bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical utility and cost modelling of the phi test to triage referrals into image-based diagnostic services for suspected prostate cancer: the PRIM (Phi to RefIne Mri) study
Authors: Kim Lois , Boxall Nicholas , George Anne , Burling Keith , Acher Pete , Aning Jonathan , McCracken Stuart , Page Toby , Gnanapragasam Vincent J.
Published: April 2020

Background

The clinical pathway to detect and diagnose prostate cancer has been revolutionised by the use of multiparametric MRI (mpMRI pre-biopsy). mpMRI however remains a resource-intensive test and is highly operator dependent with variable effectiveness with regard to its negative predictive value. Here we tested the use of the phi assay in standard clinical practice to pre-select men at the highest risk of harbouring significant cancer and hence refine the use of mpMRI and biopsies.

Methods

A prospective five-centre study recruited men being investigated through an mpMRI-based prostate cancer diagnostic pathway. Test statistics for PSA, PSA density (PSAd) and phi were assessed for detecting significant cancers using 2 definitions: ≥ Grade Group (GG2) and ≥ Cambridge Prognostic Groups (CPG) 3. Cost modelling and decision curve analysis (DCA) was simultaneously performed.

Results

A total of 545 men were recruited and studied with a median age, PSA and phi of 66 years, 8.0 ng/ml and 44 respectively. Overall, ≥ GG2 and ≥ CPG3 cancer detection rates were 64% (349/545), 47% (256/545) and 32% (174/545) respectively. There was no difference across centres for patient demographics or cancer detection rates. The overall area under the curve (AUC) for predicting ≥ GG2 cancers was 0.70 for PSA and 0.82 for phi. AUCs for ≥ CPG3 cancers were 0.81 and 0.87 for PSA and phi respectively. AUC values for phi did not differ between centres suggesting reliability of the test in different diagnostic settings. Pre-referral phi cut-offs between 20 and 30 had NPVs of 0.85–0.90 for ≥ GG2 cancers and 0.94–1.0 for ≥ CPG3 cancers. A strategy of mpMRI in all and biopsy only positive lesions reduced unnecessary biopsies by 35% but missed 9% of ≥ GG2 and 5% of ≥ CPG3 cancers. Using PH ≥ 30 to rule out referrals missed 8% and 5% of ≥ GG2 and ≥ CPG3 cancers (and reduced unnecessary biopsies by 40%). This was achieved however with 25% fewer mpMRI. Pathways incorporating PSAd missed fewer cancers but necessitated more unnecessary biopsies. The phi strategy had the lowest mean costs with DCA demonstrating net clinical benefit over a range of thresholds.

Conclusion

phi as a triaging test may be an effective way to reduce mpMRI and biopsies without compromising detection of significant prostate cancers.
Bayesian spatial modelling of childhood cancer incidence in Switzerland using exact point data: a nationwide study during 1985–2015
Authors:   for the Swiss Paediatric Oncology Group, Konstantinoudis Garyfallos ,   the Swiss National Cohort Study Group, Schuhmacher Dominic , Ammann Roland A. , Diesch Tamara , Kuehni Claudia E. , Spycher Ben D.
Published: April 2020

Background

The aetiology of most childhood cancers is largely unknown. Spatially varying environmental factors such as traffic-related air pollution, background radiation and agricultural pesticides might contribute to the development of childhood cancer. This study is the first investigation of the spatial disease mapping of childhood cancers using exact geocodes of place of residence.

Methods

We included 5947 children diagnosed with cancer in Switzerland during 1985–2015 at 0–15 years of age from the Swiss Childhood Cancer Registry. We modelled cancer risk using log-Gaussian Cox processes and indirect standardisation to adjust for age and year of diagnosis. We examined whether the spatial variation of risk can be explained by modelled ambient air concentration of NO2, modelled exposure to background ionising radiation, area-based socio-economic position (SEP), linguistic region, duration in years of general cancer registration in the canton or degree of urbanisation.

Results

For all childhood cancers combined, the posterior median relative risk (RR), compared to the national level, varied by location from 0.83 to 1.13 (min to max). Corresponding ranges were 0.96 to 1.09 for leukaemia, 0.90 to 1.13 for lymphoma, and 0.82 to 1.23 for central nervous system (CNS) tumours. The covariates considered explained 72% of the observed spatial variation for all cancers, 81% for leukaemia, 82% for lymphoma and 64% for CNS tumours. There was weak evidence of an association of CNS tumour incidence with modelled exposure to background ionising radiation (RR per SD difference 1.17; 0.98–1.40) and with SEP (1.6; 1.00–1.13).

Conclusion

Of the investigated diagnostic groups, childhood CNS tumours showed the largest spatial variation. The selected covariates only partially explained the observed variation of CNS tumours suggesting that other environmental factors also play a role.
Stakeholders’ engagement in co-producing policy-relevant knowledge to facilitate employment for persons with developmental disabilities
Authors: Khayatzadeh-Mahani Akram , Wittevrongel Krystle , Petermann Lisa , Graham Ian D. , Zwicker Jennifer D.
Published: April 2020

Background

Persons with developmental disabilities (PWDD) face a number of individual, environmental and societal barriers when seeking employment. Integrated knowledge translation (IKT) involves ongoing and dynamic interactions between researchers and stakeholders for the purpose of engaging in mutually beneficial research to address these types of multi-faceted barriers. There is a knowledge gap in the IKT literature on effective stakeholder engagement strategies outside of the dissemination stage to inform policy. In this paper, we report on a number of engagement strategies employed over a 2-year period to engage a wide range of stakeholders in different stages of an IKT project that aimed to investigate the ‘wicked’ problem of employment for PWDD.

