Standards, Options and Recommendations for the use of appetite stimulants in oncology (2000).
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Publications and source records attributed to J C Melchior.
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Infection by the human immunodeficiency virus (HIV) is characterized by progressive destruction of the immune system, which leads to recurrent opportunistic infections and malignancies, progressive debilitation and death. Malnutrition is one major complication of HIV infection and is recognized as a significant prognostic factor in advanced disease. Malnutrition is multifactorial and poorly treated during the course of HIV. Even if a standardized approach to the management of active weight loss has not been well established, early nutritional intervention is important in HIV infected patients to maximize gain of lean body mass. From early in the era of highly active antiretroviral therapy (HAART), an initial decreased incidence of malnutrition was noted only in western countries while a variety of changes in the distribution of body fat and associated metabolic abnormalities have been recognized under the banner of lipodystrophy.
The purpose of this study was to estimate the prevalence of malnutrition in outpatients on long-term oxygen therapy or home mechanical ventilation, to determine the relationships between malnutrition and impairment/disability and smoking and also to identify relevant tools for routine nutritional assessment. In 744 patients (M:F 1.68, aged 65+/-15 yrs) with chronic obstructive pulmonary disease (COPD, 40%), restrictive disorders (27%), mixed respiratory failure (15%), neuromuscular diseases (13%) and bronchiectasis (5%), body mass index (BMI), fat-free mass (FFM), serum albumin, transthyretin, 6-min walking test, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and blood gases were recorded. FFM was the most sensitive parameter for detecting malnutrition, being abnormal in 53.6% of patients, while BMI was <20 in 23.2%, serum albumin <35 g x L(-1) in 20.7%, and serum transthyretin <200 mg x L(-1) in 20%. FFM depletion predominated in neuromuscular, bronchiectasis and restrictive disorders. BMI and FFM were correlated with FEV1, FVC and 6-min walking test. In multivariate analysis a BMI<20 was related to FEV1 and smoking habits, and a low FFM to smoking, FEV1 and female sex. Malnutrition is highly prevalent in home-assisted respiratory patients and is related to causal disease, forced expiratory volume in one second, smoking and disability. Fat-free mass appeared to be the most sensitive and relevant nutritional parameter according to impairment and disability.
OBJECTIVES: Ritonavir (RTV) is a powerful inhibitor of P450 3A4 cytochorme. When given in combination with indinavir (IDV) it increases the IDV trough concentrations (Cmin) allowing a lower IDV dosage in a twice a day regimen, independently of meals. We report tolerance data and IDV Cmin levels observed in plasma and cerebrospinal fluid (CSF) in a cohort of HIV-infected patients treated with the IDV-RTV combination at different dosages of IDV and RTV. PATIENTS AND METHODS: IDV Cmin was assayed 56 times in 40 patients (few patients had received different dosages of the IDV-RTV combination). Tolerance was recorded. RESULTS: For patients given the IDV-RTV combination at the doses of 800/100 mg b.i.d., 800/200 mg b.i.d. or 400/400 mg b.i.d., the IDV Cmin was 12 times the median IDV IC95. If the Cmin/IC95 ratio was greater than 10 with the 800/100 mg b.i.d. regimen and virological success was achieved, the IDV dosage was reduced to 400 mg b.i.d. For these patients, the 400/100 mg b.i.d. IDV-RTV regimen always gave a Cmin above the IDV IC95. Median Cmin for IDV in CSF was 146 ng/ml (range 71-881 ng/ml), above the IDV IC95. It was possible to control most of the adverse effects by reducing dosage after obtaining the IDV pharmacological levels. Definitive interruption of treatment was required in only 2 cases at mean follow-up of 7.9 months. DISCUSSION: The IDV-RTV combination should be used to improve observance of antiretroviral treatments and reduce the risk of virological failure related to low plasma levels. The IDV-RTV combination at 800/100 mg b.i.d. is a useful protocol when IDV efficacy alone is the goal. The 400/400 mg b.i.d. IDV-RTV regimen is an interesting alternative when efficacy of both inhibitors is the goal. Drug assays should be systematic to adapt individual dosages and limit the risk of adverse effects.
