Comparative effectiveness of interventions for cancer treatment-related cognitive impairment in adult cancer survivors: protocol for a systematic review.

BACKGROUND: Cancer treatment-related cognitive impairment (CTRCI) can substantially reduce the quality of life of cancer survivors. Many treatments of CTRCI have been evaluated in randomized controlled trials (RCTs), including psychological interventions, pharmacologic interventions, and other therapies. There is a pressing need to establish the benefits and harms of previously studied CTRCI treatments. The proposed systematic review and network meta-analyses will assess the relative efficacy and safety of competing interventions for the management of CTRCI. METHODS: In consultation with the review team, an experienced medical information specialist will draft electronic search strategies for MEDLINE®, Embase, CINAHL, PsycINFO, and the Cochrane Trials Registry. We will seek RCTs of interventions for the treatment of CTRCI in adults with any cancer, except cancers/metastases of the central nervous system. Due to the anticipated high search yields, dual independent screening of citations will be expedited by use of an artificial intelligence/machine learning tool. The co-primary outcomes of interest will be subjective and objective cognitive function. Secondary outcomes of interest will include measures of quality of life, mental and physical health symptoms, adherence to treatment, and harms (overall and treatment-related harms and harms associated with study withdrawal), where feasible, random-effects meta-analyses and network meta-analyses will be pursued. We will address the anticipated high clinical and methodological heterogeneity through meta-regressions, subgroup analyses, and/or sensitivity analyses. DISCUSSION: The proposed systematic review will deliver a robust comparative evaluation of the efficacy and safety of existing therapies for the management of CTRCI. These findings will inform clinical decisions, identify evidence gaps, and identify promising therapies for future evaluation in RCTs.

Quality assessment of cancer patient education materials: the current state of systemic therapy patient education in fourteen cancer centres across Ontario, Canada.

PURPOSE: Most patients diagnosed with cancer are administered systemic therapy and these patients are counselled and given printed education (PE) materials. High rates of low health literacy highlight the need to evaluate the quality of these PE materials. METHODS: A current state assessment of the quality of PE materials was conducted in Ontario, Canada. Patient education leaders from 14 cancer centres submitted print materials on the topic of systemic cancer therapy to the assessment team. To report adherence to PE quality and health literacy best practices, the following validated measures were used: readability (FRY, SMOG and Flesch Reading Ease), understandability and actionability (Patient Education Materials Assessment Tool (PEMAT)). Materials at grade level 6 or lower and with PEMAT scores greater than 80% were considered to meet health literacy best practices. RESULTS: A total of 1146 materials were submitted; 366 met inclusion criteria and 83 were selected for assessment. Most materials scored below the 80% target for understandability (x̄ = 73%, 31-100%) and actionability (x̄ = 68%, 20-100%), and above the recommended grade 6 readability level (x̄ = grade 9) meaning that the majority did not meet quality standards or best practices. CONCLUSION: Results suggest that there is significant opportunity to improve the quality of PE materials distributed by cancer centres. The quality of PE materials is a critical safety and equity consideration when these materials convey important safety and self-care directives.

Analytic and numerical solutions to the seismic wave equation in continuous media.

This paper presents two approaches to mathematical modelling of a synthetic seismic pulse, and a comparison between them. First, a new analytical model is developed in two-dimensional Cartesian coordinates. Combined with an initial condition of sufficient symmetry, this provides a valuable check for the validity of the numerical method that follows. A particular initial condition is found which allows for a new closed-form solution. A numerical scheme is then presented which combines a spectral (Fourier) representation for displacement components and wave-speed parameters, a fourth-order Runge-Kutta integration method, and an absorbing boundary layer. The resulting large system of differential equations is solved in parallel on suitable enhanced performance desktop hardware in a new software implementation. This provides an alternative approach to forward modelling of waves within isotropic media which is efficient, and tailored to rapid and flexible developments in modelling seismic structure, for example, shallow depth environmental applications. Visual comparisons of the analytic solution and the numerical scheme are presented.

