What constitutes a "clinical trial"?: A survey of oncology professionals

<p>Abstract</p> <p>Background</p> <p>What constitutes a "clinical trial" is inconsistently defined in the medical literature. With an initiative by Cancer Care Ontario (CCO) to report institutional clinical trials activity across the province of Ontario, Canada, we sought to investigate the variability in the interpretation of the term by local oncology professionals.</p> <p>Methods</p> <p>A survey amongst the physicians and nurses at the Juravinski Cancer Centre at Hamilton Health Sciences, Ontario was conducted. The survey included 12 summaries of local clinical research studies, and respondents were asked which they believed represented a clinical trial. Subsequently, they were asked which of the same 12 studies they believed should be labeled as clinical trials when considering separate definitions provided by CCO and by the Ontario Cancer Research Network (OCRN).</p> <p>Results</p> <p>A total of 66 (54%) of 123 surveys were completed; 32/46 (70%) by physicians, 21/59 (36%) by primary care nurses, and 13/18 (72%) by clinical trial nurses. Without a standardized definition, all studies, 12/12, were considered to be clinical trials by at least 50% of respondents. When provided with the CCO definition only 6/12 studies were considered to be clinical trials by the majority of respondents, while with the OCRN definition it was 9/12 studies. Studies evaluating natural health products, non-traditional medical interventions, and non-randomized studies with standard interventions consistently ranked the lowest, regardless of the definition used.</p> <p>Conclusion</p> <p>Oncology professionals appear to have a broadly inclusive baseline definition of what constitutes a clinical trial. Establishing rigor and consistency in the definition of a clinical trial is important for any program, institutional or jurisdictional based comparisons of clinical trials activity, especially when used as a quality indicator of patient care.</p

Quantification of structural changes in the corpus callosumin children with profound hypoxic-ischaemic brain injury

Background Birth-related acute profound hypoxic–ischaemic brain injury has specific patterns of damage including the paracentral lobules. Objective To test the hypothesis that there is anatomically coherent regional volume loss of the corpus callosum as a result of this hemispheric abnormality. Materials and methods Study subjects included 13 children with proven acute profound hypoxic–ischaemic brain injury and 13 children with developmental delay but no brain abnormalities. A computerised system divided the corpus callosum into 100 segments, measuring each width. Principal component analysis grouped the widths into contiguous anatomical regions. We conducted analysis of variance of corpus callosum widths as well as support vector machine stratification into patient groups. Results There was statistically significant narrowing of the mid–posterior body and genu of the corpus callosum in children with hypoxic–ischaemic brain injury. Support vector machine analysis yielded over 95% accuracy in patient group stratification using the corpus callosum centile widths. Conclusion Focal volume loss is seen in the corpus callosum of children with hypoxic–ischaemic brain injury secondary to loss of commissural fibres arising in the paracentral lobules. Support vector machine stratification into the hypoxic–ischaemic brain injury group or the control group on the basis of corpus callosum width is highly accurate and points towards rapid clinical translation of this technique as a potential biomarker of hypoxic–ischaemic brain injur

Cell migration leads to spatially distinct but clonally related airway cancer precursors

Background Squamous cell carcinoma of the lung is a common cancer with 95% mortality at 5 years. These cancers arise from preinvasive lesions, which have a natural history of development progressing through increasing severity of dysplasia to carcinoma in situ (CIS), and in some cases, ending in transformation to invasive carcinoma. Synchronous preinvasive lesions identified at autopsy have been previously shown to be clonally related. Methods Using autofluorescence bronchoscopy that allows visual observation of preinvasive lesions within the upper airways, together with molecular profiling of biopsies using gene sequencing and loss-of-heterozygosity analysis from both preinvasive lesions and from intervening normal tissue, we have monitored individual lesions longitudinally and documented their visual, histological and molecular relationship. Results We demonstrate that rather than forming a contiguous field of abnormal tissue, clonal CIS lesions can develop at multiple anatomically discrete sites over time. Further, we demonstrate that patients with CIS in the trachea have invariably had previous lesions that have migrated proximally, and in one case, into the other lung over a period of 12 years. Conclusions Molecular information from these unique biopsies provides for the first time evidence that field cancerisation of the upper airways can occur through cell migration rather than via local contiguous cellular expansion as previously thought. Our findings urge a clinical strategy of ablating high-grade premalignant airway lesions with subsequent attentive surveillance for recurrence in the bronchial tree

Place of death in patients with lung cancer: a retrospective cohort study from 2004-2013

