A population-based study on trajectories of HER2 status during neoadjuvant chemotherapy for early breast cancer and metastatic progression.

BACKGROUND: This study aimed to investigate the distribution and changes of HER2 status in untreated tumours, in residual disease and in metastasis, and their long-term prognostic implications. METHODS: This is a population-based cohort study of patients treated with neoadjuvant chemotherapy for breast cancer during 2007-2020 in the Stockholm-Gotland region which comprises 25% of the entire Swedish population. Information was extracted from the National Breast Cancer Registry and electronic patient charts to minimize data missingness and misclassification. RESULTS: In total, 2494 patients received neoadjuvant chemotherapy, of which 2309 had available pretreatment HER2 status. Discordance rates were 29.9% between primary and residual disease (kappa = 0.534), 31.2% between primary tumour and metastasis (kappa = 0.512) and 33.3% between residual disease to metastasis (kappa = 0.483). Adjusted survival curves differed between primary HER2 0 and HER2-low disease (p < 0.001), with the former exhibiting an early peak in risk for death which eventually declined below the risk of HER2-low. Across all disease settings, increasing the number of biopsies increased the likelihood of detecting HER2-low status. CONCLUSION: HER2 status changes during neoadjuvant chemotherapy and metastatic progression, and the long-term behaviours of HER2 0 and HER2-low disease differ, underscoring the need for obtaining tissue biopsies and for extended follow-up in breast cancer studies.

Flourish, fight or flight: health in self-employment over time-associations with individual and business resources.

PURPOSE: Using COR theory to study developments of health and other key resources in self-employed workers in Sweden over 6 years, this study: (1) explored whether the heterogenous group of self-employed workers contained subgroups with different health trajectories, (2) investigated whether these were more typical for certain individuals (with respect to age, gender, sector, education, employment status), and (3) compared the different health trajectories regarding resource development in mental well-being, business resources, employment status, work ability. METHOD: The study used data from the Swedish longitudinal occupational survey of health (SLOSH) and included participants working as self-employed or combiner (N = 2642). RESULT: Five trajectories were identified with latent class growth curve model analysis (LCGM). Two health trajectories with (1) very good, respective (2) good stable health (together comprising 78.5% of the participants), (3) one with moderate stable health (14.8%), (4) one with a U-shaped form (1.9%), and (5) one with low, slightly increasing health (4.7%). The first two trajectories flourish: they maintained or increased in all key resources and were more likely to remain self-employed. Trajectories three and five consist of those who fight to maintain or increase their resources. Workers in the U-shaped health trajectory show signs of fight and flight after loss in health and other key resources. CONCLUSIONS: Studying subgroups with different resource developments over time was suitable to understand heterogeneity in self-employed workers. It also helped to identify vulnerable groups that may benefit from interventions to preserve their resources.

Trends in Uveal Melanoma Presentation and Survival During Five Decades: A Nationwide Survey of 3898 Swedish Patients.

Background: In contrast to most other cancers, uveal melanoma (UM) is characterized by an absence of major improvements in patient survival during the last several decades. In this study, we examine changes in incidence rates, patient age and tumor size at diagnosis, treatment practices and survival for patients diagnosed in Sweden during the period 1960-2010. Methods: All patients diagnosed with posterior UM between January 1st, 1960, and December 31st, 2009, in Sweden, were included (n = 3898). Trends in incidence, primary treatment modality, patient age and tumor size were analyzed. Disease-specific survival was plotted in Kaplan-Meier curves and the cumulative incidence of UM-related mortality was evaluated in competing risk analysis. Results: Crude (6.5-11.6 cases/million/year) and age-standardized incidence rates (5.6-9.6 cases/million/year) varied between individual years during the study period, but both had a stable linear trend overall (p ≥ 0.12). Gradually, plaque brachytherapy with ruthenium-106 replaced enucleation as the most common primary treatment. The mean patient age at diagnosis increased from 59.8 years in 1960 to 66.0 in 2009. Conversely, the mean tumor size became gradually smaller during the period. In linear regression, the basal diameter and tumor apical thickness decreased with a slope coefficient of -0.03 mm (p = 0.012) and -0.05 mm (p = 1.2 × 10-5) per year after 1960, respectively. Patients diagnosed after 1990 had significantly better disease-specific survival than patients diagnosed before 1990 (p = 2.0 × 10-17). Similarly, the cumulative incidence of UM-related mortality was highest for patients diagnosed 1960-1969 and 1970-1979, with slightly lower incidences for patients diagnosed 1980-1989 and even lower for those diagnosed after 1990 (p = 7.1 × 10-13). The incidence of mortality from other causes than UM did not differ between periods (p = 0.16). Conclusion: In the period from 1960-2010, crude and age-standardized incidence rates of UM have remained stable in Sweden. Several other aspects have changed: Plaque brachytherapy with ruthenium-106 has replaced enucleation as the most common primary treatment modality; patients have become older and their tumors smaller at the time of diagnosis; and their survival has improved. This might indicate a beneficial survival effect of earlier diagnosis and treatment, but the potential influence from lead-time bias should be taken into consideration.

