Performance characteristics of diagnostic assays for schistosomiasis in Ontario, Canada.

Introduction: Due to lower intensity of infection and greater intervals from last exposure, parasitologic detection methods for schistosomiasis are poorly sensitive in non-endemic areas, challenging accurate diagnosis. Methods: We evaluated parasitologic versus indirect detection methods for schistosomiasis. We included specimens submitted for Schistosoma serology, and stool for ova and parasite microscopy. Three real-time PCR assays targeting Schistosoma mansoni and S. haematobium were performed. Primary outcome measures were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), where both microscopy and serology were the composite reference standard against serum PCR. Results: Of 8168 serum specimens submitted for Schistosoma serology, 638 (7.8%) were reactive and 6705 (82.1%) were non-reactive. Of 156,771 stool specimens submitted for ova and parasite testing, 46 (0.03%) were positive for eggs of S. mansoni. Four (0.5%) urine specimens were positive for eggs of S. haematobium. Combined serum PCRs targeting S. mansoni had a sensitivity and specificity of 27.8% (95% CI = 18.3-39.1%) and 100% (95% CI = 83.9-100%), respectively, with PPV of 100% (95% CI = 100%) and NPV of 26.9% (95% CI = 24.3-29.7%). The one serum sample positive for S. haematobium was also detectable by our S. haematobium PCR. No cross-reactivity was observed for all three PCR assays. Conclusions: Although serology is highly sensitive, parasitologic tests signify active infection, but are limited by low population-level sensitivity, particularly in non-endemic settings. Although serum PCR offered no performance advantage over stool microscopy, its role in diagnostic parasitology should be pursued due to its high-throughput and operator-independent nature.

Inflammatory bowel disease later diagnosed as strongyloides colitis in migrants to Canada: a case series.

Strongyloides colitis is a gastrointestinal manifestation of the parasitic infection, Strongyloides stercoralis, which may be misdiagnosed and treated as ulcerative colitis (UC) in patients presenting in non-endemic regions. Treatment of Strongyloides colitis as UC can lead to a lethal hyperinfection syndrome. Therefore, prior to commencing immunosuppressive treatment of UC, it is essential to use diagnostic markers to differentiate the two etiologies. In this case series, we discuss two migrant patients who were previously diagnosed with UC and treated accordingly who presented to our clinic for further investigation of suspected parasitic infection.

Chikungunya: An Emerging Public Health Concern.

Purpose of Review: The worldwide spread of chikungunya over the past two decades calls for greater knowledge and awareness of the virus, its route of transmission, methods of diagnosis, and the use of available treatment and prevention measures. Recent Findings: Chikungunya virus infection, an Aedes mosquito-borne febrile disease, has spread from Africa and Asia to Europe and the Americas and from the tropics and subtropics to temperate regions. International travel is a pivotal influence in the emergence of chikungunya as a global public health threat, as evidenced by a growing number of published reports on travel-related chikungunya infections. The striking features of chikungunya are arthralgia and arthritis, and the disease is often mistaken for dengue. Although mortality is low, morbidity can be profound and persistent. Current treatment for chikungunya is supportive; chikungunya vaccines and therapeutics are in development. Travelers planning to visit areas where the mosquito vectors are present should be advised on preventive measures. Summary: Chikungunya is an emerging disease in the Americas. Frequent travel, the presence of at least two competent mosquito species, and a largely naïve human population in the Western Hemisphere create a setting conducive to future outbreaks. Awareness of the disease and its manifestations is critical to effectively and safely manage and limit its impact. Vaccines in late-stage clinical trials offer a new pathway to prevention.

2018 in review: five hot topics in tropical medicine.

The year 2018 heralded many new developments in the field of tropical medicine, including licensure of novel drugs for novel indications, licensure of existing drugs for existing indications but in novel settings, and globalized outbreaks of both vector-borne and zoonotic diseases. We herein describe five top stories in tropical medicine that occurred during 2018, and illuminate the practice-changing development within each story.

A systematic review of methodologies, endpoints, and outcome measures in randomized trials of radiation therapy-induced nausea and vomiting.

