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1.
Lung ; 201(1): 17-23, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36746812

RESUMO

PURPOSE: Asthma is a common comorbidity in patients with bronchiectasis and has been shown to increase the risk of bronchiectasis exacerbations. This paper explores the impact of comorbid asthma on patients receiving intravenous antibiotic treatment for bronchiectasis exacerbations. METHODS: This was a post hoc analysis of the Meropenem randomised controlled trial of 90 patients that had intravenous antibiotic treatment for bronchiectasis exacerbations. The participants were split into two groups: group 1 (asthma and bronchiectasis) and group 2 (bronchiectasis). The authors assessed response to treatment and time to next exacerbation. RESULTS: There were 38 participants in group 1 and 34 participants in group 2. The groups were found to be comparable in terms of age, sex, and bronchiectasis severity (median (95% CI) group 1 and then group 2 data): age 64.0(59.3, 68.6) and 63.6(57.9, 69.4) years old, p = 0.8; 57.9% and 64.7% female, p = 0.6; Bronchiectasis Severity Index 11.1(9.8, 12.4) and 10.1(8.2, 12.0), p = 0.3. There was a similar response to treatment between the groups, but group 1 were found to relapse early by day 14, 31.6% in group 1 and 11.8% in group 2, p = 0.03. In the Cox proportional hazards model, asthma was the only independent risk factor for early relapse by day 14 (odds ratio (95% CI) 3.16 (1.02-9.79), p = 0.047). CONCLUSION: The clinical response to treatment was similar but patients with coexisting asthma were at increased risk of early relapse within 14 days of stopping intravenous antibiotic therapy. CLINICAL TRIAL REGISTRATION: NCT02047773.


Assuntos
Asma , Bronquiectasia , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Antibacterianos/uso terapêutico , Asma/tratamento farmacológico , Doença Crônica , Comorbidade , Progressão da Doença
2.
Eur Respir J ; 58(6)2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34112732

RESUMO

BACKGROUND: There is a lack of evidence to guide the duration of intravenous antibiotics for bronchiectasis exacerbations. AIMS: The aim of this study was to assess whether it is feasible, based on bacterial load, to shorten intravenous antibiotics during exacerbations and whether 14 days of treatment is superior. METHODS: We recruited participants requiring intravenous antibiotics for exacerbations. Participants were randomised into two groups: to receive antibiotics for 14 days (14-day group) or to have a shorter duration of treatment based on bacterial load (bacterial load-guided group (BLGG)). Bacterial load was checked on days 0, 7, 10, 14 and 21. If the bacterial load was <106 CFU·mL-1 on day 7 or day 10 in the BLGG, antibiotics were stopped the following day. RESULTS: A total of 47 participants were in the 14-day group and 43 were in the BLGG. 88% of participants in the BLGG were able to stop antibiotics by day 8 and potentially 81% of participants in the 14-day group could have stopped antibiotics at day 8. There was a nonsignificant trend for increased clinical improvement by day 21 in the 14-day group compared to the BLGG. However, overall group data showed the median (interquartile range) time to next exacerbation was 27.5 days (12.5-60 days) in the 14-day group and 60 days (18-110 days) in the in BLGG (p=0.0034). In a Cox proportional hazard model, participants in the 14-day group were more likely to experience exacerbations (HR 1.80, 95% CI 1.16-2.80, p=0.009) than those in the BLGG, and those with mild bronchiectasis were less likely to experience exacerbations than patients with more severe bronchiectasis (HR 0.359, 95% CI 0.13-0.99, p=0.048). CONCLUSIONS: Bacterial load-guided therapy is feasible in most exacerbations requiring intravenous antibiotics. There was a nonsignificant trend for increased clinical improvement by day 21 with 14 days of antibiotics compared with bacterial load-guided therapy but paradoxically there was a prolonged time to next exacerbation in the BLGG.


Assuntos
Bronquiectasia , Antibacterianos/uso terapêutico , Carga Bacteriana , Bronquiectasia/tratamento farmacológico , Progressão da Doença , Estudos de Viabilidade , Humanos
3.
Inorg Chem ; 55(21): 11560-11569, 2016 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-27740751

RESUMO

Six new anionic bismuth-oxido clusters containing trifluoroacetate ligands were prepared. These include two new Bi6O8 clusters: [M(NCMe)2(H2O)4]3[Bi6(µ3-O)4(µ3-OH)4(CF3CO2)12] with an octahedral Bi6O4(OH)4 core (M = Ni, 1a; Co, 1b) and four Bi4O2 clusters, {[Co(NCMe)6][Bi4(µ3-O)2(CF3CO2)10]}n (2a), {[Co{HC(MeCO)2(MeCNH)}2][Bi4(µ3-O)2(CF3CO2)10]·2[CF3CO2]·2[CF3CO2H]·2[H2O]}n (2b), {[Cu(NCMe)4]2[Bi4(µ3-O)2(CF3CO2)10]·2[CF3CO2H]}n (2c), and {[Me4N]2[Bi4(µ3-O)2(CF3CO2)10]·2[CF3CO2H]}n (2d). These are among the first bismuth-oxido anionic clusters synthesized, and the first to have transition metal countercations. The Bi6O8 anion in 1a and 1b is a high-symmetry octahedron. Additionally, two of the new Bi4O2 clusters are arranged in 1D polymeric structures via bridging carboxylate ligands. The cation in compound 2c had not been previously characterized and was also observed in the synthesis of [Co{HC(MeCO)2(MeCNH)}2][Bi(NO3)6] (3). The new compounds were characterized using single crystal X-ray crystallography and elemental analysis.

