摘要:

Directly Observed Therapy Shortcourse (DOTS) is composed of five distinct elements: political commitment; microscopy services; drug supplies; surveillance and monitoring systems and use of highly efficacious regimens; and direct observation of treatment. The difference in the way the term ‘DOTS’ as defined by WHO and interpreted by many observers has led to some misunderstanding. WHO generally uses the term to mean the five components of DOTS. But the word ‘DOTS’ is an acronym for Directly Observed Therapy Shortcourse. Many workers therefore interpret DOTS purely as direct supervision of therapy. DOTS is not an end in itself but a means to an end. In fact it has two purposes, to ensure that the patient with tuberculosis (TB) completes therapy to cure and to prevent drug resistance from developing in the community.The main criticism of DOTS rightly derives from the fact that some properly conducted randomized, controlled trials of directly observed therapy with or without the other components have shown no benefit from it. The problem is that it is impossible to design a study of modern directly observed therapy against the previous self-administered, poorly-resourced programs. As soon as a study is implemented, the attention to patients in the control (non-directly observed therapy) arm inevitably improves from the previous non-trial service situation. What is of concern is that in some trials less than 70% cure rates were achieved even in the direct observation arm.With no new drugs or adjuvant treatment available to bring the length of treatment down to substantially less than 6 months, DOTS offers the best means we have at our disposal for TB control.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

The nuclear factor kappa B (NF-κB) transcription factor plays a key role in the induction of pro-inflammatory gene expression, leading to the synthesis of cytokines, adhesion molecules, chemokines, growth factors and enzymes. Results of studies inin vitroandin vivomodels of inflammation and malignancy have also suggested central roles for NF-κB in programmed cell death, or apoptosis.NF-κB plays a central role in a variety of acute and chronic inflammatory diseases. In the common lung diseases associated with a significant inflammatory component such as severe sepsis, acute lung injury, acute respiratory distress syndrome, cystic fibrosis and asthma, the pathogenic roles of NF-κB have been extensively investigated. In COPD, activation of NF-κB has been implicated in disease pathogenesis but its exact role is less clearly demonstrable in this heterogeneous patient population. However, the principal risk factor for COPD, cigarette smoking, is strongly associated with NF-κB activation.Activation of NF-κB has been demonstrated in mineral dust diseases and probably plays a role in the pathogenesis of these chronic illnesses. NF-kB also plays a variety of roles in lung cancer including resistance to chemotherapy, inhibition of tumorigenesis and inducing expression of antiapoptotic genes. The complex NF-κB pathway offers a variety of potential molecular targets for chemotherapeutic intervention. A variety of agents aimed at modulating NF-κB activity are in various stages of investigation.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

