An evaluation of the impact of the prospective payment system on antidepressant use in nursing home residents

OBJECTIVES: To determine the impact of the prospective payment system (PPS) for skilled nursing facilities on the pharmacologic treatment of depression. METHODS: We used a quasi-experimental study comparing the pharmacological treatment rates for depression in the pre-PPS period (1997) to the post-PPS period (2000) in 8149 residents with documented depression living in over 500 nursing facilities in Ohio. Logistic regression models adjusting for clustering effects of residents residing in homes using generalized estimating equations provided estimates of the PPS effect on use of any antidepressant and the use of selective serotonin reuptake inhibitors (SSRIs). We evaluated the extent to which the PPS effect was modified by organizational characteristics, including structural characteristics, resource characteristics, and staff resources available in the homes. RESULTS: Overall, there was no difference in the likelihood of any antidepressant [odds ratio (OR), 1.05; 95% confidence interval (CI), 0.93 to 1.18, resident-adjusted model] or an SSRI being used (OR, 0.98; 95% CI, 0.86 to 1.12, resident-adjusted model) after the introduction of PPS compared with 1997 when this reimbursement system was not in place (referent group). These trends did not appear to be modified substantially by organizational characteristics. CONCLUSION: Although PPS did not appear to have influenced the treatment of depression in nursing homes, systems that provide checks and balances in relation to PPS are warranted.     

Generation of embryonic stem cells and transgenic mice expressing green fluorescence protein in midbrain dopaminergic neurons

We have generated embryonic stem (ES) cells and transgenic mice with green fluorescent protein (GFP) inserted into the Pitx3 locus via homologous recombination. In the central nervous system, Pitx3-directed GFP was visualized in dopaminergic (DA) neurons in the substantia nigra and ventral tegmental area. Live primary DA neurons can be isolated by fluorescence-activated cell sorting from these transgenic mouse embryos. In culture, Pitx3-GFP is coexpressed in a proportion of ES-derived DA neurons. Furthermore, ES cell-derived Pitx3-GFP expressing DA neurons responded to neurotrophic factors and were sensitive to DA-specific neurotoxin N-4-methyl-1, 2, 3, 6-tetrahydropyridine. We anticipate that the Pitx3-GFP ES cells could be used as a powerful model system for functional identification of molecules governing mDA neuron differentiation and for preclinical research including pharmaceutical drug screening and transplantation. The Pitx3 knock-in mice, on the other hand, could be used for purifying primary neurons for molecular studies associated with the midbrain-specific DA phenotype at a level not previously feasible. These mice would also provide a useful tool to study DA fate determination from embryo- or adult-derived neural stem cells.     

Arterial stiffness, endothelial function and novel pharmacological approaches

1. Despite over half a century of intensive research, cardiovascular disease remains the leading cause of death world wide. Nevertheless, a number of risk factors for cardiovascular disease have been identified, such as hypertension and serum cholesterol, and therapies targeting such factors are effective in reducing cardiovascular and total mortality. Arterial stiffness is an additional independent risk factor for cardiovascular disease and strategies aimed at lowering arterial stiffness may be effective in reducing cardiovascular risk. However, in order to exploit fully the therapeutic potential of this approach, it is necessary first to understand the physiological and pathophysiological factors regulating the stiffness of the large arteries. 2. Until recently, stiffness was thought to depend largely upon structural components within the arterial wall, such as elastin and collagen and the distending pressure. However, we now recognize that arterial smooth muscle also regulates vessel stiffness and that a number of locally derived and circulating factors, including nitric oxide (NO), endothelin-1 and the natriuretic peptides, contribute to the short-term or functional regulation of large artery stiffness. Changes in the balance between these factors and, in particular, a reduction in NO production may well explain why conditions such as hypercholesterolaemia and diabetes are themselves associated with arterial stiffening before the development of manifest atherosclerosis. 3. The importance of smooth muscle in regulating arterial stiffness suggests that direct pharmacological manipulation of stiffness may be possible, thus providing novel therapeutic strategies to reduce cardiovascular risk. Furthermore, differences in the effect of existing drugs on larger artery stiffness may explain, in part, why some drugs produce better clinical outcomes than others.     

