Clinical and financial analysis of an acute palliative care unit in an oncological department.

The aim of this article is to describe the clinical activity and medical intervention of an acute model of palliative care unit (APC), as well as the reimbursement procedures and economic viability. A sample of 504 patients admitted at an APC in 1 year was surveyed. Indications for admission, pain and symptom intensity, analgesic treatments, procedures, instrumental examinations and modalities of discharge were recorded. For each patient, tariff for reimbursement was calculated according to the existent disease related grouping (DRG) system. The mean age was 62 years, and 246 patients were males. The mean hospital stay was 5.4 days. Pain control was the most frequent indication for admission. All patients had laboratory tests and several instrumental examinations. Almost all patients were prescribed one or more opioids at significant doses, and different routes of administration, as well as medication as needed. 59 patients received blood cell transfusions and 34 interventional procedures. Only 40 patients died in the unit, 11 of them being sedated at the end of life. Treatment efficacy was considered optimal and mild in 264 and 226 patients respectively. A mean of 3019 euros for admission was reimbursed by the Health Care System. APCs are of paramount importance within an oncological department, as they provide effective and intensive treatments during the entire course of disease, providing a simultaneous and integrated approach. Our findings also suggest both a cost and quality incentive for oncological departments to develop APC.

Transmucosal fentanyl vs intravenous morphine in doses proportional to basal opioid regimen for episodic-breakthrough pain.

The use of supplemental doses of opioids is commonly suggested to manage breakthrough pain. A comparative study of intravenous morphine (IV-MO) and oral transmucosal fentanyl citrate (OTFC) given in doses proportional to the basal opioid regimen was performed in 25 cancer patients receiving stable opioid doses. For each episode, when it occurred and 15 and 30 min after the treatment, pain intensity and opioid-related symptoms were recorded. Fifty-three couples of breakthrough events, each treated with IV-MO and OTFC, were recorded. In episodes treated with IV-MO, pain intensity decreased from a mean of 6.9 to 3.3 and to 1.7 at T1 and T2, respectively. In episodes treated with OTFC, pain intensity decreased from a mean of 6.9 to 4.1 and to 2.4 at T1 and T2, respectively. Statistical differences between the two treatments were found at T1 (P=0.013), but not at T2 (P=0.059). Adverse effects were comparable and were not significantly related with the IV-MO and OTFC doses. Intravenous morphine and OTFC in doses proportional to the scheduled daily dose of opioids were both safe and effective, IV-MO having a shorter onset than OTFC. Future comparative studies with appropriate design should compare titration methods and proportional methods of OTFC dosing.

Differential effects of COX inhibitors against beta-amyloid-induced neurotoxicity in human neuroblastoma cells.

Retrospective epidemiological studies have suggested that chronic treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) provides some degree of protection from Alzheimer's disease (AD). Although most NSAIDs inhibit the activity of cyclooxygenase (COX), the rate-limiting enzyme in the production of prostanoids from arachidonic acid (AA), the precise mechanism through which NSAIDs act upon AD pathology remains to be elucidated. Classical NSAIDs like indomethacin inhibit both the constitutive COX-1 and the inducible COX-2 enzymes. In the present work, we characterize the protective effect of the indomethacin on the neurotoxicity elicited by amyloid-beta protein (A beta, fragments 25-35 and 1-42) alone or in combination with AA added exogenously as well as its effects on COX-2 expression. We also compared the neuroprotective effects of indomethacin with the selective COX-1, COX-2 and 5-LOX inhibitors, SC-560, NS-398 and NDGA, respectively. Our results show that indomethacin protected from A beta and AA toxicity in naive and differentiated human neuroblastoma cells with more potency than SC-560 while, NS-398 only protected neurons from AA-mediated toxicity. Present results suggest that A beta toxicity can be reversed more efficiently by the non-selective COX inhibitor indomethacin suggesting its role in modulating the signal transduction pathway involved in the mechanism of A beta neurotoxicity.

Local anesthetic switching for intrathecal tachyphylaxis in cancer patients with pain.

IMPLICATIONS: Switching from bupivacaine to lidocaine may improve intrathecal morphine analgesia in advanced cancer patients, possibly because of different spinal mechanisms limiting the hyperalgesic processes.

Opioid plasma concentration during switching from morphine to methadone: preliminary data.

