On-site treatment of avalanche victims: Scoping review and 2023 recommendations of the international commission for mountain emergency medicine (ICAR MedCom).

INTRODUCTION: The International Commission for Mountain Emergency Medicine (ICAR MedCom) developed updated recommendations for the management of avalanche victims. METHODS: ICAR MedCom created Population Intervention Comparator Outcome (PICO) questions and conducted a scoping review of the literature. We evaluated and graded the evidence using the American College of Chest Physicians system. RESULTS: We included 120 studies including original data in the qualitative synthesis. There were 45 retrospective studies (38%), 44 case reports or case series (37%), and 18 prospective studies on volunteers (15%). The main cause of death from avalanche burial was asphyxia (range of all studies 65-100%). Trauma was the second most common cause of death (5-29%). Hypothermia accounted for few deaths (0-4%). CONCLUSIONS AND RECOMMENDATIONS: For a victim with a burial time ≤ 60 minutes without signs of life, presume asphyxia and provide rescue breaths as soon as possible, regardless of airway patency. For a victim with a burial time > 60 minutes, no signs of life but a patent airway or airway with unknown patency, presume that a primary hypothermic CA has occurred and initiate cardiopulmonary resuscitation (CPR) unless temperature can be measured to rule out hypothermic cardiac arrest. For a victim buried > 60 minutes without signs of life and with an obstructed airway, if core temperature cannot be measured, rescuers can presume asphyxia-induced CA, and should not initiate CPR. If core temperature can be measured, for a victim without signs of life, with a patent airway, and with a core temperature < 30 °C attempt resuscitation, regardless of burial duration.

Evaluating Escherichia coli removal performance in stormwater biofilters: a laboratory-scale study.

Biofilters are common, low energy technologies used for the treatment of urban stormwater. While they have shown promising results for the removal of stormwater microorganisms, certain factors affect their performance. Hence, this study investigated the effects of particle-microbial interaction, inflow concentration, antecedent microbial levels and plant species on microbial removal capacity. A biofilter column study was set up to evaluate removal performance and a sequential filtration procedure was used to estimate microbial partitioning. The columns were dosed with different concentrations of free phase Escherichia coli only and E. coli mixed with stormwater sediment. Results indicate that the microbial removal is significantly affected by inflow concentration and antecedent microbial levels. Leaching was only observed when a relatively low inflow concentration event occurred within a short period after a very high inflow concentration event. Finally, Lomandra longifolia showed better removal compared with Carex appressa.

Retention of mouth-to-mouth, mouth-to-mask and mouth-to-face shield ventilation.

BACKGROUND: Retention of mouth-to-mouth, mouth-to-mask and mouth-to-face shield ventilation techniques is poorly understood. METHODS: A prospective randomised clinical trial was undertaken in January 2004 in 70 candidates randomly assigned to training in mouth-to-mouth, mouth-to-mask or mouth-to-face shield ventilation. Each candidate was trained for 10 min, after which tidal volume, respiratory rate, minute volume, peak airway pressure and the presence or absence of stomach inflation were measured. 58 subjects were reassessed 1 year later and study parameters were recorded again. Data were analysed with ANOVA, chi(2) and McNemar tests. RESULTS: Tidal volume, minute volume, peak airway pressure, ventilation rate and stomach inflation rate increased significantly at reassessment with all ventilation techniques compared with the initial assessment. However, at reassessment, mean (SD) tidal volume (960 (446) vs 1008 (366) vs 1402 (302) ml; p<0.05), minute volume (12 (5) vs 13 (7) vs 18 (3) l/min; p<0.05), peak airway pressure (14 (8) vs 17 (13) vs 25 (8) cm H(2)O; p<0.05) and stomach inflation rate (63% vs 58% vs 100%; p<0.05) were significantly lower with mouth-to-mask and mouth-to-face shield ventilation than with mouth-to-mouth ventilation. The ventilation rate at reassessment did not differ significantly between the ventilation techniques. CONCLUSIONS: One year after a single episode of ventilation training, lay persons tended to hyperventilate; however, the degree of hyperventilation and resulting stomach inflation were lower when a mouth-to-mask or a face shield device was employed. Regular training is therefore required to retain ventilation skills; retention of skills may be better with ventilation devices.