Guidelines for day-case surgery 2019: Guidelines from the Association of Anaesthetists and the British Association of Day Surgery.

Guidelines are presented for the organisational and clinical management of anaesthesia for day-case surgery in adults and children. The advice presented is based on previously published recommendations, clinical studies and expert opinion.

Evaluation of a multidisciplinary burn care journal club: Lessons learned.

BACKGROUND: Journal clubs allow discussion of the quality and findings of recent publications. However, journal clubs have not historically been multidisciplinary. Burn care is recognized as a true collaborative care model, including regular multidisciplinary rounds. Since 2011 we have offered a multidisciplinary burn journal club at our institution. We present an evaluation of the factors that have made the sessions successful to facilitate others to commence their own club. METHODS: At the end of each journal club session participants anonymously completed a structured evaluation. Five-point scales were used to evaluate understanding, meeting objectives, presentation and appropriateness of information. Qualitative questions were asked to identify beneficial factors, suggestions for improvements, ideas for future sessions and feedback for the facilitator. RESULTS: Attendance grew from six to a maximum of 19. Members included physicians, nurses, dieticians, physiotherapists, occupational therapists, social workers, basic scientists and students. Presentations were undertaken by all of these disciplines. Ratings improved steadily over time. Understanding increased from a score of 4.5 to 4.8; meeting objectives from 4 to 4.9; satisfaction with method of presentation from 4.3 to 4.9 and with level of information from 3 to 4.9. CONCLUSIONS: Over time, the journal club has evolved to better meet the needs of our team. Successful multidisciplinary journal club implementation requires identification of champions and ongoing evaluation. APPLICABILITY OF RESEARCH TO PRACTICE: The success of the journal club has been possible through the engagement of the entire burn team. Champions within each discipline, facilitated discussion and evaluation tools have helped nurture a nonthreatening team based learning environment.

A comparison of cup-to-disc ratio estimates by fundus biomicroscopy and stereoscopic optic disc photography in the Tema Eye Survey.

PurposeTo determine if there are systematic differences in cup-to-disc ratio (CDR) grading using fundus biomicroscopy compared to stereoscopic disc photograph reading.MethodsThe vertical cup-to-disc ratio (VCDR) and horizontal cup-to-disc ratio (HCDR) of 2200 eyes (testing set) were graded by glaucoma subspecialists through fundus biomicroscopy and by a reading center using stereoscopic disc photos. For validation, the glaucoma experts also estimated VCDR and HCDR using stereoscopic disc photos in a subset of 505 eyes that they had assessed biomicroscopically. Agreement between grading methods was assessed with Bland-Altman plots.ResultsIn both sets, photo reading tended to yield small CDRs marginally larger, but read large CDRs marginally smaller than fundus biomicroscopy. The mean differences in VCDR and HCDR were 0.006±0.18 and 0.05±0.18 (testing set), and -0.053±0.23 and -0.028±0.21 (validation set), respectively. The limits of agreement were ~0.4, which is twice as large as the cutoff of clinically significant CDR difference between methods. CDR estimates differed by 0.2 or more in 33.8-48.7% between methods.ConclusionsThe differences in CDR estimates between fundus biomicroscopy and stereoscopic optic disc photo reading showed a wide variation, and reached clinically significance threshold in a large proportion of patients, suggesting a poor agreement. Thus, glaucoma should be monitored by comparing baseline and subsequent CDR estimates using the same method rather than comparing photographs to fundus biomicroscopy.

Promoting early presentation of breast cancer in women over 70 years old in general practice.

