A highly pathogenic avian influenza virus H5N1 clade 2.3.4.4 detected in Samara Oblast, Russian Federation.

Avian influenza (AI) is a global problem impacting birds and mammals, causing economic losses in commercial poultry farms and backyard settings. In 2022, over 8,500 AI cases were reported worldwide, with the H5 subtype being responsible for many outbreaks in wild and domestic birds. In the territory of the Russian Federation, outbreaks of AI have been massively reported since 2020, both among domestic bird species and wild bird species. Wild migratory birds often serve as natural reservoirs for AI viruses, and interactions between bird species can lead to the emergence of new, highly pathogenic variants through genetic recombination between strains. In order to combat the widespread outbreaks of the disease and potential risks of further spread in 2021, monitoring studies were conducted in the Samara Oblast, the southeastern region of European Russian Federation. These studies aimed to diagnose and characterize circulating AI virus variants among wild migratory birds during waterfowl hunting in areas of mass nesting. Among the 98 shot birds, a highly pathogenic A/H5N1 AI virus was detected in a Eurasian Teal from the Bolshechernigovsky district. It was classified into clade 2.3.4.4 based on the cleavage site structure of HA. Phylogenetic analysis showed a high relatedness of the identified strain in the Samara Oblast with field isolates from Russia, Nigeria, Bangladesh, and Benin. The article emphasizes the importance of monitoring AI virus spread in both wild and poultry, highlighting the need for timely information exchange to assess risks. Further comprehensive studies are necessary to understand virus dissemination pathways.

Imaging Changes and Outcomes of Patients Undergoing Active Monitoring for Ductal Carcinoma In Situ: Seven-Year Follow-up Study.

RATIONALE AND OBJECTIVES: To determine the imaging changes and their associated positive predictive value (PPV) for invasive breast cancer in women undergoing active monitoring for ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: In this seven-year follow-up retrospective IRB-exempted cohort study, we reviewed patients diagnosed with DCIS who elected active monitoring between 2003 and 2022 at a single academic institution. Imaging characteristics, histopathology at initial diagnosis, and subsequent follow-up were recorded. Low-risk DCIS was defined as low or intermediate grade and hormone receptor (HR) positive (estrogen and/or progesterone receptor positive) disease diagnosed in women at least 40 years of age. Progression was defined as subsequent ipsilateral invasive breast cancer diagnosis. RESULTS: There were 39 patients with a median age of 58.4 years (IQR: 51.1-69.6 years) and a median follow-up of 4.3 years (range: 0.6-16.4 years). Nearly two thirds of patients (64%, 25/39) had stable imaging (range: 0.6-16.4 years) and remained progression-free during active monitoring. Among the remaining 14 patients (36%), there were 24 imaging findings which prompted 22 subsequent core needle biopsies (range: 1-3 biopsies per patient) and two surgical biopsies. The PPV of invasive cancer was 29% (7/24) overall and 38% (3/8) for masses, 33% (3/9) for calcifications, 17% (1/6) for non-mass enhancement, and 0% (0/1) for architectural distortion. CONCLUSION: Of the radiographic changes prompting an additional biopsy, development of a new mass (38%) and new calcifications (33%) had the highest PPV for invasive progression. Close imaging follow-up should be a critical component for patients undergoing monitoring for DCIS.

Safety profile of methotrexate used off-label in ectopic pregnancy: an active monitoring study based on a Chinese hospital pharmacovigilance system.

OBJECTIVE: Methotrexate (MTX) is characterized as first-line therapy although its indication of ectopic pregnancy is off-label use. We aimed to conduct a retrospective cohort study to investigate the incidence, characteristics of adverse drug reactions (ADRs) of MTX, provide valuable insights for medical workers. METHODS: Basing on China Hospital Pharmacovigilance System (CHPS), a retrospective analysis was performed to evaluate the safety of MTX (n = 672). An active monitoring model was set to detect ADR signals from the hospital information system. Frequency, Common Terminology Criteria for Adverse Events (CTCAE) grade proportion and association of dose exposure with ADRs were presented as outcomes. RESULTS: The total incidence of ADRs was 54.0%. Anaemia (37.6%) was the most frequent ADR, followed by hepatic function abnormal (11.3%), hyperuricemia (6.1%), neutropenia (4.6%), leukopenia (4.0%), and dyslipidaemia (2.5%). For the composition of all ADRs, CTCAE grade one, two and three dominated for 86.3%, 12.1% and 1.6%, respectively. The severity of hepatic function abnormal was more serious in the two-dose exposed group (p = .021), while other types of ADRs had no statistical or clinical differences. Logistic regression analysis showed the incidence of any ADRs (OR 1.87 [1.31-2.64]; p = .001), hepatic function abnormal (OR 2.75 [1.69-4.48]; p < .001), dyslipidaemia (OR 5.15 [1.87-14.13]; p = .001) were significantly higher in the two-dose exposed group. After adjusted, the positive associations were still maintained. CONCLUSIONS: MTX is quite safe in ectopic pregnancy, despite its mild to moderate hematotoxicity, hepatotoxicity and nephrotoxicity. Taking CHPS can present the accurate denominator of the incidence of adverse drug reactions into account, our study advocates that it may have great potential to be used as an active monitoring tool for off-label drug use risk management.