PURPOSE: Clinical trials in radiation therapy-induced nausea and vomiting (RINV) appear to have varied methodologies, endpoints, and outcome measures. This complicates trial comparisons, weakens practice guideline recommendations, and contributes to variability in supportive care patterns of practice. We systematically reviewed RINV trials to describe and compare their pertinent design features. MATERIALS AND METHODS: Ovid versions of the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, EMBASE, and MEDLINE to January/February 2017 were searched for adult phase III trials of RINV management strategies. Key abstracted data included trial interventions and eligibility criteria, standard radiation therapy (RT) metrics, symptom assessment procedures, symptom definitions and grading systems, pre-specified and reported endpoints, and other outcome measures. RESULTS: From 1166 references identified in the initial database search, we selected 34 trials for analysis that collectively randomized 4529 patients (median 61, range 11-1492). Twenty-eight trials (82%) were published prior to the year 2000. Twenty-seven trials (79%) involved multiple fraction RT and 7 (21%) single fraction RT. Twenty-four trials (71%) evaluated prophylactic interventions, 9 (26%) rescue interventions, and 1 trial did not specify. Thirty-three trials (97%) evaluated pharmacologic interventions. Twenty trials (59%) had patient report symptoms, 5 (15%) healthcare professionals or researchers, and 10 (29%) did not specify. Nausea was not defined in any trial but was reported as a stand-alone symptom in 26 trials (76%) and was graded in 20 (59%), with categorical qualitative scales being the most common method. Vomiting was defined in 3 trials (9%), was reported as a stand-alone symptom in 17 (47%), and was graded in 7 (21%), with continuous numerical scales being the most common method. Retching was defined in 3 trials, was not reported as a stand-alone symptom in any trial, and was graded in 1 (3%). Twenty-one trials (62%) created compound symptom measures that combined individual symptoms. Fifteen trials (44%) reported "emetic episode/event" measures but only 9 defined them. Seventeen trials (50%) reported complicated endpoints (e.g., "response," "control," "success") that combined multiple symptom or compound symptom measures, but 7 did not define them comprehensively. Ten trials (29%) defined a primary endpoint a priori. CONCLUSIONS: Methodologies, endpoints, and outcome measures varied considerably among 34 randomized trials in RINV.

Single fraction conventional external beam radiation therapy for bone metastases: a systematic review of randomised controlled trials.

PURPOSE: To determine the optimal dose of single fraction conventional palliative radiation therapy for the relief of pain caused by bone metastases. MATERIAL AND METHODS: Ovid version of EMBASE and EMBASE Classic, MEDLINE, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were searched for relevant randomised controlled trials. Pain response data were standardised according to the clinical trial endpoints recommended by the International Bone Metastases Consensus Working Party. RESULTS: From 2696 references we selected 26 articles for review. These described 24 trials that cumulatively randomised 3233 patients to 28 single fraction arms: two arms received 4 Gy, one 5 Gy, one 6 Gy, twenty-two 8 Gy, one 10 Gy and one 8-15 Gy. Eighty-four percent of all patients received 8 Gy and this imbalance precluded formal modelling analyses for different doses. Efficacy endpoints and pain assessment times varied. In general, higher doses produced better pain response rates. The overall (OR) and complete (CR) pain response rates for different doses according to available intention-to-treat (ITT) and assessable patient (A) figures were: 4 Gy [OR(ITT)=23-47%, OR(A)=44-47%, CR(ITT)=15-18%, CR(A)=15-26%], 5 Gy [OR(A)=72%, CR(A)=55%], 6 Gy [OR(ITT&A)=65%, CR(ITT&A)=21%], 8 Gy [OR(ITT)=21-81%, OR(A)=31-93%, CR(ITT)=9-52%, CR(A)=14-57%], 10 Gy [OR(A)=84%, CR(A)=39%]. In trials that directly compared different single fraction doses, 8 Gy was statistically superior to 4 Gy. CONCLUSIONS: 8 Gy was by far the most commonly administered single fraction dose within 24 randomised trials of conventional radiation therapy for the palliation of bone metastases. 8 Gy should be the standard dose against which future treatments are compared due to its reproducible pain response rate and its established safe profile. The optimal dose for the relief of pain remains an open question, however, 8 Gy produced statistically superior pain response rates compared to 4 Gy in trials directly comparing those doses, and in general across all trials doses of 8 Gy or more produced numerically superior pain response rates compared to doses less than 8 Gy.

A Framework for Successful Remediation within Allied Health Programs: Strategies Based on Existing Literature.

The effective assessment methods of various health and allied health educational programs frequently work to identify trainees in difficulty who may require assistance to improve their academic and practical performances. However, although the methods of assessing trainees are often well-established, the essential skills for dealing with a trainee in difficulty are largely underdeveloped across curricula, and research within the field remains limited. This article reviews remediation in medicine and allied health professional programs based on existing literature. The literature suggests that successful remediation involves multiple steps, including prompt problem identification, meeting with the student on an individual basis to develop a learner-centered strategy, and development of an action plan. Remediation requires multiple assessors and several assessment tools, feedback and reassessment, all underpinned by documentation, written policies, and proactive involvement in supporting the identified students. Remediation, when based on a learner-centered approach, can be extremely effective, allowing the majority of remedial students to overcome their difficulties and succeed in their academic endeavors.

The Informational Needs of Prostate Cancer Patients Treated with Radical Prostatectomy Regarding Adjuvant or Salvage Radiotherapy: Determinants of Community Health Pilot Project.

