Short Course Of Therapy Research Articles

Short-Course Therapy with Rifampin plus Isoniazid, Compared with Standard Therapy with Isoniazid, for Latent Tuberculosis Infection: A Meta-analysis

A major difficulty associated with the use of standard therapy with isoniazid for latent tuberculosis infection is poor patient adherence to therapy because of the prolonged course required. Shorter courses of therapy involving > or =2 drugs have been proposed as an alternative to standard therapy, but they have not undergone enough testing. We performed a meta-analysis to determine the equivalence of daily short-course therapy with rifampin plus isoniazid for 3 months and standard therapy with isoniazid for 6-12 months. The end points that were evaluated were development of active tuberculosis, severe adverse drug reactions, and death. We searched published information in the Cochrane Library, MEDLINE, and Embase databases, as well as unpublished information in the Cambridge Scientific Abstracts Internet database, Conference Papers Index, AIDS and Cancer Research Abstracts, and ClinicalTrials.gov. We also scanned the reference lists of articles. We only included trials in which individuals were randomly allocated to receive treatment. Two reviewers independently applied the criteria for trial selection, assessed trial quality, and extracted data. Five trials comprising 1926 adults from Hong Kong, Spain, and Uganda were identified. The mean duration of follow-up varied from 13 to 37 months. Overall, development of active tuberculosis was equivalent in association with both regimens (pooled risk difference, 0%; 95% confidence interval [CI], -1% to 2%; percentage of total variation across the studies that is the result of heterogeneity rather than chance [I2], 0%; P=.86). Severe adverse effects were reported with a similar frequency for both regimens (pooled risk difference, -1%; 95% CI, -7% to 5%) but with statistically significant heterogeneity detected (I2, 78%; P=.001). However, a subanalysis of high-quality trials (including 74% of the sample size) suggested that both regimens were equally safe. In 3 trials (comprising 1390 patients) that provided data on mortality, the regimens showed equivalence (pooled risk difference, -1%; 95% CI, -4% to 2%; I2, 2.7%; P=.38). Short-course therapy with rifampin plus isoniazid was equivalent to standard therapy with isoniazid in terms of efficacy, the proportion of severe side effects that occurred, and mortality.

Short-Course Antimicrobial Therapy for the Treatment of Pneumonia

Duration of antimicrobial therapy for the treatment of pneumonia has been inconsistent and is typically at the discretion of the prescriber. Themost common durations of therapy are 7, 10, or 14 days, but courses of 14 days or longer have also been used. Newer data support the use of clinical data to identify resolution of infection, such as defervescence, normalizing white blood cell count, and absence of infiltrate on chest radiograph. Discontinuation of antimicrobials 48 to 72 hours after such clinical resolution may allow for shorter courses of therapy with equivalent efficacy as the more arbitrary end points of 7 to 14 days. The intent of this article is to review the rationale, potential benefit, and relevant studies pertaining to the use of short-course antimicrobial regimens for the treatment of community-acquired and ventilatorassociated pneumonia.

Telithromycin: A Novel Agent for the Treatment of Community-Acquired Upper Respiratory Infections

The ketolides are a new subclass of macrolides, and telithromycin is the first of these agents to be approved. Modifications to the basic macrolide structure result in enhanced activity against penicillin- and erythromycin-resistant respiratory pathogens. It is therefore an option in the treatment of mild to moderate community-acquired respiratory infections, such as pneumonia, acute exacerbations of chronic bronchitis, pharyngitis/tonsillitis, and sinusitis. Telithromycin also offers the advantages of once-daily dosing and a shorter course of therapy in certain infections. Comparative clinical trials, although limited and involving only a small number of resistant organisms, showed the equivalence of telithromycin to existing therapies, although telithromycin generally had a higher frequency of mild to moderate gastrointestinal adverse effects. Further clinical and safety data, especially in patients with resistant organisms, are needed.

