COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

Background rates of adverse events of special interest for COVID-19 vaccines: A multinational Global Vaccine Data Network (GVDN) analysis.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) project was established in 2021 under the multinational Global Vaccine Data Network (GVDN) consortium to facilitate the rapid assessment of the safety of newly introduced vaccines. This study analyzed data from GVDN member sites on the background incidence rates of conditions designated as adverse events of special interest (AESI) for COVID-19 vaccine safety monitoring. METHODS: Eleven GVDN global sites obtained data from national or regional healthcare databases using standardized methods. Incident events of 13 pre-defined AESI were included for a pre-pandemic period (2015-19) and the first pandemic year (2020). Background incidence rates (IR) and 95% confidence intervals (CI) were calculated for inpatient and emergency department encounters, stratified by age and sex, and compared between pre-pandemic and pandemic periods using incidence rate ratios. RESULTS: An estimated 197 million people contributed 1,189,652,926 person-years of follow-up time. Among inpatients in the pre-pandemic period (2015-19), generalized seizures were the most common neurological AESI (IR ranged from 22.15 [95% CI 19.01-25.65] to 278.82 [278.20-279.44] per 100,000 person-years); acute disseminated encephalomyelitis was the least common (<0.5 per 100,000 person-years at most sites). Pulmonary embolism was the most common thrombotic event (IR 45.34 [95% CI 44.85-45.84] to 93.77 [95% CI 93.46-94.08] per 100,000 person-years). The IR of myocarditis ranged from 1.60 [(95% CI 1.45-1.76) to 7.76 (95% CI 7.46-8.08) per 100,000 person-years. The IR of several AESI varied by site, healthcare setting, age and sex. The IR of some AESI were notably different in 2020 compared to 2015-19. CONCLUSION: Background incidence of AESIs exhibited some variability across study sites and between pre-pandemic and pandemic periods. These findings will contribute to global vaccine safety surveillance and research.

Magnetic resonance imaging of the internal auditory meatus for vestibular schwannoma in ENT practice: a retrospective analysis with literature and guidelines review.

OBJECTIVES: Magnetic resonance imaging scans of the internal acoustic meatus are commonly requested in the investigation of audio-vestibular symptoms for potential vestibular schwannoma. There have been multiple studies into protocols for requesting magnetic resonance imaging for vestibular schwannoma, but none have been reported based on UK National Institute for Health and Care Excellence guidelines for investigating audio-vestibular symptoms. This study intended to identify the local magnetic resonance imaging detection rates and patterns of vestibular schwannoma, and to audit the conformity of scan requests with the National Institute for Health and Care Excellence guidelines, with a review of relevant literature. METHOD: A retrospective analysis of 1300 magnetic resonance imaging scans of the internal acoustic meatus, compared against National Institute for Health and Care Excellence guidelines, was conducted over two years. RESULTS AND CONCLUSION: Sixteen scans were positive for vestibular schwannoma, with a detection rate of 1.23 per cent. All positive cases fit the guidelines; three of these could have been missed using other criteria. A total of 281 requests did not meet the guideline criteria but revealed no positive results, supporting the use of National Institute for Health and Care Excellence guidelines in planning magnetic resonance imaging scans for audio-vestibular symptoms.

COVID-19 Pandemic and Maternal Perspectives.

Aim Coronavirus (COVID-19) pandemic has affected perinatal women worldwide. Our study aimed to describe the opinions of perinatal women about COVID-19 related knowledge, attitude, and practices. Methods Pregnant and Postnatal women (n=223) were included and those who did not consent, and less than 16 weeks' gestation, were excluded. SPSS version 26 was used for descriptive statistics. Results Most of the women had good knowledge about COVID 19 regarding its nature, transmission, & symptoms. Their information sources were news (139/206=67.5%) and the internet (85/206=41%). Women understood the uncertainty around its effect on pregnancy; as it is a novel infection. A substantial number of women were concerned (130/206=63%), upset by social isolation (86/206=42%), negatively impacted by the visitor restrictions in hospital (154/206=75%), and faced COVID-19 related reduced household finances (97/206=47%). Most of them used hand washing (201/206=98%) & social distancing (191/206=93%) as preventive measures. They reported compromised contact with General Physician (GP) service as compared to the hospital service (85/206=41% Vs 31/206=15% respectively) during the pandemic. Conclusions The main challenges of the COVID-19 pandemic for perinatal women are the jeopardized GP & hospital services & psychological distress. It is imperative to incorporate telemedicine & virtual visits to tackle the burden of the COVID-19 pandemic. Perinatal women, are particularly vulnerable to the psychological impacts of the COVID-19 pandemic & societal lockdown, thus necessitating holistic interventions.

