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1.
J Cardiothorac Vasc Anesth ; 38(1): 118-122, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37923595

RESUMO

More than 300,000 adults have cardiac surgery in the United States annually, and most undergo intraoperative transesophageal echocardiography (TEE). This patient population is often older with multiple comorbidities, increasing their risk for complications for even routine procedures. Major morbidity or mortality caused by TEE is rare, and it is unknown how often such complications lead to malpractice lawsuits. The authors identified 13 cases out of 2,564 in a closed claims database that involved TEE and reviewed their etiology. Esophageal injury accounted for most of the suits, and only 2 were related to diagnosis. Most expert reviews deemed the care provided by the anesthesiologist to be appropriate.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Imperícia , Adulto , Humanos , Estados Unidos , Anestesiologistas , Ecocardiografia Transesofagiana/efeitos adversos , Bases de Dados Factuais
2.
Langmuir ; 38(9): 2840-2851, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35192365

RESUMO

Molecular dynamics (MD) force fields for lipids and ions are typically developed independently of one another. In simulations consisting of both lipids and ions, lipid-ion interaction energies are estimated using a predefined set of mixing rules for Lennard-Jones (LJ) interactions. This, however, does not guarantee their reliability. In fact, compared to the quantum mechanical reference data, Lorentz-Berthelot mixing rules substantially underestimate the binding energies of Na+ ions with small-molecule analogues of lipid headgroups, yielding errors on the order of 80 and 130 kJ/mol, respectively, for methyl acetate and diethyl phosphate. Previously, errors associated with mixing force fields have been reduced using approaches such as "NB-fix" in which LJ interactions are computed using explicit cross terms rather than those from mixing rules. Building on this idea, we derive explicit lipid-ion cross terms that also may implicitly include many-body cooperativity effects. Additionally, to account for the interdependency between cross terms, we optimize all cross terms simultaneously by performing high-dimensional searches using our ParOpt software. The cross terms we obtain reduce the errors due to mixing rules to below 10 kJ/mol. MD simulation of the lipid bilayer conducted using these optimized cross terms resolves the structural discrepancies between our previous simulations and small-angle X-ray and neutron scattering experiments. These results demonstrate that simulations of lipid bilayers with ions that are accurate up to structural data from scattering experiments can be performed without explicit polarization terms. However, it is worth noting that such NB-fix cross terms are not based on any physical principle; a polarizable lipid model would be more realistic and is still desired. Our approach is generic and can be applied to improve the accuracies of simulations employing mixed force fields.


Assuntos
Bicamadas Lipídicas , Simulação de Dinâmica Molecular , Íons/química , Bicamadas Lipídicas/química , Reprodutibilidade dos Testes , Termodinâmica
3.
Eur Respir J ; 56(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32366485

RESUMO

BACKGROUND: Global tuberculosis policy increasingly emphasises broad tuberculosis impacts and highlights the lack of evidence concerning tuberculosis-related quality of life (QOL). METHODS: Participants were recruited in 32 Peruvian communities between July 13, 2016 and February 24, 2018 and followed-up until November 8, 2019. Inclusion criteria were age ≥15 years for "patients" (n=1545) starting treatment for tuberculosis disease in health centres; "contacts" (n=3180) who shared a patient's household for ≥6 h·week-1; and randomly selected "controls" (n=277). The EUROHIS-QOL questionnaire quantified satisfaction with QOL, health, energy, activities of daily living (ADL), self, relationships, money and living place. FINDINGS: Newly diagnosed tuberculosis was most strongly associated with lower QOL scores (p<0.001). Patients initially had lower QOL than controls for all EUROHIS-QOL questions (p≤0.01), especially concerning health, ADL and self. Lower initial QOL in patients predicted adverse treatment outcomes and scores <13 points had 4.2-fold (95% CI 2.3-7.6) increased risk of death versus those with higher QOL scores (both p<0.001). Patient QOL was re-assessed 6 months later, and for patients with successful treatment QOL became similar to participants who had never had tuberculosis, whereas patients who did not complete treatment continued to have low QOL (p<0.001). Multidrug-resistant tuberculosis was associated with lower QOL before and during treatment (both p<0.001). Contacts had lower QOL if they lived with a patient who had low QOL score (p<0.0001) or were a caregiver for the patient (p<0.001). CONCLUSIONS: Tuberculosis was associated with impaired psychosocioeconomic QOL which recovered with successful treatment. Low QOL scores predicted adverse treatment outcome. This brief EUROHIS-QOL eight-item questionnaire quantified the holistic needs of tuberculosis-affected people, potentially guiding patient-centred care.


