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1.
Anaesthesia ; 78(3): 343-355, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36517981

RESUMO

Clinical emergencies can be defined as unpredictable events that necessitate immediate intervention. Safety critical industries have acknowledged the difficulties of responding to such crises. Strategies to improve human performance and mitigate its limitations include the provision and use of cognitive aids, a family of tools that includes algorithms, checklists and decision aids. This systematic review evaluates the usefulness of cognitive aids in clinical emergencies. Following a systematic search of the electronic databases, we included 13 randomised controlled trials, reported in 16 publications. Each compared cognitive aids with usual care in the context of an anaesthetic, medical, surgical or trauma emergency involving adults. Most trials used only clinicians in the development and testing of the cognitive aids, and only some trials provided familiarisation with the cognitive aids before they were deployed. The primary outcome was the completeness of care delivered to the patient. Cognitive aids were associated with a reduction in the incidence of missed care steps from 43.3% to 11% (RR (95%CI) 0.29 (0.15-0.16); p < 0.001), and the quality of evidence was rated as moderate. The use of cognitive aids was related to decreases in the incidence of errors, increases in the rate of correctly performed steps and improvement in the clinical teamwork skills scores, non-technical skills scores, subjective conflict resolution scores and the global assessment of team performance. Cognitive aids had an inconsistent influence on the time to first intervention and time to complete care of the patient's condition. It is possible that this was a reflection of how common or rare the crisis in question was as well as the experience and expertise of the clinicians and team. Sufficient thought should be applied to the development of the content and design of cognitive aids, with consideration of the pre-existing guideline ecosystem. Cognitive aids should be tested before their deployment with adequate clinician and team training.


Assuntos
Ecossistema , Emergências , Adulto , Humanos , Lista de Checagem , Algoritmos , Cognição
2.
J Postgrad Med ; 69(1): 21-26, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36255013

RESUMO

Objective: To evaluate questions asked during the informed consent process by adult participants in a COVID-19 vaccine regulatory study conducted at our center in 2020. Methods: After approval by the IEC, informed consent documents and consent narratives were evaluated. We collated the total number and nature of questions. We then looked at the association between education, gender, socio-economic status, employment status, the language of consent, and number of questions. Between-group comparison (female vs male, unemployed vs employed, primary school vs secondary school vs graduate vs post-graduates, upper vs upper-middle vs middle vs lower middle vs lower) for the number of questions asked was done using univariate analysis followed by multivariate regression analysis with post hoc Tukey's test. Independent variables were gender, employment status, education and socioeconomic status and the dependent variable was the number of questions asked by the participant. All analyses were done at 5% significance. Content analysis was done in addition by creating categories after evaluation and coding them. Results: A total of N = 129 consents from the same number of participants were evaluated. A total of N = 127/129 participants asked at least one question. Sixty-seven percent of participants asked questions related to the study procedure, followed by 44.9% of participants who asked questions related to the safety of vaccine or placebo. A total of N = 295 questions were asked by the 127 participants. In content analysis, 149/295 (50.5%) questions were on study-related procedures followed by one quarter 76/295 (25.8%) based on safety associated with Investigational Product. Very few participants [2.4%] asked about post-trial access as the regulatory trial was a placebo-controlled trial. None of the independent variables were found to be associated with the number of questions. Conclusion: The majority of the questions asked by the participants were about study-related procedures and vaccine safety. No association was found between any of the independent variables and the number of questions asked. However, there were differences in the demographics of the trial participants between the pandemic and pre-pandemic era.


Assuntos
COVID-19 , Vacinas , Adulto , Humanos , Masculino , Feminino , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Centros de Atenção Terciária , Consentimento Livre e Esclarecido
3.
Anaesthesia ; 76 Suppl 1: 100-109, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33426668

