[Allowing a patient in a vegetative state to die in hospital under the direction of a nursing-home physician]. / Het laten sterven van een patiënt in een vegetatieve toestand in het ziekenhuis met de verpleeghuisarts als hoofdbehandelaar.

In the case of a 52-year-old man, who was in a vegetative state after resuscitation following an unwitnessed cardiac arrest, the nursing-home physician assumed responsibility for the total treatment in a transfer unit of the hospital. His systematic, multidisciplinary approach enabled direction of the complex situation in which many medical and paramedical personnel were involved. When an airway infection occurred as a complication shortly after responsibility for the patient had been assumed, the nursing-home physician could take a well-considered decision to withdraw medical treatment on the basis of the treatment plan which had been formulated in a short time and contact with the family. In clinical practice it is difficult to determine the most appropriate moment to withdraw all medical therapy, including artificial nutrition and hydration, in order to prevent a hopeless vegetative state. This case illustrates how hospital physicians and nursing-home physicians may cooperate during the 'waiting phase' of the clinical course of a vegetative state. A hopeless vegetative state can be prevented by using these transmural possibilities for cooperation, including an early input of knowledge and experience about the long-term course of a vegetative state.

Nutrient support in hematopoietic cell transplantation.

High-dose cytoreduction and hematopoietic stem cell infusion form the basis for treatment of hematologic cancers, defects or failure of hematopoiesis, and some solid tumors. As an antitumor therapy, allogeneic hematopoietic cell transplantation (HCT) is superior to autologous HCT by induction of a graft-vs-tumor effect. However, recipients of allografts suffer higher transplant-related mortality owing to graft-vs-host disease (GVHD). Nutrition support research must recognize that HCT is a heterogeneous modality whose short and long-term outcomes are affected by transplant type, preparative regimens, diagnosis, disease stage, age, and nutritional status. The field of HCT will diversify further as lower dose cytoreduction and mixed chimerism grafts allow expansion of the technique to older patients and to other diseases.

Impact of a randomized, controlled trial of liberal vs conservative hospital discharge criteria on energy, protein, and fluid intake in patients who received marrow transplants.

OBJECT: To determine if adult patients who received marrow transplants had faster resumption of oral energy and nutrient intake and shorter duration of intravenous (i.v.) fluid requirement if discharged from the hospital earlier than is customary. DESIGN: Randomized, controlled trial of patients remaining hospitalized because of inadequate oral intake. Consenting patients were assigned randomly to remain hospitalized (hospital group) or be discharged to an ambulatory setting (ambulatory group). SUBJECTS: Seventy-eight patients of the Fred Hutchinson Cancer Research Center who were consuming less than 33% of estimated energy requirement and requiring up to 3,000 mL of fluids per day intravenously. INTERVENTION: Participants received nutrition counseling by a registered dietitian to promote resumption of oral intake. Daily oral intake records were analyzed to determine energy and nutrient content. MAIN OUTCOME MEASURES: Days after study enrollment to consume 33% of energy and protein requirements and total number of days of i.v. fluid support were analyzed by group until discharge from the center, approximately 100 days after transplantation. STATISTICAL ANALYSES: Demographic data were defined by group means. Differences between treatment procedures were determined by Cox regression analysis. No variables were confounding. RESULTS: The hospital group took fewer days than the ambulatory group to resume oral energy intake (4.5 vs 8.0, P = .004) and to discontinue i.v. fluids (30.5 vs 48.5, P = .019). There was no difference between groups in days of parenteral nutrition support (P = .817) or days to resume oral protein intake (P = .470). APPLICATIONS/CONCLUSIONS: Oral and gastrointestinal complications delay resumption of oral energy and protein intakes after transplantation. Earlier hospital discharge can achieve cost savings but may delay resumption of oral energy intake. Because of continued high-risk nutrition status and potential for rapid change in medical status, nutrition assessment and counseling are necessary in both the hospital and ambulatory setting to promote resumption of oral intake and discontinuation of i.v. fluids.

Hereditary neuropathy with liability to pressure palsies. Phenotypic differences between patients with the common deletion and a PMP22 frame shift mutation.

In six families with hereditary neuropathy with liability to pressure palsies (HNPP) the 17p11.2 deletion was absent, but single strand conformation-analysis and subsequent sequencing demonstrated a heterozygous G-insertion in a stretch of six Gs at nt 276281 of the PMP22 gene, resulting in a frame shift after Gly94. Haplotype comparison of the six families revealed common ancestry. We compared the phenotype of 23 patients from these six families with the phenotype of 63 patients of 17 families with the common deletion. The patients with the G-insertion showed the clinical, electrophysiological and morphological characteristics of common HNPP, but in addition they had significantly more neuropathic features, mimicking hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT1). To explain this distinct phenotype we suggest that, by translation of the mutated gene, a markedly changed polypeptide is formed without the normal cytoplasmic C-terminal of the native protein, resulting in a loss of function similar to that with the common deletion, but exerting an extra disturbance of Schwann cell functions, probably by hampering normal myelin formation or maintenance.

