Adrenal Suppression in Children During the Treatment for Acute Lymphoblastic Leukemia Beyond Induction.

BACKGROUND: Adrenal suppression (AS) is an iatrogenic, life-threatening condition that can occur after glucocorticoid exposure. Despite recognition that AS occurs after induction phase treatment in children with acute lymphoblastic leukemia (ALL), the risk of AS in phases beyond induction is unknown. We conducted a pilot study in pediatric patients with ALL to ascertain whether the risk of AS persists in post-induction phases of treatment. PROCEDURE: Patients diagnosed between 12 months to younger than 18 years with B or T-ALL and starting any new phase of treatment were eligible for the study. Relapsed or infant ALL were excluded. Low dose ACTH stimulation testing (LDST), measurement of albumin and cortisol binding globulin were performed in all patients. Screening for symptoms of AS was done. RESULTS: Twenty-four patients enrolled in the study. One was diagnosed with clear AS. Five others had a borderline cortisol peak, representing possible mild AS. Symptoms were nonspecific and did not help distinguish patients with normal LDST from those with borderline or abnormal results. CONCLUSION: Patients on treatment for ALL continue to be at risk of AS beyond induction treatment. Although this risk appears small, physicians must be vigilant as patients may be asymptomatic but could develop adrenal crisis during treatment.

Hypoglycemia Associated With PEG-asparaginase and 6-MP Therapy During Treatment of Acute Lymphoblastic Leukemia in Pediatric Patients: A Case Series.

BACKGROUND: Asparaginases are a mainstay treatment for pediatric acute lymphoblastic leukemia (ALL). Recent reports identified hypoglycemia associated with asparaginases. Other reports describe hypoglycemia associated with 6-mercaptopurine (6-MP), another fundamental ALL therapy. Little is known about the risk of hypoglycemia associated with ALL therapy, an adverse event that puts children at risk of decreased level of consciousness, seizures, and possibly negative neurocognitive sequelae. METHODS: We performed a retrospective chart review of 6 children with hypoglycemia during ALL treatment in our institution from May 2016 to August 2019. Timing and duration of hypoglycemia relative to polyethylene glycol (PEG)-asparaginase, 6-MP, and corticosteroids were determined. Laboratory values of the critical sample were collected. RESULTS: The median age was 2.75 (interquartile range: 1.88 to 3.63) years. Three patients had trisomy 21. The onset of hypoglycemia was 5 to 19 days after the most recent PEG-asparaginase administration or 6 to 7 months after initiating daily 6-MP. Sixteen hypoglycemic events were documented, and 9/16 had a critical sample drawn. Six events were hypoketotic, associated with PEG-asparaginase. Three were ketotic, associated with 6-MP. Two patients required treatment with diazoxide and cornstarch. CONCLUSIONS: Hypoglycemia associated with PEG-asparaginase occurred later and lasted longer than previous reports with l-asparaginase, with the likely mechanism being hyperinsulinism. 6-MP was associated with ketotic hypoglycemia.

Perception of Treatment Success and Impact on Function with Antibiotics or Appendectomy for Appendicitis: A Randomized Clinical Trial with an Observational Cohort.

OBJECTIVE: To compare secondary patient reported outcomes of perceptions of treatment success and function for patients treated for appendicitis with appendectomy vs. antibiotics at 30 days. SUMMARY BACKGROUND DATA: The Comparison of Outcomes of antibiotic Drugs and Appendectomy trial found antibiotics noninferior to appendectomy based on 30-day health status. To address questions about outcomes among participants with lower socioeconomic status, we explored the relationship of sociodemographic and clinical factors and outcomes. METHODS: We focused on 4 patient reported outcomes at 30 days: high decisional regret, dissatisfaction with treatment, problems performing usual activities, and missing >10 days of work. The randomized (RCT) and observational cohorts were pooled for exploration of baseline factors. The RCT cohort alone was used for comparison of treatments. Logistic regression was used to assess associations. RESULTS: The pooled cohort contained 2062 participants; 1552 from the RCT. Overall, regret and dissatisfaction were low whereas problems with usual activities and prolonged missed work occurred more frequently. In the RCT, those assigned to antibiotics had more regret (Odd ratios (OR) 2.97, 95% Confidence intervals (CI) 2.05-4.31) and dissatisfaction (OR 1.98, 95%CI 1.25-3.12), and reported less missed work (OR 0.39, 95%CI 0.27-0.56). Factors associated with function outcomes included sociodemographic and clinical variables for both treatment arms. Fewer factors were associated with dissatisfaction and regret. CONCLUSIONS: Overall, participants reported high satisfaction, low regret, and were frequently able to resume usual activities and return to work. When comparing treatments for appendicitis, no single measure defines success or failure for all people. The reported data may inform discussions regarding the most appropriate treatment for individuals. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02800785.

