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Objectives: To quantify the carbon footprint from a sample of pharma industry sponsored phase III trials. To develop an approach that can readily be applied to future trials by AstraZeneca and other trial sponsors., Design: Life cycle assessment including all the sources of carbon emissions associated with a completed, an ongoing and a planned clinical trial. The methodology followed the guidance on appraising the sustainability of Care Pathways, developed by the UK National Health Service in collaboration with parties across the healthcare system., Setting: Three multicentre late phase trials. One completed heart failure trial, one ongoing oncology trial and one asthma trial with the addition of devices to be representative of current practice., Participants: The three trials had a total number of 7412 participants., Main Outcome Measures: Total carbon emissions from each trial, the drivers of those emissions and the emissions per patient., Results: The total carbon footprint for the cardiovascular trial was calculated as 2498 tonnes carbon dioxide equivalents (CO 2 e), the first 3 years of the oncology trial resulted in 1632 tonnes CO 2 e and the respiratory trial 1437 tonnes CO 2 e., Conclusions: We have shown that it is feasible to perform a retrospective life cycle assessment to appraise the carbon footprint of large clinical trials and confirmed that phase III trials result in significant emissions. Having identified all the drivers of emissions and their magnitude, we are well placed to develop a plan for achieving net-zero carbon clinical trials. Now it is possible to expand the use of life cycle assessment to planned studies so that scientific aims can be achieved with a minimum of carbon emissions. We encourage other trialists to apply the same methodology as a necessary first step in reducing the carbon footprint of clinical trials., Competing Interests: Competing interests: DÖ and NM are employees of AstraZeneca and may own stock or stock options. JS, TC and MC are employees of ERM., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Clinical trials in the research setting have demonstrated that primary human papillomavirus (HPV)-based screening results in greater protection against cervical cancer compared with cytology, but evidence from real-life implementation was missing. To evaluate the effectiveness of HPV-based cervical screening within a real-life screening program, the organized, population-based cervical screening program in the capital region of Sweden offered either HPV- or cytology-based screening in a randomized manner through a randomized healthcare policy (RHP)., Methods and Findings: A total of 395,725 women aged 30 to 64 years that were invited for their routine cervical screening visit were randomized without blinding to either cytology-based screening with HPV triage (n = 183,309) or HPV-based screening, with cytology triage (n = 212,416 women) between September 1, 2014 and September 30, 2016 and follow-up through June 30, 2017. The main outcome was non-inferior detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Secondary outcomes included superiority in CIN2+ detection, screening attendance, and referral to histology. In total, 120,240 had a cervical screening sample on record in the study period in the HPV arm and 99,340 in the cytology arm and were followed for the outcomes of interest. In per-protocol (PP) analyses, the detection rate of CIN2+ was 1.03% (95% confidence interval (CI) 0.98 to 1.10) in the HPV arm and 0.93% (0.87 to 0.99) in the cytology arm (p for non-inferiority <0.0001; odds ratio (OR) 1.11 (95% CI 1.02 to 1.22)). There were 46 cervical cancers detected in the HPV arm (0.04% (0.03 to 0.06)) and 48 cancers detected in the cytology arm (0.05% (0.04 to 0.07)) (p for non-inferiority <0.0001; OR 0.79 (0.53 to 1.18)). Intention-to-screen (ITS) analyses found few differences. In the HPV arm, there was a modestly increased attendance after new invitations (68.56% (68.31 to 68.80) vs. 67.71% (67.43 to 67.98); OR 1.02 (1.00 to 1.03)) and increased rate of referral with completed biopsy (3.89% (3.79 to 4.00) vs. 3.53% (3.42 to 3.65); OR 1.10 (1.05 to 1.15)). The main limitations of this analysis are that only the baseline results are presented, and there was an imbalance in invitations between the study arms., Conclusions: In this study, we observed that a real-life RHP of primary HPV-based screening was acceptable and effective when evaluated against cytology-based screening, as indicated by comparable participation, referral, and detection rates., Trial Registration: ClinicalTrials.gov NCT01511328., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To explain apparent differences among mammography screening services in Sweden using individual data on participation in screening and with breast cancer-specific survival as an outcome., Methods: We analysed breast cancer survival data from the Swedish Cancer Register on breast cancer cases from nine Swedish counties diagnosed in women eligible for screening. Data were available on 38,278 breast cancers diagnosed and 4312 breast cancer deaths. Survival to death from breast cancer was estimated using the Kaplan-Meier estimate, for all cases in each county, and separately for cases of women participating and not participating in their last invitation to screening. Formal statistical comparisons of survival were made using proportional hazards regression., Results: All counties showed a reduction in the hazard of breast cancer death with participation in screening, but the reductions for individual counties varied substantially, ranging from 51% (95% confidence interval 46-55%) to 81% (95% confidence interval 74-85%). Survival rates in nonparticipating women ranged from 53% (95% confidence interval 40-65%) to 74% (95% confidence interval 72-77%), while the corresponding survival in women participating in screening varied from 80% (95% confidence interval 77-84%) to 86% (95% confidence interval 83-88%), a considerably narrower range., Conclusions: Differences among counties in the effect of screening on breast cancer outcomes were mainly due to variation in survival in women not participating in screening. Screening conferred similarly high survival rates in all counties. This indicates that the performance of screening services was similar across counties and that detection and treatment of breast cancer in early-stage reduces inequalities in breast cancer outcome.