Evolving Treatment Paradigms for Low-Risk Ductal Carcinoma In Situ: Imaging Needs.

Ductal carcinoma in situ (DCIS) is a nonobligate precursor to invasive cancer that classically presents as asymptomatic calcifications on screening mammography. The increase in DCIS diagnoses with organized screening programs has raised concerns about overdiagnosis, while a patientcentric push for more personalized care has increased awareness about DCIS overtreatment. The standard of care for most new DCIS diagnoses is surgical excision, but nonsurgical management via active monitoring is gaining attention, and multiple clinical trials are ongoing. Imaging, along with demographic and pathologic information, is a critical component of active monitoring efforts. Commonly used imaging modalities including mammography, ultrasound, and MRI, as well as newer modalities such as contrast-enhanced mammography and dedicated breast PET, can provide prognostic information to risk stratify patients for DCIS active monitoring eligibility. Furthermore, radiologists will be responsible for closely surveilling patients on active monitoring and identifying if invasive progression occurs. Active monitoring is a paradigm shift for DCIS care, but the success or failure will rely heavily on the interpretations and guidance of radiologists.

Comparison of Outcomes of Active Surveillance in Intermediate-Risk Versus Low-Risk Localised Prostate Cancer Patients: A Systematic Review and Meta-Analysis.

Currently, there is no clear consensus regarding the role of active surveillance (AS) in the management of intermediate-risk prostate cancer (IRPC) patients. We aim to analyse data from the available literature on the outcomes of AS in the management of IRPC patients and compare them with low-risk prostate cancer (LRPC) patients. A comprehensive literature search was performed, and relevant data were extracted. Our primary outcome was treatment-free survival, and secondary outcomes were metastasis-free survival, cancer-specific survival, and overall survival. The DerSimonian-Laird random-effects method was used for the meta-analysis. Out of 712 studies identified following an initial search, 25 studies were included in the systematic review. We found that both IRPC and LRPC patients had nearly similar 5, 10, and 15 year treatment-free survival rate, 5 and 10 year metastasis-free survival rate, and 5 year overall survival rate. However, cancer-specific survival rates at 5, 10, and 15 years were significantly lower in IRPC compared to LRPC group. Furthermore, IRPC patients had significantly inferior long-term overall survival rate (10 and 15 year) and metastasis-free survival rate (15 year) compared to LRPC patients. Both the clinicians and the patients can consider this information during the informed decision-making process before choosing AS.

Active monitoring versus an abduction device for treatment of infants with centered dysplastic hips: study protocol for a randomized controlled trial (TReatment with Active Monitoring (TRAM)-Trial).

BACKGROUND: Developmental Dysplasia of the Hip (DDH) is one of the most common pediatric orthopedic disorders, affecting 1-3% of all newborns. The optimal treatment of centered DDH is currently under debate. This randomized controlled trial aims to study the (cost-)effectiveness of active monitoring versus abduction treatment for infants with centered DDH. METHODS: This is a multicenter, parallel-group, open-label, non-inferiority randomized controlled trial studying the (cost-)effectiveness of active monitoring versus abduction treatment for infants with centered DDH in fourteen hospitals in the Netherlands. In total, 800 infants with centered DDH (Graf IIa-/IIb/IIc), aged 10-16 weeks, will be randomly allocated to the active monitoring or abduction treatment group. Infants will be followed up until the age of 24 months. The primary outcome is the rate of normal hips, defined as an acetabular index lower than 25 degrees on an antero-posterior radiograph, at the age of 12 months. Secondary outcomes are the rate of normal hips at the age of 24 months, complications, time to hip normalization, the relation between baseline patient characteristics and the rate of normal hips, compliance, costs, cost-effectiveness, budget impact, health-related quality of life (HRQoL) of the infant, HRQoL of the parents/caregivers, and parent/caregiver satisfaction with the treatment protocol. DISCUSSION: The outcomes of this randomized controlled trial will contribute to improving current care-as-usual for infants with centered DDH. TRIAL REGISTRATION: Dutch Trial Register, NL9714, registered September 6, 2021. https://clinicaltrialregister.nl/en/trial/29596.

