Age-related macular degeneration: cost-of-illness issues

Macular degeneration refers to the breakdown of cells in the centre of the retina. Some degeneration is an inevitable consequence of the aging process; however, when this is associated with loss of sight in the central part of the field of vision an underlying pathology is considered present. Among those aged 55 years, the prevalence of the disease in the US was estimated at 1% rising to approximately 15% among those aged 80 years. Other studies estimate the prevalence of the disease to be higher and to be increasing. The main effect of the disease is to reduce the ability of the individual to engage in everyday activities that require clear central vision. It may also be associated with elevated risks of depression and increased levels of dependency. Currently there is no effective treatment for the majority of patients. For a minority (< 10%) laser photocoagulation therapy may be effective in reducing the risk of severe vision loss. Another treatment, photodynamic therapy, is in development and many others are at an experimental stage. This review sought to establish current knowledge on the cost of illness associated with age-related macular degeneration (ARMD). A search of the literature, together with direct communication with researchers in related fields and patient support/advocacy groups, was undertaken to ascertain current knowledge on the cost of illness of ARMD. While literature on the disease is extensive and literature on treatments is emerging, no substantive information on direct or indirect costs was found although evidence that loss of earnings may occur is beginning to emerge. Some information does exist on cost of illness in diabetic retinopathy, a disease with similarities to ARMD, though even for this disease gaps in knowledge are apparent and wide variations exhibited. Given current knowledge, it is not possible to report on the cost of illness for ARMD with confidence. The lack of information on the cost of illness in ARMD presents difficulties for researchers and policy makers in assessing the cost effectiveness of the existing treatment, as well as new treatments as they become available. Given developments in treatments and the increasing prevalence of the disease, it is important that cost-of-illness information is gathered for ARMD.     

Bcl-2 Is a Useful Prognostic Marker in Dukes’ B Colon Cancer

Background: Currently, the use of adjuvant therapy specifically in Dukes B colon cancers is controversial, emphasizing the importance of identifying prognostic markers to select patients for such therapy. Bcl-2 plays an important role in apoptosis regulation of solid tumors, such as colon and breast cancer, and is normally expressed in the base of the colonic crypts. The purpose of this study is to determine whether or not bcl-2 expression can be used to predict survival in Dukes B colon cancer patients.Methods: Charts of 76 patients operated on at the Royal Victoria Hospital from 1986 to 1992 were reviewed. Bcl-2 staining was done with the avidin-biotin-peroxidase complex method using commercially available monoclonal bcl-2 antibodies. Two pathologists graded the intensity of bcl-2 staining on a scale of 0–3 and estimated the percentage of tumor cells staining positively (T-percent). Univariate and multiple regression of factors on overall survival (OS) and disease-free survival (DFS) was done with a Cox proportional hazards model and Kaplan-Meier survival curves.Results: The mean age was 71.2 years, with 41 female and 35 male patients. Mean tumor size was 5.4 cm with tumor grades of 19 well, 52 moderate, and 5 poorly differentiated. Tumors expressing bcl-2 had a similar DFS (P = .14) but a significantly improved OS (P = .04) compared with the bcl-2 negative tumors. The risk ratio for DFS was 0.49 (95% CI, 0.19–1.26) and for OS was 0.35 (95% CI, 0.13–0.94).Conclusions: These data indicate that enhanced bcl-2 expression, specifically in Dukes B colon carcinomas, is associated with improved survival. Thus, patients whose tumors do not express bcl-2 should be considered for adjuvant therapy.Presented at the 51st Annual Meeting of the Society of Surgical Oncology, San Diego, California, March 26–29, 1998.     