Assuntos
Qualidade de Vida , Tuberculose Resistente a Múltiplos Medicamentos , Atividades Cotidianas , Adolescente , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Resultado do Tratamento
4.
Clin Infect Dis ; 66(12): 1846-1857, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29272346

RESUMO

Background: In sub-Saharan Africa, 25.5 million people are living with human immunodeficiency virus (HIV), representing 70% of the global total. The need for second-line antiretroviral therapy (ART) is projected to increase in the next decade in keeping with the expansion of treatment provision. Outcome data are required to inform policy. Methods: We performed a systematic review and meta-analysis of studies reporting the virological outcomes of protease inhibitor (PI)-based second-line ART in sub-Saharan Africa. The primary outcome was virological suppression (HIV-1 RNA <400 copies/mL) after 48 and 96 weeks of treatment. The secondary outcome was the proportion of patients with PI resistance. Pooled aggregate data were analyzed using a DerSimonian-Laird random effects model. Results: By intention-to-treat analysis, virological suppression occurred in 69.3% (95% confidence interval [CI], 58.2%-79.3%) of patients at week 48 (4558 participants, 14 studies), and in 61.5% (95% CI, 47.2%-74.9%) at week 96 (2145 participants, 8 studies). Preexisting resistance to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) increased the likelihood of virological suppression. Major protease resistance mutations occurred in a median of 17% (interquartile range, 0-25%) of the virological failure population and increased with duration of second-line ART. Conclusions: One-third of patients receiving PI-based second-line ART with continued NRTI use in sub-Saharan Africa did not achieve virological suppression, although among viremic patients, protease resistance was infrequent. Significant challenges remain in implementation of viral load monitoring. Optimizing definitions and strategies for management of second-line ART failure is a research priority. Prospero Registration: CRD42016048985.


Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Inibidores da Protease de HIV/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , África Subsaariana/epidemiologia , Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral/genética , Feminino , HIV-1 , Humanos , Masculino , Mutação , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resposta Viral Sustentada , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Viremia/tratamento farmacológico
5.
Trop Med Int Health ; 23(8): 850-859, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29862612

RESUMO

OBJECTIVES: Mobile phone interventions have been advocated for tuberculosis care, but little is known about access of target populations to mobile phones. We studied mobile phone access among patients with tuberculosis, focusing on vulnerable patients and patients who later had adverse treatment outcomes. METHODS: In a prospective cohort study in Callao, Peru, we recruited and interviewed 2584 patients with tuberculosis between 2007 and 2013 and followed them until 2016 for adverse treatment outcomes using national treatment registers. Subsequently, we recruited a further 622 patients between 2016 and 2017. Data were analysed using logistic regression and by calculating relative risks (RR). RESULTS: Between 2007 and 2013, the proportion of the general population of Peru without mobile phone access averaged 7.8% but for patients with tuberculosis was 18% (P < 0.001). Patients without access were more likely to hold a lower socioeconomic position, suffer from food insecurity and be older than 50 years (all P < 0.01). Compared to patients with mobile phone access, patients without access at recruitment were more likely to subsequently have incomplete treatment (20% vs. 13%, RR = 1.5; P = 0.001) or an adverse treatment outcome (29% vs. 23% RR = 1.3; P = 0.006). Between 2016 and 2017, the proportion of patients without access dropped to 8.9% overall, but remained the same (18%) as in 2012 among the poorest third. CONCLUSION: Access to mobile phones among patients with tuberculosis is insufficient, and rarest in patients who are poorer and later have adverse treatment outcomes. Thus, mobile phone interventions to improve tuberculosis care may be least accessed by the priority populations for whom they are intended. Such interventions should ensure access to mobile phones to enhance equity.