Quality of life outcomes in incidental and operated meningiomas (QUALMS): a cross-sectional cohort study.

INTRODUCTION: Few studies have evaluated meningioma patients' longer-term health-related quality of life (HRQoL) following diagnosis and treatment, particularly in those with incidental, actively monitored tumours. METHODS: A single-center, cross-sectional study was completed. Adult patients with surgically managed or actively monitored meningioma with more than five years of follow-up were included. The patient-reported outcome measures RAND SF-36, EORTC QLQ-C30 and QLQ-BN20 were used to evaluate HRQoL. HRQoL scores were compared to normative population data. Outcome determinants were evaluated using multivariate linear regression analysis. RESULTS: 243 patient responses were analyzed, and the mean time from diagnosis was 9.8 years (range 5.0-40.3 years). Clinically relevant, statistically significant HRQoL impairments were identified across several SF-36 and QLQ-C30 domains. Increasing education level (ß = 2.9, 95% CI 0.9 to 4.9), P = .004), employment (ß = 7.7, 95% CI 2.2 to 13.1, P = .006) and absence of postoperative complications (ß=-6.7, 95% CI -13.2 to (-)0.3, P = .041) were associated with a better QLQ-C30 summary score. Other tumour and treatment variables were not. CONCLUSION: This study highlights the longer-term disease burden of patients with meningioma nearly one decade after diagnosis or surgery. Patients with actively monitored meningioma have similar HRQoL to operated meningioma patients. Healthcare professionals should be mindful of HRQoL impairments and direct patients to sources of support as needed.

Epidemiological characteristics of foodborne norovirus infectious diarrhea in Jiangsu Province in 2015-2020 / 公共卫生与预防医学

Objective To analyze the epidemiological characteristics of norovirus infectious diarrhea in the active monitoring of foodborne diseases in Jiangsu Province from 2015 to 2020, so as to provide reference for the prevention and control of foodborne diseases caused by norovirus. Methods Norovirus positive diarrhea cases were collected from sentinel hospitals in 13 districts and cities of Jiangsu Province, and their epidemiological and clinical characteristics were analyzed. Results Atotal of 3 620 norovirus positive cases were detected and isolated from 61 489 samples. The main serotype was GII (71.97%), the onset season was winter and spring, and the onset age was 1-3 years old and 14-34 years old. There was no significant difference in norovirus positive rate between different sexes, and the main symptom was diarrhea (incidence rate was 92.10%), Meat and meat products (20.20%) were the main types of suspected exposed foods. Conclusion Norovirus infection has obvious seasonal characteristics, and the population is generally susceptible. It is high in children and young people, and meat food was the main suspicious exposure food. We should continue to improve the ability of active monitoring, identification, early warning and control of foodborne diseases, so as to reduce the occurrence of foodborne diseases.

Retrospective investigation and analysis of pertussis in Ninghai County， Zhejiang Province from 2018 to 2019 / 上海预防医学

ObjectiveTo characterize the incidence of laboratory confirmed pertussis cases by immunization status in Ninghai County， and to provide evidence for improving pertussis prevention and control strategy in Ninghai County. MethodsData of reported pertussis cases in Ninghai County from 2018 to 2019 were collected through the National Notifiable Infectious Disease Reporting System. The immunization history of vaccines related to pertussis was collected through the Ningbo Immunization Planning Information Management System and field investigation. Descriptive epidemiological methods were used to analyze the collected data. ResultsThe respiratory secretions collected in the 64 cases tested positive for nucleic acid of Bordetella pertussis bacilli， of which 56.25% aged 0‒1 year. They were mainly pre-school children. No adolescent or adult case was reported. All cases had whooping cough. Of the cases， 78.13% had an increase in white blood cell count， 62.5% had an increase in lymphocyte percentage， 59.38% had completed three or more doses of pertussis vaccination， 69.39% had a time interval of >1 year between the onset and last dose of pertussis vaccination， and 31.25% reported close contact with pertussis patients before the onset. The misdiagnosis rate of pertussis was as high as 92.19%. In contrast， the prevalence of anti-pertussis IgG antibody in health population was 1.05%. ConclusionFurther improvement in the laboratory testing capacity can help clarify the diagnosis of pertussis. Generally， children aged 0-1 year are mainly affected， of which vast majority have received at least one dose of pertussis vaccination. Clinical symptoms are characterized by whooping cough. Additionally， elevated white blood cells and lymphocytes should be on the alert to pertussis infection.

