RESUMEN
BACKGROUND: Patients with oesophageal/gastro-oesophageal junction adenocarcinoma (EAC) not showing early metabolic response (EMR) to chemotherapy have poorer survival and histological response rates <5%. We investigated whether tailoring neoadjuvant therapy can improve outcomes in these patients. PATIENTS AND METHODS: Patients with resectable EAC were enrolled and randomised into two single-arm, multicentre phase II trials. After induction cisplatin and 5-fluorouracil (CF), all were assessed by day 15 positron emission tomography (PET). Patients with an EMR [maximum standardised uptake values (SUVmax) ≥35% reduction from baseline to day 15 PET] received a second CF cycle then oesophagectomy. Non-responders were randomised 1 : 1 to two cycles of CF and docetaxel (DCF, n = 31) or DCF + 45 Gy radiotherapy (DCFRT, n = 35) then oesophagectomy. The primary end point was major histological response (<10% residual tumour) in the oesophagectomy specimen; secondary end points were overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LR). RESULTS: Of 124 patients recruited, major histological response was achieved in 3/45 (7%) with EMR, 6/30 (20%) DCF, and 22/35 (63%) DCFRT patients. Grade 3/4 toxicities occurred in 12/45 (27%) EMR (CF), 13/31 (42%) DCF, and 25/35 (71%) DCFRT patients. No treatment-related deaths occurred. LR by 3 years was seen in 5/45 (11%) EMR, 10/31 (32%) DCF, and 4/35 (11%) DCFRT patients. PFS [95% confidence interval (CI)] at 36 months was 47% (31% to 61%) for EMR, 29% (15% to 45%) for DCF, and 46% (29% to 61%) for DCFRT patients. OS (95% CI) at 60 months was 53% (37% to 67%) for EMR, 31% (16% to 48%) for DCF, and 46% (29% to 61%) for DCFRT patients. CONCLUSIONS: EMR is associated with favourable OS, PFS, and low LR. For non-responders, the addition of docetaxel augmented histological response rates, but OS, PFS, and LR remained inferior compared with responders. DCFRT improved histological response and PFS/LR outcomes, matching the EMR group. Early PET/CT has the potential to tailor therapy for patients not showing an early response to chemotherapy. TRIAL REGISTRATION: ACTRN12609000665235.
Asunto(s)
Adenocarcinoma , Neoplasias Esofágicas , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Docetaxel/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Humanos , Recurrencia Local de Neoplasia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Resultado del TratamientoRESUMEN
Laboratory-based diagnosis of infectious diseases is evolving quickly. New technologies and new tests are frequently commercialized, and although guidelines for their proper clinical validation do exist, these are often at the national or regional level. Therefore, the guidelines remain open to interpretation, and are not always applied properly. One of the main questions is how a high level of test quality can be maintained by European legislation. How can product quality be reliably and independently assessed and how can the penetration of sub-standard assays in the European market be managed and hopefully prevented? We here propose that local initiatives, including external quality assessment, public health initiatives, and close multidisciplinary collaborations between manufacturers and academic research institutes, may accelerate decision-making. Vigilance in test quality assessment and legal simplification are important key concepts warranting selective use of those diagnostic tests that comply with the highest quality standards.
Asunto(s)
Técnicas Microbiológicas/normas , Técnicas Microbiológicas/tendencias , Técnicas de Diagnóstico Molecular/normas , Técnicas de Diagnóstico Molecular/tendencias , Europa (Continente) , Humanos , Control de CalidadRESUMEN
Antimicrobial resistance is a serious threat and compromises the management of infectious disease. This has particular significance in relation to infections of the respiratory tract, which are the lead cause of antibiotic prescribing. Education is fundamental to the correct use of antibiotics. A novel open access curriculum has been developed in the context of a European Union funded research project Genomics to combat Resistance against Antibiotics in Community-acquired lower respiratory tract infections in Europe (GRACE http://www.grace-lrti.org). The curriculum was developed in modular format and populated with clinical and scientific topics relevant to community-acquired lower respiratory tract infections. This curriculum informed the content of a series of postgraduate courses and workshops and permitted the creation of an open access e-Learning portal. A total of 153 presentations matching the topics within the curriculum together with slide material and handouts and 104 webcasts are available through the GRACE e-Learning portal, which is fully searchable using a 'mindmap' to navigate the contents. Metrics of access provided a means for assessing usage. The GRACE project has permitted the development of a unique on-line open access curriculum that comprehensively addresses the issues relevant to community-acquired lower respiratory tract infections and has provided a resource not only for personal learning, but also to support independent teaching activities such as lectures, workshops, seminars and course work.