Assuntos
Telefone Celular/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Telemedicina/estatística & dados numéricos , Tuberculose/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Peru , Pobreza/estatística & dados numéricos , Estudos Prospectivos , Envio de Mensagens de Texto/estatística & dados numéricos , Tuberculose/terapia
6.
PLoS Med ; 14(10): e1002406, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29040271

RESUMO

In a Perspective accompanying Sylvia and colleagues, Carlton Evans and colleagues discuss the challenge of squaring policies around tuberculosis diagnosis with the realities of clinical practice in small villages and low-resource settings.


Assuntos
Atenção à Saúde/legislação & jurisprudência , Qualidade da Assistência à Saúde , Tuberculose/diagnóstico , Tuberculose/terapia , Humanos
7.
Biochim Biophys Acta Biomembr ; 1859(12): 2297-2307, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28882547

RESUMO

Dissimilarities in the bulk structure of bilayers composed of ether- vs ester-linked lipids are well-established; however, the atomistic interactions responsible for these differences are not well known. These differences are important in understanding of why archaea have a different bilayer composition than the other domains of life and why humans have larger concentrations of plasmalogens in specialized membranes? In this paper, we simulate two lipid bilayers, the ester linked dipalmitoylphosphatidylcholine (DPPC) and the ether lined dihexadecylphosphatidylcholine (DHPC), to study these variations. The structural analysis of the bilayers reveals that DPPC is more compressible than DHPC. A closer examination of dipole potential shows DHPC, despite having a smaller dipole potential of the bilayer, has a higher potential barrier than DPPC at the surface. Analysis of water order and dynamics suggests DHPC has a more ordered, less mobile layer of water in the headgroup. These results seem to resolve the issue as to whether the decrease in permeability of DHPC is due to of differences in minimum area per lipid (A0) or diffusion coefficient of water in the headgroup region (Dhead) (Guler et al., 2009) since we have shown significant changes in the order and mobility of water in that region.


Assuntos
1,2-Dipalmitoilfosfatidilcolina/química , Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Éteres Fosfolipídicos/química , Água/química , Cinética , Permeabilidade , Eletricidade Estática , Temperatura , Termodinâmica
9.
Bull World Health Organ ; 95(4): 270-280, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28479622

RESUMO

OBJECTIVE: To evaluate the impact of socioeconomic support on tuberculosis preventive therapy initiation in household contacts of tuberculosis patients and on treatment success in patients. METHODS: A non-blinded, household-randomized, controlled study was performed between February 2014 and June 2015 in 32 shanty towns in Peru. It included patients being treated for tuberculosis and their household contacts. Households were randomly assigned to either the standard of care provided by Peru's national tuberculosis programme (control arm) or the same standard of care plus socioeconomic support (intervention arm). Socioeconomic support comprised conditional cash transfers up to 230 United States dollars per household, community meetings and household visits. Rates of tuberculosis preventive therapy initiation and treatment success (i.e. cure or treatment completion) were compared in intervention and control arms. FINDINGS: Overall, 282 of 312 (90%) households agreed to participate: 135 in the intervention arm and 147 in the control arm. There were 410 contacts younger than 20 years: 43% in the intervention arm initiated tuberculosis preventive therapy versus 25% in the control arm (adjusted odds ratio, aOR: 2.2; 95% confidence interval, CI: 1.1-4.1). An intention-to-treat analysis showed that treatment was successful in 64% (87/135) of patients in the intervention arm versus 53% (78/147) in the control arm (unadjusted OR: 1.6; 95% CI: 1.0-2.6). These improvements were equitable, being independent of household poverty. CONCLUSION: A tuberculosis-specific, socioeconomic support intervention increased uptake of tuberculosis preventive therapy and tuberculosis treatment success and is being evaluated in the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project.


