta, 2004-2014.

OBJECTIVES: Neighbourhood-level deprivation is associated with hospitalization related to respiratory infections; however, hospitalizations exclude many who seek care with less severe respiratory illnesses. Another major seasonal contributor to respiratory illness-associated healthcare burdens are influenza-like illness (ILI)-related emergency department (ED) visits. We investigated associations between area-level social and material deprivation and ILI-related ED use. STUDY DESIGN: This is a retrospective ecological study. METHODS: We linked ILI-related ED visit data (2004-2014) for Edmonton, Alberta to a Canadian area-level material and social deprivation index, categorizing deprivation into quintiles. Using a multivariable Poisson model with log population as the offset, we modelled the relationship between visit rates and material and social deprivation adjusting for week and season, age, sex and the interaction between age and sex. RESULTS: We included 67,585 ILI-related ED visits, representing 1075.5 (95% confidence interval (CI) = 1067.4-1083.6) visits per 100,000 person-years. ILI-related visit rates increased as each of material and social deprivation increased; increases were slightly greater for material deprivation. Comparing the most deprived quintile to the least deprived quintile: for material deprivation, ILI-related ED visit rates were two times higher (rate ratio (RR) = 2.00, 95% CI = 1.96-2.05); and, for social deprivation, one-and-a-half times higher (RR = 1.47, 95% CI = 1.44-1.51). CONCLUSIONS: Higher area-level material and social deprivation were associated with higher ILI-related ED visit rates. These findings can be used to identify areas that may need additional public health and healthcare resources and to improve targeting of prevention strategies. Understanding differentials in healthcare use such as this may be especially relevant to ensuring equity of outcomes for pandemic preparedness planning.

Bodies without names: A retrospective review of unidentified decedents at Salt River Mortuary, Cape Town, South Africa, 2010 - 2017.

BACKGROUND: Decedents who remain unidentified and/or unclaimed following postmortem investigations are an international occurrence. Salt River Mortuary (SRM), one of the largest and busiest mortuaries in Cape Town, South Africa, also experiences this burden; however, little is known about the nature of these cases. OBJECTIVES: To review all cases admitted to SRM between 1 January 2010 and 31 December 2017 (n=26 960), with the objectives of quantifying the number of decedents who remained unidentified, and to better understand circumstances surrounding death and the identification methods that were attempted. METHODS: Data pertaining to unidentified cases were collected from mortuary burial records and medicolegal case files. Data were analysed using Microsoft Excel 2013 (Microsoft, USA). RESULTS: Over the 8-year period, 2 476 cases (mean 9.2% of caseload per annum) admitted to SRM remained unidentified. Bodies underwent an autopsy after a median of 3 days after a death declaration. However, in cases of decomposition, skeletonisation or other physical inhibitors of visual identification (n=345; 14.1%), the time between death and autopsy was undetermined owing to the overall lack of entomology analyses. Approximately 56.9% (n=1 408) of cases were between 20 and 50 years of age, and were predominantly males (78.7%). Unnatural injury-related deaths accounted for 32.4% of unidentified deaths, with firearms, assault and stabbings contributing approximately one-third each. With regard to identification attempts, forensic anthropology was requested in only 1.5% of these cases, and DNA analysis appeared to be used in only 23.6% of cases. Data pertaining to secondary identifiers, forensic odontology and fingerprint analyses were not formally recorded. CONCLUSIONS: The relatively short time interval between death declaration and postmortem examination suggests that DNA analysis should be more regularly utilised. Furthermore, it is urged that other ancillary investigations should be more regularly employed; that there is a greater collaboration between stakeholders and identification attempts; and that results are centrally recorded.

A support programme for secondary prevention in patients with transient ischaemic attack and minor stroke (INSPiRE-TMS): an open-label, randomised controlled trial.