Asunto(s)
Investigación Biomédica/educación , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Curriculum , Farmacorresistencia Bacteriana , Educación en Salud/métodos , Acceso a la Información , Instrucción por Computador , Unión Europea , Genómica , Humanos , Internet , Enfermedades Pulmonares/tratamiento farmacológico , Difusión por la Web como AsuntoRESUMEN
We performed a Web-based survey on attitudes and uptake of H1N1 influenza vaccination among members of two European societies, namely the European Respiratory Society and the European Society of Clinical Microbiology and Infectious Diseases. A multidisciplinary panel developed a questionnaire that examined physicians' and members' knowledge, attitudes and practice about seasonal and pandemic (H1N1) influenza vaccination. In all, 1334 healthcare workers from 83 countries (785 men and 549 women, mean age 45 ± 7 years) accessed and completed the survey. Safety concerns about vaccines was the main reason reported by 451/1285 respondents for not being vaccinated. More than 30% of 1282 respondents considered the management of communication on the flu pandemic by health authorities to be insufficient. The results of this survey should help health authorities to better design future steps for the successful vaccination of healthcare workers.
Asunto(s)
Encuestas de Atención de la Salud , Personal de Salud , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Vacunación/estadística & datos numéricos , Adolescente , Niño , Preescolar , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Gripe Humana/epidemiología , Internet , Masculino , Encuestas y Cuestionarios , Adulto JovenRESUMEN
A taskforce has now been formed with representatives from the Department of Health's Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infection (ARHAI), the Hospital Infection Society (HIS), the Department of Health (England) and the Health Protection Agency. The aims of the ARHAI/HIS Taskforce on Sporicidal Disinfectants are: to develop an accepted standard for laboratory testing of disinfectants which claim to have activity against C. difficile spores; to develop a network of laboratories with capability to perform in vitro assays of sporicidal activity of disinfectants; and to explore the creation of a national quality assessment scheme for laboratories which perform in vitro assays of sporicidal activity of disinfectants.
Asunto(s)
Clostridioides difficile/efectos de los fármacos , Desinfectantes/farmacología , Pruebas de Sensibilidad Microbiana/normas , Esporas Bacterianas/efectos de los fármacos , Clostridioides difficile/fisiología , Reino UnidoRESUMEN
Ectonucleoside triphosphate diphosphohydrolase type 5 (ENTPD5, also CD39L4) is a soluble enzyme that hydrolyzes purine nucleoside diphosphates. Genetic inactivation of ENTPD5 in mice (Entpd5(-/-)) resulted in 2 major histopathologic lesions: hepatopathy and aspermia. The hepatopathy was progressive and characterized by centrilobular hepatocyte hypertrophy, oval cell proliferation, bile staining of Kupffer cells, and hepatocyte degeneration with increasing incidence and severity of degenerative lesions, development of multiple foci of cellular alteration, and hepatocellular neoplasia with age. Greatly increased proliferation of hepatocytes in young adult as well as aged Entpd5(-/-) mice was demonstrated by Ki67 immunohistochemistry and 5'-bromo-3'-deoxyuridine incorporation. Of 15 Entpd5(-/-) mice between 44 and 69 weeks of age, all showed foci of cellular alteration in the liver, and at least 6 of 15 developed hepatocellular carcinoma (HCC), hepatocellular adenoma, or both. Significantly, none of these lesions were observed in 13 wild-type Entpd5(+/+) littermates. These findings, combined with the historically low incidence (about 5%) of HCC in mice up to 2 years of age with the same genetic background, strongly suggest that loss of Entpd5 promotes hepatocellular neoplasia in mice. In humans, ENTPD5 has been found to be identical to the PCPH proto-oncogene, and dysregulation of this gene has been demonstrated in some human cancers. This mouse model could contribute to the understanding of the influence of ENTPD5/PCPH on cellular proliferation and neoplasia.
