The effect of parotid gland-sparing intensity-modulated radiotherapy on salivary composition, flow rate and xerostomia measures.

OBJECTIVES: To describe parotid gland (PG) saliva organic and inorganic composition and flow rate changes, after curative intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC), and analyse the relationship between PG saliva analytes and xerostomia measures. METHODS AND MATERIALS: Twenty-six patients recruited to five prospective phase 2 or 3 trials which assessed toxicity and efficacy of IMRT by HNC subsite, provided longitudinal PG saliva. Salivary flow rate, and subjective and objective xerostomia measures were prospectively collected and saliva tested for inorganic and organic analytes. Statistical comparisons of longitudinal analyte changes and analysis for a relationship between dichotomized xerostomia score and saliva analytes were performed. RESULTS: One hundred and forty-two PG saliva samples from 26 patients were analysed. At 3-6 months after IMRT, stimulated and unstimulated saliva showed significantly decreased flow rate, total protein (TP) secretion rate, phosphate concentration and increased lactoferrin (LF) concentration. Stimulated saliva alone had elevated LF secretion rate and beta-2-microglobulin (B2 M) concentration with decreased calcium (Ca2+ ) and magnesium (Mg2+ ) concentrations and Ca2+ secretion rate. At >12 months, under stimulated and unstimulated conditions, increased LF concentration and decreased Mg2+ and phosphate concentration persisted and, in stimulated saliva, there was decreased potassium (K+ ) and Mg2+ concentration. Unstimulated TP secretion rate was lower in the presence of high-grade xerostomia. Otherwise, no relationship between xerostomia grade and PG salivary flow rate, TP and Ca2+ secretion rate was found. CONCLUSION: Fewer significant differences in PG saliva analytes >12 months after IMRT indicate good functional recovery. Residual xerostomia after IMRT will only be further reduced by addressing the sparing of subsites of the PG or other salivary gland tissues, in addition to the PG.

Neurobiological and psychological evidence of chronic stress in prostate cancer patients.

To measure the prevalence and severity of Generalised Anxiety Disorder (GAD), hypo- and hypercortisolaemia, and their association in a sample of prostate cancer (PCa) patients, 97 Australian PCa patients completed a background questionnaire and the GAD-7, and provided a sample of saliva collected 30-45 min after waking. The mean GAD7 score was 9.67 (SD = 3.09), and prevalence rates for current anxiety were higher than those reported for non-PCa males of a similar age. Mean salivary cortisol concentrations (30.78 nmol/L, SD = 13.97 nmol/L) were also higher than for age-comparative non-PCa men. There was a significant inverse correlation between GAD and cortisol (r = -. 209, p < .05), and four subgroups of GAD-cortisol patients were able to be identified, with evidence of both hyper- and hypocortisolaemia. These findings provide initial neurobiological evidence of the chronic and profound nature of stress experienced by PCa patients, and also suggest a possible measure that might be used to identify most at-risk PCa patients.

Macrobenthos and megabenthos responses to long-term, large-scale hypoxia on the Louisiana continental shelf.

The macrobenthos and megabenthos responses to long-term, recurring hypoxia on the Louisiana continental shelf were compared at four locations with different historical (2000-2010) episodes of annual exposure to bottom-water hypoxia. Measurements of abundance, biomass, species diversity, and community composition of the two size classes of benthos suggested that the macrobenthic response is driven chiefly by tolerance to hypoxia, whereas the megabenthic response was affected by the ability to migrate and the availability/unavailability of macrobenthos prey at the sediment surface. The site exposed to the historically lowest average bottom-water dissolved oxygen (BWDO) concentration exhibited the lowest species diversity for macrobenthos and the highest species diversity for megabenthos, exemplifying the differential effects of hypoxia on different size classes. The high diversity and smaller average size of the megabenthos at the lowest DO site was due to high abundance of invertebrates and a preponderance of small, less vagile fishes that appeared to remain in the area after larger dominant sciaenids had presumably emigrated. The average size and the depth of habitation in the sediment of macrobenthos prey may have also influenced the abundance and biomass of megabenthos foragers.

Total Mucosal Irradiation with Intensity-modulated Radiotherapy in Patients with Head and Neck Carcinoma of Unknown Primary: A Pooled Analysis of Two Prospective Studies.

AIMS: To determine the clinical outcomes of an intensity-modulated radiotherapy technique for total mucosal irradiation (TM-IMRT) in patients with head and neck carcinoma of unknown primary (HNCUP). MATERIALS AND METHODS: A single-centre prospective phase II trial design was used in two sequential studies to evaluate TM-IMRT for HNCUP. Patients were investigated for primary tumour site using examination under anaesthetic and biopsies, computed tomography ± magnetic resonance imaging (MRI) or 18-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT). Patients received IMRT to the potential primary tumour sites and elective cervical nodes. Concomitant chemotherapy was used in patients who received primary radiotherapy or those with nodal extracapsular extension. RESULTS: Thirty-six patients with HNCUP were recruited; 72% male. Twenty-five patients (69.4%) had p16-positive disease. Two year mucosal and local nodal control rates were 97.1% (95% confidence interval 91.4-100) and 89.8% (78.4-100), respectively. One mucosal primary was detected 7.3 months after TM-IMRT and three patients died from recurrent/metastatic squamous cell carcinoma of the head and neck. Twelve patients (33%) developed grade 3 (Late Effects in Normal Tissue-Subjective, Objective, Management and Analytical; LENT-SOMA) dysphagia with a 1 year enteric tube feeding rate of 2.7%. The high-grade subjective xerostomia rate (LENT-SOMA) at 24 months after IMRT was 15%. CONCLUSIONS: At a median follow-up of 36.1 months, the use of TM-IMRT was associated with good local control. Toxicity was comparable with previously reported TM-IMRT regimens encompassing similar mucosal volumes.