RESUMO

Moderate-to-severe postoperative pain persists for longer than the duration of single-shot peripheral nerve blocks and hence continues to be a problem even with the routine use of regional anaesthesia techniques. The administration of local anaesthetic adjuncts, defined as the concomitant intravenous or perineural injection of one or more pharmacological agents, is an attractive and technically simple strategy to potentially extend the benefits of peripheral nerve blockade beyond the conventional maximum of 8-14 hours. Historical local anaesthetic adjuncts include perineural adrenaline that has been demonstrated to increase the mean duration of analgesia by as little as just over 1 hour. Of the novel local anaesthetic adjuncts, dexmedetomidine and dexamethasone have best demonstrated the capacity to considerably improve the duration of blocks. Perineural dexmedetomidine and dexamethasone increase the mean duration of analgesia by up to 6 hour and 8 hour, respectively, when combined with long-acting local anaesthetics. The evidence for the safety of these local anaesthetic adjuncts continues to accumulate, although the findings of a neurotoxic effect with perineural dexmedetomidine during in-vitro studies are conflicting. Neither perineural dexmedetomidine nor dexamethasone fulfils all the criteria of the ideal local anaesthetic adjunct. Dexmedetomidine is limited by side-effects such as bradycardia, hypotension and sedation, and dexamethasone slightly increases glycaemia. In view of the concerns related to localised nerve and muscle injury and the lack of consistent evidence for the superiority of the perineural vs. systemic route of administration, we recommend the off-label use of systemic dexamethasone as a local anaesthetic adjunct in a dose of 0.1-0.2 mg.kg-1 for all patients undergoing surgery associated with significant postoperative pain.


Assuntos
Anestesia por Condução/métodos , Anestésicos Locais , Bloqueio Nervoso/métodos , Sedação Consciente , Humanos , Hipnóticos e Sedativos , Nervos Periféricos
4.
Anaesthesia ; 76(1): 101-117, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32385856

RESUMO

Traditionally, pain relief for abdominal surgery has centred on epidural analgesia, but transversus abdominis plane block is increasingly being used. Our aim was to compare the analgesic efficacy and the side-effect profile of transversus abdominis plane block with epidural analgesia in a systematic review with meta-analysis and trial sequential analysis. After a systematic search of the electronic databases, we identified 18 randomised controlled trials with 1220 patients. Confirmed by trial sequential analysis, our first co-primary outcome, postoperative pain score at rest at 12 h, was decreased by a mean difference (95%CI) of 0.69 (0.12-1.27; p = 0.02) with epidural analgesia compared with transversus abdominis plane block, with the quality of evidence graded as low. No difference was found for the second co-primary outcome, postoperative pain score at rest at 24 h, with the quality of evidence rated as very low. Relative to transversus abdominis plane block, epidural analgesia further reduced the need for intravenous morphine-equivalent consumption during the 0-24 h interval by a mean difference (95%CI) of 5.91 mg (2.34-9.49; p = 0.001) at the expense of an increased incidence of hypotension at 72 h, with a risk ratio (95%CI) of 5.88 (2.08-16.67; p < 0.001). Our meta-analysis was limited by detection and performance bias, significant statistical heterogeneity and publication bias. In view of the minimal clinically important difference in postoperative pain scores, epidural analgesia was interpreted to not be clinically different to transversus abdominis plane block after abdominal surgery. With transversus abdominis plane block, the increase in intravenous morphine-equivalent consumption at 24 h should be balanced against the decreased risk of hypotension at 72 h. In choosing between epidural analgesia and transversus abdominis plane block, potential benefits should be balanced against the reported risk of harm, although the confidence in the evidence varied, underlining the uncertainty in our estimates.


Assuntos
Abdome/cirurgia , Músculos Abdominais , Anestesia Epidural/métodos , Bloqueio Nervoso/métodos , Humanos
5.
Anaesthesia ; 76(6): 818-831, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32981051