A screening program for abdominal aortic aneurysm (AAA), inviting 65-year-old men, was started in Stockholm in 2010 (2.3 million inhabitants). The aim was to present a long-term follow-up of men participating in screening, as well as AAA repair and ruptures among nonparticipants. Demographics were collected for men with screening detected with AAA 2010 to 2016 (n = 672) and a control group with normal aortas at screening (controls, n = 237). Medical charts and regional Swedvasc (Swedish Vascular registry) data were analyzed for aortic repair for men born 1945 to 1951. Ultrasound maximum aortic diameter (AD) as well as Aortic Size Index (ASI) was recorded. Participation was 78% and prevalence of AAA was 1.2% (n = 672). Aortic repair rates correlated with high ASI and AD. During the study period, 22% of the AAA patients were treated with the elective repair; 35 men in surveillance died (5.2%), non-AAA-related causes (82.9%) dominated, followed by unknown causes among 4 (11.4%), and 2 (5.7%) possibly AAA-related deaths. Abdominal aortic aneurysm rupture rate was higher among nonparticipants (0.096% vs 0.0036%, P < .001). The low dropout rate confirms acceptability of follow-up after screening. The efficacy is shown by the much higher rupture rate among the nonparticipating men.

Background: It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death., Methods: Among 549,091 women, covering approximately 30% of the Swedish screening-eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression., Results: Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51-0.68 [P < .001]) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66-0.84 [P < .001])., Conclusions: Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens., (© 2020 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

High screening participation in the population is essential for optimal prevention of cervical cancer. Offering a high-risk human papillomavirus (HPV) self-test has previously been shown to increase participation. In this randomized health services study, we evaluated four strategies with regard to participation. Women who had not attended organized cervical screening in 10 years were eligible for inclusion. This group comprised 16,437 out of 413,487 resident women ages 33-60 (<4% of the screening target group). Among these 16,437 long-term nonattenders, 8,000 women were randomized to either (i) a HPV self-sampling kit sent directly; (ii) an invitation to order a HPV self-sampling kit using a new open source eHealth web application; (iii) an invitation to call a coordinating midwife with questions and concerns; or (iv) the standard annual renewed invitation letter with prebooked appointment time (routine practice). Overall participation, by arm, was (i) 18.7%; (ii) 10.7%; (iii) 1.9%; and (iv) 1.7%. The relative risk of participation in Arm 1 was 11.0 (95% CI 7.8-15.5), 6.3 (95% CI 4.4-8.9) in Arm 2 and 1.1 (95% CI 0.7-1.7) in Arm 3, compared to Arm 4. High-risk HPV prevalence among women who returned kits in study Arms 1 and 2 was 12.2%. In total, 63 women were directly referred to colposcopy from Arms 1 and 2; of which, 43 (68.3%) attended and 17 had a high-grade cervical lesion (CIN2+) in histology (39.5%). Targeting long-term nonattending women with sending or offering the opportunity to order self-sampling kits further increased the participation in an organized screening program., (© 2019 UICC.)

