ABSTRACT
BACKGROUND: World Health Organization approved vaccines have demonstrated relatively high protection against moderate to severe COVID-19. Prospective vaccine effectiveness (VE) designs with first-hand data and population-based controls are nevertheless rare. Neighborhood compared to hospitalized controls, may differ in compliance to non-pharmacuetical interventions (NPI) compliance, which may influence VE results in real-world settings. We aimed to determine VE against COVID-19 intensive-care-unit (ICU) admission using hospital and community-matched controls in a prospective design. METHODS: We conducted a multicenter, observational study of matched cases and controls (1:3) in adults â§18 years of age from May to July 2021. For each case, a hospital control and two community controls were matched by age, gender, and hospital admission date or neighborhood of residence. Conditional logistic regression models were built, including interaction terms between NPIs, lifestyle behaviors, and vaccination status; the model's ß coefficients represent the added effect these terms had on COVID-19 VE. RESULTS: Cases and controls differed in several factors including education level, obesity prevalence, and behaviors such as compliance with routine vaccinations, use of facemasks, and routine handwashing. VE was 98·2% for full primary vaccination and 85·6% for partial vaccination when compared to community controls, and somewhat lower, albeit not significantly, compared to hospital controls. A significant added effect to vaccination in reducing COVID-19 ICU admission was regular facemask use and VE was higher among individuals non-compliant with the national vaccine program, and/or tonroutine medical visits during the prior year. CONCLUSION: VE against COVID-19 ICU admission in this stringent prospective case-double control study reached 98% two weeks after full primary vaccination, confirming the high effectiveness provided by earlier studies. Face mask use and hand washing were independent protective factors, the former adding additional benefit to VE. VE was significantly higher in subjects with increased risk behaviors.
Subject(s)
COVID-19 , Vaccine Efficacy , Adult , Humans , Chile/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , Life Style , COVID-19 Vaccines , Case-Control StudiesABSTRACT
A critical challenge during volcanic emergencies is responding to rapid changes in eruptive behaviour. Actionable advice, essential in times of rising uncertainty, demands the rapid synthesis and communication of multiple datasets with prognoses. The 2020-2021 eruption of La Soufrière volcano exemplifies these challenges: a series of explosions from 9-22 April 2021 was preceded by three months of effusive activity, which commenced with a remarkably low level of detected unrest. Here we show how the development of an evolving conceptual model, and the expression of uncertainties via both elicitation and scenarios associated with this model, were key to anticipating this transition. This not only required input from multiple monitoring datasets but contextualisation via state-of-the-art hazard assessments, and evidence-based knowledge of critical decision-making timescales and community needs. In addition, we share strategies employed as a consequence of constraints on recognising and responding to eruptive transitions in a resource-constrained setting, which may guide similarly challenged volcano observatories worldwide.
Subject(s)
Disasters , Volcanic EruptionsABSTRACT
OBJECTIVES: Helicobacter pylori (H. pylori) is the primary cause of gastric cancer and eradication in healthy adults has proven effective in decreasing cancer incidence. H. pylori is acquired largely in early childhood, however, the benefits of eradication in children are controversial. We aimed to determine the effect of H. pylori eradication on clinical and laboratory markers associated with gastric damage in apparently healthy school-aged children. METHODS: This was a pilot non-blinded trial including 61 children persistently infected with H. pylori who were randomized to eradication/no treatment and followed for at least 12 months, evaluating clinical and blood markers (Pepsinogen I (PGI) and II (PGII) determined by ELISA) associated with gastric damage. The treatment consisted of a sequential scheme including 7 days of omeprazole + amoxicillin followed by 7 days of omeprazole + clarithromycin + metronidazole; adherence and tolerance were surveyed. Eradication rates were assessed by stool antigen detection or urea breath test 1 month following treatment every 4 months thereafter to detect reinfection. RESULTS: Eradication occurred in 30/31 treated children (median age: 8.8, range: 7.9-10.8) and in 0/30 non-treated controls (median age: 8.6, range: 7.9-11) (p < .001). Treatment was associated with mild transient symptoms (altered taste, nocturnal upper abdominal pain, nausea, and diarrhea). Baseline frequency of symptoms was low and eradication did not change symptoms compared to controls. PGI, PGII, and anti-H. pylori seropositivity were similar in both groups at baseline and significantly decreased only in eradicated patients; PGI (92.5 vs. 74.4, p < .001), PGII (15.2 vs. 8.9, p < .001) levels, and frequency of anti-H. pylori seropositivity (100 vs. 68%, p < .001) respectively. Four eradicated children (13%) were reinfected during follow-up. CONCLUSIONS: H. pylori eradication therapy in apparently asymptomatic school-aged children was well tolerated and associated with decreased serum PGI and PGII levels. Future studies should expand on the middle-long-term effect of early H. pylori eradication, especially on preventing gastric cancer.