Assuntos
Antibioticoprofilaxia/métodos , Antituberculosos/administração & dosagem , Família , Apoio Social , Tuberculose/prevenção & controle , Adolescente , Antibioticoprofilaxia/economia , Antituberculosos/economia , Criança , Pré-Escolar , Feminino , Educação em Saúde/organização & administração , Visita Domiciliar , Humanos , Lactente , Masculino , Programas de Rastreamento/organização & administração , Assistência Médica/organização & administração , Peru , Pobreza , Avaliação de Programas e Projetos de Saúde , Tuberculose/tratamento farmacológico , Adulto Jovem
10.
Cochrane Database Syst Rev ; 12: CD007124, 2016 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-27933615

RESUMO

BACKGROUND: Carbamazepine (CBZ) is a commonly used drug for epilepsy that is associated with troublesome adverse events including dizziness, double vision, drowsiness, poor co-ordination and unsteadiness. These adverse events often occur during peaks in drug plasma concentration. These adverse events may limit the daily dose of CBZ that can be tolerated and reduce the chances of seizure control in patients who require high doses. A controlled-release formulation of CBZ delivers the same dose over a longer period of time when compared to a standard immediate-release formulation, thereby reducing post-dose peaks in CBZ plasma concentration and potentially reducing adverse events.This is an updated version of the original Cochrane review published in Issue 12, 2014. OBJECTIVES: To determine the efficacy of immediate-release CBZ (IR CBZ) versus controlled-release CBZ (CR CBZ) in patients diagnosed with epilepsy.The following review questions were investigated.(1) For newly diagnosed patients commencing CBZ, how do IR and CR formulations compare for efficacy and tolerability?(2) For patients on established treatment with IR CBZ but experiencing unacceptable adverse events, what is the effect on seizure control and the tolerability of a switch to a CR formulation versus remaining on the IR formulation? SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register, CENTRAL, and MEDLINE (Ovid) from inception to 30 August 2016. SELECTION CRITERIA: Randomised controlled trials comparing IR CBZ to CR CBZ in patients commencing monotherapy and patients presently treated with IR CBZ but experiencing unacceptable adverse events.Primary outcome measures included measures of seizure frequency, incidence of adverse events, proportion of patients with treatment failure and quality of life measures. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted the data and recorded relevant information on a standardised data extraction form. We used the Cochrane risk of bias tool to assess the methodological quality of included studies.The heterogeneity of the included trials with respect to the reporting of outcomes resulted in only a narrative, descriptive analysis being possible for both the categorical and time-to-event data. MAIN RESULTS: Ten trials (296 participants) fulfilled the criteria for inclusion in this review. Only one study had a low risk of bias. Two studies had a high risk of bias and the rest of the studies were rated as unclear risk of bias. One trial included patients with newly diagnosed epilepsy and nine included patients on treatment with IR CBZ.Eight trials reported heterogeneous measures of seizure frequency with conflicting results. A statistically significant difference was observed in only one trial, with patients prescribed CR CBZ experiencing fewer seizures than patients prescribed IR CBZ.Nine trials reported measures of adverse events. There was a trend in favour of CR CBZ with four trials reporting a statistically significant reduction in adverse events compared to IR CBZ. A further two trials reported fewer adverse events with CR CBZ but the reduction was not statistically significant. One trial found no difference in adverse events, and another trial reported more adverse events in the CR CBZ group than the IR CBZ group, although the increase was not statistically significant. AUTHORS' CONCLUSIONS: For this update no new eligible studies were identified and the conclusions drawn from the initial review remain unchanged.At present, data from trials do not confirm or refute an advantage for CR CBZ over IR CBZ for seizure frequency or adverse events in patients with newly diagnosed epilepsy.For trials involving epilepsy patients already prescribed IR CBZ, no conclusions can be drawn concerning the superiority of CR CBZ with respect to seizure frequency.There is a trend for CR CBZ to be associated with fewer adverse events when compared to IR CBZ. A change to CR CBZ may therefore be a worthwhile strategy in patients with acceptable seizure control on IR CBZ but experiencing unacceptable adverse events. The included trials were of small size and of poor methodological quality limiting the validity of this conclusion.Randomised controlled trials comparing CR CBZ to IR CBZ and using clinically relevant outcomes are required to inform the choice of CBZ preparation for patients with newly diagnosed epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Epilepsia/tratamento farmacológico , Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Preparações de Ação Retardada/efeitos adversos , Preparações de Ação Retardada/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Org Biomol Chem ; 13(5): 1463-9, 2015 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-25474271

RESUMO

The LFA-1 inhibitor and leukocyte adhesion suppressor BIRT-377 was prepared in high enantiomeric excess by desymmetrization of dimethyl 2-p-bromobenzyl-2-methylmalonate, followed by condensation of the resulting carboxylic acid with 3,5-dichloroaniline, saponification of the remaining ester and Curtius rearrangement as the key steps. When Curtius rearrangement preceded the condensation step, (ent)-BIRT-377 was similarly obtained in high ee.