Phase II study of intravenous CI-958 in metastatic colorectal adenocarcinoma.

In a multicenter, phase II trial, CI-958, a benzothiopyranoindazole DNA intercalator, was administered to 18 patients who had not received prior chemotherapy for metastatic colorectal cancer. The drug was given by intravenous infusion at a dose of 700 mg/m2 every 21 days. There were no objective responses. Grades III and IV toxic effects were limited to granulocytopenia in 42% of courses and anemia in 5% of courses. There was one case of grade III increase in transaminases. Our results show that at this dose and schedule, CI-958 lacks activity against colorectal cancer.

Dose-response trial of megestrol acetate in advanced breast cancer: cancer and leukemia group B phase III study 8741.

PURPOSE: To investigate whether dose escalation of megestrol acetate (MA) improves response rate and survival in comparison with standard doses of MA. PATIENTS AND METHODS: Three hundred sixty-eight patients with metastatic breast cancer, positive and/or unknown estrogen and progesterone receptors, zero or one prior trial of hormonal therapy, and no prior chemotherapy for metastatic disease were prospectively randomized into three groups. The groups of patients received either MA 160 mg/d (one tablet per day), MA 800 mg/d (five tablets per day), or MA 1,600 mg/d (10 tablets per day). RESULTS: Patient characteristics were well balanced in the three treatment groups. Three hundred sixty-six patients received treatment and were included in the analyses. The response rates were 23%, 27%, and 27% for the 160-mg, 800-mg, and 1,600-mg arms, respectively. Response duration correlated inversely with dose. Median durations of response were 17 months, 14 months, and 8 months for the 160-mg, 800-mg, and 1,600-mg arms, respectively. No significant differences in the treatment arms were noted for time to disease progression or for survival; survival medians were 28 months (low dose), 24 months (mid dose) and 29 months (high dose). The most frequent and troublesome toxicity, weight gain, was dose-related, with approximately 20% of patients on the two higher-dose arms reporting weight gain of more than 20% of their prestudy weight, compared with only 2% in the 160-mg dose arm. CONCLUSION: With a median follow-up of 8 years, these results demonstrate no advantage for dose escalation of MA in the treatment of metastatic breast cancer.

Schedule dependency of 21-day oral versus 3-day intravenous etoposide in combination with intravenous cisplatin in extensive-stage small-cell lung cancer: a randomized phase III study of the Cancer and Leukemia Group B.