Perceived treatment helpfulness and cost in chronic pain rehabilitation

OBJECTIVE: This article examines the perceived helpfulness of treatment components in comprehensive interdisciplinary pain management programs as they relate to cost. DESIGN: Patient satisfaction results assessed by the Treatment Helpfulness Questionnaire (THQ) and treatment costs were compared for 309 subjects at three comprehensive interdisciplinary chronic pain management centers. All subjects completed the THQ immediately after treatment, and follow-up data were gathered 3 to 6 months after the end of treatment at two of the three centers. RESULTS: Ratings of treatment helpfulness were not found to be related to either demographic or medical variables. Mean THQ ratings for many treatment modalities did differ significantly between centers, but subjects at all centers generally gave higher THQ ratings to psychological and educational therapies than to physical therapy and medical modalities both at posttreatment and at follow-up evaluations. More costly treatments generally did not receive higher ratings than less costly ones. THQ ratings tended to decline modestly from posttreatment to follow-up evaluations. CONCLUSIONS: For the selected population of patients undergoing comprehensive interdisciplinary pain management, educational and psychological approaches received high ratings of helpfulness at a relatively low cost. Further research is needed to address whether comparative patient satisfaction data can be used at pain centers to produce improved outcomes at reduced costs.     

Dose-intensive,Time-compressed Procarbazine,CCNU, Vincristine (PCV) with Peripheral Blood Stem Cell Support and Concurrent Radiation in Patients with Newly Diagnosed High-grade Gliomas

The dose intensity of the PCV regimen can be doubled using peripheral blood stem cell (PBSC) support. This study sought to determine the feasibility of giving dose-intensive PCV concurrently with radiation therapy. Twelve patients, age 3.2–22.7 years, median 7.5 years, with newly diagnosed high grade gliomas were enrolled. Diagnoses included diffuse intrinsic brainstem gliomas (BSG) (n=6), glioblastoma (n=4), anaplastic astrocytoma (n=2). PBSCs were harvested prior to chemotherapy with G-CSF priming. Chemotherapy consisted of CCNU 130 mg/m² and vincristine 1.5 mg/m² on day 0, and procarbazine 150 mg/m² on days 1–7. PBSCs were reinfused on day 9 of each course. Four courses of chemotherapy were administered every 28 days or when blood counts recovered. The first course was administered the week prior to RT, the second course began on week 3 of RT and the third and fourth course were given after RT. Hematologic toxicity was mild and the majority of courses were given on schedule. Five of six patients with diffuse BSG showed clinical improvement and three showed a radiographic response; however, only one remains alive 12+ months from diagnosis. All four patients with non-brainstem large-volume tumors showed clinical deterioration and radiographic progression during or shortly after RT. MRI scans showed massive edema and enhancement. Median time to radiographic progression was five months. Median overall survival was 11 months. We conclude that dose-intensive, time-compressed PCV given concurrently with large-volume RT appears to result in unacceptable toxicity in patients with large residual tumors.     

Gold nanoparticles with a monolayer of doxorubicin-conjugated amphiphilic block copolymer for tumor-targeted drug delivery

Gold (Au) nanoparticles (NPs) stabilized with a monolayer of folate-conjugated poly(l-aspartate-doxorubicin)-b-poly(ethylene glycol) copolymer (Au-P(LA-DOX)-b-PEG-OH/FA) was synthesized as a tumor-targeted drug delivery carrier. The Au-P(LA-DOX)-b-PEG-OH/FA NPs consist of an Au core, a hydrophobic poly(l-aspartate-doxorubicin) (P(LA-DOX)) inner shell, and a hydrophilic poly(ethylene glycol) and folate-conjugated poly(ethylene glycol) outer shell (PEG-OH/FA). The anticancer drug, doxorubicin (DOX), was covalently conjugated onto the hydrophobic inner shell by acid-cleavable hydrazone linkage. The DOX loading level was determined to be 17 wt%. The Au-P(LA-DOX)-b-PEG-OH/FA NPs formed stable unimolecular micelles in aqueous solution. The size of the Au-P(LA-DOX)-b-PEG-OH/FA micelles were determined as 24–52 and 10–25 nm by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The conjugated DOX was released from the Au-P(LA-DOX)-b-PEG-OH/FA micelles much more rapidly at pH 5.3 and 6.6 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. Cellular uptake of the Au-P(LA-DOX)-b-PEG-OH/FA micelles facilitated by the folate-receptor-mediated endocytosis process was higher than that of the micelles without folate. This was consistent with the higher cytotoxicity observed with the Au-P(LA-DOX)-b-PEG-OH/FA micelles against the 4T1 mouse mammary carcinoma cell line. These results suggest that Au-P(LA-DOX)-b-PEG-OH/FA NPs could be used as a carrier with pH-triggered drug releasing properties for tumor-targeted drug delivery.     

