Is there a role for survivorship care plans in advanced cancer?

PURPOSE: The Institute of Medicine (2006) has recommended that cancer survivors completing treatment receive a survivorship care plan (SCP). The survivorship needs in advanced cancer have been overlooked and understudied. The potential role of SCPs for survivors with advanced or metastatic cancer is unknown and was explored in this study. METHODS: We conducted two focus groups of survivors with advanced or metastatic cancer. Participants reviewed a sample JourneyForward™ SCP modified for advanced cancer. Sessions were audiotaped and transcribed; transcripts and field notes were evaluated using inductive content analysis. RESULTS: Sixteen survivors with metastatic cancer participated: 12 (75 %) were female, 15 (94 %) were white, and median age was 66 (range 55-80); 9 participants had breast cancer, 4 colon, 2 prostate, and 1 ovarian cancer. Participants believed that an SCP would be most helpful after initial diagnosis and treatment, but not as helpful once the cancer progressed. They thought a "cancer care plan" focusing solely on the current management would be better to concisely summarize the treatment plan and time frame for the next segment of care for those with advanced cancer. Most participants endorsed the need to have written information to reinforce verbal information received during medical visits since it was difficult to remember information provided. Participants expected their oncologist to assume primary responsibility for coordination of the care plan, but anticipated an important supportive role for primary care providers. To this end, they emphasized the need for better communication between providers. CONCLUSIONS: A cancer care plan developed by the oncologist, similar to an SCP but more focused on current management, may be more useful for survivors with advanced cancer. Exploring this topic in larger groups of more diverse survivors with advanced cancer will help to elucidate the details a written plan of care should contain, and how to promote effective coordination between oncology and primary care providers. IMPLICATIONS FOR CANCER SURVIVORS: There are many transitions of care along the cancer journey. A written plan of care, similar to an SCP, may be useful for survivors with advanced cancer.

Cardiac effect of short-term experimental weight gain and loss in dogs.

During 12 weeks, 18 normal dogs were fed a high-caloric diet intended to induce obesity (weight-gain phase). For the next 12 weeks (weight-loss phase), all dogs were fed a diet calculated to provide maintenance needs. During this second phase, dogs were randomly assigned to three groups differing only in their exercise regimen: group 1 dogs were not exercised, group 2 dogs were exercised three times each week on a treadmill, group 3 dogs were similarly exercised and outfitted with a vest holding additional weights. Echocardiographic data were obtained at baseline and following both the weight-gain and weight-loss phases. The weight-gain phase of the study was associated with an increase in bodyweight (31.4 per cent), decrease in body density (3.9 per cent) and an increase in left ventricular (LV) myocardial cross-sectional area in all groups. Cardiac hypertrophy was variably reversible during the weight-loss phase, with complete recovery for group 1, partial recovery for group 2 and no recovery in group 3. Regardless of group, weight loss was associated with a significant increase in LV diameter, a reduction of heart rate and an increase in heart rate-corrected isovolumetric relaxation time.

Congenital ureteral ectopia in continent and incontinent-related Entlebucher mountain dogs: 13 cases (2006-2009).

BACKGROUND: Ectopic ureters (EUs) associated with varying combinations of urinary incontinence, hydronephrosis, and urinary tract infection have been identified in related North American Entlebucher Mountain Dogs. OBJECTIVES: To characterize the disease phenotype in affected dogs and evaluate possible modes of inheritance. ANIMALS: Twenty client-owned Entlebucher Mountain Dogs. Nine dogs had clinical signs of urinary tract disease. METHODS: Prospective case series in which 17 dogs were evaluated with excretory urography, ultrasonography, and urethrocystoscopy. Three additional dogs were evaluated by necropsy alone. Clinical and pedigree histories from 165 North American Entlebuchers were compiled for analysis. RESULTS: Eleven female and 2 male dogs were found to have EUs. Six females and 1 male were continent. Bilateral intravesicular ectopic ureters (IVEUs) were identified in 9 dogs, bilateral extravesicular ectopic ureters (EVEUs) in 3 dogs, and 1 dog had IVEU and EVEU. Hydronephrosis was identified in 5 dogs, 3 of which had bilateral IVEUs. Two necropsied dogs had bilateral hydronephrosis with presumed ureterovesical junction obstruction associated with chronic granulation tissue or lymphoplasmacytic inflammation. Twenty-six dogs with EUs were identified in the pedigree. Because of incomplete penetrance, mode of inheritance could not be determined. CONCLUSIONS AND CLINICAL IMPORTANCE: Ureteral ectopia is common in North American Entlebucher Mountain Dogs and clinical signs alone could not reliably predict disease phenotype. EVEUs were associated with urinary incontinence and occasionally hydronephrosis. IVEUs were clinically silent or associated with hydronephrosis. Further analyses are necessary to confirm and characterize the hereditary nature of the disorder.

Exercising stall-housed gestating gilts: effects on lameness, the musculo-skeletal system, production, and behavior.

Lameness in breeding-age gilts and sows is a major cause of culling, resulting in increased economic losses and welfare concerns. This study determined if exercise during gestation would affect the musculo-skeletal system, production variables, and behavior. Gilts were blocked by BW and assigned to 1 of 3 treatment groups: control (n = 10; no exercise), low exercise (n = 14; 122 m/d for 5 d/wk), and high exercise (n = 14; 122 m/d for 2 d/wk and 427 m/d for 3 d/wk). All gilts were stall-housed during gestation, and gilts were exercised between d 35 and 110 of gestation. Lameness score, BCS, BW, and blood were taken at multiple points before gestation, and during gestation and lactation. Blood serum was analyzed for carboxy-terminal telopeptide of type I collagen. Sow lying behavior was recorded for 3 d after farrowing. Farrowing data included litter weight and size at birth and weaning, and preweaning mortality. After weaning, 38 sows were slaughtered and muscles and the bones of the left fore- and hind-limbs were harvested. Bone density and quality were determined by computed tomography (CT) scans, dual energy x-ray scans, and bone-breaking force tests. The control group took longer to lie down than both exercise groups, and the low exercise group took longer to lie down than the high exercise group (P < 0.05). The number of pigs weaned was greater in the high exercise group than the control group (P < 0.05). Piglet preweaning mortality was greatest in the control group compared with both exercise groups (P < 0.05). The low exercise treatments exhibited a greater bone density (CT) in the humerus, radius, and tibia compared with that of the control group (P < 0.05). The bone density (CT) of the humerus in the low exercise group was greater than that of the high exercise group (P = 0.03). Breaking force in the humerus and femur was greater (P < 0.05) in the low exercise group than the control group. Breaking force in the tibia of the high exercise group was greater than the control group (P = 0.01). The tibia of both the low and high exercise groups had a greater breaking force (P < 0.05) than the control group. Although there was no benefit of exercise on lameness, differences in bone density and quality, lying behavior, and piglet survivability may provide useful insight into alternative housing for sows.

Sodium zeolite a supplementation and its impact on the skeleton of dairy calves.

Twenty calves were placed on study at 3 days of age and were placed according to birth order into one of two groups: SS, which received 0.05% BW sodium zeolite A (SZA) added to their milk replacer, and CO, which received only milk replacer. Blood samples were taken on days 0, 30, and 60 for osteocalcin (OC) and deoxypyridinoline (DPD) analysis. On day 60, the calves were euthanized, and synovial fluid, articular cartilage, and both fused metacarpals were collected for bone quality analyses such as architecture and mechanical properties, mineral composition, and glycosaminoglycan concentration. There were no differences in OC concentrations because of treatment (p = 0.12), and CO calves had lower DPD concentrations than SS calves (p = 0.01), but the OC-to-DPD ratio was not different between treatments (p = 0.98). No differences in bone architecture or mechanical properties were detected. SZA supplementation increased cortical bone (p = 0.0002) and articular cartilage (p = 0.05) aluminum content. Glycosaminoglycan concentrations were not different in synovial fluid or cartilage. Supplementation of SZA appeared to alter the rate of bone turnover without altering bone strength. Aluminum concentrations in the bone and cartilage increased, which may be a concern, although the long-term consequences of such remain to be determined.