Subject(s)
Anti-Ulcer Agents , Helicobacter Infections , Helicobacter pylori , Adult , Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Anti-Ulcer Agents/therapeutic use , Biomarkers , Child , Child, Preschool , Clarithromycin/therapeutic use , Drug Therapy, Combination , Helicobacter Infections/diagnosis , Helicobacter Infections/drug therapy , Humans , Laboratories , Pepsinogen C , SchoolsABSTRACT
There has been a noticeable shift in discussions about cervical cancer, moving from prevention to elimination. Interventions such as FASTER, human papillomavirus (HPV) vaccination and HPV screening are innovative intervention strategies which can be utilized to begin a path to elimination. To explore the feasibility of the FASTER strategy, an evaluation was carried out in eight primary health-care centers within the Tlalpan Health-Jurisdiction of Mexico City between March 2017 and August 2018. A mixed methods approach was used to evaluate three components: infrastructure, patient acceptability, and health-care professionals' perceptions. This included checklists of requirements for the infrastructure rollout of FASTER and interviews with women and health-care professionals. Nearly all (93%) of the 3,474 women aged 25-45 years accepted HPV vaccination as part of a combined vaccination and screening program. The main reason for acceptance was prevention, while having doubts about the vaccine's benefits was the main reason for refusal. Most of the 24 health-care professionals had a positive opinion toward HPV vaccination and identified the need to increase dissemination, inform the population clearly and concisely and currently extend the age range for vaccination. The evaluation of eight primary health-care centers showed they had the necessary infrastructure for the development of a joint HPV prevention strategy, but many centers required improvements to become more efficient. Together these findings suggest that although HPV vaccine acceptance was high, there is the need to increase education and awareness among potential vaccine recipients and health-care professionals to implement the FASTER strategy.
Subject(s)
Health Knowledge, Attitudes, Practice , Mass Screening , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/administration & dosage , Primary Health Care/statistics & numerical data , Vaccination/methods , Adult , Feasibility Studies , Female , Humans , Mexico , Middle Aged , Patient Acceptance of Health Care , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/virologyABSTRACT
OBJECTIVES: To develop an exposure and risk assessment model to estimate listeriosis infection risks for Peruvian women. METHODS: A simulation model was developed utilising Listeria monocytogenes concentrations on kitchen and latrine surfaces in Peruvian homes, hand trace data from Peruvian women and behavioural data from literature. Scenarios involving varying proportions of uncontaminated, or 'clean', surfaces and non-porous surfaces were simulated. Infection risks were estimated for 4, 6 and 8 h of behaviours and interactions with surfaces. RESULTS: Although infection risks were estimated across scenarios for various time points (e.g. 4, 6, 8 h), overall mean estimated infection risks for all scenarios were ≥ 0.31. Infection risks increased as the proportions of clean surfaces decreased. Hand-to-general surface contacts accounted for the most cumulative change in L. monocytogenes concentration on hands. CONCLUSIONS: In addition to gaining insights on how human behaviours affect exposure and infection risk, this model addressed uncertainties regarding the influence of household surface contamination levels. Understanding the influence of surface contamination in preventing pathogen transmission in households could help to develop intervention strategies to reduce L. monocytogenes infection and associated health risks.