Introduction: Many patients with cancer die in an acute hospital bed, which has been frequently identified as the least preferred location, with psychological and financial implications. This study looks at place and cause of death in patients with lung cancer and identifies which factors are associated with dying in an acute hospital bed versus at home. Methods and Findings: We used the National Lung Cancer Audit linked to Hospital Episode Statistics and Office for National Statistics data to determine cause and place of death in those with lung cancer; both overall and by cancer Network. We used multivariate logistic regression to compare features of those who died in an acute hospital versus those who died at home. Results: Of 143627 patients identified 40% (57678) died in an acute hospital, 29% (41957) died at home and 17% (24108) died in a hospice. Individual factors associated with death in an acute hospital bed compared to home were male sex, increasing age, poor performance status, social deprivation and diagnosis via an emergency route. There was marked variation between cancer Networks in place of death. The proportion of patients dying in an acute hospital ranged from 28% to 48%, with variation most notable in provision of hospice care (9% versus 33%). Cause of death in the majority was lung cancer (86%), with other malignancies, chronic obstructive pulmonary disease (COPD) and ischaemic heart disease (IHD) comprising 9% collectively. Conclusions: A substantial proportion of patients with lung cancer die in acute hospital beds and this is more likely with increasing age, male sex, social deprivation and in those with poor performance status. There is marked variation between Networks, suggesting a need to improve end-of-life planning in those at greatest risk, and to review the allocation of resources to provide more hospice beds, enhanced community support and ensure equal access

Mississippi River and Sea Surface Height Effects on Oil Slick Migration

Millions of barrels of oil escaped into the Gulf of Mexico (GoM) after the 20 April, 2010 explosion of Deepwater Horizon (DH). Ocean circulation models were used to forecast oil slick migration in the GoM, however such models do not explicitly treat the effects of secondary eddy-slopes or Mississippi River (MR) hydrodynamics. Here we report oil front migration that appears to be driven by sea surface level (SSL) slopes, and identify a previously unreported effect of the MR plume: under conditions of relatively high river discharge and weak winds, a freshwater mound can form around the MR Delta. We performed temporal oil slick position and altimeter analysis, employing both interpolated altimetry data and along-track measurements for coastal applications. The observed freshwater mound appears to have pushed the DH oil slick seaward from the Delta coastline. We provide a physical mechanism for this novel effect of the MR, using a two-layer pressure-driven flow model. Results show how SSL variations can drive a cross-slope migration of surface oil slicks that may reach velocities of order km/day, and confirm a lag time of order 5–10 days between mound formation and slick migration, as observed form the satellite analysis. Incorporating these effects into more complex ocean models will improve forecasts of slick migration for future spills. More generally, large SSL variations at the MR mouth may also affect the dispersal of freshwater, nutrients and sediment associated with the MR plume

Elimination of Active Trachoma after Two Topical Mass Treatments with Azithromycin 1.5% Eye Drops

Trachoma is the leading cause of infectious blindness worldwide, accounting for 1.3 million cases of blindness. Although it has disappeared in many regions of the world, trachoma is still endemic in Africa, Eastern Mediterranean, Latin America, Asia, and Australia. The WHO has currently set a target of 2020 for controlling trachoma to a low enough level that resulting blindness will not be a major public health concern. Topical tetracycline was for a long time the recommended treatment for active trachoma, but compliance to the regimen is extremely poor. Azithromycin has properties that make it an ideal treatment for Chlamydia trachomatis: high efficacy, intracellular accumulation, and a long tissue half-life. There is now a new mass treatment of trachoma by azithromycin 1.5% eye drops which is as effective as the oral route. In the test health district of Kolofata, Cameroon, the prevalence of trachoma among children dramatically decreased from 31% to less than 5% after 2 treatments. A third treatment was performed in January 2010. An epidemiological surveillance is implemented to see if this removal will be permanent. It also avoids misuse of oral azithromycin and the eye drops are directly treating the site of the infection

Association between the plasma/whole blood lead ratio and history of spontaneous abortion: a nested cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Blood lead has been associated with an elevated risk of miscarriage. The plasmatic fraction of lead represents the toxicologically active fraction of lead. Women with a tendency to have a higher plasma/whole blood Pb ratio could tend towards an elevated risk of miscarriage due to a higher plasma Pb for a given whole blood Pb and would consequently have a history of spontaneous abortion.</p> <p>Methods</p> <p>We studied 207 pregnant Mexico City residents during the 1^sttrimester of pregnancy, originally recruited for two cohorts between 1997 and 2004. Criteria for inclusion in this study were having had at least one previous pregnancy, and having valid plasma and blood Pb measurements. Pb was measured in whole blood and plasma by inductively coupled plasma mass spectrometry using ultra-clean techniques. History of miscarriage in previous pregnancies was obtained by interview. The incidence rate of spontaneous abortion was defined as the proportion of previous pregnancies that resulted in miscarriage. Data were analyzed by means of Poisson regression models featuring the incidence rate of spontaneous abortion as the outcome and continuous or categorized plasma/blood Pb ratios as predictor variables. All models were adjusted for age and schooling. Additionally, logistic regression models featuring inclusion in the study sample as the outcome were fitted to assess potential selection bias.</p> <p>Results</p> <p>The mean number of miscarriages was 0.42 (range 0 to 4); mean Pb concentrations were 62.4 and 0.14 μg/L in whole blood and plasma respectively. Mean plasma/blood Pb ratio was 0.22%. We estimated that a 0.1% increment in the plasma/blood Pb ratio lead was associated to a 12% greater incidence of spontaneous abortion (p = 0.02). Women in the upper tertile of the plasma/blood Pb ratio had twice the incidence rate of those in the lower tertile (p = 0.02). Conditional on recruitment cohort, inclusion in the study sample was unrelated to observable characteristics such as number of abortions, number of pregnancies, blood Pb levels, age schooling, weight and height.</p> <p>Conclusion</p> <p>Women with a large plasma/whole blood Pb ratio may be at higher risk of miscarriage, which could be due to a greater availability of placental barrier-crossing Pb.</p

