Treatment of tuberculosis: is our knowledge adequate?

Tuberculosis remains a global problem even after the excellent drugs available to cure it. Inappropriate and inadequate treatment leads to acquired drug resistance, which may result in treatment failure and spread of resistant organisms to other persons. Our study was aimed at finding out the current status of knowledge, attitude and practice of resident doctors and consultants medical institutes in two different parts of India. All the residents and consultants were given a questioner containing twenty questions based on WHO guidelines for treatment of tuberculosis and the positive responses were calculated. The results were tabulated in the form of percentage of correct responses to individual queries. 80 doctors responded by filling up the questioner. None of the respondents could correctly answer all 20 questions. Only four could answer more than 75% questions correctly and only 17 could answer at least 50% of the questions correctly. 17.5% respondents could not even answer 25% questions correctly. The details of answer to individual queries presents a dismal picture. This study looked at their present knowledge attitude and treatment practice of a very common but serious disease like tuberculosis and the inadequacy of our knowledge in this regards should make us think about reshaping our policies for managing tuberculosis.     

Does Depression Reduce the Effectiveness of Behavioral Weight Loss Treatment?

Limited evidence suggests that depression is associated with poorer outcomes in behavioral weight loss programs; however, people with major depression are typically excluded from weight loss intervention trials. This study examined the effect of depression on women's participation and weight loss in behavioral treatment. Non–treatment seeking obese women over 40 years of age with major depressive disorder (MDD, n = 65) and without MDD (n = 125) were recruited into a 26-session group intervention. Primary analyses compared participants' mean weight change from baseline to 6 and 12 months; at 6 months, women with MDD lost a mean of 3.8 kg vs 4.3 kg for women without MDD (t = 0.54, p = .59). At 12 months, women with MDD lost 3.0 kg and women without MDD lost 3.6 kg (t = 0.44, p =.66). Women who attended at least 12 treatment sessions lost more weight than women who attended fewer sessions, regardless of depression status (ie, there was no significant interaction between depression and session attendance). Results suggest that depression should not be an exclusion criterion for weight loss intervention programs.     

Treatment of autoimmune disease: time for a paradigm shift?

Current treatment of human autoimmune diseases (AIDs) was developed empirically and relies mostly on non-selective suppression of the immune system. Traditional non-selective immunosuppressants such as corticosteroids, cyclophosphamide, and methotrexate and more novel means such as monoclonal antibodies to CD3, CD4, or CD25 do not discriminate between pathogenic and beneficial T cells. Importantly, the severe side effects seen with current therapies are related to the fact that these treatments not only suppress the pathogenic disease-inducing cells, but also cells influential in combating infections and killing malignant cells. Severe infections and malignancies are the inevitable result of non-selective immune suppression. Many of the novel forms of therapy of AID were developed in experimental animals, and their translation to the human disease was associated with the revelation of unexpected and sometimes catastrophic side effects. These surprises underscore the major differences between the relative simplicity of the experimental model and the complexity of the human disease. How can this current state of treatment of AID be improved? Which principles should guide us in the design of new treatments? This review attempts to offer a new look at these questions.     

Treatment of severe forms of paracoccidioidomycosis: is there a role for corticosteroids?

Despite their immunosuppressive effects, corticosteroids have long been used as adjunct therapy (aCST) in the treatment of infectious diseases. The rationale is that in certain infections it is necessary to decrease the exacerbated host's inflammatory response, which can otherwise result in tissue damage and organ dysfunction. In fact, a major concern in treating paracoccidioidomycosis (PCM) is the host's intense inflammatory response to Paracoccidioides brasiliensis, which can be further intensified by antifungal therapy. Depending on its localization, this immunological phenomenon may be life threatening or result in permanent sequels, as is the case for some patients with cerebral or laryngeal involvement. However, the literature on aCST in paracoccidioidomycosis treatment is scarce and as a result we present our recent experience in the management of four patients with severe PCM manifestations, i.e., cerebral paracoccidioidal granuloma, laryngeal stenosis, compressive abdominal mass, and exacerbated inflammatory response with tissue destruction. In addition to the antifungal therapy, these patients required aCST, which probably promoted their clinical improvement and/or prevented serious complications. We suggest that aCST: (a) can potentially help in the management of selected cases of severe forms of PCM, particularly when there is a risk of acute complications, and (b) that it can be used safely provided that the risk-benefit ratio is carefully weighed. Well-controlled, prospective studies of aCST in the treatment of severe cases of paracoccidioidomycosis are needed to better define its role in the management of PCM.     

Treatment of Latent Tuberculosis Infection in HIV: Shorter or Longer?