OBJECTIFS: Développer un modèle d'exposition et d'évaluation des risques pour estimer les risques d'infection par la listériose chez les femmes péruviennes. MÉTHODES: Un modèle de simulation a été développé en utilisant des concentrations de Listeria monocytogenes sur la surface des cuisines et des latrines dans des foyers péruviens, des données de traces de mains de femmes péruviennes et des données comportementales de la littérature. Des scénarios impliquant différentes proportions de surfaces non contaminées ou «propres¼ et de surfaces non poreuses ont été simulés. Les risques d'infection ont été estimés pour 4, 6 et 8 heures de comportements et d'interactions avec les surfaces. RÉSULTATS: Bien que les risques d'infection aient été estimés pour tous les scénarios à différents moments (par ex. à 4, 6 ou 8 heures), les risques d'infection globaux moyens estimés pour tous les scénarios étaient ≥ 0,31. Les risques d'infection augmentaient à mesure que les proportions de surfaces propres diminuaient. Les contacts entre la main et les surfaces générales contribuent pour le plus de changement cumulatif de la concentration de L. monocytogenes sur les mains. CONCLUSIONS: En plus de comprendre comment les comportements humains affectent l'exposition et le risque d'infection, ce modèle a traité des incertitudes quant à l'influence des niveaux de contamination des surfaces ménagers. Comprendre l'influence de la contamination de surface dans la prévention de la transmission d'agents pathogènes dans les ménages pourrait aider à développer des stratégies d'intervention pour réduire l'infection à L. monocytogenes et les risques associés pour la santé.
Subject(s)
Hygiene , Listeria monocytogenes/isolation & purification , Listeriosis/epidemiology , Colony Count, Microbial/methods , Colony Count, Microbial/statistics & numerical data , Female , Humans , Peru/epidemiology , Risk AssessmentABSTRACT
The impact of increases in drought frequency on the Amazon forest's composition, structure and functioning remain uncertain. We used a process- and individual-based ecosystem model (ED2) to quantify the forest's vulnerability to increased drought recurrence. We generated meteorologically realistic, drier-than-observed rainfall scenarios for two Amazon forest sites, Paracou (wetter) and Tapajós (drier), to evaluate the impacts of more frequent droughts on forest biomass, structure and composition. The wet site was insensitive to the tested scenarios, whereas at the dry site biomass declined when average rainfall reduction exceeded 15%, due to high mortality of large-sized evergreen trees. Biomass losses persisted when year-long drought recurrence was shorter than 2-7 yr, depending upon soil texture and leaf phenology. From the site-level scenario results, we developed regionally applicable metrics to quantify the Amazon forest's climatological proximity to rainfall regimes likely to cause biomass loss > 20% in 50 yr according to ED2 predictions. Nearly 25% (1.8 million km2 ) of the Amazon forests could experience frequent droughts and biomass loss if mean annual rainfall or interannual variability changed by 2σ. At least 10% of the high-emission climate projections (CMIP5/RCP8.5 models) predict critically dry regimes over 25% of the Amazon forest area by 2100.
Subject(s)
Droughts , Forests , Biomass , Carbon Dioxide/pharmacology , Computer Simulation , Geography , Models, Theoretical , Plant Transpiration/drug effects , Plant Transpiration/physiology , Rain , South AmericaABSTRACT
Noroviruses (NoVs) are one of the leading causes of acute gastroenteritis, including both outbreaks and endemic infections. The development of preventive strategies, including vaccines, for the most susceptible groups (children <5years of age, the elderly and individuals suffering crowding, such as military personnel and travelers) is desirable. However, NoV vaccine development has faced many difficulties, including genetic/antigenic diversity, limited knowledge on NoV immunology and viral cycle, lack of a permissive cell line for cultivation and lack of a widely available and successful animal model. Vaccine candidates rely on inoculation of virus-like particles (VLPs) formed by the main capsid protein VP1, subviral particles made from the protruding domain of VP1 (P-particles) or viral vectors with a NoV capsid gene insert produced by bioengineering technologies. Polivalent vaccines including multiple NoV genotypes and/or other viruses acquired by the enteric route have been developed. A VLP vaccine candidate has reached phase II clinical trials and several others are in pre-clinical stages of development. In this article we discuss the main challenges facing the development of a NoV vaccine and the current status of prevailing candidates.