Objective: Using quantitative Faecal Immunochemical Test (FIT) in colorectal cancer screening enables adjustment of the cut-off for a positive test. As men have higher stool blood levels and higher prevalence of colorectal neoplasia, different cut-off levels can be chosen for men and women. We evaluated participation and positivity rates switching from guaiac-based faecal occult blood test (gFOBT) (Hemoccult®) to FIT (OC-Sensor), using gender-specific cut-offs., Methods: The colorectal cancer screening programme of Stockholm-Gotland, Sweden, started in 2008 and invited individuals aged 60-69 to biennial testing using gFOBT. From 1 October 2015 the test was switched to FIT, with positivity cut-offs of 40 (200) and 80 (400) µg Hb/g (ng/mL) faeces for women and men, respectively. The first year was evaluated for compliance and positivity, number of reminders and incorrect/inadequate tests, compared with gFOBT in the preceding 12-month period., Results: There were 127,030 and 87,269 individuals invited to screening with gFOBT and FIT, respectively. The change of test increased overall participation by 11.9% (95% confidence interval 11.5%-12.3%) from 56.5% to 68.4% ( p < 0.001). The increase was larger in men (14.3%) than women (9.7%), and in those aged 60-64 (14.2%) than those aged 65-69 (8.7%). The positivity rate was 2.6% in women and 2.5% in men. There was a lower rate of reminders and incorrect/inadequate tests with FIT., Conclusions: Within a well-organised colorectal cancer screening programme, changing the test from gFOBT to FIT markedly increased participation, especially among men, and in the younger age group. With a lower cut-off in women than men, the positivity rate was similar.

The purpose of this case report was to assess whether patient-specific implants (PSI: Xillocs) and soft tissue flaps contribute in reconstructing large mandibular defects. Five patients with a medical situation and history not suitable for free microvascular bone flaps were operated with PSI and evaluated. The mean follow-up time was 12 months. The excellent fit, convenient surgery, and esthetic outcome were seen as the major advantages. The PSI can, in the authors' experience, be considered as a useful alternative provided they are well embedded by viable tissue and attached to vital resection margins of the recipient bone.

Objectives: The organized population-based screening programme for abdominal aortic aneurysm in Stockholm, Sweden, started in 2010. An examination fee was initially charged, but later removed because of a policy change. We examined the effect on screening attendance of removing the fee., Methods: The periods before and after removing the examination fee were compared with regard to screening attendance, overall, by municipality and by district., Results: Screening attendance was 79.2% in the period with an examination fee and 79.9% in the period without an examination fee (p = 0.1787), with no significant change in screening attendance between the periods., Conclusions: Although removing examination fees has been shown to have a positive impact on attendance in other screening programmes, we did not find this association in our study.

Statement of Problem: Evaluate the effect of orbital prosthesis retained by implants through a specific quality of life (QOL) questionnaire provides important information on patients QOL, great incentive for the multidisciplinary team and public health support to continue work in this area., Purpose: The objective of the study was to evaluate patient satisfaction with orbital implant-supported prostheses using an adapted quality of life questionnaire., Materials and Methods: Forty five patients using orbital implant-supported prostheses for a period ranging from six to 120 months. The subjects answered a questionnaire that consisted of 10 questions covering appearance, retention, conspicuousness, self-confidence, difficulty of placement, difficulty of removal, cleaning, limitation of activities, discomfort of tissues, and recommendation of the method to other patients. Answers were expressed using a visual 100-mm scale. The arithmetic mean of the responses was converted into a percentage to represent the satisfaction index., Results: Patients demonstrated a high level of satisfaction on all items, with the lowest rate being for aesthetics and the highest being for recommending the method to other patients. High satisfaction rates regarding the placement and removal of the prosthesis, discomfort to the tissues, and cleaning suggest the ease of handling of the prosthesis. High satisfaction with retention, self-confidence, conspicuousness of the prosthesis, and limitation of activities indicated an association with a better social life., Conclusions: The results showed that use of bone anchorage technique of extraoral prostheses provided a high level of satisfaction among patients, confirming that osseointegrated implants are a very important resource for the rehabilitation of orbital deformities., (© 2018 Wiley Periodicals, Inc.)

Register for new drugs in cancer care provides a picture of how the drugs are used in the daily clinical practice Today, an increasing number of cancer drugs are approved before traditional well-controlled phase 3 studies have been conducted and in many registration studies there is no participation of Swedish departments. This article describes the general experience of a caregiver initiated systematic follow-up of new cancer drugs that shows the possibility of obtaining a picture of the drug's use in routine care. From the register "New Pharmaceuticals in Cancer care", registrations from Stockholm-Gotland region are reported. The structure of the registry can be used with advantage in other therapeutic areas than cancer and can be supplemented with data from national and regional registers as well as quality registers including patient experiences. The knowledge is important to many actors in health care and can contribute to an evidence based, patient-safe and equal healthcare in accordance with current guidelines.

