Tuberculosis surveillance and its discontents: the ethical paradox.

In June 2017, the World Health Organization issued the Guidelines on Ethical Issues in Public Health Surveillance. Using the frame of public health ethics, the guidance declared that countries have an affirmative duty to undertake surveillance and that the global community had an obligation to support those countries whose resources limited their capacity. The centrality of TB surveillance has long been recognized as a matter of public health practice and ethics. Nevertheless, contemporary global realities make clear that TB surveillance falls far short of the goal of uniform notification. It is this reality that necessitated the paradoxical turn to research studies that require informed consent and human subjects' ethical review, the very burdens that mandated notification were designed to overcome.

A multi-stop time-of-flight spectrometer for the measurement of positron annihilation-induced electrons in coincidence with the Doppler-shifted annihilation gamma photon.

In this study, we describe an advanced multi-functional, variable-energy positron beam system capable of measuring the energies of multiple "positron-induced" electrons in coincidence with the Doppler-shifted gamma photon resulting from the annihilation of the correlated positron. The measurements were carried out using the unique characteristics of the digital time-of-flight spectrometer and the gamma spectrometer available with the advanced positron beam system. These measurements have resulted in (i) the first digital time-of-flight spectrum of positron annihilation-induced Auger electrons generated using coincident signals from a high-purity Ge detector and a micro-channel plate, (ii) a two-dimensional array of the energy of Doppler-broadened annihilation gamma and the time-of-flight of positron-annihilation induced Auger electrons/secondary electrons measured in coincidence with the annihilation gamma photon, and (iii) the time-of-flight spectra of multiple secondary electrons ejected from a bilayer graphene surface as a result of the impact and/or annihilation of positrons. The novelty of the gamma-electron coincidence spectroscopy has been demonstrated by extracting the Doppler-broadened spectrum of gamma photons emitted due to the annihilation of positrons exclusively with 1s electrons of carbon. The width of the extracted Doppler-broadened gamma spectrum has been found to be consistent with the expected broadening of the annihilation gamma spectrum due to the momentum of the 1s electrons in carbon.

Rates of cannabis use in patients with cancer.

Background: A comprehensive assessment of cannabis use by patients with cancer has not previously been reported. In this study, we aimed to characterize patient perspectives about cannabis and its use. Methods: An anonymous survey about cannabis use was offered to patients 18 years of age and older attending 2 comprehensive and 2 community cancer centres, comprising an entire provincial health care jurisdiction in Canada (ethics id: hreba-17011). Results: Of 3138 surveys distributed, 2040 surveys were returned (65%), with 1987 being sufficiently complete for analysis (response rate: 63%). Of the respondents, 812 (41%) were less than 60 years of age; 45% identified as male, and 55% as female; and 44% had completed college or higher education.Of respondents overall, 43% reported any lifetime cannabis use. That finding was independent of age, sex, education level, and cancer histology. Cannabis was acquired through friends (80%), regulated medical dispensaries (10%), and other means (6%). Of patients with any use, 81% had used dried leaves.Of the 356 patients who reported cannabis use within the 6 months preceding the survey (18% of respondents with sufficiently complete surveys), 36% were new users. Their reasons for use included cancer-related pain (46%), nausea (34%), other cancer symptoms (31%), and non-cancer-related reasons (56%). Conclusions: The survey demonstrated that prior cannabis use was widespread among patients with cancer (43%). One in eight respondents identified at least 1 cancer-related symptom for which they were using cannabis.

Auger electron emission initiated by the creation of valence-band holes in graphene by positron annihilation.

Auger processes involving the filling of holes in the valence band are thought to make important contributions to the low-energy photoelectron and secondary electron spectrum from many solids. However, measurements of the energy spectrum and the efficiency with which electrons are emitted in this process remain elusive due to a large unrelated background resulting from primary beam-induced secondary electrons. Here, we report the direct measurement of the energy spectra of electrons emitted from single layer graphene as a result of the decay of deep holes in the valence band. These measurements were made possible by eliminating competing backgrounds by employing low-energy positrons (<1.25 eV) to create valence-band holes by annihilation. Our experimental results, supported by theoretical calculations, indicate that between 80 and 100% of the deep valence-band holes in graphene are filled via an Auger transition.