Asunto(s)
Regulación Enzimológica de la Expresión Génica/fisiología , Hepatitis/genética , Neoplasias Hepáticas/genética , Proteínas Oncogénicas/genética , Proteínas Oncogénicas/metabolismo , Espermatogénesis/genética , Envejecimiento , Animales , Femenino , Hepatitis/enzimología , Hígado/patología , Masculino , Ratones , Ratones Noqueados , Proto-Oncogenes MasRESUMEN
BACKGROUND: Non-anatomical liver resections have become more common in the management of colorectal liver metastases. This study examined survival and patterns of recurrence following surgery for colorectal liver metastases. METHODS: Data were collected prospectively on all patients who had hepatic surgery for colorectal liver metastases at St James' University Hospital, Leeds between 1993 and May 2003, and analysed with respect to type of resection. RESULTS: A total of 96 patients underwent non-anatomical liver resection, 280 patients had an anatomical resection, and 108 patients had a combined procedure. There was no significant difference in overall survival between the anatomical and non-anatomical groups (hazard ratio 1.14 (95 per cent confidence interval 0.60 to 2.17); P = 0.691). Intrahepatic recurrence was significantly less common in the anatomical group, whereas morbidity and mortality rates were lower in the non-anatomical group. On multivariable analysis, multiple metastases and poorer primary T stage predicted poorer overall survival and a positive resection margin predicted poorer disease-free survival. CONCLUSION: Non-anatomical resection can be performed with lower rates of surgical morbidity and mortality than anatomical resection, and does not disadvantage the patient in terms of overall survival.
Asunto(s)
Neoplasias Colorrectales , Hepatectomía/métodos , Neoplasias Hepáticas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Hepatectomía/estadística & datos numéricos , Humanos , Tiempo de Internación , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
The incidence of nosocomial disease caused by Gram-negative pathogens is increasing, and infections caused by Enterobacter, Klebsiella, Acinetobacter, Escherichia coli and Pseudomonas aeruginosa are more commonly refractive to traditional antimicrobial agents, including aminoglycosides, fluoroquinolones and broad-spectrum cephalosporins. The most important mechanism of resistance to beta-lactam antibiotics among Gram-negative bacilli involves the production of beta-lactamases. Extended-spectrum beta-lactamases are particularly worrisome, since they are often associated with multidrug resistance phenotypes, which can pose a significant therapeutic challenge. Novel agents for the treatment of Gram-negative infections are uncommon, as recent emphasis has been placed on the development of agents targeting drug-resistant strains of Gram-positive bacteria, e.g., streptococci, enterococci and staphylococci. Tigecycline, a semi-synthetic derivative of minocycline, has a unique and novel mechanism of action, which not only allows this agent to overcome the well-known tet gene-encoded resistance mechanisms, but also maintains its activity against Gram-negative pathogens producing a broad array of extended-spectrum beta-lactamases. Tigecycline is the first example of a new class of glycylcyclines with activity against a wide range of clinically important Gram-negative pathogens. Tigecycline has potent antimicrobial activity, and has been associated with an excellent therapeutic response in animal infection models and recently reported clinical trials, which reflect the effectiveness of tigecycline against pathogens causing intra-abdominal, skin and soft-tissue infections, including susceptible or multidrug-resistant strains of most Enterobacteriaceae, as well as anaerobic pathogens.
