RESUMO
BACKGROUND: Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, but their existence and relative frequency in clinical disease are unclear, as is how to target resistance. PATIENTS AND METHODS: Longitudinal mutation and methylation profiling of circulating tumour (ct)DNA was carried out in 47 patients with metastatic BRCA1-, BRCA2- or PALB2-mutant breast cancer treated with HRD-targeted therapy who developed progressive disease-18 patients had primary resistance and 29 exhibited response followed by resistance. ctDNA isolated at multiple time points in the patient treatment course (before, on-treatment and at progression) was sequenced using a novel >750-gene intron/exon targeted sequencing panel. Where available, matched tumour biopsies were whole exome and RNA sequenced and also used to assess nuclear RAD51. RESULTS: BRCA1/2 reversion mutations were present in 60% of patients and were the most prevalent form of resistance. In 10 cases, reversions were detected in ctDNA before clinical progression. Two new reversion-based mechanisms were identified: (i) intragenic BRCA1/2 deletions with intronic breakpoints; and (ii) intragenic BRCA1/2 secondary mutations that formed novel splice acceptor sites, the latter being confirmed by in vitro minigene reporter assays. When seen before commencing subsequent treatment, reversions were associated with significantly shorter time to progression. Tumours with reversions retained HRD mutational signatures but had functional homologous recombination based on RAD51 status. Although less frequent than reversions, nonreversion mechanisms [loss-of-function (LoF) mutations in TP53BP1, RIF1 or PAXIP1] were evident in patients with acquired resistance and occasionally coexisted with reversions, challenging the notion that singular resistance mechanisms emerge in each patient. CONCLUSIONS: These observations map the prevalence of candidate drivers of resistance across time in a clinical setting, information with implications for clinical management and trial design in HRD breast cancers.
Assuntos
Antineoplásicos , Neoplasias da Mama , Feminino , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Recombinação Homóloga , Mutação , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Proteína 1 de Ligação à Proteína Supressora de Tumor p53RESUMO
The power of citizen science to contribute to both science and society is gaining increased recognition, particularly in physics and biology. Although there is a long history of public engagement in agriculture and food science, the term 'citizen science' has rarely been applied to these efforts. Similarly, in the emerging field of citizen science, most new citizen science projects do not focus on food or agriculture. Here, we convened thought leaders from a broad range of fields related to citizen science, agriculture, and food science to highlight key opportunities for bridging these overlapping yet disconnected communities/fields and identify ways to leverage their respective strengths. Specifically, we show that (i) citizen science projects are addressing many grand challenges facing our food systems, as outlined by the United States National Institute of Food and Agriculture, as well as broader Sustainable Development Goals set by the United Nations Development Programme, (ii) there exist emerging opportunities and unique challenges for citizen science in agriculture/food research, and (iii) the greatest opportunities for the development of citizen science projects in agriculture and food science will be gained by using the existing infrastructure and tools of Extension programmes and through the engagement of urban communities. Further, we argue there is no better time to foster greater collaboration between these fields given the trend of shrinking Extension programmes, the increasing need to apply innovative solutions to address rising demands on agricultural systems, and the exponential growth of the field of citizen science.
Assuntos
Agricultura/tendências , Participação da Comunidade , Alimentos , Pesquisa/tendências , Agricultura/normas , Pesquisa/normas , Estados UnidosRESUMO
Pulmonary remodeling is an important feature of asthma physiopathology that can contribute to irreversible changes in lung function. Although neurokinins influence lung inflammation, their exact role in the extracellular matrix (ECM) remodeling remains to be determined. Our objective was to investigate whether inactivation of capsaicin-sensitive nerves modulates pulmonary ECM remodeling in animals with chronic lung inflammation. After 14 days of capsaicin (50 mg/kg, sc) or vehicle administration, male Hartley guinea pigs weighing 250-300 g were submitted to seven inhalations of increasing doses of ovalbumin (1, 2.5, and 5 mg/mL) or saline for 4 weeks. Seventy-two hours after the seventh inhalation, animals were anesthetized and mechanically ventilated and the lung mechanics and collagen and elastic fiber content in the airways, vessels and lung parenchyma were evaluated. Ovalbumin-exposed animals presented increasing collagen and elastic fiber content, respectively, in the airways (9.2 ± 0.9; 13.8 ± 1.2), vessels (19.8 ± 0.8; 13.4 ± 0.5) and lung parenchyma (9.2 ± 0.9; 13.8 ± 1.2) compared to control (P < 0.05). Capsaicin treatment reduced collagen and elastic fibers, respectively, in airways (1.7 ± 1.1; 7.9 ± 1.5), vessels (2.8 ± 1.1; 4.4 ± 1.1) and lung tissue (2.8 ± 1.1; 4.4 ± 1.1) of ovalbumin-exposed animals (P < 0.05). These findings were positively correlated with lung mechanical responses to antigenic challenge (P < 0.05). In conclusion, inactivation of capsaicin-sensitive nerve fibers reduces pulmonary remodeling, particularly collagen and elastic fibers, which contributes to the attenuation of pulmonary functional parameters.
