Time series analysis of the incidence of acute upper respiratory tract infections, COVID-19 and the use of antibiotics in Finland during the COVID-19 epidemic : a cohort study of 833 444 patients

Objective To evaluate the trajectories of acute upper respiratory tract infections (URTIs), COVID-19, and the use of antibiotics in Finland during the COVID-19 epidemic. Design Population-based cohort study. Setting Electronic medical records from a nationwide healthcare chain in Finland. Participants 833 444 patients from a cohort of 1 970 013 Finns who had used medical services between 2017 and 2020. Main outcome measures Number of weekly patients of acute URTIs, COVID-19, and the prescribed number of antibiotics in Finland between 6 January 2020 and 21 June 2020. We estimated the respective expected numbers from 1 March 2020 onward using autoregressive integrated moving average model from 1 January 2017 to 1 March 2020. We assessed the public interest in COVID-19 by collecting Google search trend frequencies. Results There was a rapid increase in COVID-related internet searches between weeks 10 and 12. At the same time, there was a 106% increase in diagnoses of acute URTIs, from 410 per 100 000 inhabitants to 845 per 100 000. The first COVID-19 cases were diagnosed on week 11. Prescriptions for URTI-related antibiotics declined by 71% (403 per 100 000 to 117 per 100 000) between weeks 11 and 15 while no relevant change took place in prescriptions of antibiotics for urinary tract infections. Conclusions At the beginning of the epidemic, many people contacted healthcare professionals with relatively mild symptoms, as indicated by the reduced rate of URTI-antibiotics prescriptions. Our findings indicate that health service providers should be prepared for rapid variations in service demand. Securing access of true COVID-19 patients to proper diagnostics, care and isolation measures may help in preventing the spread of the disease.Peer reviewe

First-in-human Phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours

Background Bromodomain and extra-terminal domain (BET) proteins are reported to be epigenetic anti-cancer drug targets. This first-in-human study evaluated the safety, pharmacokinetics and preliminary anti-tumour activity of the BET inhibitor ODM-207 in patients with selected solid tumours. Methods This was an open-label Phase 1 study comprised of a dose escalation part, and evaluation of the effect of food on pharmacokinetics. ODM-207 was administered orally once daily. The dose escalation part was initiated with a dose titration in the initial cohort, followed by a 3 + 3 design. Results Thirty-five patients were treated with ODM-207, of whom 12 (34%) had castrate-resistant prostate cancer. One dose-limiting toxicity of intolerable fatigue was observed. The highest studied dose achieved was 2 mg/kg due to cumulative toxicity observed beyond the dose-limiting toxicity (DLT) treatment window. Common AEs included thrombocytopenia, asthenia, nausea, anorexia, diarrhoea, fatigue, and vomiting. Platelet count decreased proportionally to exposure with rapid recovery upon treatment discontinuation. No partial or complete responses were observed. Conclusions ODM-207 shows increasing exposure in dose escalation and was safe at doses up to 2 mg/kg but had a narrow therapeutic window.Peer reviewe

Comparing modular and personal service delivery in specialised outpatient care : A survey of haematology and oncology patient preferences

Background Oncology and haematology are shifting from inpatient to outpatient care, requiring new care delivery models. This study compares preferences of oncology patients treated by named nurses in a traditional specialty-focused day hospital and haematology patients treated without named nurses in a modularised day hospital. Methods Questionnaires to explore patient preferences on number of treating nurses and named nurses, and satisfaction in day hospital care were distributed to 300 haematology and 410 oncology patients. Binomial logistic regressions were performed to study how background variables influenced preferences for having (i) a named nurse or (ii) maximum three treating nurses in the day hospital. Results In 2016, 156 (52%) haematology and 289 (70%) oncology surveys were completed and returned. Both groups were satisfied with day hospital care. Haematology patients preferred named nurses less often than oncology patients (odds ratio (OR) = 0.09, p <0.0005). Haematology patients were less likely to prefer a maximum of three treating nurses (OR = 0.12, p <0.0005). Conclusion This study suggests that patients can be satisfied with outpatient care with or without named nurses. However, as several factors affect patient satisfaction and experience, more in-depth research is needed to understand how modularisation and patient preferences may be linked.Peer reviewe

Kalliiden lääkkeiden käyttöönotosta suositus

Kalliit lääkkeet on otettava käyttöön yhdenmukaisella prosessilla. Ei ole tarkoituksenmukaista, että sairaanhoitopiirit kilpailisivat keskenään erilaisella lääkekirjolla, varsinkaan silloin kun on ¬kysymyksessä hyvin kallis hoito. Pelisäännöt on nyt tehty