Les recommandations en vigueur pour la prise en charge de l'acidocétose diabétique pédiatrique.

Pour traiter l'acidocétose diabétique pédiatrique, il faut porter une attention particulière aux liquides et aux électrolytes pour limiter le risque de complications, telles qu'une lésion cérébrale, associée à une morbidité et une mortalité élevées. L'incidence d'œdème cérébral en cas d'acidocétose diabétique n'a pas diminué malgré les protocoles visant la limitation des liquides qui s'appuient sur la restriction de la réanimation liquidienne initiale. Selon de nouvelles données probantes, l'administration précoce de liquides isotoniques n'entraîne pas de risque supplémentaire et peut améliorer les résultats cliniques chez certains patients. Les protocoles et les directives cliniques sont adaptés et axés particulièrement sur la surveillance et le remplacement initiaux et continus des liquides et des électrolytes. Il est maintenant recommandé de commencer par une réanimation à l'aide de liquides isotoniques chez tous les patients dans les 20 à 30 minutes suivant leur arrivée à l'hôpital, suivie par la réplétion du déficit volumique sur une période de 36 heures, en association avec une perfusion d'insuline et des suppléments d'électrolytes, ainsi qu'avec la surveillance et la prise en charge attentives d'une éventuelle lésion cérébrale.

Current recommendations for management of paediatric diabetic ketoacidosis.

Treatment of paediatric diabetic ketoacidosis (DKA) includes careful attention to fluids and electrolytes to minimize the risk of complications such as cerebral injury (CI), which is associated with high morbidity and mortality. The incidence of cerebral edema in paediatric DKA has not decreased despite the use of fluid-limiting protocols based on restricting early fluid resuscitation. New evidence suggests that early isotonic fluid therapy does not confer additional risk and may improve outcomes in some patients. Protocols and clinical practice guidelines are being adjusted, with a particular focus on recommendations for initial and ongoing fluids and electrolyte monitoring and replacement. Initial isotonic fluid resuscitation is now recommended for all patients in the first 20 to 30 minutes after presentation, followed by repletion of volume deficit over 36 hours in association with an insulin infusion, electrolyte supplementation, and careful monitoring for and management of potential CI.

Patient and public involvement in the design and conduct of a large, pragmatic observational trial to investigate recurrent, high-risk non-muscle-invasive bladder cancer.

BACKGROUND: Patient-centered approaches to research design are particularly important for diseases with complex treatment decision-making, such as recurrent, high-grade non-muscle-invasive bladder cancer (NMIBC). The objective of this article is to describe patient and public involvement (PPI) in designing a large, pragmatic observational trial and to articulate barriers, challenges, and lessons learned for future design. METHODS: Through multistakeholder involvement, a large, pragmatic observational trial was designed to investigate the outcomes of high-risk, recurrent NMIBC, and it was titled Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer (CISTO). CISTO's design used the Guidance for Reporting Involvement of Patients and the Public 2 reporting checklist for PPI and built on prior engagement infrastructure in partnership with the Bladder Cancer Advocacy Network. RESULTS: CISTO's PPI began with research prioritization to identify the highest priority questions facing patients with NMIBC. A pragmatic observational study design was selected and refined through stakeholder input. PPI included patients and caregivers organized into an advocate advisory board and clinicians, researchers, payers, and industry representatives organized into an external advisory board. An engagement plan was created to define the stages of PPI and the level and nature of the involvement of each group. PPI was measured quantitatively and qualitatively through evaluation surveys and iterative feedback from board members, with changes made for continuous improvement. CONCLUSIONS: Through intentional PPI, CISTO aims to produce pragmatic and generalizable results that will allow patients to make informed decisions for recurrent, high-risk NMIBC based on their personal experiences. LAY SUMMARY: Involving patients and other stakeholders in research ensures that it reflects the outcomes that matter most to them. This is especially important when research focuses on conditions in which patients face difficult decisions about treatment options. This article describes the key role that stakeholders played in shaping the Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer (CISTO) study. It compares treatments for recurrent noninvasive bladder cancer and describes how stakeholders were engaged to design and develop the study and the practices that supported their involvement.

Clinical outcomes of patients with and without HIV hospitalized with COVID-19 in England during the early stages of the pandemic: a matched retrospective multi-centre analysis (RECEDE-C19 study).