Assuntos
Animais , Cobaias , Masculino , Remodelação das Vias Aéreas/efeitos dos fármacos , Asma/patologia , Capsaicina/farmacologia , Colágeno/efeitos dos fármacos , Tecido Elástico/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Asma/metabolismo , Doença Crônica , Colágeno/metabolismo , Denervação , Tecido Elástico/metabolismo , Matriz Extracelular/metabolismo , Pulmão/patologia , OvalbuminaRESUMO
Pulmonary remodeling is an important feature of asthma physiopathology that can contribute to irreversible changes in lung function. Although neurokinins influence lung inflammation, their exact role in the extracellular matrix (ECM) remodeling remains to be determined. Our objective was to investigate whether inactivation of capsaicin-sensitive nerves modulates pulmonary ECM remodeling in animals with chronic lung inflammation. After 14 days of capsaicin (50 mg/kg, sc) or vehicle administration, male Hartley guinea pigs weighing 250-300 g were submitted to seven inhalations of increasing doses of ovalbumin (1, 2.5, and 5 mg/mL) or saline for 4 weeks. Seventy-two hours after the seventh inhalation, animals were anesthetized and mechanically ventilated and the lung mechanics and collagen and elastic fiber content in the airways, vessels and lung parenchyma were evaluated. Ovalbumin-exposed animals presented increasing collagen and elastic fiber content, respectively, in the airways (9.2 ± 0.9; 13.8 ± 1.2), vessels (19.8 ± 0.8; 13.4 ± 0.5) and lung parenchyma (9.2 ± 0.9; 13.8 ± 1.2) compared to control (P < 0.05). Capsaicin treatment reduced collagen and elastic fibers, respectively, in airways (1.7 ± 1.1; 7.9 ± 1.5), vessels (2.8 ± 1.1; 4.4 ± 1.1) and lung tissue (2.8 ± 1.1; 4.4 ± 1.1) of ovalbumin-exposed animals (P < 0.05). These findings were positively correlated with lung mechanical responses to antigenic challenge (P < 0.05). In conclusion, inactivation of capsaicin-sensitive nerve fibers reduces pulmonary remodeling, particularly collagen and elastic fibers, which contributes to the attenuation of pulmonary functional parameters.
Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Asma/patologia , Capsaicina/farmacologia , Colágeno/efeitos dos fármacos , Tecido Elástico/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Animais , Asma/metabolismo , Doença Crônica , Colágeno/metabolismo , Denervação , Tecido Elástico/metabolismo , Matriz Extracelular/metabolismo , Cobaias , Pulmão/patologia , Masculino , OvalbuminaRESUMO
Candida biofilms are microbial communities, embedded in a polymeric matrix, growing attached to a surface, and are highly recalcitrant to antimicrobial therapy. These biofilms exhibit enhanced resistance against most antifungal agents except echinocandins and lipid formulations of amphotericin B. In this study, biofilm formation by different Candida species, particularly Candida albicans, C. tropicalis, and C. parapsilosis, was evaluated, and the effect of caspofungin (CAS) was assessed using a clinically relevant in vitro model system. CAS displayed in vitro activity against C. albicans and C. tropicalis cells within biofilms. Biofilm formation was evaluated after 48 h of antifungal drug exposure, and the effects of CAS on preformed Candida species biofilms were visualized using scanning electron microscopy (SEM). Several species-specific differences in the cellular morphologies associated with biofilms were observed. Our results confirmed the presence of paradoxical growth (PG) in C. albicans and C. tropicalis biofilms in the presence of high CAS concentrations. These findings were also confirmed by SEM analysis and were associated with the metabolic activity obtained by biofilm susceptibility testing. Importantly, these results suggest that the presence of atypical, enlarged, conical cells could be associated with PG and with tolerant cells in Candida species biofilm populations. The clinical implications of these findings are still unknown.
Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Equinocandinas/farmacologia , Candida/ultraestrutura , Caspofungina , Humanos , Lipopeptídeos , Microscopia Eletrônica de VarreduraRESUMO
SETTING: A 150-bed public Brazilian hospital that serves as reference hospital for tuberculosis (TB) patients. OBJECTIVE: To evaluate the use of personal respiratory protection by health care workers (HCWs) as a measure to reduce TB occupational risk. DESIGN: One hundred and forty-five HCWs were randomly observed for the use of a N95 respirator when entering high-risk areas or performing high-risk procedures. RESULTS: N95 respirators were infrequently used, even for high-risk procedures such as endotracheal intubation (25%) and respiratory aspiration (12%), and in high-risk areas such as the respirology ward (69.2%), emergency department (29.5%), intensive care unit (8.8%), and TB room isolation (39.5%). Facial-seal leakage was observed in 39% of HCWs due to failure to wear the mask with a tight facial fit as directed. CONCLUSION: Respirator use as a sole control measure is inadequate in any setting and is not cost-effective in resource-limited settings. Alternative or additional measures are clearly needed in hospitals with a high incidence of active TB admissions, specially following recent recommendations from the WHO, which consider personal respiratory protection as the third line of defense for TB control, indicated when TB risk cannot be adequately reduced by administrative and engineering controls.
Assuntos
Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Doenças Profissionais/prevenção & controle , Dispositivos de Proteção Respiratória , Tuberculose Pulmonar/prevenção & controle , Pessoal Técnico de Saúde , Brasil , Humanos , Dispositivos de Proteção Respiratória/estatística & dados numéricosRESUMO
SETTING: Four general Brazilian hospitals. OBJECTIVE: To assess the occupational risk of Mycobacterium tuberculosis (TB) in participating hospitals. DESIGN: In phase one of this longitudinal study, a cross-sectional survey documented baseline tuberculin skin test (TST) positivity rates. In phase two, TST conversion rates were evaluated in participants with an initial negative two-step TST. TST conversion data were analyzed to determine risk factors for TB infection using an increase of > or = 10 mm compared to baseline TST. RESULTS: The initial TST positivity rate was 63.1%; the follow-up TST conversion rate was 10.7 per 1000 person-months (p-m). Hospital of employment, recent bacille Calmette-Guerin (BCG) vaccination, nosocomial TB exposure, and employment as a nurse were independent risk factors for TST conversion. Hospitals without TB infection control measures had higher conversion rates than those with control measures (16.0 vs. 7.8/ 1000 p-m, P < 0.001). CONCLUSIONS: This study indicates an important occupational risk of infection in health care settings with a high TB incidence. Longitudinal TST studies are a valuable tool to assess the occupational risk of TB, even in BCG-vaccinated populations, and should be used to direct limited resources for infection control.
Assuntos
Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Recursos Humanos em Hospital , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vacina BCG , Brasil , Feminino , Hospitais Gerais , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/etiologia , Fatores de Risco , Estudos Soroepidemiológicos , Teste Tuberculínico , Tuberculose/etiologia , Tuberculose/prevenção & controleRESUMO
Infectious disease is the most significant cause of morbidity and mortality in allotransplantation because of heavy immunosuppression. Brain abscesses caused by melanized fungi have been found occasionally and are an example of this complication. In this paper, we describe a case in a 61-year-old black man, who received a cadaveric kidney transplantation in December 1993, followed by triple therapy with cyclosporine, azathioprine, and prednisone. The patient developed right hemiparesis at the beginning of April 1998. A computed tomography scan showed a mass in the left parieto-temporal region of the brain. The patient underwent surgery and a brown-colored encapsulated brain abscess was resected. Histology of the tissue revealed a large number of pigmented fungal hyphae. Culture in a Sabouraud dextrose medium with cyclohexamide and chloramphenicol at 25 degrees C resulted in the growth of dark-green colonies. The fungus identified was Cladophialophora bantiana, based on characteristic microscopic features and on growth at 40 degrees C. The abscess recurred in spite of treatment with fluconazole. The patient was submitted to a second brain surgical procedure and was treated with amphotericin B in addition to fluconazole. Ten days later the patient's blood cultures became positive for Escherichia coli. After 3 days the patient died due to septic shock.