OBJECTIVE: The August 1997 Directive of the Direction of General Health in France extended indications for antiretroviral treatment to risk of HIV exposure by sexual intercourse or syringe sharing. In November 1997, in collaboration with the Hauts-de-Seine MedicoJudiciary center, the Infectious Disease unit of the Raymond Poincaré Garches Hospital established a health care and anti-HIV prophylaxis clinic for victims of sexual assault. We report here the experience in 1998 and 1999. PATIENTS AND METHODS: Between January 1998 and December 1999, 109 victims of sexual assault, 105 women and 4 men, mean age 24.7 +/- 10.6 years attended the clinic. RESULTS: Mean delay from assault to antiretroviral tritherapy (AZT, 3TC, indinavir) was 18.35 +/- 17.39 hours. Mean duration of antiretroviral treatment was 17.4 +/- 11.8 days. HIV screening in perpetrators enabled early interruption of the antiretroviral treatment in 23 cases (21.1%). Sixty-two victims (62%) were still in follow-up at W4/W7. Excellent compliance to tritherapy was observed in these subjects. Clinical intolerance was observed in 46.6% with nausea-vomiting in 91.4% of the cases. Adverse effects led to interruption of indinavir in 5 cases. Initial HIV serology was negative in all cases and no case of HIV seroconversion was observed. Among the 23 known perpetrators, one was HIV-positive with an HIV-RNA at 88,000 copies. Sixty-one victims (55.9%) had been previously vaccinated against the hepatitis B virus; 16 victims were vaccinated after the assault. There were no cases of hepatitis B virus seroconversion. Search for chlamydiae in vaginal secretions was positive in 3 cases and chlamydia serology demonstrated a seroconversion in 1 case. There was no case of syphylitic seroconversion and no case of gonococcal or trichomonas infection. CONCLUSION: The low rate of attendance for follow-up in regards to the gravity of the potential risk of HIV and/or hepatitis B virus transmission and the burden and cost of the antiretroviral treatment highlight the need for better medico-psycho-social support for rape victims. For the victims who attended the clinic, antiretroviral treatment was generally well accepted and well tolerated.
In 1999 the Council of Europe decided to collect information regarding Nutrition programmes in hospitals and for this purpose a network consisting of national experts from eight of the Partial Agreement member states was established. The aim was to review the current practice in Europe regarding hospital food provision, to highlight deficiencies and to issue guidelines to improve the nutritional care and support of hospitalized patients. Five major problems seemed to be common in this context: 1) lack of clearly defined responsibilities; 2) lack of sufficient education; 3) lack of influence of the patients; 4) lack of co-operation among all staff groups; and 5) lack of involvement from the hospital management. To solve the problems highlighted, a combined 'team-effort' is needed from national authorities and all staff involved in the nutritional care and support, including hospital managers.
OBJECTIVES: To assess the amount of nutrients delivered, prescribed, and required for critically ill patients and to identify the reasons for discrepancies between prescriptions and requirements and between prescriptions and actual delivery of nutrition. DESIGN: Prospective cohort study. SETTING: Twelve-bed medical intensive care unit in a university-affiliated general hospital. PATIENTS: Fifty-one consecutive patients, receiving nutritional support either enterally or intravenously for > or = 2 days. We followed patients for the first 14 days of nutritional delivery. MEASUREMENTS AND MAIN RESULTS: The amount of calories prescribed and the amount actually delivered were recorded daily and compared with the theoretical energy requirements. A combined regimen of enteral and parenteral nutrition was administered on 58% of the 484 nutrition days analyzed, and 63.5% of total caloric intake was delivered enterally. Seventy-eight percent of the mean caloric amount required was prescribed, and 71% was effectively delivered. The amount of calories actually delivered compared with the amount prescribed was significantly lower in enteral than in parenteral administration (86.8% vs. 112.4%, p < .001). Discrepancies between prescription and delivery of enterally administered nutrients were attributable to interruptions caused by digestive intolerance (27.7%, mean daily wasted volume 641 mL), airway management (30.8%, wasted volume 745 mL), and diagnostic procedures (26.6%, wasted volume 567 mL). Factors significantly associated with a low prescription rate of nutritional support were the administration of vasoactive drugs, central venous catheterization, and the need for extrarenal replacement. CONCLUSIONS: An inadequate delivery of enteral nutrition and a low rate of nutrition prescription resulted in low caloric intake in our intensive care unit patients. A large volume of enterally administered nutrients was wasted because of inadequate timing in stopping and restarting enteral feeding. The inverse correlation between the prescription rate of nutrition and the intensity of care required suggests that physicians need to pay more attention to providing appropriate nutritional support for the most severely ill patients.
CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for home parenteral or enteral nutrition in adult cancer patients. METHODS: Data were identified by searching Medline, Cancerlit, web sites and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 72 independent reviewers. RESULTS: The main recommendations for home parenteral or enteral nutrition in adult cancer patients are: 1) Home parenteral or enteral nutrition concerns cancer patients with malnutrition or with inadequate/impossible oral intake, during therapy of because of therapeutic after-effects (standard). Same indications apply for home and hospital artificial nutrition (standard). 2) Patients need a multidisciplinary follow-up (oncologists, nutritionists, and pain specialists), and this follow-up will make treatment adaptations according to the nutritional status possible (recommendation, expert agreement). An active participation of patients and/or their family circle is very important (standard). 3) The benefit of home parenteral or enteral nutrition on the quality of life of terminally ill patients (vs. hydration) has not been demonstrated. When life expectancy is below 3 months, and the Karnofsky index below 50, the drawbacks of home artificial nutrition are more important than its advantages. In this case, home parenteral or enteral nutrition is not recommended (recommendation, expert agreement). 4) Prospective clinical trials are recommended to evaluate the impact of home nutrition on quality of life in cancer patients (expert agreement). 5) The use of educational booklets that mention the telephone number of a referent health care and what to do when a problem happens (e.g. fever on home parenteral nutrition) is recommended (expert agreement). In France, patients should be referred to authorized home parenteral nutrition centres (recommendation, expert agreement).
CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the National Federation of Comprehensive Cancer Centres (FNCLCC), the 20 French Cancer Centers and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for nutritional support in adult patients with advanced or terminal cancer. METHODS: Data were identified by searching Medline, web sites and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 95 independent reviewers. RESULTS: The main recommendations for nutritional support in adult patients with advanced or terminal cancer are: 1) Palliative care has been defined in a consensual way and is governed by the law (standard). Nutritional support is a palliative care which aim is to maintain and restore the "well-being" of the patient (standard). 2) Digestive symptoms and nutritional troubles are frequently noted in patients with advanced or terminal cancer (standard, level of evidence B2). Karnofsky index (KPS) and performance status (PS) are functional scores with a prognostic value and have to be used (standard, level of evidence B2). 3) Anorexia has a bad predictive value in patients with advanced or terminal cancer (standard, level of evidence B2). 4) In France, patients with advanced or terminal cancer are referred to medical institutions, palliative care units or remained at home (standard). Patients need a multidisciplinary follow-up (standard). An active participation of patients and/or their family circle is very important and physicians have to pay attention for their opinions (standard). 5) Dietetic counseling can help patients to improve their alimentation and its drawbacks (standard). 6) Palliative nutritional care often includes medicinal treatments (standard). 7) Artificial nutrition can slow down nutritional degradation, avoid dehydration and improve quality of life in patients with advanced stage cancer (especially head and neck cancer for enteral nutrition and digestive occlusions for parenteral nutrition) and unable to eat adapted meals (standard, level of evidence C). 8) When life expectancy is below 3 months with a KPS 3/4 50% (or PS > 2), artificial nutrition is not recommended (recommendation, expert agreement). 9) The assessment of nutritional care in patients with advanced or terminal cancer has to include functional scores measurement, quality of life and satisfaction degree of the patient and/or their family (standard, expert agreement).
Highly-active antiretroviral therapy (HAART) has lead to a dramatic decrease in the morbidity of patients infected with the human immunodeficiency virus (HIV). However, metabolic side effects, including lipodystrophy-associated (LD-associated) dyslipidemia, have been reported in patients treated with antiretroviral therapy. This study was designed to determine whether successful HAART was responsible for a dysregulation in the homeostasis of tumor necrosis factor-alpha (TNF-alpha), a cytokine involved in lipid metabolism. Cytokine production was assessed at the single cell level by flow cytometry after a short-term stimulation of peripheral blood T cells from HIV-infected (HIV(+)) patients who were followed during 18 months of HAART. A dramatic polarization to TNF-alpha synthesis of both CD4 and CD8 T cells was observed in all patients. Because it was previously shown that TNF-alpha synthesis by T cells was highly controlled by apoptosis, concomitant synthesis of TNF-alpha and priming for apoptosis were also analyzed. The accumulation of T cells primed for TNF-alpha synthesis is related to their escape from activation-induced apoptosis, partly due to the cosynthesis of interleukin-2 (IL-2) and TNF-alpha. Interestingly, we observed that LD is associated with a more dramatic TNF-alpha dysregulation, and positive correlations were found between the absolute number of TNF-alpha CD8 T-cell precursors and lipid parameters usually altered in LD including cholesterol, triglycerides, and the atherogenic ratio apolipoprotein B (apoB)/apoA1. Observations from the study indicate that HAART dysregulates homeostasis of TNF-alpha synthesis and suggest that this proinflammatory response induced by efficient antiretroviral therapy is a risk factor of LD development in HIV(+) patients.
CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the use of appetite stimulants in oncology. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 55 independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the use of appetite stimulants in oncology are: 1) Corticosteroids and the synthetic progestogens (megestrol acetate and medroxyprogesterone acetate) are appetite stimulants. 2) They can be useful in managing anorexia and weight loss in cancer patients, especially in the palliative setting, despite the potential side-effects of these agents. 3) The most effective way of using these drugs is not known. Inclusion in clinical trials is recommended. 4) Cyproheptadine, metoclopramide, nandrolone and pentoxif line should not be used outside prospective clinical trials. 5) Hydrazine sulfate should not be used.
BACKGROUND: A syndrome of lipodystrophy, associated with hypertriglyceridaemia, hypercholesterolaemia, hyperinsulinaemia and peripheral insulin resistance has been reported in protease inhibitor (PI)-treated HIV-infected patients. Because lipid metabolism, fat mass distribution and insulin resistance are partly regulated by steroid hormones, we questioned whether lipodystrophy is related to hormonal perturbations. OBJECTIVE: To evaluate serum lipid and steroid hormone concentrations in HIV-positive men on highly active antiretroviral therapy (HAART) in order to determine whether dyslipidaemia, peripheral loss of fatty tissue and central fat accumulation are related to steroid hormone modifications. DESIGN: A cross-sectional study. METHODS: Thirty-seven HIV-1-positive men on HAART, 23 of whom had symptoms of lipodystrophy, according to a subjective clinical score of lipodystrophy (SCSL), were tested. Serum concentrations of cholesterol, triglycerides and their subclasses, apolipoproteins and steroid hormones, including cortisol, dehydroepiandrosterone (DHEA), DHEA sulphate, androstenedione, testosterone and dihydrotestosterone were measured. RESULTS: Serum cholesterol, very low density lipoprotein (VLDL) cholesterol, triglycerides, VLDL triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL) triglycerides, apolipoprotein B (ApoB) and atherogenic ratios of cholesterol:HDL cholesterol, LDL cholesterol:HDL cholesterol and ApoB:apolipoprotein A1 (ApoA1) were significantly increased in lipodystrophy-positive compared with lipodystrophy-negative men. The serum cortisol level was similar in lipodystrophy-positive versus lipodystrophy-negative men, but was elevated compared with controls. Serum DHEA was significantly lower in lipodystrophy-positive versus lipodystrophy-negative men and, consequently, the cortisol:DHEA ratio was increased in lipodystrophy-positive patients. A positive correlation was found between the cortisol:DHEA ratio and increased levels of atherogenic lipids. In addition, the SCSL was positively correlated with dyslipidaemia and the cortisol:DHEA ratio. CONCLUSION: This study demonstrates an association between the cortisol:DHEA ratio, lipid alterations and lipodystrophy. This syndrome might result from an imbalance between peripheral lipolysis and lipogenesis, both regulated by cortisol and DHEA.