Assuntos
Esterases/metabolismo , Imidazolidinas/química , Imidazolidinas/síntese química , Fígado/enzimologia , Antígeno-1 Associado à Função Linfocitária/metabolismo , Suínos , Animais , Técnicas de Química Sintética , Imidazolidinas/farmacologia , Estereoisomerismo
14.
RNA ; 18(10): 1796-804, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22912485

RESUMO

miRNAs are ∼22-nt RNAs that bind to the Argonaute family of proteins and have important regulatory roles in plants and animals. Here, we show that miRNAs exhibit targeting activity in cells when delivered as single strands that are 5'-phosphorylated and that contain 2'-fluoro ribose modifications. Length preferences, chemical modification sensitivity, and genome-wide seed-based targeting all suggest that this activity is Ago-based. Activity could be enhanced by annealing of segmented passenger strands containing non-nucleic acid spacers. Furthermore, screening of randomly generated sequences identified pyrimidine rich 3' cassette sequences that increased single strand activity. These results provide an initial step in the development of single-stranded miRNA mimics for therapeutic use.


Assuntos
DNA de Cadeia Simples/síntese química , MicroRNAs/química , Mimetismo Molecular , Sequência de Bases , Clonagem Molecular , DNA de Cadeia Simples/química , Fluoretos/síntese química , Fluoretos/química , Técnicas de Silenciamento de Genes/instrumentação , Técnicas de Silenciamento de Genes/métodos , Células HCT116 , Ensaios de Triagem em Larga Escala , Humanos , Análise em Microsséries , Mimetismo Molecular/fisiologia , Dados de Sequência Molecular , Fosforilação , Ribose/síntese química , Ribose/química , Transfecção
15.
Bioconjug Chem ; 25(8): 1556-64, 2014 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-25072845

RESUMO

Monoclonal antibodies are one of the most useful and ubiquitous affinity reagents used in the biological sciences. Immunostaining of fixed and live cells for microscopy or cytometry measurements frequently employs fluorescently labeled antibodies, in particular fluorescein-labeled antibodies. This dye emits light at a wavelength overlapping with cellular autofluorescence, making it difficult to measure antibody binding to proteins of relatively low copy number or in cells of high green autofluorescence. A number of high affinity fluorescein binding antibodies and antibody domains have been developed that quench the dye's fluorescence. Using a fluorescein-binding recombinant antibody domain genetically fused to a fluorogen activating protein (FAP), we demonstrate a molecular converter capable of binding and quenching fluorescein, while binding and activating a fluorogenic triarylmethane dye. This reagent converts fluorescein conjugates to far-red fluorescent probes, where cellular autofluorescence is low, improving signal-to-background of cell-based antibody binding measurements by ∼7-fold. Microscopy experiments show colocalization of both fluorescein and MG fluorescence. This dual affinity fluorescein-quenching-FAP can also be used to convert fluorescein to the red fluorescing MG fluorogen on biological molecules other than antibodies.


Assuntos
Fluoresceína/química , Corantes Fluorescentes/química , Luz , Proteínas Recombinantes de Fusão/química , Anticorpos de Cadeia Única/química , Sequência de Aminoácidos , Animais , Biotina/química , Células CHO , Cricetinae , Cricetulus , Dextranos/química , Estabilidade de Medicamentos , Células HEK293 , Humanos , Fotodegradação , Polietilenoglicóis/química , Razão Sinal-Ruído , Espectrometria de Fluorescência , Coloração e Rotulagem
16.
Cochrane Database Syst Rev ; (12): CD007124, 2014 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-25470302