Surveillance results of foodborne diseases in Jinan in 2013 - 2021 / 公共卫生与预防医学

Objective To understand the epidemiological and etiological characteristics of foodborne diseases in Jinan City, and to provide targeted measures for the prevention and control of foodborne diseases. Methods Data were collected from the reporting system of two sentinel hospitals for active surveillance of foodborne diseases in Jinan City from 2013 to 2021, and pathogens were detected in stool/anal swab samples of the cases. Constituent ratio was used for enumeration data, and χ2 test was used for comparison of detection rates. Results A total of 5,417 cases of foodborne diseases were reported in the two sentinel hospitals in Jinan from 2013 to 2021, and most of them were children aged 0-5 years (48.57%). The high incidence period of foodborne diseases was from May to August (53.72%). The main clinical symptoms were digestive system symptoms. Meat and meat products accounted for the largest number of suspected exposed foods (13.89%), and home-made food was the main exposure source (45.83%). The total detection rate of pathogens was 38.40%, mainly Escherichia coli (24.22%), and the detection rate of norovirus was 17.76%. There was a significant difference in the detection rate of pathogenic bacteria before and after the establishment of Healthy City (χ2=107.22, P <0.001). Conclusion The high-risk population for foodborne diseases is children aged 0 to 5 years old. Summer and fall are the high incidence seasons, with E. coli and norovirus as predominant pathogens. It is necessary to continue to strengthen the monitoring of foodborne diseases in high-risk seasons and infants, improve the food safety awareness of high-risk groups, increase monitoring sentinel hospitals, and expand the coverage. In addition, relevant departments should take corresponding prevention and control measures to reduce the occurrence of foodborne diseases.

Detection of pediatric drug-induced kidney injury signals using a hospital electronic medical record database.

Background: Drug-induced kidney injury (DIKI) is one of the most common complications in clinical practice. Detection signals through post-marketing approaches are of great value in preventing DIKI in pediatric patients. This study aimed to propose a quantitative algorithm to detect DIKI signals in children using an electronic health record (EHR) database. Methods: In this study, 12 years of medical data collected from a constructed data warehouse were analyzed, which contained 575,965 records of inpatients from 1 January 2009 to 31 December 2020. Eligible participants included inpatients aged 28 days to 18 years old. A two-stage procedure was adopted to detect DIKI signals: 1) stage 1: the suspected drugs potentially associated with DIKI were screened by calculating the crude incidence of DIKI events; and 2) stage 2: the associations between suspected drugs and DIKI were identified in the propensity score-matched retrospective cohorts. Unconditional logistic regression was used to analyze the difference in the incidence of DIKI events and to estimate the odds ratio (OR) and 95% confidence interval (CI). Potentially new signals were distinguished from already known associations concerning DIKI by manually reviewing the published literature and drug instructions. Results: Nine suspected drugs were initially screened from a total of 652 drugs. Six drugs, including diazepam (OR = 1.61, 95%CI: 1.43-1.80), omeprazole (OR = 1.35, 95%CI: 1.17-1.54), ondansetron (OR = 1.49, 95%CI: 1.36-1.63), methotrexate (OR = 1.36, 95%CI: 1.25-1.47), creatine phosphate sodium (OR = 1.13, 95%CI: 1.05-1.22), and cytarabine (OR = 1.17, 95%CI: 1.06-1.28), were demonstrated to be associated with DIKI as positive signals. The remaining three drugs, including vitamin K1 (OR = 1.06, 95%CI: 0.89-1.27), cefamandole (OR = 1.07, 95%CI: 0.94-1.21), and ibuprofen (OR = 1.01, 95%CI: 0.94-1.09), were found not to be associated with DIKI. Of these, creatine phosphate sodium was considered to be a possible new DIKI signal as it had not been reported in both adults and children previously. Moreover, three other drugs, namely, diazepam, omeprazole, and ondansetron, were shown to be new potential signals in pediatrics. Conclusion: A two-step quantitative procedure to actively explore DIKI signals using real-world data (RWD) was developed. Our findings highlight the potential of EHRs to complement traditional spontaneous reporting systems (SRS) for drug safety signal detection in a pediatric setting.