The Met66 allele of the functional Val66Met polymorphism in the brain-derived neurotrophic factor gene confers protection against neurocognitive dysfunction in systemic lupus erythematosus.

BACKGROUND: A common functional polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met) was previously associated with diminished episodic memory performance in healthy people. As cognitive function is commonly impaired in patients with systemic lupus erythematosus (SLE), the association of the BDNF Val66Met with neurocognitive function was studied. OBJECTIVE: To study the association of the BDNF Val66Met with neurocognitive function in a cohort of patients with SLE. METHODS: Cognitive function was assessed in 59 patients with SLE with no previous or current central nervous system involvement. Cognitive tests were grouped into five domains (memory, attention/executive function, visuospatial skills, motor function and psychomotor speed) and used to obtain domain Z scores, reflecting the difference between averaged scores of performance on individual tests and published norms in each domain. Genotyping was carried out using a 5'-nuclease assay with 99.9% accuracy. Unpaired t test was used to assess the relationship between genotypes and cognitive function, whereas the effect of possible confounders was assessed in a multivariate analysis. RESULTS: Patients carrying the Met66 allele scored significantly higher on psychomotor, attention/executive and motor function tests, resulting in significantly higher domain Z scores for the psychomotor (p = 0.005) and motor (p = 0.002) domains. CONCLUSIONS: The BDNF Met66 allele was associated with better cognitive functioning in the psychomotor and motor domains, even after controlling for differences in ethnicity, sex, depression status and prednisone treatment. These data suggest that the BDNF Met66 allele confers protection against the decline of motor and psychomotor cognitive functions in patients with longstanding SLE.

Impact of supplement withdrawal and wheat middling inclusion on bone metabolism, bone strength, and the incidence of bone fractures occurring at slaughter in pigs.

The objective of this study was to determine if supplement withdrawal (omission of dietary vitamin and trace mineral premixes and 2/3 of inorganic P) 28-d preslaughter and the feeding of wheat middlings (dietary concentrations of 5, 15, or 30% from weaning to 16 kg, 16 to 28 kg, and 28 kg to slaughter, respectively) affect bone metabolism, bone strength, bone density, and the incidence of bone fractures at slaughter in pigs. Crossbred barrows (n = 64) were assigned to a 2 x 2 factorial arrangement of treatments (with or without supplement withdrawal, and with or without wheat middlings). Serum was collected on d 0, 14, and 27 of the preslaughter withdrawal period to determine changes in the concentrations of osteocalcin, an indicator of bone formation, and pyridinoline, an indicator of bone resorption. The serum osteocalcin and pyridinoline concentrations on d 14 and 27 were analyzed as change from the d-0 concentration. At slaughter, radiographs of the lumbar vertebrae and of the right and left femurs were taken to determine the incidence of bone fractures. Third metacarpal bones were analyzed for bone mineral density, peak load, ultimate shear stress, and percent ash. Supplement withdrawal increased (P < 0.05) serum osteocalcin and pyridinoline concentrations, indicating an increase in osteoblast activity and bone resorption. Supplement withdrawal decreased (P < 0.01) bone mineral density, peak load, ultimate shear stress, and percent ash of the metacarpal bones. Dietary wheat middling inclusion did not alter bone quality. Neither supplement withdrawal nor wheat middling inclusion affected the incidence of bone fractures at slaughter. The results of this study indicate that removing inorganic P, vitamin premix, and trace mineral premix for 28 d preslaughter increases bone turnover and decreases bone quality.

The effect of bilateral glossopharyngeal nerve anaesthesia on swallowing in horses.

