Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study.

BACKGROUND: In the DESTINY-Breast03 clinical trial, trastuzumab deruxtecan (T-DXd) showed superior progression-free survival and overall survival versus trastuzumab emtansine (T-DM1) and manageable safety in patients with human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer. Here, patient-reported outcomes (PROs) are reported along with hospitalization data. PATIENTS AND METHODS: Patients in DESTINY-Breast03 were assessed for prespecified PRO measures, including European Organization for Research and Treatment of Cancer quality of life (EORTC-QoL) questionnaires [the oncology-specific EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) and breast cancer-specific EORTC QLQ-BR45] and the generic EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L) visual analogue scale. Analyses included change from baseline, time to definitive deterioration (TDD), and hospitalization-related endpoints. RESULTS: EORTC QLQ-C30 baseline global health status (GHS) scores for T-DXd (n = 253) and T-DM1 (n = 260) were similar, with no clinically meaningful change (<10-point change from baseline) while on either treatment (median treatment duration: T-DXd, 14.3 months; T-DM1, 6.9 months). TDD analyses of QLQ-C30 GHS (primary PRO variable) and all other prespecified PROs (QLQ-C30 subscales, the QLQ-BR45 arm symptoms scale, and the EQ-5D-5L visual analogue scale) suggested T-DXd was numerically favored over T-DM1 based on TDD hazard ratios. Of all randomized patients, 18 (6.9%) receiving T-DXd versus 19 (7.2%) receiving T-DM1 were hospitalized, and the median time to first hospitalization was 219.5 versus 60.0 days, respectively. CONCLUSIONS: In DESTINY-Breast03, EORTC GHS/QoL was maintained on both therapies throughout treatment, indicating that despite the longer treatment duration with T-DXd versus T-DM1, health-related QoL did not worsen on T-DXd. Furthermore, TDD hazard ratios numerically favored T-DXd over T-DM1 in all prespecified variables of interest including pain, suggesting T-DXd may delay time until health-related QoL deterioration compared with T-DM1. Median time to first hospitalization was three times longer with T-DXd versus T-DM1. Together with reported improved efficacy and manageable toxicity, these results support the overall benefit of T-DXd for patients with HER2+ metastatic breast cancer.

A cross-sectional, multicentre, epidemiological study on human papillomavirus (HPV) type distribution in adult women diagnosed with invasive cervical cancer in Belgium.

OBJECTIVE: Despite an advanced national cervical cancer screening and vaccination programme cervical cancer is still the third most frequent diagnosed gynaecological tumour in Belgium. The goal of this study is to present the Belgian data of a cross-sectional, multicentre, epidemiological study on human papillomavirus (HPV) type distribution in adult women diagnosed with invasive cervical cancer (ICC) conducted in 12 European countries. MATERIAL AND METHODS: Centres in four major Belgian cities (Antwerp, Brussels, Ghent and Liège) participated in this study. Tissue samples from women with ICC were collected from the period 2001 - 2008. All slides were centrally reviewed and analysed for HPV. The total enrolled cohort included 278 subjects. RESULTS: The histologically eligible cohort comprised of 255 patients (mean age 51.3 ± 15.1 years) and 237 were confirmed HPV positive (mean age 50.6 ± 14.9 years). A single HPV infection was present in 95.8%. The five most frequent HPV types were HPV 16 (68.7%), HPV18 (12.3%), HPV 31 (6.2%), HPV 33 (5.3%) and HPV 45 (1.8%). Multiple HPV types were present in 3.4%, with two HPV types in 2.5% and three HPV types in 0.8%. In the various HPV type combinations observed in multiple infected women, HPV 31 (62.5%) and HPV 33 (50.0%) were the most frequent. The ratio of adenocarcinoma (ADC) versus squamous cell carcinoma (SCC) cases in the histologically eligible cohort was 1:8. Compared to the pooled European data the Belgium HPV 16 is 1.1, HPV 33 is 1.2 and HPV 31 is 1.7 higher and the HPV 18 is 0.8 and HPV 45 is 0.34 lower. CONCLUSION: The 5 most frequent HPV types in Belgium are the same as in the rest of Europe, but the distribution is different. Cervical cancer screening should therefore be HPV type specific and HPV prophylactic vaccination should also focus on other types then HPV 16 and HPV 18. A national registry is needed in order to follow the trends of HPV types in the society and to measure the impact of prevention, for which the data presented in this study can be an important basis.

Incidence and clinical presentation of acute otitis media in children aged <6 years in European medical practices.

