Examination of osteoarthritis and subchondral bone alterations within the stifle joint of an ovariectomised ovine model.

The exact relationship between osteoporosis and osteoarthritis is still a matter for debate for many. The ovariectomised ewe is frequently used as a model for osteoporosis, resulting in significant alterations in bone morphometry and turnover in both trabecular and subchondral bone after 1 year. This study examines whether ovariectomy has any impact on development of osteoarthritis within the ovine stifle joint at the same time point. In addition, we investigate whether there are any significant correlations present between articular cartilage degeneration and alterations in microstructural parameters or turnover rates in the underlying bone. Twenty-two sheep were examined in this study; 10 of the sheep underwent ovariectomy and 12 were kept as controls. Five distinctive fluorochrome dyes were administered intravenously at 12-week intervals to both groups, to label sites of bone turnover. All animals were then sacrificed 12 months postoperatively. Although most specimens showed some evidence of osteoarthritis, no measurable difference between the two study groups was detected. Osteoarthritis was associated with a thinning of the subchondral plate, specifically the subchondral cortical bone; however, whereas previous studies have suggested a link between trabecular thinning and osteoarthritis, this was not confirmed. No correlation was found between osteoarthritis and bone turnover rates of either the subchondral trabecular bone or bone plate. In conclusion, despite the fact that ovariectomy results in marked morphological and structural changes in the ovine stifle joint at 1-year postoperatively, no evidence was found to suggest that it plays a direct role in the aetiology of osteoarthritis.

Tooth-surface-specific effects of xylitol: randomized trial results.

The Xylitol for Adult Caries Trial was a three-year, double-blind, multi-center, randomized clinical trial that evaluated the effectiveness of xylitol vs. placebo lozenges in the prevention of dental caries in caries-active adults. The purpose of this secondary analysis was to investigate whether xylitol lozenges had a differential effect on cumulative caries increments on different tooth surfaces. Participants (ages 21-80 yrs) with at least one follow-up visit (n = 620) were examined at baseline, 12, 24, and 33 months. Negative binomial and zero-inflated negative binomial regression models were used to estimate incidence rate ratios (IRR) for xylitol's differential effect on cumulative caries increments on root and coronal surfaces and, among coronal surfaces, on smooth (buccal and lingual), occlusal, and proximal surfaces. Participants in the xylitol arm developed 40% fewer root caries lesions (0.23 D2FS/year) than those in the placebo arm (0.38 D2FS/year; IRR = 0.60; 95% CI [0.44, 0.81]; p < .001). There was no statistically significant difference between xylitol and control participants in the incidence of smooth-surface caries (p = .100), occlusal-surface caries (p = .408), or proximal-surface caries (p = .159). Among these caries-active adults, xylitol appears to have a caries-preventive effect on root surfaces (ClinicalTrials.gov NCT00393055).

Subchondral osteopenia and accelerated bone remodelling post-ovariectomy - a possible mechanism for subchondral microfractures in the aetiology of spontaneous osteonecrosis of the knee?

Osteopenia and subchondral microfractures are implicated in the aetiology of spontaneous osteonecrosis of the knee (SPONK). The ovine tibia shows significant alterations of the trabecular architecture within the subchondral bone of the medial tibial plateau post-ovariectomy (OVX), including reduced trabecular bone volume fraction. We hypothesise that accelerated subchondral bone resorption may also play a role in increasing microfracture risk at this site. Twenty-two sheep were examined in this study; 10 of the sheep underwent OVX, while the remainder (n = 13) were kept as controls (CON). Five fluorochrome dyes were administered intravenously at 12-week intervals via the jugular vein to both groups, to label sites of bone turnover. These animals were then killed at 12 months post-operatively. Bone turnover was significantly increased in the OVX group in both trabecular bone (2.024 vs. 1.047 no. mm(-2) ; P = 0.05) and within the subchondral bone plate (4.68 vs. 0.69 no. mm(-2) ; P < 0.001). In addition to the classically described turnover visible along trabecular surfaces, we also found visual evidence of intra-trabecular osteonal remodelling. In conclusion, this study shows significant alterations in bone turnover in both trabecular bone and within the subchondral bone plate at 1 year post-OVX. Remodelling of trabecular bone was due to both classically described hemi-osteonal and intra-trabecular osteonal remodelling. The presence of both localised osteopenia and accelerated bone remodelling within the medial tibial plateau provide a possible mechanism for subchondral microfractures in the aetiology of SPONK. Further utilisation of the OVX ewe may be useful for further study in this field.

