Historical Matched Controls Research Articles

Mechanical Insufflation–Exsufflation Improves Outcomes for Neuromuscular Disease Patients with Respiratory Tract Infections

The efficacy of mechanical insufflation-exsufflation, in addition to standard chest physical treatments, was investigated as a first-line intervention for patients with neuromuscular diseases with respiratory tract infections and airway mucous encumbrance. The short-term outcomes of 11 consecutive neuromuscular disease patients with respiratory tract infections and tracheobronchial mucous encumbrance who were administered mechanical insufflation-exsufflation and conventional chest physical treatments in an intensive care unit were compared with the outcomes of 16 historical matched controls who had received chest physical treatments alone. Treatment failure was defined as the need for cricothyroid "minitracheostomy" or endotracheal intubation, despite treatment. The number of subjects administered bronchoscopy-assisted aspiration during the hospital stay was also compared. Treatment failure was significantly lower (P < 0.05) in the mechanical insufflation-exsufflation group than in the conventional chest physical treatments group (2/11 vs. 10/16 cases). The use of bronchoscopy-assisted aspiration was similar in the two groups (5/11 vs. 6/16 cases). Mechanical insufflation-exsufflation did not produce serious side effects and was well tolerated by all subjects. Provision of mechanical insufflation-exsufflation in combination with standard chest physical treatments may improve the management of airway mucous encumbrance in neuromyopathic patients; its use should be included in the noninvasive approach to treatment of respiratory tract infections with impaired mucous clearance.

Cytomegalovirus prophylaxis with ganciclovir in kidney transplant recipients receiving induction antilymphocyte antibodies

Background Cytomegalovirus (CMV) is one of the serious viral infections after organ transplantation, especially in patients receiving anti-lymphocyte antibodies. Prevention of the infection using antiviral chemotherapy (ganciclovir) has gained interest in the transplant community due to the availability of quantitative methods for viral detection and monitoring. Methods Forty-six CMV seropositive kidney transplant recipients were assigned to receive induction immunosuppression with anti-thymocyte globulin (ATG, Fresenius). Prophylactic intravenous ganciclovir was administered for 2 weeks at a dose of 5 mg/kg/d (adjusted to kidney function) starting from the day of surgery. Patients were monitored regularly for CMV infection or disease over 1 year posttransplant. The time to CMV manifestation, the number of antigenemia assay-positive cells, the clinical severity of infection, the incidence of acute rejection, the graft function, and the duration of hospital stay were evaluated. This group was compared to a historical matched control cohort ( n = 37) transplanted earlier who did not receive prophylactic ganciclovir. Result The incidence of CMV disease was significantly less among the prophylaxis than the control group (6/46 patients [13%] vs 16/37 patients [43.2%], P = < .004). The time to develop CMV manifestations was much longer in the prophylaxis group than in the control group (median 92 vs 32 days, P ≤ .001). Conclusion Two weeks intravenous ganciclovir prophylaxis significantly reduced the onset and severity of CMV disease among kidney transplant recipients receiving induction with anti-lymphocyte antibodies.

Autologous stem cell transplantation for nasal NK/T-cell lymphoma: a progress report on its value

Nasal NK/T-cell lymphoma is an Epstein–Barr virus-related, highly aggressive but localized disease in Orientals. The median survival is <1 year. Here, we update our experience on 18 patients treated with autologous stem cell transplantation (ASCT). Two patients died of mucositis and septicemia during ASCT. Relapse occurred in nine cases, including six local relapses. Compared with patients treated in remission, all patients treated in active or disseminated disease died of early relapse. Within this cohort, there was no significant survival difference between patients treated in first (CR1, n = 7) or second (CR2, n = 5) complete remissions. However, among consecutive cases analyzed, the patients receiving ASCT at CR1 showed a trend towards better overall survival compared with historical matched controls (P = 0.064). Disease relapse beyond 6 months was not seen after ASCT. Our retrospective data suggest that ASCT in CR1 is a viable consolidation therapy for local-stage NK/T lymphoma, but a randomized trial is needed to prove any definite survival benefit. For patients with relapsed, refractory or extranasal disease, early consideration for allogeneic transplantation and alternative therapy may be warranted.

