Identification of a claims data "signature" and economic consequences for treatment-resistant depression

BACKGROUND: Major depressive disorder (MDD) is a debilitating condition with significant economic consequences. Conservative estimates indicate that between 10% and 20% of all individuals with MDD are treatment resistant. The objectives for this study were (1) to use current treatment strategies identified in the literature to evaluate the validity of studying treatment-resistant depression (TRD) using claims data and (2) to estimate cost differences between TRD-likely and TRD-unlikely patients identified by use of treatment patterns. METHOD: The data source consisted of medical, pharmaceutical, and disability claims from a Fortune 100 manufacturer for 1996 through 1998 (N = 125,242 continuously enrolled beneficiaries between the ages of 18 and 64 years). The sample included individuals with medical or disability claims for MDD (NMDD = 4186). A treatment pattern algorithm was applied to classify adult MDD patients into TRD-likely (NTRD = 487) and TRD-unlikely groups. Resource utilization and costs were compared among TRD-likely and TRD-unlikely patients and a random sample of average beneficiaries (i.e., 10% of all beneficiaries) for 1998. RESULTS: Consistent with the epidemiologic literature, the algorithm classified 12% of the MDD sample as TRD-likely. Mean annual costs were $10,954 for TRD-likely patients, $5025 for TRD-unlikely patients, and $3006 for average beneficiaries. TRD-likely patients used almost twice as many medical services as did TRD-unlikely patients and incurred significantly greater indirect costs (p < .0001). CONCLUSION: It is feasible to use an administrative dataset to develop a claim-based treatment algorithm to identify TRD-likely patients. Resource utilization by TRD-likely patients was substantial, not only for direct treatment of depression but also for treatment of comorbid medical conditions. Additionally, TRD imposed on employers substantial indirect costs resulting from high rates of depression-associated disability.     

Elevated homocysteine levels in young male patients with schizophrenia

OBJECTIVE: Elevated plasma homocysteine has been found to be a risk factor for Alzheimer's disease as well as cerebral vascular disease, suggesting that some risk factors can accelerate or increase the severity of several CNS disease processes. The authors measured plasma homocysteine levels in patients with chronic schizophrenia in their catchment area. METHOD: A one-way analysis of covariance with age and sex as covariates was performed on the total plasma homocysteine levels of 193 patients with schizophrenia compared with 762 subjects without the diagnosis of schizophrenia who were evaluated in a screening program for employee health. RESULTS: The effect of schizophrenia was marked: the mean homocysteine level was 16.3 micro M (SD=11.8) in patients with schizophrenia compared with 10.6 micro M (SD=3.6) in healthy comparison subjects. The difference between groups was almost entirely attributable to the homocysteine levels of young male patients with schizophrenia. CONCLUSIONS: Elevated levels of homocysteine in young male patients with schizophrenia could be related to the pathophysiology of aspects of this illness.     

Complex regional pain syndromes in children and adolescents

Background: The purpose of the present paper was to assess efficiency of treatment and long-term functional outcome of complex regional pain syndromes (CRPS) in children who were treated in the chronic pain clinic at a major tertiary hospital in Israel.
Methods: The files of 14 children with CRPS were analyzed retrospectively. Demographic data, initiating event, referring source, time needed for referral to pain clinic, clinical evaluation, treatment, recurrence and complications were recorded.
Results: Fourteen children with CRPS types I and II were included in the study. Girls were affected in 71%. Lower extremities were affected in 57%. The median time from onset of symptoms to seeking medical help was 4.46 weeks (range 2–82 weeks). The median time to referral to pain clinic was 24.51 weeks (range 1.2–94). In 45% the referral source was the pediatrician. A total of 85.8% of patients were referred to various consultations before the pain clinic. Most children had reduced pain and improved function on non-invasive treatment approach. Invasive treatments were used in 28.5%. Full or partial recovery was accomplished in 93%. Recurrence was observed in 29%.
Conclusions: CRPS in children and adolescents is still underdiagnosed, although many of the epidemiologic features of pediatric CRPS are similar in different countries/cultures. Early recognition and management is the major factor in improving outcome and preventing resistant CRPS, but even children with delayed diagnosis still have a good outcome. The management of this disease by an experienced multidisciplinary team is recommended. Because psychosocial factors play an important role, it is recommended to provide psychological evaluation and cognitive behavioral treatment as soon as possible.     

A case of ascities decrease in malignant peritoneal mesothelioma by weekly intra-peritoneal administration of cisplatin and paclitaxel

We report a case of malignant peritoneal mesothelioma (MPM) in a 63-year-old man. He had body weight loss and abdominal distension for one month, and was admitted to our hospital. Abdominal sonography showed a large mass occupying the right lower abdomen and an existence of a lot of ascites. Computed tomography and magnetic resonance image showed a lot of ascites and omentum cake. Cytology of the ascites was Class V but its histological classification was unknown. Then we performed biopsy of the tumor into the omentum with abdominal sonography. The histological diagnosis was MPM because the tumor cells showed positive for calretinin. He received a combination chemotherapy of weekly intra-peritoneal administration of cisplatin (70 mg/ day) and paclitaxel (100 mg/day). The ascites was decreased and per os (PO) was possible, but omentum cake was not changed. MPM was poor in prognosis and the control of ascites was difficult. We suggest that the chemotherapy of intra-peritoneal administration was a better procedure than others to control ascites with malignant tumors.     