Tyloses are ingrowths of parenchyma cells into the lumen of embolized xylem vessels, thereby protecting the remaining xylem from pathogens. They are found in heartwood, sapwood, and in abscission zones and can be induced by various stresses, but their molecular triggers are unknown. Here, we report that down-regulation of PECTIN METHYLESTERASE1 (PtxtPME1) in aspen (Populus tremula × tremuloides) triggers the formation of tyloses and activation of oxidative stress. We tested whether any of the oxidative stress-related hormones could induce tyloses in intact plantlets grown in sterile culture. Jasmonates, including jasmonic acid (JA) and methyl jasmonate, induced the formation of tyloses, whereas treatments with salicylic acid (SA) and 1-aminocyclopropane-1-carboxylic acid (ACC) were ineffective. SA abolished the induction of tyloses by JA, whereas ACC was synergistic with JA. The ability of ACC to stimulate tyloses formation when combined with JA depended on ethylene (ET) signaling, as shown by a decrease in the response in ET-insensitive plants. Measurements of internal ACC and JA concentrations in wild-type and ET-insensitive plants treated simultaneously with these two compounds indicated that ACC and JA regulate each other's concentration in an ET-dependent manner. The findings indicate that jasmonates acting synergistically with ethylene are the key molecular triggers of tyloses., (© 2017 American Society of Plant Biologists. All Rights Reserved.)

High-throughput analytical techniques to assess the chemistry of lignocellulosic plant material are crucial to plant cell-wall research. We have established an analytical platform for this purpose and demonstrated its usefulness with two applications. The system is based on analytical pyrolysis, coupled to gas chromatography/mass spectrometry - a technique particularly suited for analysis of lignocellulose. Automated multivariate-based data-processing methods are used to obtain results within a few hours after analysis, with an experimental batch of 500 analyzed samples. The usefulness of multivariate sample discrimination methods and hierarchical clustering of samples is demonstrated. We have analyzed an Arabidopsis mutant collection consisting of 300 samples representing 31 genotypes. The mutant collection is presented through cluster analysis, based on chemotypic difference, with respect to wild type. Further, we have analyzed 500 thin sections from five biological replicate trees to create a spatial highly resolved profile of the proportions of syringyl-, guaiacyl- and p-hydroxyphenyl lignin across phloem, developing and mature wood in aspen. The combination of biologically easy to interpret information, the low demand of sample amount and the flexibility in sample types amenable to analysis makes this technique a valuable extension to the range of established high-throughput biomaterial analytical platforms., (© 2015 The Authors. Physiologia Plantarum published by John Wiley & Sons Ltd on behalf of Scandinavian Plant Physiology Society.)

The transcription factor MYB103 was previously identified as a member of the transcriptional network regulating secondary wall biosynthesis in xylem tissues of Arabidopsis, and was proposed to act on cellulose biosynthesis. It is a direct transcriptional target of the transcription factor SECONDARY WALL ASSOCIATED NAC DOMAIN PROTEIN 1 (SND1), and 35S-driven dominant repression or over-expression of MYB103 modifies secondary wall thickness. We identified two myb103 T-DNA insertion mutants and chemically characterized their lignocellulose by pyrolysis/GC/MS, 2D NMR, FT-IR microspectroscopy and wet chemistry. The mutants developed normally but exhibited a 70-75% decrease in syringyl (S) lignin. The level of guaiacyl (G) lignin was co-ordinately increased, so that total Klason lignin was not affected. The transcript abundance of FERULATE-5-HYDROXYLASE (F5H), the key gene in biosynthesis of S lignin, was strongly decreased in the myb103 mutants, and the metabolomes of the myb103 mutant and an F5H null mutant were very similar. Other than modification of the lignin S to G ratio, there were only very minor changes in the composition of secondary cell-wall polymers in the inflorescence stem. In conclusion, we demonstrate that F5H expression and hence biosynthesis of S lignin are dependent on MYB103., (© 2012 The Authors The Plant Journal © 2012 Blackwell Publishing Ltd.)

The option, for practical and ethical reasons, to replace animal plasma with human plasma for calibration standards was successfully applied to 73 analytical methods developed in our laboratory during the last years. The animals used for obtaining blank plasma could then be reduced with a number corresponding to about 25% of mice or 5% of rats in ordinary one-month toxicology studies. This is of important public concern and also in accordance with the 3R-strategy. The methods were successfully validated for determination of drug concentrations in plasma from rat, dog, mouse, rabbit and cynomolgus monkey. Reproducibility of study samples from dosed animals was established, showing a mean accuracy of 100.8% with a CV of 7.2% (n=1339). The purpose of this paper is to present a scientific basis for the alternative approach to adopt human plasma matrix for calibration standards, which will reduce animal use, without compromising the quality of appropriately validated assays. Additional advantages are cheaper and simplified plasma maintenance and the possibility to validate methods for several species in the same analytical batch., (Copyright © 2010 Elsevier B.V. All rights reserved.)