Subchondral trabecular structural changes in the proximal tibia in an ovine model of increased bone turnover.

Ovariectomized (OVX) sheep are now considered to be useful models for a variety of metabolic bone disorders. The specific aim of this study was to determine the effects of ovariectomy on the structural parameters and material density of the subchondral bone of the ovine tibial plateau as measured by microcomputed tomography (MicroCT). Twenty-three sheep were examined in this study; 10 of the sheep underwent ovariectomy (OVX), and the remainder (n=13) were kept as controls (CON). These animals were then sacrificed at 12 months post-operatively. Three-dimensional analyses were performed of osteochondral samples (15 mm deep) which were obtained from the medial tibial plateau using MicroCT. Bone volume fraction of the subchondral trabecular bone was reduced in the ovariectomized sheep as compared to control animals (0.439 vs. 0.483, P=0.038). Trabeculae were also significantly thinner in the OVX group (0.220 vs. 0.252 mm, P=0.010), with reduced connectivity density (7.947 vs. 11.524 mm(-3) , P=0.014). There was a trend towards lower numbers of individual trabeculae present in the OVX group as compared to controls, but this did not reach significance (2.817 vs. 3.288 mm(-1) , P=0.1). There was also increased trabecular separation in the OVX group, which again fell short of significance (0.426 vs. 0.387 mm, P=0.251). There was no difference in hydroxyapatite concentration (HA) between the two groups (929 vs. 932 mgHA cm(-3) , P=0.687). In conclusion, significant alterations of the trabecular architecture under the tibial plateau were observed following 12 months of oestrogen-deficiency in this ovine model. Despite these marked morphological and structural density differences, the material densities were equal in the two groups.

The system of belief inventory (SBI-15): a validation study in Israel.

This study focused on the validation of measures assessing religiosity by means of three self-report instruments: the System of Belief Inventory (SBI-15R), the Religious Orientation Inventory (ROI), and the Index of Core Spiritual Experiences (INSPIRIT). These instruments were developed and validated previously in the United States. The study measured the extent to which the self-reports maintain their validity when administered in a different country with its own distinct language, culture and religion (e.g. Israel). It was found that all three self-reports have very good external validity and high convergent reliability, with the SBI demonstrating extremely high internal reliability.

Persistent symptoms among survivors of Hodgkin's disease: an explanatory model based on classical conditioning.

Persistent symptoms of nausea, distress, and vomiting triggered by reminders of cancer treatment were examined among 273 Hodgkin's disease survivors, 1 to 20 years posttreatment. Prevalence rates were high for distress and nausea but low for vomiting. Retrospective report of anticipatory symptoms during treatment was the strongest predictor of persistent symptoms, suggesting that treatment-induced symptoms are less likely to persist if conditioning does not occur initially. Time since treatment was also a significant predictor, with patients more recently treated more likely to experience persistent symptoms. Thus, an explanatory model based on classical conditioning theory successfully predicted presence of persistent symptoms. Symptoms also were associated with ongoing psychological distress, suggesting that quality of life is diminished among survivors with persistent symptoms. Recommendations for prevention and treatment of symptoms are discussed.

Improving the human side of cancer care: psycho-oncology's contribution.