REASONS FOR PERFORMING STUDY: Dysfunction of the glossopharyngeal nerve has been implicated as a cause of dysphagia in horses. However, recent studies have indicated that this is not the case. OBJECTIVES: To determine whether bilateral glossopharyngeal nerve anaesthesia would cause dysphagia in horses or result in measurable alterations in the timing, function, or sequence of swallowing. METHODS: Swallowing was evaluated in 6 normal horses with and without bilateral glossopharyngeal nerve anaesthesia. Swallowing dynamics were assessed subjectively and objectively based on time from prehension of food until swallowing, number of tongue movements until initiation of swallowing, depth of bolus at the base of the tongue prior to initiation of swallow and evidence of tracheal aspiration using fluoroscopy and endoscopy. RESULTS: There was no evidence of aspiration or dysphagia in horses before or after bilateral glossopharyngeal nerve block. No observed or measured differences in swallowing sequence or function could be detected in blocked compared to unblocked horses. However, there was a trend in blocked horses for the number of tongue pushes and the time to swallowing to be increased. CONCLUSIONS: Glossopharyngeal nerve function may not be essential for normal swallowing function in otherwise healthy horses. POTENTIAL RELEVANCE: Clinically, normal swallowing is not an appropriate test of glossopharyngeal nerve function and dysphagic horses should not be assumed to have glossopharyngeal nerve dysfunction.

Psychiatric and neuropsychological characterization of Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS) is a rare, single-gene, malformation syndrome that includes central polydactyly, hypothalamic hamartoma, bifid epiglottis, endocrine dysfunction, and other anomalies. The syndrome has variable clinical manifestations and is inherited in an autosomal dominant pattern. We sought to determine whether psychiatric disorders and/or neuropsychological impairment were characteristic of PHS. We prospectively conducted systematic neuropsychiatric evaluations with 19 PHS subjects ranging in age from 7 to 75 years. The evaluation included detailed clinical interviews, clinician-rated and self-report instruments, and a battery of neuropsychological tests. Seven of 14 adult PHS subjects met diagnostic criteria for at least one DSM-IV Axis I disorder. Three additional subjects demonstrated developmental delays and/or neuropsychological deficits on formal neuropsychological testing. However, we found no characteristic psychiatric phenotype associated with PHS, and the frequency of each of the diagnoses observed in these subjects was not different from that expected in this size sample. The overall frequency of psychiatric findings among all patients with PHS cannot be compared to point prevalence estimates of psychiatric disease in the general population because of biased ascertainment. This limitation is inherent to the study of behavioral phenotypes in rare disorders. The general issue of psychiatric evaluation of rare genetic syndromes is discussed in light of this negative result.

Short-duration exercise and confinement alters bone mineral content and shape in weanling horses.

The hypothesis that short-duration exercise may ameliorate the decrease in bone mass observed with confinement was investigated with 18 quarter horses (nine colts and nine fillies) weaned at 4 mo of age and placed into box stalls. After a 5-wk adjustment period, individuals were grouped by age and weight, and then divided randomly into three treatment groups: 1) group housed; 2) confined with no exercise; and 3) confined with exercise. The confined and exercised groups were housed in 3.7 m x 3.7 m box stalls for the 56-d duration of the trial. The exercised group was sprinted 82 m/d, 5 d/wk, in a fenced grass alleyway. The weanlings were led down an alleyway, turned loose in a small pen, and then released and allowed to run back down the alley. The group horses were housed together in a 992-m2 drylot with free access to exercise. On d 0, 28, and 56, dorsopalmar and lateromedial radiographs of the left third metacarpal bone were taken to estimate changes in bone mineral content and cortical widths. Mean values of medial, lateral, and total radiographic bone aluminum equivalence increased over time (P < 0.05), whereas dorsal and palmar radiographic bone aluminum equivalence did not change significantly. Dorsal, medial, and total radiographic bone aluminum equivalence tended (P = 0.09) to differ by a treatment x day interaction, with values increasing over time only in the exercised group. Normalized medial and total radiographic bone aluminum equivalence tended (P < 0.1) to differ (P < 0.01) with treatment, with exercised horses having greater bone aluminum equivalence than confined horses. Dorsopalmar cortical width in exercised horses was greater than on d 56 (treatment x day; P = 0.07). The dorsopalmar medullary cavity decreased in exercised vs. group-housed horses (P = 0.027), whereas dorsal and medial cortical width tended to increase only in the exercised horses (treatment x day; P < 0.01). This study indicated that a short-duration exercise protocol might be effective in improving bone mass and therefore skeletal strength in horses.