Method

Our engagement plan included multiple linked strategies and was designed to ensure the meaningful engagement of, and knowledge co-production with, stakeholders. We held two participatory consensus-building stakeholder policy dialogue events to co-produce knowledge utilising the nominal group technique and the modified Delphi technique. A total of 31 and 49 stakeholders engaged in the first and second events, respectively, from six key stakeholder groups. Focused engagement strategies were employed to build on the stakeholder dialogues for knowledge mobilisation and included a focus group attended only by PWDD, a stakeholder workshop attended only by policy/decision-makers, a webinar attended by human resources professionals and employers, and a current affairs panel attended by the general public.

Results

Our findings suggest that the level of engagement for each stakeholder group varies depending on the goal and need of the project. Our stakeholder dialogue findings highlight the inherent challenges in co-framing and knowledge co-production through the meaningful engagement of multiple stakeholders who hold different ideas and interests. Focused outreach is needed to foster relationships and trust for meaningful engagement.

Conclusions

In addition to providing guidance on how to implement adaptable meaningful engagement strategies, these findings contribute to discussions on how IKT projects are planned and funded. More studies to explore effective mechanisms for engaging a wide range of stakeholders in IKT research are needed. More evidence of successful engagement strategies employed by researchers to achieve meaningful knowledge co-production is also key to advancing the discipline.
Use of game fauna by Fulni-ô people in Northeastern Brazil: implications for conservation
Authors: da Silva Josivan Soares , do Nascimento André Luiz Borba , Alves Rômulo Romeu Nóbrega , Albuquerque Ulysses Paulino
Published: April 2020

Background

Due to the influence of several factors on the hunting of game meat, we investigated how the seasonality of the environment, the abundance, and the biomass of wild animals, as well as the proximity to these resources, can affect the hunting.

Methods

The research was developed with the Fulni-ô people in the municipality of Águas Belas, Agreste of Pernambuco, Northeast of Brazil. In order to do this, we applied snowball sampling to select the participants. Data from potentially useful game species were obtained from lists and semi-structured interviews to register their particular kind of uses, capture periods (daytime, night, or both), preferences, and perceived abundance. The hunters who allowed their game meat captured to be weighed and identified were followed for 1 year.

Results

Our records pointed to a vast repertoire of potentially hunting animals. However, we did not verify relationships between the abundance, seasonality, and biomass of the animals that were hunted by the Fulni-ô. We observed a total of 209,866 (kg) of game meat hunted in the studied group, belonging to 23 species, distributed in three taxonomic groups, the birds being the most representative group with 59% of total reported.

Conclusion

Such consumption by the group is well below in terms of biomass when compared to other ethnic or local groups in other regions of Brazil, or in Caatinga areas, characterizing an activity much more of cultural character than subsistence. Also, the use of game meat among the Fulni-ô seems to be actively directed to the preferred species, suggesting that in the case of an urbanized indigenous community, where other sources of income are available, the demand for game meat is lower when compared to other ethnic groups.
Modified Stoppa as an alternative surgical approach for fixation of anterior fracture acetabulum: a randomized control clinical trial
Authors: Al Adawy Ahmed Saleh , Aziz Abdel Hamid Abdel , El Sherief Faisal Ahmed , Mahmoud Wael Shaban , Mabrook Mahmoud , Hassan Yaser El-Sayed
Published: April 2020

Background

Fracture acetabulum is a challenging, difficult to treat orthopedic injury due to its location and associated concomitant injuries. The modified Stoppa approach for reduction of fracture acetabulum improves access to quadrilateral surface and posterior column and is considered to be advantageous in many facets of the surgery.

Methods

A randomized controlled clinical study was conducted to provide an update on our experience with modified Stoppa as a favorable surgical approach in acetabular fractures. In the period between 2015 and 2017; 18 patients with acetabular fractures operated by the classical ilioinguinal approach were retrospectively reviewed through their medical records as a controlled group and selected 20 patients with acetabular fractures were operated in the period between 2017 and 2019 using the modified Stoppa approach, as a clinical case group. The two groups were compared regarding operative data and postoperative clinical data, complications, and follow up. Cases were operated in Al Zahraa University Hospital and Nasr City Insurance Hospital by the same surgeon and one of the co-authors.

Results

(Group A) those operated by ilioinguinal approach and (Group B) those operated using Stoppa approach. The whole study included 25 males (66%); mean age was 41.8 ± 8.42 (range 18-65) years. The mean follow-up period was 18.5 months with 5 patients lost to follow-up. Both column fractures were observed in most of the patients (45%). We observed anatomical reduction, excellent clinical outcome scores in 75% of patients of group B (p= 0.030), and less complications.