Body image and compulsive exercise: are there associations with depression among university students?

PURPOSE: Mental health problems among university students have been reported to be significantly increasing and suggested to be associated with college drop-out. Body dissatisfaction and compulsive exercise are both constructs relevant for mental health problems in general and eating disorders in particular. This study examined associations between body dissatisfaction, compulsive exercise and self-reported symptoms of depression among Swedish university students. METHODS: Participants (n = 4262) are students in an ongoing cohort study, and data from the baseline assessment were used. Four linear regression models were built to explore the associations between body dissatisfaction, compulsive weight control exercise and depressive symptoms. RESULTS: Our findings showed that females reported higher levels of body dissatisfaction than males. Body dissatisfaction and compulsive exercise were associated with self-reported symptoms of depression in this non-clinical population. Results showed that compulsive exercise was negatively associated with reported symptoms of depression, while body dissatisfaction was positively associated with symptoms of depression. CONCLUSION: In line with previous research, there was a gender difference in body dissatisfaction where females displayed higher levels of dissatisfaction than males.  Body dissatisfaction was  positively associated with reported symptoms of depression, suggesting support of previous research indicating body dissatisfaction to increase mental health problems. Compulsive exercise was negatively associated with symptoms of depression suggesting a behavior negatively reinforced, supporting both constructs to be of interest for reported symptoms of depression in a non-clinical population of Swedish university students. LEVEL OF EVIDENCE: III, cohort study. TRIAL REGISTRATION: http://clinicaltrials.gov/ID : NCT04465435.

Comparing Depressive Symptoms, Emotional Exhaustion, and Sleep Disturbances in Self-Employed and Employed Workers: Application of Approximate Bayesian Measurement Invariance.

Studies investigating differences in mental health problems between self-employed and employed workers have provided contradictory results. Many of the studies utilized scales validated for employed workers, without collecting validity evidence for making comparisons with self-employed. The aim of this study was (1) to collect validity evidence for three different scales assessing depressive symptoms, emotional exhaustion, and sleep disturbances for employed workers, and combinators; and (2) to test if these groups differed. We first conducted approximate measurement invariance analysis and found that all scales were invariant at the scalar level. Self-employed workers had least mental health problems and employed workers had most, but differences were small. Though we found the scales invariant, we do not find them optimal for comparison of means. To be more precise in describing differences between groups, we recommend using clinical cut-offs or scales developed with the specific purpose of assessing mental health problems at work.

Ruthenium-106 versus iodine-125 plaque brachytherapy of 571 choroidal melanomas with a thickness of ≥5.5 mm.