Assuntos
Ascomicetos/isolamento & purificação , Abscesso Encefálico/microbiologia , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Transplante de Rim/efeitos adversos , Encéfalo/diagnóstico por imagem , Abscesso Encefálico/diagnóstico por imagem , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico por imagem , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is a global surveillance study established in 1999 to monitor antibacterial resistance of respiratory tract organisms. Thirteen centers from Argentina, Brazil and Mexico participated during 1999-2000; they collected 1806 isolates (Streptococcus pneumoniae 518, Haemophilus influenzae 520, Moraxella catarrhalis 140, Staphylococcus aureus 351, S. pyogenes 277). Overall, 218 (42.1%) of the S. pneumoniae isolates had reduced susceptibility to penicillin, 79 (15.3%) were penicillin-resistant and 79 (15.3%) were erythromycin-resistant. Mexico had the highest prevalence of penicillin (76.5%) and erythromycin (31.2%) resistance. Of 77 erythromycin-resistant S. pneumoniae tested for resistance genotype, 43 possessed mef(A), 33 possessed erm(B) and 1 possessed both erm(B) and mef(A) mechanism. All S. pneumoniae isolates were fully susceptible to telithromycin, linezolid, teicoplanin and vancomycin. Among H. influenzae isolates, 88 (16.9%) produced beta-lactamase, ranging from 11% (Brazil) to 24.5% (Mexico). Among M. catarrhalis isolates, 138 (98.6%) produced beta-lactamase. Twenty-four (8.7%) of the S. pyogenes isolates were erythromycin-resistant; resistance being attributable to mefA (n=18), ermTR (n=5) and ermB (n=1). All H. influenzae, M. catarrhalis and S. pyogenes were fully susceptible to telithromycin. Methicillin resistance was found in 26.5% of the S. aureus isolates (Argentina 15%; Mexico 20%; Brazil 31.3%). Telithromycin was effective against 97.7% of methicillin-susceptible isolates. PROTEKT confirms that antibacterial resistance is an emerging problem in Latin America. The previously reported high levels of pneumococcal resistance to the beta-lactam and macrolides were exceeded. New agents that do not induce resistance or that exert low selective pressure, e.g. telithromycin, are essential to safeguard future antibacterial efficacy.
Assuntos
Antibacterianos/uso terapêutico , Eritromicina/uso terapêutico , Resistência às Penicilinas , Infecções Respiratórias/tratamento farmacológico , Antibacterianos/farmacologia , Argentina/epidemiologia , Brasil/epidemiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Resistência a Múltiplos Medicamentos , Eritromicina/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/isolamento & purificação , Humanos , México/epidemiologia , Testes de Sensibilidade Microbiana , Moraxella catarrhalis/efeitos dos fármacos , Moraxella catarrhalis/isolamento & purificação , Vigilância da População , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pyogenes/efeitos dos fármacos , Streptococcus pyogenes/isolamento & purificaçãoRESUMO
PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is a global surveillance study established in 1999 to monitor antibacterial resistance of respiratory tract organisms. Thirteen centers from Argentina, Brazil and Mexico participat ed during 1999-2000; they collected 1,806 isolates (Streptococcus pneumoniae 518, Haemophilus influenzae 520, Moraxella catarrhalis 140, Staphylococcus aureus 351, S. pyogenes 277). Overall, 218 (42.1 percent) of the S. pneumoniae isolates had reduced susceptibility to penicillin, 79 (15.3 percent) were penicillin-resistant and 79 (15.3 percent) were erythromycin-resistant. Mexico had the highest prevalence of penicillin (76.5 percent) and erythromycin (31.2 percent) resistance. Of 77 erythromycin-resistant S. pneumoniae tested for resistance genotype, 43 possessed mef(A), 33 possessed erm(B) and 1 possessed both erm(B) and mef(A) mechanism. All S. pneumoniae isolates were fully susceptible to telithromycin, linezolid, teicoplanin and vancomycin. Among H. influenzae isolates, 88 (16.9 percent) produced b-lactamase, ranging from 11 percent (Brazil) to 24.5 percent (Mexico). Among M. catarrhalis isolates, 138 (98.6 percent) produced b-lactamase. Twenty-four (8.7 percent) of the S. pyogenes isolates were erythromycin-resistant; resistance being attributable to mefA (n=18), ermTR (n=5) and ermB (n=1). All H. influenzae, M. catarrhalis and S. pyogenes were fully susceptible to telithromycin. Methicillin resistance was found in 26.5 percent of the S. aureus isolates (Argentina 15 percent; Mexico 20 percent; Brazil 31.3 percent). Telithromycin was effective against 97.7 percent of methicillin-susceptible isolates. PROTEKT confirms that antibacterial resistance is an emerging problem in Latin America. The previously reported high levels of pneumococcal resistance to the b-lactam and macrolides were exceeded. New agents that do not induce resistance or that exert low selective pressure, e.g. telithromycin, are essential to safeguard future antibacterial efficacy