Neoadjuvant chemotherapy and radiotherapy for large extremity soft-tissue sarcomas

Purpose Treatment of extremity soft-tissue sarcomas yields excellent local control, but distant failure is common with large, high-grade tumors. A regimen of preoperative chemotherapy consisting of mesna, adriamycin, ifosfamide, and dacarbazine (MAID) interdigitated with radiotherapy followed by resection and postoperative chemotherapy with or without radiotherapy was designed to improve treatment outcome. We report the mature outcome data on 48 treated patients and compare them with the data of an historical matched control patient population. Methods and materials Adult patients with high-grade extremity soft-tissue sarcomas ≥8 cm were treated with three cycles of preoperative chemotherapy combined with 44 Gy of radiotherapy followed by surgery. Three cycles of postoperative MAID were planned. For patients with positive surgical margins, 16 Gy was delivered postoperatively. Results All 48 patients (M0) received the MAID protocol treatment, and their outcome was superior to that of the historical control patients. The 5-year actuarial local control, freedom from distant metastasis, disease-free survival, and overall survival rate was 92% and 86% ( p = 0.1155), 75% and 44% ( p = 0.0016), 70% and 42% ( p = 0.0002), and 87% and 58% ( p = 0.0003) for the MAID and control patient groups, respectively. Acute hematologic toxicity in the MAID group included febrile neutropenia in 12 patients (25%). Wound healing complications occurred in 14 (29%) of 48 MAID patients. One MAID patient developed late fatal myelodysplasia. Conclusion After aggressive chemoradiation and surgery, these patients showed a significant reduction in distant metastases, with a highly significant gain in disease-free and overall survival compared with a historical control group. On the basis of this experience, the Radiation Therapy Oncology Group conducted a multi-institutional trial.

Use of matched historical controls to evaluate the anti-fracture efficacy of once-a-week risedronate

Placebo controls are essential to assess anti-fracture efficacy of new osteoporosis therapies, but inclusion of a placebo arm in a subsequent clinical trial may be limited by practical or ethical considerations; in these cases, use of an historical control may be appropriate. A recent active-controlled study of risedronate 35 mg once a week demonstrated that this regimen produces increases in bone mineral density (BMD) that are comparable to those seen with the risedronate 5 mg daily dose, which has proven anti-fracture efficacy. To assess the anti-fracture efficacy of this new regimen, we have analyzed the fracture data collected in an active controlled study of risedronate dosing regimens (the Once-a-Week study) using matched historical control data from previous placebo-controlled trials. Women in the Once-a-Week study were matched for age, years since menopause, BMD, and prevalent vertebral fracture status, with placebo patients in the Vertebral Efficacy of Risedronate Therapy (VERT) trials forming an historical placebo group. We also constructed an historical active treatment group from the 5 mg daily arm of the VERT trials for comparison with the 5 mg daily and 35 mg once weekly treatment groups in the Once-a-Week study. Data were obtained from the risedronate 5 mg daily group (n=480) and 35 mg once-a-week group (n=485) in the Once-a-Week study and historical control groups representing daily placebo patients (n=114, matched from 993) and risedronate 5 mg daily patients (n=120; matched from 990) in the VERT studies. Patients received calcium supplementation (1000 mg daily); vitamin D was given if baseline serum 25-hydroxyvitamin D levels were low. Over 1 year, new vertebral fracture risk in the 35 mg once-a-week group was reduced by 77% relative to the historical placebo group (1.2% versus 5.0%; RR 0.23; 95% CI, 0.54 to 0.91, P=0.018), similar to the 1-year risk reduction observed in the VERT trials of risedronate 5 mg daily (61-65%). The incidence of new vertebral fractures in the three active treatment groups was similar: 1.7% in the historical risedronate 5 mg group, 1.5% in the risedronate 5 mg daily group from the Once-a-Week study, and 1.2% in the 35 mg once-a-week group. Risedronate 35 mg once a week appears as effective as the 5 mg daily dose in reducing the risk of new vertebral fractures in the first year of treatment. The use of appropriate historical control data provides an approach to the assessment of fracture effects in osteoporosis trials for which placebo-controlled data are not available.