Asunto(s)
Antibacterianos/farmacología , Minociclina/análogos & derivados , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/genética , Humanos , Pruebas de Sensibilidad Microbiana , Minociclina/farmacología , Minociclina/uso terapéutico , Resistencia a la Tetraciclina , Tigeciclina , Resistencia betalactámica , beta-Lactamasas/genéticaRESUMEN
AIMS: The aim of this study was to report the results of surgery for multiple colorectal liver metastases on patient outcome. METHODS: This was a review of 484 consecutive patients who underwent liver resection for colorectal liver metastases between 1993 and 2003. The cohort was divided into 2 groups, those with 1-3 metastases and those with "multiple" metastases, namely 4 or more lesions. The later group was subdivided into those with less than 8 ("several") or 8 or more ("numerous") separate lesions. MAIN OUTCOME MEASURES: the post-operative hospital stay was calculated and morbidity and mortality were assessed. RESULTS: On multivariate analysis the presence of multiple metastases was the only predictor for both poorer overall survival (p=0.007) and disease-free survival (p=0.031). However, when patients with multiple metastases are analysed in detail this survival disadvantage appears to be only present in patients with numerous (8 or more) lesions. CONCLUSION: Although patients with multiple metastases appear to have a poorer outcome, significant number of patients with multiple metastases survive to 5 years or more and should not be denied surgery. Patients with numerous (8 or more) metastases showed a poorer survival disadvantage. These patients need alternative treatment speculatives.
Asunto(s)
Neoplasias Colorrectales/patología , Hepatectomía/métodos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The increase in microorganisms that have developed resistance to currently available antimicrobial agents has become a major cause for concern worldwide. These organisms are widespread in hospitals but also occur increasingly in the community. Some of these strains are multiresistant and the agents available to treat infections caused by them are few and dwindling. Over recent years there have been a number of responses by national, international and professional bodies to this situation, many aimed at curbing this unprecedented growth in resistance, but there is an increasing recognition that a major problem in the management of infections caused by such organisms is the paucity of new drugs, vaccines and diagnostic aids. A conference, organized by the Specialist Advisory Committee on Antimicrobial Resistance (SACAR) on behalf of the UK Department of Health and sponsored by the BSAC, was held in Birmingham in December 2005 with the aim of addressing these problems. Conference attendees included those from academia, industry, funding agencies, healthcare management, the European Medicines Agency (EMEA), the European Centre for Disease Prevention and Control (ECDC), European Directorates and representatives of EU governments. Following a number of keynote presentations which identified major issues, there were a series of workshops which addressed specific questions and produced a number of recommendations. These recommendations were discussed by all delegates. The lack of new anti-infectives and the reasons for this were discussed in some detail. Major pharmaceutical companies no longer find this area as financially rewarding as other therapeutic areas while smaller biotechnology companies, who are seen as more innovative, are hampered by a lack of funding. In spite of a few marked successes, the use of vaccines has had minimal impact in the field of bacterial infections, and progress in this field also suffers from a lack of funding. Diagnostics could aid in the better use of antibacterials but need greater acceptance in the healthcare system, which does not generally appreciate their cost-efficacy. The major recommendations were as follows: (i) Increased efforts are needed to reduce the spread of resistant strains both in the environment and in hospitals--these include improved hygiene and decreased use of some antimicrobials. (ii) Surveillance of resistance is a key factor and improved technology (e.g. IT systems) is needed to improve the potential for surveillance data to inform clinical practice. (iii) Rapid, sensitive and specific diagnostics are urgently needed and the issue of reimbursement needs to be addressed. (iv) More accurate estimates of the cost-efficacy of using anti-infectives and diagnostics are urgently needed. (v) Vaccine technology is available but is underused for the prevention of bacterial infections, particularly those caused by organisms resistant to antimicrobials. (vi) Incentives are required to encourage large pharmaceutical companies to partner small biotechnology companies, which are more innovative and have the potential to deliver the new drugs, diagnostics and vaccines. Modifications to the international regulatory requirements for drug licensing could have a major impact on the time and thus the costs of developing new agents.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Farmacorresistencia Bacteriana , Farmacorresistencia Bacteriana Múltiple , Antibacterianos/farmacología , Infecciones Bacterianas/diagnóstico , Aprobación de Drogas , Industria Farmacéutica , Utilización de Medicamentos , Unión Europea , Humanos , Inmunoterapia/economía , Pruebas de Sensibilidad Microbiana , Tecnología Farmacéutica/economía , Vacunas/uso terapéuticoRESUMEN