The incidence of lower respiratory tract infection (LRTI) in women of child-bearing age is approximately 64 per 1000 population. The spectrum of illness ranges from acute bronchitis, which is very common, through influenza virus infection and exacerbations of underlying lung disease, to pneumonia, which, fortunately is uncommon (<1.5% LRTI), but can be severe.Acute bronchitis is generally mild, self-limiting and usually does not require antibacterial therapy. Influenza virus infection in pregnant women has been recently related to increased hospitalization for acute cardiorespiratory conditions. At present, the safety of the newer neuraminidase inhibitors for the treatment of influenza virus infection has not been established in pregnancy and they are not routinely recommended. In influenza virus infection complicated by pneumonia, antibacterial agents active againstStaphylococcus aureusandStreptococcus pneumoniaesuperinfection should be used.There are few data on infective complications of asthma or COPD in pregnancy. The latter is rare, as patients with COPD are usually male and aged over 45 years. Management is the same as for nonpregnant patients.The incidence and mortality of pneumonia in pregnancy is similar to that in nonpregnant patients. Infants born to pregnant patients with pneumonia have been found to be born earlier and weigh less than controls. Risk factors for the development of pneumonia include anemia, asthma and use of antepartum corticosteroids and tocolytic agents. Based on the few available studies, the main pathogens causing pneumonia areS. pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniaeand viruses. β-Lactam and macrolide antibiotics therefore remain the antibiotics of choice in terms of both pathogen coverage and safety in pregnancy. In HIV-infected pregnant patients, recurrent bacterial pneumonia, but notPneumocystis cariniipneumonia (PCP), is more common than in nonpregnant patients. Trimethoprim/sulfamethoxazole (cotrimoxazole) has not definitely been associated with adverse clinical outcomes despite theoretical risks. Currently it is still the treatment of choice in PCP, where mortality remains high.In conclusion, there are few data specifically related to pregnant women with different types of LRTI. Where data are available, no significant differences compared with nonpregnant patients have been identified. In considering the use of any therapeutic agent or investigation in pregnant patients with LRTI, safety aspects must be carefully weighed against potential benefit. Otherwise, management strategies should not differ from those for nonpregnant patients. Further research in this area is warranted.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Infection withLegionellaspp. is an important cause of serious community- and hospital-acquired pneumonia, occurring sporadically and in outbreaks. Outbreaks of Legionnaires’ disease have recently received considerable media attention, and some factors indicate that the problem will increase in future. Infection withLegionellaspp. ranks among the three most common causes of severe pneumonia in the community setting, and is isolated in 1–40% of cases of hospital-acquired pneumonia. Underdiagnosis and underreporting are high. Only 2–10% of estimated cases are reported. Detection of a single case should not be considered an isolated sporadic event, but rather indicative of unrecognized cases.There are no clinical features unique to Legionnaires’ disease; however, suspicion should be raised by epidemiologic information commensurate with the diagnosis and the presence of headache, confusion, hyponatremia, elevated creatine kinase and/or severe pneumonia. An arterial oxygen partial pressure <60mm Hg on presentation and progression of pulmonary infiltrates despite appropriate antibacterial therapy should always alert clinicians to this cause.Macrolides, fluoroquinolones and rifampin (rifampicin) are the most widely used drugs in treatment. Fluoroquinolones or azithromycin are the treatment of choice in immunosuppressed patients and those with severe pneumonia. Incorporation of the legionella urinary antigen test in emergency departments in hospitals and progressive improvement in this test will, in the near future, permit appropriate diagnosis and treatment of this frequent, sometimes severe, illness.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Descriptive studies have shown an association between eosinophils, interleukin (IL)-5 and pathophysiological processes in patients with atopic asthma. These observations have led to an interest in the eosinophil as the pathogenic cell responsible for many of the clinical features of asthma including symptoms of wheeze, shortness of breath and cough, along with the physiological events such as airway hyperresponsiveness (AHR) and changes in lung function.IL-5 is one of the key cytokines responsible for eosinopoiesis in the bone marrow, along with recruitment and survival of eosinophils in the tissues. In view of this, IL-5 has been an attractive target for the development of anti-IL-5 monoclonal antibodies, inhibiting its action.The results of preclinical studies are viewed as encouraging. Preclinical development involved studies in mice, guinea-pigs and cynomolgus monkeys, with conflicting results in terms of changes in blood and bronchoalveolar lavage eosinophils, AHR and pulmonary resistance. These may be attributed to interspecies differences and to the different models used. Monoclonal antibodies directed against IL-5 have been used in at least four studies involving patients with asthma. Those preliminary studies have shown clear reductions in both blood and sputum eosinophils but no significant changes in physiological parameters of AHR, the late asthmatic reaction or in lung function or symptoms. As in the animal studies, these results suggest a dissociation between eosinophils, AHR, lung function and symptoms of asthma, which may be explained by the multitude of cells involved in the pathogenesis of asthma.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Management of recurrent malignant pleural effusion, a common complication of malignancy, poses a challenge to clinicians. Although almost one century has elapsed since the introduction of the pleurodesis procedure, the ideal approach and best agent are still to be defined. Optimally, pleurodesis should be done at the bedside with a minimally invasive procedure, and suitable agents to achieve pleural symphysis should be inexpensive, available worldwide and free of adverse effects. To date, no substance completely fulfills these requirements.Silver nitrate should be considered for pleurodesis because of its low cost and ease of handling. Although talc has been used most frequently to induce pleurodesis, reports of death due to acute respiratory failure have raised concerns about the safety of this agent. Tetracycline, an effective alternative used in the past, is no longer commercially available. This agent has been substituted with derivatives of tetracycline, such as minocycline and doxycycline with success rates similar to those with tetracycline. Several antineoplastic agents have been injected into the pleural space with the aim of producing pleural symphysis, the most representative of this group being bleomycin.Recent knowledge of the molecular mechanisms involved in pleural inflammation has brought into focus new substances, such as transforming growth factor β and vascular endothelial growth factor, which may be used as pleurodesis agents in the future. Nevertheless, more studies are necessary to better define the potential of these substances in the induction of pleural symphysis.Ideally, a sclerosing agent should be cost-effective, available worldwide and easily administered. Talc will probably stand as the preferred agent to be used for pleurodesis in malignant pleural effusion because of its efficacy, easy manipulation and handling. However, further investigation is necessary to minimize adverse effects related to talc.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

BackgroundThe efficacy and safety of Symbicort®1(budesonide and formoterol in a single inhaler) were compared with those of a high dose of the commonly used corticosteroid fluticasone propionate in patients with moderate persistent asthma.MethodsThis randomized, double-blind, double-dummy, parallel-group study involved 373 patients with asthma (mean age 42 years; FEV178% of predicted; reversibility 21%). After a 2-week run-in period, during which patients received budesonide 200μg twice daily, they were randomly assigned to treatment with either Symbicort®Turbuhaler®(budesonide/formoterol 160/4.5μg, one inhalation twice daily) or Flovent®/Flixotide®Diskus™ (fluticasone propionate 250μg twice daily) for 12 weeks.ResultsSignificantly greater increases in morning PEF, the primary efficacy variable, were observed in patients treated with budesonide/formoterol compared with fluticasone propionate (27.4 L/min vs 7.7 L/min; p < 0.001). Evening PEF and clinic FEV1also favored budesonide/formoterol compared with fluticasone propionate (p < 0.001), as did use of reliever medication (p = 0.04) and the proportion of reliever-free days (p < 0.001). There were also numerical improvements in symptom-free days (60.4% vs 55.5%), night-time awakenings (7.9% vs 9.6%) and asthma-control days (57.8% vs 52.4%) in favor of budesonide/formoterol. The risk of an exacerbation was reduced by 32% in the budesonide/formoterol group compared with the fluticasone propionate group (p < 0.05). Both treatments were well tolerated.ConclusionSymbicort®(budesonide/formoterol in a single inhaler) was more effective than a high dose of fluticasone propionate in improving lung function, reducing use of reliever medication and improving control of moderate persistent asthma.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Respiratory Medicine is a vast and evolving area for researchers, primary care physicians and specialists. To help keep you up-to-date with the latest advances worldwide on all aspects of drug therapy and management of respiratory disorders, this section of the journal brings you information selected from the drug therapy reporting serviceInpharma Weekly1. The following reports are selected from the latest issues, summarizing the most important research and development news, clinical studies, treatment guidelines, pharmacoeconomic and adverse reaction news, and expert opinion pieces published across a broad range of literature sources.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS