Biomedical subjects

C Sessa

Publications and source records attributed to C Sessa.

At least 19 recordsLinked to original sources

PubMed2002

Patients' estimation of overall treatment burden: why not ask the obvious?

PURPOSE: We investigated the clinical validity of patients' estimation of overall treatment burden. This measure was expected to be responsive to the wide spectrum of reactions on treatment and thus less precise for specific effects. PATIENTS AND METHODS: After the first chemotherapy within a randomized, double-blind trial of the prophylaxis for delayed emesis (SAKK 90/95), 249 patients documented nausea and vomiting daily for 6 days. Over the whole period, they estimated nausea/vomiting (N/V) burden and overall treatment burden by linear analog-self assessment (LASA) indicators and documented other side effects. RESULTS: At day 6, the two burden indicators were moderately correlated (r = 0.58) in accordance with their different concepts. No, partial, or total control of delayed emesis (days 2 to 6) was reflected in a consistent pattern by both indicators, with a stronger and more significant effect (P <.001) on changes in N/V burden than overall treatment burden. In contrast, toxicity other than N/V, assessed independently by patients and physicians, was mainly associated with overall treatment burden. Patients who indicated at least one other side effect rated their overall burden substantially higher than those with no indication of other toxicity (P <.0001). Physician-rated toxicity had a similar effect (P <.0001). CONCLUSION: A direct patient estimation of overall treatment burden by a LASA indicator may serve as an end point in clinical trials, particularly when treatments with different toxicity profiles are being compared. It is complementary to physicians' ratings of specific toxicities and a major component of patient-rated symptom checklists and quality-of-life measures.

Aged↗

PubMed2002

Population pharmacokinetic and dynamic analysis of the topoisomerase I inhibitor lurtotecan in phase II studies.

Population pharmacokinetic-dynamic analysis was prospectively integrated in a broad phase II program of lurtotecan (GI147211), a novel camptothecin derived topoisomerase I inhibitor, to determine the population pharmacokinetic profile in a larger population, to estimate individual pharmacokinetic parameters and to investigate relationships with clinical outcome. A sparse sampling method was applied during course one, which involved two sampling time-points. A Bayesian algorithm was used to estimate individual pharmacokinetic parameters, in particular total plasma clearance (CL) and volume of distribution. In total, samples were collected of 109 (63%) of 173 patients. Pharmacokinetic-dynamic evaluation could be carried out successfully in 85 (78%) of the sampled patients. CL of lurtotecan showed substantial variability (mean 87 +/- 28 L/h) and was of the same magnitude as in the phase I studies where full pharmacokinetic curves were used. Residual variability in the population estimate of CL was 9.9%. No significant relationships were observed between exposure parameters and toxicity nor likelihood of tumor response, however the latter relationship may well have been obscured by the heterogeneity of the studied population. Prospective implementation of large scale population pharmacokinetic-dynamic analysis is feasible and important to establish whether interpatient variability in drug exposure is a major determinant of toxicity or activity.

Adult↗

PubMed2001

Phase I-II study of escalating doses of amifostine combined with high-dose cyclophosphamide.

PURPOSE: To evaluate the feasibility and clinical effects of increasing doses of amifostine administered four times in 1 day with high-dose (HD) cyclophosphamide (CTX). METHODS: A group of 16 patients with a diagnosis of lymphoma were treated with HD-CTX given at a total dose of 7 g/m2 subdivided into four doses, each preceded by increasing doses of amifostine. A group of 12 lymphoma patients previously treated with the same HD-CTX regimen was used as historical controls. RESULTS: The dose of amifostine was escalated in cohorts of three patients each from 4x570 mg/m2 to 4x910 mg/m2 without severe toxic effects. Further patients were treated at the highest dose level. Side effects included a fall in blood pressure (always less than 20% of baseline value), asymptomatic hypocalcemia (from a median value of 2.4 to 1.7 mmol/l) and a decrease in creatinine clearance (from a median value of 102 to 85 ml/min). The parameters of hematotoxicity for patients treated in the study were not significantly different from those of the historical control patients. CONCLUSIONS: Amifostine can be given safely at a dose of 910 mg/m2 four times in 1 day in combination with HD-CTX. With this schedule amifostine did not show a myeloprotective effect.

Adolescent↗

PubMed2001

High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel.

BACKGROUND: Clinically overt central nervous system (CNS) involvement occurs in 10%-15% of patients with advanced breast cancer. PATIENTS AND METHODS: The International Breast Cancer Study Group (IBCSG) conducted a dose-finding phase I trial of epirubicin (E) and docetaxel (D) as first-line therapy in advanced breast cancer patients. The study was expanded into a phase II at the recommended doses of E 90 mg/m2 and D 75 mg/m2 every three weeks. From July 1996 to May 1998, a total of 92 patients (median age 50 years) entered the two studies. RESULTS: Twenty-eight out of ninety-two patients treated with the combination of E and D (30%) developed CNS metastases (95% confidence limits, 26%-35%), which were cerebral in twenty-five patients, leptomeningeal in two, and both in one. Of these 28 patients, 19 (68%) had an objective response. Median time for the development of CNS metastases from the start of chemotherapy was 15 months (range 5-42), if excluding the 6 patients presenting CNS progression within 3 months from start of treatment. It is notable that 11 patients (39%) had progression in the CNS only. Median survival from appearance of brain metastases in the whole group was only three months (range 1-22). C-erbB-2 overexpression was found in 14 out of 16 patients (87%) in whom the assay was performed (3+ in 10, 2+ in 1 and 1+ in 3 cases). CONCLUSIONS: As anthracycline- and taxane-containing regimens are increasingly used both in the metastatic and in the adjuvant setting, a careful monitoring of any neurological symptom is advisable. Our preliminary observation on the possible increase of incidence of CNS involvement in patients with advanced breast cancer receiving this effective drug combination requires further evaluation.

Adult↗

PubMed2001

Development of distamycin-related DNA binding anticancer drugs.

The relatively low therapeutic index of the clinically used alkylating agents is probably related to the fact that these compounds cause DNA damage in a relatively unspecific manner, mainly involving guanine-cytosine rich stretches of DNA present in virtually all genes, therefore inducing unselective growth inhibition and death, both in neoplastic and in highly proliferative normal tissues. These considerations explain why in the last twenty years there has been an increasing interest in the identification of compounds which can target DNA with a much higher degree of sequence specificity than that of conventional alkylators. Minor groove binders (MGBs) are one of the most widely studied class of alkylating agents characterised by a high level of sequence specificity. The prototype of this class of drugs is distamycin A which is an antiviral compound able to interact, non-covalently, in theminor groove of DNA in A-T rich regions. It is not cytotoxic against tumour cells and thus has been used as a carrier for targeting cytotoxic alkylating moieties in theminor groove of DNA. The benzoyl mustard derivative of distamycin A, tallimustine, was found to be able to alkylate the N(3) of adenine in theminor groove of DNA only in the target hexamer 5'-TTTTGA or 5'-TTTTAA. Tallimustine was investigated in the clinic and was not successful because it causes severe bone marrow toxicity. The screening of other distamycin derivatives, which maintain antitumour activity and exhibit much lower toxicity against human bone marrow cells than tallimustine led to the identification of brostallicin (PNU-166196) which is currently under early clinical investigation. Although MGBs which bind DNA in A-T rich regions have not fulfilled the expectations, it is too early to draw definitive conclusions on this class of compounds. The peculiar bone-marrow toxicity observed in the clinic both with tallimustine or with CC-1065 derivatives is not necessarily a feature of all MGBs, as indicated by recent evidence obtained with brostallicin and other structurally unrelated MGBs (e.g., ET-743).

Animals↗

PubMed2001

Docetaxel and epirubicin in advanced breast cancer.

In an International Breast Cancer Study Group phase I/II program, 70 patients with advanced breast cancer received up to eight courses of 75 mg/m2 docetaxel combined with 90 mg/m(2) epirubicin, every 3 weeks. G-CSF was not administered prophylactically. Grade 4 neutropenia occurred in 88% of cycles that were not supported by G-CSF. However, febrile neutropenia affected only 24% of cycles. It occurred after the first cycle in 56% of cases and was managed by oral antibiotics in 52% of cases. When supportive G-CSF was administered, the incidence of febrile neutropenia fell to 3% and grade 4 neutropenia to 41%. Only 6% of patients experienced a greater than 20% reduction in left ventricular ejection fraction and no severe, irreversible cardiotoxicity was observed. The overall response rate (RR) was 66% and median time to progression was 4.5 months. The RR was similar in patients with prior adjuvant chemotherapy and patients with predominantly visceral disease. These data and those of comparable series suggest that the combination of epirubicin and docetaxel is tolerable and active, and that it should be further developed clinically.

Antibiotics, Antineoplastic↗

PubMed2001

Risk factors of atherosclerosis and saphenous vein endothelial function.

BACKGROUND: Impaired vasomotor function has been suggested as playing a role in the pathophysiology of atherosclerosis and it may also affect the late patency of bypass grafts. We evaluated, in vitro, the influence of risk factors of atherosclerosis on saphenous vein endothelial function in patients with cardiovascular diseases. METHODS: Forty-five saphenous vein rings with intact (E+) and denuded endothelium (E-) were studied. The following drugs were used: norepinephrine (NE), acetylcholine (Ach), histamine (H) and serotonine (5-HT). RESULTS: Contraction to norepinephrine (n=15) showed a maximal tension of 783+/-115 percent that was increased in diabetics, smokers, and patients with hypertension. There was a wide range of response to acetylcholine in rings with intact endothelium (n=25), (mean relaxation 16.4+/-1.7 percent, ranging from -22.2 percent to 45 percent) with relaxation (26+/-1.1 percent) and contraction (-11+/-1.2 percent); relaxation was reduced in patients with hypertension and in diabetics (7.4+/-2.6 percent vs non diabetics 24.4+/-1.73 percent; p<0.01). Five of the 12 veins from diabetics exibited contraction (10+/-1.48 percent). Histamine (n=15) caused moderate relaxation at low doses (25+/-2.46 percent) followed by contraction at higher concentrations (184+/-5.7 percent). This was greater in diabetics (193+/-6.8 percent vs non diabetics 157+/-5.3 percent; p=0.045) while in preparations without endothelium (n=10) only relaxation was obtained (45+/-2.89 percent). Contraction (242+/-7.4 percent) was observed in response to serotonine (n=15) that was not affected by endothelial removal. In this study saphenous vein: (1) exhibited a wide range of responses to acetylcholine; (2) evoked marked contraction to norepinephrine and serotonine; (3) elicited contraction in response to histamine that was endothelium-dependent, suggesting the production or the release of an endothelium-derived-contracting-factor (EDCF). CONCLUSIONS: Saphenous vein is able to secrete a contracting factor in patients with risk factors of atherosclerosis and above all diabetes. The mechanisms that regulate the balance between the relaxing and contracting factors and how the endothelial cells become the source of the substances with vasoconstrictor activity remain to be determined.

Acetylcholine↗

PubMed2000

Classical (HIV-negative) cutaneous Kaposi's sarcoma: a case report and a short review of the literature.