Opioid switching is often used to improve the opioid response in cancer patients experiencing poor analgesia or adverse effects. However, no data are available on plasmatic changes of opioids and their metabolites during these phases, and whether there exists a relationship with the clinical events. In a prospective study of 10 consecutive cancer patients on oral morphine but with uncontrolled pain (greater >4 on a numerical scale of 0 to 10) and/or moderate to severe opioid adverse effects (on a level of 2 and 3 of a verbal scale) and not responsive to adjuvant medications, switching to oral methadone was performed using a fixed ratio of 5:1, leaving extra-doses of 1/5 of the daily dose of methadone calculated as needed. Blood samples were obtained at the same hour for four days, before the switching, and then on day 1, 2, and 3. The intensity of pain and the adverse effects were assessed daily to calculate the switching score before and after switching. Completed blood samples were obtained in 9 patients. One patient was separately considered, because of his renal impairment. Significant improvements in pain intensity as well as adverse effects within an average period of 1-2 days were observed. Morphine, morphine-6-glucuronide, and morphine-3-glucuronide were progressively cleared from plasma to almost disappear within three days. Methadone rapidly achieved a stable concentration in 1-2 days. The doses of methadone were changed, but not significantly, and tended to decrease in the following days, according to the clinical situation. The results of this study confirm the need to stop rapidly morphine, and to use a priming dose of methadone, rather than using progressive decrements and increments of morphine and methadone, respectively, during opioid switching. This method allows for a rapid clearance of morphine and its metabolites are rapidly cleared, except in patients with renal failure. Opioid plasma changes substantially overlap the clinical changes observed in these patients, in terms of benefit between analgesia and adverse effects.

Cisplatin and vinorelbine in advanced and/or metastatic adenocarcinoma of the endometrium: a new highly active chemotherapeutic regimen.

PURPOSE: To date the systemic treatment of recurrent and/or metastatic adenocarcinoma of the endometrium (EAC), using both chemotherapy and hormonotherapy (HT), is far from satisfactory. The significant activity of vinorelbine (VNR), a relatively new semisynthetic vinca alkaloid, demonstrated in advanced breast cancer, bronchial adenocarcinoma, and in head and neck cancer, prompted us to carry out a phase II trial employing the combination of cisplatin and VNR in a pluri-institutional series of patients with recurrent and/or metastatic EAC. PATIENTS AND METHODS: Thirty-five patients affected by recurrent and/or metastatic EAC have been treated with CDDP 80 mg/m2 on day 1 plus VNR 25 mg/m2 i.v. bolus on days 1 + 8. This cycle was repeated every 21 days. After three cycles patients were restaged for objective response. Analysis of response rate and duration, overall survival, and toxicity pattern were the main aims of the study. RESULTS: Twenty out of thirty-five patients achieved a major objective response for an overall response rate of 57% (95% confidence limits (CL): 39%-74%). Four patients had a complete response (11%; 95% CL: 3%-27%) with a median progression-free survival (PFS) of eight hundred fourteen days, while sixteen patients had a partial response (46%; 95% CL: 29%-63%) with a median PFS of one hundred eighty-four days. Six patients had stable disease and nine progressed. All patients who achieved a clinical complete response had only a single site of disease at entry, but no association was noted between number of involved sites and likehood of achieving PR. Median overall survival was 240 days, while that of patients with complete and partial response was 855 and 300 days, respectively. Treatment was quite well tolerated with few cases of grade 3-4 myelosuppression. Alopecia was virtually absent and neurotoxicity was mild. One patient complained of an acute pain syndrome at the tumor site. CONCLUSIONS: The CDDP + VNR regimen is quite active against recurrent and/or metastatic endometrial adenocarcinoma, at least in terms of objective response rate which is among the highest ever reported in medical literature. However. duration of objective response and median overall survival are in the disappointing range reported for other regimens. In our opinion the CDDP plus VNR regimen is good enough to be compared to the anthracycline-based regimens and may represent the basis for future development of newer active polychemotherapeutic schedules.

Outcomes of admitted geriatric trauma victims.

Conflicting data exist as to the outcome of elderly victims of trauma. With recent improved outcomes for functional recovery, aggressive management of these patients has been advocated. The purpose of this study is to determine outcomes of admitted elderly trauma victims based on initial mechanism of injury and the degree to which other factors affected their overall outcome. A prospective study involving admitted patients > or =65 years was performed at an urban university center from September 15, 1996 until August 31, 1997. Patients sustaining any potentially serious form of trauma were included. Data about mechanism of injury (MOI), comorbid conditions, preinjury medications, types of injuries sustained, length of stay, functional outcome, and ultimate disposition were recorded. Two hundred thirty-nine consecutive patients were enrolled. Mean age was 78.1 +/- 8.1 years. There were 130 women (54%) and 109 men (46%). MOI was as follows: 132 low-mechanism falls (LMFs), 64 high-mechanism motor vehicle crashes (HMMVCs), 22 high-mechanism falls (HMFs), 8 pedestrian versus car (PVCs), and 13 other types. Mean length of stay surviving beyond the ED was 12.9 days. 8 patients were either DOA or died in the ED. There were 19 in-hospital deaths. Deaths were seen in 14% of HMMVCs, 13.6% HMFs, 9.1% LMFs, 25% PVCs, and 7.7% for other mechanisms. Overall outcomes by mechanism were categorized as functional (or baseline), fair, alive but poor, and dead. Functional outcomes were seen in 76.6% of HMMVCs, 81.8% of HMFs, 84.1% of LMFs, 50% of PVCs, and 84.6% for all other injuries. Forty-five percent were discharged home, 26% went to rehabilitation units, 16% went to nursing homes, and 11% died; the remaining 2% were either transferred to a psychiatric facility or to another hospital. Preexisting comorbid conditions did not appear to play a significant role in the ultimate outcomes of these patients. Severity of injury was the leading determinant of death, but severely injured patients often had functional outcomes. Elderly trauma victims most often achieve functional outcomes despite multiple or severe injuries.