In order to compare the nutritional status of tuberculosis (TB) patients who were human immunodeficiency virus (HIV)-seropositive with those who were seronegative, we carried out a cross-sectional anthropometric and biochemical assessment, together with bioelectrical impedance analysis (BIA) of the nutritional status of TB patients hospitalized in the Department of Internal Medicine, Bujumbura University Hospital, Burundi, East Africa. Of the 65 TB patients (33 pulmonary, 6 extrapulmonary, and 26 disseminated TB), 50 (76.9%) were HIV-seropositive (HIV+). When assessed according to anthropometric, BIA, and biochemical variables, HIV+ TB patients had more pronounced malnutrition than HIV- patients. Similar results were obtained when the comparison was restricted to patients with only pulmonary TB: HIV+ patients were more malnourished than HIV- patients. The results according to anthropometric measurements were: weight loss (13.5% of HIV- patients versus 26.4% of HIV+ patients, P = 0.005), body mass index (18.6 versus 15.1, P = 0.003), fat free mass (FFM) (13.9 versus 11.9, P < 0.01), and body fat (BF) (4.55 versus 3.71, P = 0.03) expressed per unit height2. BIA showed that the difference in FFM between HIV- and HIV+ TB pulmonary patients was mostly due to a decrease in body cellular mass. Measurements of albumin, prealbumin, and transferrin showed a marked decrease in all three markers in HIV+ TB pulmonary patients. The nutritional status of HIV+ patients with disseminated versus pulmonary TB was similar. The nutritional status of HIV+ TB patients is far worse than that of HIV- TB patients. In such patients, anthropometry underestimates the degree of malnutrition because it does not account for the water component of FFM. Nutritional status should be assessed and nutritional intervention should be provided in an attempt to improve the prognosis of TB patients, especially those who are infected by HIV.
Malnutrition is a frequent complication of human immunodeficiency virus (HIV) infection and is associated with a poor prognosis. To compare different measures of nutritional status in HIV-infected patients, we prospectively studied 88 outpatients seen at a Paris AIDS outpatient clinic for routine follow-up examinations. Nutritional status was assessed according to body weight loss (BWL, 4 classes), anthropometry, bioelectric impedance analysis (BIA), and subjective global assessment of nutritional status (SGA). Malnutrition was diagnosed in 22.4% of subjects using SGA, and 37.1% by BWL. SGA rapidly detected a worsening of nutritional status, while BWL detected malnutrition at an earlier stage. A good correlation was found between SGA class and body composition assessed by anthropometry and BIA. Deteriorating nutritional status diagnosed by SGA correlated with the CDC HIV disease class. SGA, a simple nutritional assessment, can serve as a basis for prescribing artificial nutrition, while BWL detects malnutrition at an earlier stage.
OBJECTIVE: To determine the prevalence and analyse the characteristics and causes of malnutrition among inpatients in an HIV highly endemic area. DESIGN: Prospective cross-sectional study. SETTING: Department of Internal Medicine, University Hospital, Bujumbura, Burundi. SUBJECTS: 226 adult inpatients. MAIN OUTCOMES MEASURES: Evaluation of nutritional status using anthropometry. Degree of malnutrition defined by the percentage of body weight loss (BWL), calculated by reference to the usual body weight. RESULTS: Among the 226 patients recruited (mean age: 34.4 +/- 11.9 y, M:F sex ratio: 1.72), 102 (45.1%) were HIV seropositive. 62 (60.8%) of these HIV seropositive were AIDS cases. The AIDS defining criterion was 'wasting syndrome' for 25 (40.3%) and opportunistic infection (OI) for 37 (59.7%) including 34 cases of tuberculosis (TB). The nutritional status of 119/226 patients (52.7%) was normal (BWL < or = 10%). Moderate malnutrition (10% < or = BWL < or = 20%) was observed in 47 (20.8%) and severe malnutrition (BWL > 20%) was observed in 60 (26.5%). HIV seroprevalence and, among HIV seropositive subjects, the percentage of AIDS cases increased according to decreasing level of nutrition (Chi2 for trends: P < 0.001 in both instances). The fat free mass mass of malnourished subjects was lower and the fat body mass was higher among HIV seropositive subjects than HIV seronegative subjects. Among HIV seropositive subjects, malnutrition was associated with TB (P < 0.001) and dysphagia (P < 0.05). Among HIV seronegative subjects, malnutrition was associated with decreased food availability (P < 0.003) and TB (P < 0.05). One week after admission, the mortality rate was higher among HIV seropositive subjects (10.8%) than seronegative subjects (2.4%, P=0.009). Other factors associated with death were decreased fat free mass (P < 0.01) and tricipital skinfold thickness (P < 0.04). CONCLUSIONS: The prevalence of malnutrition is high among the inpatients investigated. Main factors are HIV infection and TB. Strategies adapted to the African context should be developed to prevent, detect and treat malnutrition and associated factors, particularly among HIV seropositive subjects.
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