Intensive Therapy In Patients Research Articles

Deleterious Effects of Increased Body Weight Associated with Intensive Insulin Therapy for Type 1 Diabetes: Increased Blood Pressure and Worsened Lipid Profile Partially Negate Improvements in Life Expectancy

SUMMARYObjective: Weight gain is an unwanted side effect of improved glycaemic control in type 1 diabetes, associated with increased blood pressure (BP) and worsening lipid profiles. While improved glycaemic control per se should improve long-term patient outcomes, increases in BP and worsening lipid profiles may counteract these benefits. The aim of this modelling study was to assess whether the increased body weight and associated worsening of lipid profile and blood pressure would negate the improvements in glycaemic control seen with intensive therapy in patients with type 1 diabetes.Methods: A validated diabetes model projected life expectancy (LE), quality-adjusted LE (QALE) and total lifetime costs of complications in type 1 diabetes cohorts with the characteristics of patients from the Diabetes Control and Complications Trial (DCCT). The following four cohorts (A–D) were created based on increased body weight under either conventional or intensive therapy: A) conventional glycaemic control in the subgroup with lowest weight-gain quartile after 6.5 years (HbA1c increased by 11% from baseline); B) conventional control in the highest weight-gain quartile (no change in HbA1c from baseline); C) intensive control in the lowest quartile of weight gain (with 16.1% decrease in HbA1c, but no increase in weight or associated BP, and improved lipid profile); D) intensive control in the highest quartile of weight gain (with 21% decrease in HbA1c, increased systolic BP of 6 mmHg, and worsened lipid profile). Data were derived from DCCT and other published sources.Results: Intensive control, even with weight gain, led to major improvements in LE and QALE, and reduction in costs of complications versus conventional therapy. Intensive therapy with no weight increase led to a higher LE (increased by 0.57 years) and higher QALE (increased by 0.28 years) and lower costs of complications (reduced by $523/patient), compared to intensive therapy with the highest quartile of weight gain.Conclusions: Concerns about weight gain should not deter intensive insulin therapy. However, the value of improving glycaemic control without increasing body weight (and associated increased BP and worsening of lipid profile) has been confirmed.

Treatment-induced anaemia and its potential clinical impact in patients receiving sequential high dose chemotherapy for metastatic testicular cancer.

First-line sequential high dose chemotherapy is under investigation in patients with ‘poor prognosis’ metastatic germ cell tumours in order to improve survival. Despite the use of autologous peripheral blood stem cell transplantation and granulocyte colony stimulating factor chemotherapy dose intensification is associated with severe haematotoxicity including anaemia, which may significantly affect quality of life and tolerability of chemotherapy. This study investigates the frequency and degree of anaemia in patients receiving first-line sequential high dose chemotherapy for metastatic testicular cancer and the impact of anaemia on treatment outcome. A total of 101 newly diagnosed patients with ‘poor prognosis’ metastatic nonseminomatous germ cell tumours were treated with one cycle of standard VIP followed by three cycles of HD-VIP-chemotherapy (etoposide, ifosfamide, cisplatin) within a large phase I/II study. Differential blood cell counts were taken prior, during and after every cycle of chemotherapy. Additionally, the numbers of red blood cell and platelet transfusions were recorded. Kaplan–Meier analyses were performed to correlate pre-treatment and post-treatment haemoglobin values to response and overall survival. Forty-eight per cent of the patients were classified anaemic (haemoglobin <12 g dl−1) prior to the start of chemotherapy. The application of sequential HD-VIP resulted in median haemoglobin nadirs between 7.8 g dl−1 (range 5.5–11.1 g dl−1) in the first cycle and 7.6 g dl−1 (range 6.0–11.4 g dl−1) in the third cycle despite the frequent use of red blood cell transfusions. Almost all patients (99%) had haemoglobin levels <10 g dl−1 at some timepoint during first-line sequential high dose chemotherapy. Overall, 97 patients received red blood cell transfusions with a median of 10 units (range 2–25) per patient during the four consecutive cycles of therapy. The time to first transfusion was shortest in patients with the lowest initial haemoglobin values. While there was no prediction of response or outcome by baseline haemoglobin-levels, a significant survival difference in favour of patients with a haemoglobin value >10.5 g dl−1 after completion of four cycles of therapy (at leukocyte recovery after the last cycle) compared to those with haemoglobin values <10.5 g dl−1 was found with 3-year overall survival rates of 87% vs 68%, respectively (P<0.05). Severe anaemia is a very frequent side effect of sequential dose intensive therapy in patients with germ cell cancer, with almost all patients becoming transfusion dependent. Despite the frequent use of red blood cell transfusions, median haemoglobin nadirs remained about 7.5–8 g dl−1 during therapy. A correlation of haemoglobin-values after completion of therapy to overall treatment outcome was found.British Journal of Cancer (2002) 87, 1066–1071. doi:10.1038/sj.bjc.6600629 www.bjcancer.com© 2002 Cancer Research UK

Impact of complete remission with intensive therapy in patients with responsive multiple myeloma.