Comparative multidisciplinary prediction of survival in patients with advanced cancer.

PURPOSE: The expected survival of patients with metastatic cancer can significantly impact decisions regarding treatment, care setting, and future planning. We evaluated the prognostication ability of a multidisciplinary team (MDT) experienced in providing supportive care and palliative radiotherapy. METHODS: After clinical assessment of consecutive patients, survival predictions were independently made by each MDT member. Patient demographics, factors influencing predictions, and dates of death were collected. Clinical predictions of survival (CPS) were considered correct if within 30 days of actual survival (AS). Summary statistics and Kaplan-Meier estimates of overall survival were obtained. Correlations between actual and CPS were calculated using Spearman's correlation coefficient. Multivariate logistic regression analysis identified factors associated with prognostication accuracy. RESULTS: A total of 395 predictions (06/2010-07/2012) were made by eight disciplines. Average age was 68 years, 68.3 % of patients were male, and 48.4 % had lung cancer. Median AS was 87 days (95 % CI 66-102 days). Survival was over-estimated 72.4 % (286/395) of the time with r = 0.54 (p < 0.0001) for all predictions across all disciplines. In addition, 30.3 % (36/119) of radiation therapist (RTT) predictions were correct compared to 30.1 % (22/73) of nurses', 28.7 % (43/150) of physicians', and 15.1 % (8/53) of allied health (AH) providers. There were no differences in accuracy by discipline except for the RTT versus AH groups (p = 0.04). Factors most frequently cited as influencing correct predictions were Karnofsky performance status (KPS), extent of disease, and histology. KPS was the only significant variable on multivariate analysis (p ≤ 0.04). CONCLUSION: MDT members providing collaborative care for advanced cancer patients utilize similar factors in predicting survival with comparable accuracy.

Do results of the EORTC dummy run predict quality of radiotherapy delivered within multicentre clinical trials?

OBJECTIVE: The European Organisation for the Research and Treatment of Cancer (EORTC) Radiation Oncology Group (ROG) has performed radiotherapy quality assurance (QA) in clinical trials, including dummy runs (DR) and individual case reviews (ICR), since 1991. We investigated the influence of DR results on subsequent QA and patient outcomes. METHODS: EORTC ROG studies were reviewed for DR inclusion, QA and mature clinical outcomes. A DR was classified as a failure if corrections necessitated re-submission. ICR were graded as acceptable, minor or major deviation overall. Fisher's exact test characterised potential correlations and the Mantel-Haenszel statistic quantified pooled odds ratios (OR). RESULTS: DR and ICR data were available from 12 and 3 protocols, respectively. The proportion of institutions successful at first DR attempt varied per trial from 5.6% to 68.8%. Participants were 3.2 times more likely to pass at first attempt after previous DR participation (p=0.0002). Pooled OR for an acceptable ICR was 1.69 (p=0.06) for institutions successful at DR first attempt. The effect of DR participation was not significantly correlated with patient outcome in the trial available for analysis. CONCLUSIONS: Implementing QA measures in ROG clinical trials should ensure optimal radiotherapy delivery. Centres which previously participated in a DR were significantly more likely to be successful at subsequent QA procedures.

Development of clinical trial protocols involving advanced radiation therapy techniques: the European Organisation for Research and Treatment of Cancer Radiation Oncology Group approach.