Conclusion

Our findings indicated that the modified Stoppa approach is the most convenient approach when surgery is required and achieved favorable results in the treatment of anterior acetabular fractures because it improves visualization in lateral compression injuries and allows treatment of both column fractures with single incision. Hence, it is recommended as an alternative to ilioinguinal approach in developing countries. Further, larger-scale comparative studies of the two surgical modalities for different acetabular fracture types and long-term complications are recommended.

Trial registration

A retrospective registration is proceeding through Clinicaltrials.gov.

Level of evidence

Level III, therapeutic clinical study
Correction to: Remotely controlled mandibular positioning of oral appliance therapy during polysomnography and drug-induced sleep endoscopy compared with conventional subjective titration in patients with obstructive sleep apnea: protocol for a randomized crossover trial
Authors: Dieltjens Marijke , Braem Marc J. , Op de Beeck Sara , Vroegop Anneclaire V. M. T. , Kazemeini Elahe , Van de Perck Eli , Beyers Jolien , Kastoer Chloé , Wouters Kristien , Willemen Marc , Verbraecken Johan A. , Vanderveken Olivier M.
Published: April 2020

Following publication of the original article [1], the authors reported that Fig. 1 had not been corrected based on the reviewer’s comments. The correct Fig. 1 is presented below.
Assessment of Borrelia miyamotoi in febrile patients and ticks in Alsace, an endemic area for Lyme borreliosis in France
Authors: Boyer Pierre H. , Koetsveld Joris , Zilliox Laurence , Sprong Hein , Talagrand-Reboul Émilie , Hansmann Yves , de Martino Sylvie Josiane , Boulanger Nathalie , Hovius Joppe W. , Jaulhac Benoît
Published: April 2020

Background

Borrelia miyamotoi is a relapsing fever Borrelia species transmitted by ticks of the Ixodes ricinus complex. Human disease caused by B. miyamotoi was first described in Russia and later in the USA and Japan. Additionally, five cases of meningoencephalitis in immunocompromised patients and one case in an apparently immunocompetent patient were described.

Methods

We investigated the presence of B. miyamotoi in I. ricinus nymphs and in patients suspected of human granulocytic anaplasmosis, in Alsace (France), an endemic area for I. ricinus ticks and Lyme borreliosis, using direct (PCR) and indirect diagnosis (glycerophosphoryldiester-phosphodiesterase (GlpQ) serology).

Results

Borrelia miyamotoi was found in 2.2% of 4354 ticks collected between 2013 and 2016. None of the 575 blood samples, collected from the patients suspected of HGA, was found positive for B. miyamotoi by PCR. Acute and late sera from 138 of these 575 patients were available. These paired sera were tested for IgM and IgG antibodies against the B. miyamotoi GlpQ antigen. A total of 14 out of 138 patients had at least one positive parameter (i.e. anti-GlpQ IgG and/or IgM). One patient seroconverted for IgG, and three had isolated IgM in the acute serum. These three patients were treated with doxycycline which could have prevented seroconversion. After reviewing clinical data and other biological tests performed, co-exposure among different microorganisms vectored by ticks or serological cross-reactivity could not be ruled out in these different cases. One patient had persistent IgG, which strongly suggests previous exposure to B. miyamotoi.

Conclusions

Humans can be exposed to B. miyamotoi through tick bites in Alsace. We present serological data for possible B. miyamotoi exposure or infection of patients with fever after tick bite. Future studies should determine the incidence, clinical course and burden of this emerging tick-borne disease in other parts of Western Europe.
Characterization of immortalized human islet stromal cells reveals a MSC-like profile with pancreatic features
Authors: Villard Orianne , Armanet Mathieu , Couderc Guilhem , Bony Claire , Moreaux Jerome , Noël Daniele , DeVos John , Klein Bernard , Veyrune Jean-Luc , Wojtusciszyn Anne
Published: April 2020

Background

Mesenchymal stromal cells (MSCs) represent an interesting tool to improve pancreatic islet transplantation. They have immunomodulatory properties and secrete supportive proteins. However, the functional properties of MSCs vary according to many factors such as donor characteristics, tissue origin, or isolation methods. To counteract this heterogeneity, we aimed to immortalize and characterize adherent cells derived from human pancreatic islets (hISCs), using phenotypic, transcriptomic, and functional analysis.

Methods

Adherent cells derived from human islets in culture were infected with a hTERT retrovirus vector and then characterized by microarray hybridization, flow cytometry analysis, and immunofluorescence assays. Osteogenic, adipogenic, and chondrogenic differentiation as well as PBMC proliferation suppression assays were used to compare the functional abilities of hISCs and MSCs. Extracellular matrix (ECM) gene expression profile analysis was performed using the SAM (Significance Analysis of Microarrays) software, and protein expression was confirmed by western blotting.

Results

hISCs kept an unlimited proliferative potential. They exhibited several properties of MSCs such as CD73, CD90, and CD105 expression and differentiation capacity. From a functional point of view, hISCs inhibited the proliferation of activated peripheral blood mononuclear cells. The transcriptomic profile of hISCs highly clusterized with bone marrow (BM)-MSCs and revealed a differential enrichment of genes involved in the organization of the ECM. Indeed, the expression and secretion profiles of ECM proteins including collagens I, IV, and VI, fibronectin, and laminins, known to be expressed in abundance around and within the islets, were different between hISCs and BM-MSCs.