Ovarian small cell carcinoma: a rare neoplasm in a 15-year-old female.

Abdominal masses in children are uncommon. Ovarian neoplasms are uncommon in young children and adolescents, and typically are benign. Small cell carcinoma of the ovary is an extremely rare condition, with a very poor prognosis. We report the case of a 15-year-old female who presented to the emergency department with abdominal distention, abnormal vaginal bleeding, and constipation secondary to a large intra-abdominal mass, ultimately diagnosed as ovarian small cell carcinoma.

Sternoclavicular joint injuries.

Injuries to the sternoclavicular (SC) joint are infrequently encountered. However, retrosternal SC joint dislocations are potentially life-threatening injuries which must be recognized by the examining physician and treated as soon as possible. Plain radiography often fails to fully distinguish SC joint injuries, and computed tomography has emerged as the diagnostic modality of choice for defining the injury complex and surrounding injuries. We have encountered 6 cases of SC joint injuries over the past 3 years and describe their presentation and management.

Geriatric trauma: outcomes of elderly patients discharged from the ED.

This study was undertaken to investigate which patients 65 years of age or older have adverse outcomes after discharge from the emergency department (ED) after an injury. Patients were enrolled prospectively at an urban university center from September 15, 1996, until August 31, 1997. Patients sustaining any potentially serious form of injury were included. Data about comorbid conditions, preinjury medications, and types of injuries sustained were recorded. Patients were contacted at home at least 30 days after discharge and were questioned about their overall health, need for admission since ED discharge, and whether any complications developed. One hundred five consecutive patients were enrolled, but 5 patients were lost to follow-up. There were 74 low-mechanism falls (LMFs), 11 low-mechanism motor vehicle crashes (LMMVCs), 8 high-mechanism motor vehicle crashes (HMMVCs), 3 high-mechanism falls (HMFs), and 4 other types of injuries. Follow-up ranged from 30 to 147 days, with a mean of 49 days. On follow-up, 88 patients were doing well, 9 were fair, and 3 were doing poorly; of the latter, their poor health was unrelated to their injuries. Complications included 2 extremity infections and 1 poorly healing wound. Eleven patients were seen in an ED within the first 30 days after injury, 6 of whom for problems related to their initial injury or its management. These results show that there is a subset of elderly victims of trauma who may be safely discharged home after appropriate evaluation. Return visits to the ED were just as often related to comorbid conditions as to initial injury.

Injury patterns with snowboarding.

Snowboarding is a winter sport that has shown a considerable increase in popularity during the last 2 decades. As a result, there has been a continued rise in the number of visits to the emergency department (ED) for injuries sustained while snowboarding. Previous studies have concluded that those injured tend to be male, younger, and more inexperienced than their alpine skiing counterparts. This study examines the injury patterns seen in one ED during peak winter sport recreational months over a 5-year period. This retrospective review describes 71 patients with a broad spectrum of injury patterns, but reports a higher incidence of head and spinal injuries than previously documented. Furthermore, recommendations to prevent future injuries as well as education for first responders and physicians regarding the high likelihood of serious injury is discussed.

Good outcomes of open pelvic fractures.

While pelvic fractures are common injuries, those which communicate with an open wound are much less commonly encountered. These injuries have been associated with high morbidity and mortality in previous studies. We investigated our experience with open pelvic fractures retrospectively over a 79-month period. A total of 17 patients were identified, representing 2.7% of all pelvic fractures seen during this time period. There were no fatalities among the 15 patients who were not in cardiac arrest on arrival. Associated injuries were present in all patients. Functional outcome was good in eight patients and fair in seven. Although open pelvic fractures are severe injuries, survival in our study was 100% in those not arriving in cardiac arrest.