A web-based personalized decision support tool for patients diagnosed with ductal carcinoma in situ: development, content evaluation, and usability testing.

PURPOSE: Patients diagnosed with ductal carcinoma in situ (DCIS) face trade-offs when deciding among different treatments, including surgery, radiation, and endocrine therapy. A less chosen option is active monitoring. While evidence from clinical trials is not yet available, observational studies show comparable results for active monitoring and immediate treatment on cancer outcomes in select subgroups of patients. We developed and tested a web-based decision support tool (DST) to help patients explore current knowledge about DCIS and make an informed choice. METHODS: The DST, an interactive web application, was informed by literature reviews and formative work with patients, breast surgeons, and health communication experts. We conducted iterative interviews to evaluate the DST content among women with and without a history of breast cancer, as well as breast cancer experts. For usability testing, we conducted an online survey among women with and without a history of breast cancer. RESULTS: For content evaluation, 5 women with and 10 women without a history of DCIS were interviewed. The sample included 11 White and 4 non-White women, with a mean age of 64 years. The expert sample consisted of 5 attendings and a physician assistant. The feedback was used to add, clarify, or reorganize information in the DST. For usability testing, 22 participants with a mean age of 61 years were recruited including 15 White and 7 Black women and 6 women with a history of DCIS. The mean usability score was 3.7 out of 5. Most participants (86%) found that the DST provided unbiased information about treatments. To improve usability, we reduced the per-page content and added navigation cues. CONCLUSION: Content and usability evaluation showed that the DST helps patients explore trade-offs of active monitoring and immediate treatment. By adopting a personalized approach, the tool will enable informed decisions aligned with patients' values and expectations.

Real World Safety of Shujin Jianyao Pills in 3 033 Cases Under Intensive Hospital Monitoring Based on Active Monitoring / 中国实验方剂学杂志

ObjectiveTo further assess the safety of clinical application of Shujin Jianyao pills after marketing and find its potential risk factors as early as possible， to obtain the real world medication situation of Shujin Jianyao pills and its incidence of adverse reactions and clinical characteristics， and to explore the factors affecting the occurrence of adverse drug reactions （ADR）. MethodIn this study， prospective， large-sample， multi-center and intensive whole-hospital monitoring with continuous registration was carried out， combined with telephone follow-up visits 2-4 weeks after the end of medication， for whole treatment course monitoring among patients. In addition， the three-level quality control was strictly implemented in the monitoring process. The study used a proprietary electronic data management system for data management， and SAS 9.4 and R software were used for statistical analysis. ResultFrom May 2018 to July 2020， the study completed the safety monitoring of 3 033 patients taking Shujin Jianyao pills in 30 clinical departments of 25 hospitals in China. A total of 36 ADR cases （49 times） were confirmed by expert assessment on data and supervision quality and expert interpretation of ADR. ConclusionAccording to the World Health Organization （WHO）， the symptoms of adverse reactions were mainly classified into occasional adverse reactions （0.1%≤ADR<1%： abdominal distension， oral ulcer， dry mouth， constipation） and rare adverse reactions （0.01%≤ADR<0.1%： loss of appetite， rash， fatigue， increased ALT， increased creatinine， dizziness， stomachache， stomach distension， liver discomfort， pruritus， dysphoria， acid regurgitation， numbness in mouth， abdominal pain， sore throat， earache， tinnitus）. Moreover， through the synthetic minority oversampling technique （SOMTE） combined with logistic regression， the following factors might affect ADR： taking Shujin Jianyao pills for 1-14 days， aged 46-65， 66-80 and 81 and above as well as combined use of atorvastatin， cobamamide， calcitriol capsules， Gushukang capsules， glucosamine， nifedipine， methylcobalamin， metformin， Tenghuang Jiangu pills， Bugu tablets， and diclofenac sodium sustained-release tablets. This study provided a real world basis for the safety and standardized use of Shujin Jianyao pills in clinical practice.

Using Population-Based Structures to Actively Monitor AEFIs during a Mass Immunization Campaign-A Case of Measles-Rubella and Polio Vaccines.