BACKGROUND: The contribution of HIV to COVID-19 outcomes in hospitalized inpatients remains unclear. We conducted a multi-centre, retrospective matched cohort study of SARS-CoV-2 PCR-positive hospital inpatients analysed by HIV status. METHODS: HIV-negative patients were matched to people living with HIV (PLWH) admitted from 1 February 2020 to 31 May 2020 up to a 3:1 ratio by the following: hospital site, SARS-CoV-2 test date ± 7 days, age ± 5 years, gender, and index of multiple deprivation decile ± 1. The primary objective was clinical improvement (two-point improvement or better on a seven-point ordinal scale) or hospital discharge by day 28, whichever was earlier. RESULTS: A total of 68 PLWH and 181 HIV-negative comparators were included. In unadjusted analyses, PLWH had a reduced hazard of achieving clinical improvement or discharge [adjusted hazard ratio (aHR) = 0.57, 95% confidence interval (CI): 0.39-0.85, p = 0.005], but this association was ameliorated (aHR = 0.70, 95% CI: 0.43-1.17, p = 0.18) after additional adjustment for ethnicity, frailty, baseline hypoxaemia, duration of symptoms prior to baseline, body mass index (BMI) categories and comorbidities. Baseline frailty (aHR = 0.79, 95% CI: 0.65-0.95, p = 0.011), malignancy (aHR = 0.37, 95% CI 0.17, 0.82, p = 0.014) remained associated with poorer outcomes. The PLWH were more likely to be of black, Asian and minority ethnic background (75.0% vs 48.6%, p = 0.0002), higher median clinical frailty score [3 × interquartile range (IQR): 2-5 vs, 2 × IQR: 1-4, p = 0.0069), and to have a non-significantly higher proportion of active malignancy (14.4% vs 9.9%, p = 0.29). CONCLUSIONS: Adjusting for confounding comorbidities and demographics in a matched cohort ameliorated differences in outcomes of PLWH hospitalized with COVID-19, highlighting the importance of an appropriate comparison group when assessing outcomes of PLWH hospitalized with COVID-19.

Factors associated with hypothermia within the first 6 hours of life in infants born at ≥340 weeks' gestation: a multivariable analysis.

BACKGROUND: Lack of appropriate temperature management has been associated with significant adverse outcomes in preterm and low birthweight neonates. There is a lack of similar investigations in the late preterm (340-366) and term (≥370) neonate population. Our aim was to identify key risk factors as well as clinical outcomes associated with hypothermia in this population. METHODS: A retrospective chart review was conducted at the Ottawa Hospital including all eligible infants ≥340 weeks' gestation over a one-month period in November 2020. Infant, maternal, and delivery room variables were collected, including prematurity, maternal temperature, delivery mode, birthweight, and premature rupture of membranes, as well as clinical outcomes such as NICU/SCN admission and length of stay. Regression models were generated, adjusted for covariates, and stepwise regression was performed. RESULTS: Four hundred forty infants were included in the analysis; 26.8% (118/440) were hypothermic within 6 hours of delivery. In the multivariable analysis, prematurity, low 5 minute Apgar score (< 7) or need for resuscitation, maternal hypertension, and absence of premature rupture of membranes > 18 hours or suspected maternal infection were significantly associated with hypothermia within 6 hours of delivery (p < 0.05). Multivariable analysis of clinical outcomes demonstrated a significant association between hypothermia within 6 hours of delivery and NICU/SCN admission (OR = 2.87; 95% CI 1.36, 6.04), need for respiratory support or diagnosis of respiratory distress syndrome (OR = 3.94; 95% CI 1.55, 10.50), and length of stay (exp(ß) = 1.20; 95% bootstrap CI 1.04, 1.37). CONCLUSIONS: Our results suggest there are similar factors associated with hypothermia in our study population of infants born at ≥340 weeks' gestation compared to prior studies in preterm and low-birthweight infants. Furthermore, hypothermia is associated with higher risk of adverse outcomes, which highlights the need to prevent hypothermia in all newborns.

'They can stigmatize you': a qualitative assessment of the influence of school factors on engagement in care and medication adherence among adolescents with HIV in Western Kenya.