Clinical outcomes were assessed in 68 consecutive patients with multiple myeloma of high or intermediate tumor mass that had responded to VAD or dexamethasone-based therapy and were consolidated with early intensive therapy and autologous stem cell transplantation. Results were compared with those of 50 comparable patients who refused or were unable to receive intensive treatment for socioeconomic reasons. Following high-dose therapy, the rate of CR increased from 6 to 37%, with median survival prolonged by 10 months. Survival of 21 patients with disease converted from PR to CR (median 8.3 years) was significantly longer than that of similarly-treated patients who remained in PR (median 5.0 years). CR of myeloma represents the major surrogate marker of long survival and the primary goal of myeloablative treatment for patients in PR. Twelve of 18 patients with rapid reduction of myeloma protein (T(1/2) < 0.5 months), and myeloma protein reduction to <1.0 g/dl after primary therapy achieved CR (67%), identifying pretransplant features favorable to intensive therapy. Among 35 patients with slower reduction or higher residual myeloma protein, CR occurred in eight patients (23%) (P < 0.01), for whom other treatments should be considered. The kinetics of response to initial therapy should be considered in selecting patients more likely to achieve CR and consequent long survival after intensive treatment.

Interventional methods in the complex of respiratory support of subcompensated respiratory insufficiency in grave pneumonias

The interventional method algorythm in grave pneumonias accompanied by pronounced respiratory insufficiency is developed. As a result of the use of the given algorythm the normalization of homeostasis parameters came fast; positive roentgenologic dynamics, the improvement of indications of central and peripheric hemodynamics were observed. The algorythm developed can serve as an important addition to the complex of intensive therapy in patients of the given contingent.

Hemostatic abnormalities and the severity of illness in patients at the onset of clinically defined sepsis. Possible indication of the degree of endothelial cell activation?

To find out whether changes within the hemostatic system are related to the severity of illness and organ failure in patients at the onset of clinically defined sepsis and to find some indications for the contribution of endothelial cell activation or perturbation to the patient's status. The following measurements were undertaken: Acute Physiology and Chronic Health Evaluation (APACHE) II score, multiple organ failure (MOF) score, plasma levels of thrombin-antithrombin III complexes (TAT), antithrombin III (AT III), protein C antigen, factor XII, and plasminogen activator inhibitor type 1 antigen (PAI-1), neopterin, and interleukin 6 (IL-6). A prospective case series study. Intensive care unit (ICU) of the Department of Internal Medicine, Justus Liebig University, Giessen, Germany. 28 consecutive patients (11 females, 17 males; mean age 58 years) with clinically defined sepsis. Eleven patients were admitted from the surgical ICU (9 after elective surgery, 2 after trauma surgery). The operations were done 1-26 days (mean 14 days) prior to the onset of sepsis. At the onset of sepsis we found elevated plasma levels of TAT, PAI-1, neopterin, and IL-6, and lowered plasma levels of AT III, factor XII, and protein Cantigen. Neopterin, PAI-1, IL-6, and factor XII showed a statistically significant correlation with the APACHE II score. The MOF score is significantly correlated with IL-6 and neopterin. The extent of hemostatic abnormalities was related to increasing levels of IL-6. Clinical evidence of a septic process is most likely to be preceded by activation of the hemostatic system, the vascular endothelium, and the monocyte/macrophage system. IL-6 may have a regulatory function for hemostasis in inflammation. Laboratory monitoring could be helpful in deciding whether to start early intensive therapy in patients at risk for sepsis.

Optimization of high-dose therapy for the treatment of patients with metastatic breast cancer