Intravenous lipid dose and incidence of bacteremia and fungemia in patients undergoing bone marrow transplantation.

Experimental data have implicated intravenous lipids as being immunosuppressive, yet evidence that lipids are associated with an increase in clinically documented infections is sparse. A prospective trial conducted in patients with hematologic malignancies who were undergoing bone marrow transplantation compared the incidence of bacteremia and fungemia during the first month after the transplant. Patients (n = 512) were randomly assigned to receive 6-8% (low dose) or 25-30% (standard dose) of total daily energy as a 20% lipid emulsion. An adaptive randomization scheme stratified for treatments that might influence infection outcome (hematopoietic growth factors, fluconazole, graft-versus-host disease prophylaxis with steroids, pentoxifylline, intravenous immunoglobulin, and total body irradiation). The transplant type (autologous, related family donor, or unrelated donor) did not differ in distribution between treatment groups. Of the evaluable patients (n = 482), 55 patients in the standard-dose lipid group developed bacteremia or fungemia compared with 54 in the low-dose lipid group. The log-rank test comparing the time to first infection found no association between the incidence of bacteremia or fungemia and intravenous lipid (P = 0.95). Similar results were found when analyzed as intent-to-treat (P = 0.98), when bacterial or fungal infections at all sites were included (P = 0.94), and when the observation period was extended to 60 d (P = 0.58 for blood infections, P = 0.77 for infections at all sites). These data indicate that moderate amounts of intravenous lipid rich in linoleic acid are not associated with an increased incidence of bacterial or fungal infections in patients undergoing bone marrow transplantation and receiving total parenteral nutrition.

Bone density loss during treatment of chronic GVHD.

Nine adult patients 31-47 (median 39) years of age treated with prednisone and cyclosporin A (CsA) for chronic graft-versus-host disease (GVHD) were evaluated for biochemical factors associated with skeletal turnover at initiation of immunosuppressive therapy (3 months after marrow transplant) and 9 months later (follow-up). Absorptiometry studies of the wrist and lumbar spine were also performed. Serum levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D) were decreased at enrollment, particularly in the six males. Values for all nine patients remained low at follow-up. Levels of serum 25-hydroxycholecalciferol (25(OH)D), parathyroid hormone, and ionized calcium were normal at enrollment and follow-up. Mean urine hydroxyproline and calcium levels were elevated at enrollment, suggesting increased bone resorption; the mean values decreased to the high normal range at follow-up. Urine magnesium excretion was elevated in eight of nine patients at baseline and remained elevated at follow-up in three of eight evaluable patients. Single and dual photon absorptiometry of the wrist and spine, respectively, and dual energy X-ray absorptiometry of the spine, were utilized to evaluate bone mineral density over time. The precision of these tests was, respectively, +/- 3.5%, +/- 3.1% and +/- 1.0%. Results showed a significant ( > 2.5 times the precision) decrease over 9 months in bone mineral density in three of five evaluable males and all three females. The findings indicate increased collagen and bone turnover, increased urinary magnesium and calcium excretion and a significant risk of osteoporosis in patients receiving treatment for chronic GVHD. Preventive measures, including gonadal hormone replacement in females, should be initiated early after transplantation. Further studies are needed to identify patients at highest risk of bone loss and to monitor the effects of preventive therapy.

Safe handling of antineoplastic drugs. Results of a survey.

As research continues to highlight the risks involved in handling antineoplastic drugs, the health services are giving increased attention to safety measures. In order to establish what protective measures nursing staff employ and what they know about antineoplastic drugs, a survey was carried out in The Netherlands. The questions were based on the self-study modules by Dunne and the (American) Oncology Nursing Society. A total of 1,373 questionnaires were distributed in 10 hospitals. Of these, 824 were returned, which represents a response rate of 60%. Over two-thirds (68%) of the nursing staff reported that they were involved, on a daily or weekly basis, in caring for patients being treated with antineoplastic drugs. In the view of 94% of the nurses, protective measures are effective. While administering antineoplastic drugs, 91% of the respondents said that they wore gloves, 21% said that they wore a gown, 18% wore a mask, and 3% used goggles. While handling excreta, fewer nurses applied safety measures. Thirty-nine percent of the respondents knew that latex gloves offer a greater degree of protection than PVC gloves. It appeared that there was not one Dutch hospital whose guidelines for the safe handling of antineoplastic material were completely up-to-date and that nurses do not always follow the guidelines established.