The European Organisation for Research and Treatment of Cancer (EORTC) Master Protocol for phase III radiation therapy (RT) studies was published in 1995 to define in a consistent sequence the parameters which must be addressed when designing a phase III trial 'from the rationale to the references'. This was originally implemented to assist study investigators and writing committees, and to increase homogeneity within Radiation Oncology Group (ROG) study protocols. However, RT planning, delivery, treatment verification and quality assurance (QA) have evolved significantly over the last 15 years and clinical trial protocols must reflect these developments. The goal of this update is to describe the incorporation of these developments into the EORTC-ROG protocol template. Implementation of QA procedures for advanced RT trials is also briefly described as these essential elements must also be clearly articulated. This guide may assist both investigators participating in current ROG trials and others involved in writing an advanced RT trial protocol.

Optimizing pain relief in a specialized outpatient palliative radiotherapy clinic: contributions of a clinical pharmacist.

PURPOSE: Bone metastases are the most common cause of cancer pain, with palliative radiotherapy (RT) the mainstay of treatment. However, relief from RT may be delayed, incomplete, or short-lived and therefore optimized pharmacologic therapy is essential. Our objective was to describe the contribution of the clinical pharmacist (CP) to an outpatient palliative RT clinic. METHODS: The Edmonton Symptom Assessment System, an 11-point scale for measuring nine symptoms, and other validated screening tools were administered, and a medication history performed by the CP. Baseline CP assessment also included opioid toxicity, need for supportive medications, and drug interactions. Anonymized clinical information was collected prospectively and descriptive statistics were compiled including themes of counselling performed by the CP. RESULTS: The CP reviewed 114 patients over 140 clinic visits (01/2007-12/2008). Median age was 68.3 years, 68.4% were male and 36.8% had prostate cancer. All symptoms improved or stabilized in ≥ 80% by 4 weeks. Median pain score was 6/10 (SD 2.6) at baseline, and 2.1/10 (SD 2.4) by week 4. Average morphine equivalent daily dose was 76.8 mg at baseline and 44.5 mg at week 4. CP assessment included screening for opioid toxicity (87.9%), recommending a change in analgesic (28.9%), and liaison with the community pharmacy (17.1%). Medication counselling took place in 84.3% of visits, on bowel routine (85.6% of the time), opioids (82.2%), and hydration (40.7%). CONCLUSIONS: The CP plays a key role in holistic patient assessment and optimization of pharmacologic therapy, contributing to improved symptom control of patients receiving palliative RT.

Attitudes of Canadian radiation oncologists towards post-lumpectomy radiotherapy for elderly women with stage I hormone-responsive breast cancer.

AIMS: Post-lumpectomy breast radiation is the standard of care for all patient subgroups. However, elderly women with stage I breast cancer on adjuvant tamoxifen therapy have a 4% risk of local recurrence after lumpectomy without adjuvant breast radiation. The purpose of this study was to explore the attitudes of Canadian radiation oncologists who treat breast cancer with respect to their use of adjuvant post-lumpectomy radiotherapy, and their willingness to implement a decision aid for this patient population. MATERIALS AND METHODS: The questionnaire was mailed to 141 Canadian radiation oncologists who treat breast cancer. The respondents were asked to complete an online survey consisting of four parts: (1) demographic information; (2) factors determining post-lumpectomy radiation treatment decisions; (3) hypothetical case scenarios; (4) interest in using a decision aid in their practice. RESULTS: Among the 61 (43%) physicians who completed the survey, there was substantial response variation. After contraindications to radiotherapy, patient overall health and patient preference had the greatest influence on their decision to offer radiotherapy to this patient subgroup. Margin status and use of hormonal therapy were given less importance. For each of the case scenarios, 60-83% of physicians (depending on the case scenario) would offer the patient a choice; far fewer (12-57%) would be comfortable not irradiating. Sixty-four per cent of respondents welcomed the concept of a decision aid for this population. CONCLUSIONS: Although there is significant variation in practice patterns and attitudes among radiation oncologists regarding post-lumpectomy radiotherapy for elderly, low-risk breast cancer patients, the vast majority value patient choice and would be willing to use a decision aid designed for this population in their practice.