We conducted an epidemiological, observational cohort study to determine the incidence and complications of acute otitis media (AOM) in children aged <6 years. Data on physician-diagnosed AOM were collected from retrospective review of medical charts for the year preceding enrolment and then prospectively in the year following enrolment. The study included 5776 children in Germany, Italy, Spain, Sweden, and the UK. AOM incidence was 256/1000 person-years [95% confidence interval (CI) 243-270] in the prospective study period. Incidence was lowest in Italy (195, 95% CI 171-222) and highest in Spain (328, 95% CI 296-363). Complications were documented in <1% of episodes. Spontaneous tympanic membrane perforation was documented in 7% of episodes. Both retrospective and prospective study results were similar and show the high incidence during childhood in these five European countries. Differences by country may reflect true differences and differences in social structure and diagnostic procedures.

Associations of long- and short-term air pollution exposure with markers of inflammation and coagulation in a population sample.

BACKGROUND: Exposure to elevated levels of ambient air pollutants can lead to adverse cardiovascular effects. Potential mechanisms include systemic inflammation and perturbation of the coagulation balance. OBJECTIVES: To investigate long- and short-term effects of air pollution exposure on serum levels of inflammatory (IL-6, TNF-alpha and CRP) and coagulation (fibrinogen and PAI-1) markers relevant for cardiovascular pathology. METHODS: The study group consisted of a population sample of 1028 men and 508 women aged 45-70 years from Stockholm. Long-term air pollution exposure was assessed using spatial modelling of traffic-related NO(2) and heating-related SO(2) emissions at each subject's residential addresses over retrospective periods of 1, 5 and 30 years. Short-term exposure was assessed as averages of rooftop measurements over 12-120 h before blood sampling. RESULTS: Long-term exposures to both traffic-NO(2) and heating-SO(2) emissions showed consistent associations with IL-6 levels. 30-year average traffic-NO(2) exposure was associated with a 64.5% (95% CI 6.7% to 153.8%) increase in serum IL-6 per 28.8 microg/m(3) (corresponding to the difference between the 5th and 95th percentile exposure value), and 30-year exposure to heating-SO(2) with a 67.6% (95% CI 7.1% to 162.2%) increase per 39.4 microg/m(3) (5th-95th percentile value difference). The association appeared stronger in non-smokers, physically active people and hypertensive subjects. We observed positive non-significant associations of inflammatory markers with NO(2) and PM(10) during 24 h before blood sampling. Short-term exposure to O(3) was associated with increased, and SO(2) with decreased, fibrinogen levels. CONCLUSIONS: Our results suggest that exposure to moderate levels of air pollution may influence serum levels of inflammatory markers.

Traffic-related air pollution in relation to respiratory symptoms, allergic sensitisation and lung function in schoolchildren.

BACKGROUND: Urban air pollution can trigger asthma exacerbations, but the effects of long-term exposure to traffic-related air pollution on lung function or onset of airway disease and allergic sensitisation in children is less clear. METHODS: All 2107 children aged 9-14 years from 40 schools in Rome in 2000-1 were included in a cross-sectional survey. Respiratory symptoms were assessed on 1760 children by parental questionnaires (response rate 83.5%). Allergic sensitisation was measured by skin prick tests and lung function was measured by spirometry on 1359 children (77.2%). Three indicators of traffic-related air pollution exposure were assessed: self-reported heavy traffic outside the child's home; the measured distance between the child's home and busy roads; and the residential nitrogen dioxide (NO2) levels estimated by a land use regression model (R2 = 0.69). RESULTS: There was a strong association between estimated NO2 exposure per 10 microg/m3 and lung function, especially expiratory flows, in linear regression models adjusted for age, gender, height and weight: -0.62% (95% CI -1.05 to -0.19) for forced expiratory volume in 1 s as a percentage of forced vital capacity, -62 ml/s (95% CI -102 to -21) for forced expiratory flow between 25% and 75% of forced vital capacity and -85 ml/s (95% CI -135 to -35) for peak expiratory flow. The other two exposure indicators showed similar but weaker associations. The associations appeared stronger in girls, older children, in children of high socioeconomic status and in those exposed to parental smoking. Although lifetime asthma was not an effect modifier, there was a suggestion of a larger effect on lung function in subjects with a positive prick test. Multiple logistic regression models did not suggest a consistent association between traffic-related air pollution exposure and prevalence of respiratory symptoms or allergic sensitisation. CONCLUSION: The results of this study suggest that residential traffic-related air pollution exposure is associated with reduced expiratory flows in schoolchildren.

Increased prevalence of hypertension in a population exposed to aircraft noise.

OBJECTIVES: To investigate whether there is a relation between residential exposure to aircraft noise and hypertension. METHODS: The study population comprised two random samples of subjects aged 19-80 years, one including 266 residents in the vicinity of Stockholm Arlanda airport, and another comprising 2693 inhabitants in other parts of Stockholm county. The subjects were classified according to the time weighted equal energy and maximum aircraft noise levels at their residence. A questionnaire provided information on individual characteristics including history of hypertension. RESULTS: The prevalence odds ratio for hypertension adjusted for age, sex, smoking, and education was 1.6 (95% confidence interval (95% CI) 1.0 to 2.5) among those with energy averaged aircraft noise levels exceeding 55 dBA, and 1.8 (95% CI 1.1 to 2.8) among those with maximum aircraft noise levels exceeding 72 dBA. An exposure-response relation was suggested for both exposure measures. The exposure to aircraft noise seemed particularly important for older subjects and for those not reporting impaired hearing ability. CONCLUSIONS: Community exposure to aircraft noise may be associated with hypertension.