BACKGROUND: Up to 50% of antibiotic usage in hospitals is inappropriate. In hospitals infections caused by antibiotic-resistant bacteria are associated with higher mortality, morbidity and prolonged hospital stay compared with infections caused by antibiotic-susceptible bacteria. Clostridium difficile associated diarrhoea (CDAD) is a hospital acquired infection that is caused by antibiotic prescribing. OBJECTIVES: To estimate the effectiveness of professional interventions that alone, or in combination, are effective in promoting prudent antibiotic prescribing to hospital inpatients, to evaluate the impact of these interventions on reducing the incidence of antimicrobial resistant pathogens or CDAD and their impact on clinical outcome. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care (EPOC) specialized register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE from 1980 to November 2003. Additional studies were obtained from the bibliographies of retrieved articles SELECTION CRITERIA: We included all randomised and controlled clinical trials (RCT/CCT), controlled before and after studies (CBA) and interrupted time series (ITS) studies of antibiotic prescribing to hospital inpatients. Interventions included any professional or structural interventions as defined by EPOC. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed quality. MAIN RESULTS: Sixty six studies were included and 51 (77%) showed a significant improvement in at least one outcome. Six interventions only aimed to increase treatment, 57 interventions aimed to decrease treatment and three interventions aimed to both increase and decrease treatment. The intervention target was the decision to prescribe antibiotics (one study), timing of first dose (six studies), the regimen (drug, dosing interval etc, 61 studies) or the duration of treatment (10 studies); 12 studies had more than one target. Of the six interventions that aimed to increase treatment, five reported a significant improvement in drug outcomes and one a significant improvement in clinical outcome. Of the 60 interventions that aimed to decrease treatment 47 reported drug outcomes of which 38 (81%) significantly improved, 16 reported microbiological outcomes of which 12 (75%) significantly improved and nine reported clinical outcomes of which two (22%) significantly deteriorated and 3 (33%) significantly improved. Five studies aimed to reduce CDAD. Three showed a significant reduction in CDAD. Due to differences in study design and duration of follow up it was only possible to perform meta-regression on a few studies. AUTHORS' CONCLUSIONS: The results show that interventions to improve antibiotic prescribing to hospital inpatients are successful, and can reduce antimicrobial resistance or hospital acquired infections.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infección Hospitalaria/tratamiento farmacológico , Farmacorresistencia Bacteriana , Pautas de la Práctica en Medicina , Humanos , Pacientes Internos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Clinical microbiology should have a physical presence, but not necessarily on-site diagnostic laboratory facilities, in each hospital to ensure a quality laboratory-based infection service and strong professional interaction with clinicians. The adoption of industrial practices and the introduction of new costly molecular techniques raise the possibility that non-microbiological functions of laboratory management could be left to management professionals. This remains highly controversial; the advantages must be contrasted with the potential to disrupt the traditional managerial responsibility of the microbiologist and the links between the laboratory and clinical staff. Managers and healthcare professionals must resolve this issue, perhaps with the support of the ESCMID. Views varied, according to current professional arrangements and size of the laboratory and population served, on whether there should be a common laboratory for microbiology and other pathology disciplines with joint access to new high-technology techniques, or whether microbiology must continue as a separate facility. Clinical microbiology and infection control were viewed as core services that must be present even in smaller hospitals. Larger community hospitals and teaching centres require a full complement of expertise in laboratory and clinical practice. Integration of these disciplines within a department of infection is an emerging concept. A concern was the shortfall in trained expertise because of the ageing nature of current specialists. The importance of recruiting talented new graduates was emphasised. The importance of this topic led to a recommendation that an ESCMID working party be established to investigate the current arrangements of infection services in Europe and to make recommendations for the future organisation.