Objective. To determine the effect of chemorespon siveness and dose intensity on event-free survival (EFS) for metastatic breast cancer patients following high-dose chemotherapy and autologous stem cell rescue. Design. This is a retrospective review of data from three allocated, parallel, dose escalation, high dose phase I/II trials. Setting. These trials were carried out at H. Lee Moffitt Cancer, Tampa, Florida. Patients. Since October 1989, 215 patients with metastatic (stage IV) breast cancer receiving the following high-dose treatment regimens with stem cell rescue: (1) ifosfamide, carboplatin, and etoposide (ICE); (2) mitoxantrone and thiotepa (MITT); and (3) Taxol, Novantrone, thiotepa (TNT). Intervention. Patients received either escalating doses of ICE (ifosfamide 6000 to 24,000 mg/m 2, carboplatin 1200 to 2100 mg/m2, etoposide 1800 to 3000 mg/m2), or MITT (mitoxantrone 45 to 105 mg/m2, thiotepa 900 to 1350 mg/m2) or TNT (thiote pa 900 mg/m2, Novantrone 45 to 75 mg/m2, Taxol 120 to 360 mg/m2) followed by stem cell rescue. Patients were then grouped by degree of dose inten sity and chemoresponsiveness. Main Outcome Measures. EFS curves were generated by the Kaplan-Meier product limit method and compared by log rank or Kruskal-Wallis analysis. Events were defined as disease progression or death (from whatever cause) which ever came first. P values reported are two-tailed. Results. Probability of EFS (±SE) for all 215 metastatic breast cancer patients treated with ICE divided by degree of dose intensity (Phase I—lower dose intensity vs Phase II— higher dose intensity) at 3 years is 2.4 ± 2.3% for Phase I patients as compared with 18.4 ± 3.8% for phase II patients (P = .0951). The EFS for Phase II anthracycline responsive patients (n = 42) at 2 years is 36 ± 10%, 33 ± 19%, 29 ± 17% for MITT, ICE dose 11 through 15, and ICE dose level 16, respectively. The EFS for TNT at 5 months is 43 ± 19%. Overall percentages of toxic deaths were higher for patients receiving MITT (32%) and TNT (29%) as compared with the patients receiving ICE (8%) (P = .24). These differences are mainly attributed to an increased risk of cardiac toxicity in patients treated with MITT or TNT. All phase II patients (n = 139) treated with ICE, MITT and TNT were categorized by chemotherapy sensitivity status, the EFS at 3 years for the anthracycline responsive group is 31 ± 8%, as compared with for the anthracycline refractory/mini- ICE (lower doses of ICE) responsive group 19 ± 9% and 0% for the refractory group (P = .004). Conclusions. These results suggest that ICE, MITT, and TNT in the high-dose setting suggests that there may be a therapeutic advantage for delivering "highest" dose intensive therapy in patients with metastatic breast cancer. When all phase II patients treated with ICE, MITT, and TNT were categorized by chemotherapy sensitivity status, a significant differ ence in EFS among the three categories of sensitivity to anthracyclines and mini-ICE was observed. Further study of dose intensity in the setting of high-dose therapy for the treatment of metastatic breast cancer is warranted.

Marrow transplantation for Hodgkin's disease: points to ponder.

High dose chemotherapy with autologous marrow rescue has been shown to be useful in achieving long term disease free survival in patients with recurrent or relapsed Hodgkin’s disease.I4 However, high dose chemotherapy with autologous bone marrow transplantation (ABMT) is not uniformly curative and 40-70% of patients undergoing such therapy still relap~e.~.~ New treatment strategies for cohorts of patients at high risk of relapse after dose intensive therapy and ABMT need to be developed. The group at Genoa in collaboration with various investigators has been investigating the potential utility of dose intensive therapy and ABMT for patients deemed to be at high risk of relapse following standard dose therapy e.g. MOPP, ABVD or MOPP/ABVD.* Entry criteria to this multi-national trial include presence of extra-nodal disease, B symptoms, increased liver function tests and other prognostic variables. These factors have been identified as being important for prognosis after standard dose thera~y.~.’ In the experience at New York Medical College factors that influence overall and disease free survival after dose intensive therapy are not identical to variables that influence survival after standard dose therapy. While investigating the utility of dose intensive therapy for patients at risk of relapse, one should consider the impact and influence of prognostic factors that have been identified as being significant for patients undergoing dose intensive therapy. Since 1987 a series of dose intensive chemotherapy regimens were employed in the treatment of patients presenting to New York Medical College. Patients with refractory or resistant disease were eligible to receive 2

Noninvasive blood glucose sensors based on near-infrared spectroscopy.

Research into noninvasive devices for self-monitoring of blood glucose is mainly based on near-infrared spectroscopy. Such a device is particularly desirable in the intensive therapy of patients with diabetes mellitus to achieve optimal metabolic control through frequent glucose testing. The state of noninvasive assay technology is presented. Using diffuse reflectance spectra of mucous lip tissue has advantages and drawbacks compared with tissue transmittance experiments. Different approaches have been proposed in the patent literature; however, current technology requires further significant improvements, particularly within the lower normal and hypoglycemic glucose concentration ranges.