BACKGROUND: Prostate cancer patients face important treatment decisions. The role of adjuvant and salvage radiotherapy (RT) is now less controversial in terms of the timing of the treatment after radical prostatectomy, because few randomized trials demonstrated the benefit of early RT in terms of biochemical control and improved survival. PURPOSE: To evaluate the informational needs of prostate patients referred to Odette Cancer Centre for post-prostatectomy adjuvant or salvage RT. In addition, we investigated how social determinants of health, such as income and education affected these needs. METHODS: A needs assessment questionnaire was developed and piloted among 10 prostate cancer patients. A 4-point Likert scale was used to examine patients' knowledge and understanding of various aspects of post-prostatectomy RT. RESULTS: The most frequent patient response corresponded to having "some" knowledge about the topic (Likert scale 3), except for two items, which included knowledge about survival rates for different treatment options and management of side effects related to radiation treatment (Likert scale 2: "a little"). No causative relationship was found between the patients' income and/or education, and their knowledge of various treatment aspects. CONCLUSIONS: This study demonstrated that even though our patients had some knowledge about prostate cancer and its treatments, they may still require more information regarding the management of RT-related side effects, local recurrence, and survival rates after post-prostatectomy RT. These findings will be used to conduct a thorough informational needs assessment to aid in the future development and testing of an educational tool for patients with prostate cancer after radical prostatectomy, that will assist them in making decisions about their adjuvant or salvage treatment options.

Would larger radiation fields lead to a faster onset of pain relief in the palliation of bone metastases?

PURPOSE: Hemibody irradiation has been shown to relieve bony metastatic pain within 24-48 hours of treatment, whereas for local external beam radiation, onset of pain relief is 1-4 weeks after radiation. The primary objective of this study is to examine whether there is a relationship between the areas of radiation treatment and onset of pain relief. METHODS AND MATERIALS: From Jan 1999 to Jan 2002, a total of 653 patients with symptomatic bone metastases were treated with external beam radiation. Pain scores and analgesic consumption were recorded at baseline and Weeks 1, 2, 4, 8, and 12. The areas of radiation treatment for all patients were calculated, then correlated with the response and analyzed in various ways. We first compared pain score alone with mean radiation field size. Second, we combined pain score and analgesic consumption. Last, we implemented the International Consensus end points for pain score and analgesic intake. RESULTS: Assessment of 653 patients showed no significant correlation comparing pain scores alone with radiation field area, with the exception of Week 4 for partial responders. Again, no significant correlation was found when combining both analgesic intake and pain score against radiation field size. Even when implementing the International Consensus end point definitions for radiation response, the only significant correlation between radiation field size and response was observed in Week 2 for partial response. CONCLUSION: There was no statistical significance between mean areas of radiation treatment with the onset of pain relief.

Genetic analysis indicates that transcription factors AP-2alpha and Pax6 cooperate in the normal patterning and morphogenesis of the lens.

PURPOSE: The similar lens phenotypes observed in mice with mutations in the genes encoding either Pax6 or AP-2alpha suggested that these transcription factors work together to regulate specific signaling cascades during lens development. In this study we examined the overlapping expression patterns of Pax6 and AP-2alpha in the developing mouse lens and further investigated their potential cooperative roles through the creation of double heterozygote mice. METHODS: Colocalization of Pax6 and AP-2alpha expression patterns were performed on sections of mouse embryos at embryonic days 9.5, 10.5, 13.5, and 16 as well as on adult sections using immunofluorescence. To test the potential cooperation between these two transcription factors, two mouse strains heterozygous for the genes encoding either Pax6 or AP-2alpha were bred together to produce double heterozygous Pax6(+/lacZ)/AP-2alpha(+/-) mice. Histological examination was then performed on both embryonic and post-natal sections in order to compare double heterozygous Pax6(+/lacZ)/AP-2alpha(+/-) eyes to single heterozygote and wildtype eyes. RESULTS: Examination of the developmental stages showed distinct colocalization of Pax6 and AP-2alpha protein in the anterior lens epithelium. However, Pax6 expression continued further into the transitional zone of the lens whereas AP-2alpha expression ceased just prior to the region where epithelial cells differentiate into fiber cells. Histological investigation of embryonic and post-natal mutant mouse eyes showed that while single Pax6 heterozygote mice exhibited remnants of a corneal-lenticular adhesion, the lens and cornea were physically separated. In contrast, the Pax6(+/lacZ)/AP-2alpha(+/-) double heterozygotes displayed a distinct lens stalk, which protruded towards the surface of the cornea, creating a direct corneal-lenticular attachment. CONCLUSIONS: Colocalization of Pax6 and AP-2alpha was mainly observed in the proliferating central lens epithelium, the same region in which the lens stalk phenotype was observed in the double heterozygous Pax6(+/lacZ)/AP-2alpha(+/-) eyes. The more severe phenotype observed in these double heterozygous mice, as compared to the single heterozygotes, suggests that Pax6 and AP-2alpha may work synergistically to control lens development.