Stage migration in breast cancer: surgical decisions concerning isolated tumour cells and micro-metastases in the sentinel lymph node

Aims: Sentinel lymph node biopsy has replaced the axillary lymph node dissection (ALND) in primary surgery for breast cancer in many hospitals and is expected to become the standard of care in due time. Since the sentinel lymph node is subjected to more extensive pathologic examination than the lymph nodes in the axillary dissection specimen, more patients are found to be node positive (N+); however many of them contain micro-metastases (≤2mm). The consequence may be an overshoot of therapy: additional surgery for non-metastatic lymph nodes or systemic adjuvant therapy.Methods:We examined 34 (out of a series of 38) clinically T1 (cT1) patients who had a SLN biopsy with or without ALND and compared them to a matched historical control group.Results: Twenty-one of 34 (62%) patients showed tumour cells in their SLN's. From these 21 patients in 13 (62%) the SLNs contained isolated tumour cells, of which 10 (77%) were detected only by immunohistochemistry (IHC), in four (19%) the SLNs contained micrometastases, and in four (19%) macrometastases. From 16 patients with isolated tumour cells or micrometastases in the SLN who underwent a regular ALND one had an H&E detected isolated tumour cell in a non-SLN and one patient with isolated tumour cells in the SLN who did not get a regular ALND developed an axillary recurrence 11 months after the primary treatment. On the other hand, three of four (75%) patients with macrometastases in the SLN had pathologically involved non-SLNs. In the majority (70%) of patients of the historical control group no lymph node involvement was seen. The percentage of macrometastases staged as lymph node positive in the control group was the same as in the studied group.Conclusion: Most patients with cT1 breast cancer with isolated tumour cells or micrometastases in the SLN will not benefit from additional axillary dissection; 88% had a negative ALND. Since we cannot select the group that will benefit from ALND, this is still indicated in case of isolated tumour cells or micrometastases in the SLN. Since most of the affected SLNs show isolated tumour cells and are classified as pN0(i+), stage migration due to more meticulous pathologic examination does not occur according to the TNM classification. However some patients do not benefit from the introduction of the SLN, due to the high incidence of isolated tumour cells or micrometastases in the SLN. Many more patients than expected still end up with an ALND.

Collection of More Hematopoietic Progenitor Cells with Large Volume Leukapheresis in Patients with Multiple Myeloma

Reinfusion of mobilized peripheral blood stem cells (PBSC) after high dose chemotherapy accelerates hematopoietic recovery. Because of the relatively low content of hematopoietic progenitors in the peripheral blood even after mobilization, multiple leukapheresis procedures are necessary to reach the required target number of CD34 cells to ensure prompt engraftment post-transplantation. Our previous studies have shown that the highest proportions of hematopoietic progenitors cells (CD34) are collected during the first three days of apheresis, whereas peak levels of myeloma cells are observed during subsequent days. Therefore, large volume leukapheresis (LVL), defined as processing of greater than 3 blood volumes or a total of at least 15 liters, was explored in 23 myeloma patients, undergoing 91 procedures; 14 patients were mobilized with high dose cyclophosphamide (6g/m2) and hematopoietic growth factors and 9 with G-CSF only. CD34 yields were measured separately for the first and last two hours of collection. We observed no decrease in CD34 cells/kg during the last two hours of collection and when the LVL collections were compared to historical matched controls, mobilized with the same regimen, the median quantity of CD34 cells/kg/liter collected remained equivalent during all days of apheresis. When compared to G-CSF only, mobilization with high dose cyclophosphamide appeared to result in superior hematopoietic stem cell collections. Interestingly, the G-CSF group experienced a progressive decrease in platelets during consecutive days of LVL, while the opposite was seen in the cyclophosphamide group. LVL procedures were not associated with a higher complication rate than standard volume apheresis. We conclude that LVL procedures allow collection of more CD34 cell per session while not jeopardizing progenitor cell collections during subsequent sessions. Since more CD34 cells are collected, fewer days are required to attain the optimal target of progenitor cells. This should result in PBSC grafts with less tumor contamination.