BACKGROUND: Episcleral brachytherapy is the most common eye-preserving treatment for medium-sized choroidal melanomas. γ-emitting iodine-125 (125I) and ß-emitting ruthenium-106 (106Ru) are widely used. The latter is however generally reserved for thinner tumours (<6 mm). In this study, we compare ocular and patient survival in thicker tumours treated with the respective radioisotope. METHODS: All patients with ≥5.5 mm thick choroidal melanomas who were treated with plaque brachytherapy at a single institution between 1 November 1979 and 31 December 2015 were included (n=571). Size-controlled Cox regression HRs for postbrachytherapy enucleation, repeated brachytherapy and melanoma-related mortality were calculated, as well as Kaplan-Meier disease-specific survival and relative 10-year survival in matched subgroups. RESULTS: 317 patients were treated with 106Ru and 254 with 125I. The rate of repeated brachytherapy was significantly higher among patients treated with 106Ru (8%) than with 125I (1%, p<0.001). Size-controlled Cox regression HRs for postbrachytherapy enucleation (125I vs 106Ru 0.7, p=0.083) and melanoma-related mortality were not significant (125I vs 106Ru 1.1, p=0.63). Similarly, Kaplan-Meier disease-specific and relative 10-year survival was comparable in matched groups of 5.5-7.4 mm (relative survival 106Ru 59%, 125I 56%) and ≥7.5 mm thick tumours (relative survival 106Ru 46%, 125I 44%). CONCLUSIONS: Rates of repeated brachytherapy were significantly higher among patients treated with 106Ru versus 125I for thick choroidal melanomas. There were, however, no significant differences in rates of enucleation or patient survival.

Anatomic alterations in aging and age-related diseases of the eye.

PURPOSE: We described anatomic age-related changes in the human eye to determine potential areas of investigation that may lead to identifying eyes at risk for age-related disease. METHODS: A descriptive review of anatomic changes in the eye related to aging was performed in the context of current areas of investigation. The review was performed specifically for differing anatomic ocular structures, including cornea, trabecular meshwork, lens, uveal tract, Bruch's membrane, retina, RPE, vitreous, sclera, and optic nerve. RESULTS: Age-related changes occur in all ocular tissues. The cornea flattens and there is an attrition of endothelial cells. The shape of the trabecular meshwork changes and there is a loss of trabecular endothelium. The lens grows and becomes cataractous. The ciliary body becomes collagenized, there are choroidal vascular changes, and Bruch's membrane thickens. Retinal vessels become hyalinized and there is a loss of rods before cones in the macula. RPE morphometric changes occur with aging. The vitreous becomes liquefied and there is a loss of vitreous compartmentalization. The sclera becomes rigid and may become calcified. The optic nerve exhibits structural changes with age. CONCLUSIONS: There are numerous anatomic age-related changes in the human eye. Current areas of investigation related to these changes include adaptive optics scanning laser ophthalmoscopy imaging of the RPE mosaic in the context of aging, and drug delivery devices that overcome age-related alterations to retinal and macular perfusion.

Preoperative sub-Tenon's capsule injection of ropivacaine in conjunction with general anesthesia in retinal detachment surgery.

OBJECTIVE: To evaluate the effects of preoperative sub-Tenon's capsule injection of ropivacaine on intraoperative hemodynamics, postoperative pain, nausea, and recovery in patients undergoing scleral buckling surgery under general anesthesia (GA). DESIGN: Randomized double-masked controlled clinical trial. PARTICIPANTS: Ninety-eight patients with primary rhegmatogenous retinal detachment undergoing scleral buckling surgery under GA. METHODS: Random allocation to either preoperative sub-Tenon's capsule injection of 3 ml of 0.75% ropivacaine or sub-Tenon's capsule injection of 3 ml of saline (controls) immediately before a scleral buckling procedure under GA. Intraoperative monitoring of hemodynamic parameters, need of analgesia with sevoflurane and alfentanil, time in the recovery unit, measurements of pain and nausea on the visual analog scale (VAS) up to 12 hours postoperatively, and consumption of analgesics and antiemetics was recorded. MAIN OUTCOME MEASURES: Intraoperative systolic blood pressure (BP); bradycardia; minimum alveolar concentration (MAC) of sevoflurane; maximum postoperative VAS scores of pain and nausea; time in recovery unit; and total need of alfentanil, ketobemidone, dextropropoxyphene, and dixyrazine. RESULTS: Ninety-seven patients were analyzed (48 in the ropivacaine group and 49 controls). A significantly lower intraoperative systolic BP (104+/-6 vs. 112+/-7 mmHg; P = 0.004), less need of sevoflurane (1.33+/-0.19 vs. 1.56+/-0.23; P = 0.03), and shorter time in the recovery unit (67+/-9 vs. 76+/-16 minutes; P = 0.01) were observed in the ropivacaine group. Maximum VAS pain scores were 50+/-21 in the control group and 36+/-25 in the ropivacaine group (P = 0.05), with a significantly lower consumption of opioids (ketobemidone) in the ropivacaine group (3.6+/-3.5 vs. 1.3+/-2.0 mg). No significant difference was observed regarding nausea or need of dixyrazine or dextropropoxyphene postoperatively. CONCLUSIONS: Preoperative sub-Tenon's capsule injection of ropivacaine in scleral buckling surgery under GA lowers the intraoperative systolic BP, reduces the amount of inhalable sevoflurane needed, and enhances postoperative vigilance through reduction of pain and need of opioids.