RESUMO

The aim of this systematic review and meta-analysis was to examine the efficacy, time taken and the safety of neuraxial blockade performed for obstetric patients with the assistance of preprocedural ultrasound, in comparison with the landmark palpation method. The bibliographic databases Central, CINAHL, EMBASE, Global Health, MEDLINE, Scopus and Web of Science were searched from inception to 13 February 2020 for randomised controlled trials that included pregnant women having neuraxial procedures with preprocedural ultrasound as the intervention and conventional landmark palpation as the comparator. For continuous and dichotomous outcomes, respectively, we calculated the mean difference using the inverse-variance method and the risk ratio with the Mantel-Haenszel method. In all, 22 trials with 2462 patients were included. Confirmed by trial sequential analysis, preprocedural ultrasound increased the first-pass success rate by a risk ratio (95%CI) of 1.46 (1.16-1.82), p = 0.001 in 13 trials with 1253 patients. No evidence of a difference was found in the total time taken between preprocedural ultrasound and landmark palpation, with a mean difference (95%CI) of 50.1 (-13.7 to 113.94) s, p = 0.12 in eight trials with 709 patients. The quality of evidence was graded as low and very low, respectively, for these co-primary outcomes. Sub-group analysis underlined the increased benefit of preprocedural ultrasound for those in whom the neuraxial procedure was predicted to be difficult. Complications, including postpartum back pain and headache, were decreased with preprocedural ultrasound. The adoption of preprocedural ultrasound for neuraxial procedures in obstetrics is recommended and, in the opinion of the authors, should be considered as a standard of care, in view of its potential to increase efficacy and reduce complications without significant prolongation of the total time required.


Assuntos
Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Anestesia Epidural/métodos , Anestesia Obstétrica/métodos , Palpação/métodos , Ultrassonografia/métodos , Espaço Epidural/anatomia & histologia , Feminino , Humanos , Gravidez
6.
Anaesthesia ; 76(3): 393-403, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32621529

RESUMO

Caesarean delivery is the most commonly performed inpatient surgical procedure globally. Pain after caesarean delivery is moderate to severe if not adequately treated, and is a primary anaesthetic concern for patients. Transversus abdominis plane and quadratus lumborum blocks are fascial plane blocks that have the potential to improve analgesia following caesarean delivery. Although proponents of the quadratus lumborum block suggest that this technique may provide better analgesia compared with transversus abdominis plane block, there are limited data directly comparing these two techniques. We, therefore, performed a systematic review and network meta-analysis to compare transversus abdominis plane and quadratus lumborum block approaches, seeking randomised controlled trials comparing both techniques to each other, or to control, with or without intrathecal morphine. In all, 31 trials with 2188 patients were included and our primary outcome, the cumulative intravenous morphine equivalent consumption at 24 h, was reported in 12 trials. In the absence of intrathecal morphine, transversus abdominis plane and quadratus lumborum blocks were equivalent, and both were superior to control (moderate-quality evidence). In the presence of intrathecal morphine, no differences were found between control, transversus abdominis plane and quadratus lumborum blocks (moderate-quality evidence). Similar results were found for resting and active pain scores at 4-6 h, 8-12 h, 24 h and 36 h, although quadratus lumborum block was associated with lower pain scores at 36 h when compared with transversus abdominis plane block (very low-quality evidence). However, transversus abdominis plane block was associated with a reduced incidence of postoperative nausea and vomiting (moderate-quality evidence) and sedation when compared with inactive control following intrathecal morphine administration (low-quality evidence). There are insufficient data to draw definitive conclusions, but transversus abdominis plane and quadratus lumborum block appear to be superior to control in the absence of intrathecal morphine, but provide limited additional benefit over inactive control when intrathecal morphine is also used.


Assuntos
Músculos Abdominais/efeitos dos fármacos , Analgesia Obstétrica/métodos , Cesárea , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Feminino , Humanos , Metanálise em Rede , Gravidez
7.
J Endocrinol Invest ; 43(7): 925-934, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31927747

RESUMO

BACKGROUND: Thyroid nodules (TN) are detected in a small number of asymptomatic children and adolescents but are more frequently malignant (22-26%) than in adults leading some clinicians to perform thyroid ultrasound (US) for all children with goiter or autoimmune thyroiditis (AIT). Our study was designed to determine if suspicious clinical features predict the presence of TN in children with goiter or AIT so that US could be performed on those at highest risk. METHODS: This was a retrospective review of 223 children and adolescents with goiter or AIT evaluated at a single institution. US was not performed on all patients. It is our practice to define glands that are large, firm, or nodular to palpation as "suspicious". Suspicious glands were interrogated by US and if TN was confirmed, this was further evaluated by fine-needle aspiration followed by surgery if indicated. RESULTS: The median age was 12.9 years with 74.4% female. TN were confirmed by US in 16.6% of all patients but only 4.8% of those with AIT. By univariate analysis, TN were more common in those with family history of TN or differentiated thyroid carcinoma (DTC), thyroid asymmetry, and lower thyrotropin (TSH) levels. Differentiated thyroid carcinoma (DTC) was identified in 10.8% of TN and 1.8% of all patients. Firmness was significantly more common in patients with DTC (p = 0.0013). CONCLUSION: TN were less common in those with AIT than reported in previous studies, suggesting that clinical features might fail to identify the majority of TN in patients with AIT. However, patients with asymmetric thyroid and a family history of TN or DTC have greatest risk for TN.