Vaginal evisceration.

Intestinal evisceration through the vagina is exceptionally rare. We report the cases of two patients presenting with this unusual clinical condition. Predisposing factors and management of vaginal evisceration are discussed.

Tension pneumoperitoneum caused by blunt trauma.

Tension pneumoperitoneum (TPP), the accumulation of free intraabdominal air under pressure, is a rare event. TPP usually occurs from bowel surgery or bowel perforations. Less commonly, TPP occurs in the presence of pneumothoraces or during positive pressure ventilation. Trauma has rarely been a reported cause of TPP. The cases of 2 patients with TPP after blunt trauma are reported. The pathophysiology and management of TPP are discussed.

Sex hormone-binding globulin, its membrane receptor, and breast cancer: a new approach to the modulation of estradiol action in neoplastic cells.

The role of human Sex Hormone-Binding Globulin (SHBG), the plasma carrier of sex steroids, and its membrane receptor, SHBG-R, in estrogen-dependent breast cancer has been investigated in our laboratory in the past few years. SHBG-R is expressed in MCF-10 A cells (not neoplastic mammary cells), MCF-7 cells (breast cancer, ER positive) and in tissue samples from patients affected with ER positive breast cancer, but not in estrogen-insensitive MDA-MB 231 cells. The SHBG/SHBG-R interaction, followed by the binding of estradiol to the complex protein/receptor, causes a significant increase of the intracellular levels of cAMP, but does not modify the amount of estradiol entering MCF-7 cells. The estradiol-induced proliferation of MCF-7 cells is inhibited by SHBG, through SHBG-R, cAMP and PKA. Similarly, the proliferation rate of tissue samples positive for SHBG-R was significantly lower than the proliferation rate of negative samples. SHBG and SHBG-R could thus trigger a 'biologic' anti-estrogenic pathway. In order to get a more detailed knowledge of this system, we first examined the frequence of the reported mutated form of SHBG in 255 breast cancer patients. The mutated SHBG is characterized by a point mutation (Asp 327 --> Asn) causing an additional N-glycosylation site, which does not affect the binding of steroids to SHBG. The frequence of the mutation was significantly higher (24.5%) in estrogen-dependent breast cancers than in healthy control subjects (11.6%). This observation confirms the close relationship between SHBG and estrogen-dependent breast cancer and suggests that the mutation could modify SHBG activity at cell site. Lastly, the possibility of using SHBG to modulate the estradiol action in breast cancer was further studied by transfecting MCF-7 cells with an expression vector carrying the SHBG cDNA (study in collaboration with G.L. Hammond). Transfected cells are able to produce significant amount of SHBG in their medium, but their SHBG-R is reduced to undetectable levels. The SHBG produced by transfected MCF-7 cells is, however, able to inhibit estradiol-induced proliferation of MCF-7 cells expressing a functional receptor. Thus, the local production of SHBG obtained with transfection could be a useful tool to control cell growth in estrogen-dependent breast cancer.

The additionally glycosylated variant of human sex hormone-binding globulin (SHBG) is linked to estrogen-dependence of breast cancer.

Sex Hormone-Binding Globulin (SHBG), the plasma carrier for androgens and estradiol, inhibits the estradiol-induced proliferation of breast cancer cells through its membrane receptor, cAMP, and PKA. In addition, the SHBG membrane receptor is preferentially expressed in estrogen-dependent (ER+/PR+) breast cancers which are also characterized by a lower proliferative rate than tumors negative for the SHBG receptor. A variant SHBG with a point mutation in exon 8, causing an aminoacid substitution (Asp 327-->Asn) and thus, the introduction of an additional N-glycosylation site, has been reported. In this work, the distribution of the SHBG variant was studied in 255 breast cancer patients, 32 benign mammary disease patients, and 120 healthy women. The presence of the SHBG mutation was evaluated with PCR amplification of SHBG exon 8 and Hinf I restriction fragment length polymorphism (RFLP) procedure. This technique allowed us to identify 54 SHBG variants (53 W/v and 1 v/v) in breast cancer patients (21.2%), 5 variants (4 W/v and 1 v/v) in benign mammary disease patients (15.6%), and 14 variants (W/v) in the control group (11.6%). The results of PCR and RFLP were confirmed both by nucleotide sequence of SHBG exon 8 and western blot of the plasma SHBG. No differences in the mean plasma level of the protein were observed in the three populations. The frequency of the SHBG variant was significantly higher in ER+/PR+ tumors and in tumors diagnosed in patients over 50 years of age than in the control group. This observation suggests the existence of a close link between the estrogen-dependence of breast cancer and the additionally glycosylated SHBG, further supporting a critical role of the protein in the neoplasm.