BACKGROUND: Delay in presentation contributes to poorer survival of older women with breast cancer. Research has shown the effectiveness of the promoting early presentation (PEP) intervention when delivered by radiographers in the NHS Breast Screening Programme. This paper investigates the effectiveness of the intervention when delivered by practice nurses in general practice. METHODS: The Breast Cancer Awareness Measure was used to compare participants' awareness of breast cancer before, 1 month after and 12 months after the delivery of the PEP intervention. Five hundred and fifty-six women aged over 70 years took part, 308 of whom returned all three surveys. RESULTS: The intervention was associated with increased awareness of non-lump breast symptoms and reported breast check frequency. There was a marked increase in breast cancer awareness which persisted for 12 months. Less than 5% of women were classified as 'breast cancer aware' before the intervention, rising to over 25% 1 month afterwards. This percentage dropped slightly after 1 year to just below 20%. CONCLUSION: Delivery of the PEP intervention in general practice was very effective at raising the awareness of breast cancer among older women. Primary care settings are well placed to enhance the reach of this kind of intervention to at-risk women.

Cancer symptom awareness and barriers to symptomatic presentation in England--are we clear on cancer?

BACKGROUND: Low cancer awareness may contribute to delayed diagnosis and poor cancer survival. We aimed to quantify socio-demographic differences in cancer symptom awareness and barriers to symptomatic presentation in the English population. METHODS: Using a uniquely large data set (n=49 270), we examined the association of cancer symptom awareness and barriers to presentation with age, gender, marital status and socio-economic position (SEP), using logistic regression models to control for confounders. RESULTS: The youngest and oldest, the single and participants with the lowest SEP recognised the fewest cancer symptoms, and reported most barriers to presentation. Recognition of nine common cancer symptoms was significantly lower, and embarrassment, fear and difficulties in arranging transport to the doctor's surgery were significantly more common in participants living in the most deprived areas than in the most affluent areas. Women were significantly more likely than men to both recognise common cancer symptoms and to report barriers. Women were much more likely compared with men to report that fear would put them off from going to the doctor. CONCLUSIONS: Large and robust socio-demographic differences in recognition of some cancer symptoms, and perception of some barriers to presentation, highlight the need for targeted campaigns to encourage early presentation and improve cancer outcomes.

Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray.

In areas without newborn screening for severe combined immunodeficiency (SCID), disease-defining infections may lead to diagnosis, and in some cases, may not be identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired rubella infections at 13 months of age. Immunological evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, the presence of CD8(+) T cells, poor lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom-designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the IL7R gene. Mosaicism for wild-type allele (20-30%) was detected in pretransplant blood and buccal DNA and maternal engraftment (5-10%) demonstrated in pretransplant blood DNA. This may be responsible for the patient's unusual immunological phenotype compared to classical interleukin (IL)-7Rα deficiency. Disseminated VZV was controlled with anti-viral and immune-based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T cell receptor excision circle (TREC) analyses completed on neonatal Guthrie cards identified absent TREC. This case emphasizes the danger of live viral vaccination in severe combined immunodeficiency (SCID) patients and the importance of newborn screening to identify patients prior to high-risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic aetiology for SCID patients.

Risk factors for delay in symptomatic presentation: a survey of cancer patients.

BACKGROUND: Delay in symptomatic presentation leading to advanced stage at diagnosis may contribute to poor cancer survival. To inform public health approaches to promoting early symptomatic presentation, we aimed to identify risk factors for delay in presentation across several cancers. METHODS: We surveyed 2371 patients with 15 cancers about nature and duration of symptoms using a postal questionnaire. We calculated relative risks for delay in presentation (time from symptom onset to first presentation >3 months) by cancer, symptoms leading to diagnosis and reasons for putting off going to the doctor, controlling for age, sex and deprivation group. RESULTS: Among 1999 cancer patients reporting symptoms, 21% delayed presentation for >3 months. Delay was associated with greater socioeconomic deprivation but not age or sex. Patients with prostate (44%) and rectal cancer (37%) were most likely to delay and patients with breast cancer least likely to delay (8%). Urinary difficulties, change of bowel habit, systemic symptoms (fatigue, weight loss and loss of appetite) and skin symptoms were all common and associated with delay. Overall, patients with bleeding symptoms were no more likely to delay presentation than patients who did not have bleeding symptoms. However, within the group of patients with bleeding symptoms, there were significant differences in risk of delay by source of bleeding: 35% of patients with rectal bleeding delayed presentation, but only 9% of patients with urinary bleeding. A lump was a common symptom but not associated with delay in presentation. Twenty-eight percent had not recognised their symptoms as serious and this was associated with a doubling in risk of delay. Embarrassment, worry about what the doctor might find, being too busy to go to the doctor and worry about wasting the doctor's time were also strong risk factors for delay, but were much less commonly reported (<6%). INTERPRETATION: Approaches to promote early presentation should aim to increase awareness of the significance of cancer symptoms and should be designed to work for people of the lowest socioeconomic status. In particular, awareness that rectal bleeding is a possible symptom of cancer should be raised.