Classical Kaposi's sarcoma is a sporadic disease with a markedly higher incidence in the Mediterranean area. The two original forms of this disease, the Caucasian (classical) and the African, are now well-documented entities. The immunosuppression-related form is a new, recently described subset of the disease, arising from the human immune deficiency virus (HIV) infection and/or the widespread use of immunosuppressive treatments. Cutaneous lesions are the most common manifestation of classical Kaposi's sarcoma. The case described in the present report is characterised by a history of slowly evolving disease affecting the lower extremities without spread to thoracic or abdominal organs, a lengthy remission following initial radiation therapy, and local relapse with a further remission after a second course of radiation. Current treatments, in particular radiation therapy, achieve disease control or at least control of disease-related symptoms (mainly pain) in most cases, even when cure is not possible.

Aged↗

PubMed2000

Critical hand ischemia after angioaccess surgery: diagnosis and treatment.

Severe hand ischemia is an uncommon complication of angioaccess surgery. Prompt recognition is necessary to prevent finger necrosis and permanent nerve damage. Treatment should relieve symptoms without compromising dialysis access. From January 1989 to September 1999, we treated critical hand ischemia in 23 patients (16 men, 7 women), including 8 diabetic patients with a total of 19 arteriovenous fistulas (AVF) and 4 arteriovenous grafts (AVG). In 21 patients, the symptom was critical ischemia, with finger necrosis occurring in 7 patients. In the remaining two patients, the manifestation was acute ischemia due to venous thrombosis. Four patients required finger amputation. Fifteen patients (65%) had previous AVF on the lateral extremity. The mean number of previous AVF in this group was 2.5 (range, 2 to 6). Various treatments were used for arterial insufficiency (n = 20), including ligation of the fistula (n = 8), distal revascularization-interval ligation (DRIL) (n = 4), bypass (n = 4), sympathectomy (n = 1), ligation of the radial artery (n = 1), medical therapy (n = 1), and banding technique (n = 1). Medical therapy and banding relieved symptoms after thrombosis of the AVF. Through the use of DRIL, healing of finger necrosis (n = 3) and improvement of symptoms (n = 1) were achieved. The findings of this study indicate that severe hand ischemia occurs mainly in diabetic patients with multiple previous AVF and finger arteriopathy. DRIL is the conservative treatment of choice, since it can be used to achieve both symptomatic relief and maintenance of dialysis access.

Adult↗

PubMed2000

[Inframalleolar bypass in limb salvage. Late results].

STUDY OBJECTIVE: The objective of this retrospective study was to report the long-term results of distal revascularization at the ankle in patients with critical ischemia. PATIENTS AND METHODS: From January 1989 to November 1999, 50 inframalleolar bypasses were performed in 49 patients (35 males and 14 females with a mean age of 75 years [range: 51 to 95 years]). Twenty-five patients (50%) were diabetics. All patients presented with critical ischemia of the lower limb. Distal anastomosis was performed at the retromalleolar posterior tibial artery in 28 cases (56%), pedal artery in 20 cases (40%) and distal fibular artery in two cases (4%). Bypasses were performed using a greater saphenous vein (n = 38), a cryopreserved arterial allograft (n = 9), or a PTFE graft (n = 2). A composite graft with greater saphenous vein and arterial allograft was performed in two cases. RESULTS: There were two early postoperative deaths. One patient presented a blow-out of the distal anastomosis that required bypass ligation and subsequent leg amputation. Early thrombosis of the graft occurred in four cases, leading to major amputation in three cases. No patients were lost to follow-up and mean follow-up was 26.7 months (range: 1 to 86 months). Graft thrombosis occurred in 15 patients and led to amputation in 6 cases. Bypass graft patency rate was 72% and 61% at 1 year and 3 years, respectively, yielding a 80% limb salvage rate at 3 years. The 3-year actuarial survival rate was 53%. CONCLUSION: Inframalleolar bypasses are a valuable tool in patients with critical ischemia. The lower limb salvage rate is satisfactory in this elderly population. Based on this experience, angiography with good run-off and, when necessary, a surgical approach to verify patency of the arteries at the ankle should always be performed before undertaking a major amputation.

Aged↗

PubMed2000

Clinical and pharmacological phase I study with accelerated titration design of a daily times five schedule of BBR3464, a novel cationic triplatinum complex.