Gene expression profiles correlate with the morphology and metastasis characteristics of renal cell carcinoma cells

Renal cell carcinoma (RCC) shows various clinical behaviors, and currently surgical modalities are the only effective therapy against this cancer. To discern the genomic background affecting clinical characteristics such as metastasis, we analyzed the gene expression profiles of the RCCs by DNA microarray using cell lines originating from primary or metastatic lesions. RNA was extracted from ten SKRC RCC cell lines and gene expression profiling was performed using a cDNA microarray of nearly 4,000 human cDNA clones. We compared the gene expression profiles between these SKRC cell lines and the normal renal proximal tubular cell line and among SKRC cell lines that showed different characteristics. The clustering of the selected 62 genes revealed similar profiling patterns between SKRC-17 and SKRC-29 cells that were derived from metastatic RCC lesions. Another cell line from a metastatic lesion, SKRC-52, with a unique spindle-shaped morphology, had a different pattern of expression profiling from the other cell lines. We found several genes up-regulated in the cell lines from metastatic lesions; transgelin, which is reportedly involved in cell proliferation and migration, was up-regulated in SKRC-52. The unique profiling pattern of gene expression clearly correlated with cell morphology and metastatic potential. Such profiling might contribute to identifying the genes involved in the clinical characteristics of RCC.     

Rationale and clinical experience with epidermal growth factor receptor inhibitors in gynecologic malignancies

Opinion statement The family of epidermal growth factor receptors (EGFRs) is overexpressed in many gynecologic malignancies. Extensive preclinical studies of these receptors demonstrate that they play an important role in supporting the growth of a wide variety of malignancies and that interruption of receptor function or signaling from these receptors leads to inhibition of tumor growth or in certain cases tumor regression. Recently, many therapeutic agents targeting this receptor have entered the clinic and phase II clinical studies have demonstrated activity in lung cancer, colon cancer, and head and neck malignancies. Phase II trials of both small molecule inhibitors of EGFR and antibody-based inhibitors are underway in both cervical and ovarian cancer and emerging data suggests that their activity in unselected women with advanced gynecologic malignancies is very modest. Recently, molecular analysis of lung cancers has identified that the response to small molecule inhibitors of EGFR is highly correlated with activating mutations within the EGFR. It is possible that these agents will be highly effective in a small subset of patients with gynecologic malignancies whose tumors are dependent on EGFR signaling, perhaps through an activating mutation in EGFR or its downstream pathway. Until additional research can identify the subset of patients most likely to benefit from this targeted therapy, treatment for women with gynecologic malignancies with EGFR inhibitors should be limited to investigational trials. It is critical that these trials have access to tissue of responding and nonresponding patients so to determine the rational use of these agents in the treatment of gynecologic malignancies.     

Substrates of the prostate-specific serine protease prostase/KLK4 defined by positional-scanning peptide libraries

BACKGROUND: Prostase/KLK4 is a member of the human kallikrein (KLK) gene family that is expressed in prostate epithelial cells under the regulation of androgenic hormones. In this study, we sought to characterize the substrate specificity of KLK4 in order to gain insight into potential physiological roles of the enzyme. METHODS: A chimeric form of KLK4 was constructed in which the pro-region of KLK4 was replaced with the signal and propeptide sequence of trypsinogen (proT-KLK4) to create an activation site susceptible to enterokinase cleavage. proT-KLK4 was expressed in Drosophila S2 cells, purified, and activated with enterokinase to generate mature KLK4. The extended substrate specificity of KLK4 was defined by screening tetrapeptide positional scanning synthetic combinatorial libraries (PS-SCL). RESULTS: The preferred P1-P4 positions as determined by PS-SCL were: P1-Arg; P2-Gln/Leu/Val; P3-Gln/Ser/Val; P4-Ile/Val. The trypsin-like specificity of KLK4 was further confirmed using synthetic chromogenic peptides. Based upon the optimal cleavage site residues, a database search for potential KLK4 substrates identified several proteins with potential roles mediating normal prostate physiology or neoplastic growth including KLK3/PSA, parathyroid hormone-related peptide (PTHrP), and members of the bone morphogenetic protein (BMP) family. Recombinant KLK4 was able to activate pro-PSA/KLK3 and degrade members of the insulin-like growth factor (IGF) binding protein (IGFBP) family. CONCLUSIONS: These results identify potential KLK4 substrates that may serve to define the role of this protease in normal prostate physiology, and facilitate studies of the consequences of KLK4 expression in pathological conditions.     

Right ventricular pressure-volume loops using simultaneous radionuclide angiography with a multiwire gamma camera and right heart catheterization

BACKGROUND: The purpose of this study was to generate right ventricular (RV) pressure-volume loops (PVLs) from time-activity curves obtained by first-pass radionuclide angiography (RNA) and RV pressures obtained by right heart catheterization. METHODS AND RESULTS: Short-lived tantalum 178 was used to obtain first-pass RNA at baseline (n = 31), after nitroglycerin (n = 5), or after the conclusion of cardiac catheterization (n = 13). From the radionuclide-derived RV ejection fraction and thermodilution stroke volume, the RV end-diastolic volume and end-systolic volume were measured. Special proprietary software was developed and used to integrate the pressure and the RNA data. The mean heart rate was 80 +/- 17 beats/min; RV ejection fraction, 39% +/- 12%; RV end-diastolic volume, 217 +/- 79 mL; RV end-systolic volume, 142 +/- 74 mL; and RV end-diastolic pressure, 10 +/- 7 mm Hg. The RV PVLs were of high quality and reproducible. CONCLUSIONS: This study provides proof of concept of the feasibility of generating RV PVL; the short half-life (10 minutes) and low energy (59 keV) of Ta-178 allow the generation of multiple loops at low radiation exposure. Such studies could be performed at the bedside and provide a wealth of information that may have clinical and research merits.