Celiac artery adjuvant chemotherapy. Results of a prospective trial.

Celiac artery infusion (CAI) seems to be a qualified and successful method for adjuvant treatment of pancreatic cancer. To improve the dismal prognosis of resected pancreatic cancer patients, we performed postoperative regional chemotherapy via the celiac axis. From 1994-1995, 20 patients with pancreatic cancer (18 ductal adenocarcinoma, 2 cystadenocarcinoma) received adjuvant celiac axis intra-arterial infusions (CAI) after resection of their tumors. Sixteen patients had macroscopically complete tumor removal (R0/R1 resection, 80% of the patients), whereas four patients had gross residual disease remaining after resection (R2 resection, 20% of the patients). Postoperative tumor stages were UICC I in 1 patient, UICC II in 3 patients, and UICC III in 16 patients. CAI was performed for six postoperative cycles via catheters placed into the celiac artery using Seldinger's technique. The chemotherapeutic protocol consisted of mitoxantrone (Novantron), Wyeth-Lederle (Münster, Germany) 10 mg/m2 (d 1), folinic acid (Leucovorin, Wyeth-Lederle, or Rescuvolin, Medac, Hamburg, Germany) 170 mg/m2 for 10 min, followed by 5-FU (Fluoroblastin, Farmitalia, Freiburg, Germany) 600 mg/m2 for 120 min (d 2-4), and Cisplatin (Cisplatin-medac, Medac) 60 mg/m2 (d 5). The cycles were repeated after a rest period of 4 wk. Cisplatin infusions were accompanied by supportive antiemetic (8 mg Tropisetrone i.v. [Navoban, Sandoz, Nürnberg, Germany] and 8 mg Dexametason i.v.) and diuretic measures. Toxicity WHO III occurred in 8% of 100 cycles, and no toxic side effects WHO IV were encountered. The median survival of 21 mo in the treated group was nearly twice as long as the 9.3 mo of a historical matched control group (p < 0.0003). CAI seems to be a qualified and successful method for adjuvant treatment of pancreatic cancer.

The use of simultaneous radiotherapy and 5-fluouracil in patients with inoperable squamous cell lung cancer

Over a 2-year period, 17 patients with histologically proven squamous cell carcinoma of the bronchus, assessed as inoperable or incurable on surgical or medical grounds, were treated with palliative radiotherapy and a concurrent 120-h infusion of 5-flurouracil, at a dosage of 1 g/day. The treatment was found to be well tolerated with no major toxicity. The degree of palliation and survival obtained was found to be no different to that of a historical matched control group, treated with radiotherapy alone, with median survival in the two groups of 35 weeks and 42 weeks respectively (log rank test P greater than 0.69). We conclude that although a non-toxic treatment regime, no benefit was obtained by the addition of 5-flurouracil to palliative radiotherapy.

Impact of Preadmission Evaluations on Elective Hospitalization of Children

It was hypothesized that a well-organized evaluation of children scheduled for elective medical admission would: (1) significantly reduce average length of stay; (2) meet with parent satisfaction; and (3) significantly reduce health care costs. To test this hypothesis, a system of preadmission procedures was established for patients scheduled for elective medical admission to a 332-bed tertiary care pediatric hospital, and the impact of the system on these three parameters was evaluated. Compared with 167 concurrent control patients and 379 historical matched control patients, a highly significant shortening of length of hospital stay was associated with the preadmission program. Preadmission evaluation was associated with a reduction of 2.31 days in mean hospital stay and of three days in median stay as compared with number of days for concurrent control patients (P less than .01). Patient and staff satisfaction was high. The extension of such a program to most elective medical admissions should result in significant savings in health care costs and reduction in family inconvenience.