Subject(s)
Norovirus/pathogenicity , Viral Vaccines/therapeutic use , Acute Disease , Animals , Bioengineering/methods , Caliciviridae Infections/immunology , Caliciviridae Infections/prevention & control , Capsid Proteins/immunology , Gastroenteritis/immunology , Gastroenteritis/prevention & control , Humans , Norovirus/immunologyABSTRACT
Most, if not all, human cancers exhibit altered epigenetic signatures that promote aberrant gene expression that contributes to cellular transformation. Historically, attempts to pharmacologically intervene in this process have focused on DNA methylation and histone acetylation. More recently, genome-wide studies have identified histone and chromatin regulators as one of the most frequently dysregulated functional classes in a wide range of cancer types. These findings have provided numerous potential therapeutic targets including many that affect histone methylation. These include histone lysine methyltransferases such as enhancer of zeste homolog 2 and DOT1L, protein arginine methyltransferases such as protein arginine methyltransferase 5, and histone lysine demethylases such as lysine-specific demethylase 1. This review presents the rationale for targeting histone methylation in oncology and provides an update on a few key targets that are being investigated in the clinic.
Subject(s)
Epigenesis, Genetic , Histone-Lysine N-Methyltransferase/antagonists & inhibitors , Histones/genetics , Molecular Targeted Therapy/methods , Neoplasms/drug therapy , Antimetabolites, Antineoplastic/pharmacology , Antimetabolites, Antineoplastic/therapeutic use , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Histone Demethylases/genetics , Histone Demethylases/metabolism , Histone-Lysine N-Methyltransferase/genetics , Histones/metabolism , Humans , Methylation/drug effects , Neoplasms/genetics , Protein Processing, Post-Translational/drug effectsABSTRACT
The Co4O4 cubane is a representative structural model of oxidic cobalt oxygen-evolving catalysts (Co-OECs). The Co-OECs are active when residing at two oxidation levels above an all-Co(III) resting state. This doubly oxidized Co(IV)2 state may be captured in a Co(III)2(IV)2 cubane. We demonstrate that the Co(III)2(IV)2 cubane may be electrochemically generated and the electronic properties of this unique high-valent state may be probed by in situ spectroscopy. Intervalence charge-transfer (IVCT) bands in the near-IR are observed for the Co(III)2(IV)2 cubane, and spectroscopic analysis together with electrochemical kinetics measurements reveal a larger reorganization energy and a smaller electron transfer rate constant for the doubly versus singly oxidized cubane. Spectroelectrochemical X-ray absorption data further reveal systematic spectral changes with successive oxidations from the cubane resting state. Electronic structure calculations correlated to experimental data suggest that this state is best represented as a localized, antiferromagnetically coupled Co(IV)2 dimer. The exchange coupling in the cofacial Co(IV)2 site allows for parallels to be drawn between the electronic structure of the Co4O4 cubane model system and the high-valent active site of the Co-OEC, with specific emphasis on the manifestation of a doubly oxidized Co(IV)2 center on O-O bond formation.
ABSTRACT
Zika virus (ZIKV) is a mosquito-borne flavivirus with a significant public health impact highlighted by the ongoing epidemic in the Americas. We describe a 44-year-old male presenting to our tropical medicine center with complaints of fever, headache, joint pain, and rash after recent travel to Guyana. The patient subsequently developed gait imbalance and lower extremity weakness with clinical examination, cerebrospinal fluid studies, and magnetic resonance imaging of the spine consistent with a diagnosis of Guillain-Barré syndrome (GBS). ZIKV infection was confirmed via detection of ZIKV RNA in urine by polymerase chain reaction. The patient was treated with intravenous immunoglobulin and experienced near-complete neurologic recovery, reporting ongoing mild paresthesia up to 2 months later. This case highlights the diagnostic challenges posed by ZIKV and underscores the need for clinician awareness of the potential for neurological complications such as GBS with ZIKV infection.