Nine months of daily isoniazid is efficacious in treating latent M. tuberculosis infection, but completion rates are low, limiting treatment effectiveness. In 2011, three important studies were published involving novel regimens for the treatment of latent M. tuberculosis infection. At least 36 months of isoniazid was more effective than 6 months of isoniazid in one study, but not in another-both of which were conducted among tuberculin skin test positive HIV-infected adults living in high tuberculosis incidence settings. Three months of once-weekly isoniazid plus rifapentine or twice-weekly isoniazid plus rifampin (both given under direct observation) resulted in tuberculosis rates similar to those seen with 6 months of isoniazid among HIV-infected persons in high tuberculosis incidence settings. Three months of once-weekly, directly-observed isoniazid plus rifapentine was at least as effective as 9 months of daily isoniazid among predominantly HIV-uninfected persons living in low and medium tuberculosis incidence countries. The 3-month once-weekly isoniazid plus rifapentine regimen demonstrates promise for treatment of latent M. tuberculosis infection in HIV-infected persons.     

Is There a Role for Antibiotics in the Treatment of Asthma?

Emerging evidence suggests an association between some asthma and pulmonary infection by the atypical organisms Chlamydia pneumoniae and Mycoplasma pneumoniae, but a causal role for infection remains unproven and controversial. Most acute exacerbations of asthma are triggered by acute infections that are due to viral respiratory pathogens, not to bacteria or atypical organisms. Administration of antibiotics for acute exacerbations of asthma has been shown to be ineffective. Most evidence linking atypical infections to asthma is consistent with a promoting role for chronic infection in producing persistent asthma symptoms. Preliminary studies suggest that prolonged (>/=6 weeks) administration of doxycycline or macrolides may eradicate C. pneumoniae from respiratory secretions and improve long term, not acute, asthma symptoms. Randomised, controlled trials are currently under way to investigate the effectiveness of these prolonged courses of macrolides and azalides (roxithromycin, clarithromycin and azithromycin) in adults with stable persistent asthma. Traditional courses (7 to 10 days) of any antibiotic are incapable of eradicating chronic C. pneumoniae or M. pneumoniae infection; furthermore, beta-lactam and sulphonamide-based antibiotics that are commonly prescribed in acute respiratory syndromes are ineffective against these atypical organisms. Unless the goal is to treat documented sinusitis associated with asthma, it is inappropriate to prescribe traditional courses of any antibiotic for acute asthma exacerbations; whether longer courses of antibiotics should be prescribed to eradicate chronic atypical infections and decrease persistent asthma severity remains to be established.     

Could Hormones Make a Difference in the Treatment of Juvenile Rheumatoid Arthritis?

Adrenal androgens dehydroepiandrosterone (DHEA; prasterone) and its sulphated form (DHEA-S) are among the most abundant hormonal steroids in men and nonpregnant women. Deficiencies of these adrenal androgens are associated with autoimmune disorders such as rheumatoid arthritis (RA). Recent studies from our laboratory have also identified low levels of adrenal androgens in the serum and synovial fluid of patients with juvenile rheumatoid arthritis (JRA). These findings support and complement those already published for RA and other autoimmune diseases. Because of the paucity of data on the hormonal status of patients with JRA, studies on the relationship between hypoandrogenicity and predisposition to develop JRA, and/or disease progression have not been conducted. In addition, despite the rapid expansion of research in the clinical use of these adrenal androgens in hyperlipidaemia, atherosclerosis, obesity, diabetes mellitus, insulin resistance and hypertension, their potential beneficial effects in JRA/RA have not been fully investigated. In fact, clinical trials of adrenal androgens in RA have only been conducted for the treatment of systemic lupus erythematosus. Further studies using prospective approaches are necessary to provide a unified consensus on the hormonal status of patients with JRA (as well as those with RA). This overview of our knowledge of the putative role(s) of hormones in arthritis will hopefully stimulate researchers in basic science and rheumatologists to synergistically collaborate in the effective translation of such knowledge to new clinical approaches.     

Monitoring Treatment of Patients with Pulmonary Tuberculosis: Can PCR Be Applied?