A case-control study of mastitis: nasal carriage of Staphylococcus aureus

BACKGROUND: Mastitis is a common problem for breastfeeding women. Researchers have called for an investigation into the possible role of maternal nasal carriage of S. aureus in the causation of mastitis in breastfeeding women. METHODS: The aim of the study was to investigate the role of maternal S. aureus nasal carriage in mastitis. Other factors such as infant nasal S. aureus carriage, nipple damage, maternal fatigue and oversupply of milk were also investigated. A case-control design was used. Women with mastitis (cases, n = 100) were recruited from two maternity hospitals in Melbourne, Australia (emergency departments, breastfeeding clinics and postnatal wards). Breastfeeding women without mastitis (controls, n = 99) were recruited from maternal and child health (community) centres and the rooms of a private obstetrician. Women completed a questionnaire and nasal specimens were collected from mother and baby and placed in charcoal transport medium. Women also collected a small sample of milk in a sterile jar. RESULTS: There was no difference between nasal carriage of S. aureus in breastfeeding women with mastitis (42/98, 43%) and control women (45/98, 46%). However, significantly more infants of mothers with mastitis were nasal carriers of S. aureus (72/88, 82%) than controls (52/93, 56%). The association was strong (adjusted OR 3.23, 95%CI 1.30, 8.27) after adjustment for the following confounding factors: income, private health insurance, difficulty with breastfeeding, nipple damage and tight bra. There was also a strong association between nipple damage and mastitis (adjusted OR 9.34, 95%CI 2.99, 29.20). CONCLUSION: We found no association between maternal nasal carriage of S. aureus and mastitis, but nasal carriage in the infant was associated with breast infections. As in other studies of mastitis, we found a strong association between nipple damage and mastitis. Prevention of nipple damage is likely to reduce the incidence of infectious mastitis. Mothers need good advice about optimal attachment of the baby to the breast and access to skilled help in the early postpartum days and weeks

Acquiring a pet dog significantly reduces stress of primary carers for children with autism spectrum disorder: a prospective case control study

This study describes the impact of pet dogs on stress of primary carers of children with Autism Spectrum Disorder (ASD). Stress levels of 38 primary carers acquiring a dog and 24 controls not acquiring a dog were sampled at: Pre-intervention (17 weeks before acquiring a dog), post-intervention (3–10 weeks after acquisition) and follow-up (25–40 weeks after acquisition), using the Parenting Stress Index. Analysis revealed significant improvements in the intervention compared to the control group for Total Stress, Parental Distress and Difficult Child. A significant number of parents in the intervention group moved from clinically high to normal levels of Parental Distress. The results highlight the potential of pet dogs to reduce stress in primary carers of children with an ASD

Functional and neurometabolic asymmetry in SHR and WKY rats following vasoactive treatments

A lateralized distribution of neuropeptidase activities in the frontal cortex of normotensive and hypertensive rats has been described depending on the use of some vasoactive drugs and linked to certain mood disorders. Asymmetrical neuroperipheral connections involving neuropeptidases from the left or right hemisphere and aminopeptidases from the heart or plasma have been suggested to play a role in this asymmetry. We hypothesize that such asymmetries could be extended to the connection between the brain and physiologic parameters and metabolic factors from plasma and urine. To assess this hypothesis, we analyzed the possible correlation between neuropeptidases from the left and right frontal cortex with peripheral parameters in normotensive (Wistar Kyoto [WKY]) rats and hypertensive rats (spontaneously hypertensive rats [SHR]) untreated or treated with vasoactive drugs such as captopril, propranolol and L-nitro-arginine methyl ester. Neuropeptidase activities from the frontal cortex were analyzed fluorometrically using arylamide derivatives as substrates. Physiological parameters and metabolic factors from plasma and urine were determined using routine laboratory techniques. Vasoactive drug treatments differentially modified the asymmetrical neuroperipheral pattern by changing the predominance of the correlations between peripheral parameters and central neuropeptidase activities of the left and right frontal cortex. The response pattern also differed between SHR and WKY rats. These results support an asymmetric integrative function of the organism and suggest the possibility of a different neurometabolic response coupled to particular mood disorders, depending on the selected vasoactive drug.This work was supported by the Ministry of Science and Innovation through project no. SAF 2008 04685 C02 01