Conclusion

We generated a new human cell line from pancreatic islets, with MSCs properties and retaining some pancreatic specificities related to the production of ECM proteins. hISCs appear as a very promising tool in islet transplantation by their availability (as a source of inexhaustible source of cells) and ability to secrete a supportive “pancreatic” microenvironment.
The evolving role of Fourier-transform mid-infrared spectroscopy in genetic improvement of dairy cattle
Authors: Tiplady K. M. , Lopdell T. J. , Littlejohn M. D. , Garrick D. J.
Published: April 2020

Over the last 100 years, significant advances have been made in the characterisation of milk composition for dairy cattle improvement programs. Technological progress has enabled a shift from labour intensive, on-farm collection and processing of samples that assess yield and fat levels in milk, to large-scale processing of samples through centralised laboratories, with the scope extended to include quantification of other traits. Fourier-transform mid-infrared (FT-MIR) spectroscopy has had a significant role in the transformation of milk composition phenotyping, with spectral-based predictions of major milk components already being widely used in milk payment and animal evaluation systems globally. Increasingly, there is interest in analysing the individual FT-MIR wavenumbers, and in utilising the FT-MIR data to predict other novel traits of importance to breeding programs. This includes traits related to the nutritional value of milk, the processability of milk into products such as cheese, and traits relevant to animal health and the environment. The ability to successfully incorporate these traits into breeding programs is dependent on the heritability of the FT-MIR predicted traits, and the genetic correlations between the FT-MIR predicted and actual trait values. Linking FT-MIR predicted traits to the underlying mutations responsible for their variation can be difficult because the phenotypic expression of these traits are a function of a diverse range of molecular and biological mechanisms that can obscure their genetic basis. The individual FT-MIR wavenumbers give insights into the chemical composition of milk and provide an additional layer of granularity that may assist with establishing causal links between the genome and observed phenotypes. Additionally, there are other molecular phenotypes such as those related to the metabolome, chromatin accessibility, and RNA editing that could improve our understanding of the underlying biological systems controlling traits of interest. Here we review topics of importance to phenotyping and genetic applications of FT-MIR spectra datasets, and discuss opportunities for consolidating FT-MIR datasets with other genomic and molecular data sources to improve future dairy cattle breeding programs.
Pilot trial of a group cognitive behavioural therapy program for comorbid depression and obesity
Authors: Lores Taryn , Musker Michael , Collins Kathryn , Burke Anne , Perry Seth W. , Wong Ma-Li , Licinio Julio
Published: April 2020

Background

Depression and obesity are significant global health concerns that commonly occur together. An integrated group cognitive behavioural therapy program was therefore developed to simultaneously address comorbid depression and obesity.

Methods

Twenty-four participants (63% women, mean age 46 years) who screened positively for depression with a body mass index ≥25 were recruited from a self-referred general population sample. The group therapy program (10 two-hour weekly sessions) was examined in a single-arm, before-after pilot trial, conducted in a behavioural health clinic in Adelaide, Australia. Primary outcomes included survey and assessment-based analyses of depression, anxiety, body image, self-esteem, and weight (kg), assessed at four time-points: baseline, post-intervention, three-months and 12-months post program. Eighteen participants (75%) completed the program and all assessments.

Results

Significant improvements in depression, anxiety, self-esteem and body shape concern scores, several quality of life domains, eating behaviours and total physical activity (among others) – but not weight – were observed over the course of the trial.

Conclusions

Results from this pilot trial suggest that combining interventions for depression and obesity may be useful. Further development of the program, particularly regarding the potential for physical health benefits, and a randomised controlled trial, are warranted.

Trial registration

Trial registration: ANZCTR, ACTRN12617001079336, 13 July 2017. Retrospectively registered after date of the first consent (6 July 2017), but before the date of the first intervention session (20 July 2017).
Religion and mental health: a narrative review with a focus on Muslims in English-speaking countries
Authors: Ibrahim Ahmed , Whitley Rob
Published: April 2020

Numerous commentators have noted a historic ambivalence between religion and psychiatry. However, a growing body of evidence indicates an association between mental health and various religious activities, both private and public. As such, there are growing calls for greater religious sensitivity among mental health clinicians, to help unlock the potentially healing aspects of religiosity. So far, most literature from English-speaking countries has focused on Christianity and mental health, with little attention paid to Muslim mental health. This is the fastest growing religion in English-speaking countries, and the mental health of Muslims in these countries is under-researched. As such, the present paper summarises new directions in the mental health and religion literature, with a focus on the mental health of Muslims in English-speaking countries.
Perinatal mental health around the world: priorities for research and service development in the USA
Authors: Schiller Crystal Edler , Cohen Matthew J. , O'Hara Michael W.
Published: April 2020

The perinatal mental health field is growing rapidly, which has yielded innovations in both prevention and treatment. To realise the potential of these innovations to transform clinical practice, further investment in research and clinical service development is required. Clinical services must be expanded by providing increased access to specialty care and education for front-line clinicians. Research is needed to develop a personalised medicine approach to understanding the complex aetiologies of perinatal depression and optimising treatments to promote both remission and long-term recovery. Such initiatives will require policies to prioritise federal research funding and healthcare coverage for perinatal depression.
Cognitive side-effects of electroconvulsive therapy: what are they, how to monitor them and what to tell patients
Authors: Porter Richard J. , Baune Bernhard T. , Morris Grace , Hamilton Amber , Bassett Darryl , Boyce Philip , Hopwood Malcolm J. , Mulder Roger , Parker Gordon , Singh Ajeet B. , Outhred Tim , Das Pritha , Malhi Gin S.
Published: April 2020

Background

Electroconvulsive therapy (ECT) is recommended in treatment guidelines as an efficacious therapy for treatment-resistant depression. However, it has been associated with loss of autobiographical memory and short-term reduction in new learning.