Environmental tobacco smoke and myocardial infarction among never-smokers in the Stockholm Heart Epidemiology Program (SHEEP).

An increased risk for myocardial infarction (MI) related to environmental tobacco smoke (ETS) exposure has previously been reported, but several aspects of the association are still uncertain. We studied the MI risk associated with ETS exposure among 334 nonfatal never-smoking MI cases and 677 population controls, 45-70 years of age, in Stockholm County. A postal questionnaire with a telephone follow-up provided information on ETS exposure and other potential risk factors for MI. After adjustment for age, gender, hospital catchment area, body mass index, socioeconomic status, job strain, hypertension, diet, and diabetes mellitus, the odds ratio for MI was 1.58 (95% confidence interval = 0.97-2.56) for an average daily exposure of 20 cigarettes or more from the spouse. Combined exposure from spouse and work showed an increasing odds ratio for MI, up to 1.55 (95% confidence interval = 1.02-2.34) in the highest category of weighted duration, that is, more than 90 "hour-years" of exposure (1 "hour-year" = 365 hours, or 1 hour per day for 1 year). In addition, more recent exposure appeared to convey a higher risk. Our data confirm an increased risk of MI from exposure to ETS and suggest that intensity of spousal exposure, combined exposure from spouse and work, and time since last exposure are important.

Health effects resulting from nitrogen dioxide exposure in an indoor ice arena.

We investigated an outbreak of acute respiratory illness among adolescent ice-hockey players in an indoor ice arena in Stockholm that had a propane-powered ice-resurfacing machine. We administered questionnaires to all players, as well as to a reference group that had played ice hockey in indoor arenas with electric ice-resurfacing machines. In the exposed group, 55 subjects (55.6%) experienced acute respiratory symptoms, compared with 4 (7.1%) in the reference group (relative risk = 7.8; 95% confidence interval = 3.0, 20.3). The risk for pulmonary symptoms increased as time spent on the ice increased. Levels of nitrogen dioxide up to 2358 microg/m3 (1250 ppb) were detected during simulated conditions of the incident. The most likely cause of the outbreak was the high level of nitrogen dioxide that resulted from poor ventilation and a malfunctioning ice-resurfacing machine. Propane-fueled ice-resurfacing machines should not be used in indoor ice arenas.

Eosinophilic gastroenteritis in the pediatric patient.

Eosinophilic gastroenteritis is a diagnosis to be entertained whenever a patient had abdominal complaints accompanied by striking peripheral eosinophilia. A definitive diagnosis is of greater importance in this illness, since undiagnosed cases often undergo needless exploratory surgery. An infant seen at 2 years, 10 months of age with abdominal pain, nausea, and vomiting was found to have a white blood cell count of 50,000/cu mm with 54% eosinophils and eosinophilic ascites. An antral tissue biopsy yielded a diagnosis of eosinophilic gastroenteritis after many studies had been made to exclude other diagnoses. Treatment with intermittent courses of prednisone kept the patient relatively asymptomatic over the period of 20 years during which she remained under our care. Immunologic studies shed no light on the etiology of this patient's disorder. The literature dealing with diffuse, infiltrative eosinophilic gastroenteritis is reviewed.

Dietary essential fatty acids in cystic fibrosis.

Analyses of serum lipids of children with cystic fibrosis (CF) have indicated a deficiency in essential fatty acids (EFA). In view of a report that intravenous administration of soybean oil emulsions normalized sweat sodium values in CF children, we studied the effects of orally administered essential fatty acids (as corn oil) for one year. Some improvement was noted in all patients, but no one consistent factor predominated. However, arachidonic acid, which was found only in trace amounts or was absent in sera of all children with CF before the clinical trial, was increased significantly in the sera after the oral administration of EFA for one year. Other findings included a significant decrease in sweat sodium and T3 in most patients.

Cystic fibrosis and hypertrophic osteoarthropathy in children. Report of three cases.

Three patients with cystic fibrosis were noted to have swelling of knee and ankle joints during exacerbation of their lung disease. Synovial fluid was analyzed in one patient and the synovium underwent biopsy in another. These studies excluded other causes of arthritis but did not contribute any new information on the nature of secondary hypertrophic osteoarthropathy. Radiological examination of long bones confirmed the diagnosis of hypertrophic osteoarthropathy in all three patients. Since many patients with cystic fibrosis survive longer, more instances of hypertrophic osteoarthropathy are expected in the future.