RESUMO

BACKGROUND: Epilepsy is defined as the tendency to spontaneous, excessive neuronal discharge manifesting as seizures. It is a common disorder with an incidence of 50 per 100,000 per year and a prevalence of 0.5% to 1% in the developed world (Hauser 1993).Carbamazepine (CBZ) is a widely used antiepileptic drug that is associated with a number of troublesome adverse events including dizziness, double vision and unsteadiness. These often occur during peaks in drug plasma concentration. The occurrence of such adverse events may limit the daily dose that can be tolerated and reduce the chances of seizure control for patients requiring higher doses (Vojvodic 2002). A controlled-release formulation of carbamazepine delivers the same dose over a longer period of time when compared to a standard formulation, thereby reducing post-dose peaks and potentially reducing adverse events associated with peak plasma levels. OBJECTIVES: To determine the efficacy of immediate-release CBZ (IR CBZ) versus controlled-release CBZ (CR CBZ) in patients diagnosed with epilepsy.The following review questions were investigated.(1) For newly diagnosed patients commencing CBZ, how do IR and CR formulations compare for efficacy and tolerability?(2) For patients on established treatment with IR CBZ but experiencing unacceptable adverse events, what is the effect on seizure control and the tolerability of a switch to a CR formulation versus remaining on the IR formulation? SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register (10 November 2014), Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO) 11 November 2014, and MEDLINE (Ovid, 1946 to 11 November 2014). SELECTION CRITERIA: Randomised controlled trials comparing IR CBZ to CR CBZ in patients commencing monotherapy and patients presently treated with IR CBZ but experiencing unacceptable adverse events.Primary outcome measures include seizure frequency, incidence of adverse events, proportion of patients with treatment failure and quality of life measures. DATA COLLECTION AND ANALYSIS: The methodological quality of each study was assessed with respect to study design, type of control, method and concealment of allocation, blinding and completeness of follow up, and the presence of blinding for assessment of non-fatal outcomes. We did not make use of an overall quality score.Two review authors (GP, MS) independently extracted the data and recorded relevant information on a standardised data extraction form. The trials were assessed for inclusion.The heterogeneity of the included trials resulted in only a narrative, descriptive analysis being possible for both the categorical and time-to-event data. MAIN RESULTS: Ten trials fulfilled the criteria for inclusion in this review. One trial included patients with newly diagnosed epilepsy and nine included patients on treatment with IR CBZ.Eight trials reported heterogeneous measures of seizure frequency with conflicting results. A statistically significant difference was observed in only one trial, with patients prescribed CR CBZ experiencing fewer seizures than patients prescribed IR CBZ.Nine trials reported measures of adverse events. There was a trend in favour of CR CBZ with four trials reporting a statistically significant reduction in adverse events compared to IR CBZ. A further two trials reported fewer adverse events with CR CBZ but the reduction was not statistically significant. One trial found no difference, with a further trial reporting increased adverse events in the CR CBZ group although the increase was not statistically significant. AUTHORS' CONCLUSIONS: At present, data from trials do not confirm or refute an advantage for CR CBZ over IR CBZ for seizure frequency or adverse events in patients with newly diagnosed epilepsy.For trials involving epilepsy patients already prescribed IR CBZ, no conclusions can be drawn concerning the superiority of CR CBZ with respect to seizure frequency.There is a trend for CR CBZ to be associated with fewer adverse events when compared to IR CBZ. A change to CR CBZ may therefore be a worthwhile strategy in patients with acceptable seizure control on IR CBZ but experiencing unacceptable adverse events. The included trials were of small size, had poor methodological quality and possessed a high risk of bias, limiting the validity of this conclusion.Randomised controlled trials comparing CR CBZ to IR CBZ and using clinically relevant outcomes are required to inform the choice of CBZ preparation for patients with newly diagnosed epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Epilepsia/tratamento farmacológico , Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Preparações de Ação Retardada/efeitos adversos , Preparações de Ação Retardada/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Cochrane Database Syst Rev ; (2): CD007124, 2014 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-24488654