OBJECTIVES: To define the maximum tolerated dose (MTD), the toxicity and pharmacokinetic profile of BBR3464, a novel triplatinum complex. PATIENTS AND METHODS: Fourteen patients with advanced solid tumors not responsive to previous antitumor treatments received BBR 3464 on a daily x 5 schedule every twenty-eighth day. The drug was given as a one-hour infusion with pre-and post-treatment hydration (500 ml in one hour) and no antiemetic prophylaxis. The starting dose was 0.03 mg/m2/day. A modified accelerated titration escalation design was used. Total and free platinum (Pt) concentrations in plasma and urine were assessed by ICP-MS on days 1 and 5 of the first cycle. RESULTS: Dose was escalated four times up to 0.17 mg/m2/day. Short-lasting neutropenia and diarrhea of late onset were dose-limiting and defined the MTD at 0.12 mg/m2. Nausea and vomiting were rare, neither neuro- nor renal toxic effects were observed. BBR3464 showed a rapid distribution phase of 1 hour and a terminal half-life of several days. At 0.17 mg/m2 plasma Cmax and AUC on day 5 were higher than on day 1, indicating drug accumulation. Approximately 10% of the equivalent dose of BBR3464 (2.2%-13.4%) was recovered in a 24-hour urine collection. CONCLUSIONS: The higher than expected incidence of neutropenia and GI toxicity might be related to the prolonged half-life and accumulation of total and free Pt after daily administrations. Lack of nephrotoxicity and the low urinary excretion support the use of the drug without hydration. The single intermittent schedule has been selected for clinical development.

Adolescent↗

PubMed2000

Phase I and pharmacologic study of weekly gemcitabine and paclitaxel in chemo-naïve patients with advanced non-small-cell lung cancer.

BACKGROUND: Gemcitabine (GEM) and paclitaxel (TAX) are active, non-cross-resistant drugs in non-small-cell lung cancer (NSCLC). We performed a phase I study to determine the maximum-tolerated dose (MTD), antitumor activity and pharmacokinetics of GEM and TAX given weekly in chemo-naïve patients with advanced NSCLC. PATIENTS AND METHODS: Escalating doses of GEM (800-2000 mg/m2) and TAX (60-100 mg/m2) were administered on days 1, 8, 15 every 4 weeks to 35 patients with advanced NSCLC. Plasma pharmacokinetics of TAX and GEM was assessed at the three higher dose-levels. RESULTS: Dose-escalation was discontinued in absence of MTD because of increased cumulative toxicity leading to dose modification or treatment delay at levels 6 and 7 (TAX 100 mg/m2 plus GEM 1750 and, respectively, 2000 mg/m2). Hematological toxicity included grade 4 neutropenia in 3% of cycles, grade 3 thrombocytopenia in one cycle and febrile neutropenia in three cycles. Maximal non-hematological toxicity was grade 3 elevation in serum transaminases and grade 2 neuro-sensory toxicity in 8% and 5% of cycles, respectively. At the two higher dose-levels a non-linear pharmacokinetics of GEM was observed with a remarkable variability of Cmax and AUC. No pharmacokinetic interactions were reported. Objectives responses were seen at all dose levels, with an overall response rate of 43% (95% confidence interval (95% CI): 25.5%-62.6%) in 30 evaluable patients. CONCLUSIONS: The weekly administration of GEM and TAX is very well tolerated, and has shown promising antitumor activity in NSCLC. In view of the cumulative toxicity and of the pharmacokinetic profile of GEM, doses of 1500 mg/m2 of GEM and 100 mg/m2 of TAX are recommended for phase II studies.

Adult↗

PubMed2000

Second-line treatment of small-cell lung cancer with the camptothecin-derivative GI147211: a study of the EORTC Early Clinical Studies Group (ECSG).