Personality Disorders Over Time: Precursors, Course, and Outcome

Personality Disorders Over Time: Precursors, Course, and Outcome

Once-daily ofloxacin otic solution for otitis externa

Problem: To evaluate the efficacy and safety of a 7-day regimen of ofloxacin otic 0.3% solution administered once daily to treat otitis externa (OE). Methods: This was an open-label, multicenter, multinational study (involving 58 sites in the U.S. and Central America). Ofloxacin otic 0.3% solution was administered once daily for the treatment of OE in patients over 6.0 months of age with stable or exacerbating OE of more than 2-weeks’ duration. Five drops were instilled once daily in each infected ear of 196 patients aged 6.1 months to 12 years (mean ± SD = 8.1 ± 3.3 years), and 10 drops in the ears of 294 patients 13 years and older (35.6 ± 16.0 years). Secretion or exudate specimens were obtained for microbiological analysis. Results: After 7 days of therapy, 298 of 439 clinically evaluable patients (67.9%) were considered cured and 121 (27.6%) clinically improved. At a follow-up visit 710 days later, 398 (90.7%) were considered clinically cured. Forty-three bacterial species were isolated from 253 patients who were clinically and microbiologically evaluable. Overall pathogen eradication rate was 95.7%. The most commonly isolated pathogen, Pseudomonas aeruginosa, was eradicated in 153/158 patients (96.8%). Staphylococcus aureus was eradicated in 31/32 patients (96.9%). No serious adverse events occurred during the study. The most commonly reported nonserious adverse event (11.2% of patients) was a transient increase in earache. Conclusion: Ofloxacin otic 0.3% solution is a safe and effective treatment for OE when administered once daily for 7 days. Significance: Fewer daily dosing and shorter course of therapy will enhance adherence to treatment. Support: None reported.

New approaches and therapeutic modalities for the prevention and treatment of recurrent HCV after liver transplantation

1. The currently available interferon-based therapeutic regimens are not optimal for the treatment of recurrent hepatitis C after liver transplantation. 2. Many patients have contraindications to use of the drugs, dose reductions limit exposure to effective doses in most patients, and the therapy is labor intensive for the transplantation staff. 3. Better strategies are needed to control hepatitis C virus infection in the transplantation setting. Aggressive treatment of infected patients before they develop cirrhosis or hepatic decompensation may eliminate the need for transplantation in some and reduce the chance for posttransplantation recurrence in others. 4. Infusions of neutralizing antibodies or short courses of therapy with potent antiviral drugs in the peritransplantation period may reduce the chance of infection of the graft. 5. New antiviral strategies, including use of oligonucleotides and viral enzyme inhibitors, may prove useful in the future, but these agents are just beginning to be tested in clinical trials in human beings.

Short‐course therapy with imiquimod 5% cream for solar keratoses: A randomized controlled trial

A dual-centre, randomized, double-blind, vehicle-controlled study was conducted to evaluate the safety and efficacy of short courses of therapy with imiquimod 5% cream in clearing >/=75% of baseline solar keratoses (SK) within a field of treatment. Subjects with 5-15 baseline SK within one treatment area (scalp, forehead and temples, or both cheeks) were randomized to apply imiquimod or vehicle cream to the entire treatment area three times a week for 3 weeks. Subjects were assessed 4 weeks after completing the first course for clearance of lesions. Subjects with <75% clearance were commenced on a second 3-week course of study cream. Subjects with >/=75% clearance were followed up until study completion without further therapy. All subjects were evaluated at the study endpoint of 14 weeks after initiating therapy for assessment of the primary outcome (>/=75% clearance of baseline solar keratoses). Twenty-one out of 29 (72%) imiquimod-treated subjects cleared >/=75% of baseline lesions compared with 3/10 (30%) subjects using the vehicle cream (Fisher's exact test, P = 0.027). Imiquimod was well tolerated. The present study has a short follow-up endpoint, but suggests that imiquimod is a potential therapeutic alternative in patients with SK.

New approaches and therapeutic modalities for the prevention and treatment of recurrent HCV after liver transplantation.