Asunto(s)
Control de Enfermedades Transmisibles , Enfermedades Transmisibles/diagnóstico , Infección Hospitalaria/prevención & control , Necesidades y Demandas de Servicios de Salud , Medicina , Microbiología , Especialización , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/terapia , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/epidemiología , Infección Hospitalaria/terapia , Educación Médica , Europa (Continente) , Política de Salud , Administración Hospitalaria , Humanos , Profesionales para Control de Infecciones/educación , Laboratorios , Microbiología/educaciónRESUMEN
It would be difficult to envision the practice of infectious diseases over the past 20 years without the availability of the glycopeptide antibiotics. The two agents currently in clinical use, vancomycin and teicoplanin, have proven remarkably versatile in many common applications. Several attributes of these agents account for this favourable profile: (i) their broad spectrum of activity against Gram-positive bacteria, including strains resistant to many other antimicrobials; (ii) their favourable pharmacokinetic properties that allow the once- or twice-daily dosing regimens that have made out-of-hospital therapy possible; and (iii) their generally good safety profiles which, along with their structural dissimilarity to beta-lactam and other antimicrobials, permits their use in many patients who are intolerant of other antibiotic regimens. It is not entirely surprising, therefore, that despite more than 40 years of clinical use and the interim appearance of bacterial strains resistant to this drug class, there remains continued interest in the development of newer members of the glycopeptide antibiotic class. This paper is intended to provide a global overview of the efficacy and safety of glycopeptide antibiotics currently in use, as background to understanding the need for and potential roles of new agents of this class.
Asunto(s)
Antibacterianos/efectos adversos , Antibacterianos/farmacología , Teicoplanina/efectos adversos , Teicoplanina/farmacología , Vancomicina/efectos adversos , Vancomicina/farmacología , Farmacorresistencia Bacteriana , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Hepatitis C virus (HCV) infection is a major public health problem. Up to 3% of the world's population is infected with HCV, and at least 200 000 adults in the UK carry the virus. Of those exposed to HCV, 80% become chronically infected, and at least 30% of carriers develop chronic liver disease, including cirrhosis and hepatocellular carcinoma. This review provides an overview of selected features of the molecular biology and pathogenesis of HCV infection, and thereafter discusses in detail the epidemiology of HCV, the hepatic and extra-hepatic diseases caused by the virus, and the current treatment options for both acute and chronic virus infection. The special cases of healthcare workers, prison inmates and individuals coinfected with human immunodeficiency virus and HCV are considered in detail.
Asunto(s)
Hepatitis C/tratamiento farmacológico , Infecciones por VIH/complicaciones , Personal de Salud , Hepacivirus/genética , Hepatitis C/epidemiología , Hepatitis C/prevención & control , Humanos , PrisionesRESUMEN
It has been shown that some antibiotics can modify cytokine production. We have examined the effect of rifampicin on secretion of interleukin-1beta (IL-1beta), IL-6, IL-10, and tumor necrosis factor alpha (TNF-alpha) by lipopolysaccharide (LPS)-stimulated or heat killed staphylococci (Pansorbin) stimulated monocytes. Secretion of IL-1beta and TNF-a were significantly inhibited (P<0.002) whereas secretion of IL-6 and IL-10 were significantly increased (P<0.003) by rifampicin treated mononuclear cells. Rifampicin had immunomodulatory effects through its capacity to alter the secretion of tested cytokines by human monocytes.