Impact of availability of direct-acting antivirals for hepatitis C on Canadian hospitalization rates, 2012-2016.

BACKGROUNDS: Hospitalizations associated with hepatitis C virus (HCV) infection and liver disease increased on average by 6.0% per year from 2004 to 2010 in Canada and were projected (in 2010) to increase by another 4% by 2016. The first generation of direct-acting antivirals (DAAs) became available in 2012. In 2014, a second generation of effective and well-tolerated DAA therapy was authorized in Canada. The impact of DAA therapy on the HCV-associated disease burden in Canada has not been documented. OBJECTIVES: To assess the potential impact of DAA therapy on the disease burden by a) comparing the actual hospitalization rates associated with HCV infection and liver disease following the introduction of DAAs in Canada with the 2010 baseline projection and b) documenting the associated uptake of anti-HCV therapy. METHODS: The hospital records of inpatients diagnosed with chronic HCV and chronic liver disease were extracted from the Canadian Discharge Abstract Database (DAD) by fiscal year for 2004-2016. We compared the actual number of hospitalizations to the baseline projection by year and for selected 5-year birth cohorts (1925-1989). The monthly number of new prescriptions for anti-HCV regimens was extracted from the IQVIA CDH CompuScript database (formerly IMS Health), aggregated to annual levels by age group and compared with hospitalization trends. RESULTS: Compared to the baseline projection, there was a slight reduction in hospitalizations in 2014/15 and 2015/16. This slight reduction was followed by a more significant decline in 2016/17 (32% below expected; 95% confidence interval [CI]: 27%-37%). The largest declines were observed for patients born before 1960 (age 55 or older) at 40% below expected in 2016/17. The number of new anti-HCV prescriptions increased from 5,484 in fiscal year 2012/13 to a peak of 17,775 in 2015/2016. The number of new prescriptions corresponds to approximately 1.3 and five times the number of hospitalizations in 2012/13 and 2015/16, respectively. CONCLUSIONS: In Canada there has been a modest decrease in HCV and liver-related hospitalizations following a significant increase in uptake of second-generation DAAs in 2015. However, the burden is still high. Linked health administrative databases created to monitor the disease burden in the new treatment era should provide additional insight with the linkage of treatment history and disease stage to individual outcomes.

Trends in hepatocellular carcinoma incidence and survival among people with hepatitis C: An international study.

This study evaluates trends in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct-acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995-2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001-2012/2013/2014, respectively) and mortality (1995-2013/2014/2015, respectively). Age-standardized HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58 487, 84 529 and 31 924 people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%) had an HCC diagnosis. Since mid-2000s, HCC diagnosis numbers increased in all jurisdictions. Age-standardized HCC incidence rates remained stable in BC and Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93, 10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis remained stable in BC (0.8 years in 2001-2006 and 2007-2011) and NSW (0.9 years in 2001-2006 and 2007-2013) and improved in Scotland (0.7 years in 2001-2006 to 1.5 years in 2007-2014). Across the settings, HCC burden increased, individual-level risk of HCC remained stable or increased, and HCC survival remained extremely low. These findings highlight the minimal impact of HCC prevention and management strategies during the interferon-based HCV treatment era and form the basis for evaluating the impact of DAA therapy in the coming years.

Shift in disparities in hepatitis C treatment from interferon to DAA era: A population-based cohort study.