Recognition of cancer warning signs and anticipated delay in help-seeking in a population sample of adults in the UK.

BACKGROUND: Not recognising a symptom as suspicious is a common reason given by cancer patients for delayed help-seeking; but inevitably this is retrospective. We therefore investigated associations between recognition of warning signs for breast, colorectal and lung cancer and anticipated time to help-seeking for symptoms of each cancer. METHODS: Computer-assisted telephone interviews were conducted with a population-representative sample (N=6965) of UK adults age ≥ 50 years, using the Awareness and Beliefs about Cancer scale. Anticipated time to help-seeking for persistent cough, rectal bleeding and breast changes was categorised as >2 vs ≤ 2 weeks. Recognition of persistent cough, unexplained bleeding and unexplained lump as cancer warning signs was assessed (yes/no). Associations between recognition and help-seeking were examined for each symptom controlling for demographics and perceived ease of health-care access. RESULTS: For each symptom, the odds of waiting for >2 weeks were significantly increased in those who did not recognise the related warning sign: breast changes: OR=2.45, 95% CI 1.47-4.08; rectal bleeding: OR=1.77, 1.36-2.30; persistent cough: OR=1.30, 1.17-1.46, independent of demographics and health-care access. CONCLUSION: Recognition of warning signs was associated with anticipating faster help-seeking for potential symptoms of cancer. Strategies to improve recognition are likely to facilitate earlier diagnosis.

Differences in cancer awareness and beliefs between Australia, Canada, Denmark, Norway, Sweden and the UK (the International Cancer Benchmarking Partnership): do they contribute to differences in cancer survival?

BACKGROUND: There are wide international differences in 1-year cancer survival. The UK and Denmark perform poorly compared with other high-income countries with similar health care systems: Australia, Canada and Sweden have good cancer survival rates, Norway intermediate survival rates. The objective of this study was to examine the pattern of differences in cancer awareness and beliefs across these countries to identify where these might contribute to the pattern of survival. METHODS: We carried out a population-based telephone interview survey of 19079 men and women aged ≥ 50 years in Australia, Canada, Denmark, Norway, Sweden and the UK using the Awareness and Beliefs about Cancer measure. RESULTS: Awareness that the risk of cancer increased with age was lower in the UK (14%), Canada (13%) and Australia (16%) but was higher in Denmark (25%), Norway (29%) and Sweden (38%). Symptom awareness was no lower in the UK and Denmark than other countries. Perceived barriers to symptomatic presentation were highest in the UK, in particular being worried about wasting the doctor's time (UK 34%; Canada 21%; Australia 14%; Denmark 12%; Norway 11%; Sweden 9%). CONCLUSION: The UK had low awareness of age-related risk and the highest perceived barriers to symptomatic presentation, but symptom awareness in the UK did not differ from other countries. Denmark had higher awareness of age-related risk and few perceived barriers to symptomatic presentation. This suggests that other factors must be involved in explaining Denmark's poor survival rates. In the UK, interventions that address barriers to prompt presentation in primary care should be developed and evaluated.

Breast cancer awareness and barriers to symptomatic presentation among women from different ethnic groups in East London.

