Which patients with hepatitis C virus should be treated?

Since the National Institutes of Health (NIH) Consensus Conference in 1997, our understanding of the natural history of hepatitis C (HCV) infection and our ability to treat patients has improved. Thus, a large number of clinical studies, confounding terminology, and a growing dilemma in targeting particular populations for treatment who have HCV infection, will continue to be at the forefront of clinical research and treatment. In this report, we examine which HCV-infected populations of patients should be treated. Beginning with treatment guidelines from the NIH Consensus Conference, and a brief overview of the terminology used in the HCV literature, we subsequently review data regarding treatment outcomes based on HCV viral load, genotype, and various epidemiological factors. Similarly, more challenging treatment strategies are discussed for patients with HCV infection, including those with ongoing psychiatric disorders, patients who are coinfected with the human immunodeficiency virus and HCV, and those patients with normal serum transaminases. Finally, a review and guidelines about other HCV treatment dilemmas, including patients with chronic renal failure on hemodialysis, patients who have undergone renal transplantation, and treatment of patients acutely exposed to HCV are also addressed.     

How should patients 80 years of age or older with colorectal carcinoma be treated?

PURPOSE: The aim of this study was to determine how extensive resection affects operative morbidity, mortality, and long-term survival in elderly patients with colorectal cancer. METHODS: A total of 119 patients 80 years of age or older were given a diagnosis of colorectal carcinoma at our hospital between 1985 and 1997. Eleven patients who did not undergo surgery were excluded. The remaining 108 patients underwent laparotomy and were reviewed. Serum levels of interleukin-6 were measured perioperatively in 22 patients to assess the degree of operative stress. RESULTS: Potentially curative resection was performed in 64 (88.9 percent) of the 72 patients in the active performance status group and 13 (36.1 percent) of the 36 patients in the sedentary performance status group (P < 0.001). The in-hospital mortality rate was 8.3 percent in group the active performance status group and 38 percent in the sedentary performance status group (P = 0.007). Patients in the sedentary performance status group and those who underwent emergency operations had higher levels of IL-6 than patients in the active performance status group or those who underwent elective operations. CONCLUSIONS: Preoperative performance status, operative curability, and tumor stage have a significant impact on outcome in patients with colorectal cancer who are 80 years of age or older. Knowledge of early postoperative response of IL-6 is useful in predicting postoperative mortality and morbidity in this subgroup of patients.     

Cardiovascular disease in lupus patients: should all patients be treated with statins and aspirin?

Premature coronary heart disease (CHD) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). In certain age groups, the risk can be >50 times that of an age-matched population. This population also has an increased prevalence of several key classic risk factors that contribute to the CHD development. Chronic inflammation, anti-phospholipid antibodies and exposure to steroid therapy are also likely to have an impact. We have adopted a proactive approach to classic risk factor management with 'ideal targets' based on viewing SLE as a CHD equivalent condition. In this context, a significant proportion of SLE patients (approximately 30%) will require statins and the majority would be treated with aspirin prophylaxis. Better control of the underlying inflammatory disease is also likely to play an important role and the relative safety of anti-malarials allows their consideration as an adjunct in a large proportion of patients. Well-conducted clinical trials are now needed to advance beyond these initial recommendations.     

Where should adolescents with ALL be treated?

Currently, 50% of adolescents with ALL are treated by adult teams and 50% by paediatric teams (following either adult or paediatric protocols). The aim of this paper is to review the results obtained with first-line chemotherapy and with haematopoietic SCT (HSCT) in adolescents with ALL. Disease biology and host factors are responsible for the differences observed between adolescents and other age categories. The outcome of adolescents with ALL after first-line chemotherapy is poorer as compared with children, although better as compared with adults. Recent studies have shown that adolescents who were enrolled in paediatric trials achieved better results than those who were enrolled in adult trials. This is most likely because of several differences, including protocol design, dose intensity and use of HSCTs, as well as better compliance to treatment and better supportive care. Disparities in the attitude towards treatment between paediatric and adult wards might also contribute to the better outcome that is observed in paediatric institutions. Indications for HSCT in children with ALL are well defined by international protocols. Only very high-risk paediatric patients are eligible for HSCT in CR1, whereas in adult trials, allogeneic or autologous HSCT are frequently offered, even to standard-risk patients in CR1. The outcome of adolescents given HSCT is poorer than in children, though better than in adults. Improving both psychosocial support during therapy and physical exercise habits represent further challenges for teams involved in the treatment of adolescents. Cooperation between paediatric and adult haematologists would surely improve the ability to recruit as many patients as possible and would promote progress in the research on adolescents. In conclusion, redefining age limits according to risk-based strategies, as well as encouraging multi-centre cooperation, should be taken into consideration to improve the outcome of this age category. Adolescents should be referred to research treatment teams that have experience in the management of paediatric ALL and they should be enrolled in international cooperative studies.     

Asymptomatic bacteriuria. Which patients should be treated?