PURPOSE: This was a randomized phase III study to test the schedule dependency of etoposide given as a conventional 3-day intravenous (IV) regimen versus a prolonged 21-day oral regimen for extensive-stage small-cell lung cancer (SCLC). Both regimens contained IV cisplatin. The objectives were to compare survival (primary end point) and to establish response rates, failure-free survival, and toxicity (secondary end points). PATIENTS AND METHODS: Patients with untreated measurable or assessable disease and normal organ function were eligible. Randomization was stratified according to performance status 0 versus 1 or 2. Treatment consisted of etoposide 130 mg/m2/d IV for 3 days and cisplatin 25 mg/m2/d IV for 3 days every 21 days for eight courses (schedule 1) versus etoposide 50 mg/m2/d orally for 21 days and cisplatin 33 mg/m2/d IV for 3 days every 28 days for six courses (schedule 2). In 1990, bioavailability of oral etoposide was assumed to be 50%, and the study was designed to deliver the same total doses of etoposide and cisplatin on both regimens over 24 weeks without the use of growth factors. RESULTS: Between December 1990 and October 1993, 306 eligible patients were entered. Of these, 69% were male and 66% were > or = 60 years of age; 21% had a performance status of 0, 47% a performance status of 1, and 32% a performance status of 2; 156 were randomized to receive schedule 1 and 150 to receive schedule 2. Overall median survival estimates were 9.5 and 9.9 months (difference not significant) for schedule 1 and schedule 2, respectively. The 95% confidence interval (CI) for overall survival, 8 to 11 months, was the same for both schedules, with 126 and 117 deaths on schedule 1 and 2, respectively. Both schedules also resulted in the same median failure-free survival estimate of 7 months (95% CI, 6 to 8 months on either schedule). Complete and partial responses were observed in 15% and 42% of patients on schedule 1 and 14% and 47% on schedule 2, respectively. The overall maximal hematologic toxicities grade 3 and 4 for leukocytes, neutrophils, platelets, and hemoglobin were, respectively, as follows: schedule 1, 62%, 85%, 32%, and 32%; schedule 2, 83%, 83%, 52%, and 53%. Lethal toxicity due to neutropenia and infection occurred in 4% of patients on schedule 1 and 10% on schedule 2 (difference not statistically significant). CONCLUSION: The two schedules of etoposide in combination with cisplatin did not result in differences in treatment outcome with respect to tumor response and survival. However, a significantly greater rate of severe or life-threatening hematologic toxicity was noted on the 21-day oral etoposide treatment schedule.

Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma.

BACKGROUND: Adjuvant chemotherapy is widely used for breast cancer and is known to extend survival. Some clinicians seek a greater survival benefit by increasing the intensity of the dose, whereas others lower it to diminish toxicity. METHODS: The Cancer and Leukemia Group B (CALGB) conducted a randomized trial of different levels of doses and dose intensity (dose per unit of time) of adjuvant chemotherapy in 1572 women with node-positive, stage II breast cancer who were assigned to three treatment groups. One group received 400 mg of cyclophosphamide per square meter of body-surface area and 40 mg of doxorubicin per square meter once every 28 days and 400 mg of fluorouracil per square meter twice every 28 days, for six cycles. Another group received 50 percent higher doses of the three drugs (600 mg, 60 mg, and 600 mg, respectively) but for only four cycles, so that the total dose was identical in these two groups but the dose intensity was higher in the first. The third group of women received half the total dose used in the other two groups and at half the dose intensity used in the second group. RESULTS: After a median of 3.4 years of follow-up, the women treated with a high or moderate dose intensity had significantly longer disease-free survival (P < 0.001) and overall survival (P = 0.004) than those treated with a low dose intensity, in three-way log-rank comparisons. However, the difference in survival between the two groups treated with a moderate or high dose intensity was not significant. These results are consistent with either a dose-response effect or a threshold level of the dose or dose intensity. CONCLUSIONS: The doses of chemotherapy used to treat breast cancer, especially early breast cancer, should not be reduced if the maximal benefit is to be achieved.

Interleukin-2 activity in patients with extensive small-cell lung cancer: a phase II trial of Cancer and Leukemia Group B.