Asunto(s)
Citocinas/metabolismo , Terapia de Inmunosupresión , Monocitos/efectos de los fármacos , Monocitos/inmunología , Rifampin/farmacología , Células Cultivadas , Citocinas/efectos de los fármacos , Humanos , Interleucina-1/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Probabilidad , Sensibilidad y Especificidad , Estadísticas no Paramétricas , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The development and clinical use of antimicrobial agents continue to evolve in line with new science, understanding and needs. While antimicrobial resistance remains an important determinant for drug development and therapeutic choice, pharmacokinetic and pharmacodynamic parameters are having an ever-increasing importance in defining performance targets for new and established agents. Recently licensed new therapies are largely directed at serious hospital-associated Gram-positive infections, whereas in the community, therapeutic choice remains dependent on well-established agents from limited classes of antimicrobials. In order to maximise the benefits from such agents, it is appropriate that dosage regimens and antibacterial choices be reviewed in the light of new knowledge, particularly in the area of pharmacokinetics and pharmacodynamics. Antimicrobial resistance continues to evolve, notably within respiratory pathogens, therefore steps must be taken to maintain optimum therapeutic outcomes and also limit the development and spread of resistant strains. Whilst changes in patient and physician attitudes and behaviour towards better quality prescribing are important, new agents must also be developed to provide adequate coverage for resistant pathogens. Development times for novel agents and classes of antimicrobials are long, with uncertain safety profiles and chances of success. Thus, the development of new formulations of existing agents, designed to overcome current resistance patterns, constitutes a potentially important additional strategy towards appropriate prescribing.
Asunto(s)
Antibacterianos/farmacocinética , Antibacterianos/normas , Infecciones Bacterianas/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones Bacterianas/microbiología , Diseño de Fármacos , Farmacorresistencia Bacteriana , Infecciones por Haemophilus/tratamiento farmacológico , Infecciones por Haemophilus/microbiología , Haemophilus influenzae/efectos de los fármacos , Humanos , Infecciones Neumocócicas/tratamiento farmacológico , Infecciones Neumocócicas/microbiología , Infecciones del Sistema Respiratorio/microbiología , Streptococcus pneumoniae/efectos de los fármacosRESUMEN
OBJECTIVES: To evaluate the pattern of emergency adult medical admissions during the winter period and the usefulness of sales of over-the-counter cough/cold remedies as a predictor of these. METHODS: The databases of a single NHS trust acute unit and pharmacy outlets in its catchment area were analyzed retrospectively, comparing numbers of emergency admissions, ICD-10 discharge codes, local electronic point-of-sale (EPOS) and national sales data. RESULTS: Over nine consecutive winter periods from 1992/3, peak admissions always occurred within a defined ten-day period from 29th December to 9th January. Emergency admissions increased significantly during this period (P = 0.0002). Pharmaceutical/retail data were available for three consecutive winters 1998/99, 1999/2000 and 2000/2001, none of which coincided with increased influenza activity nationally. Acute respiratory illness as defined by International Classification of Diseases, 10th edition (ICD-10) discharge coding did not appear to contribute to the increase in admissions at the peak. However, National and Local EPOS sales were positively correlated with admissions and the rate of EPOS sales exceeded an empiric threshold of 1000 units per week two weeks prior to the admissions peak in each year. CONCLUSIONS: Emergency admissions over the winter period are increasing and can be expected within a period of only ten days each year. No firm relationship between acute respiratory illness and admissions could be defined but local EPOS data may give up to two weeks warning of the peak in admissions and merits further prospective evaluation.