Asymptomatic bacteriuria is common in both the community nursing home and hospital settings. Few data, however, are available about the potential complications arising from asymptomatic bacteriuria (eg, the development of symptomatic infection and renal damage) for various patient populations and for various medical conditions. On the basis of data in the literature, we believe that neonates and preschool children with asymptomatic bacteriuria should be treated. Pregnant women and "nonelderly" (less than 60 years old) men should be treated. We do not think that school-age children, nonpregnant, nonelderly women, or elderly men and women need antimicrobial treatment if their urinary tracks are normal. In addition, antimicrobial treatment is recommended for patients with asymptomatic bacteriuria and abnormal urinary tracts and those undergoing clean intermittent catheterization, genitourinary manipulation, or instrumentation. Patients with long-term indwelling catheters should not be treated. The treatment of asymptomatic bacteriuria in patients with short-term indwelling catheters and those with ileal conduits is controversial. These treatment recommendations should not necessarily be accepted as the standards of practice, since treatment is often controversial due to the lack of published data describing the natural course of asymptomatic bacteriuria in various patient populations.     

Hypertriglyceridemia-why, when and how should it be treated?

Summary The relationship between serum triglyceride levels and cardiovascular disease has remained enigmatic despite four decades of research. The majority of the available evidence tends to support the role of hypertriglyceridemia as an independent risk factor for cardiovascular disease. However, there are no guidelines recommending a target triglyceride level for prevention of cardiovascular disease. The focus of lipid lowering therapy still remains the reduction of global cardiovascular risk by optimizing LDL cholesterol levels. Therapeutic options for triglyceride-lowering include lifestyle modification and pharmacological agents, such as fibrates, omega 3 fatty acids and niacin. Post-hoc analyses of the Helsinki Heart Study, Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial and Bezafibrate Infarction Prevention Study suggest a beneficial effect of the treatment of hypertriglyceridemia with fibrates, mainly in obese subjects with insulin resistance. However, in order to establish the actual clinical relevance of lowering triglyceride levels, prospective trials need to be conducted with the specific purpose of studying the effects of triglyceride reduction on clinical end points, i. e. coronary events and stroke.      

Survey of the negativation of bacteriologic tests in patients with active pulmonary tuberculosis: how long should the isolation be?

The risk of contamination by contact with patients with tuberculosis is reduced by isolation of patients until negativation of direct sputum analysis for the research of tuberculosis bacilli. To evaluate the efficacy of this isolation, we compared, in 32 patients with active tuberculosis, the results of direct examination and culture of the sputum and the clinical outcome. Thirty-two successive patients hospitalized in the same internal medicine unit, received antituberculosis drugs and had 3 sputum examinations per week with direct analysis and culture until negativation of the 3 direct examinations. Then, isolation ended. At the time of direct-negativation, 14 of the 32 patients kept positive cultures. In the 18 remaining subjects, the cultures became negative, about seven days before direct-negativation. Patients with negative cultures had more frequently weight increase (83% versus 71%), were more rapidly without fever (11 days versus 19 days), had less cough and had less severe radiologic disease (50% versus 75%) compared to patients with positive cultures but these differences were not statistically significant due to the small sample size. In tuberculosis patients, 3 successive negative direct sputum examinations do not eliminate the risk of tuberculosis transmission, specially to hospitalized or immunocompromised patients. The risk of contamination in these cases, although unknown, may be weak. Terminating isolation should not be based on sputum examination alone, but also on other factors such as the clinical course (resolution of cough and fever, weight), the initial number of bacilli, and the severity of the radiological lesions.     

What is healthcare-associated pneumonia, and how should it be treated?

PURPOSE OF REVIEW: In contrast to patients at risk for hospital-acquired pneumonia or mechanically ventilated patients at risk for ventilator-associated pneumonia, healthcare-associated pneumonia is a relatively new clinical entity that includes a spectrum of adult patients who have close association with acute care hospitals or reside in chronic care settings that increase their risk for pneumonia caused by multi-drug-resistant bacteria. Multi-drug-resistant pathogens include methicillin-resistant Staphylococcus aureus and Gram-negative bacilli, such as Pseudomonas aeruginosa, extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, and Acinetobacter species. New guidelines for the management and prevention of hospital-acquired pneumonia, ventilator-associated pneumonia and healthcare-associated pneumonia from the American Thoracic Society and the Infectious Diseases Society of America were published in 2005 and are highlighted in this article. RECENT FINDINGS: Recent data indicate that types of multi-drug-resistant pathogens may vary in different healthcare settings, and that individuals infected with multi-drug-resistant pathogens are more likely to receive inappropriate initial antibiotic therapy, which may result in poorer outcomes in terms of patient morbidity, mortality and increased length of hospital stay. SUMMARY: This review highlights key points in the new recommendations and principles for initiating, de-escalating and stopping antibiotic therapy in individuals with healthcare-associated pneumonia. Widespread implementation of these guidelines is needed in healthcare institutions in order to reduce patient morbidity, mortality, and healthcare costs.