Assuntos
Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/epidemiologia , Adolescente , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Bócio/diagnóstico , Bócio/epidemiologia , Bócio/patologia , Humanos , Masculino , Pediatria/métodos , Prognóstico , Estudos Retrospectivos , Medição de Risco , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Tireoidite Autoimune/diagnóstico , Tireoidite Autoimune/epidemiologia , Tireoidite Autoimune/patologia , Ultrassonografia , Virginia/epidemiologia
8.
Br J Dermatol ; 176(4): 1048-1055, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27534703

RESUMO

BACKGROUND: The health resource utilization associated with managing patients with hidradenitis suppurativa (HS) in England is unknown. OBJECTIVES: To describe the characteristics of patients with HS and hospital resource use associated with management of HS in England. METHODS: A retrospective cohort study using Hospital Episode Statistics data. Patients with a primary diagnostic code for HS (ICD-10 code L73·2) during an inpatient admission (n = 11 359) between 1 April 2007 and 31 December 2013 were identified; patients with code L73·2 attending only as outpatients were excluded. Data for all inpatient, outpatient and accident and emergency admissions during the study period were extracted. RESULTS: Of the 11 359 patients, 10 832 had a first recorded inpatient HS diagnostic code (index spell) during the study period (female 7569, 69·9%). The mean age at the index spell was 39 ± 13·1 years in men and 36 ± 11·7 years in women. There were 65 544 inpatient spells during the study period; 7202 (63·4%) patients underwent nonelective spells, 4128 (36.3%) elective spells and 9790 (86·2%) day-case attendances. There were 43 773 accident and emergency attendances during the study period in 8716 (76·7%) patients. There were 303 204 outpatient appointments in 11 203 patients (mean 27·1 per patient); 4827 (42·5%) of the study population attended dermatology, 8087 (71·2%) general surgery and 4111 (36·2%) plastic surgery. Based on the mean number of spells per patient per year, the mean hospital resource utilization cost for a patient with HS was £2027 per patient per year. CONCLUSIONS: HS is associated with a large burden of hospital attendances for young patients of working age and high National Health Service resource costs.


Assuntos
Hidradenite Supurativa/economia , Hospitalização/economia , Adulto , Agendamento de Consultas , Serviço Hospitalar de Emergência/estatística & dados numéricos , Inglaterra , Feminino , Recursos em Saúde/estatística & dados numéricos , Hidradenite Supurativa/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Estudos Retrospectivos , Adulto Jovem
11.
Am J Transplant ; 16(7): 2202-7, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26932575

RESUMO

Since March 26, 2012, the Kidney Donor Profile Index (KDPI) has been provided with all deceased-donor kidney offers, with the goal of improving the expanded criteria donor (ECD) indicator. Although an improved risk index may facilitate identification and transplantation of marginal yet viable kidneys, a granular percentile system may reduce provider-patient communication flexibility, paradoxically leading to more discards ("labeling effect"). We studied the discard rates of the kidneys recovered for transplantation between March 26, 2010 and March 25, 2012 ("ECD era," N = 28 636) and March 26, 2012 and March 25, 2014 ("KDPI era," N = 29 021) using Scientific Registry of Transplant Recipients (SRTR) data. There was no significant change in discard rate from ECD era (18.1%) to KDPI era (18.3%) among the entire population (adjusted odds ratio [aOR] = 0.97 1.041.10 , p = 0.3), or in any KDPI stratum. However, among kidneys in which ECD and KDPI indicators were discordant, "high risk" standard criteria donor (SCD) kidneys (with KDPI > 85) were at increased risk of discard in the KDPI era (aOR = 1.07 1.421.89 , p = 0.02). Yet, recipients of these kidneys were at much lower risk of death (adjusted Risk Ratio [aRR] = 0.56 0.770.94 at 2 years posttransplant) compared to those remaining on dialysis waiting for low-KDPI kidneys. Our findings suggest that there might be an unexpected, harmful labeling effect of reporting a high KDPI for SCD kidneys, without the expected advantage of providing a more granular risk index.