Temporary organ substitution by hemoperfusion through suspension of active donor hepatocytes in a total complex of intensive therapy in patients with acute hepatic insufficiency

The results of intensive therapy and temporary organ substitution by hemoperfusion through a suspension of active hepatocytes in 126 patients suffering from acute hepatic insufficiency (AHI) induced by virus B hepatitis, virus non-A, non-B hepatitis, acute toxic hepatitis, active liver cirrhosis, sepsis leptospirosis long-term subhepatic jaundice are presented in this paper. Hepatic encephalopathia confirmed both clinically and electroencephalographically was registered in all the patients. The patients were subdivided into two groups: a complex of commonly used curative measures according to the intensive therapy for AHI was applied in Group A (67 patients); in Group B (59 patients), alongside with the above measures, temporary organ substitution by hemoperfusion through a suspension of active porky hepatocytes was also performed. The lethality in Group A made up 59% and that in Group B was 37%.

Prognostic significance of vacuoles in L1 lymphoblasts in childhood acute lymphoblastic leukaemia: a report from Children's Cancer Study Group.

From February 1975 to February 1977, 880 patients with acute lymphoblastic leukaemia were enrolled on Children's Cancer Study Group protocol 141 designed to evaluate prognostic factors and more intensive therapy for patients with poor prognosis. 765 diagnostic bone marrow aspirates from 23 institutions were available for classification using the French-American-British system. 60 of 615 patients with L1 morphology had vacuolated lymphoblasts. Patients with vacuolated lymphoblasts had a better disease-free survival (P = 0.14) and a significantly better survival (P = 0.03) but the presence of vacuoles was associated with a low initial WBC and an age range associated with improved prognosis for disease-free and over-all survival.

Langzeitintubation in der Intensivtherapie

Establishment and securing of a clear airway is of high importance in intensive therapy of patients in otorhinolaryngology. For this purpose long-term intubation has in the latest years proved in comparison with tracheotomy, especially since more suited tubes are now available. Both methods, however, are not competitive. Their indications depend upon the particular needs of each patient and the availabilities of personnel and equipment.

FIVE YEARS' EXPERIENCE WITH THE CHEMOTHERAPY OF METASTATIC CHORIOCARCINOMA AND RELATED TROPHOBLASTIC TUMORS IN WOMEN

Abstract In 63 women with metastatic trophoblastic disease, intensive chemotherapy with the folic acid antagonist amethopterin supplemented in some by vincaleukoblastine, an oncolytic plant alkaloid, has led to complete remission in 30 patients who have been free of hormonal, radiological, or physical evidence of residual disease for from 6 months to 5 years. Seven patients now in incomplete remission continue on treatment. In addition, of the 26 patients who have died, 22 had obtained substantial but incomplete remission. Such remissions were characterized by marked suppression of tumor, in many instances leaving a persistently elevated hormone titer as the only evidence of persistent disease. Such incomplete remissions have lasted from 1 month to more than 43 months. The hazards of toxicity attendant upon this intensive form of chemotherapy may be largely obviated by proper case selection, by less intensive therapy in patients with liver or renal impairment, and by adequate supportive medical and nursing care, thus rendering the risk involved clinically acceptable. The highly variable clinical course of choriocarcinoma and related trophoblastic disease, with its indeterminate frequency of spontaneous regression, renders an exact appraisal of therapeutic accomplishment very difficult. However, the present data clearly establish the substantial therapeutic value of intensive chemotherapy in women with metastatic tumors of trophoblastic origin.

Five years' experience with the chemotherapy of metastatic choriocarcinoma and related trophoblastic tumors in women

In 63 women with metastatic trophoblastic disease, intensive chemotherapy with the folic acid antagonist amethopterin supplemented in some by vincaleukoblastine, an oncolytic plant alkaloid, has led to complete remission in 30 patients who have been free of hormonal, radiological, or physical evidence of residual disease for from 6 months to 5 years. Seven patients now in incomplete remission continue on treatment. In addition, of the 26 patients who have died, 22 had obtained substantial but incomplete remission. Such remissions were characterized by marked suppression of tumor, in many instances leaving a persistently elevated hormone titer as the only evidence of persistent disease. Such incomplete remissions have lasted from 1 month to more than 43 months.The hazards of toxicity attendant upon this intensive form of chemotherapy may be largely obviated by proper case selection, by less intensive therapy in patients with liver or renal impairment, and by adequate supportive medical and nursing care, thus rendering the risk involved clinically acceptable.The highly variable clinical course of choriocarcinoma and related trophoblastic disease, with its indeterminate frequency of spontaneous regression, renders an exact appraisal of therapeutic accomplishment very difficult. However, the present data clearly establish the substantial therapeutic value of intensive chemotherapy in women with metastatic tumors of trophoblastic origin.