BACKGROUND: During 2001 to 2005, 1-year breast cancer survival was low in ethnically diverse East London. We hypothesised that this was due to low breast cancer awareness and barriers to symptomatic presentation, leading to late stage at diagnosis in women from ethnic minorities. We examined ethnic differences in breast cancer awareness and barriers to symptomatic presentation in East London. METHODS: We carried out a population-based survey of 1515 women aged 30+ using the Cancer Research UK Breast Cancer Awareness Measure. We analysed the data using logistic regression adjusting for age group and level of deprivation. RESULTS: South Asian and black women had lower breast cancer awareness than white women. South Asian women, but not black women, reported more emotional barriers to seeking medical help than white women. White women were more likely than non-white women to report worry about wasting the doctor's time as a barrier to symptomatic presentation. CONCLUSION: Interventions to promote early presentation of breast cancer for South Asian and black women should promote knowledge of symptoms and skills to detect changes, and tackle emotional barriers to symptomatic presentation and for white women tackle the idea that going to the doctor to discuss a breast symptom will waste the doctor's time.

A promoting early presentation intervention increases breast cancer awareness in older women after 2 years: a randomised controlled trial.

BACKGROUND: We have developed the Promoting Early Presentation (PEP) Intervention to equip older women with the knowledge, skills, confidence and motivation to present promptly with breast symptoms, and thereby improve survival from breast cancer. The PEP Intervention consists of a 10-min interaction between a radiographer and an older woman, supported by a booklet. Our previous report showed that at 1 year, the PEP intervention increased the proportion who were breast cancer aware compared with usual care. METHODS: We randomised 867 women aged 67-70 years attending for their final routine appointment on the National Health Service Breast Screening Programme to receive the PEP Intervention, a booklet alone or usual care. The primary outcome was breast cancer awareness measured using a validated questionnaire asking about knowledge of breast cancer symptoms, knowledge that the risk of breast cancer increases with age and breast checking behaviour. RESULTS: At 2 years, the PEP Intervention increased the proportion who were breast cancer aware compared with usual care (21 vs 6%; odds ratio 8.1, 95% confidence interval 2.7-25.0). CONCLUSIONS: The uniquely large and sustained effect of the PEP Intervention on breast cancer awareness increases the likelihood that a woman will present promptly should she develop breast cancer symptoms up to many years later.

Dyskeratosis congenita: a combined immunodeficiency with broad clinical spectrum--a single-center pediatric experience.

BACKGROUND: Dyskeratosis Congenita (DKC) is a syndrome characterized by immunodeficiency, bone marrow failure, somatic abnormalities, and cancer predisposition resulting from defective telomere maintenance. The immunologic features of DKC remain under diagnosed and under treated despite the fact that immunodeficiency is a major cause of premature mortality in DKC. METHODS: This study undertook a retrospective review of 7 DKC patients diagnosed at the Children's Hospital of Philadelphia. In parallel, we reviewed previously reported immunologic findings in DKC patients. RESULTS: Immunologic abnormalities (lymphopenia, low B-cell numbers, hypogammaglobulinemia, and decreased T-cell function) were the most frequent laboratory findings at initial presentation, preceding the development of significant anemia or thrombocytopenia. Recurrent sinopulmonary or opportunistic infections were present in 6/7 patients. Infant-onset patients had more severe immunologic and somatic features (particularly severe enteropathy). CONCLUSION: In DKC, development of immunologic abnormalities can precede bone marrow failure, highlighting the importance of proper immunodeficiency management to minimize morbidity and premature mortality in this disease.

SP-D and regulation of the pulmonary innate immune system in allergic airway changes.