BACKGROUND: Chemotherapy may induce overall (complete plus partial) response rates of more than 50% and complete response rates up to 25% in extensive small-cell lung cancer (stage IIIB or IV), but survival is generally limited to 8-12 months. Interleukin-2 (IL-2) has demonstrated activity against this disease in vitro and has produced regression in melanoma and renal cell carcinoma. PURPOSE: The purpose of this study was to determine in a prospective, nonblinded, phase II trial the activity of IL-2 in patients with extensive small-cell lung cancer who had not achieved complete remission with chemotherapy. METHODS: The 68 patients eligible for the study were initially treated with at least one dose of combination chemotherapy with cisplatin, doxorubicin, cyclophosphamide, and etoposide (PACE). Of the 50 who did not obtain complete remission with PACE, 24 who had measurable or evaluable disease and whose medical condition allowed further therapy were treated with IL-2. Beginning 3 weeks after the last dose of PACE, IL-2 was administered intravenously at 4.5 million Nutley units/m2 per day as a continuous infusion for 96 hours, followed by a 3-day rest. The planned duration of therapy was 8 weeks. RESULTS: Of the 24 patients eligible to receive IL-2, four (17%) with measurable disease or evaluable but not measurable disease obtained a complete response after IL-2 therapy; one (4%) patient had a partial response. The overall response rate was 21%. Complete responses continued for 8, 9, and more than 11 months in three patients; the remaining patient developed acute myelomonocytic leukemia while in complete remission approximately 8 months after the start of IL-2 therapy. Only five of the 24 patients were able to complete the planned 8 weeks of IL-2 therapy. Therapy was discontinued in 11 patients because of life-threatening side effects, in six because of disease progression, and in two who withdrew from the study, probably related to IL-2 toxicity. CONCLUSIONS: These results indicate that IL-2 has some activity in extensive small-cell lung cancer and suggest that IL-2 is not cross-resistant with PACE therapy. IMPLICATIONS: Further studies are needed to define the optimum timing, dose, and schedule of IL-2 and to determine whether the agent has a role in the therapy of small-cell lung cancer.

A randomized clinical trial comparing melphalan/prednisone with or without interferon alfa-2b in newly diagnosed patients with multiple myeloma: a Cancer and Leukemia Group B study.

PURPOSE: This clinical trial was designed to compare the effectiveness of the standard melphalan and prednisone regimen to that of melphalan, prednisone, and interferon in patients with untreated multiple myeloma. PATIENTS AND METHODS: Between October 1985 and March 1988, 278 patients were accrued to a multi-institutional, randomized clinical trial. Responding patients were treated for 2 years before termination of therapy. RESULTS: After a median follow-up of 23 months, the overall remission rate for the melphalan/prednisone treatment group was 44% compared with 33% for the group receiving melphalan/prednisone/interferon alfa-2b. The durations of response and survival were identical for the two treatment groups. Median survival was 3.17 years on melphalan/prednisone treatment and 3.0 years on melphalan/prednisone/interferon alfa-2b treatment. Both hematologic and nonhematologic toxicities were greater in the melphalan/prednisone/interferon alfa-2b treatment group, but were usually of a mild or moderate degree and did not interfere with the completion of therapy. The frequency of deaths in the two treatment groups attributable to the treatment itself was similar. CONCLUSION: This study shows no advantage to the concomitant delivery of interferon alfa-2b with standard melphalan and prednisone as initial treatment for patients with multiple myeloma.

A phase II study of recombinant interleukin-2 with or without recombinant interferon-beta in non-Hodgkin's lymphoma. A study of the Cancer and Leukemia Group B.

Interleukin-2 (IL-2) and interferon-beta (IFN-beta) have demonstrated activity against lymphoid malignancies, presumably mediated by the augmentation of lymphokine-activated killer (LAK) cell and natural killer (NK) cell activity. There is in vitro and in vivo evidence to suggest that the combination of IL-2 and IFN-beta is synergistic. The Cancer and Leukemia Group B (CALGB) conducted a randomized phase II trial of IL-2 with or without IFN-beta in 49 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). Overall toxicity was severe, with 17 patients experiencing life-threatening toxicity. Three patients had treatment-related deaths. Responses were noted in seven patients (17%). There were no meaningful differences between treatment arms in toxicity profile, response rate, or modulation of in vivo NK and LAK activity. We conclude that IL-2 with or without IFN-beta is not effective therapy for NHL in the doses and schedule used in this study.

Phase II study of echinomycin in patients with advanced breast cancer: a report of Cancer and Leukemia Group B protocol 8641.