BACKGROUND: GI147211, a 10,11-ethylenedioxy substituted analogue of camptothecin (CPT), was brought into clinical development because of its higher water solubility and greater potency as compared to topotecan (TPT). The antitumor activity of GI147211 as second-line therapy in small-cell lung cancer (SCLC) was assessed after stratification of patients in refractory (no response to initial treatment or relapse within three months from last cycle) and chemosensitive (relapse more than three months from last cycle). PATIENTS AND METHODS: Sixty-seven patients were entered in the study and sixty-two were evaluable for response, twenty-eight in the refractory and thirty-four in the chemosensitive group. All patients had received 1 line of chemotherapy; radiation had also been given in 29 cases, 6 in the refractory and 23 in the chemosensitive group. GI147211 was administered at 1.2 mg/m2/day as 30-min infusion for five consecutive days every three weeks. RESULTS: The overall response rate was 16.6% (11 of 66 patients; 95% confidence interval (95% CI): 8.5%-27.5%), 10.3% (3 of 29 patients; 95% CI: 2.2%-27%) in the refractory and 21.1% (8 of 37 patients; 95% CI: 9.5%-37%) in the chemosensitive group. Only partial responses (PR) were observed with a median duration of PR of 4.8 months (5.7 months in the refractory and 5.2 in the chemosensitive group). Hematological toxicity consisted mainly of neutropenia (grades 3-4 in 25% of cycles) and thrombocytopenia (grades 3-4 in 23% of cycles); non-hematological toxicity was mild to moderate and consisted of nausea (22% of cycles), vomiting (11%), malaise (34%). CONCLUSIONS: At the dose and schedule tested GI147211 is an active new agent for second-line treatment of SCLC; the antitumor activity and toxicity profile are comparable to those observed with TPT which remains the leading CPT analogue for salvage treatment. Interest has been renewed in the clinical development of GI147211 by preclinical data with the liposomal formulation showing an increased therapeutic index.

Adult↗

PubMed2000

Activity and toxicity of GI147211 in breast, colorectal and non-small-cell lung cancer patients: an EORTC-ECSG phase II clinical study.

BACKGROUND: GI147211 is a water-soluble synthetic analogue of camptothecin showing promising in vivo and in vitro antitumor activity and an acceptable toxicity profile. PATIENTS AND METHODS: Between April 1995 and November 1996, 67 eligible patients with pretreated breast cancer (25 patients) and chemo-naïve colorectal (19 patients) and non-small-cell lung cancer (23 patients) were entered into three multicentric, non-randomized phase II trials. Treatment schedule consisted of intravenous GI1147211 administered at a dose of 1.2 mg/m2/day for five consecutive days every three weeks. RESULTS: Hematological toxicity was common with grade 3-4 neutropenia in 54% of patients and neutropenic fever together or not associated with infection in 14.5% of patients. Grade 3-4 thrombocytopenia and grade 2-4 anemia were observed in 20% and in 68% of patients, respectively. Non-hematological toxicity was generally mild to moderate and consisted mainly of gastrointestinal toxicity, asthenia and alopecia. A dose-escalation to 1.5 mg/m2/d was feasible in 17 (25%) patients. The antitumor activity of GI1147211 was moderate in breast cancer patients (3 partial responses (PRs), response rate (RR) 13%) and minimal in non-small cell lung cancer patients (2 PRs, RR 9%). No objective responses were obtained in colorectal patients. CONCLUSIONS: GI147211, at the dose and schedule employed in this study, showed an acceptable safety profile but a modest antitumor activity in the examined tumor types.

Adult↗

PubMed2000

Epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer: a multicentric phase I-II study.