Uveal melanoma: a study on incidence of additional cancers in the Swedish population.

PURPOSE: To investigate the occurrence of other primary malignancies before and after diagnosis of uveal melanoma in a Swedish population. METHODS: In the Swedish Cancer Registry 2995 patients with uveal melanoma were notified during the period 1960 to 1998. In the same registry, a search for additional malignancies among these patients was performed. A matched case-control study with 2,916 patients and 14,577 population control subjects was set up for malignancies before diagnosis of uveal melanoma. Malignancies after diagnosis of uveal melanoma were evaluated in 2,995 patients through standardized incidence ratios (SIRs), based on the expected rates in the Swedish population. RESULTS: Before the diagnosis of uveal melanoma, the odds ratio (OR) for the risk of cancer was 1.25 (95% CI: 0.98-1.59). No significantly increased risk was found for any specific malignancy. The OR for cutaneous melanoma was 1.74 (95% CI: 0.78-3.89). The risk of subsequent cancers was increased, SIR 1.13 (95% CI: 1.02-1.26). After reevaluation of archival specimens, the SIR of a cutaneous melanoma's developing after a uveal melanoma was found to be 1.75 (95% CI: 0.87-3.12). CONCLUSIONS: An increased risk of second primary cancers was observed among Swedish patients with uveal melanoma. Metastases from uveal melanoma were found to be misclassified as cutaneous melanoma or as primary liver cancer.

Ruthenium brachytherapy for uveal melanoma, 1979-2003: survival and functional outcomes in the Swedish population.

PURPOSE: To evaluate observed and relative survival rates, enucleation rates, and visual outcome after ruthenium 106 brachytherapy for uveal melanoma. DESIGN: Retrospective cases series from the Swedish national referral center. PARTICIPANTS: Five hundred seventy-nine patients (579 eyes) with choroidal or ciliary body melanomas, including 55 tumors more than 7 mm in height, treated with ruthenium episcleral plaques from January, 1979, through April, 2003. METHODS: Clinical and radiotherapy data were extracted from a dedicated database, and survival status was determined through population registries. Tumor size was classified according to the Collaborative Ocular Melanoma Study criteria. The 5- and 10-year relative survival rates were estimated, and univariate and multivariate regression models were constructed for predictive factors on observed survival, enucleation, and visual deterioration. MAIN OUTCOME MEASURES: Observed and relative survival rate, proportion of secondary enucleation, deterioration of visual acuity to less than 0.5, respectively, to 0.1 or worse. RESULTS: Tumors were classified as small in 10.5%, medium in 78.4%, and large in 9.2% of patients. The 5- and 10-year observed overall survival rates were 83.3% and 71.5%, respectively, and the corresponding relative rates were 95.5% and 94%, respectively. Factors predicting survival were tumor diameter, patient age, and secondary enucleation. One hundred six patients (18%) underwent enucleation up to 14 years after plaque treatment. The only predictive factor for enucleation was tumor size. At 5 years, 31% of the patients retained 0.5 visual acuity or better, and 49% retained better than 0.1 visual acuity. Predictive factors for visual deterioration were visual acuity and distance from posterior tumor border to the foveola. CONCLUSIONS: After ruthenium brachytherapy for uveal melanoma, the survival rates and visual outcomes in this population-based investigation were similar to previously published results. The eye was retained in 81.7% of patients. Careful patient selection (presently we only treat melanomas 7 mm or smaller in height) and life-long monitoring for recurrences is warranted.