Active vaccine pharmacovigilance complements the standard passive or spontaneous surveillance system, which suffers from low reporting rates. This study aimed at utilizing population-based structures to report and profile adverse events following immunization (AEFI) with the measles and rubella vaccine (MR), or MR in combination with the bivalent oral polio vaccine (bOPV 1&3) (MR & bOPV), during mass vaccination in Uganda. Caretakers of children at home (less than 5 years) and schoolgoing children were followed up on and encouraged to report any AEFIs on day one, 2-3 days, 10 days, and 14 days after vaccination at school by their teachers and at-home, community-based village health teams. Out of 9798 children followed up on, 382 (3.9%) reported at least one AEFI, and in total, 517 AEFIs were reported. For MR, high temperature (21%), general feeling of weakness (19.3%), and headache (13%) were the most reported AEFIs, though there were variations on the days when they were reported. For the combination dose of MR & bOPV, high temperature (44%), rash (17%), general feeling of weakness (13%), and diarrhoea (8%) were the most common adverse events following immunization reported by caretakers. All 382 children cleared the AEFIs within 2 days, with 343 (90%) children reporting mild or moderate AEFIs and only 39 (10%) reporting severe AEFIs. The reported AEFIs are known and are mentioned in the vaccine leaflets with similar severity classification. Rates of AEFIs differed with the number of days after receiving the immunization. Conclusion: Active surveillance for AEFIs provides additional important information to national vaccine regulatory bodies. It reassures the public that vaccines are safe and that their safety is being taken seriously in Uganda, which would improve vaccine acceptability and confidence in the health system. Piggybacking on existing structures such as village health team members (for children at home) and teachers (for schoolgoing children) facilitates reaching vaccine recipients and increases reporting rates. Therefore, studies using active reporting of AEFIs should be conducted at regular intervals to report the overall incidence of AEs and to monitor trends and changes.

Lifetime Health and Economic Outcomes of Active Surveillance, Radical Prostatectomy, and Radiotherapy for Favorable-Risk Localized Prostate Cancer.

OBJECTIVES: To estimate the lifetime health and economic outcomes of selecting active surveillance (AS), radical prostatectomy (RP), or radiation therapy (RT) as initial management for low- or favorable-risk localized prostate cancer. METHODS: A discrete-event simulation model was developed using evidence from published randomized trials. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Costs were included from a public payer perspective in Australian dollars. Outcomes were discounted at 5% over a lifetime horizon. Probabilistic and scenario analyses quantified parameter and structural uncertainty. RESULTS: A total of 60% of patients in the AS arm eventually received radical treatment (surgery or radiotherapy) compared with 90% for RP and 91% for RT. Although AS resulted in fewer treatment-related complications, it led to increased clinical progression (AS 40.7%, RP 17.6%, RT 19.9%) and metastatic disease (AS 13.4%, RP 6.1%, RT 7.0%). QALYs were 10.88 for AS, 11.10 for RP, and 11.13 for RT. Total costs were A$17 912 for AS, A$15 609 for RP, and A$15 118 for RT. At a willingness to pay of A$20 000/QALY, RT had a 61.4% chance of being cost-effective compared to 38.5% for RP and 0.1% for AS. CONCLUSIONS: Although AS resulted in fewer and delayed treatment-related complications, it was not found to be a cost-effective strategy for favorable-risk localized prostate cancer over a lifetime horizon because of an increase in the number of patients developing metastatic disease. RT was the dominant strategy yielding higher QALYs at lower cost although differences compared with RP were small.

Treatment breaks in first line treatment of advanced colorectal cancer: An individual patient data meta-analysis.

BACKGROUND: Intermittent systemic anti-cancer therapy in patients with advanced colorectal cancer (aCRC) may improve quality of life without compromising overall survival (OS). We aimed to use individual patient data meta-analysis (IPDMA) from multiple randomised controlled trials evaluating intermittent strategies to inform clinical practice. We also aimed to validate whether thrombocytosis as a predictive biomarker identified patients with significantly reduced OS receiving a complete treatment break. PATIENTS AND METHODS: An IPDMA of intermittent strategy impact on survival was undertaken, including all relevant trials in which data were available. Intermittent strategies were classified into two groups: a planned stopping of all therapy ("treatment break strategy"; 6 trials; 2,907 patients) or to the same treatment omitting oxaliplatin ("maintenance strategy"; 3 trials; 1,271 patients). The primary analysis sample was of patients successfully completing induction therapy. Additionally, a pre-planned analysis of the predictive value of thrombocytosis on survival under a continuous versus an intermittent strategy was undertaken. RESULTS: All trials had comparable inclusion criteria. The overall IPDMA of intermittent therapy versus continuous therapy demonstrated no detriment in OS (HR = 1.03 [95% CI 0.93-1.14]), whether from complete break (HR 1.04 [95% CI 0.87-1.26]) or maintenance strategies (HR 0.99 [95% CI 0.87-1.13]). Thrombocytosis was confirmed as a marker of poor prognosis in aCRC, but did not predict for OS detriment from treatment break strategies (interaction HR = 0.97 [95% CI 0.66-1.40] compared to continuous therapy). CONCLUSION: The highest levels of evidence from this IPDMA indicate no detriment in survival for patients receiving an intermittent therapy strategy, either for maintenance or complete break strategies. Although, thrombocytosis is confirmed as a marker of poor prognosis, it is not predictive of poor outcome for patients treated with intermittent therapy. An intermittent chemotherapy strategy can therefore be applied irrespective of baseline platelet count and does not result in inferior OS compared to continuous chemotherapy.