High-intensity exercise of short duration alters bovine bone density and shape.

The ability of short-duration high-intensity exercise to stimulate bone formation in confinement was investigated using immature Holstein bull calves as a model. Eighteen bull calves, 8 wk of age, were assigned to one of three treatment groups: 1) group-housed (GR, which served as a control), 2) confined with no exercise (CF), or 3) confined with exercise (EX). The exercise protocol consisted of running 50 m on a concrete surface once daily, 5 d/wk. Confined calves remained stalled for the 42-d duration of the trial. Blood samples were taken to analyze concentrations of osteocalcin and deoxypyridinoline, markers of bone formation and resorption. At the completion of the trial, calves were humanely killed, and both forelegs were collected. The fused third and fourth metacarpal bone was scanned using computed tomography for determination of cross-sectional geometry and bone mineral density. Three-point bending tests to failure were performed on metacarpal bones. The exercise protocol resulted in the formation of a rounder bone in EX as well as in increased dorsal cortex thickness compared with those in the GR and CF. The exercised calves had a significantly smaller medullary cavity than CF and GR (P < 0.01) and a larger percentage of cortical bone area than CF (P < 0.01). Dorsal, palmar, and total bone mineral density was greater in EX than in CF (P < 0.05), and palmar and total bone mineral densities were greater (P < 0.05) in EX than in GR. There was a trend for the bones of EX to have a higher fracture force than CF (P < 0.10). Osteocalcin concentrations normalized from d 0 were higher in EX than CF (P < 0.05). Therefore, the exercise protocol altered bone shape and seemed to increase bone formation comparison with the stalled and group-housed calves.

Multipotential osteosarcoma with various mesenchymal differentiations in a young dog.

Apparently synchronous, aggressive, mixed mesenchymal tumors in the right tibia, right femur, left femur, and rib cage produced multiple microscopic metastases in the lungs and macroscopic metastases in the liver, kidney, and spleen in a 1.5-year-old, neutered male, mixed-breed dog. No primary soft tissue tumor mass was present. Microscopically, the neoplasm exhibited osteosarcomatous, chondrosarcomatous, liposarcomatous, leiomyosarcomatous, fibrosarcomatous, angiosarcomatous, and leukocytic differentiation and was diagnosed as a multipotential osteosarcoma with various mesenchymal differentiation. Immunohistochemically, the neoplasm was cytoplasmically immunoreactive for vimentin, osteonectin, osteocalcin, CD 18, CD 31, desmin, and muscle-specific actin. Oil Red O staining was positive within liposarcomatous areas. Skeletal metastases from a primary bone tumor are exceedingly rare in human and veterinary medicine. However, the history, clinical signs, location, microscopic and immunohistochemical features were similar to those described in aggressive, poorly differentiated osteosarcomas of children. In addition, the wide range of mesenchymal tissue differentiation of this neoplasm was unusual, and to the authors' knowledge, an osteosarcoma with this degree of multiple differentiation has not been previously reported in the dog.

Influence of trotting and supplemental weight on metacarpal bone development.

The use of weight-training to alter bone strength has not been investigated in horses. Recognising that bone responds to loading, we studied the effect of carrying weight on bone development during training. Seventeen horses were divided into 3 groups: controls exercised counterclockwise in a free-flow exerciser; the weight group performed the same exercise carrying progressively increasing weight up to 45 kg and the weight supplement group also received a myo-anabolic supplement. Radiographic equivalence measure of bone mineral content of zones of the third metacarpi (MCIII) was determined on 4 occasions: baseline (Day 108), pre-conditioning following 108 days stall confinement (Day 0), mid-conditioning (Day 39) and end-conditioning (Day 78). Stall confinement resulted in loss of mineral in lateral and medial cortices of both MCIII. During conditioning, weight-carrying increased mineral deposition in lateral and medial cortices of MCIII of the left (inside) leg compared with controls. In the right leg, controls had lower mineral content of the lateral cortex at Day 39 than weight-carrying horses but no differences between treatments were recorded at Day 78. Markers of bone metabolism did not change from baseline to pre-conditioning, but increased from Day 0 to 39 and 78 for all groups. This study demonstrates the benefits to bone mineral deposition in the third metacarpi of carrying weight when trained at low speeds and re-emphasises the potential for bone loss when not given sufficient exercise.