International variations in radiotherapy fractionation for bone metastases: geographic borders define practice patterns?

Although it may be argued that single fraction (SF) radiotherapy (RT) should be regarded as the standard palliative treatment for pain due to uncomplicated bone metastases, its widespread clinical use is still underexploited. In this chapter, the authors discuss a number of surveys investigating doctors and patients' preferences for palliative RT schedules, discuss the possible reasons for this phenomenon, and suggest potential strategies to increase the use of SF.

Dexamethasone for the prophylaxis of radiation-induced pain flare after palliative radiotherapy for symptomatic bone metastases: a phase II study.

AIMS: Pain flare occurs in over one-third of patients receiving palliative radiotherapy for bone metastases. A single dose of dexamethasone can decrease the incidence of pain flare during the first 2 days immediately after radiotherapy. We conducted a phase II prospective study to investigate the prophylactic role of prolonged dexamethasone. MATERIALS AND METHODS: Patients with bone metastases treated with a single 8Gy were prescribed 8mg dexamethasone just before palliative radiotherapy and for 3 consecutive days after treatment. Worst pain score and analgesic consumption data were collected at baseline and daily for 10 days after treatment. Analgesic consumption was converted into a total daily oral morphine equivalent dose in the analysis. Pain flare was defined (a priori) as a two-point increase in worst pain on an 11-point numeric rating scale compared with baseline with no decrease in analgesic intake, or a 25% increase in analgesic intake with no decrease in worst pain score. To distinguish pain flare from progressive disease, we required that the worst pain score and analgesic intake returned to baseline levels after the increase/flare. RESULTS: Forty-one patients were evaluable (32 men, nine women). Their median age was 67 years. The overall incidence of pain flare was 9/41 (22%) within 10 days after the completion of radiotherapy. Most (55%) of these pain flares occurred on day 5. Absence of pain flare was 34/41(83%) and 39/41 (95%) for days 1-5 and 6-10 after the completion of radiotherapy, respectively. CONCLUSION: Dexamethasone is effective in the prophylaxis of radiotherapy-induced pain flare after palliative radiotherapy for bone metastases. Randomised studies are needed to confirm this finding.

The rapid access palliative radiotherapy program: blueprint for initiation of a one-stop multidisciplinary bone metastases clinic.

GOALS OF WORK: Radiotherapy (RT) for palliation of pain due to bone metastases (BM) is effective but underutilized likely due to the traditional practice of separate clinic visits for consultation, treatment planning, and RT delivery. However, recent evidence proves one RT treatment is as effective as multiple for analgesia, enabling investigation of an alternative model of RT delivery, the rapid access palliative radiotherapy program (RAPRP). MATERIALS AND METHODS: Prior to the start of the program, needs assessment was performed to determine the composition of the optimal team. Screening tools were implemented to streamline holistic, multidisciplinary assessment. An advertising strategy, treatment and research protocols, and mechanisms for patient feedback were established. After RAPRP implementation, patient outcomes such as symptom relief were tracked. MAIN RESULTS: Eighty-six patients with painful BM were referred over the 25-week pilot. Median age was 69.9 years; 64% had prostate cancer, and median performance status was 70. Patient-rated pain was on average 6.1/10 at baseline, improving to 2.6/10 by week 4 post-RT. On average, 6.2 symptoms were reported (baseline) compared to 5.2 (week 4). Team members assessed 10-100% of patients and were successful in stabilizing or improving all symptoms in >75% contacted at week 4. One hundred percent of patients surveyed were satisfied with their experience. CONCLUSIONS: Early needs assessment was advantageous in determining the optimal team and methods of assessment for our 'one-stop' BM clinic. This approach was successful in improving pain and other symptoms, and the convenience of seeing multiple providers on 1 day was appreciated by the patients.

Effects of orally administered tetracycline on the intestinal community structure of chickens and on tet determinant carriage by commensal bacteria and Campylobacter jejuni.