We evaluated the shift in the characteristics of people who received interferon-based hepatitis C virus (HCV) treatments and those who received recently introduced direct-acting antivirals (DAAs) in British Columbia (BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon-based treatments including pegylated interferon/ribavirin (PegIFN/RBV) with/without boceprevir or telaprevir, DAAs with RBV or PegIFN/RBV, and newer interferon-free DAAs. Of 11 886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon-free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or PegIFN/RBV. Compared to those receiving interferon-based treatment, people with HIV co-infection (adjusted odds ratio [aOR]: 2.96, 95% CI: 2.31-3.81), cirrhosis (aOR: 1.77, 95% CI: 1.45-2.15), decompensated cirrhosis (aOR: 1.72, 95% CI: 1.31-2.28), diabetes (aOR: 1.30, 95% CI: 1.10-1.54), a history of injection drug use (aOR: 1.34, 95% CI: 1.09-1.65) and opioid substitution therapy (aOR: 1.30, 95% CI: 1.01-1.67) were more likely to receive interferon-free DAAs. Socio-economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58-0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV-co-infected), although gaps remain for the socio-economically marginalized populations.

Role of primary T-cell immunodeficiency and hepatitis B coinfection on spontaneous clearance of hepatitis C: The BC Hepatitis Testers Cohort.

T-cell host immune response against hepatitis C virus (HCV) has been suggested to play an important role in determining HCV infection outcome. However, data from human studies are not available. This study examined the effect of primary T-cell deficiency along with other factors on the spontaneous clearance of HCV in a large population-based cohort in British Columbia, Canada. The BC Hepatitis Testers Cohort includes all individuals tested for HCV in BC in 1990-2013 linked with data on their medical visits, hospitalizations and prescription drugs. HCV-positive individuals with at least one valid HCV PCR test on/after HCV diagnosis (n=46 783) were included in this study. To examine factors associated with the spontaneous clearance of HCV, multivariable logistic regression was fitted on the full sample, and Cox proportional hazards model on the HCV seroconverters. Spontaneous clearance was observed in 25.1% (n=11 737) of those tested for HCV. After adjusting for potential confounders, the odds of spontaneous clearance of HCV was lower in people with primary T-cell immunodeficiency (adjusted odds ratio [aOR]: 0.55, 95% CI: 0.32-0.94), and higher in females (aOR: 1.61, 95% CI: 1.54-1.68) and in those coinfected with HBV (aOR: 2.31, 95% CI: 1.93-2.77). Similar results were observed in HCV seroconverters except HBV coinfection was not significant. In conclusion, primary T-cell immunodeficiency is associated with a lower spontaneous clearance of HCV while female sex and coinfection with HBV are associated with a higher spontaneous clearance.

Interim estimates of influenza vaccine effectiveness in 2012/13 from Canada's sentinel surveillance network, January 2013.

The 2012/13 influenza season in Canada has been characterised to date by early and moderately severe activity, dominated (90%) by the A(H3N2) subtype. Vaccine effectiveness (VE) was assessed in January 2013 by Canada's sentinel surveillance network using a test-negative case-control design. Interim adjusted-VE against medically attended laboratory-confirmed influenza A(H3N2) infection was 45% (95% CI: 13-66). Influenza A(H3N2) viruses in Canada are similar to the vaccine, based on haemagglutination inhibition; however, antigenic site mutations are described in the haemagglutinin gene.

Revascularization grading in endovascular acute ischemic stroke therapy.

BACKGROUND: Recanalization and angiographic reperfusion are key elements to successful endovascular and interventional acute ischemic stroke (AIS) therapy. Intravenous recombinant tissue plasminogen activator (rt-PA), the only established revascularization therapy approved by the US Food & Drug Administration for AIS, may be less effective for large artery occlusion. Thus, there is enthusiasm for endovascular revascularization therapies, which likely provide higher recanalization rates, and trials are ongoing to determine clinical efficacy and compare various methods. It is anticipated that clinical efficacy will be well correlated with revascularization of viable tissue in a timely manner. METHOD: Reporting, interpretation, and comparison of the various revascularization grading methods require agreement on measurement criteria, reproducibility, ease of use, and correlation with clinical outcome. These parameters were reviewed by performing a Medline literature search from 1965 to 2011. This review critically evaluates current revascularization grading systems. RESULTS AND CONCLUSION: The most commonly used revascularization grading methods in AIS interventional therapy trials are the thrombolysis in cerebral ischemia (TICI, pronounced "tissy") and thrombolysis in myocardial ischemia (TIMI) scores. Until further technical and imaging advances can incorporate real-time reliable perfusion studies in the angio-suite to delineate regional perfusion more accurately, the TICI grading system is the best defined and most widely used scheme. Other grading systems may be used for research and correlation purposes. A new scale that combines primary site occlusion, lesion location, and perfusion should be explored in the future.