Assuntos
Seleção do Doador , Sobrevivência de Enxerto , Transplante de Rim , Sistema de Registros/estatística & dados numéricos , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Adulto , Cadáver , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Transplantados
12.
Am J Transplant ; 16(7): 2077-84, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26752290

RESUMO

Choosing between multiple living kidney donors, or evaluating offers in kidney paired donation, can be challenging because no metric currently exists for living donor quality. Furthermore, some deceased donor (DD) kidneys can result in better outcomes than some living donor kidneys, yet there is no way to compare them on the same scale. To better inform clinical decision-making, we created a living kidney donor profile index (LKDPI) on the same scale as the DD KDPI, using Cox regression and adjusting for recipient characteristics. Donor age over 50 (hazard ratio [HR] per 10 years = 1.15 1.241.33 ), elevated BMI (HR per 10 units = 1.01 1.091.16 ), African-American race (HR = 1.15 1.251.37 ), cigarette use (HR = 1.09 1.161.23 ), as well as ABO incompatibility (HR = 1.03 1.271.58 ), HLA B (HR = 1.03 1.081.14 ) mismatches, and DR (HR = 1.04 1.091.15 ) mismatches were associated with greater risk of graft loss after living donor transplantation (all p < 0.05). Median (interquartile range) LKDPI score was 13 (1-27); 24.2% of donors had LKDPI < 0 (less risk than any DD kidney), and 4.4% of donors had LKDPI > 50 (more risk than the median DD kidney). The LKDPI is a useful tool for comparing living donor kidneys to each other and to deceased donor kidneys.


Assuntos
Tomada de Decisão Clínica , Rejeição de Enxerto/epidemiologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Doadores Vivos , Medição de Risco/métodos , Adulto , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Estados Unidos/epidemiologia
13.
Br J Dermatol ; 174(5): 970-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26801356

RESUMO

More than 50 interventions have been used to treat hidradenitis suppurativa (HS), and so therapy decisions can be challenging. Our objective was to summarize and appraise randomized controlled trial (RCT) evidence for HS interventions in adults. Searches were conducted in Medline, Embase, CENTRAL, LILACS, five trials registers and abstracts from eight dermatology conferences until 13 August 2015. Two review authors independently assessed study eligibility, extracted data and assessed methodological quality. Primary outcomes were quality of life and adverse effects of the interventions. Twelve trials, from 1983 to 2015, investigating 15 different interventions met our inclusion criteria. The median trial duration was 16 weeks and the median number of participants was 27. Adalimumab 40 mg weekly improved the Dermatology Life Quality Index (DLQI) by 4·0 points, which equates to the minimal clinically important difference for the scale, compared with placebo (95% confidence interval -6·5 to -1·5 points). Evidence quality was reduced to 'moderate' because the results are based on only a single study. Adalimumab 40 mg every other week was ineffective in a meta-analysis of two studies comprising 124 participants. Infliximab 5 mg kg(-1) improved the DLQI score by 8·4 points after 8 weeks in a moderate-quality study completed by 33 of 38 participants. Etanercept 50 mg twice weekly was ineffective. Inclusion of a gentamicin sponge prior to primary closure did not improve outcomes. Other interventions, including topical and oral antibiotics, were investigated by relatively small studies, preventing treatment recommendations due to imprecision. More, larger RCTs are required to investigate most HS interventions, particularly oral treatments and surgical therapy. Moderate-quality evidence suggests that adalimumab given weekly and infliximab are effective, whereas adalimumab every other week is ineffective.