Subject(s)
Guillain-Barre Syndrome/diagnosis , Zika Virus Infection/diagnosis , Adult , Epidemics , Guillain-Barre Syndrome/complications , Guillain-Barre Syndrome/drug therapy , Guyana , Humans , Immunoglobulins, Intravenous/therapeutic use , Magnetic Resonance Imaging , Male , RNA, Viral/isolation & purification , Travel , Zika Virus , Zika Virus Infection/complicationsABSTRACT
BACKGROUND: Replacement of the trivalent oral poliovirus vaccine (tOPV) with bivalent types 1 and 3 oral poliovirus vaccine (bOPV) and global introduction of inactivated poliovirus vaccine (IPV) are major steps in the polio endgame strategy. In this study, we assessed humoral and intestinal immunity in Latin American infants after three doses of bOPV combined with zero, one, or two doses of IPV. METHODS: This open-label randomised controlled multicentre trial was part of a larger study. 6-week-old full-term infants due for their first polio vaccinations, who were healthy on physical examination, with no obvious medical conditions and no known chronic medical disorders, were enrolled from four investigational sites in Colombia, Dominican Republic, Guatemala, and Panama. The infants were randomly assigned by permuted block randomisation (through the use of a computer-generated list, block size 36) to nine groups, of which five will be discussed in this report. These five groups were randomly assigned 1:1:1:1 to four permutations of schedule: groups 1 and 2 (control groups) received bOPV at 6, 10, and 14 weeks; group 3 (also a control group, which did not count as a permutation) received tOPV at 6, 10, and 14 weeks; group 4 received bOPV plus one dose of IPV at 14 weeks; and group 5 received bOPV plus two doses of IPV at 14 and 36 weeks. Infants in all groups were challenged with monovalent type 2 vaccine (mOPV2) at 18 weeks (groups 1, 3, and 4) or 40 weeks (groups 2 and 5). The primary objective was to assess the superiority of bOPV-IPV schedules over bOPV alone, as assessed by the primary endpoints of humoral immunity (neutralising antibodies-ie, seroconversion) to all three serotypes and intestinal immunity (faecal viral shedding post-challenge) to serotype 2, analysed in the per-protocol population. Serious and medically important adverse events were monitored for up to 6 months after the study vaccination. This study is registered with ClinicalTrials.gov, number NCT01831050, and has been completed. FINDINGS: Between May 20, 2013, and Aug 15, 2013, 940 eligible infants were enrolled and randomly assigned to the five treatment groups (210 to group 1, 210 to group 2, 100 to group 3, 210 to group 4, and 210 to group 5). One infant in group 1 was not vaccinated because their parents withdrew consent after enrolment and randomisation, so 939 infants actually received the vaccinations. Three doses of bOPV or tOPV elicited type 1 and 3 seroconversion rates of at least 97·7%. Type 2 seroconversion occurred in 19 of 198 infants (9·6%, 95% CI 6·2-14·5) in the bOPV-only groups, 86 of 88 (97·7%, 92·1-99·4) in the tOPV-only group (p<0·0001 vs bOPV-only), and 156 of 194 (80·4%, 74·3-85·4) infants in the bOPV-one dose of IPV group (p<0·0001 vs bOPV-only). A further 20 of 193 (10%) infants in the latter group seroconverted 1 week after mOPV2 challenge, resulting in around 98% of infants being seropositive against type 2. After a bOPV-two IPV schedule, all 193 infants (100%, 98·0-100; p<0·0001 vs bOPV-only) seroconverted to type 2. IPV induced small but significant decreases in a composite serotype 2 viral shedding index after mOPV2 challenge. 21 serious adverse events were reported in 20 patients during the study, including two that were judged to be possibly related to the vaccines. Most of the serious adverse events (18 [86%] of 21) and 24 (80%) of the 30 important medical events reported were infections and infestations. No deaths occurred during the study. INTERPRETATION: bOPV provided humoral protection similar to tOPV against polio serotypes 1 and 3. After one or two IPV doses in addition to bOPV, 80% and 100% of infants seroconverted, respectively, and the vaccination induced a degree of intestinal immunity against type 2 poliovirus. FUNDING: Bill & Melinda Gates Foundation.