Assuntos
Humanos , Antibacterianos/uso terapêutico , Eritromicina/uso terapêutico , Resistência às Penicilinas , Infecções Respiratórias/tratamento farmacológico , Antibacterianos/farmacologia , Argentina/epidemiologia , Brasil/epidemiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Resistência a Múltiplos Medicamentos , Eritromicina/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/isolamento & purificação , Testes de Sensibilidade Microbiana , México/epidemiologia , Moraxella catarrhalis/efeitos dos fármacos , Moraxella catarrhalis/isolamento & purificação , Vigilância da População , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pyogenes/efeitos dos fármacos , Streptococcus pyogenes/isolamento & purificaçãoRESUMO
BACKGROUND: A hospital-wide, traditional prospective surveillance for nosocomial infections was commenced in 1992 in Centro Geral de Pediatria in Minas Gerais, Brazil, to describe the epidemiology of nosocomial infection in this pediatric hospital and to implement cross-infection prevention and control policies. METHODS: We performed a prospective cohort nosocomial infection surveillance of all patients receiving acute care according to the hospital-wide and intensive care unit components of the National Nosocomial Infections Surveillance System from January 1993 to December 1997 (14,892 discharges; 131,764 patient-days). The Centers for Disease Control and Prevention (Atlanta) 1988-definitions and the Brazilian Ministry of Health-Legislation 930 (1992) were used. RESULTS: The average overall nosocomial infection rate per 1000 patient-days was 8.9 in units 2 and 3 and 16.4 in the pediatric intensive care unit. Over time, the overall hospital infection rate decreased from 16.6 nosocomial infections per 1000 patient-days in 1993 to 7.0 in 1997 (P <.05). We believe this can be attributed to interventions and data reporting during the period. The five most frequent sites of infections were eye-ear-nose-throat (38%), skin (22%), pneumonia (12%), soft tissue (5%) and laboratory-confirmed bloodstream infection (4%). In the pediatric intensive care unit, the most frequent nosocomial infection sites were pneumonia related to mechanical ventilators (22%), with rates ranging from 0 to 42 per 1000 ventilator-days; and sepsis related to central lines (11%), with rates ranging from 0 to 32 per 1000 central line-days. CONCLUSIONS: Describing the epidemiology of nosocomial infections in this hospital enabled us to establish infection occurrence, distribution, and expected incidence, as well as to recognize trends and keep track of possible outbreaks. The knowledge acquired through this surveillance allowed us to target more specific and continuous quality improvement projects, to upgrade health care quality in pediatric public hospitals in Brazil, and to implement preventive strategies. Methods from the National Nosocomial Infections Surveillance System can be successfully applied in pediatric public hospitals in Brazil.
Assuntos
Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Controle de Infecções/métodos , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Brasil/epidemiologia , Criança , Estudos de Coortes , Hospitais Pediátricos/normas , Hospitais Pediátricos/estatística & dados numéricos , Hospitais Públicos/normas , Hospitais Públicos/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva Pediátrica/normas , Política Organizacional , Estudos Prospectivos , Vigilância de Evento Sentinela , Estados UnidosRESUMO
Infection control activities in developing countries have increased substantially during the last decade, particularly in certain regions of the world. Pressure to improve hospital care cost-effectiveness, the emergence of highly resistant microorganisms, the perception of healthcare worker occupational hazards, and public claims for improved health assistance quality have been important factors responsible for this development. A major challenge for infection control personnel in developing countries is to sustain this development.