Assuntos
Hidradenite Supurativa/tratamento farmacológico , Adalimumab/administração & dosagem , Administração Oral , Adulto , Antagonistas de Androgênios/administração & dosagem , Antibacterianos/administração & dosagem , Clindamicina/administração & dosagem , Acetato de Ciproterona/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Etanercepte/administração & dosagem , Etinilestradiol/administração & dosagem , Gentamicinas/administração & dosagem , Humanos , Infliximab/administração & dosagem , Norgestrel/administração & dosagem , Qualidade de Vida , Resultado do Tratamento , Técnicas de Fechamento de Ferimentos
14.
Bioorg Med Chem Lett ; 26(16): 4030-5, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27397497

RESUMO

A series of novel dihydropyrimidine derivatives bearing an imidazole nucleus at C-4 position were synthesized in excellent yields via Biginelli multi-component reaction. The newly synthesized compounds were characterized by IR, (1)H NMR, (13)C NMR and Mass spectroscopy. In vitro antitubercular evaluation of all the newly synthesized compounds 4a-p against Mycobacterium tuberculosis (Mtb) H37Rv showed, 4j (MIC: 0.39µg/mL; SI: >25.64), 4m (MIC: 0.78µg/mL; SI: >12.82) and 4p (MIC: 0.39µg/mL; SI: 24.10) as the most promising lead analogues. Compounds 4j, 4m and 4p displayed effective reduction in residual Mtb growth within the tuberculosis-infected macrophage model. Further, molecular docking study of active molecules 4j, 4m and 4p against Mycobacterium tuberculosis dihydrofolate reductase (Mtb DHFR) proved their potency as Mtb DHFR inhibitors acting as potential leads for further development. Pharmacokinetic properties leading to drug-likeness were also predicted for most active molecules 4j, 4m and 4p.


Assuntos
Antituberculosos/síntese química , Antagonistas do Ácido Fólico/química , Pirimidinas/química , Tetra-Hidrofolato Desidrogenase/metabolismo , Antituberculosos/farmacologia , Sítios de Ligação , Domínio Catalítico , Desenho de Fármacos , Antagonistas do Ácido Fólico/síntese química , Antagonistas do Ácido Fólico/farmacologia , Imidazóis/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/enzimologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Relação Estrutura-Atividade , Tetra-Hidrofolato Desidrogenase/química
15.
Bioorg Med Chem Lett ; 26(7): 1776-83, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26920799

RESUMO

A series of indole and pyridine based 1,3,4-oxadiazole derivatives 5a-t were synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG both in active and dormant state. Compounds 5b, 5e, 5g and 5q exhibited very good antitubercular activity. All the newly synthesized compounds 5a-t were further evaluated for anti-proliferative activity against HeLa, A549 and PANC-1 cell lines using modified MTT assay and found to be noncytotoxic. On the basis of cytotoxicity and MIC values against Mycobacterium bovis BCG, selectivity index (SI) of most active compounds 5b, 5e, 5g and 5q was calculated (SI=GI50/MIC) in active and dormant state. Compounds 5b, 5e and 5g demonstrated SI values ⩾10 against all three cell lines and were found to safe for advance screening. Compounds 5a-t were further screened for their antibacterial activity against four bacteria strains to assess their selectivity towards MTB. In addition, the molecular docking studies revealed the binding modes of these compounds in active site of enoyl reductase (InhA), which in turn helped to establish a structural basis of inhibition of mycobacteria. The potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for further optimization.


Assuntos
Antituberculosos/química , Antituberculosos/farmacologia , Mycobacterium bovis/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Oxidiazóis/química , Oxidiazóis/farmacologia , Animais , Linhagem Celular , Humanos , Indóis/química , Indóis/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Mycobacterium bovis/enzimologia , Mycobacterium tuberculosis/enzimologia , Piridinas/química , Piridinas/farmacologia , Relação Estrutura-Atividade , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Tuberculose/veterinária
16.
Am J Transplant ; 15(1): 149-54, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25359393