Aims

To provide clinically useful guidelines to aid clinicians in informing patients regarding the cognitive side-effects of ECT and in monitoring these during a course of ECT, using complex data.

Method

A Committee of clinical and academic experts from Australia and New Zealand met to the discuss the key issues pertaining to ECT and cognitive side-effects. Evidence regarding cognitive side-effects was reviewed, as was the limited evidence regarding how to monitor them. Both issues were supplemented by the clinical experience of the authors.

Results

Meta-analyses suggest that new learning is impaired immediately following ECT but that group mean scores return at least to baseline by 14 days after ECT. Other cognitive functions are generally unaffected. However, the finding of a mean score that is not reduced from baseline cannot be taken to indicate that impairment, particularly of new learning, cannot occur in individuals, particularly those who are at greater risk. Therefore, monitoring is still important. Evidence suggests that ECT does cause deficits in autobiographical memory. The evidence for schedules of testing to monitor cognitive side-effects is currently limited. We therefore make practical recommendations based on clinical experience.

Conclusions

Despite modern ECT techniques, cognitive side-effects remain an important issue, although their nature and degree remains to be clarified fully. In these circumstances it is useful for clinicians to have guidance regarding what to tell patients and how to monitor these side-effects clinically.
A cohort pilot study on therapeutic vaccination of advanced melanoma patients with dendritic cells loaded with multiple peptides or electroporated with mRNA
Authors: Neyns B. , Corthals J. , De Grève J. , De Greef C. , Coulie P. G. , Thielemans K.
Published: April 2020

18011

Background: Therapeutic vaccination of melanoma patients with tumor specific antigenic peptides has been associated with increased frequency of anti-vaccine CTL precursor frequencies in peripheral blood and objective tumor regression in a low percentage of patients. Methods: We investigated the safety and activity of two autologous dendritic cell-based vaccines in 2 sequential cohorts of advanced melanoma patients. Patients first underwent a leucapheresis. Following enrichment in a semi-closed culture system using Cell Factories (Nunc), adherent cells were cultured in RPMI 1640 medium supplemented with 1% heat-inactivated autologous plasma, 500U/ml IL-4 and 1000 U/ml GM-CSF for 6 days and cryo-preserved. Upon thawing, DC were pulsed with 8 peptides or electroporated with synthetic mRNA encoding 7 antigens. Dendritic cell vaccines were administered by intradermal and subcutaneous biweekly injections for a total of 6 times (= cycle 1). Thereafter vaccination was repeated every 6w until clinical deterioration or patient refusal. Frequencies of blood anti-vaccine CTL were estimated by in vitro restimulation in limiting dilution conditions followed by detection with tetramer assay. Results: Fifteen patients were recruited (9M/6F; median age was 49 y, range 28–81). Seven HLA-A2 patients were treated with peptide pulsed DC (cohort A) and 7 patients (4 HLA-A2 and 3 HLA-A1) with mRNA electroporated DC (cohort B). One patient was sequentially treated with both vaccines. Five patients in cohort A and 3 patients in cohort B completed the first treatment cycle of 6 bi-weekly vaccinations (cycle 1 is ongoing in 3 patients of cohort B). Toxicity was limited to grade 1 or 2 local skin reactions at the vaccine administration sites in all patients. In cohort B one patient qualified for stable disease and 2 other patients with progressive disease displayed regression of individual metastases. A >10-fold increase in CTL precursor frequency was observed in 2 out of 3 patients of cohort A that have been analyzed at present. Conclusions: Vaccination of melanoma patients with peptide pulsed or mRNA electroporated autologous DC vaccines was found to be feasible and safe. Updated results will be presented at the meeting.

[Table: see text]
Phase II study of temozolomide and celecoxib in the treatment of metastatic melanoma
Authors: Hakim R. , Poggi R. , Pantaleo M. , Benedetti G. , Brandi G. , Zannetti G. , Astorino M. , Fanello S. , Dell’arte S. , Biasco G.
Published: April 2020