Twenty-five women with advanced histologically documented stage IV recurrent or inoperable breast cancer were enrolled on a phase II study of echinomycin administered at a dose of 1.2 mg/m2 intravenously over 30 minutes weekly for 4 weeks followed by a two week rest period. Seventy-six percent of patients had visceral dominant disease at study entry and all patients had previously received chemotherapy. One of 21 eligible patients had a partial response lasting 147 days. The median survival for this group of patients was 5.9 months and the median time to treatment failure was 1.7 months. Nausea and vomiting was the primary toxic effect and was severe or life-threatening in 43% of patients. Transient elevation of liver enzymes occurred in 30% of patients. Bone marrow suppression was not significant. Echinomycin as employed in this study did not demonstrate significant antitumor activity in previously treated patients with advanced breast cancer.

Carboplatin and vinblastine in advanced non-small-cell lung cancer: a phase II study.

Between July 2, 1987, and August 21, 1987, Cancer and Leukemia Group B (CALGB) conducted a phase II evaluation of carboplatin (CBDCA) and vinblastine (VBL) in advanced non-small-cell lung cancer. Of the 58 patients who entered the study, 55 were eligible and produced follow-up data. Chemotherapy, which was carried out in 28-day cycles, consisted of 4 mg/m2 VBL given on days 1 and 3 and 125 mg/m2 CBDCA given on days 1-3. Partial responses were observed in 10 cases (18%), and 1 patient (2%) exhibited regression of evaluable disease. No complete responses were achieved. The overall objective response rate was 20%. The median survival was 6.1 months, and the median time to treatment failure was 3.3 months. Life-threatening (grade 4) toxicity was mainly leukopenia (20%), followed by anemia (7%), infection (4%), thrombocytopenia (2%), fever (2%), nausea and vomiting (2%), and weight loss (2%). There were two deaths due to infection. The results of this study demonstrate that the combination CBDCA/VBL is active in advanced NSCLC; however, whether this combination is more active than either CBDCA or VBL alone is unknown.

Phase II study of continuous-infusion diaziquone in relapsed/refractory acute nonlymphocytic leukemia.

A total of 74 patients with relapsed/refractory acute nonlymphocytic leukemia were entered in a phase II trial of diaziquone (AZQ) administered by continuous infusion at a dose of 28 mg/m2 a day for 5 days. Complete remission (CR) was achieved in 12 of the 67 evaluable patients (18%), all occurring in relapsed patients (12 of 55, 22%). There were eight partial responders (one of whom was in the refractory group). Three of these had normal M-1 bone marrow but did not meet peripheral blood criteria for CR. The median duration of CR was 13.6 weeks (range, 4-40+). Nonhematologic toxicity was mild to moderate and easily manageable. Hematologic toxicity was severe or life threatening in all patients. This study confirms the activity of AZQ when given as a continuous infusion to patients with relapsed acute nonlymphocytic leukemia.

Are the elderly predisposed to toxicity from cancer chemotherapy? An investigation using data from the Eastern Cooperative Oncology Group.

Cancer management of the elderly is a topic which has received relatively little attention. This is surprising in view of the fact that approximately 50% of all cancers occur in patients over 65 years of age. In this paper, six terminated studies of the Eastern Cooperative Oncology Group involving approximately 3000 cancer patients have been examined to characterize the nature and extent of the susceptibility to toxicity of elderly patients undergoing chemotherapy for cancer. The six studies were restricted to three primary sites: lung, breast, and colorectum. The results indicate that elderly cancer patients in the study did not experience any increase in the frequency or severity of the toxicity of chemotherapy. The data do not indicate any systematic bias in patient selection with respect to important clinical variables such as performance status, prior treatment, and presence of liver metastases. Compliance with dosage regimen as prescribed by the protocol was similar for each age group during the course of studies. Comparability was further indicated by the fact that the response rates among the elderly were equivalent to the rest of the patient population. The results have important implications for cancer management of the elderly.

Erythroleukemia in a renal transplant recipient.

A 53-year-old male developed acute erythroleukemia three years after renal transplantation. He had received three years of immunosuppressive therapy with azathioprine. A preleukemia phase associated with chromosome abnormalities was recognized. Azathioprine has been associated with chromosome abnormalities. The chronic stimulation of an abnormal erythroid clone by transplantation may have hastened the development of erythroleukemia.