Subject(s)
Antibodies, Neutralizing/immunology , Immunity, Humoral/immunology , Immunity, Mucosal/immunology , Intestinal Mucosa/immunology , Poliomyelitis/prevention & control , Poliovirus Vaccine, Inactivated/therapeutic use , Poliovirus Vaccine, Oral/therapeutic use , Virus Shedding/immunology , Colombia , Dominican Republic , Drug Therapy, Combination , Feces/virology , Female , Guatemala , Humans , Immunization Schedule , Infant , Latin America , Male , Panama , Poliomyelitis/immunology , Seroconversion , Single-Blind MethodABSTRACT
OBJECTIVE: Ascending thoracic aortic aneurysm (ATAA) in patients with bicuspid aortic valve (BAV) commonly dilate asymmetrically compared with patients with tricuspid aortic valve (TAV). This discrepancy in aneurysm geometry led us to hypothesize that microarchitectural differences underlie the observed asymmetric dilatation pattern. The purpose of this study was to characterize the microarchitectural distinctions of the extracellular matrix of the 2 phenotypes with a focus on the proportion of radially oriented elastin and collagen fibers in different circumferential aortic regions. METHODS: Aortic tissue rings were obtained just distal to the sinotubular junction from patients with BAV or TAV undergoing elective aneurysm repair. They were sectioned into three circumferentially based regions according to adjacent aortic sinus segment (left coronary sinus [L], right coronary sinus [R], or noncoronary sinus [N]). Multiphoton microscopy was used to quantify and characterize the number of radially oriented elastin and collagen fibers. RESULTS: There were fewer radially oriented fibers in medial region N and medial-intimal region R of BAV-ATAAs when compared with TAV-ATAAs (medial region N, amplitude of angular undulation of elastin = 10.67° ± 1.35° vs 15.58° ± 1.91°; P = .041; medial-intimal region R, amplitude of angular undulation of elastin = 9.83° ± 0.83° vs 14.72° ± 1.64°; P = .015). Conversely, fibers became more radially oriented in the medial-intimal region L of BAV-ATAA when compared with TAV-ATAA (amplitude of angular undulation of collagen = 18.67° ± 0.95° vs 14.56° ± 1.37°; P = .041). CONCLUSIONS: The differential pattern of fiber orientation noted between L and N-R regions help explain the unique pattern of greater curvature dilatation of BAV-ATAA. The distinctions noted in matrix microarchitecture may form the basis of differing aneurysm geometries and aortic wall integrities in ATAAs arising in these different valve morphologies.
Subject(s)
Aorta, Thoracic/pathology , Aortic Aneurysm, Thoracic/etiology , Aortic Valve/abnormalities , Extracellular Matrix/ultrastructure , Heart Valve Diseases/complications , Adult , Aged , Aged, 80 and over , Aorta, Thoracic/physiopathology , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/physiopathology , Bicuspid Aortic Valve Disease , Elasticity , Female , Heart Valve Diseases/diagnosis , Humans , Male , Middle AgedABSTRACT
An orthogonal chromatography methodology for the enrichment of host cell protein (HCP) species relative to monoclonal antibody (mAb) products was developed and applied for the successful enrichment of HCP from post-Protein A process pools for seven different mAb products. An advanced two-dimensional liquid chromatography/mass spectrometry platform (2D-LC/MS(E) ) was utilized to demonstrate that the HCP enriched material was representative, in terms of species content, to pre-enriched process pools. The HCP enrichment methodology was scaled up for two different mAb products, and this process relevant enriched HCP material was used to conduct advanced spike challenge studies to demonstrate the utility of the approach for the understanding of (1) quantitative HCP clearance, (2) individual species clearance, and (3) species clearance redundancy across polishing chromatography steps. The combined ability to enrich process relevant HCP, detect individual HCP species with 2D-LC/MS(E) technology, and conduct advanced challenge studies with process relevant material surmounts prior limitations to high integrity process challenge study implementation, and facilitates significant process understanding for development of risk-based control strategies and strategic process design. This also demonstrates implementation of a foundational strategy for conducting spike-challenge studies using process-relevant impurities isolated from processes of interest using orthogonal approaches.
