IntroductionTo examine the impact of the COVID-19 pandemic on mortality, we estimated excess all-cause mortality in 24 countries for 2020 and 2021, overall and stratified by sex and age.MethodsTotal, ...age-specific and sex-specific weekly all-cause mortality was collected for 2015–2021 and excess mortality for 2020 and 2021 was calculated by comparing weekly 2020 and 2021 age-standardised mortality rates against expected mortality, estimated based on historical data (2015–2019), accounting for seasonality, and long-term and short-term trends. Age-specific weekly excess mortality was similarly calculated using crude mortality rates. The association of country and pandemic-related variables with excess mortality was investigated using simple and multilevel regression models.ResultsExcess cumulative mortality for both 2020 and 2021 was found in Austria, Brazil, Belgium, Cyprus, England and Wales, Estonia, France, Georgia, Greece, Israel, Italy, Kazakhstan, Mauritius, Northern Ireland, Norway, Peru, Poland, Slovenia, Spain, Sweden, Ukraine, and the USA. Australia and Denmark experienced excess mortality only in 2021. Mauritius demonstrated a statistically significant decrease in all-cause mortality during both years. Weekly incidence of COVID-19 was significantly positively associated with excess mortality for both years, but the positive association was attenuated in 2021 as percentage of the population fully vaccinated increased. Stringency index of control measures was positively and negatively associated with excess mortality in 2020 and 2021, respectively.ConclusionThis study provides evidence of substantial excess mortality in most countries investigated during the first 2 years of the pandemic and suggests that COVID-19 incidence, stringency of control measures and vaccination rates interacted in determining the magnitude of excess mortality.
Objective. It has been suggested that the incidence of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is higher in northern than in southern ...Europe. Recent epidemiological studies showed the loss of the previously described geographical north-south gradient. The aim of this study was to investigate the incidence of UC and CD in Primorsko-goranska County, Croatia. Material and methods. In the period 1 January 2000 to 31 December 2004 (5 years) all new patients diagnosed with IBD were prospectively identified according to a standard protocol for case ascertainment and definition. A total of 178 residents (81 F, 97 M) were newly diagnosed as having IBD during the study period. Of these, 70 had UC and 100 CD. Eight patients had indeterminate IBD. The data on patients were collected using a data form completed by gastroenterologists. Results. Annual age-standardized incidence rates were 4.3/105 (95% CI 2.6-6.0) for UC and 7.0/105 (95% CI 3.4-10.6) for CD. The highest incidence rate was observed in the age group 35-44 years for UC and the 25-34 years age group for CD. The incidence of IBD was higher in the urban than in the rural population, with the exception of on the islands. Conclusions. The incidence of IBD was higher than previously observed in Croatia. Our results suggest that CD incidence rates in the northern coastal part of Croatia are currently comparable with those reported in northern Europe.
Although estimates of suboptimal adherence to oral corticosteroids in asthma range from 30% to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to ...be particularly high.
What is the prevalence of suboptimal adherence detected by self-reporting and direct measures? Is suboptimal adherence associated with disease activity?
Data were included from individuals with severe asthma taking part in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study and prescribed daily oral corticosteroids. Participants completed the Medication Adherence Report Scale, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid chromatography-mass spectrometry.
Data from 166 participants were included in this study: mean (SD) age, 54.2 (± 11.9) years; FEV1, 65.1% (± 20.5%) predicted; female, 58%; 37% completing the Medication Adherence Report Scale reported suboptimal adherence; and 43% with urinary corticosteroid data did not have detectable prednisolone or metabolites in their urine. Good adherence by both methods was detected in 49 of the 142 (35%) of participants in whom both methods were performed; adherence detection did not match between methods in 53%. Self-reported high adherers had better asthma control and quality of life, whereas directly measured high adherers had lower blood eosinophil levels.
Low adherence is a common problem in severe asthma, whether measured directly or self-reported. We report poor agreement between the two methods, suggesting some disassociation between self-assessment of medication adherence and regular oral corticosteroid use, which suggests that each approach may provide complementary information in clinical practice.
Abstract
Background
To understand the impact of the COVID-19 pandemic on mortality, this study investigates overall, sex- and age-specific excess all-cause mortality in 20 countries, during 2020.
...Methods
Total, sex- and age-specific weekly all-cause mortality for 2015–2020 was collected from national vital statistics databases. Excess mortality for 2020 was calculated by comparing weekly 2020 observed mortality against expected mortality, estimated from historical data (2015–2019) accounting for seasonality, long- and short-term trends. Crude and age-standardized rates were analysed for total and sex-specific mortality.
Results
Austria, Brazil, Cyprus, England and Wales, France, Georgia, Israel, Italy, Northern Ireland, Peru, Scotland, Slovenia, Sweden, and the USA displayed substantial excess age-standardized mortality of varying duration during 2020, while Australia, Denmark, Estonia, Mauritius, Norway, and Ukraine did not. In sex-specific analyses, excess mortality was higher in males than females, except for Slovenia (higher in females) and Cyprus (similar in both sexes). Lastly, for most countries substantial excess mortality was only detectable (Austria, Cyprus, Israel, and Slovenia) or was higher (Brazil, England and Wales, France, Georgia, Italy, Northern Ireland, Sweden, Peru and the USA) in the oldest age group investigated. Peru demonstrated substantial excess mortality even in the <45 age group.
Conclusions
This study highlights that excess all-cause mortality during 2020 is context dependent, with specific countries, sex- and age-groups being most affected. As the pandemic continues, tracking excess mortality is important to accurately estimate the true toll of COVID-19, while at the same time investigating the effects of changing contexts, different variants, testing, quarantine, and vaccination strategies.
Axillary clearance in early breast cancer aims to improve locoregional control and provide staging information but is associated with undesirable morbidity. We therefore investigated whether avoiding ...axillary surgery in older women would result in improved quality of life (QL) with similar disease-free survival (DFS) and overall survival (OS).
Between 1993 and 2002, women > or = 60 years old with clinically node-negative operable breast cancer in whom adjuvant tamoxifen was considered indicated regardless of pathologic nodal status were randomly assigned to primary surgery plus axillary clearance (Sx + Ax) followed by tamoxifen (Tam) versus Sx without Ax followed by Tam for 5 consecutive years. The primary end point was QL reported by the patient and by physician assessment.
A total of 473 patients (234 to Sx + Ax, 239 to Sx) were randomly assigned. The median age was 74 years; 80% had estrogen receptor-positive disease. In both the patients' subjective assessment of their QL and the physicians' perception of the patients' QL, the largest adverse QL effects of Ax were observed from baseline to the first postoperative assessment, but the differences tended to disappear in 6 to 12 months. At a median follow-up of 6.6 years, results for Sx + Ax and Sx yielded similar DFS (6-year DFS, 67% v 66%; hazard ratio HR Sx + Ax/Sx, 1.06; 95% CI, 0.79 to 1.42; P = .69) and OS (6-year OS, 75% v 73%; HR Sx + Ax/Sx, 1.05; 95% CI, 0.76 to 1.46; P = .77).
Avoiding axillary clearance for women > or = 60 years old who have clinically node-negative disease and receive Tam for endocrine-responsive disease yields similar efficacy with better early QL.
Because this recombinant is potentially very useful and commercially available, we wanted to evaluate its diagnostic utility and compare it with the nApi m 1 allergen in a routine clinical laboratory ...setting by analyzing a large group of patients with well-defined honeybee venom allergy before adopting its use in our clinical practices.
This is a European Commission (EC)-funded ongoing study known as the LAMS (Latin American Screening) study, where PAP smear/liquid-based cytology and screening colposcopy were compared with i) three ...optional screening tools visual inspection with acetic acid (VIA), or Lugol's iodine (VILI), cervicography and with ii) Hybrid Capture II from a) conventional samples and from b) self-samples, in women at different risk for cervical cancer in Brazil and Argentina.
During 2002-2003, a cohort of 12,107 women attending four clinics: Campinas (CA), Sao Paulo (SP), Porto Alegre (PA) and Buenos Aires (BA), were interviewed for risk factors, and examined using the 8 diagnostic arms. Colposcopy was performed for women positive in any test and for 5% of women with baseline PAP-negative and 20% of HCII-negatives. All high-grade lesions (CIN2/3) were treated, and low-grade CIN are prospectively followed-up.