Use of biomass fuel and acute respiratory infections in rural Pakistan.

OBJECTIVE: To evaluate the association between use of biomass fuel and acute respiratory infection (ARI) episodes in children aged ≤5 years in Pakistan. DESIGN: Cross-sectional study. METHODS: Cluster sampling was used to select 566 children from 379 households in August-September 2007 in a rural setting in Pakistan. Information was collected on ARI episodes during the previous month and type of fuel used for cooking. Poisson regression with robust variance estimation was used to assess the association between use of biomass fuel and ARI episodes, adjusting for potential confounders. RESULTS: The incidence of ARI was 7 episodes/child/year. In the adjusted model, the incidence of ARI was higher in children living in houses where biomass fuel was used and who accompanied their mothers while cooking compared with children living in houses where fossil fuel was used and who did not accompany their mothers while cooking [rate ratio (RR) 2.6, 95% confidence interval (CI) 1.5-4.5]. Compared with the latter group, the incidence of ARI was also higher in children living in houses where biomass fuel was used but who did not accompany their mothers during cooking (RR 1.5, 95% CI 1.2-1.9), and in children living in houses where fossil fuel was used and who accompanied their mothers while cooking (RR 1.9, 95% CI 1.3-2.8). CONCLUSION: Use of biomass fuel and presence of a child in the kitchen during cooking were associated with increased incidence of ARI in children aged ≤5 years.

Cross-reactive antibody to swine influenza A(H3N2) subtype virus in children and adults before and after immunisation with 2010/11 trivalent inactivated influenza vaccine in Canada, August to November 2010.

In pre- and post-immunisation sera from children (17-120 months-old) and adults (20-59 years-old) immunised with 2010/11 trivalent inactivated influenza vaccine, we assessed age-related patterns of sero-susceptibility and vaccine-induced cross-reactive antibodies to a representative swine H3N2 (swH3N2) and a related ancestral human H3N2 (A/Sydney/5/1997) influenza virus. Few children but a greater proportion of adults showed pre-immunisation haemagglutination inhibition titres ≥40 to either virus. Titres increased with age among children but decreased in adults. Fewer than 20% showed a four-fold rise in antibody titres to either virus following immunisation. Further investigation is warranted to guide ongoing risk assessment and response to emerging swine H3N2 viruses.

Health care risk factors among women and personal behaviours among men explain the high prevalence of hepatitis C virus infection in Karachi, Pakistan.

To estimate the prevalence and identify factors associated with hepatitis C virus (HCV) infection among men and women in Karachi, Pakistan. We conducted a cross-sectional study of adult men and women in a peri-urban community of Karachi (Jam Kandah). Households were selected through systematic sampling from within all villages in the study area. All available adults within each household were interviewed about potential HCV risk factors. A blood specimen was collected to test for anti-HCV antibodies by enzyme immunoassay. We used generalized estimating equations while accounting for correlation of responses within villages to identify the factors associated with HCV infection. Of 1997 participants, 476 (23.8%) were anti-HCV positive. Overall, HCV infection was significantly associated with increasing age, ethnicity, and having received > or =2 blood transfusions, > or =3 hospitalizations, dental treatment and >5 injections among women. Among women, > or =2 blood transfusions [adjusted odds ratio (aOR) = 2.32], >5 injections during the past 6 months (aORs = 1.47), dental treatment (aOR = 1.31) and increasing age(aOR = 1.49), while among men, extramarital sexual intercourse (aOR = 2.77), at least once a week shave from barber (aOR = 5.04), > or =3 hospitalizations (aOR = 2.50) and increasing age (aOR = 1.28) were associated with HCV infection. A very high prevalence of HCV was found in the study population. Among women, unsafe health care practices, while among men extramarital sex, shaving from a barber and hospitalizations were associated with HCV infection. Efforts are needed to improve the safety of medical procedures to reduce the transmission of HCV in Pakistan [Corrections made in Summary after initial online publication.].

High-risk behaviours among juvenile prison inmates in Pakistan.