18015

Background: There is increasing evidence that the expression of Cyclo-oxygenase 2 correlates with development and progression of malignant melanoma. Celecoxib (C) has demonstrated some kind of activity in monotherapy in melanoma. Temozolomide (T) has consistent activity in melanoma, either as monotherapy or in combination. We designed a phase II study to determine the efficacy and toxicity of the combination of Celecoxib and Temozolomide in advanced melanoma as first line of therapy Methods: From January 2004 to October 2005, 13 patients with metastatic melanoma were enrolled in the study. There were 4 males and 9 females. The median age was 59 years. Patients received Temozolomide 200/mg/mq day po for 5 days every 4 weeks and Celecoxib 400 mg BID for 10 days every 4 weeks. Results: Among 12 evaluable patients there were 4 partial responses (30.8%), no complete response or disease stabilization. Progression occurred in 8 patients (61.5%). The median TTP was 3.14 months and the median survival was 9.06 months. The median number of cycles was 2, only 2 patients completed four cycles of treatment. Most commonly seen toxicities were nausea/vomiting (46%), fatigue (93%), thrombocytopenia (15.3%), leukopenia (7.6%). Two patients discontinued the treatment due to grade 4 thrombocytopenia. Conclusions: The combination of Temozolomide and Celecoxib is safe, manageable and provides clinical benefit, but its activity is not superior to standard therapy.

No significant financial relationships to disclose.
Tolerability of pegylated liposomal doxorubicin 20 mg/m2 every 2 weeks in the management of solid or hematologic malignancies
Authors: Staddon A. P. , Kilcoyne S. , Latham J. N. , Henry D. H.
Published: April 2020

18500

Background: Pegylated liposomal doxorubicin (PLD, DOXIL) was developed to decrease the cardiotoxicity risk associated with conventional doxorubicin. However, hand-foot syndrome (HFS) and mucositis are more common with PLD 50 mg/m2 every 4 weeks (q4w) than with 20 mg/m2 q3w (all grades: HFS, 37.4% vs 3.4%; mucositis, 37.4% vs 6.8%). A lower dose intensity of PLD 10 mg/m2/wk (40 mg/m2 vs 50 mg/m2 q4w) was reported to have similar efficacy in ovarian cancer but reduced incidence of HFS and mucositis. This study evaluated the tolerability of the lower dose intensity using a 20 mg/m2 q2w regimen in patients (pts) with Kaposi’s sarcoma (KS), hematologic tumors, and solid tumors. Methods: This retrospective chart review included pts who received PLD as a component of care at a single community oncology clinic between January 2000 and December 2004. Demographics, PLD dosing, and tolerability were recorded. Data were censored for pts with an initial PLD dose other than 20 mg/m2 q2w. Results: Of the 157 pts given PLD, 79 received an initial dose of 20 mg/m2 q2w. Tumors included 47 KS, 8 hematologic (3 multiple myeloma, 4 lymphoma, 1 leukemia), and 24 solid (8 breast, 5 gynecologic, 3 colorectal, 2 liver, 2 lung, 2 sarcoma, 1 prostate, 1 thyroid). Median cumulative dose was 220 mg/m2 (range, 20–2320 mg/m2); 34 pts (31 KS, 0 hematologic, 3 solid) received >300 mg/m2 and 14 pts (13 KS, 1 solid) received >550 mg/m2. No signs (eg, decreased LVEF) or treatment-related symptoms of cardiotoxicity (eg, shortness of breath) were reported. Incidence of HFS and mucositis are reported in the Table . One HFS and 1 mucositis led to PLD discontinuation. Conclusions: Regardless of tumor type, PLD 20 mg/m2 q2w appears well tolerated. No cardiotoxicity was observed, even at cumulative doses >550 mg/m2. Rates of HFS and mucositis were lower than reported previously with a 50 mg/m2 q4w schedule. Prospective studies in larger populations are warranted to further examine the efficacy of the PLD 20 mg/m2 q2w schedule and dose intensity.

[Table: see text]

[Table: see text]
Dose and duration of dexamethasone in patients with high grade gliomas (HGG): Relationship to steroid myopathy (SM)
Authors: Blakeley J. O. , Peng T. , Ye X. , Grossman S. A.
Published: April 2020

18517

Background: Steroids are critical in the management of HGG due to their ability to control peri-tumoral edema. Myopathy is a disabling complication of steroids leading to loss of ambulation and respiratory compromise. We sought to describe the use of steroids in the first 8 months after the diagnosis of HGG and its relationship to SM. Methods: Charts of all adults with HGG diagnosed and treated at Johns Hopkins Hospital from June 2004 to May 2005 were reviewed. Patients who died in less than 8 months were excluded. Starting steroid dose, subsequent documented doses, initial date and dates of change were recorded. Only charts with the phrase “steroid myopathy” were defined as SM positive. Results: Twenty-eight patients met all inclusion criteria. The mean age was 57.2 ± 8.7 years and 19 (67.8%) were males. All patients (100%) received steroids. Dexamethasone was used exclusively. Ninety-three percent of patients received >16mg/day and 36% were on >16mg/day for at least a month. The average daily dose was 15.3 ± 7.1 mg. Mean cumulative dose was 2.8 ± 1.8 grams. The median peak dose was 40mg/day (range 16–120mg/day). Median days on steroids was 224 days (range 5–224 days) from diagnosis and 67.8% of patients were on continuous steroids for 8 months. Eleven (39% [95% CI: 22%-59%]) of the 28 patients were defined as SM. Seven of the 11 (63.6%) SM patients required wheelchairs versus two (11.8%) without SM (p = 0.004). Days on steroid was significantly longer (p = 0.012) in the SM group (214 ± 32 days) versus the non-SM group (155 ± 81days). No strong evidence supported differences between groups in total dose, average daily dose, peak dose or days on high dose steroids. Conclusions: Patients with HGG are exposed to high doses of steroids for long periods. SM was noted in 39% of our patients and most required wheelchairs within 8 months of diagnosis. These figures are likely significant underestimates given the amount of steroids administered and the retrospective nature of this study. Our data confirm prior reports of an association between duration of steroid use and SM. The findings highlight the need to prevent SM using alternate dosing schedules and agents and to develop effective treatment interventions for SM.