To assess whether PCR is applicable for monitoring the efficacy of antituberculous treatment, respiratory specimens obtained during treatment and follow-up from sputum smear-positive tuberculosis (TB) patients were examined. First, results of smear, culture, and PCR for Mycobacterium tuberculosis complex (MTB) and an internal inhibition control (MCC) were correlated retrospectively on 1,601 respiratory specimens from patients with no previous cultures of MTB. MTB optical density (OD) values increased to a maximum level of 3.5 to 4.0, with both increasing numbers of acid-fast bacilli and CFU. MTB/MCC OD ratios also increased with both smear and culture grading and correlated significantly better with both than the MTB OD value. Second, changes in MTB OD values and MTB/MCC OD ratios were compared with microscopy and culture for MTB in monthly sputa obtained during treatment and follow-up in 22 smear-positive pulmonary TB patients. Declines in MTB/MCC OD ratios during antituberculous treatment and follow-up were observed. Patients with moderate disease reached the baseline after 6 to 8 months of standard antituberculous treatment regimen, whereas patients with extensive disease were predicted to reach the baseline 1 year or more after the initiation of treatment. Although PCR detects both dead and live bacteria, we believe that PCR can be used to assess the efficacy of antituberculous treatment since increases or slow reductions in MTB/MCC OD ratios would indicate nonoptimal treatment, noncompliance, reduced bioavailability of drugs, or resistant strains of MTB and thereby would identify patients at risk for treatment failure or reactivation.     

Assessing the Role of Treatment Manuals: Have They Become Necessary but Nonsufficient Ingredients of Change?

We argue that the controversies and ambivalence surrounding treatment manuals are in part due to three somewhat inconsistent functions that these manuals serve, or may soon be serving: (1) to provide detailed guidelines to clinicians, (2) to operationalize developmental steps in psychotherapy research programs, and (3) to serve as a list of options that might soon be guiding, and potentially dictating, treatment reimbursements. We also argue that although the slow pace of scientific development is at odds with the immediate needs of clinicians, the inconsistency between the first and second functions of treatment manuals is not a problem per se—it simply reflects the intrinsic dilemma underlying the Boulder model. A key problem, however, is the possibility that our current state of empirical knowledge might be used in the near future as the main basis for prescribing psychotherapy (i.e., the inconsistency between the second and third functions of manuals). Treatment manuals are described as necessary but nonsufficient tools that may be best used as the "first line of attack" in narrowly defined treatment conditions. The creation of a new task force is suggested to delineate such treatment conditions, to generate possible guidelines for addressing clinical situations that have not yet been empirically investigated, and to recommend future research directions to improve psychotherapy effectiveness. Finally, clinicians and researchers are encouraged to use a treatment strategy that has been empirically supported to entice third-party payers to fund future psychotherapy research.     

CRRT in Treatment of Severe Renal Failure

CLINICAL MATERIALS　　We have treated38severe renal failure patients with CRRT in recentyears,in-cluding1 6 patients with traumas or after operation,6 patients with epidemic hemor-rhagenic fever,3patients with hemolytic uremia,3patiens with septic shock,3pa-tients with Adams Syndrome caused by potassemia,2 patiens with cardiacrest,and5anothers.Complications36 hypotension,1 8cardiac function failure,7arrhythmia,5respiratory failure,1 5digestive tractbleeding.1 cerebral hemorrhage,5hydro…     

Will the Advent of Antileukotriene Therapy Lead to Changes in Asthma Treatment Guidelines?

Leukotrienes are bronchoconstrictor and pro-inflammatory mediators implicated in asthma. Drugs that block leukotriene synthesis or activity are set to become the first major breakthrough in asthma therapy for 25 years. Antileukotriene drugs block bronchoconstriction after challenge with allergen, aspirin or exercise, and in clinical trials in patients with asthma they improve baseline lung function, reduce night-time awakenings, improve daytime symptom scores and halve the number of acute exacerbations. They are likely to be used as oral prophylactic therapy to reduce the dosage of corticosteroids right across the spectrum of asthma severity. Further studies on possible long term anti-inflammatory effects are currently in progress.     

Does Hemopoietic Stem Cell Transplantation Have a Role in Treatment of Severe Rheumatoid Arthritis?

Based on animal models and limited clinical experience, there is considerable interest in use of high-dose immunosuppression followed by hemopoietic stem cell transplantation as treatment for severe rheumatoid arthritis. Because of its relatively low treatment-related mortality and morbidity, autologous transplantation is a more attractive option than allogeneic transplantation for initial clinical trials, even though anecdotal reports suggest that allogeneic transplantation has a greater likelihood of bringing about long-term disease control. The approach remains experimental with many unanswered questions such as the value and safety of high-dose therapy without transplantation, the need for T cell purging, the possible deleterious effects of post-transplant hemopoietic growth factors and the potential of mini allogeneic transplantation (a process whereby intense immunosuppression is combined with less intense myelosuppression). To achieve quick progress it is essential that clinical trials be carefully designed with all cases being reported to the Autoimmune Disease Stem Cell Project Database.