School-related factors may influence retention in care and adherence to antiretroviral therapy (ART) among adolescents with human immunodeficiency virus (HIV). We analyzed data from in-depth interviews with 40 adolescents with HIV (aged 14 -19 years), 40 caregivers of adolescents with HIV, and 4 focus group discussions with healthcare workers to evaluate contextual factors affecting adherence to ART and clinic attendance among adolescents, with a focus on the school environment. Informed by Anderson's Model of Health Services Utilization, transcripts were systematically coded and synthesized to identify school-related themes. All groups identified the school environment as a critical barrier to engagement in HIV care and medication adherence for adolescents with HIV. Adolescent participants reported inflexible school schedules and disclosure to school staff as the biggest challenges adhering to clinic appointments and ART. Adolescents described experiencing stigma and discrimination by peers and school staff and would adjust when, where and how often they took ART to avoid inadvertent disclosure. Boarding school students faced challenges because they had limited private space or time. Caregivers were often instrumental in navigating school permissions, including identifying a treatment supporter among school staff. Additional research engaging school staff may guide interventions for schools to reduce stigma and improve adherence and retention.

Elevated Sound Levels in the Neonatal Intensive Care Unit: What Is Causing the Problem?

BACKGROUND: Premature and sick neonates may require weeks of hospitalization in a noisy neonatal intensive care unit (NICU) environment with sound levels that may reach 120 decibels. The American Academy of Pediatrics recommends a maximum sound level of 45 decibels. PURPOSE: To measure sound levels in a level III NICU and to describe contributing environmental factors. METHODS: Descriptive quantitative study. Sound levels were measured using a portable sound meter in an open-bay level III NICU. Contributing environmental factors were recorded and analyzed. RESULTS: Mean sound levels for day, evening, and night shifts were 83.5, 83, and 80.9 decibels, respectively. Each period of time exceeded the recommended guidelines 90% of the time and was almost double the American Academy of Pediatrics' recommendation. Multiple linear regression findings demonstrated significant factors associated with elevated sound levels including number of neonates, number of people, number of alarms, acuity level, and shift type. Observational data explain 14.5% of elevated sound levels. IMPLICATIONS FOR PRACTICE: An understanding of baseline sound levels and contributing environmental factors is the first step in developing strategies to mitigate excessive noise in the NICU. IMPLICATIONS FOR RESEARCH: Research should focus on effective and sustainable ways to reduce sound levels in the NICU, including inside the isolette, in order to provide an environment that is conducive to optimal growth and neurodevelopment for preterm and sick infants.

Minimally Invasive Postmortem Intestinal Tissue Sampling in Malnourished and Acutely Ill Children Is Feasible and Informative.

BACKGROUND: Intestinal disorders such as environmental enteric dysfunction (EED) are prevalent in low- and middle-income countries (LMICs) and important contributors to childhood undernutrition and mortality. Autopsies are rarely performed in LMICs but minimally invasive tissue sampling is increasingly deployed as a more feasible and acceptable procedure, although protocols have been devoid of intestinal sampling to date. We sought to determine (1) the feasibility of postmortem intestinal sampling, (2) whether autolysis precludes enteric biopsies' utility, and (3) histopathologic features among children who died during hospitalization with acute illness or undernutrition. METHODS: Transabdominal needle and endoscopic forceps upper and lower intestinal sampling were conducted among children aged 1 week to 59 months who died while hospitalized in Blantyre, Malawi. Autolysis ratings were determined for each hematoxylin and eosin slide, and upper and lower intestinal scoring systems were adapted to assess histopathologic features and their severity. RESULTS: Endoscopic and transabdominal sampling procedures were attempted in 28 and 14 cases, respectively, with >90% success obtaining targeted tissue. Varying degrees of autolysis were present in all samples and precluded histopathologic scoring of 6% of 122 biopsies. Greater autolysis in duodenal samples was seen with longer postmortem interval (Beta = 0.06, 95% confidence interval, 0.02-0.11). Histopathologic features identified included duodenal Paneth and goblet cell depletion. Acute inflammation was absent but chronic inflammation was prevalent in both upper and lower enteric samples. Severe chronic rectal inflammation was identified in children as young as 5.5 weeks. CONCLUSIONS: Minimally invasive postmortem intestinal sampling is feasible and identifies histopathology that can inform mortality contributors.

Examining the Relationship Between Gastroschisis and Placental Fetal Vascular Malperfusion.

INTRODUCTION: Gastroschisis is a congenital malformation characterized by intestinal herniation through an abdominal wall defect. Despite its unknown pathogenesis, known risk factors include maternal smoking, alcohol use, and young maternal age. Previous work has shown that gastroschisis is associated with placental delayed villous maturation, and the goal of this study was to assess for additional associated placental pathologies that may help clarify the pathogenesis of gastroschisis. METHODS: We conducted a retrospective slide review of 29 placentas of neonates with gastroschisis. Additionally, we reviewed pathology reports from one control group of 30 placentas with other congenital malformations. Gross and histological data were collected based on a standardized rubric. RESULTS: Gastroschisis was associated with increased placental fetal vascular malperfusion (FVM) in 62% of cases (versus 0% of controls, p < 0.0001). It was also associated with increased placental villous maldevelopment in 76% of cases (versus 3% of controls, p < 0.0001). CONCLUSION: Our study demonstrates an association between gastroschisis and FVM. While FVM could be the consequence of vascular disruption due to the ventral location of gastroschisis, it could also reflect estrogen-induced thrombosis in early pregnancy. Further research is needed to separate these possibilities and determine the cause of the placental FVM observed in gastroschisis.