BACKGROUND: The combination of anthracyclines and taxanes is currently considered the first choice chemotherapy in advanced breast cancer (ABC) and considerable emphasis has been placed on programs exploring the safest and most efficient way to integrate these classes of drugs in both the metastatic and, more recently, the adjuvant setting. We report here the overall results of the combination of epidoxorubicin (E) 90 mg/m2 and docetaxel (D) 75 mg/m2 as first-line chemotherapy in ABC. PATIENTS AND METHODS: A total of 70 patients were entered in the initial dose-finding study (20 patients) and in the subsequent extended phase II trial (50 patients). Overall 54% of patients had dominant visceral disease and 57% had at least two metastatic sites. Adjuvant anthracyclines were allowed in the phase II part of the study based on the lack of cardiac toxicity observed in the phase I study at a median cumulative E dose of 480 mg/m2. A maximum of eight cycles of the combination was allowed, and cardiac function was monitored at baseline and after every second course by echocardiography. RESULTS: Overall, the median number of cycles administered with the combination was 4 (range 3-8). Neutropenia was confirmed to be the main haematological toxicity, with granulocyte colony-stimulating factor (G-CSF) support required in 44% of the cycles. Febrile neutropenia occurred in 12% of cycles of the combination but 52% of the episodes could be managed on an outpatient basis with oral antibiotics. Overall, the median cumulative dose of E, including prior adjuvant anthracyclines, was 495 mg/m2 (range 270-1020 mg/m2). One patient who received adjuvant E together with radiotherapy to the left chest wall developed fully reversible clinical signs of cardiotoxicity and a significant decrease of LVEF to 35% after a cumulative E dose of 870 mg/m2, with four additional patients (6%) developing asymptomatic and transient decline of resting LVEF. The overall response rate (ORR) in 68 evaluable patients was 66% (95% confidence interval (95% CI): 54%-73%). A comparable antitumour activity of 71% was reported in the group of patients with a prior adjuvant chemotherapy with anthracyclines. After an overall median follow-up time of 22 months (range 4-39+), the median time to progression (TTP) was 4.5 months and the median duration of response was 8 months (range 3-16). No pharmacokinetic (Pk) interaction could be demonstrated between E and D when given simultaneously and sequentially with a one-hour interval. CONCLUSIONS: The combination of E and D in a multiinstitutional setting is an active and safe regimen in poor-prognosis patients with ABC. New combinations and schedules are worth considering in an attempt to further improve disease response and long-term control of the disease.

Adult↗

PubMed2000

Proposing phase I studies: patients', relatives', nurses' and specialists' perceptions.

PURPOSE: As of now the primary objective of studies on informed consent in phase I trials has been to assess patients' expectations and reasons for participation. We have previously shown that the quantity of information provided through a procedure of subsequent oral interviews with patients was adequate while the attention paid by the physician to the emotional needs and concerns of patients was not. We wanted therefore to assess and compare the perceptions of the information provided about the investigational study of patients, relatives, the research nurse and the investigator responsible for the phase I trial and the impact this information had on the patients' level of anxiety and depression. PATIENTS AND METHODS: The participation to a phase I study was proposed to patients through two subsequent interviews, the latter attended also by patients' relatives, the research nurse and the investigator coordinating the phase I trial. After the second interview, attendees were requested to complete a questionnaire assessing the principal reason for participating in the study and the informative, emotional and interactive dimension of the information. Patients were also requested to complete the Hospital Anxiety and Depression (HAD) scale before and after the second interview. RESULTS: The completed questionnaires of 31 of 42 patients were retrieved and analysed. The possibility to benefit from the study was indicated as the main reason for participating by 59% of the patients while it was judged to be the case in 78% and 86% of the patients by the nurse and the investigator, respectively. The information was judged to be clear and sufficient in almost all cases by all attendees, while the investigator judged that a lower percentage of patients felt at ease and could express their main worries during the interview, had been helped and were less worried after it than it was judged by the nurse and the relatives. Patients' state of anxiety and depression was not adversely affected by the information provided. CONCLUSIONS: Informing patients on the option of receiving an investigational treatment within a phase I study is feasible and can be done in a way felt appropriate by patients and relatives, nursing and medical professionals. Providing information in an appropriate manner does not increase patients' anxiety and depression. Divergence between the aims and interests of the investigators and patients might explain the difference in the evaluation of physician, a problem which could perhaps be partially overcome by the application of innovative phase I designs.