OBJECTIVES: To assess the sexual- and drug-use-related risk behaviours of male juvenile detainees in Karachi, Pakistan. DESIGN: Cross-sectional study. METHODS: A cross-sectional study was conducted of prison inmates aged 15-21 years in Karachi Juvenile Prison in 2002. In total, 321 inmates were interviewed about sexual orientation and behaviours, and knowledge about human immunodeficiency virus (HIV) and sexually transmitted infections (STIs). Urine specimens were collected and tested for Chlamydia trachomatis and Neisseria gonorrhoeae using ligase chain reaction. RESULTS: A substantial proportion (n=111, 34.6%) of the participants were sexually active. Sixty-two (19%) and 67 (21%) had had sex with a male or female before incarceration, respectively. Twenty-seven (8.4%) participants had an STI, and 50% of the 109 sexually active participants had had multiple sexual partners. Use of addictive substances was associated with sexual activity. The mean knowledge score computed from the sum of 16 items was 4.7, with a median of 2.9. A large proportion (40%) of participants knew about condoms, but very few (3.4%) had ever used one. The mean+/-standard deviation risk score from nine items was 2.4+/-1.7. On the basis of behavioural and biological markers, 117 (36.4%) participants had high-risk behaviour. In multivariate logistic regression analysis, knowledge, risk perception and age were predictive of higher risk. CONCLUSIONS: HIV risk behaviours are common among adolescent inmates. Although inmates do have knowledge about modes of transmission and condom use, the use of condoms is significantly low. Interventions are needed for behavioural change among this group.

Intra-arterial recanalization techniques for patients 80 years or older with acute ischemic stroke: pooled analysis from 4 prospective studies.

BACKGROUND AND PURPOSE: Previous studies have demonstrated limited benefit with endovascular procedures such as stent placement in octogenarians. We evaluated the safety and effectiveness of intra-arterial recanalization techniques to treat ischemic stroke in patients 80 years or older presenting within 6 hours of symptom onset. MATERIALS AND METHODS: We pooled the data from 4 prospective studies by evaluating intra-arterial recanalization techniques for treatment of ischemic stroke. Clinical and radiologic evaluations were performed before treatment and at 24 hours, 7 to 10 days, and 1 to 3 months after treatment. We performed multivariate analyses to evaluate the effect of ages 80 years and older on angiographic recanalization, favorable outcome (modified Rankin scale of 0-2), and mortality rate at 1 to 3 months. RESULTS: A total of 101 patients were treated in the 4 protocols. Of these, 24 were 80 years or older. There was no significant difference between the 2 age groups in sex, initial stroke severity, time to treatment, site of vascular occlusion, and rate of symptomatic and asymptomatic intracranial hemorrhage (ICH). In logistic regression analysis, age 80 years or older was associated with a lower likelihood of a favorable outcome (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.13-1.2; P = .11) and recanalization (OR, 0.36; 95% CI, 0.12-1.1; P = .07) and with higher mortality rate (OR, 3.17; 95% CI, 1.05-9.55; P = .04) after adjusting for study protocol. After adjusting for recanalization in addition to study protocol, the older age group still had a lower likelihood of favorable outcomes (OR, 0.34; 95% CI, 0.1-1.1; P = .07) and higher mortality rates (OR, 3.62; 95% CI, 1.15-11.36; P = .027). CONCLUSIONS: Our study demonstrates that patients 80 years and older are at higher risk for poor outcome at 1 to 3 months following intra-arterial recanalization techniques. This relationship is independent of recanalization rate and symptomatic ICH supporting the role of other mechanisms.

Late endovascular revascularization in acute ischemic stroke based on clinical-diffusion mismatch.