Time series analysis of the incidence of acute upper respiratory tract infections, COVID-19 and the use of antibiotics in Finland during the COVID-19 epidemic: a cohort study of 833 444 patients

Objective: To evaluate the trajectories of acute upper respiratory tract infections (URTIs), COVID-19, and the use of antibiotics in Finland during the COVID-19 epidemic.Design: Population-based cohort study.Setting: Electronic medical records from a nationwide healthcare chain in Finland.Participants: 833 444 patients from a cohort of 1 970 013 Finns who had used medical services between 2017 and 2020.Main outcome measures: Number of weekly patients of acute URTIs, COVID-19, and the prescribed number of antibiotics in Finland between 6 January 2020 and 21 June 2020. We estimated the respective expected numbers from 1 March 2020 onward using autoregressive integrated moving average model from 1 January 2017 to 1 March 2020. We assessed the public interest in COVID-19 by collecting Google search trend frequencies.Results: There was a rapid increase in COVID-related internet searches between weeks 10 and 12. At the same time, there was a 106% increase in diagnoses of acute URTIs, from 410 per 100 000 inhabitants to 845 per 100 000. The first COVID-19 cases were diagnosed on week 11. Prescriptions for URTI-related antibiotics declined by 71% (403 per 100 000 to 117 per 100 000) between weeks 11 and 15 while no relevant change took place in prescriptions of antibiotics for urinary tract infections.Conclusions: At the beginning of the epidemic, many people contacted healthcare professionals with relatively mild symptoms, as indicated by the reduced rate of URTI-antibiotics prescriptions. Our findings indicate that health service providers should be prepared for rapid variations in service demand. Securing access of true COVID-19 patients to proper diagnostics, care and isolation measures may help in preventing the spread of the disease.</p

Association of Angiopoietin-2 and Ki-67 Expression with Vascular Density and Sunitinib Response in Metastatic Renal Cell Carcinoma

The Angiopoietin-2 (Ang2, Angpt2) growth factor is a context-dependent antagonist/agonist ligand of the endothelial Tie2 receptor tyrosine kinase and known to promote tumour angiogenesis and metastasis. Angiopoietin antagonists have been tested in clinical cancer trials in combination with VEGF-based anti-angiogenic therapy, including sunitinib, which is widely used as a first-line therapy for metastatic renal cell carcinoma (mRCC). However, little is known about Ang2 protein expression in human tumours and the correlation of tumour Ang2 expression with tumour vascularization, tumour cell proliferation and response to anti-angiogenic therapies. Here, we evaluated, using immunohistochemistry, the expression of Ang2, CD31 and the cell proliferation marker Ki-67 in the primary kidney cancer from 136 mRCC patients, who received first-line sunitinib after nephrectomy. Ang2 protein expression was restrained to RCC tumour vessels, and correlated with tumour vascularization and response to sunitinib. High pre-therapeutic Ang2 expression, and more strongly, combined high expression of both Ang2 and CD31, were associated with a high clinical benefit rate (CBR). Low cancer Ki-67 expression, but not Ang2 or CD31 expression, was associated with favourable progression-free (PFS) and overall survival (OS) as compared to patients with high Ki-67 expression (PFS 6.5 vs. 10.6 months, P = 0.009; OS, 15.7 vs. 28.5 months, P = 0.015). In summary, in this study to investigate endothelial Ang2 in mRCC patients treated with first-line sunitinib, high cancer Ang2 expression was associated with the CBR, but not PFS or OS, whereas low Ki-67 expression was significantly associated with long PFS and OS.Peer reviewe

Spatial immunoprofiling of the intratumoral and peritumoral tissue of renal cell carcinoma patients