Assuntos
Controle de Infecções , Efeitos Psicossociais da Doença , Infecção Hospitalar/economia , Países em Desenvolvimento , Surtos de Doenças , Resistência Microbiana a Medicamentos , Resistência a Múltiplos Medicamentos , Humanos , Saúde OcupacionalAssuntos
Transplante de Coração , Complicações Pós-Operatórias , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Doença de Chagas/diagnóstico , Doença de Chagas/terapia , Transplante de Coração/imunologia , Humanos , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/prevenção & controle , Infecção da Ferida CirúrgicaRESUMO
OBJECTIVES: To examine the role of the laboratory in nosocomial infection control from January 1993 to December 1996 in Centro Geral de Pediatria of Hospital Foundation of Minas Gerais state. METHODS: Follow -up of 101,139 patient-days (11,147 discharges + deaths + transfers) in the wards and intensive care unit by using the National Nosocomial Infection Surveillance (NNIS) system proposed by the Centers for Disease Control and Prevention (CDC- Atlanta). Prospective surveillance of nosocomial infections at all sites was performed according to the hospital - wide (since 1992) and intensive care unit (since 1996) NNIS components. The CDC definitions since 1988 and Brazilian Ministry of Health regulation number 930 since 1992 were used to diagnose the nosocomial infections. RESULTS: The five most frequent nosocomial pathogens (from a total of 139 isolates) were Klebsiella sp = 24.5%; S. aureus = 18%; P. aeruginosa = 13.7%; E. coli = 12.9%; S. epidermidis = 12.2%. The percentage of identification of pathogens isolated from nosocomial infection sites has increased from 6.2% in 1993 to 13.3% in 1995 and 28.2% in 1996 (p< 0.001) and so has the attempt to isolate the pathogens: 7.5% in 1993, 16.1% in 1995, 33.8% in 1996 (p< 0.001). The time interval taken for lab results (from specimen collected to microbiology result) has decreased from the average of ten days in 1993 to six days in 1996 (p = 0.001). CONCLUSIONS: The continuing education and improved communication among infection control personnel, pediatricians, surgeons and members of the laboratory have proven to play a key role in the epidemiology of nosocomial infections by defining their etiologies in the Centro Geral de Pediatria. A task force to determine the microbiology has been achieved by the understanding of all clinicians that it is important to treat their patients specifically. The NNIS method applied to Brazilian hospitals has shown its impact on the microbiology lab role in nosocomial infection control as well.
RESUMO
OBJECTIVE: To assess the magnitude of nosocomial infections (NI) in general hospitals of Belo Horizonte. DESIGN: Multicenter point-prevalence study of nosocomial infections. SETTING: All of the 11 general hospitals of Belo Horizonte that have more than 20 beds, from August 27 to October 5, 1992. RESULTS: Of the 2,339 patients surveyed, 267 patients had 328 nosocomial infections. The global prevalence rate of NI was 14.0%, ranging from 4.6% to 27.3% in the hospitals surveyed. The most prevalent infections were found to be pneumonia and surgical-wound infections, representing 19.5% and 19.2%, respectively, of the total infections. The highest prevalence rates of NI were observed in the cardiac surgery (31.9%), pediatric (27.2%), and orthopedic (20.7%) services. The most frequently isolated microorganisms were Staphylococcus aureus, Escherichia coli, Pseudomonas species, and Klebsiella species. CONCLUSION: The study allowed a thorough evaluation of the NI distribution profile in Belo Horizonte, Minas Gerais, Brazil, and showed it to be a serious public health problem that requires interinstitutional efforts so that effective action can be taken.