1. The currently available interferon-based therapeutic regimens are not optimal for the treatment of recurrent hepatitis C after liver transplantation. 2. Many patients have contraindications to use of the drugs, dose reductions limit exposure to effective doses in most patients, and the therapy is labor intensive for the transplantation staff. 3. Better strategies are needed to control hepatitis C virus infection in the transplantation setting. Aggressive treatment of infected patients before they develop cirrhosis or hepatic decompensation may eliminate the need for transplantation in some and reduce the chance for posttransplantation recurrence in others. 4. Infusions of neutralizing antibodies or short courses of therapy with potent antiviral drugs in the peritransplantation period may reduce the chance of infection of the graft. 5. New antiviral strategies, including use of oligonucleotides and viral enzyme inhibitors, may prove useful in the future, but these agents are just beginning to be tested in clinical trials in human beings.

Cutaneous infections in the elderly: diagnosis and management.

Over the past several years there have been many advances in the diagnosis and treatment of cutaneous infectious diseases. This review focuses on the three major topics of interest in the geriatric population: herpes zoster and postherpetic neuralgia (PHN), onychomycosis, and recent advances in antibacterial therapy. Herpes zoster in adults is caused by reactivation of the varicella-zoster virus (VZV) that causes chickenpox in children. For many years acyclovir was the gold standard of antiviral therapy for the treatment of patients with herpes zoster. Famciclovir and valacyclovir, newer antivirals for herpes zoster, offer less frequent dosing. PHN refers to pain lasting > or = 2 months after an acute attack of herpes zoster. The pain may be constant or intermittent and may occur spontaneously or be caused by seemingly innocuous stimuli such as a light touch. Treatment of established PHN through pharmacologic and nonpharmacologic therapy will be discussed. In addition, therapeutic strategies to prevent PHN will be reviewed. These include the use of oral corticosteroids, nerve blocks, and treatment with standard antiviral therapy. Onychomycosis, or tinea unguium, is caused by dermatophytes in the majority of cases, but can also be caused by Candida and nondermatophyte molds. Onychomycosis is found more frequently in the elderly and in more males than females. There are four types of onychomycosis: distal subungual onychomycosis, proximal subungual onychomycosis, white superficial onychomycosis, and candidal onychomycosis. Over the past several years, new treatments for this disorder have emerged which offer shorter courses of therapy and greater efficacy than previous therapies. The treatment of bacterial skin and skin structure infections in the elderly is an important issue. There has been an alarming increase in the incidence of gram-positive infections, including resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant pneumococci. While vancomycin has been considered the drug of last defense against gram-positive multidrug-resistant bacteria, the late 1980s saw an increase in vancomycin-resistant bacteria, including vancomycin-resistant enterococci (VRE). More recently, strains of vancomycin-intermediate resistant S. aureus (VISA) have been isolated. Gram-positive bacteria, such as S. aureus and Streptococcus pyogenes are often the cause of skin and skin structure infections, ranging from mild pyodermas to complicated infections including postsurgical wound infections, severe carbunculosis, and erysipelas. With limited treatment options, it has become critical to identify antibiotics with novel mechanisms of activity. Several new drugs have emerged as possible therapeutic alternatives, including linezolid and quinupristin/dalfopristin.

The effect of aerial parts of Echinacea on the circulating white cell levels and selected immune functions of the aging male Sprague–Dawley rat

Echinacea is one of the most widely used over-the-counter herbal preparations that purport to “improve immune system function”, especially when taken as a short course of therapy (6–8 weeks). Since many purchasers are older individuals, a double-blind, placebo-controlled study was performed to investigate whether Echinacea could affect total and differential white cell counts, phagocytic activity and interleukin (IL-2) levels in 12-month-old, healthy, male Sprague–Dawley rats when administered over an 8-week period. Echinacea (50 mg/kg of aerial parts) mixed with peanut butter or peanut butter alone was fed to 16 rats, which were receiving regular food and water ad libitum. Cell counts and immune functions were determined on rat tail vein blood on a weekly basis. Echinacea significantly increased circulating total white cell counts during the first 2 weeks of administration, and IL-2 levels during the final 5 weeks of the study period ( p<0.05). Differential counts were altered during the entire 8-week study, with mononuclear cells significantly increased to the detriment of granulocytes ( p<0.05). No such changes were observed in animals given peanut butter alone. No difference was observed in phagocytic function between animals given Echinacea or peanut butter alone. These studies suggest that aerial components of Echinacea affect both mononuclear cell levels and circulating IL-2 levels in older animals.