Prediction of survival: a comparison between two subjective health measures in an elderly population

A large amount of evidence shows that the subjective evaluation of health is a predictor of survival in many different populations. Subjective health (SH) is measured using different types of measures such as a general evaluation of health or a comparative evaluation of health. The aim of this study was to compare the prediction of survival by two measures of SH (a general measure and an age-related measure) and evaluate the association with other variables in an elderly population. The baseline survey was conducted during 1994, covering 1138 men and women aged over 70. The survival status was ascertained 7 years later. After adjustment for age, sex, education, marital status, perceived socioeconomic status and presence of diseases the two SH measures were found to be predictors of mortality, but only in men. In men, there was no significant difference between the two types of SH measures in their prediction of mortality. Also in men, when there was only one or no disease, being married had a protective effect compared with not being married when both types of SH measures were used. In elderly women, the association between the two types of SH and survival diminished after adjusting for the various variables. However, the general SH measure may be the preferable measure to use when needed. Education in women was associated with mortality only via the age-related SH measure.     

Radiosensitization of colon cancer cell lines by docetaxel: mechanisms of action

The radiation-modifying action of docetaxel in experimental systems is well established. Docetaxel is also an increasingly important drug for the treatment of cancer in concurrent radiotherapy protocols. However, the mechanisms of docetaxel radiosensitization are not fully understood. We have investigated the magnitude and mechanisms of docetaxel radiosensitization in vitro in four human colorectal cancer cell lines (SW480, SW707, SW48, and HT29) with widely differing radiosensitivities. Cell survival curves were generated for a range of docetaxel concentrations (5-20 nM) alone and for X-rays (1-5 Gy) +/- 10 or 20 nM docetaxel (for 24 h before irradiation). Cell cycle distributions and apoptotic frequencies were measured during the treatments. Sensitivity to docetaxel alone was similar in all cell lines and could be attributed to massive induction of apoptosis (60-80% by 24 h). Radiosensitivity varied widely; the surviving fractions at 2 Gy in the most resistant (HT29) and most sensitive (SW28) lines were 0.81 and 0.13, respectively. Exposure to 10 nM docetaxel induced a progressive accumulation of SW480, SW707, and SW48 cells in G2/M. After 24 h, 55-70% of the cells were in G2/M. It is likely, therefore, that accumulation in this radiosensitive phase of the cell cycle contributes significantly to radiosensitization by the drug.     

Aetiology and prevalence of lower limb lymphoedema following treatment for gynaecological cancer

OBJECTIVE: To determine the prevalence and incidence of lower limb lymphoedema (LLL) in a cohort of women who had treatment for gynaecological cancer between May 1995 and April 2000. DESIGN: A retrospective survey. SETTING: The study took place at an urban referral centre in an Australian tertiary referral women's hospital. SAMPLE: The data collection was based on 66% of 743 women on the database of the Gynaecological Cancer Centre. METHODS: Interviews and assessments were conducted to determine the status of lower limbs; medical records were reviewed for age, weight, site and type of cancer and treatment. MAIN OUTCOME MEASURES: Leg swelling, diagnosed lower limb lymphoedema, no swelling of the legs and type of surgery were determined as the main outcome measures. RESULTS AND CONCLUSIONS: The diagnosis of lower limb lymphoedema was made in 18% of the total sample: 53% of these were diagnosed within 3 months of treatment, a further 18% within 6 months, 13% within 12 months and the remaining 16% up to 5 years following treatment. Women most at risk for developing LLL were those who had treatment for vulvar cancer with removal of lymph nodes and follow up radiotherapy. For this subsample, the prevalence was 47%. The finding that LLL occurs within the first year is earlier than hitherto generally believed. It is therefore imperative for all health professionals to include care and assessment of the legs particularly during the immediate pre- and postoperative period.