4.
Emerg Infect Dis ; 17(7): 1248-55, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21762579

RESUMO

The simian parasite Plasmodium knowlesi causes severe human malaria; the optimal treatment remains unknown. We describe the clinical features, disease spectrum, and response to antimalarial chemotherapy, including artemether-lumefantrine and artesunate, in patients with P. knowlesi malaria diagnosed by PCR during December 2007-November 2009 at a tertiary care hospital in Sabah, Malaysia. Fifty-six patients had PCR-confirmed P. knowlesi monoinfection and clinical records available for review. Twenty-two (39%) had severe malaria; of these, 6 (27%) died. Thirteen (59%) had respiratory distress; 12 (55%), acute renal failure; and 12, shock. None experienced coma. Patients with uncomplicated disease received chloroquine, quinine, or artemether-lumefantrine, and those with severe disease received intravenous quinine or artesunate. Parasite clearance times were 1-2 days shorter with either artemether-lumefantrine or artesunate treatment. P. knowlesi is a major cause of severe and fatal malaria in Sabah. Artemisinin derivatives rapidly clear parasitemia and are efficacious in treating uncomplicated and severe knowlesi malaria.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária , Plasmodium knowlesi/fisiologia , Injúria Renal Aguda/fisiopatologia , Adulto , Antimaláricos/uso terapêutico , Artemeter , Artemisininas/uso terapêutico , Artesunato , Cloroquina/administração & dosagem , Cloroquina/uso terapêutico , Etanolaminas/administração & dosagem , Etanolaminas/uso terapêutico , Feminino , Fluorenos/administração & dosagem , Fluorenos/uso terapêutico , Hospitais Urbanos , Humanos , Lumefantrina , Malária/sangue , Malária/diagnóstico , Malária/tratamento farmacológico , Malária/mortalidade , Malária/parasitologia , Malária/fisiopatologia , Malásia/epidemiologia , Microscopia , Pessoa de Meia-Idade , Parasitemia/sangue , Seleção de Pacientes , Plasmodium knowlesi/efeitos dos fármacos , Reação em Cadeia da Polimerase , Quinina/administração & dosagem , Quinina/uso terapêutico , Síndrome do Desconforto Respiratório/fisiopatologia , Índice de Gravidade de Doença , Choque/fisiopatologia , Taxa de Sobrevida
5.
J Thorac Cardiovasc Surg ; 159(2): 592-599, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31607495

RESUMO

OBJECTIVE: Transposition of the great arteries or Taussig-Bing anomaly with concomitant aortic arch obstruction is uncommon, with limited data on long-term outcomes after arterial switch operation and aortic arch obstruction repair. This study sought to determine outcomes of patients undergoing arterial switch operation and aortic arch obstruction repair at a single institution. METHODS: From 1983 to 2015, 844 patients underwent an arterial switch operation for biventricular repair at The Royal Children's Hospital. Eighty-three (9.8%, 83/844) patients underwent an arterial switch operation and aortic arch obstruction repair. RESULTS: Fifty-five (66%, 55/83) patients had transposition of the great arteries. and 28 (34%, 28/83) patients had Taussig-Bing anomaly. Fifty-nine (71%, 59/83) patients underwent arterial switch operation and aortic arch obstruction repair as a single-stage procedure, and 24 (29%, 24/83) patients underwent arterial switch operation and aortic arch obstruction repair as a 2-stage procedure. There were 5 early deaths (6.0%, 5/83). Follow-up was available for 74 (95%) of the 78 survivors. Median follow-up was 13.3 years (interquartile range, 7.3-19.3 years; range, 1-30 years). There were no late deaths. Freedom from reintervention was 77%, 71%, and 68% at 5, 10, and 20 years, respectively. Reintervention was more common compared with patients without aortic arch obstruction (P < .001). Reintervention for right-sided obstruction was more common compared with patients without aortic arch obstruction (P = .006). CONCLUSIONS: Patients with transposition of the great arteries or Taussig-Bing anomaly with associated aortic arch obstruction have a higher reintervention rate, especially for right-sided obstruction. Closer monitoring of this subgroup of patients is warranted.