Of the 12,107 women, the following baseline data are available: epidemiological data (n=11,996), conventional PAP smears (n=10,363), LBC, SurePATH (n=320), LBC, DNA-Citoliq (n=1,346), VIA (n=12.067), VILI (n=3,061), cervicography (n=279), screening colposcopy (n=3,437), HCII conventional (n=4,710), HCII self-sampling (n=246) and cervical biopsies (n=1,524). The four sub-cohorts differ significantly in all their baseline data on the implicated risk factors of cervical cancer, consonant with their origin from regions with different cancer incidence. Around 95% of all PAP smears were negative, with slight variations in the prevalence of LSIL and HSIL between the four centers. Significant differences were found in the detection rates of abnormal findings in VIA, VILI and colposcopy between the four centers (p=0.0001). The prevalence of HPV was practically identical (16.5-18.8%) in all four cohorts (p=0.486), with no differences in the relative viral loads. Biopsy results were different depending on whether the women underwent screening colposcopy (BA) or elective colposcopy (others).
Four cohorts with significantly different baseline data are available, and prospective follow-up of these women permits analysis of whether variations in cervical cancer incidence in these regions is due to i) different natural history of the precursor lesions, or ii) due to different levels of exposure to the known risk factors.
New approaches are needed to guide personalized treatment of asthma.
To test if urinary eicosanoid metabolites can direct asthma phenotyping.
Urinary metabolites of prostaglandins (PGs), cysteinyl ...leukotrienes (CysLTs), and isoprostanes were quantified in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes) study including 86 adults with mild-to-moderate asthma (MMA), 411 with severe asthma (SA), and 100 healthy control participants. Validation was performed internally in 302 participants with SA followed up after 12-18 months and externally in 95 adolescents with asthma.
Metabolite concentrations in healthy control participants were unrelated to age, body mass index, and sex, except for the PGE
pathway. Eicosanoid concentrations were generally greater in participants with MMA relative to healthy control participants, with further elevations in participants with SA. However, PGE
metabolite concentrations were either the same or lower in male nonsmokers with asthma than in healthy control participants. Metabolite concentrations were unchanged in those with asthma who adhered to oral corticosteroid treatment as documented by urinary prednisolone detection, whereas those with SA treated with omalizumab had lower concentrations of LTE
and the PGD
metabolite 2,3-dinor-11β-PGF
. High concentrations of LTE
and PGD
metabolites were associated with lower lung function and increased amounts of exhaled nitric oxide and eosinophil markers in blood, sputum, and urine in U-BIOPRED participants and in adolescents with asthma. These type 2 (T2) asthma associations were reproduced in the follow-up visit of the U-BIOPRED study and were found to be as sensitive to detect T2 inflammation as the established biomarkers.
Monitoring of urinary eicosanoids can identify T2 asthma and introduces a new noninvasive approach for molecular phenotyping of adult and adolescent asthma.Clinical trial registered with www.clinicaltrials.gov (NCT01976767).
Cancer presenting at the medial site of the breast may have a worse prognosis compared with tumors located in external quadrants. For medial tumors, axillary lymph node staging may not accurately ...reflect the metastatic potential of the disease.
Eight-thousand four-hundred twenty-two patients randomly assigned to International Breast Cancer Study Group clinical trials between 1978 and 1999 were classified as medial site (1,622; 19%) or lateral, central, and other sites (6,800; 81%). Median follow-up was 11 years.
A statistically significant difference was observed for patients with medial tumors versus those with nonmedial tumors in disease-free survival (DFS; 10-year DFS, 46% v 48%; HR, 1.10; 95% CI, 1.02 to 1.18; P = .01) and overall survival (10-year OS 59% v 61%; HR, 1.09; 1.01 to 1.19; P = .04). This difference increased after adjustment for other prognostic factors (HR, 1.22; 95% CI, 1.13 to 1.32 for DFS; and HR, 1.24; 95% CI, 1.14 to 1.35 for OS; both P = .0001). The risk of relapse for patients with medial presentation was largest for the node-negative cohort and for patients with tumors larger than 2 cm. In the subgroup of 2,931 patients with negative axillary lymph nodes, 10-year DFS was 61% v 67%, and OS was 73% v 80% for medial versus nonmedial sites, respectively (HR 1.33; 95% CI, 1.15 to 1.54; P = .0001 for DFS; and HR 1.40; 95% CI, 1.17 to 1.67; P = .0003 for OS).
Tumor site has a significant prognostic utility, especially for axillary lymph node-negative disease, that should be considered in therapeutic algorithms. New staging procedures such as biopsy of the sentinel internal mammary nodes or novel imaging methods should be further studied in patients with medial tumors.
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