Return to work of breast cancer survivors: a systematic review of intervention studies.

BACKGROUND: Breast cancer management has improved dramatically in the past three decades and as a result, a population of working age women is breast cancer survivor. Interventions for breast cancer survivors have shown improvements in quality of life and in physical and psychological states. In contrast, efforts aimed at stimulating re-employment and return-to-work interventions for breast cancer survivors have not kept pace. The objective of this review was to study the effects and characteristics of intervention studies on breast cancer survivors in which the outcome was return to work. METHODS: The Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2006), Medline, Ovid, EMBASE and PsychInfo were systematically searched for studies conducted between 1970 to February 2007. Intervention studies for female breast cancer survivors that were focused on return to work were included. RESULTS: Our search strategy identified 5219 studies. Four studies out of 100 potentially relevant abstracts were selected and included 46-317 employed women who had had mastectomy, adjuvant therapy and rehabilitation, with the outcome return to work. The intervention programs focused on improvement of physical, psychological and social recovery. Although a substantial percentage (between 75% to 85%) of patients included in these studies returned to work after rehabilitation, it is not clear whether this proportion would have been lower for patients without counseling or exercise, or any other interventions, as three out of four studies did not include a comparison group. CONCLUSION: The most important finding of this review is the lack of methodologically sound intervention studies on breast cancer survivors with the outcome return to work. Using evidence from qualitative and observational studies on cancer and the good results of intervention studies on return to work programs and vocational rehabilitation, return to work interventions for breast cancer survivors should be further developed and evaluated.

Altered hemodynamics in chick embryos after extraembryonic venous obstruction.

OBJECTIVE: To obtain insight into hemodynamics during abnormal cardiac development, a chick model was developed recently in which a spectrum of conotruncal anomalies, in combination with abnormal semilunar valves and/or pharyngeal arch artery malformations, was induced through extraembryonic venous obstruction (venous clip) at stage 17 (70-h incubation). METHODS: In chick embryos of stage 24 and stage 34 control (n = 8; n = 21) and with venous clip (n = 11; n = 18), we simultaneously measured dorsal flow velocities with a 20-MHz pulsed Doppler velocity meter and dorsal aortic (stage 24) and vitelline artery (stage 34) blood pressures with a servo-null system. After the hemodynamic recordings were collected, all 58 embryos were subjected to morphological examination. The hemodynamic data were correlated with the morphology. Statistical comparison was performed between control and experimental values. RESULTS: At stage 24, venous clip embryos showed impaired looping. Physiologically, only a decrease in peak acceleration was found in these embryos (p < 0.05). At stage 34, a spectrum of conotruncal malformations was seen, that consisted of a ventricular septal defect in combination with abnormal semilunar valves and/or pharyngeal arch malformations. A dextroposed aorta in combination with a ventricular septal defect was diagnosed as double-outlet right ventricle. Hemodynamically, peak systolic and mean velocities, peak systolic and mean blood flows and stroke volume were increased while the heart rate was reduced after placement of the venous clip (p < 0.05). In both stages, pressure readings showed no statistically significant differences between control and experimental embryos. CONCLUSION: Our findings suggest that the hemodynamic changes seen in venous clip embryos reflect the presence of a compensatory mechanism.

Diminished growth of atrioventricular cushion tissue in stage 24 retinoic acid-treated chicken embryos.

Stage 34 chicken hearts have shown a spectrum of looping disturbances, changed hemodynamics, and changed growth of both right ventricular myocardium and atrioventricular cushion tissue after retinoic acid treatment. To obtain more information about the onset of the malformations we studied stage 24, the stage between the previously studied stage 34 and the moment of treatment. Sixteen stage 24 chicken embryos were examined after treatment with 1 microg all-trans retinoic acid at stage 15 and compared with 6 sham operated embryos. Morphological examination was supported by graphic reconstructions. Absolute volumes of atrial, atrioventricular, and ventricular myocardia were measured by a point counting method. The absolute volumes of the endocardial cushions were measured as well. Fifteen (15/16) retinoic acid-treated hearts did not show marked malformations as far as could be detected with our current macroscopic and microscopic techniques. One (1/16) retinoic acid-treated heart showed an abnormal tubular C-shape with a less bended inner curvature and with an abnormal horizontally oriented atrioventricular canal. The dorsal cushion tissue of this atrioventricular canal was discontinuous with the dorsal mesocardium and covered the malpositioned myocardial border between the atrium and the atrioventricular canal. The volume measurements did show a difference between retinoic acid treatment and sham operations. The retinoic acid-treated hearts showed a significant volume decrease of the atrioventricular cushions. No significant differences were found in the volumes of the ventricular myocardium compared to the sham operated embryos. We hypothesize that, between stages 15 and 24, retinoic acid directly affects the myocardial wall and the cushion tissue formation. In the present material this has resulted in decreased atrioventricular cushion growth, in changed hemodynamics, and in a severe looping disturbance of one embryo. We further hypothesize that, between stages 24 and 34, the malformations with minor looping disturbances will become apparent. Thus, development beyond stage 24 would result in the spectrum of looping disturbances as has been found at stage 34. These latter morphological malformations would lead to increasing hemodynamic changes, resulting in changes in growth as a secondary effect.

Disturbed vagal nerve distribution in embryonic chick hearts after treatment with all-trans retinoic acid.