There is a growing concern that antibiotic usage in animal production has selected for resistant food-borne bacteria. Since tetracyclines are common therapeutic antibiotics used in poultry production, we sought to evaluate the effects of oral administration on the resistance of poultry commensal bacteria and the intestinal bacterial community structure. The diversity indices calculated from terminal restriction fragment length polymorphism (T-RFLP) analysis of 16S rRNA amplicons did not indicate significant changes in the cecal bacterial community in response to oxytetracycline. To evaluate its effects on cultivable commensals, Enterococcus spp., Escherichia coli, and Campylobacter spp. were isolated from the cecal droppings of broiler chickens. Enterococcus spp. and E. coli expressed tetracycline MICs of >8 microg/ml and harbored a variety of tet resistance determinants regardless of the tetracycline exposure history of the birds. The enterococcal isolates possessed tetM (61%), tetL (25.4%), and tetK (1.3%), as well as tetO (52.5%), the determinant known to confer a tetracycline resistance phenotype in Campylobacter jejuni. E. coli isolates harbored tetA (32.2%) or tetB (30.5%). Tetracycline MICs remained at <2 microg/ml for Campylobacter isolates before and after tetracycline treatment of the chickens, even though isolates expressing MICs of >16 mug/ml were commonly cultured from flocks that did not receive oxytetracycline. The results imply that complex ecological and genetic factors contribute to the prevalence of antibiotic resistance arising from resistance gene transfer in the production environment.

The polio narratives: dialogues with FDR.

As a group of accounts that span the decades from the mid-1940s to the present, the published polio narratives enable us to align their shifting perceptions of disability with social, cultural, and technological change. This paper identifies two distinct groups of narratives. Authors of the first group, writing between the mid-1930s and mid-1950s--a period of relative prosperity, conformity, and homogeneity--were uncomfortable with radical movements, diversity, and conflict; their narratives typically told of either full or substantial recovery. Beginning in the mid-1950s--the period of both McCarthy and the Civil Rights movement--a second wave of narratives begins to tell stories of partial to serious disability; typically, they reflect on a lifetime of coping with chronic disability. Both sets of narratives, however, represent a dialogue with Franklin Delano Roosevelt. Roosevelt himself, journalists, and the National Foundation for Infantile Paralysis all helped to create and promote a core polio narrative featuring FDR's triumph over disease and disability that would become a national myth. Yet while the early narratives reinforced the core elements of the Roosevelt myth, the later ones began to challenge them.

The effect of mannanoligosaccharides, bambermycins, and virginiamycin on performance of large white male market turkeys.

A study was conducted to evaluate the effects of mannanoligosaccharides (MOS), bambermycins (BAM), and virginiamycin (VIR) on the growth performance of male turkeys. Hybrid Large White male poults were assigned to six dietary treatments: control, MOS, BAM, VIR, MOS+BAM (MB), and MOS+VIR (MV). All diets were formulated to meet NRC (1994) nutrient requirements. There were eight replicate floor pens per treatment with 20 birds per pen reared from 1 to 140 d. Body weight and feed conversion (FC) were collected at 3-wk intervals and at 20 wk of age. Mortality and culled birds were recorded daily. All treatments except MV significantly (P < 0.05) increased 20 wk BW. Body weight was increased at 12 wk by BAM, whereas VIR increased BW at Weeks 12 and 15. All treatments improved FC for Weeks 0 to 3, whereas VIR, MB, and MV improved FC for Weeks 0 to 12 and 0 to 18. There were no treatment effects on cumulative mortality or cull rate. Dietary supplemental MOS, BAM, and VIR resulted in improved growth performance of Large White turkeys. These results indicate that MOS may be utilized as an alternative to antibiotic growth promotants to improve turkey performance.

A novel delivery of oxytetracycline in turkey breeder hens.