RESUMO

BACKGROUND: Epilepsy is defined as the tendency to spontaneous, excessive neuronal discharge manifesting as seizures. It is a common disorder with an incidence of 50 per 100,000 per year and a prevalence of 0.5% to 1% (Hauser 1993) in the developed world.Carbamazepine (CBZ) is a widely used antiepileptic drug that is associated with a number of troublesome adverse events including dizziness, double vision and unsteadiness. These often occur during peaks in plasma concentration. The occurrence of such adverse events may limit the daily dose that can be tolerated and reduce the chances of seizure control for patients requiring higher doses (Vojvodic 2002). A controlled-release formulation of carbamazepine delivers the same dose over a longer period of time when compared to a standard formulation, thereby reducing post-dose peaks and potentially reducing adverse events associated with peak plasma levels. OBJECTIVES: To determine the efficacy of immediate-release CBZ (IR CBZ) versus controlled-release CBZ (CR CBZ) in patients diagnosed with epilepsy. The following hypotheses were tested.(1) For newly diagnosed patients commencing CBZ, how do immediate-release and controlled-release formulations compare for efficacy and tolerability?(2) For patients on established treatment with immediate-release CBZ but experiencing unacceptable adverse events, what is the effect on seizure control and tolerability of a switch to a controlled-release formulation versus remaining on the immediate-release formulation? SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialised Register (5 September 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2013) in The Cochrane Library and MEDLINE (1946 to 5 September 2013). SELECTION CRITERIA: Randomised controlled trials comparing IR CBZ to CR CBZ in patients commencing monotherapy and patients presently treated with IR CBZ but experiencing unacceptable adverse events.Primary outcome measures include seizure frequency, incidence of adverse events, proportion with treatment failure and quality of life measures. DATA COLLECTION AND ANALYSIS: The methodological quality of each study was assessed with respect to study design, type of control, method and the concealment of allocation, blinding and completeness of follow up, and the presence of blinding for assessment of non-fatal outcomes. We did not make use of an overall quality score.Two review authors (GP, MS) independently extracted the data and recorded relevant information on a standardised data extraction form. Results were assessed for inclusion.The heterogeneity of the included trials resulted in only a narrative, descriptive analysis being possible for both the categorical and time-to-event data. MAIN RESULTS: Ten trials fulfilled the criteria for inclusion in this review. One trial included patients with newly diagnosed epilepsy and nine included patients on treatment with IR CBZ.Eight trials reported heterogeneous measures of seizure frequency with conflicting results. A statistically significant difference was observed in only one trial, with patients prescribed CR CBZ experiencing fewer seizures than patients prescribed IR CBZ.Nine trials reported measures of adverse events. There was a trend in favour of CR CBZ with four trials reporting a statistically significant reduction in adverse events compared to IR CBZ. A further two trials reported fewer adverse events with CR CBZ but the reduction was not statistically significant. One trial found no difference, with a further trial reporting increased adverse events in the CR CBZ group although not statistically significant. AUTHORS' CONCLUSIONS: At present, data from trials do not confirm or refute an advantage for CR CBZ over IR CBZ for seizure frequency or adverse events in patients with newly diagnosed epilepsy.For trials involving epilepsy patients already prescribed IR CBZ, no conclusions can be drawn concerning the superiority of CR CBZ with respect to seizure frequency.There is a trend for CR CBZ to be associated with fewer adverse events when compared to IR CBZ. A change to CR CBZ may therefore be a worthwhile strategy in patients with acceptable seizure control on IR CBZ but experiencing unacceptable adverse events. The included trials were of small size, poor methodological quality and possessed a high risk of bias, limiting the validity of this conclusion.Randomised controlled trials comparing CR CBZ to IR CBZ and using clinically relevant outcomes are required to inform the choice of CBZ preparation for patients with newly diagnosed epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Epilepsia/tratamento farmacológico , Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Preparações de Ação Retardada/efeitos adversos , Preparações de Ação Retardada/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Forensic Sci Int ; 361: 112137, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971141