Preventive services for the elderly: would coverage affect utilization and costs under Medicare?

OBJECTIVES: This study was undertaken to determine whether adding a benefit for preventive services to older Medicare beneficiaries would affect utilization and costs under Medicare. METHODS: The demonstration used an experimental design, enrolling 4195 older, community-dwelling Medicare recipients. Medicare claims data for the 2 years in which the preventive visits occurred were compared for the intervention (n = 2105) and control (n = 2090) groups. Monthly allowable charges for Part A and Part B services and number of hospital discharges and ambulatory visits were compared. RESULTS: There were no significant differences in the charges between the groups owing to the intervention, although total charges were somewhat lower for the intervention group even when the cost of the intervention was included. Charges for both groups rose significantly as would be expected for an aging population. A companion paper describes a modest health benefit. CONCLUSIONS: There appears to be a modest health benefit with no negative cost impact. This finding gives an early quantitative basis for the discussion of whether to extend Medicare benefits to include a general preventive visit from a primary care clinician.

Developing a quality improvement database using health insurance data: a guided tour with application to Medicare's National Claims History file.

Health policy researchers are increasingly turning to insurance claims to provide timely information on cost, utilization, and quality trends in health care markets. This research offers an in-depth description of how to systematically transform raw inpatient and ambulatory claims data into useful information for health care management and research using the Health Care Financing Administration's National Claims History file as an example. The topics covered include: (a) understanding the contents and architecture of claims data, (b) creating analytic files from raw claims, (c) technical innovations for health policy studies, (d) assessing data accuracy, (d) the costs of using claims data, and (e) ensuring confidentiality. In summary, claims data are found to have great potential for quality of care analysis. As in any analysis, careful development of a database is required for scientific research. The methods outlined in this study offer health data novices as well as experienced analysts a series of strategies to maximize the value of claims data for health policy analysis.

Nephrotoxic effects of primary immunosuppression with FK-506 and cyclosporine regimens after liver transplantation.

OBJECTIVE: We conducted a treatment trial to determine the relative toxicity of FK-506 and cyclosporine A (CSA) in liver transplant recipients. DESIGN: Between October 1990 and October 1991, 37 patients were enrolled in an open-labeled, randomized study of two immunosuppressive regimens after liver transplantation. MATERIAL AND METHODS: Of the 23 men and 14 women, 20 received FK-506 plus prednisone, and 17 received CSA plus prednisone and azathioprine. Renal function was assessed before and after transplantation (day 1, month 1, month 4, and month 12) by measurements of serum creatinine (SCr) and glomerular filtration rate (GFR) as determined by urinary iothalamate or creatinine clearance (or both). FK-506 trough plasma levels (enzyme immunoassay) were to be maintained between 0.2 and 5.0 ng/mL, and CSA trough blood levels (whole blood high-performance liquid chromatography) were to be maintained between 250 and 400 ng/mL. Severe nephrotoxicity was defined as sudden decreases in urine output to less than 10 mL/h or rapid increases in SCr (more than 0.5 mg/dL daily) that necessitated withdrawal of study medication for more than 48 hours. Mean patient age and values for SCr and GFR were comparable between the two groups at entry. RESULTS: Both study groups demonstrated a similar deterioration in renal function during a 12-month follow-up, although patients who received FK-506 had a significantly (P < 0.05) lower GFR when measured at 12 months than did patients treated with CSA (45 +/- 4 versus 64 +/- 6 mL/min per body surface area). Mild nephrotoxicity that responded to decreased drug doses was noted in 9 CSA-treated patients (53%) and 10 FK-506-treated patients (50%). Severe nephrotoxicity that necessitated drug withdrawal occurred in only four patients, all of whom were in the FK-506 group. These severe nephrotoxic reactions to FK-506 occurred early after transplantation, often during intravenous administration of the drug, and were not associated with poor liver allograft function or drug levels outside the therapeutic range. CONCLUSION: Both FK-506 and CSA are significantly nephrotoxic in liver transplant recipients. In this trial, however, we observed an early development of severe nephrotoxic reactions only in some patients who received FK-506.

Splitting as a defense mechanism in children of alcoholic parents.

This paper is an attempt to identify an antecedent of overt symptomatology in children of alcoholic parents. Through art and verbal productions, within the context of a structured learning experience, primitive ego defenses and severely impaired object relations can be detected. The concept of splitting vs. repression in object relations theory and its implications for the future functioning of the child is discussed. Clinical material illustrating differences between the child who utilizes mature ego defenses and the child who resorts to splitting is presented.