BACKGROUND: Patients with recent stroke or transient ischaemic attack are at high risk for a further vascular event, possibly leading to permanent disability or death. Although evidence-based treatments for secondary prevention are available, many patients do not achieve recommended behavioural modifications and pharmaceutical prevention targets in the long-term. We aimed to investigate whether a support programme for enhanced secondary prevention can reduce the frequency of recurrent vascular events. METHODS: INSPiRE-TMS was an open-label, multicentre, international randomised controlled trial done at seven German hospitals with acute stroke units and a Danish stroke centre. Patients with non-disabling stroke or transient ischaemic attack within 2 weeks from study enrolment and at least one modifiable risk factor (ie, arterial hypertension, diabetes, atrial fibrillation, or smoking) were included. Computerised randomisation was used to allocate patients (1:1) either to the support programme in addition to conventional care or to conventional care alone. The support programme used feedback and motivational interviewing strategies with eight outpatient visits over 2 years aiming to improve adherence to secondary prevention targets. The primary outcome was the composite of major vascular events consisting of stroke, acute coronary syndrome, and vascular death, assessed in the intention-to-treat population (all patients who underwent randomisation, did not withdraw study participation, and had at least one follow-up). Outcomes were assessed at annual follow-ups using time-to-first-event analysis. All-cause death was monitored as a safety outcome. This trial is registered with ClinicalTrials.gov, NCT01586702. FINDINGS: From Aug 22, 2011, to Oct 30, 2017, we enrolled 2098 patients. Of those, 1048 (50·0%) were randomly assigned to the support programme group and 1050 (50·0%) patients were assigned to the conventional care group. 1030 (98·3%) patients in the support group and 1042 (99·2%) patients in the conventional care group were included in the intention-to-treat analysis. The mean age of analysed participants was 67·4 years and 700 (34%) were women. After a mean follow-up of 3·6 years, the primary outcome of major vascular events had occurred in 163 (15·8%) of 1030 patients of the support programme group and in 175 (16·8%) of 1042 patients of the conventional care group (hazard ratio [HR] 0·92, 95% CI 0·75-1·14). Total major vascular event numbers were 209 for the support programme group and 225 for the conventional care group (incidence rate ratio 0·93, 95% CI 0·77-1·12; p=0·46) and all-cause death occurred in 73 (7·1%) patients in the support programme group and 85 (8·2%) patients in the conventional care group (HR 0·85, 0·62-1·17). More patients in the support programme group achieved secondary prevention targets (eg, in 1-year-follow-up 52% vs 42% [p<0·0001] for blood pressure, 62% vs 54% [p=0·0010] for LDL, 33% vs 19% [p<0·0001] for physical activity, and 51% vs 34% [p=0·0010] for smoking cessation). INTERPRETATION: Provision of an intensified secondary prevention programme in patients with non-disabling stroke or transient ischaemic attack was associated with improved achievement of secondary prevention targets but did not lead to a significantly lower rate of major vascular events. Further research is needed to investigate the effects of support programmes in selected patients who do not achieve secondary prevention targets soon after discharge. FUNDING: German Federal Ministry of Education and Research, Pfizer, and German Stroke Foundation.

Predicting influenza-like illness-related emergency department visits by modelling spatio-temporal syndromic surveillance data.

Predicting the magnitude of the annual seasonal peak in influenza-like illness (ILI)-related emergency department (ED) visit volumes can inform the decision to open influenza care clinics (ICCs), which can mitigate pressure at the ED. Using ILI-related ED visit data from the Alberta Real Time Syndromic Surveillance Net for Edmonton, Alberta, Canada, we developed (training data, 1 August 2004-31 July 2008) and tested (testing data, 1 August 2008-19 February 2014) spatio-temporal statistical prediction models of daily ILI-related ED visits to estimate high visit volumes 3 days in advance. Our Main Model, based on a generalised linear mixed model with random intercept, incorporated prediction residuals over 14 days and captured increases in observed volume ahead of peaks. During seasonal influenza periods, our Main Model predicted volumes within ±30% of observed volumes for 67%-82% of high-volume days and within 0.3%-21% of observed seasonal peak volumes. Model predictions were not as successful during the 2009 H1N1 pandemic. Our model can provide early warning of increases in ILI-related ED visit volumes during seasonal influenza periods of differing intensities. These predictions may be used to support public health decisions, such as if and when to open ICCs, during seasonal influenza epidemics.

A retrospective time trend study of firearm and non-firearm homicide in Cape Town from 1994 to 2013.

BACKGROUND: Gunshot injuries from interpersonal violence are a major cause of mortality. In South Africa (SA), the Firearms Control Act of 2000 sought to address firearm violence by removing illegally owned firearms from circulation, stricter regulation of legally owned firearms, and stricter licensing requirements. Over the last few years, varied implementation of the Act and police corruption have increased firearm availability. OBJECTIVES: To investigate whether changes in firearm availability in SA were associated with changes in firearm homicide rates. METHODS: This was a retrospective time trend study (1994 - 2013) using postmortem data. Time trends of firearm and non-firearm homicide rates were analysed with generalised linear models. Distinct time periods for temporal trends were assigned based on a priori assumptions regarding changes in the availability of firearms. RESULTS: Firearm and non-firearm homicide rates adjusted for age, sex and race exhibited different temporal trends. Non-firearm homicide rates either decreased or remained stable over the entire period. Firearm homicide increased at 13% annually from 1994 through 2000, and decreased by 15% from 2003 through 2006, corresponding with changes in firearm availability in 2001, 2003, 2007 and 2011. A 21% annual increase in firearm homicide after 2010 coincided with police fast-tracking new firearm licence applications. Cape Town's coloured population experienced a significantly greater increase than other population groups following additional exposure to illegal firearms from 2007. CONCLUSIONS: The strong association between firearm availability and homicide, and the reversal of a decreasing firearm homicide trend during a period of lax enforcement, provide further support for the association between reduced firearm homicide and stricter regulation.