No significant financial relationships to disclose.
Feasibility of a self-administered geriatric assessment tool for older patients with cancer
Authors: Hurria A. , Lichtman S. , Priyadarshi S. , Gardes J. , Zuckerman E. , Hamlin P. , Tew W. , Kelly E. , Abou-Alfa G. K. , Lachs M.
Published: April 2020

18519

Background: As the population ages, there is an emerging need to develop a geriatric assessment (GA) tool for oncologists to characterize the ‘functional age‘ of older patients in order to tailor treatment, stratify outcomes by factors other than chronological age, and develop interventions to optimize cancer treatment. The GA tool must be easy to administer in order to minimize burden on clinic resources. The goal of this study was to determine the feasibility of administering a brief, comprehensive, self-administered GA tool to older patients before their meeting with the oncologist. Methods: The self-administered GA tool addresses the following domains: functional status, comorbidity, psychological state, nutritional status, and social support. The measures which comprise the tool are brief, reliable, validated, predictive of mortality and morbidity in older patients, and do not require a staff member to administer. Feasibility was assessed by the following parameters: 1) % able to complete the GA tool unassisted; 2) % requiring the assistance of staff members versus non-staff members; 3) overall patient satisfaction; 4) time to complete. Results: 168 (96%) of 175 patients completed the GA tool with a mean age of 76 (range 64–92) with AJCC stages [I (33%), II (17%), III (10%), IV (39%)] across a variety of tumor types. Of the study cohort, 67% were women, 57% were married, and 89% were retired. Median time to complete the GA tool was 13 minutes and mean time was 16 minutes (SD 11, range 3–60). Most completed the GA tool on their own (75%) or received assistance from a friend or family member (20%). Only 4% required assistance from a member of the healthcare team. Patient satisfaction with the GA tool was high: 88% satisfied with the length, 92% reported no difficult questions, and 97% reported no upsetting questions. Based on the assessment scores, the following interventions were offered: referral to a social worker (38%), nutritionist (43%), visiting nurse/home health aide (30%), internist (23%), rehabilitation (13%), ENT (13%), ophthalmology (7%), and psychiatry (5%). Conclusion: This brief, comprehensive, self-administered GA tool is feasible for use in the outpatient oncology setting. Prospective trials are needed to determine the effectiveness of the interventions offered.

No significant financial relationships to disclose.
Willingness to be informed during treatment among cancer patients?
Authors: Gravis G. , Protiere C. , Tarpin C. , Viret F. , Aurran T. , Mohty M. , Viens P.
Published: April 2020

18522

Background: More than ever the question of patient’s information remains a matter of debate. Some consider information as a risk of anxiety, others see it as a way of patient implication in the treatment and allowing a better patient-physician relationship. Does the model of informed, empowered patient valid in European institution? To assess the impact, in term of anxiety, quality of life (QoL) and satisfaction, of a change in usual practice by proposing a specific structured and organized file (SSOF) including all medical information in real time. Methods: To evaluate this practice change, patients (breast or colon cancer and lymphoma) who have accepted to participate have been randomized between an “access” to the SSOF arm and a “non access” arm. The patients after being randomized in the “access” arm have had the choice to hold, or not, the SSOF. To help the patient, SSOF contains a lexical and a designed trained person was available. Anxiety (state-trait anxiety scale), Qol (EORTC QLQ-C30) and satisfaction were assessed at baseline, during and at the end of the treatment. Moreover, impact of this change was also assessed among the patients’ nurse, general practitioner and referent physician in our institution. Results: Among the 277 eligible patients, only 12 (4%) have refused to participate in the study. 134 have been randomized in the “non-access” arm and 131 in the “access” arm. A counter intuitive result was that no one of these 131 patients has refused to hold the SSOF. No statistical difference in baseline scores of QoL and anxiety scores between the two arms was observed at the time of randomization. Conclusions: First observation is that when you give the opportunity to hold an extended information all patients want to benefit from, even in French European institution.

No significant financial relationships to disclose.
Fatigue in breast cancer patients during and after radiotherapy
Authors: Rucinska M. , Langkjer S. T.
Published: April 2020