Adjuvant therapy in lymph node–positive colon cancer: Current standards and future perspectives

Abstract The significant survival benefit for adjuvant chemotherapy after a curative resection for node-positive colon cancer has been established for over a decade. The first major step in progression, from randomized trials that failed to demonstrate benefit for postoperative single-agent fluorinated pyrimidines, came with intensive immunobiochemical modulation of 5-fluorouracil for a 1-year course. Subsequent trials confirmed equivalent benefit for a shorter course of therapy, and additional improvement in disease-free and overall survival has been sought through employment of alternative modulatory agents or drug administration schedule changes. Newer cytotoxic agents, whose mechanisms of action differ from that of the fluorinated pyrimidines, have been examined in combination with 5-FU, and changes in recommendations for standard of care, based on results of these maturing data sets, are awaited. The impact of tumor molecular profiles on therapeutic prediction and rational design of new agents is expected to inform the design of future generations of clinical trials. Copyright 2002, Elsevier Science (USA). All rights reserved.

Deep Venous Thrombosis and Pulmonary Embolism.

Venous thromboembolic disease, including deep venous thrombosis (DVT) and pulmonary embolism (PE), is an under-diagnosed and under-appreciated medical problem that results in significant patient morbidity and mortality. Inadequate venous thromboprophylaxis in surgical as well as medically ill patients results in DVT and PE that negatively impact patient outcomes and increase health-care costs. A high index of clinical suspicion combined with an evidence-based use of diagnostic tests helps identify patients with acute thrombosis. Failure to accurately and promptly diagnose and treat DVT and PE can result in excess morbidity and mortality due to postthrombotic syndrome, pulmonary hypertension, and recurrent thrombosis. Conversely, unnecessary anticoagulation provides risk in the absence of any tangible benefit. The immediate commencement of parenteral anticoagulant therapy with intravenous unfractionated heparin or a subcutaneous low molecular weight heparin (LMWH) upon presentation with DVT or PE (often even before objective diagnosis confirmation) is necessary to minimize propagation, embolization, and recurrence rates. We favor weight-based LMWH therapy in most of our patients with DVT because of the ability to treat exclusively or primarily in the outpatient setting. We still admit patients with PE for a minimum duration of 2 days for close observation. Subsequent conversion to oral anticoagulation with warfarin (target INR of 2.0 to 3.0 in most patients) should include an overlap with parenteral therapy of at least 4 to 5 days and until a stable target INR has been achieved. A minimum of 3 to 6 months of anticoagulation is recommended following a first episode of idiopathic DVT and any PE. A shorter course of therapy may be sufficient following a situational (eg, after surgery and postpartum) or calf DVT. Long-term, and at times lifelong, therapy should be considered in patients with thrombosis in the setting of a persistent acquired or inherited hypercoagulable state. Thrombolytic therapy probably should be reserved for young patients with iliofemoral DVT, any patient with a threatened limb due to impending venous limb gangrene, and those with PE who have objective evidence of cardiopulmonary compromise. Unfavorable risk-to-benefit and cost-to-benefit ratios make more extensive use of thrombolytics undesirable. The prevention of the postthrombotic syndrome with fitted, graduated compression garments and age- and gender-appropriate cancer screening are indicated in all patients with DVT in an attempt to minimize morbidity and mortality. Hypercoagulable state testing is indicated when the results of individual tests will significantly impact the choice of anticoagulant, intensity of therapy, therapeutic monitoring, family screening, family planning, prognosis determination, and most of all, duration of therapy.

Brief treatment of complicated PTSD and peritraumatic responses in a client with repeated sexual victimization

The present case study describes the successful treatment of a woman with a history of sexual, physical, and psychological abuse in childhood and multiple rapes in adulthood, utilizing a relatively brief cognitive-behavioral treatment, Cognitive Processing Therapy (CPT). Treatment addressed assault-related PTSD, major depression, suicidality, compulsive self-harm behaviors, and primary and secondary dissociative responses. Treatment also addressed related issues of low self-esteem, social isolation, and the client's sense of helplessness, which had resulted in her failure to implement active self-protection strategies. Client symptomatology was tracked throughout treatment using the PTSD Symptom Scale (PSS) and the Beck Depression Inventory (BDI) at regular intervals over the course of 34 sessions and for 3 months posttermination. The relatively short course of therapy (22 weeks) and treatment strategies are described, including cognitive and behavioral components of CPT, supportive strategies, safety planning in the context of ongoing threats and victimization, and the importance of the therapeutic relationship. Particular emphasis is given to adaptation of the brief treatment to complex symptomatology and patterns of symptomatic change in relation to cognitive and behavioral intervention. Findings indicate that treatment for individuals with extensive victimization histories does not require different strategies or a significantly longer period of treatment than does treatment for those with a single traumatic experience.