Assuntos
Doenças da Aorta , Transposição das Grandes Artérias , Transposição dos Grandes Vasos , Adolescente , Adulto , Aorta Torácica/cirurgia , Doenças da Aorta/mortalidade , Doenças da Aorta/cirurgia , Transposição das Grandes Artérias/efeitos adversos , Transposição das Grandes Artérias/mortalidade , Transposição das Grandes Artérias/estatística & dados numéricos , Criança , Pré-Escolar , Seguimentos , Humanos , Estudos Retrospectivos , Transposição dos Grandes Vasos/mortalidade , Transposição dos Grandes Vasos/cirurgia , Adulto Jovem
6.
Chest ; 154(6): 1321-1329, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30300653

RESUMO

BACKGROUND: A validated clinical end point is needed to assess response to therapies in bronchiectasis. OBJECTIVES: The goal of this study was to assess the reliability, validity, and responsiveness of the incremental shuttle walk test (ISWT) as a clinical end point in bronchiectasis. METHODS: In clinically stable patients (n = 30), the ISWT was performed twice, 6 months apart. Correlation between the St. George's Respiratory Questionnaire (SGRQ) and the ISWT (n = 94) was performed. The 1-year gentamicin study was reanalyzed to assess the area under the curve (percent change of ISWT with a ≥ 4 unit improvement in total SGRQ). ISWT was performed prior to and following 14 days of antibiotics for an exacerbation (94 oral courses and 30 IV courses, n = 124) and reanalysis of the 1-year gentamicin study (n = 57). RESULTS: The ISWT did not significantly change over 6 months while clinically stable. The ISWT correlated inversely with the SGRQ (rs = -0.60; P < .0001), Bronchiectasis Severity Index score (rs = -0.44; P < .0001), and sedentary time (rs = -0.48; P = .0007) but correlated with physical activity (rs = 0.42; P = .004). The area under the curve for percent change in ISWT with ≥ 4 unit improvement in SGRQ was 0.79 (95% CI, 0.66-0.91; P = .001). A threshold of 5% improvement in the ISWT had a 92% sensitivity but 50% specificity, and from the responsiveness studies would capture 73% of all patients. CONCLUSIONS: This study confirmed the ISWT to be reliable, valid, and responsive to change in patients with bronchiectasis. The authors propose that a minimum clinically important difference of 5% improvement in the ISWT would be a useful objective end point to assess therapies in bronchiectasis.


Assuntos
Bronquiectasia , Gentamicinas/uso terapêutico , Teste de Caminhada , Idoso , Antibacterianos/uso terapêutico , Área Sob a Curva , Bronquiectasia/diagnóstico , Bronquiectasia/tratamento farmacológico , Bronquiectasia/epidemiologia , Bronquiectasia/fisiopatologia , Monitoramento de Medicamentos/métodos , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Reprodutibilidade dos Testes , Escócia/epidemiologia , Índice de Gravidade de Doença , Inquéritos e Questionários , Exacerbação dos Sintomas , Teste de Caminhada/métodos , Teste de Caminhada/normas
7.
Chest ; 152(2): 368-378, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28554732

RESUMO

BACKGROUND: There are no randomized controlled trials of statin therapy in patients with severe bronchiectasis who are chronically infected with Pseudomonas aeruginosa. METHODS: Thirty-two patients chronically infected with P aeruginosa were recruited in this double-blind cross-over randomized controlled trial. Sixteen patients were recruited in each arm, were given atorvastatin 80 mg or placebo for 3 months followed by a washout period for 6 weeks, and then crossed over and administered the alternative therapy for 3 months. RESULTS: Twenty-seven patients completed the study. Atorvastatin did not significantly improve the primary end point of cough as measured by the Leicester Cough Questionnaire (mean difference, 1.92; 95% CI for difference, -0.57-4.41; P = .12). However, atorvastatin treatment resulted in an improved St. Georges Respiratory Questionnaire (-5.62 points; P = .016) and reduced serum levels of CXCL8 (P = .04), tumor necrosis factor (P = .01), and intercellular adhesion molecule 1 (P = .04). There was a trend toward improvement in serum C-reactive protein and serum neutrophil counts (P = .07 and P = .06, respectively). We demonstrated in vitro that atorvastatin 10 µM reduced formyl-methionyl-leucyl phenylalanine-induced upregulation of CD11b expression and changes in calcium flux, reflecting an ability to decrease neutrophil activation. CONCLUSIONS: We demonstrated that atorvastatin reduced systemic inflammation and improved quality of life in patients with bronchiectasis who were infected with P aeruginosa. These effects may be due to an ability of atorvastatin to modulate neutrophil activation. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01299194; URL: www.clinicaltrials.gov.


Assuntos
Anti-Inflamatórios/administração & dosagem , Atorvastatina/administração & dosagem , Bronquiectasia/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Infecções por Pseudomonas/complicações , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Bronquiectasia/complicações , Cálcio/metabolismo , Tosse/etiologia , Estudos Cross-Over , Citocinas , Método Duplo-Cego , Esquema de Medicação , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Ativação de Neutrófilo/efeitos dos fármacos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/isolamento & purificação , Qualidade de Vida , Escarro/microbiologia , Resultado do Tratamento , Capacidade Vital/efeitos dos fármacos , Adulto Jovem
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