18537

Background: Fatigue—an unpleasant sensation of tiredness, weakness or lack of energy—is one of the most prevalent and profound symptoms caused by malignancy itself and anti-neoplastic treatment. The aim of the study was to assess the level of fatigue during and after adjuvant postoperative radiotherapy of breast cancer patients. Methods: 125 patients with breast cancer were recruited between May 2004 and September 2005 (85 after breast-conserving surgery and 40 after mastectomy). Subjective feeling of fatigue intensity was measured according to 10-score visual analog scale (VAS) before the start and once a week during radiotherapy, 14 days and 3 months after radiotherapy (48 Gy/24 fractions/5 weeks; 25 patients received boost 10 Gy/5 fractions/1 week with tumor-bed). Results: 46% of patients demonstrated non-fatigue before the start of radiotherapy. Patients after breast-conserving surgery and chemotherapy manifested higher lever of fatigue in comparison with patients after lumpectomy but without chemotherapy and patients after mastectomy with and without chemotherapy (p = 0.01). Fatigue intensity increased gradually during radiotherapy (mean fatigue-VAS before and in the last week of treatment was 1.8, 2.75 after lumpectomy and 1.25, 2.95 after mastectomy, respectively). 14 days after the end of radiotherapy fatigue intensity was still higher than before treatment (p = 0.04), but 3 months later it was lower than the pretreatment level. However, 25% of the patients defined their fatigue as 2 or more in VAS three months after radiotherapy. 15% of patients reported non-fatigue during radiotherapy. Older patients (>60 years) estimated their fatigue in the last week of treatment on lower level than younger patients (2.22 vs 2.90, p = 0.065). Patients with boost manifested only a little higher fatigue level in comparison with other patients (2.97 vs 2.52). Conclusions: Increasing fatigue was found in 85% of breast cancer patients during adjuvant radiotherapy. Three months after the end of therapy fatigue was reduced to lover then the preliminary level. There were no significant differences between patients after breast-conserving surgery and mastectomy.

No significant financial relationships to disclose.
Effectiveness,safety and tolerability of codeine in cancer patients
Authors: Moura G. L. , Giublin M. , Albini L. , Pasquini R. , Viana K. , Chicoski F.
Published: April 2020

18577

Background: In 1984 WHO guidelines for cancer pain was proposed. Codeine was selected among several others drugs when pain ladder step II was required. Since then very few comparative studies have been performed. Codein is a weak opioid and its analgesic action is not completely understood. A possible conversion into morphine is postulated. To determine efficacy, safety and tolerability of codein in advanced cancer patient we designed a prospective cohort study. Methods 150 metastatic cancer patients were studied during six months. A standard zero to then table scale for pain rating was used. The malignacies were: prostate 15 (10%), breast 42 (28%), lung 33 (22%), colon 37 (24.6%), other cancer 23 (15.3%). 62 patients were under treatment (41.3%). Results: There were: 83 M (55.3%) 67 F(44,7%) and the mean age was 62 years. Mean initial and final pain score were 7.1 and 1.3 respectively. Codein dose range from 30 mg/day to 270 mg/day (mean dose 180 mg/day). The average time of use was 13,7 months. Severe toxicity was 0% and the most often side effect was constipation (38.7%). Adjuvant drugs were used in 97 patients (64.7%) of patients. Uncontrolled pain ocurred in 17 patients (11.3%). Conclusions: During the last decade a great increase in the range of opioid agents and formulations available have emerged. Codein still represents an excellent drug for patients with long life expectancy. Side effects are manageable and are mainly constipation. Pain control was achieved in the majority of patients. Codein showed a low toxicity profile with a high compliance rate. Economic reasons must be strongly consider in poor countries and codein represents a good alternative option. Future comparative studies addressing also quality of life should be performed.

No significant financial relationships to disclose.
Identifying low-risk febrile neutropenic cancer patients in the West of Scotland
Authors: Drew Y. C. , Appleton R. , Jordan R. , White J. , Paul J.
Published: April 2020

18592

Background: Febrile neutropenia (FN) is a potentially life threatening complication of chemotherapy. In-patient treatment using intravenous antibiotics reduces FN related mortality. However, most patients with FN are at low risk of complication. Identifying them could result in new strategies such as out-patient, oral antibiotic, based treatment resulting in improved quality of life and cost savings. The Multinational Association for Supportive Care in Cancer (MASCC) and the Talcott model were developed to identify such patients. Two randomised controlled trials have shown that oral antibiotics in low risk patients are safe and effective. However are such models appropriate in populations with a high incidence of co-morbidity such as the West of Scotland? This study reviews FN admissions to our cancer centre to determine the proportion of patients that would fall into a low risk group according to the MASCC and/or Talcott models and to identify other factors that might predict for low risk. Methods: Review of FN admissions between June–December 2002. Data included: patient demographics, MASCC score, Talcott group, co-morbidity, haematological and biochemical values, prior use of antibiotics and growth factors (GFs) and whether the fever resolved without serious medical complication (FRWMC). Results: 77 episodes of FN involving 68 patients. Mean age = 51 (range 16–79). 94% involved patients with solid malignancies. Commonest tumour type was breast (29%). Patients were classified as MASCC and Talcott low risk in 52% and 31% of episodes respectively. There was a significant association between low risk MASCC score and low risk Talcott score (χ2 28.665, d.f.3, p < 0.001). Low risk MASCC was associated with FRWMC (χ2 4.193, d.f.1, p < 0.05). Multiple logistic regression of risk factors showed that high bilirubin and low albumin were associated with a worse outcome. FN mortality rate was 7.8%. Conclusions: The use of clinical risk models to identify low risk patients can predict for an uncomplicated recovery in our patients. Bilirubin and albumin values at presentation added predicted value for low risk over and above the MASCC model. Future trials may validate this observation.

No significant financial relationships to disclose.