The distribution of the vagal nerve was studied in whole-mount specimens and serial sections of chick embryos after retinoic acid treatment. White Leghorn chick embryos were treated at stage 15 either with 1 microg all-trans retinoic acid (n=11), or with the solvent dimethylsulphoxide (sham-operated embryos, n=8). Eight embryos served as normal controls. At stage 34 all 27 embryos were examined with a dissecting microscope. In order to reveal the vagal patterning, the hearts were removed and whole-mount stained with the HNK-1 antibody. In three hearts of the retinoic acid-treated group a morphologic intracardiac anomaly -- a double outlet right ventricle -- was found. To explore in depth the vagal nerve distribution in the heart, a separate set of hearts of retinoic acid embryos (n=5), sham-operated (n=4) and control embryos (n=5), was devised solely for serial sectioning and staining with the HNK-1 antibody. All hearts of retinoic acid-treated embryos showed a disturbed vagal nerve distribution both over the surface of the heart and within the heart wall. The vagal patterning was not altered in the sham-operated embryos compared to controls. It is concluded that retinoic acid disturbs the development of vagal nerve patterning regardless of the concurrent presence of intracardiac malformations. The mechanism and functional implications remain to be investigated.

Hemodynamic changes in HH stage 34 chick embryos after treatment with all-trans-retinoic acid.

To obtain insight into the hemodynamics of abnormal cardiac development, a chick embryo model was recently developed in which a spectrum of double outlet right ventricle was induced with all-trans-retinoic acid. In Hamburger and Hamilton (HH) stage 34 white Leghorn chick embryos, we simultaneously measured dorsal aortic flow velocities with a 20 MHz pulsed Doppler velocity meter and vitelline artery blood pressures with a servonull system. These measurements were performed in embryos treated at HH stage 15 with 1 microgram of all-trans-retinoic acid (n = 47), or with the solvent DMSO (n = 15), and in control embryos (n = 21). After the wave form recordings were collected, all embryos were examined histologically. Embryos treated with all-trans-retinoic acid showed in 15 cases hearts with a rightward positioned aorta with an additional subaortic ventricular septal defect and 32 cases without septation abnormalities of the heart. The hemodynamic data were correlated with the morphology. Statistical comparison was performed between control and experimental values. There was no significant discrepancy in hemodynamics of sham-operated and control embryos. Heart rate, peak systolic and mean velocities, peak systolic and mean blood flows, and peak acceleration and stroke volume were reduced in embryos treated with all-trans-retinoic acid (p < 0.01). Furthermore, in the presence of a subaortic ventricular septal defect the diameter of the dorsal aorta was reduced. Pressure readings were not statistically significant. Our findings suggest that the hemodynamic changes are the result of a decrease in cardiac contraction force.

Spectrum of looping disturbances in stage 34 chicken hearts after retinoic acid treatment.

BACKGROUND: In a recently developed chick model the teratogen retinoic acid has appeared to induce a spectrum of double outlet right ventricle, which needs further detailed evaluation. It is known that retinoic acid is able to induce cardiac malformations. Although the exact mechanism is not known, an interaction with neural crest cell function is thought to exist. METHODS: After treatment with 1 microgram all-trans retinoic acid at Hamburger and Hamilton stage 15 and reincubation until stage 34 of development 41 chicken embryos were evaluated macroscopically and microscopically, supported by graphic reconstructions. These retinoic acid treated embryos were compared with a control group (n = 8). RESULTS: The retinoic acid treated embryos could be divided in three groups. Group 1 (23/41) had an intact septum, group 2 (11/41) had an isolated ventricular septal defect (VSD), and group 3 (7/41) had a double outlet right ventricle (DORV). Besides, in the group with an intact septum 11 hearts showed an abnormal course of the subaortic outflow tract. In the group with DORV a straddling tricuspid orifice (7/8) and a double inlet left ventricle (1/8) could be distinguished. Considering the external contour, the hearts in the DORV group all showed a dextroposed arterial pole. Malformed pharyngeal arch arteries were found in all three groups (11/41) and with a great diversity. CONCLUSIONS: The present cardiac malformations in the chicken as a result of retinoic acid treatment are part of a continuous spectrum, varying from hearts with an intact ventricular septum and a normal course of the subaortic outflow tract to a double outlet right ventricle with a straddling tricuspid orifice or even a double inlet left ventricle. A remarkable observation in this spectrum concerns the correlation of malformations of the inflow and outflow tracts, which is explained as a cardiac looping disturbance. The disturbance of the looping process seems to lead to malalignment of septal components, although, in the chick, retinoic acid does not in general interfere with the formation of these septal components themselves.

Hemodynamic parameters of stage 20 to stage 35 chick embryo.

Hemodynamic parameters of the chick embryo from stage 20 (3 d of a 21-d incubation) up to stage 35 (8 d) are described. Normal values of dorsal aortic flow velocity wave forms were measured with a 20-MHz directional-pulsed Doppler velocity meter that was validated to be accurate above 5 mm/s. An analysis of variance was carried out for each of the flow velocity parameters. The correlation coefficient that represents the reproducibility was satisfactory (r > 0.90). There was a 17-fold rise in mean dorsal aortic blood flow (mm3/s). Heart rate doubled from 123 +/- 12 to 239 +/- 8 bpm, and stroke volume increased from 0.14 +/- 0.08 to 1.28 +/- 0.55 mm3. A stage-related rise was seen in peak systolic and mean velocities and peak acceleration. These data may serve as a basis for flow velocity wave form investigation and interpretation in developmental stages of cardiac malformations.