Uveal melanoma: epidemiologic aspects.

Melanomas of the ocular and adnexal structures comprise approximately 5% of all melanomas. The majority (85%) of ocular melanomas are uveal in origin; primary conjunctival and orbital melanomas are rare. The diagnosis of uveal melanoma is made by clinical examination including indirect ophthalmoscopy and by ancillary studies such as fluorescein angiography and ultrasonography. Metastases to the liver develop within 15 years after the initial diagnosis and treatment in approximately 50% of patients with posterior uveal melanoma; however, clinically evident metastatic disease at the time of initial presentation is uncommon, indicating that there is early subclinical metastasis in most cases.

Uveal melanoma survival in Sweden from 1960 to 1998.

PURPOSE: To investigate the crude and relative survival rates in patients with uveal melanoma in Sweden during the period from 1960 to 1998. METHODS: A population-based national survey revealed 2997 cases of uveal melanoma in the Swedish Cancer Registry. The survival rates were calculated by the Hakulinen life-table method, using relative survival as an estimate for deaths due to uveal melanoma. The excess mortality rates were calculated with confidence intervals for the first 15 years after diagnosis. Multivariate regression analysis was undertaken to evaluate the influence of gender, age, and calendar period on relative survival the first 5 years after diagnosis. The underlying causes of deaths in the patients with uveal melanoma, as found in the Cause of Death Registry were also investigated. RESULTS: Up to December 31, 1998, 2003 patients had died. The 5-year crude survival rate was 60.3% and the relative survival 70.1%. After 10 years, the rates were 42.5% and 59.4%, respectively. Significant excess mortality existed up to 5.5 years after diagnosis. In the multivariate model, younger age (P < 0.001) and later calendar period (P = 0.002), but not gender (P = 0.117), were associated with better relative survival. Deaths due to uveal melanoma were misclassified in the Cause of Death Registry in more than half of the cases. CONCLUSIONS: This study, covering more than 95% of the uveal melanoma cases in the Swedish population revealed an improvement in relative survival rates for patients with uveal melanoma over time and a significant excess mortality up to 5.5 years after diagnosis.

Incidence of uveal melanoma in Sweden from 1960 to 1998.

PURPOSE: To investigate the incidence of uveal melanoma in Sweden during the period from 1960 to 1998, with respect to age distribution, gender, and changes in incidence over time. METHODS: The Swedish Cancer Registry was searched for patients with uveal melanoma and cross-checked against hospital files over patients where an eye-sparing treatment had been applied, to ensure inclusion in the Registry even when no histologic specimen was available. The crude and age-standardized incidence was estimated separately for each gender. The Swedish population of 1970 to 1974 was used as a standard, and the annual change in incidence was calculated by using a regression model with logarithmic incidence numbers. RESULTS: In total, 2997 patients met the criteria, of whom 1542 were males and 1455 females. During the 39-year period, the age-standardized incidence of uveal melanoma declined significantly in the male population, from 11.7 cases/million to 8.4 cases/million (P = 0.002). The trend toward reduced incidence in females, from 10.3 to 8.7 cases/million did not reach statistical significance (P = 0.108). The annual relative change in incidence was 1% (95% CI, 0.8%-1.2%) in males and 0.7% (95% CI, 0%-1.3%) in females. The age-specific incidence revealed a significantly higher incidence among men older than 45 years (23.5 cases/million) compared with the incidence in women of the same age group (19.2 cases/million; P < 0.001). CONCLUSIONS: A Swedish national survey performed to establish the incidence of uveal melanoma during the period from 1960 to 1998 revealed a decreasing incidence in the male and a stable incidence in the female population.