RESUMO

Through both casework and research, fibres have been found to have the particularly useful ability to persist and remain exploitable after submersion. However, direct analysis of the persistence ability remains in early stages, and in particular, submersion times above a day have not been thoroughly studied. This study aims to both extend understanding of the impact of flow rate and submersion periods of up to 28 days. A blended polyester/cotton green fabric was abraded to increase transfer and then dragged over a black cotton substrate. Six replicates of these substrates were then submerged in artificial flow cells at various flow rates for 28 days. These were illuminated under UV light and photographed prior to submersion, at set times during submersion and after submersion. Another set of six replicates were imaged, submerged into a river and then recovered and re-imaged after 28 days. The population of fibres was then counted using these photographs, and a mix of one-way and two-way ANOVA tests were applied, in combination with Tukey's HSD, to detect significant differences across time and flow rate categories. Loss predominantly occurred on within the first 24 hours, in agreement with previous work. However, distinct from previous work there was a slow, approximately logarithmic loss over the balance of the submersion period. While significant differences were found between flow categories, there was no clear relationship between flow rate and persistence. The behaviour of the river samples was well-predicted by laboratory samples. 100 % fibre loss was never observed, with the maximum instead being 95.45 %. These results extend the understanding of fibre persistence on submerged substrates beyond the short submersion times in previous literature, and provide some deeper understanding of the impact of flow rate.

19.
Sci Rep ; 14(1): 1171, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216654

RESUMO

Ireland has > 50% of the EU's ocean-raised bogs; however, degradation through land-use activities has transformed them from carbon (C) sinks to sources. Given their significant role in climate mitigation, it is essential to quantify the emissions resulting from land use degradation of these ecosystems. A seven-class land-use classification system for Irish peatlands (LUCIP) was developed and mapped using Sentinel-2 imagery, random forest machine learning and Google Earth Engine. The results revealed that agricultural grassland comprised 43% of the land use on raised bogs, followed by, forestry (21%), cutover (11%), cutaway (10%) remnant peatlands (13%), waterbodies and built-up ~ 1% each. The overall accuracy of the map was 89%. The map was used to estimate CO2 emissions for four classes constituting 85% of raised bogs: cutover, cutaway, grassland, and forestry using the IPCC wetlands supplement and literature-based emission factors, we estimated emissions at ~ 1.92 (± 1.58-2.27 Mt CO2-C-yr-1) and ~ 0.68 Mt CO2-C-yr-1 (± 0.44-0.91 Mt CO2-C-yr-1) respectively. This is the first study to spatially quantify land use and related emissions from raised bogs. The results have revealed widespread degradation of these globally rare habitats, making them net emitters of CO2. The map is vital for the conservation of these ecosystems through restoration efforts, and the methodology can also be applied to other regions with similar peatland land use issues.

20.
Front Plant Sci ; 15: 1405180, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39045596

RESUMO

Introduction: Lucerne (Medicago sativa), is a cornerstone of China's livestock industry, however, due to the backward agronomic strategies and technology, lucerne in China faces cultivation challenges that result in lower productivity and quality than global standards. Therefore, we undertook a meta-analysis to evaluate the impact of five distinct fertilization types on lucerne yield and nutritional quality in various locations in China. The fertilizer practices included manure application, combined mineral fertilizer and manure application (FM), biological fertilizer application, unbalanced application of two or more mineral fertilizer types, and balanced mineral fertilizer application. Furthermore, we investigate influential factors of yield and quality of lucerne under fertilization, including climatic variables (mean annual precipitation, mean annual temperature), initial soil properties (soil organic carbon; total nitrogen, pH), and agronomic factors (seeding rate, harvest frequency, and lucerne stand age). Methods: Our study analyzed 53 published papers to discern the most beneficial fertilizer for enhancing lucerne yield and nutritional quality. Results and discussion: The results showed that the fertilizer practices, on average, significantly improved yield by 31.72% and crude protein content by 11.29%, with FM emerging as the most effective, this is because mineral fertilizers provide available nutrients for lucerne, manure provides essential organic matter for microorganisms and improve soil properties. In addition, the fertilizer practices significantly reduced neutral and acid detergent fiber contents by 6.28% and 8.50%, respectively, while increasing ash content and relative feeding value. Furthermore, climatic variables, soil properties, and planting system factors such as sowing date and harvest frequency significantly affected yield and nutritional quality. The practical implications of our results emphasize the need for balanced and strategic fertilizer application to optimize lucerne production and highlight the potential to adjust cultivation practices according to environmental conditions. Balanced and strategic fertilizer application can simultaneously improve soil properties, enhance soil carbon sequestration, and reduce the emission of greenhouse gases from the soil, which is a vital measure for realizing sustainable agricultural development.

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