Predicting the pain continuum after adolescent idiopathic scoliosis surgery: A prospective cohort study.

BACKGROUND: Chronic postsurgical pain (CPSP) affects half a million children annually in the United States, with dire socioeconomic consequences, including long-term disability into adulthood. The few studies of CPSP in children are limited by sample size, follow-up duration, non-homogeneity of surgical procedure and factors evaluated. METHODS: In a prospective study of 144 adolescents undergoing a single major surgery (spine fusion), we evaluated demographic, perioperative, surgical and psychosocial factors as predictors of a continuum of postsurgical pain: immediate, pain maintenance at 2-3 months (chronic pain/CP) and persistence of pain a year (persistent pain/PP) after surgery. RESULTS: We found an incidence of 37.8% and 41.8% for CP and PP. CP and acute pain were both significant predictors for developing PP (p-value <0.001 and 0.003). Preoperative pain and higher postoperative opioid requirement was significantly associated with CP (p = 0.015, p = 0.002), while Childhood Anxiety Sensitivity Index (p = 0.002) and surgical duration (p = 0.014) predicted PP. The final regression models had reasonable predictive accuracy (c-statistic of 0.73 and 0.83 for CP and PP, respectively). Anxiety scores and catastrophizing for child and parent were found to be significantly correlated (p = 0.005, p = 0.013 respectively). Pain trajectories revealed that 65% of patients who developed PP reported CP and high pain trends; however, 33% of those who developed PP could not be identified using solely pain criteria. CONCLUSION: Persistent postsurgical pain in children is a significant problem. It can be predicted in part by combinations of psychological and clinical variables, which may provide evidence-based measures to prevent development of CPSP in the future. SIGNIFICANCE: In a homogeneous cohort of adolescents undergoing spine fusion, we report a high incidence of persistent postsurgical pain (41.8%) predicted by child anxiety, perioperative pain, and surgical duration. Our results stress timely preventive and therapeutic strategies.

ABCC3 genetic variants are associated with postoperative morphine-induced respiratory depression and morphine pharmacokinetics in children.

Respiratory depression (RD) is a serious side effect of morphine and detrimental to effective analgesia. We reported that variants of the ATP binding cassette gene ABCC3 (facilitates hepatic morphine metabolite efflux) affect morphine metabolite clearance. In this study of 316 children undergoing tonsillectomy, we found significant association between ABCC3 variants and RD leading to prolonged postoperative care unit stay (prolonged RD). Allele A at rs4148412 and allele G at rs729923 caused a 2.36 (95% CI=1.28-4.37, P=0.0061) and 3.7 (95% CI 1.47-9.09, P=0.0050) times increase in odds of prolonged RD, respectively. These clinical associations were supported by increased formation clearance of morphine glucuronides in children with rs4148412 AA and rs4973665 CC genotypes in this cohort, as well as an independent spine surgical cohort of 67 adolescents. This is the first study to report association of ABCC3 variants with opioid-related RD, and morphine metabolite formation (in two independent surgical cohorts).

Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring.

Eosinophilic esophagitis (EoE) is diagnosed by symptoms, and at least 15 intraepithelial eosinophils per high power field in an esophageal biopsy. Other pathologic features have not been emphasized. We developed a histology scoring system for esophageal biopsies that evaluates eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces (DIS), surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Severity (grade) and extent (stage) of abnormalities were scored using a 4-point scale (0 normal; 3 maximum change). Reliability was demonstrated by strong to moderate agreement among three pathologists who scored biopsies independently (P ≤ 0.008). Several features were often abnormal in 201 biopsies (101 distal, 100 proximal) from 104 subjects (34 untreated, 167 treated). Median grade and stage scores were significantly higher in untreated compared with treated subjects (P ≤ 0.0062). Grade scores for features independent of eosinophil counts were significantly higher in biopsies from untreated compared with treated subjects (basal zone hyperplasia P ≤ 0.024 and DIS P ≤ 0.005), and were strongly correlated (R-square >0.67). Principal components analysis identified three principal components that explained 78.2% of the variation in the features. In logistic regression models, two principal components more closely associated with treatment status than log distal peak eosinophil count (PEC) (R-square 17, area under the curve (AUC) 77.8 vs. R-square 9, AUC 69.8). In summary, the EoE histology scoring system provides a method to objectively assess histologic changes in the esophagus beyond eosinophil number. Importantly, it discriminates treated from untreated patients, uses features commonly found in such biopsies, and is utilizable by pathologists after minimal training. These data provide rationales and a method to evaluate esophageal biopsies for features in addition to PEC.