Cyber-Physical System for Environmental Monitoring Based on Deep Learning.

Cyber-physical systems (CPS) constitute a promising paradigm that could fit various applications. Monitoring based on the Internet of Things (IoT) has become a research area with new challenges in which to extract valuable information. This paper proposes a deep learning classification sound system for execution over CPS. This system is based on convolutional neural networks (CNNs) and is focused on the different types of vocalization of two species of anurans. CNNs, in conjunction with the use of mel-spectrograms for sounds, are shown to be an adequate tool for the classification of environmental sounds. The classification results obtained are excellent (97.53% overall accuracy) and can be considered a very promising use of the system for classifying other biological acoustic targets as well as analyzing biodiversity indices in the natural environment. The paper concludes by observing that the execution of this type of CNN, involving low-cost and reduced computing resources, are feasible for monitoring extensive natural areas. The use of CPS enables flexible and dynamic configuration and deployment of new CNN updates over remote IoT nodes.

Modelling the lifetime cost-effectiveness of radical prostatectomy, radiotherapy and active monitoring for men with clinically localised prostate cancer from median 10-year outcomes in the ProtecT randomised trial.

BACKGROUND: Optimal management strategies for clinically localised prostate cancer are debated. Using median 10-year data from the largest randomised controlled trial to date (ProtecT), the lifetime cost-effectiveness of three major treatments (radical radiotherapy, radical prostatectomy and active monitoring) was explored according to age and risk subgroups. METHODS: A decision-analytic (Markov) model was developed and informed by clinical input. The economic evaluation adopted a UK NHS perspective and the outcome was cost per Quality-Adjusted Life Year (QALY) gained (reported in UK£), estimated using EQ-5D-3L. RESULTS: Costs and QALYs extrapolated over the lifetime were mostly similar between the three randomised strategies and their subgroups, but with some important differences. Across all analyses, active monitoring was associated with higher costs, probably associated with higher rates of metastatic disease and changes to radical treatments. When comparing the value of the strategies (QALY gains and costs) in monetary terms, for both low-risk prostate cancer subgroups, radiotherapy generated the greatest net monetary benefit (£293,446 [95% CI £282,811 to £299,451] by D'Amico and £292,736 [95% CI £284,074 to £297,719] by Grade group 1). However, the sensitivity analysis highlighted uncertainty in the finding when stratified by Grade group, as radiotherapy had 53% probability of cost-effectiveness and prostatectomy had 43%. In intermediate/high risk groups, using D'Amico and Grade group > = 2, prostatectomy generated the greatest net monetary benefit (£275,977 [95% CI £258,630 to £285,474] by D'Amico and £271,933 [95% CI £237,864 to £287,784] by Grade group). This finding was supported by the sensitivity analysis. Prostatectomy had the greatest net benefit (£290,487 [95% CI £280,781 to £296,281]) for men younger than 65 and radical radiotherapy (£201,311 [95% CI £195,161 to £205,049]) for men older than 65, but sensitivity analysis showed considerable uncertainty in both findings. CONCLUSION: Over the lifetime, extrapolating from the ProtecT trial, radical radiotherapy and prostatectomy appeared to be cost-effective for low risk prostate cancer, and radical prostatectomy for intermediate/high risk prostate cancer, but there was uncertainty in some estimates. Longer ProtecT trial follow-up is required to reduce uncertainty in the model. TRIAL REGISTRATION: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

Views of healthcare professionals about the role of active monitoring in the management of ductal carcinoma in situ (DCIS): Qualitative interview study.