Assuntos
Infecção Hospitalar/epidemiologia , Hospitais Gerais/estatística & dados numéricos , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Feminino , Departamentos Hospitalares/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
BACKGROUND: Nosocomial infection is an important public health problem in Brazil. The better to understand and address this problem, we began using the National Nosocomial Infection Surveillance (NNIS) system in five Brazilian hospitals in 1991. METHODS: Data were collected prospectively according to the NNIS protocol, by using nosocomial infection definitions from the Centers for Disease Control and Prevention. RESULTS: From January 1991 to June 1995, the overall nosocomial infection rate was 5.1% or 9.7 nosocomial infections/1000 patient-days. From the detailed epidemiologic information obtained by using the NNIS methods, interventions were designed and implemented that have reduced specific nosocomial infection rates. For example, the incidence of infection caused by methicillin-resistant Staphylococcus aureus was reduced from 0.61 infections/1000 patient-days in 1991 to 0.05 infections/1000 patient-days in 1996 (p < 0.01). The surgical site infection rate after cesarean section was reduced from 11.6% in 1993 to 5.9% in 1996 (p < 0.05). Cost savings from a program to optimize the use of antimicrobial agents in one hospital was more than $1.8 million over a 45-month period. CONCLUSION: The NNIS method was applicable in a wide variety of hospitals, even those with little or no experience with nosocomial infection surveillance. By using this method, we defined the detailed epidemiology of nosocomial infection and implemented interventions that have significantly reduced nosocomial infection rates while achieving substantial cost savings.
Assuntos
Centers for Disease Control and Prevention, U.S. , Infecção Hospitalar/prevenção & controle , Hospitais Urbanos , Controle de Infecções/organização & administração , Brasil/epidemiologia , Redução de Custos , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Humanos , Incidência , Vigilância da População , Estudos Prospectivos , Estados UnidosRESUMO
La incidencia de infecciones en cirugia pediatrica varya en la literatura internacional de 7,5 por ciento a 30 por ciento, no existiendo una diferencia significativa con los pacientes adultos. Las cifras tan variables dependen de las caracteristicas de la poblacion y de los procedimientos especificos. La clasificacion de los procedimientos por la potencialidad de contaminacion, la evaluacion del estado clinico en base a los criterios de la American Society of Anestesiology (ASA) y el tiempo de duracion de las cirugias, son las formas tradicionales de evaluar estos riesgos. El objetivo de este estudio fue evaluar el indice de Riesgo de Infeccion Quirurgica (IRIQ), propuesto por el Centers of Diseases Control and Prevention (CDC), en tres franjas etarias de la cirugia pediatrica. Fueron evaluados 773 pacientes sometidos a cirugia pediatrica en el periodo de Enero de 1993 a Diciembre de 1994. Las infecciones fueron diagnosticadas mediante una busqueda activa intra y extra hospitalaria, utilizando los criterios del CDC. La tasa de infeccion quirurgica fue del 3,5 por ciento (27/773). El potencial de contaminacion, el ASA y el tiempo de cirugia aisladamente fueron buenos predictores de riesgo de infeccion quirurgica. La asociacion de las tres variables fue mas adecuada y con menos variaciones que la relacion con la franja etaria. Recomendamos que el analisis de incidencia de infeccion en cirugia pediatrica sea realizado a traves de estadificaciones por el IRIQ
Assuntos
Cirurgia Geral , Infecção da Ferida Cirúrgica , PediatriaAssuntos
Lesões no Cotovelo , Fixação Interna de Fraturas , Fraturas da Ulna/cirurgia , Criança , Humanos , MasculinoRESUMO
A series of synthetic peptides derived from proteins encoded by open reading frames 2 and 3 (ORF2 and ORF3) of the hepatitis E virus was used in an enzyme immunoassay to determine the localization of epitopes in these proteins. Five peptides spanning almost the entire ORF3 protein sequence and 12 peptides from the ORF2 protein were synthesized. Serum samples collected from outbreaks in three different regions of the world (Turkmenistan, Kenya, and Mexico) were analyzed by a peptide-based enzyme immunoassay. Primary analysis of the peptides was accomplished with the use of serum samples obtained from Middle Asia. Four of 5 peptides from the ORF3 protein and 4 of 12 peptides from the ORF2 protein specifically reacted with antibody from sera of HEV-infected patients. Peptides representing immunodominant epitopes were used for the analysis of serum samples from outbreaks in Kenya and Mexico. The data indicate that these synthetic peptides may be used to develop a diagnostic test to detect antibody to the hepatitis E virus.