Prevalence of nutrition-related problems among long-term survivors of allogeneic marrow transplantation.

The nutritional status and prevalence of nutrition-related problems in 192 adult and child allogeneic marrow transplant recipients were evaluated 1 year after transplant in a retrospective chart review. Among these patients, 63% exhibited evidence of chronic graft-versus-host disease (GVHD) at the time of nutrition evaluation, including 44% with extensive disease who were receiving immunosuppressive therapy. Oral sensitivity was observed in 23% of all patients reviewed, and frank stomatitis occurred in 8%. The frequency of xerostomia was 18%; anorexia, 8%; reflux symptoms, 7%; diarrhea, 7%; steatorrhea, 5%; dysgeusia, 3%; and limited exercise tolerance because of dyspnea or joint contractures, 4%. Weight loss 3 to 12 months after transplant was experienced by 28%. Nutrition-related problems, changes in anthropometric indexes indicative of suboptimal nutritional status, and inadequate energy intake were observed more frequently in patients with extensive chronic GVHD than in patients without GVHD or in those with limited GVHD. Our findings indicate a high prevalence of nutrition problems among recipients of allogeneic marrow transplantation 1 year after transplant and, further, suggest the need for ongoing, community-based nutrition monitoring after discharge from a transplant center.

Food intake patterns and foodservice requirements on a marrow transplant unit.

Marrow transplantation (MT) is used for treatment of lymphomas and hematological malignancies. The preparative regimens (including high-dose chemoradiotherapy), as well as infections, medications, and graft-versus-host disease, result in nutritional complications. In order to determine foodservice needs, hospital personnel tabulated the foods requested and the daily number of meals ordered by 205 MT patients the final 14 days before their initial post-transplant hospital discharge. Oral and total (oral plus parenteral) caloric intakes were calculated from weighted food intake records using a computerized nutrient database. Per patient meal orders increased from 2.6 +/- 2.2 (SD) to 5.3 +/- 2.0 per day, and the mean number of items per day increased from 4.9 +/- 4.9 to 12.4 +/- 4.9, 14 days vs. 1 day prior to discharge. Beverages were the most frequently requested item, followed by bread products and cooked fruits and vegetables. Patients consumed approximately 60% of total calories from oral intake 1 day prior to discharge. The foodservice must be designed to provide a variety of foods served at frequent intervals to meet the needs of MT patients and thereby reduce dependence on parenteral nutrition.

Sex differences in nitrogen balance following marrow grafting for leukemia.

A sex difference in nitrogen balance was investigated in 40 adults, 21 men and 19 women, undergoing chemoradiotherapy and marrow transplantation for leukemia and receiving total parenteral nutrition. Twenty-four hour collections of urine and mixed urine-stool were analyzed for total nitrogen daily through day 14 posttransplant. Nitrogen balance, corrected for changes in blood urea nitrogen, decreased significantly over time (p less than 0.005) in both men and women, but men experienced a greater negative nitrogen balance during the time period (p less than 0.001). Mean daily nitrogen balance in men was -6.0 g for week 1 and -9.2 g for week 2, corresponding to -3.3 g and -5.6 g in women for week 1 (p less than 0.005) and 2 (p less than 0.01), respectively. The differences remained after controlling for stress level and adjusting for total calorie intakes. There were no differences in age, disease status, or nitrogen intakes per kg ideal body weight, and no effects on nitrogen balance by arm muscle area at admission, cyclosporine use, or the branched-chain amino acid content of the parenteral solution. The average rise in 3-methylhistidine excretion was 23% in men and 11% in women. These results suggest higher per kg nutrient needs in males during stress and may indicate differing metabolic responses to stress. The possibility of gender differences should be considered in research evaluating nitrogen metabolism during severe stress.

Body composition changes in marrow transplant recipients receiving total parenteral nutrition.

Nine patients with acute lymphocytic leukemia in remission, aged 12-35 years, undergoing allogeneic bone marrow transplantation (BMT) were studied for changes in body fluid balance and body composition. Body composition and fluids were assessed the first 4 weeks following BMT, using isotope dilution and anthropometry. Oral and parenteral nutrient intakes were recorded daily. Tracer dilution techniques were used to assess body fluid volumes and estimate body cell, lean body, and body fat masses. Body cell mass was lost (mean -1.62 kg, P less than 0.05) without significant changes in body fat or lean body masses. There was an expansion of the extracellular fluid compartment (mean +0.8 l, P less than 0.05) and a loss in the intracellular fluid compartment (mean -1.3 l, P less than 0.05) with little change in total body water volume. Changes in body weight correlated poorly with body cell mass or fluid volume changes. Change in arm muscle area correlated well with changes in body cell mass (r = 0.61, P less than 0.05) and lean body mass (r = 0.68, P less than 0.05), while that of arm fat area did not reflect its isotope dilution-derived counterpart. Instead, the change in arm fat area was related to shifts in fluid compartments. Prealbumin decreased significantly (mean -9.3 mg/dl, P less than 0.05), while albumin decreased slightly (mean -0.1 mg/dl), and both were related to changes in body cell mass. Nitrogen balance was negative throughout the study and the overall mean was related to the change in body cell mass (r = 0.60, P less than 0.05). Calorie and protein intakes were not associated with the changes in body composition, implying other causal factors.