Acute pulmonary toxicity after low-dose amiodarone therapy

Amiodarone-induced pulmonary toxicity is usually seen in cardiac surgical patients who have received large doses of amiodarone for ventricular arrhythmias over prolonged periods. In this report, we describe a case of amiodarone-induced pulmonary toxicity after a short course of therapy for postoperative atrial fibrillation.

Issues in the treatment of Mycobacterium tuberculosis in patients with human immunodeficiency virus infection.

The HIV/AIDS pandemic has led to a rise in the incidence of tuberculosis and an epidemic of co-infection in many developing countries. Treatment of Mycobacterium tuberculosis in persons with HIV infection presents several challenges to the clinician particularly in resource-poor countries. As will be discussed in this paper diagnosis of latent tuberculosis relies on tuberculin skin testing which has poor sensitivity and reproducibility in immunocompromised patients. The World Health Organization (WHO) recommends treatment of active tuberculosis as the primary means of global tuberculosis control. In practice treatment of active tuberculosis typically requires that a symptomatic patient self-report to a health service for evaluation and management. Even if this approach to tuberculosis control were sufficient many logistic and clinical problems remain involving tuberculosis diagnosis and therapy in the patient with HIV/AIDS. Recognizing the significant clinical and public health challenges surrounding the treatment of tuberculosis in patients with HIV infection this paper will address a number of issues relevant to the care of co-infected patients. These include current guidelines for the treatment of active tuberculosis as well as the diagnosis and treatment of latent tuberculosis in HIV-positive patients. The paper concludes with a discussion of promising new drugs for tuberculosis treatment. (excerpt)

Candiduria: When and how to treat it

The clinical finding of candiduria is often an enigmatic problem for the evaluating physician. The significance of yeast in the urine can range from procurement contamination to a sign of a life-threatening, opportunistic fungal infection. Proper evaluation requires validation of funguria, consideration of the setting in which it occurs, and the status of the patient. Provided that the patient is clinically stable, asymptomatic candiduria usually need not be treated with an antifungal agent. Rather, management should be directed at the elimination of predisposing factors, if feasible. When treatment is required, appropriate agents include amphotericin B (AmB), various lipid preparations of AmB (L-AmB), azoles, and flucytosine. Parenteral AmB is most useful against life-threatening infections in which the urinary tract is but one component of a widespread infection, or when resistant Candida are causative. Shorter courses of therapy may be preferable in certain cases. L-AmB treatment has been less sucessful. Intravesical AmB is a time-honored approach, but is best employed diagnostically rather than therapeutically. Fluconazole is presently the agent of first choice for susceptible fungi, but dosage and duration of therapy have not been established. Flucytosine is a useful alternative, especially for resistant Candida, but its toxicity must be closely monitored.

Current Management of Onychomycosis and Dermatomycoses.

Three newer oral antifungal agents, itraconazole, terbinafine and fluconazole, have revolutionized treatment of superficial mycoses. The tissue pharmacokinetics of itraconazole and terbinafine allow much shorter courses of therapy- with higher efficacy-in the treatment of onychomycosis, compared to other oral agents. Itraconazole pulse dosing and terbinafine daily dosing have shown comparable efficacy against dermatophyte onychomycosis; similar itraconazole regimens have been effective against nondermatophyte infections. Refractory clinical patterns of nail disease appear to be more responsive to oral antifungal therapy when combined with adjunctive therapy, such as debridement. These agents are effective against cutaneous dermatophytosis, with shorter treatment regimens. Tinea versicolor may be treated with a single-dose, intermittent, or daily regimen of an oral azole agent, depending on the drug selected. These newer oral antifungal agents have been proven effective against tinea capitis; effective regimens are shorter than those for griseofulvin. The safety profile of these newer agents has been very favorable.