A novel product (SQ12) for subcutaneous (SQ) injectable delivery of oxytetracycline (OTC) has been developed for use in livestock. SQ12 employs microfluidic spheres encasing OTC crystals, which allows for longer release of the OTC compared with other injectable antibiotics. The objectives of the study were to determine serum and tissue levels of SQ12 in turkey breeder hens to 14 days postinjection and to evaluate effects of SQ12 on reproductive status. Thirty photostimulated hens were housed in litter floor pens and provided with 14.5 hr of light per day in a curtain-sided facility. Six hens served as untreated controls. Twelve hens per treatment group received SQ injections in the neck with SQ12 at 11.4 (L dose group) or 22.7 mg/kg (H dose group) to assess low and high doses, respectively. Serum samples were obtained from each hen at predose and 6, 12, 24, 48, 72, 96, 168, 240, and 336 hr postinjection. All hens were euthanatized at 14 and 15 days postinjection. One-half of the hens in each treatment group were sampled (liver, lung, kidneys, and breast muscle) for tissue residue levels of OTC. The control group had no detectable OTC in serum or tissues at any sample collection time. There were no detectable serum levels of OTC in either treatment group prior to injection. The average serum concentrations of the L and H dose groups showed similar depletion curves although the H dose group was 42% higher at maximum concentration than the L group. Average tissue concentration of OTC for all tissues sampled from the H dose group was twice that of the L dose group. All tissue levels were below the OTC residue tolerance limit. SQ12 provided an extended source of OTC in serum of turkey breeder hens with no effect on reproductive status. SQ12 may provide for a novel treatment of bacterial infection in turkey breeder hens with longer lasting serum levels compared with other single injectable OTC products.

Effects of hen age, Bio-Mos, and Flavomycin on poult susceptibility to oral Escherichia coli challenge.

The effects of hen age, Escherichia coli, and dietary Bio-Mos and Flavomycin on poult performance from 1 to 21 d were studied. Day-of-hatch BUTA (BIG-6) male poults were gavaged orally (1 mL) with approximately 10(8) cfu/mL E. coli composed of four serotypes or sterile carrier broth. A mixture of the same E. coli cultures was added to the poults' water troughs to attain a concentration of approximately 10(6) cfu/mL on a weekly basis to ensure a continuous bacterial challenge. Within each E. coli split plot treatment group, poults from hens of different ages (33 and 58 wk of age) were fed diets containing Bio-Mos (1 g/kg feed), Flavomycin (2.2 mg active ingredient/kg feed), Bio-Mos plus Flavomycin, or a control diet, in a randomized complete block design. This experiment yielded eight treatments per challenge group. At Weeks 1 and 3, eight birds from each treatment from the E. coli challenged and unchallenged groups were randomly chosen for bacterial sampling of liver and intestinal tissue for coliforms, aerobic bacteria, and Lactobacillus spp. E. coli isolates from tissue samples were O serotyped. During E. coli challenge, dietary Bio-Mos and Flavomycin improved poult BW and BW gains (P < or = 0.05). When poults were not challenged with E. coli, poults from old hens had improved BW and cumulative BW gains over poults from young hens (P < or = 0.05). Cumulative 3-wk BW gains for unchallenged poults from young hens were improved by Bio-Mos and Flavomycin (P < or = 0.05) alone and in combination when compared to the control diet. Two of the four E. coli serotypes administered were recovered. Several serotypes were recovered that were not administered. It may be concluded that dietary Bio-Mos and Flavomycin can improve the overall performance of poults, especially when they are faced with an E. coli challenge.

Public health. Surveillance and privacy.

Surveillance is the radar of public health. It has provided the foundation for public health planning, intervention, and prevention. Important ethical issues regarding privacy--the extent to which name-based reporting violates the trust and assumptions made about how personal medical information will be treated--are raised by public health surveillance. This policy forum looks at the contexts of differing responses from the public health communities and general public to surveillance efforts.