Subject(s)
Antibodies, Monoclonal/analysis , Biotechnology/methods , Proteins/chemistry , Proteins/isolation & purification , Animals , CHO Cells , Chromatography, Liquid , Cricetinae , Cricetulus , Electrophoresis, Polyacrylamide Gel , Mass SpectrometryABSTRACT
INTRODUCTION: There are limited comparative data on catheter ablation of atrial fibrillation (CAAF) using the second-generation cryoballoon (CB-2) versus point-by-point radiofrequency (RF). This study examines the acute/long-term CAAF outcomes using these 2 strategies. METHODS AND RESULTS: In this multicenter, retrospective, nonrandomized analysis, procedural and clinical outcomes of 1,196 patients (76% with paroxysmal AF) undergoing CAAF using CB-2 (n = 773) and open-irrigated, non-force sensing RF (n = 423) were evaluated. Pulmonary vein isolation was achieved in 98% with CB-2 and 99% with RF (P = 0.168). CB-2 was associated with shorter ablation time (40 ± 14 min vs. 66 ± 26 min; P < 0.001) and procedure time (145 ± 49 minutes vs. 188 ± 42 minutes; P < 0.001), but greater fluoroscopic utilization (29 ± 13 minutes vs. 23 ± 14 minutes; P < 0.001). While transient (7.6% vs. 0%; P < 0.001) and persistent (1.2% vs. 0%; P = 0.026) phrenic nerve palsy occurred exclusively with CB-2, other adverse event rates were similar between CB-2 (1.6%) and RF (2.6%); P = 0.207. However, freedom from AF/atrial flutter/tachycardia at 12 months following a single procedure without antiarrhythmic therapy was greater with CB-2 (76.6%) versus RF (60.4%); P < 0.001. While this difference was evident in patients with paroxysmal AF (P < 0.001), it did not reach significance in those with persistent AF (P = 0.089). Additionally, CB-2 was associated with reduced long-term need for antiarrhythmic therapy (16.7% vs. 22.0%; P = 0.024) and repeat ablations (14.6% vs. 24.1%; P < 0.001). CONCLUSION: In this multicenter, retrospective, nonrandomized study, CAAF using CB-2 coupled with RF as occasionally required was associated with greater freedom from atrial arrhythmias at 12 months following a single procedure without antiarrhythmic therapy when compared to open-irrigated, non-force sensing RF, alone.
Subject(s)
Atrial Fibrillation/surgery , Catheter Ablation , Cryosurgery/instrumentation , Pulmonary Veins/surgery , Therapeutic Irrigation , Action Potentials , Aged , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Atrial Flutter/etiology , Brazil , Catheter Ablation/adverse effects , Cryosurgery/adverse effects , Disease-Free Survival , Equipment Design , Female , Heart Rate , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Ontario , Operative Time , Pulmonary Veins/physiopathology , Radiography, Interventional , Recurrence , Retrospective Studies , Risk Factors , Tachycardia, Supraventricular/etiology , Therapeutic Irrigation/adverse effects , Time Factors , Treatment Outcome , United StatesABSTRACT
Acute infectious gastroenteritis continues to be a leading cause of morbidity and mortality in children below 5 years of age, with the majority of deaths concentrated in 35 'low income' countries. In these countries the under five years of age mortality rates reach 100 per 1000 live births, of which a significant proportion are associated with acute diarrhea. Rotavirus, cryptosporidium, Shigella spp and enterotoxigenic Escherichia coli are the main pathogens causing disease in these settings, although other bacteria and parasites can cause moderate to severe disease in different regions and situations. Treatment of children in these setting should be focused on appropriate rehydration, early hospitalization of severely malnourished children, zinc supplementation, and in specific situations, antimicrobials should be considered. The rationale for antimicrobial use should be based on the potential benefits based on published literature and the opportunity for use. This review provides a pathogen-specific update on the potential benefits of antimicrobials and suggests an empirical management approach for children suffering an acute watery or bloody diarrhea in a resource-limited region.
Subject(s)
Anti-Infective Agents/therapeutic use , Cryptosporidiosis/therapy , Diarrhea/therapy , Dysentery, Bacillary/therapy , Escherichia coli Infections/therapy , Rotavirus Infections/therapy , Acute Disease , Child, Preschool , Cryptosporidiosis/parasitology , Developing Countries , Diarrhea/microbiology , Diarrhea/parasitology , Diarrhea/virology , Disease Management , Dysentery, Bacillary/microbiology , Escherichia coli Infections/microbiology , Fluid Therapy , Hospitalization , Humans , Poverty Areas , Rotavirus Infections/virologyABSTRACT
Outbreaks of acute gastroenteritis are a public health problem. Norovirus is known as the most common cause (50%). In Chile, immediate notification allows surveillance of these events. We describe an acute gastroenteritis outbreak that occurred in Antofagasta region, between March and April 2010. An observational study was conducted to perform the outbreak investigation. Local residents who met case definition were included. Stool samples, epidemiological surveys and environmental samples were requested. The outbreak began approximately on March 8, 2010 and lasted until April 28 with 31,036 reported cases (rate 54 per 1000 inhabitants). The most affected age group was between 25 and 44 years, and diarrhea was the main symptom (97% of cases). We determined the presence of norovirus genogroup II in clinical and environmental samples. This outbreak was caused by consumption of raw vegetables from La Chimba, which were watered and contaminated with treated sewage containing low concentration of free residual chlorine. Subsequently, the outbreak spread from person to person in a poor sanitary environment.