A curriculum for teaching psychiatric research bioethics.

Psychiatric research has received intense ethical scrutiny during the past decade. Changes in how studies are designed, reviewed by ethics boards, conducted, and reported in the literature have created a need for a systematic approach to teaching psychiatric research ethics to clinical researchers in training. The purpose of this article is to describe a model curriculum and comprehensive background reading list for training in psychiatric research bioethics. The curriculum was designed as an interactive seminar in a research fellowship program but can be adapted and incorporated into existing medical school and psychiatry residency training curricula. Participants in the seminar provide formal and informal evaluations of each session and the seminar as a whole. The seminar, now in it's third year, has been regularly attended and highly regarded by the NIMH research fellows who have participated. In response to recommendations by the participants, the content and organization of the seminar has been modified. Clinical research is both scientifically and ethically complex. Our initial experience with a formal curriculum in psychiatric research bioethics suggests that this educational activity has been both meaningful and relevant for psychiatrists training to be clinical investigators.

Dependency of detrusor contractions on calcium sensitization and calcium entry through LOE-908-sensitive channels.

1. The subcellular mechanisms regulating stimulus-contraction coupling in detrusor remain to be determined. We used Ca(2+)-free solutions, Ca(2+) channel blockers, cyclopiazonic acid (CPA), and RhoA kinase (ROK) inhibitors to test the hypothesis that Ca(2+) influx and Ca(2+) sensitization play primary roles. 2. In rabbit detrusor, peak bethanechol (BE)-induced force was inhibited 90% by incubation for 3 min in a Ca(2+)-free solution. By comparison, a 20 min incubation of rabbit femoral artery in a Ca(2+)-free solution reduced receptor-induced force by only 5%. 3. In detrusor, inhibition of sarcoplasmic reticular (SR) Ca(2+) release by 2APB, or depletion of SR Ca(2+) by CPA, inhibited BE-induced force by only 27%. The CPA-insensitive force was abolished by LaCl3. By comparison, 2APB inhibited receptor-induced force in rabbit femoral artery by 71%. 4. In the presence of the non-selective cation channel (NSCC) inhibitor, LOE-908, BE did not produce an increase in [Ca(2+)]i but did produce weak increases in myosin phosphorylation and force. 5. Inhibitors of ROK-induced Ca(2+) sensitization, HA-1077 and Y-27632, inhibited BE-induced force by approximately 50%, and in combination with LOE-908, nearly abolished force. 6. These data suggest that two principal muscarinic receptor-stimulated detrusor contractile mechanisms include NSCC activation, that elevates [Ca(2+)]i and ROK activation, that sensitizes cross bridges to Ca(2+).

Arthrocentesis of the temporomandibular joint in adult horses.

OBJECTIVE: To develop a method for arthrocentesis of the temporomandibular joint in adult horses. ANIMALS: 7 equine cadaver heads and 6 clinically normal adult horses. PROCEDURE: Fluoroscopy, contrast radiography, and computed tomography were used on cadaver specimens to locate the temporomandibular joint, identify externally palpable landmarks for joint access, guide needle placement into the joint, and illustrate regional anatomy. The arthrocentesis technique was performed on 6 live healthy adult horses to determine efficacy and safety of this procedure. RESULTS: Externally palpable structures were identified as landmarks for temporomandibular arthrocentesis, including the lateral border of the condylar process of the mandible, the zygomatic process of the temporal bone, and the lateral pericapsular fat pad. Arthrocentesis was successful in all 6 joints in the live horses, and no complications developed. CONCLUSIONS AND CLINICAL RELEVANCE: The technique identified will improve the ability to examine and treat the temporomandibular joint in horses.