Psycho-oncology is only about twenty-five years old, emerging since the diagnosis of cancer began to be revealed and honest discussions could occur about this illness. The stigma has diminished and much progress has been made in that short period. This small new field brings concepts to care that incorporate both prevention and delivery of services to reduce distress and enhance well-being. Its first dimension studies the psychological reaction of patients at all stages of the disease, as well as those of the family and healthcare staff, and the second dimension explores the psychological, social, and behavioral factors that may impact on cancer incidence and survival. Psycho-oncology has a place at the table within the oncology community, both in clinical care and in research, especially related to prevention, quality of life, symptom control, and palliative care. Psycho-oncology is part of the continuum of cancer care that includes primary and secondary prevention at one end, and survivors and palliative care at the other. Our present body of information rests on a large database of research. Implementation of what we know now could greatly improve the psychological well-being and quality of life of patients with cancer.

Stress and burnout in oncology.

This article identifies the professional stressors experienced by nurses, house staff, and medical oncologists and examines the effect of stress and personality attributes on burnout scores. A survey was conducted of 261 house staff, nurses, and medical oncologists in a cancer research hospital, and oncologists in outside clinical practices. It measured burnout, psychological distress, and physical symptoms. Each participant completed a questionnaire that quantified life stressors, personality attributes, burnout, psychological distress, physical symptoms, coping strategies, and social support. The results showed that house staff experienced the greatest burnout. They also reported greater emotional exhaustion, a feeling of emotional distance from patients, and a poorer sense of personal accomplishment. Negative work events contributed significantly to level of burnout; however, having a "hardy" personality helped to alleviate burnout. Nurses reported more physical symptoms than house staff and oncologists. However, they were less emotionally distant from patients. Women reported a lower sense of accomplishment and greater distress. The four most frequent methods of relaxing were talking to friends, using humor, drinking coffee or eating, and watching television. One unexpected finding was that the greater the perception of oneself as religious, the lower the level of burnout. Thus, while the rewards of working in oncology are usually sufficient to keep nurses and doctors in the field, they also experience burnout symptoms that vary by gender and personal attributes. House staff are most stressed and report the greatest and most severe symptoms of stress. Interventions are needed that address the specific problems of each group.

Psychosocial aspects of cancer genetics: women at high risk for breast and ovarian cancer.

In the past five years the advent of cancer genetic testing has created concern about the negative psychosocial sequelae of genetic counseling and testing. Research indicates that the women most likely to seek genetic testing are anxious about carrying a gene mutation and developing breast cancer. Women who are at high risk have poor knowledge and the expectation of being a gene-mutation carrier. High levels of distress have been shown to interfere with decision-making about genetic testing. Further, individuals who decline genetic testing may be at increased risk for depressive symptoms even more than those who are found to be gene-mutation carriers. There is great concern that inappropriate candidates will seek genetic testing. Improved education and access to genetic counseling are essential to help women make appropriate decisions about genetic testing. Strategies for the prevention of breast and ovarian cancer are explored, and methods to reduce the adverse psychosocial effects of decision-making about genetic testing and preventive treatment strategies are suggested.

Involving family members in cancer care: focus group considerations of patients and oncological providers.

Family members are an integral part of a patient's cancer care from the moment the diagnosis is delivered to the conclusion of treatment. Family members bring with them a range of emotional reactions, interpersonal dynamics and expectations for the care the patient receives. This study is part of a multi-institutional project to continue to improve the process of cancer care. In this study, 19 focus groups (11 patient and 8 provider) were conducted concerning issues related to doctor-patient communication in eight cancer centers in the United States. The content of the conversations was analyzed and thematic categories emerged that highlight the various strengths and difficulties associated with family involvement. The focus groups' comments support the need for explicit conversations between professional caregivers, patients and their loved ones, in order to negotiate the expectations and needs of each team member. Implications for clinical practice and strategies for working with family members are offered.

A pilot study of interpersonal psychotherapy by telephone with cancer patients and their partners.