Subject(s)
Caliciviridae Infections/epidemiology , Disease Outbreaks , Gastroenteritis/epidemiology , Norovirus/isolation & purification , Acute Disease , Adolescent , Adult , Caliciviridae Infections/transmission , Child, Preschool , Chile/epidemiology , Feces/virology , Female , Gastroenteritis/virology , Humans , Infant , Male , Middle AgedABSTRACT
Outbreaks of acute gastroenteritis are a public health problem. Norovirus is known as the most common cause (50%). In Chile, immediate notification allows surveillance of these events. We describe an acute gastroenteritis outbreak that occurred in Antofagasta region, between March and April 2010. An observational study was conducted to perform the outbreak investigation. Local residents who met case definition were included. Stool samples, epidemiological surveys and environmental samples were requested. The outbreak began approximately on March 8, 2010 and lasted until April 28 with 31,036 reported cases (rate 54 per 1000 inhabitants). The most affected age group was between 25 and 44 years, and diarrhea was the main symptom (97% of cases). We determined the presence of norovirus genogroup II in clinical and environmental samples. This outbreak was caused by consumption of raw vegetables from La Chimba, which were watered and contaminated with treated sewage containing low concentration of free residual chlorine. Subsequently, the outbreak spread from person to person in a poor sanitary environment.
Antecedentes: Los brotes por gastroenteritis aguda constituyen un problema de salud pública. Se conoce al norovirus como la causa más común (50%). En Chile, la vigilancia de estos eventos, se establece mediante la notificación inmediata. Objetivo: Investigar y caracterizar el brote de gastroenteritis aguda ocurrido en la Región de Antofagasta, durante los meses de marzo y abril de 2010. Método: Se efectuó un estudio observacional descriptivo para realizar la investigación de brote. Se incluyó a residentes de la región que cumplían con la definición de caso. Se solicitó muestras de deposición, encuesta epidemiológica y muestras ambientales. Resultados: Se estimó que el brote comenzó el 8 de marzo de 2010 y duró hasta el 28 de abril del mismo año; se notificaron 31. 036 casos (tasa 54 por 1.000 habitantes). El grupo de 25 y 44 años de edad fue el más afectado y la diarrea fue el síntoma predominante (97% de los casos). Se determinó la presencia de norovirus genogrupo II en muestras clínicas y ambientales. Conclusiones: El brote se originó por el consumo crudo de hortalizas que provenían del sector La Chimba, las que fueron regadas y contaminadas con agua servida tratada que contenía baja concentración de cloro libre residual y posteriormente se propagó por transmisión persona-persona, en un ambiente sanitario deficiente.
Subject(s)
Adolescent , Adult , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Caliciviridae Infections/epidemiology , Disease Outbreaks , Gastroenteritis/epidemiology , Norovirus/isolation & purification , Acute Disease , Caliciviridae Infections/transmission , Chile/epidemiology , Feces/virology , Gastroenteritis/virologyABSTRACT
The experience of a group of 9 doctors and 6 nurses, most of them younger than 30 years of age, whom were part of the several volunteer groups directed towards the most damaged earthquake regions, is described. The team had to overcome a number of intense personal emotions related with the magnitude of the destruction, especially in the "adobe"-constructed houses and villages, in order to provide useful medical support. Moving out of the hospital setting, reaching out to the community in schools and emergency posts proved to be important in rural communities. An appropriate coordination of the volunteer groups, with the simultaneous action of municipal and state health authorities, together with well-guided leadership, was critical for an effective response in the larger city of Talcahuano /Hualpén. Within the second week of the aftermath, acute respiratory and intestinal infections were the most common medical complaints together with intense -in many cases severe- emotional distress associated mostly with fear to after shakes ("replicas"), tsunami, and social unrest. The severe earthquake that struck Chile has left many lessons for the future that will need to be analyzed seriously and with the conviction that effective and timely prevention of catastrophic aftermath consequences, although costly, must be a key element of the country's development plan. More importantly, the hundreds if not thousands of volunteers from a variety of health related professions that were moved by the scenes of suffering, and whom responded to individual or group initiatives, allow to foresee that the nation has the moral stamina required to overcome the tragedy and become a better society.