BACKGROUND AND PURPOSE: A clinical-diffusion mismatch (CDM) among stroke patients presenting within 12-24 hours has been correlated with neurologic deterioration and infarct expansion. We sought to study the feasibility and safety of reperfusion therapy in a series of 11 consecutive patients fulfilling this criterion. MATERIALS AND METHODS: Patients presenting with large vessel syndromes were considered for revascularization therapy. Of these patients, we identified those presenting beyond 8 hours who scored > or =8 on the National Institutes of Health Stroke Scale (NIHSS) and had limited abnormalities on diffusion-weighted MR imaging. One- and 7-day NIHSS scores were obtained. Rates of early neurologic deterioration (END, increase in NIHSS score by > or =4 points) and early neurologic improvement (ENI, decrease in NIHSS score by > or =4 points) at 1 week were determined. Follow-up imaging was obtained to evaluate intracranial hemorrhage (ICH). RESULTS: Eleven patients were identified, 8 of whom were successfully revascularized. The mean age of all patients was 55 years with mean initial, 24-hour, and 1-week NIHSS scores of 14 +/- 4, 11 +/- 7, and 6 +/- 5, respectively, with lower scores at 24 hours and 1 week (8 +/- 5 and 4 +/- 3, respectively) among patients successfully revascularized. Eight of the treated patients (72% of the total, 100% of those successfully revascularized) experienced ENI. No patient had END or ICH. CONCLUSIONS: Endovascular treatment for acute ischemic stroke beyond 8 hours is feasible and may prevent END and promote ENI in patients fulfilling the criteria of a CDM. A prospective study is planned.

Sunscreens in human plasma and urine after repeated whole-body topical application.

BACKGROUND: The three chemical ultraviolet absorbers benzophenone-3 (BP-3), octyl-methoxycinnamate (OMC) and 3-(4-methylbenzylidene) camphor (4-MBC) are commercially used in sunscreens worldwide. Apart from sun protection, they may possess endocrine-disrupting effects in animals and in vitro. For all three compounds, only sporadic measurements of percutaneous absorption and excretion after topical application in humans have been described. METHODS: In this study, 32 healthy volunteers, 15 young males and 17 postmenopausal females, were exposed to daily whole-body topical application of 2 mg/cm(2) of sunscreen formulation at 10% (w/w) of each for 4 days. Blood concentrations were measured at 0, 1, 2, 3, 4, 24 and 96 h and urine concentrations at 0, 24, 48, 72 and 96 h. RESULTS: Almost all three sunscreens were undetectable in plasma and urine before the first application. One to 2 h after the first application, all three sunscreens were detectable in plasma. The maximum median plasma concentrations were 187 ng/mL BP-3, 16 ng/mL 4-MBC and 7 ng/mL OMC for females and 238 ng/mL BP-3, 18 ng/mL 4-MBC and 16 ng/mL OMC for men. In the females, urine levels of 44 ng/mL BP-3 and 4 ng/mL of 4-MBC and 6 ng/mL OMC were found, and in the males, urine levels of 81 ng/mL BP-3, 4 ng/mL of 4-MBC and OMC were found. In plasma, the 96-h median concentrations were higher compared with the 24-h concentrations for 4-MBC and OMC in men and for BP-3 and 4-MBC in females.

Impact of arterial reocclusion and distal fragmentation during thrombolysis among patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Arterial reocclusion and distal embolization are known complications of ischemic stroke intervention, impacting treatment strategies and device design. We sought to determine their rates of occurrence and effects on long-term outcomes during endovascular treatment of patients with acute ischemic stroke. MATERIALS AND METHODS: Retrospective analysis of data from 4 prospective acute stroke protocols was performed. Patients underwent the standard technique for parent vessel angiography followed by pharmacologic thrombolysis and/or sonographic thrombolysis and/or mechanical thrombus disruption. Certain patients also received systemic heparin or abciximab therapy. Demographic, clinical, and angiographic variables were assessed at onset, 24 hours, 1 week, and 1-3 months after the event. "Distal embolization" was defined qualitatively as appearance of an occlusion on a downstream vessel. "Arterial reocclusion" was defined as subsequent reocclusion of the target vessel after initial recanalization had been achieved. RESULTS: Arterial reocclusion occurred in 18% of these patients, whereas distal embolization occurred in 16% of the 91 patients treated in these protocols. Arterial reocclusion, but not distal embolization, was associated with a lower likelihood of favorable outcome at 1-3 months (P = .05; odds ratio, 3.9; 95% confidence interval, 0.01-0.98) after adjusting for age, initial National Institutes of Health Stroke Scale scores, sex, time to treatment, initial angiographic grade, symptomatic intracranial hemorrhage, and final recanalization. CONCLUSIONS: Arterial reocclusion and distal embolization occur in 16%-18% of patients with stroke undergoing endovascular intervention. Only arterial reocclusion is associated with poor long-term outcome. Prospective studies are needed to identify risk factors for their occurrence and possible preventive therapies.