A single-arm pilot study explored the feasibility of adapting in Interpersonal Psychotherapy (IPT) by telephone to reduce psychological distress and to enhance coping during cancer treatment. Therapy focuses on role transitions, interpersonal conflicts, and grief precipitated by cancer. Breast cancer patients receiving high-dose chemotherapy received weekly sessions with a psychologist throughout chemotherapy and for 1 month afterwards. Patients could invite one 'partner' to receive individual telephone IPT. Psychosocial functioning was assessed using standardized measures at study entry, after chemotherapy, and following telephone IPT. Accrual and participation supplied evidence of feasibility: 14 patients and 10 partners were recruited, 82.5% of those eligible. Patients had a mean of 16 sessions; partners had a mean of 11. Participants rated their satisfaction with the program between 'good' and 'excellent'. A test of the efficacy of telephone IPT requires a larger, randomized trial. In order to standardize the intervention, a treatment manual was developed. This study indicated the importance of outreach to family members as well as to cancer patients, intensive patient education about oncology treatment and the medical care setting, and psychosocial services that continue after cancer treatment has been completed.

The role of religious and spiritual beliefs in coping with malignant melanoma.

This study investigated the role of spiritual and religious beliefs in ambulatory patients coping with malignant melanoma. One-hundred and seventeen patients with melanoma being seen in an outpatient clinic completed a battery of measurements including the newly validated Systems of Belief Inventory (SBI-54). No correlation was found between SBI-54 scores and levels of distress. However, there was a correlation between greater reliance on spiritual and religious beliefs and use of an active-cognitive coping style (r = 0.46, p < 0.0001). Data suggest that use of religious and spiritual beliefs is associated with an active rather than passive form of coping. We suggest that such beliefs provide a helpful active-cognitive framework for many individuals from which to face the existential crises of life-threatening illness.

Psycho-oncology: where have we been? Where are we going?

This article reviews the development of the subspeciality of psycho-oncology and its contributions to patient care, encouraging more attention to and research into the care of the total patient: the physical, psychological, social and spiritual aspects of care. The result is enhanced quality of life as the patient is studied in the domains of living that are important, extending across the continuum of care from diagnosis to palliative care. In addition, cancer prevention and early detection depends largely on changing attitudes and behaviours that put people at greater risk. This is an important area of research for psycho-oncologists. In the past two decades, research has contributed to our understanding of the psychological responses that accompany a cancer diagnosis. Oncologists better recognise psychological distress and psychiatric disorders such as anxiety, depression and delirium (in hospitalised patients) as frequent comorbid disorders. The development of valid assessment tools for the patients' self-report has been important. Increasingly, outcome measures in controlled trials of new therapies include quality of life, and no longer look at survival alone. The future will continue to bring new challenges to psycho-oncology as patients face new challenges in treatment. A major aim of the next century will be to bring this integrated approach to all patients in an affordable manner.

A controlled trial of fluoxetine and desipramine in depressed women with advanced cancer.

BACKGROUND: This study was conducted to determine the efficacy and tolerability of fluoxetine and desipramine in treating depressive symptoms in women with cancer. METHOD: In this prospective, 6-week, double-blind, placebo-controlled trial, we compared fluoxetine with desipramine in treating depressive symptoms in 40 women diagnosed with cancer. Scales used to measure efficacy and tolerability were the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A), the Clinical and Patient's Global Impression (CGI and PGI) scales, the Functional Living Index for Cancer (FLIC), the Memorial Pain Assessment Card (MPAC), and the SF-36 Health Survey. RESULTS: Fluoxetine and desipramine treatments improved depression and anxiety symptoms. There was a trend towards significance in improvement of FLIC scores (as evidenced by greater numerical improvements with fluoxetine treatment). Fluoxetine treatment alone was associated with statistically significant improvements in MPAC Mood scale scores. Both treatments showed statistically significant improvements in the quality of life SF-36 scores in Role Emotional, Social Functioning, Mental Health, and Vitality. CONCLUSIONS: Both fluoxetine and desipramine were effective and well-tolerated in improving depressive symptoms and quality of life in women with advanced cancer. Fluoxetine may offer greater benefit to these patients, as evidenced by greater improvements in fluoxetine-treated patients on several quality of life measures. Our results, while meaningful, should be confirmed in a larger patients sample. However, experience from studies of antidepressant use in patients with advanced cancer has shown that intercurrent disease and treatment variables make it difficult to conduct large studies.

Testing for drugs of abuse in saliva and sweat.