Intravenous branched chain amino acid trial in marrow transplant recipients.

Branched chain amino acids (BCAA) improve nitrogen balance and end-organ function in surgical patients, but are untested in marrow transplant recipients. We compared nitrogen balance, urinary 3-methylhistidine-to-creatinine ratio, upper arm anthropometry, serum prealbumin, and day to peripheral engraftment in a randomized, double-blinded trial between 45% (high-leucine) and 23% BCAA intravenous solutions in 40 adult leukemia patients for 1 month following allogeneic marrow transplantation. Nutritional support, provided at approximately 30 nonprotein calories/kg and 0.21 g nitrogen/kg ideal weight, did not differ between groups. Despite greater nitrogen loss and muscle breakdown evidenced by increased 3-methylhistidine-to-creatinine ratio and loss of arm muscle area by study end in the 45% BCAA, no statistical differences were observed when nitrogen balance was compared by week and within stress level as defined by organ and infectious complications. It is likely the patients in the 45% BCAA experienced greater metabolic stress by study end. Serum prealbumin and day posttransplant to peripheral engraftment also did not differ between groups. The chances (power) of this study exceeded 85% in detecting a difference in nitrogen balance of 2.5 g during study week 1 and 4.0 g during week 2. The power during week 3 was 77% for detecting a difference of 4.0 g, and it is unlikely that the true difference exceeds this magnitude. Thus, we did not find any evidence that intravenous BCAA-enriched solutions improved nitrogen balance during the first month after marrow transplantation.

Effects of resistive exercise on skeletal muscle in marrow transplant recipients receiving total parenteral nutrition.

Skeletal muscle protein loss occurs during marrow transplantation despite total parenteral nutrition. To determine if muscle atrophy could be minimized with exercise therapy, 30 patients undergoing marrow transplantation for acute leukemia completed a prospective randomized trial to receive: (1) no therapy (controls), (2) physical therapy thrice weekly (PT3), or (3) physical therapy five times weekly (PT5). Patients were studied through 35 days posttransplant. Muscle protein status and turnover was assessed by weekly nitrogen balance, and creatinine and 3-methylhistidine excretion. Results favored a muscle protein-sparing effect of exercise, as a significant decrease in creatinine excretion in controls only suggested muscle protein loss associated with inactivity. Changes in arm muscle area correlated with energy, but not protein intake. Large individual variation, inadequate nutritional support and differences in admission arm muscle area may have clouded these results.

Parenteral nutrition in marrow transplant recipients after discharge from the hospital.

The use of parenteral nutrition (PN) following discharge from the hospital and its relation to patient characteristics were evaluated retrospectively in 246 marrow transplant recipients. PN was used in 65% of all patients. Patients with leukemia, regardless of age, sex, type of leukemia, remission status, irradiation schedule, laminar air flow isolation and donor sex match, required more frequent and more prolonged PN than patients with aplastic anemia. Children required PN most often for failure to thrive and adults for stomatitis. There was no significant difference in frequency or duration of PN among 24 patients with acute myelogenous leukemia randomized to receive cyclosporine or methotrexate therapy and among 28 patients with acute lymphoblastic leukemia randomized to interferon or no interferon. We conclude that outpatient PN presents a valuable addition to posttransplant supportive care. It shortens the duration of hospitalization both by earlier discharge of patients still requiring PN and by avoiding readmission to the hospital for the purpose of PN.

Nutritional support in marrow graft recipients with single versus double lumen right atrial catheters.

To determine the comparative efficiency of single and double lumen right atrial catheters, marrow transplant recipients were evaluated during a 26-month period retrospectively. Calories and protein infused as a percent of the amount ordered was calculated by week from initiation of total parenteral nutrition through day 28 posttransplantation. Data from 1979 reflected initial technical difficulties, showing no significant difference between groups. Patients with double lumen catheters received significantly greater (P less than 0.05) calories during the first 3 weeks after transplant in 1980 and 1981. A similar trend was seen in protein infusion. A significantly greater proportion of patients with double lumen catheters received at least 90% of the ordered total parenteral nutrition during the first 3 weeks after transplant in both years. These results suggest that the ability to infuse total parenteral nutrition in ordered amounts can be accomplished using the double lumen catheter.