RESUMO

We have previously described strong associations between frailty, a measure of physiologic reserve initially described and validated in geriatrics, and early hospital readmission as well as delayed graft function. The goal of this study was to estimate its association with postkidney transplantation (post-KT) mortality. Frailty was prospectively measured in 537 KT recipients at the time of transplantation between November 2008 and August 2013. Cox proportional hazards models were adjusted for confounders using a novel approach to substantially improve model efficiency and generalizability in single-center studies. We precisely estimated the confounder coefficients using the large sample size of the Scientific Registry of Transplantation Recipients (n = 37 858) and introduced these into the single-center model, which then estimated the adjusted frailty coefficient. At 5 years, the survivals were 91.5%, 86.0% and 77.5% for nonfrail, intermediately frail and frail KT recipients, respectively. Frailty was independently associated with a 2.17-fold (95% CI: 1.01-4.65, p = 0.047) higher risk of death. In conclusion, regardless of age, frailty is a strong, independent risk factor for post-KT mortality, even after carefully adjusting for many confounders using a novel, efficient statistical approach.


Assuntos
Idoso Fragilizado , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Complicações Pós-Operatórias , Adulto , Idoso , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/cirurgia , Testes de Função Renal , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida
17.
Stress ; : 1-9, 2015 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-26270888

RESUMO

This study was carried to ascertain whether stress responses are associated with abnormalities in glucose tolerance, insulin sensitivity and pancreatic beta cell function and risk of type 2 Diabetes Mellitus. Salivary cortisol, a marker of hypothalamic-pituitary-adrenal (HPA) axis and salivary α-amylase, a marker of sympathetic nervous system (SNS) were compared in 125 subjects of newly detected diabetes mellitus (NDDM) and normal glucose tolerance (NGT) subjects who were diagnosed on the basis of oral glucose tolerance test (OGTT). Assessment of stress in them was done through stress scales - presumptive stressful life events scale (PSLES), perceived stress scale (PSS) and sense of coherence (SOC) and correlated with these and other stress response markers. Significantly higher 10 pm salivary cortisol and post dexamethasone salivary cortisol were found in NDDM subjects as compared to NGT. 10 pm salivary cortisol correlated significantly with fasting plasma glucose (FPG), 2 h plasma glucose (2h PG) and glycated hemoglobin (HbA1c) while post dex salivary cortisol correlated with 2h PG, HbA1c and salivary α-amylase with 2h PG. Stepwise logistic regression analysis showed that body mass index (OR: 1.840), SOC (OR: 0.688) and 10 pm salivary cortisol (OR: 1.427) were the strongest predictors of NDDM. The results of the present study indicate that NDDM subjects display significantly higher chronic stress and stress responses when compared to subjects with NGT. Chronic stress and endocrine stress responses are significantly associated with glucose intolerance, insulin resistance and diabetes mellitus.

18.
Stress ; 18(5): 498-506, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26303379

RESUMO

This study was carried to ascertain whether stress responses are associated with abnormalities in glucose tolerance, insulin sensitivity and pancreatic beta cell function and risk of type 2 Diabetes Mellitus. Salivary cortisol, a marker of hypothalamic-pituitary-adrenal (HPA) axis and salivary α-amylase, a marker of sympathetic nervous system (SNS) were compared in 125 subjects of newly detected diabetes mellitus (NDDM) and normal glucose tolerance (NGT) subjects who were diagnosed on the basis of oral glucose tolerance test (OGTT). Assessment of stress in them was done through stress scales - presumptive stressful life events scale (PSLES), perceived stress scale (PSS) and sense of coherence (SOC) and correlated with these and other stress response markers. Significantly higher 10 pm salivary cortisol and post dexamethasone salivary cortisol were found in NDDM subjects as compared to NGT. 10 pm salivary cortisol correlated significantly with fasting plasma glucose (FPG), 2 h plasma glucose (2h PG) and glycated hemoglobin (HbA1c) while post dex salivary cortisol correlated with 2h PG, HbA1c and salivary α-amylase with 2h PG. Stepwise logistic regression analysis showed that body mass index (OR: 1.840), SOC (OR: 0.688) and 10 pm salivary cortisol (OR: 1.427) were the strongest predictors of NDDM. The results of the present study indicate that NDDM subjects display significantly higher chronic stress and stress responses when compared to subjects with NGT. Chronic stress and endocrine stress responses are significantly associated with glucose intolerance, insulin resistance and diabetes mellitus.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hidrocortisona/metabolismo , Resistência à Insulina , Acontecimentos que Mudam a Vida , alfa-Amilases Salivares/metabolismo , Estresse Fisiológico , Estresse Psicológico/metabolismo , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Dexametasona , Feminino , Glucocorticoides , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/metabolismo , Saliva/química , Senso de Coerência , Sistema Nervoso Simpático/metabolismo
19.
J Eur Acad Dermatol Venereol ; 29(4): 619-44, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25640693