Adult↗

PubMed2000

Prevalence and consequences of nutritional depletion in lung transplant candidates.

Nutritional status was studied in lung transplant (LT) candidates. The hypotheses were that nutritional depletion was highly prevalent and lean body mass depletion was a risk factor for a higher mortality both before and after LT. Of 78 consecutive patients listed for LT, 16 (21%) died while on the waiting list, eight (10%) were alive awaiting LT, and 54 (69%) received a graft. Mean age was 42.3+/-4.4 (mean+/-SD). Thirty-eight per cent had a diagnosis of bronchiectasis or cystic fibrosis (BRO/CF), 33% of emphysema, 20% of idiopathic pulmonary fibrosis (IPF) and 8% of primary pulmonary hypertension. Body mass index (BMI) was 20.4+/-4.3 kg.m2, weight was 87.9+/-16.6% of ideal body weight (IBW). Patients were classed into four nutritional groups according to IBW and creatinine height index (CHI): 1: weight <90% IBW and CHI <60% of predicted (28% of cases); II: weight <90% IBW and CHI > or =60% (27%); III: weight > or =90% IBW and CHI <60% (17%); IV: weight > or =90% IBW and CHI > or =60% (28%). Overall, 72% were depleted corresponding to groups 1, II and III. Lean body mass depletion occurred despite normal weight in 17% of the cases (group III). Subjects with BRO/CF were mostly in groups 1, II, III whereas IPF were concentrated in group II. Lean body mass depletion was associated with more severe hypoxaemia, reduced 6-minute walking distance and a higher mortality while awaiting. After LT, duration of mechanical ventilation, time spent in intensive care unit (ICU) was related to initial body composition. Survival after LT was lowest in group III. To conclude, nutritional depletion in lung transplant candidates is highly prevalent and should be more precisely assessed with a special reference to lean body mass since it has specific consequences both while awaiting and after lung transplant. Attempts should be made to increase lean body mass before lung transplant.

Adult↗

PubMed2000

Defining the role of extended saphenofemoral junction ligation: a prospective comparative study.

OBJECTIVE: This study explores the added effect of extended saphenofemoral junction (SFJ) ligation when the greater saphenous vein (GSV) has been eliminated from participating in thigh reflux by means of endovenous obliteration. GSV obliteration, unlike surgical stripping, can be done with or without SFJ ligation to isolate and study SFJ ligation's specific contribution to treatment results. METHODS: Sixty limbs treated with SFJ ligation and 120 limbs treated without high ligation were selected from an ongoing, multicenter, endovenous obliteration trial on the basis of their having primary varicose veins, GSV reflux, and early treatment dates. RESULTS: Five (8%) high-ligation limbs and seven (6%) limbs without high ligation with patent veins at 6 weeks or less were excluded as unsuccessful obliterations. Treatment significantly reduced symptoms and CEAP clinical class in both groups (P =.0001). Recurrent reflux developed in one (2%) of 49 high-ligation limbs and eight (8%) of 97 limbs without high ligation by 6 months (P =.273). New instances of reflux did not appear thereafter in 57 limbs followed to 12 months. Recurrent varicose veins occurred in three high-ligation limbs and four limbs without high ligation by 6 months and in one additional high-ligation limb and two additional limbs without high ligation by 12 months. Actuarial recurrence curves were not statistically different with or without SFJ ligation (P >.156), predicting greater than 90% freedom from recurrent reflux and varicosities at 1 year for both groups. CONCLUSION: These early results suggest that extended SFJ ligation may add little to effective GSV obliteration, but our findings are not sufficiently robust to warrant abandonment of SFJ ligation as currently practiced in the management of primary varicose veins associated with GSV vein reflux.

Adult↗