The airway mucosal surfaces are constantly exposed to inhaled particles that can be potentially toxic, infectious or allergenic and should elicit inflammatory changes. The proximal and distal air spaces, however, are normally infection and inflammation free due to a specialized interplay between cellular and molecular components of the pulmonary innate immune system. Surfactant protein D (SP-D) is an epithelial-cell-derived immune modulator that belongs to the small family of structurally related Ca(2+)-dependent C-type collagen-like lectins. While collectins can be detected in mucosal surfaces of various organs, SP-A and SP-D (the 'lung collectins') are constitutively expressed in the lung at high concentrations. Both proteins are considered important players of the pulmonary immune responses. Under normal conditions however, SP-A-/- mice display no pathological features in the lung. SP-D-/- mice, on the other hand, show chronic inflammatory alterations indicating a special importance of this molecule in regulating immune homeostasis and the function of the innate immune cells. Recent studies in our laboratory and others implied significant associations between changes in SP-D levels and the presence of airway inflammation both in animal models and patients raising a potential usefulness of this molecule as a disease biomarker. Research on wild-type and mutant recombinant molecules in vivo and in vitro showed that SP-D binds carbohydrates, lipids and nucleic acids with a broad spectrum specificity and initiates phagocytosis of inhaled pathogens as well as apoptotic cells. Investigations on gene-deficient and conditional over expressor mice in addition, provided evidence that SP-D directly modulates macrophage and dendritic cell function as well as T cell-dependent inflammatory events. Thus, SP-D has a unique, dual functional capacity to induce pathogen elimination on the one hand and control of pro-inflammatory mechanisms on the other, suggesting a potential suitability for therapeutic prevention and treatment of chronic airway inflammation without compromising the host defence function of the airways. This paper will review recent findings on the mechanisms of immune-protective function of SP-D in the lung.

Interventions to promote cancer awareness and early presentation: systematic review.

BACKGROUND: Low cancer awareness contributes to delay in presentation for cancer symptoms and may lead to delay in cancer diagnosis. The aim of this study was to review the evidence for the effectiveness of interventions to raise cancer awareness and promote early presentation in cancer to inform policy and future research. METHODS: We searched bibliographic databases and reference lists for randomised controlled trials of interventions delivered to individuals, and controlled or uncontrolled studies of interventions delivered to communities. RESULTS: We found some evidence that interventions delivered to individuals modestly increase cancer awareness in the short term and insufficient evidence that they promote early presentation. We found limited evidence that public education campaigns reduce stage at presentation of breast cancer, malignant melanoma and retinoblastoma. CONCLUSIONS: Interventions delivered to individuals may increase cancer awareness. Interventions delivered to communities may promote cancer awareness and early presentation, although the evidence is limited.

A randomised controlled trial of an intervention to promote early presentation of breast cancer in older women: effect on breast cancer awareness.

BACKGROUND: There is virtually no evidence for the effectiveness of interventions to promote early presentation in breast cancer. We aimed to test the efficacy of an intervention to equip older women with the knowledge, skills, confidence and motivation to detect symptoms and seek help promptly, with the aim of promoting early presentation with breast cancer symptoms. METHODS: We randomised 867 women aged 67-70 years attending for their final routine appointment on the UK NHS Breast Screening Programme to receive: a scripted 10-min interaction with a radiographer plus a booklet, a booklet alone or usual care. The primary outcome was whether or not a woman was breast cancer aware based on knowledge of breast cancer symptoms and age-related risk, and reported breast checking. RESULTS: At 1 month, the intervention increased the proportion who were breast cancer aware compared with usual care (interaction arm: 32.8% vs 4.1%; odds ratio (OR): 24.0, 95% confidence interval (CI): 7.7-73.7; booklet arm: 12.7% vs 4.1%; OR: 4.4, 95% CI: 1.6-12.0). At 1 year, the effects of the interaction plus booklet, and the booklet, on breast cancer awareness were largely sustained, although the interaction plus booklet remained much more effective. CONCLUSIONS: An intervention to equip older women with the knowledge, skills, confidence and motivation to detect breast cancer symptoms and seek help promptly increases breast cancer awareness at 1 year. Future research will evaluate whether the intervention promotes early presentation and reduces breast cancer mortality.