The detection of marijuana, cocaine, opiates, amphetamines, benzodiazepines, barbiturates, PCP, alcohol and nicotine in saliva and sweat is reviewed, with emphasis on forensic applications. The short window of detection and lower levels of drugs present compared to levels found in urine limits the applications of sweat and saliva screening for drug use determination. However, these matrices may be applicable for use in driving while intoxicated and surveying populations for illicit drug use. Although not an illicit drug, the detection of ethanol is reviewed because of its importance in driving under the influence. Only with alcohol may saliva be used to estimate blood levels and the degree of impairment because of the problems with oral contamination and drug concentrations varying depending upon how the saliva is obtained. The detection of nicotine and cotinine (from smoking tobacco) is also covered because of its use in life insurance screening and surveying for passive exposure.

Rapid screening for psychologic distress in men with prostate carcinoma: a pilot study.

BACKGROUND: As more oncology care is moved to the outpatient setting, the need for a rapid means for oncologists to identify patients with significant distress has increased. Concurrent with this move has been the pressure to reduce time spent with each patient, adding to the likelihood that a distressed patient will not be recognized and will remain untreated in the current health care environment. METHODS: A pilot program was conducted in a prostate carcinoma oncology clinic to test the feasibility of a two-stage approach that identifies patients in significant distress and refers them for treatment. Two pencil and paper self-report measures were used to detect psychologic distress in patients over the previous week: 1) The Hospital Anxiety and Depression Scale (HADS) and 2) "The Distress Thermometer." Patients who scored above an agreed upon cutoff score on either measure (HADS = 15+; Thermometer = 5+) were referred to the psychiatric liaison in the clinic for evaluation. RESULTS: Compliance in filling out the measures was excellent; only 8 of 121 patients (6.6%) refused. Thirty-one percent of evaluable patients were referred based on elevated scores. Seventeen of 29 patients actually were evaluated. Eight of 17 patients met Diagnostic and Statistical Manual (of Mental Disorders)-IV criteria for a psychiatric disorder. CONCLUSIONS: This approach for rapid screening for distress was acceptable in prostate carcinoma patients, although these older men were reluctant to agree to evaluation and treatment. This simple screening method needs further testing and the identification of barriers on the part of the patient and oncologist that impede the identification of the most distressed patients.

Comparison of psychosocial adaptation of advanced stage Hodgkin's disease and acute leukemia survivors. Cancer and Leukemia Group B.

BACKGROUND: The purpose of this study was to compare the long-term psychosocial adaptation of Hodgkin's disease and adult acute leukemia survivors. PATIENTS AND METHODS: Two hundred seventy-three Hodgkin's disease (HD) and 206 adult acute leukemia (AL) survivors were interviewed by telephone concerning their psychosocial adjustment and problems they attributed to having been treated for cancer, using identical research procedures and a common set of instruments. The following measures were used: Psychosocial Adjustment to Illness Scale (PAIS); Brief Symptom Inventory (BSI); current Conditioned Nausea and Vomiting triggered by treatment-related stimuli (CNVI); Indices of Employment, Insurance and Sexual Problems Attributed to Cancer; Negative Socioeconomic Impact of Cancer Index (NSI). All participants had been treated on one of nine Hodgkin's disease or 13 acute leukemia Cancer and Leukemia Group B (CALGB) clinical trials from 1966-1988, and had been off treatment for one year or more (mean years: HD = 5.9; AL = 5.6). RESULTS: HD survivors' risk of having a high distress score on the BSI was almost twice that found for AL survivors (odds ratio = 1.90), with 21% of HD vs. 14% of AL survivors (P < 0.05) having scores that were 1.5 standard deviations above the norm, suggestive of a possible psychiatric disorder. HD survivors reported greater fatigue (POMS Fatigue, P = 0.01; Vigor Subscales, P = 0.001), greater conditioned nausea (CNVI, P < 0.05), greater impact of cancer on their family life (PAIS Domestic Environment, P = 0.004) and poorer sexual functioning (PAIS Sexual Relationships, P = 0.0001), than AL survivors. CONCLUSIONS: Treatment-related issues may have placed HD survivors at a greater risk for problems in long-term adaptation than AL survivors.