BACKGROUND: Ductal carcinoma in situ (DCIS) is an in-situ (pre-cancerous) breast malignancy whereby malignant cells are contained within the basement membrane of the breast ducts. Increasing awareness that some low-risk forms of DCIS might remain indolent for many years has led to concern about overtreatment, with at least 3 clinical trials underway internationally assessing the safety of active monitoring for low-risk DCIS. This study aimed to understand healthcare professionals' (HCPs) views on the management options for patients with DCIS. METHODS: Qualitative study using semi-structured interviews with HCPs involved in the diagnosis and management of DCIS in Australia and New Zealand. Interviews were audio-recorded, transcribed and analysed thematically using Framework Analysis method. RESULTS: Twenty-six HCPs including 10 breast surgeons, 3 breast physicians, 6 radiation oncologists, and 7 breast care nurses participated. There was a strong overall consensus that DCIS requires active treatment. HCPs generally felt uncomfortable recommending active monitoring as a management option for low-risk DCIS as they viewed this as outside current standard care. Overall, HCPs felt that active monitoring was an unproven strategy in need of an evidence base; however, many acknowledged that active monitoring for low-risk DCIS could be appropriate for patients with significant co-morbidities or limited life expectancy. They believed that most patients would opt for surgery wherever possible. CONCLUSIONS: This study highlights the important need for robust randomised controlled trial data about active monitoring for women with low-risk DCIS, to provide HCPs with confidence in their management recommendations and decision-making.

Active monitoring, radical prostatectomy and radical radiotherapy in PSA-detected clinically localised prostate cancer: the ProtecT three-arm RCT.

BACKGROUND: Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments. OBJECTIVES: To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50-69 years. DESIGN: A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up. SETTING: Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK. PARTICIPANTS: Between 2001 and 2009, 228,966 men aged 50-69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring (n = 545), radical prostatectomy (n = 553) or radical radiotherapy (n = 545) and 997 chose a treatment. INTERVENTIONS: The interventions were active monitoring, radical prostatectomy and radical radiotherapy. TRIAL PRIMARY OUTCOME MEASURE: Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants. SECONDARY OUTCOME MEASURES: Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes. RESULTS: There were no statistically significant differences between the groups for 17 prostate cancer-specific (p = 0.48) and 169 all-cause (p = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring, n = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy, n = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy, n = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years; p = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring (n = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy (n = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy (n = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years; p < 0.001). Radical prostatectomy had the greatest impact on sexual function/urinary continence and remained worse than radical radiotherapy and active monitoring. Radical radiotherapy's impact on sexual function was greatest at 6 months, but recovered somewhat in the majority of participants. Sexual and urinary function gradually declined in the active monitoring group. Bowel function was worse with radical radiotherapy at 6 months, but it recovered with the exception of bloody stools. Urinary voiding and nocturia worsened in the radical radiotherapy group at 6 months but recovered. Condition-specific quality-of-life effects mirrored functional changes. No differences in anxiety/depression or generic or cancer-related quality of life were found. At the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year, the probabilities that each arm was the most cost-effective option were 58% (radical radiotherapy), 32% (active monitoring) and 10% (radical prostatectomy). LIMITATIONS: A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed. CONCLUSIONS: At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years. TRIAL REGISTRATION: Current Controlled Trials ISRCTN20141297. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information.

Prostate cancer is the most common cancer in men and is often found through a blood test called a prostate-specific antigen test and through biopsies of the prostate. Over the years, these tests led to the detection of many small cancers that do not cause harm. Some prostate cancers are harmful, but it is difficult to recognise them early. When cancer is still inside the prostate, the conventional treatments are surgery or radiotherapy, which carry side effects including leaking urine and difficulty getting an erection, so another option is repeat investigations at regular intervals (active monitoring), with treatments given if the cancer progresses. These options needed to be compared in a study called a 'randomised trial' in which men agree to be allocated to one of the three treatments. In the Prostate testing for cancer and Treatment (ProtecT) study, 200,000 men aged 50­69 years were invited to have a prostate-specific antigen test. Of the 82,849 men who agreed to be tested, 1643 of whom had prostate cancer that was still contained in the prostate agreed to be allocated to one of the three treatments. After an average of 10 years of follow-up, 99% of men were alive in each of the treatment groups. However, when compared with active monitoring, surgery and radiotherapy reduced the risk of disease spreading outside the prostate by half. Patients reported that urinary leakage and sexual function were worst with surgery, and sexual and bowel functions were affected by radiotherapy. Men on active monitoring had a gradual decline in their urinary and sexual function, particularly as around half of them later had surgery or radiotherapy. Radiotherapy was the treatment that seemed to be the best value for money. The findings from the Prostate testing for cancer and Treatment (ProtecT) study can help men make decisions about being tested and which treatment to have if they are found to have cancer within the prostate. We now need to find out the longer-term effects of these treatments on how long men live and their quality of life.