RESUMO

Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly the axillae, inguinal and anogenital regions. A mean disease incidence of 6.0 per 100,000 person-years and an average prevalence of 1% has been reported in Europe. HS has the highest impact on patients' quality of life among all assessed dermatological diseases. HS is associated with a variety of concomitant and secondary diseases, such as obesity, metabolic syndrome, inflammatory bowel disease, e.g. Crohn's disease, spondyloarthropathy, follicular occlusion syndrome and other hyperergic diseases. The central pathogenic event in HS is believed to be the occlusion of the upper part of the hair follicle leading to a perifollicular lympho-histiocytic inflammation. A highly significant association between the prevalence of HS and current smoking (Odds ratio 12.55) and overweight (Odds ratio 1.1 for each body mass index unit) has been documented. The European S1 HS guideline suggests that the disease should be treated based on its individual subjective impact and objective severity. Locally recurring lesions can be treated by classical surgery or LASER techniques, whereas medical treatment either as monotherapy or in combination with radical surgery is more appropriate for widely spread lesions. Medical therapy may include antibiotics (clindamycin plus rifampicine, tetracyclines), acitretin and biologics (adalimumab, infliximab). A Hurley severity grade-relevant treatment of HS is recommended by the expert group following a treatment algorithm. Adjuvant measurements, such as pain management, treatment of superinfections, weight loss and tobacco abstinence have to be considered.


Assuntos
Hidradenite Supurativa/etiologia , Hidradenite Supurativa/terapia , Guias de Prática Clínica como Assunto , Europa (Continente) , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/epidemiologia , Humanos
20.
Am J Transplant ; 14(2): 397-403, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24447652

RESUMO

We recently elucidated risk factors for early hospital readmission (EHR) following kidney transplantation (KT). We now sought to quantify the independent associations between EHR and post-KT outcomes, including late hospital readmission (LHR: 1 year after EHR window), death-censored graft loss and mortality, among Medicare-primary KT recipients (2000-2005). Of 32961 KT recipients, 7.7% had at least one readmission within 3 days of discharge, 14.8% within 7 days, 22.4% within 14 days and 30.5% within 30 days of discharge after the initial KT hospitalization. KT recipients who experienced EHR within 30 days of discharge after the initial KT hospitalization were more likely to have experienced LHR (29.6% vs. 9.0%, p<0.001) and were at 3.02 times higher (95% CI: 2.82-3.23, p<0.001) risk of LHR. Additionally, EHR was associated with death-censored graft loss (deceased donor recipients hazard ratio [HR]: 1.43, 95% CI: 1.36-1.51, p<0.001 and live donor recipients HR: 1.54, 95% CI: 1.40-1.70, p<0.001) and mortality (deceased donor recipients HR: 1.50, 95% CI: 1.43-1.58, p<0.001 and live donor recipients HR: 1.45, 95% CI: 1.32-1.60, p<0.001). Thirty days posttransplant represents a high-risk window for KT recipients and the readmissions during this window are strong predictors of adverse sequelae, particularly LHRs. Efforts should be made to implement and improve systems to reduce LHR and subsequent graft loss and mortality among recipients with EHR.


Assuntos
Rejeição de Enxerto/diagnóstico , Sobrevivência de Enxerto , Hospitalização/estatística & dados numéricos , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Readmissão do Paciente/estatística & dados numéricos , Idoso , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/mortalidade , Humanos , Doadores Vivos , Estudos Longitudinais , Masculino , Prognóstico , Fatores de Risco
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