Asunto(s)
Capacidad de Camas en Hospitales , Hospitalización/estadística & datos numéricos , Gripe Humana/epidemiología , Medicamentos sin Prescripción/administración & dosificación , Antitusígenos/administración & dosificación , Resfriado Común/tratamiento farmacológico , Recolección de Datos , Urgencias Médicas , Humanos , Farmacias , Estudios Retrospectivos , Factores de TiempoRESUMEN
The objective of the present trial was to compare the efficacy, safety, and tolerability of moxifloxacin (400 mg) given intravenously (i.v.) once daily followed by oral moxifloxacin (400 mg) for 7 to 14 days with the efficacy, safety, and tolerability of co-amoxiclav (1.2 g) administered by i.v. infusion three times a day followed by oral co-amoxiclav (625 mg) three times a day, with or without clarithromycin (500 mg) twice daily (i.v. or orally), for 7 to 14 days in adult patients with community-acquired pneumonia requiring initial parenteral therapy. A total of 628 patients were enrolled and assessed by evaluation of their clinical and bacteriological responses 5 to 7 days and 21 to 28 days after administration of the last dose of study medication. Although the trial was designed, on the basis of predefined outcomes, to demonstrate the equivalence of the two regimens, the results showed statistically significant higher clinical success rates (for moxifloxacin, 93.4%, and for comparator regimen, 85.4%; difference [Delta], 8.05%; 95% confidence interval [CI], 2.91 to 13.19%; P = 0.004) and bacteriological success rates (for moxifloxacin, 93.7%, and for comparator regimen, 81.7%; Delta, 12.06%; 95% CI, 1.21 to 22.91%) for patients treated with moxifloxacin. This superiority was seen irrespective of the severity of the pneumonia and whether or not the combination therapy included a macrolide. The time to resolution of fever was also statistically significantly faster for patients who received moxifloxacin (median time, 2 versus 3 days), and the duration of hospital admission was approximately 1 day less for patients who received moxifloxacin. The treatment was converted to oral therapy immediately after the initial mandatory 3-day period of i.v. administration for a larger proportion of patients in the moxifloxacin group than patients in the comparator group (151 [50.2%] versus 57 [17.8%] patients). There were fewer deaths (9 [3.0%] versus 17 [5.3%]) and fewer serious adverse events (38 [12.6%] versus 53 [16.5%]) in the moxifloxacin group than in the comparator group. The rates of drug-related adverse events were comparable in both groups (38.9% in each treatment group). The overall incidence of laboratory abnormalities was similar in both groups. Thus, it is concluded that monotherapy with moxifloxacin is superior to that with a standard combination regimen of a beta-lactam and a beta-lactamase inhibitor, co-amoxiclav, with or without a macrolide, clarithromycin, in the treatment of patients with community-acquired pneumonia admitted to a hospital.
Asunto(s)
Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Compuestos Aza , Claritromicina/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Quimioterapia Combinada/uso terapéutico , Fluoroquinolonas , Neumonía Bacteriana/tratamiento farmacológico , Quinolinas , Administración Oral , Adulto , Combinación Amoxicilina-Clavulanato de Potasio/administración & dosificación , Combinación Amoxicilina-Clavulanato de Potasio/efectos adversos , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antiinfecciosos/administración & dosificación , Antiinfecciosos/efectos adversos , Bacterias/efectos de los fármacos , Claritromicina/administración & dosificación , Claritromicina/efectos adversos , Infecciones Comunitarias Adquiridas/microbiología , Método Doble Ciego , Quimioterapia Combinada/administración & dosificación , Quimioterapia Combinada/efectos adversos , Femenino , Humanos , Infusiones Intravenosas , Inyecciones Intravenosas , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Moxifloxacino , Neumonía Bacteriana/microbiologíaRESUMEN
BACKGROUND: This study was undertaken to determine the quality of information on the Internet regarding laparoscopy. METHODS: Four popular World Wide Web search engines were used with the key word "laparoscopy." Advertisements, patient- or physician-directed information, and controversial material were noted. RESULTS: A total of 14,030 Web pages were found, but only 104 were unique Web sites. The majority of the sites were duplicate pages, subpages within a main Web page, or dead links. Twenty-eight of the 104 pages had a medical product for sale, 26 were patient-directed, 23 were written by a physician or group of physicians, and six represented corporations. The remaining 21 were "miscellaneous." The 46 pages containing educational material were critically reviewed. At least one of the senior authors found that 32 of the pages contained controversial or misleading statements. All of the three senior authors (LKN, NAO, GAF) independently agreed that 17 of the 46 pages contained controversial information. CONCLUSION: The World Wide Web is not a reliable source for patient or physician information about laparoscopy. Authenticating medical information on the World Wide Web is a difficult task, and no government or surgical society has taken the lead in regulating what is presented as fact on the World Wide Web.