While the abundance and phenotype of tumor-infiltrating lymphocytes are linked with clinical survival, their spatial coordination and its clinical significance remain unclear. Here, we investigated the immune profile of intratumoral and peritumoral tissue of clear cell renal cell carcinoma patients (n = 64). We trained a cell classifier to detect lymphocytes from hematoxylin and eosin stained tissue slides. Using unsupervised classification, patients were further classified into immune cold, hot and excluded topographies reflecting lymphocyte abundance and localization. The immune topography distribution was further validated with The Cancer Genome Atlas digital image dataset. We showed association between PBRM1 mutation and immune cold topography, STAG1 mutation and immune hot topography and BAP1 mutation and immune excluded topography. With quantitative multiplex immunohistochemistry we analyzed the expression of 23 lymphocyte markers in intratumoral and peritumoral tissue regions. To study spatial interactions, we developed an algorithm quantifying the proportion of adjacent immune cell pairs and their immunophenotypes. Immune excluded tumors were associated with superior overall survival (HR 0.19, p = 0.02) and less extensive metastasis. Intratumoral T cells were characterized with pronounced expression of immunological activation and exhaustion markers such as granzyme B, PD1, and LAG3. Immune cell interaction occurred most frequently in the intratumoral region and correlated with CD45RO expression. Moreover, high proportion of peritumoral CD45RO+ T cells predicted poor overall survival. In summary, intratumoral and peritumoral tissue regions represent distinct immunospatial profiles and are associated with clinicopathologic characteristics.Peer reviewe

Real-world Effectiveness and Safety of Pazopanib in Patients With Intermediate Prognostic Risk Advanced Renal Cell Carcinoma

Patients with intermediate-risk advanced renal cell carcinoma are a heterogeneous population, having either 1 or 2 risk factors. It is unclear whether all patients in this risk category should be treated similarly. A secondary analysis of the PRINCIPAL study of pazopanib found that patients can be stratified by number of risk factors and Eastern Cooperative Oncology Group performance status to more accurately predict outcomes. Introduction: The objective of this study was to determine the effectiveness and safety of pazopanib in patients with intermediate-risk advanced/metastatic renal cell carcinoma in the PRINCIPAL study (NCT01649778). Patients and Methods: Patients had clear-cell advanced/metastatic renal cell carcinoma and met intermediate-risk International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Assessments included progression-free survival, overall survival, objective response rate, and safety. We also evaluated effectiveness based on number of risk factors, age, and performance status (PS), as well as safety in older and younger patients. Results: Three hundred sixty three and 343 intermediate-risk MSKCC and IMDC patients were included, respectively. The median progression-free survival was 13.8 months (95% confidence interval [CI], 10.7-18.1 months) and 7.4 months (95% CI, 6.2-10.3 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 13.1 months (95% CI, 10.7-18.1 months) and 8.1 months (95% CI, 6.4-10.7 months) for patients with 1 and 2 IMDC risk factors, respectively. The median overall survival was not reached and was 15.2 months (95% CI, 12.3-26.5 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 33.9 months (95% CI, 33.9 months to not estimable) and 19.4 months (95% CI, 14.3 months to not estimable) with 1 and 2 IMDC risk factors, respectively. A lower overall response rate was observed with Eastern Cooperative Oncology Group PS >= 2 (vs. PS = 2) to more accurately predict outcomes. (C) 2019 Published by Elsevier Inc.Peer reviewe

Second-line targeted therapies after nivolumab-ipilimumab failure in metastatic renal cell carcinoma

Correction: Volume: 119 Pages: 200-201 DOI: 10.1016/j.ejca.2019.04.012 Published: SEP 2019Background: Nivolumab-ipilimumab demonstrated a survival benefit over sunitinib in first-line setting for metastatic renal cell carcinomas (mRCCs) and is becoming a new standard of care for naive patients with intermediate or poor risk prognosis (International mRCC Database Consortium). The efficacy of subsequent vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs) after nivolumab-ipilimumab failure remains unclear. Methods: Medical records of mRCC patients treated with nivolumab-ipilimumab, who received subsequent TKI, as part of Checkmate 214 study were reviewed in 13 institutions. Baseline characteristics, outcome data including progression-free survival (PFS), response, overall survival (OS) and toxicities were retrospectively collected. Results: Overall 33 patients received subsequent TKI after nivolumab-ipilimumab failure. Median follow-up from start of subsequent TKI is 22 months (19-NR). Best response was assessed in 30 patients: 12 partial responses (36%), 13 stable diseases (39%) and five progressive diseases (15%). Median PFS from start of TKI was 8 months [5-13]. Median PFS with first-generation (sunitinib/pazopanib) and second-generation TKI (axitinib/cabozantinib) was 8 months [5-16] and 7 months (5-NA), respectively. PFS in second line was significantly longer in patients with a long first-line duration of response to the double immune checkpoint blockade (>= 6 months) with 8 versus 5 months for short responder (= 3. Conclusion: This is the first report of outcomes with TKI, after first-line nivolumab-ipilimumab failure. Median PFS suggests a sustained benefit of TKI and supports trials investigating the optimal sequence. (C) 2018 Published by Elsevier Ltd.Peer reviewe