A dose-finding study of liposomal daunorubicin with CVP (COP-X) in advanced NHL

Background:Standard therapy for lymphoma consists of acyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P) (CHOP)combination regimen. Liposomal daunorubicin (DaunoXome®) is an alternativeto doxorubicin for patients with lymphoma because of its more favorable safetyprofile and potentially more selective uptake in lymphoma. The objectives ofthis study were to determine the maximum tolerated dose (MTD) of liposomaldaunorubucin with CVP (COP-X) and the tolerability of the regimen in patientswith indolent lymphoma. Patients and methods:Patients with low-grade andintermediate-grade lymphoma having adequate cardiac, hepatic, and renalfunction were enrolled. Patients received C 750 mg/m², V 1.4mg/m² (maximum 2.0 mg), and liposomal daunorubicin 50–100mg/m² i.v. on day 1 and P 100 mg p.o. on days 1–5. MTD wasthe liposomal daunorubicin dose associated with 20% dose-limitingtoxicity (ANC <500/mm³ for >5 days or febrile neutropenia). Results:Twenty patients, median age 59 years, were treated. Theliposomal daunorubicin MTD combined with CVP was 70–80 mg/m²,depending on patient population. No significant non-hematologic toxicityoccurred. Response rate was 44% (2 complete and 5 partial responses). Conclusions:A liposomal daunorubicin dose of 80 mg/m²in the COP-X regimen was well tolerated with little non-hematologic toxicity.     

Ventilatory impairment from pre-harvest retted flax.

A new method of retting flax recently developed to suit the United Kingdom climate has allowed the reintroduction of flax growing to this country. The weed killer glyphosate is sprayed on the crop which then rets before harvesting six weeks later. The acute bronchoconstrictor responses of 11 normal subjects to dust from dew retted and from pre-harvest retted flaxes were compared in a double blind crossover fashion. There were no significant differences in the dust levels nor in the size of the dust particles in the experimental dust room. The decreases in pulmonary function after six hours of dust inhalation were significantly larger after pre-harvest retted flax dust than after dew retted flax dust (delta FEV1, -0.21 and -0.40 1; delta MEF50, -0.72 and -1.211/s; delta sGaw (specific airway conductance), -0.17 and -0.65 kPa/s for dew retted and pre-harvest retted respectively). The subjects also reported more symptoms after inhaling pre-harvest retted flax dust. It is concluded that the acute bronchoconstrictor response to flax dust is increased by pre-harvest retting, suggesting an increased risk of byssinosis.     

Clinical Observation onChinese Herbal Medicine in Treatment of Long-term Insomnia

Ｉｎｓｏｍｎｉａｉｓａｃｏｍｍｏｎｄｉｓｏｒｄｅｒ，ｗｈｉｃｈａｆｆｅｃｔｓａｂｏｕｔ30-40%ｏｆａｄｕｌｔｓｉｎｔｈｅｗｏｒｌｄ．（1，2）Ｌｏｎｇｔｅｒｍｉｎｓｏｍｎｉａ（ＬＴＩ）ａｆｆｅｃｔｓｕｐｔｏ10%ｏｆｔｈｅｐｏｐｕｌａｔｉｏｎ．（3）Ｉｎｓｏｍｎｉａｒｅｓｕｌｔｓｉｎｓｉｇｎｉｆｉｃａｎｔｍｏｒｂｉｄｉｔｙ（4-6）ａｎｄｅｃｏｎｏｍｉｃｃｏｓｔ．（1，7）Ｈｏｗｅｖｅｒ，ａｌｌｔｈｅｃｕｒｒｅｎｔｌｙａｖａｉｌａｂｌｅｈｙｐｎｏｔｉｃｄｒｕｇｓａｒｅｆａｒｆｒｏｍｉｄｅａｌ．（8）Ａｄｖｅｒ…