Effect of corticosteroids on elevated intracellular sodium, plasma lipid peroxide levels and reduced Na(+), K(+)-ATPase activity in patients of bronchial asthma.

In view of several reports that there is a lack of balance in free radicals in case of bronchial asthma (1) the effect of free radicals on cell membrane was studied by estimating the membrane bound protein Na(+), K(+)-ATPase activity and the intracellular sodium level in patients of bronchial asthma before and after a short course (one week) of oral corticosteroid (prednisolone 0.75-1mg/kg body weight) therapy. Results showed that there is a definite statistically significant rise in free radical level and intracellular sodium level and a significant lowering of Na(+), K(+)-ATPase activity in case of untreated bronchial asthma. After short course of therapy with oral corticosteroids, the free radical level and intracellular sodium level decreased significantly, together with a significant rise of the Na(+), K(+)-ATPase activity. Also, a significant negative correlation (r=-0.74) between the lipid peroxide level and the Na(+),-K(+)-ATPase activity was found in these cases.

Newer fluoroquinolones and the management of respiratory tract infections.

Infections of the respiratory tract remain one of the leading causes of death in the United States [1]. The cost burden for bacterial infections of the upper and lower respiratory tract is tremendous; the cost alone of treating patients with communityacquired pneumonia (CAP) has recently been estimated to be close to $10 billion (US) [2]. In addition, the emergence of drugresistant pathogens presents a challenge to infectious disease clinicians. Several common respiratory tract pathogens, including Streptococcus pneumoniae and Haemophilus influenzae, have shown a progressive tendency to develop resistance to both b-lactam and non‐b-lactam antibiotics. National and international multicenter surveillance programs have been tracking the prevalence and patterns of antimicrobial resistance among respiratory tract pathogens. At the local level, these surveillance programs can be used to help guide therapeutic decisions. Newer antimicrobials for the treatment of CAP, such as the newer fluoroquinolones, offer significant advantages over existing agents, including a broader spectrum of activity, improved safety, higher bioavailability, and reduced resistance potential. These agents may also offer shorter courses of therapy, enhanced patient compliance, and potential economic savings. The newer fluoroquinolones, which have been engineered to exhibit enhanced gram-positive activity while maintaining gram-negative activity, are frequently active against resistant bacterial strains. There are 2 means by which bacteria can become resistant to fluoroquinolones: mutations in 1 or both of fluoroquinolone enzyme targets and overexpression of multidrug efflux pumps. Each fluoroquinolone has different relative activities against the enzymes, which may also vary with the type of pathogen. Enzyme targets may be more susceptible to the newer fluoroquinolones, thereby decreasing the likelihood of bacterial resistance. Knowledge of these variations is important in selecting the appropriate dosage regimen for clinical care. The discovery of multiple drug‐resistant S. pneumoniae (DRSP), which is defined as having reduced susceptibility to >2 antibacterials, has heightened the interest in fluoroquinolones. Some formerly potent antipneumococcal agents, such as the b

Brief therapy for children's mental health problems: outcomes in a rural setting.

In rural areas where specialist services are not readily accessible, there are practical advantages to providing short courses of therapy for children's mental health problems. Fifty-five parents from a rural area in South Australia completed questionnaires before and 3 months after receiving brief, family-oriented therapy from a child and adolescent mental health service. Clinically, these families were assessed as being suitable for brief therapy because the children had moderately severe emotional and behavioural problems and the families were not severely dysfunctional. The screening process sought to exclude more serious and complex presentations so those families were not included in the current study. Questionnaires measuring the severity of children's mental health problems (Child Behavior Checklist) and the degree of family dysfunction (Family Assessment Device general functioning subscale) suggested that, on average, the sample met these entry criteria. The follow-up evaluation after brief therapy found significant overall improvement in the Child Behavior Checklist scores, however some children continued to show substantial difficulties. Parents' satisfaction with therapy was related to these scores after treatment. The results suggest that brief therapy was appropriate for most of the families and that routine follow-up could help determine those who might benefit from further assistance.