Extremely low gestational age infants: Developing a multidisciplinary care bundle.

BACKGROUND: Clinical experience in managing extremely low gestational age infants, particularly those born <24 weeks' gestation, is limited in Canada. Our goal was to develop a bedside care bundle for infants born <26 weeks' gestation, with special considerations for infants of <24 weeks, to harmonize and improve quality of care. METHODS: We created a multidisciplinary working group with experience in caring for preterm infants, searched the literature from 2000 to 2019 to identify best practices for the care of extremely preterm infants and consulted colleagues across Canada and internationally. Iterative improvements were made following the Plan-Do-Study-Act methodology. RESULTS: A care bundle, created in October 2015, was divided into three time periods: initial resuscitation/stabilization, the first 72 hours and days 4 to 7, with each period subdivided in 8 to 12 care themes. Revisions and practice changes were implemented to improve skin integrity, admission temperature, timing of initiation of feeds, reliability of transcutaneous CO2 monitoring and ventilation. Of 127 infants <26 weeks admitted between implementation and end of 2019, 78 survived to discharge (61%). CONCLUSION: It will be important to determine, with ongoing auditing and further evaluation, whether our care bundle led to improvements of short- and long-term outcomes in this population. Our experience may be useful to others caring for extremely low gestational age infants.

Prioritizing research topics: a comparison of crowdsourcing and patient registry.

PURPOSE: A cornerstone of patient-centered outcome research is direct patient involvement throughout the research process. Identifying and prioritizing research topics is a critical but often overlooked point for involvement, as it guides what research questions are asked. We assess the feasibility of involving individuals with low back pain in identifying and prioritizing research topics using two approaches: an existing patient registry and an online crowdsourcing platform. We compare and contrast the diversity of participants recruited, their responses, and resources involved. METHODS: Eligible participants completed a survey ranking their five highest priority topics from an existing list and supplying additional topics not previously identified. We analyzed their responses using descriptive statistics and content analysis. RESULTS: The patient registry yielded older (mean age 72.4), mostly White (70%), and well-educated (95% high school diploma or higher) participants; crowdsourcing yielded younger (mean age 36.6 years), mostly White (82%), and well-educated (98% high school diploma or higher) participants. The two approaches resulted in similar research priorities by frequency. Both provided open-ended responses that were useful, in that they illuminate additional and nuanced research topics. Overall, both approaches suggest a preference towards topics related to diagnosis and treatment over other topics. CONCLUSION: Using a patient registry and crowdsourcing are both feasible recruitment approaches for engagement. Researchers should consider their approach, community, and resources when choosing their recruitment approach, as each approach has its own strengths and weaknesses. These approaches are likely most appropriate to supplement or to complement in-person and ongoing engagement strategies.

Prediction of the Transporter-Mediated Drug-Drug Interaction Potential of Dabrafenib and Its Major Circulating Metabolites.

The BRAF inhibitor dabrafenib was recently approved for the treatment of certain BRAF V600 mutation-positive tumors, either alone or in combination therapy with the mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2 inhibitor, trametinib. This article presents the dabrafenib transporter-mediated drug-drug interaction (DDI) risk assessment, which is currently an important part of drug development, regulatory submission, and drug registration. Dabrafenib and its major circulating metabolites (hydroxy-, carboxy-, and desmethyl-dabrafenib) were investigated as inhibitors of the clinically relevant transporters P-gp, BCRP, OATP1B1, OATP1B3, OCT2, OAT1, and OAT3. The DDI Guidance risk assessment decision criteria for inhibition of BCRP, OATP1B1 and OAT3 were slightly exceeded and therefore a minor DDI effect resulting from inhibition of these transporters remained possible. Biliary secretion is the major excretion pathway of dabrafenib-related material (71.1% of orally administered radiolabeled dose recovered in feces), whereas urinary excretion was observed as well (22.7% of the dose). In vitro uptake into human hepatocytes of the dabrafenib metabolites, but not of dabrafenib parent compound, was mediated, at least in part, by hepatic uptake transporters. The transporters responsible for uptake of the pharmacologically active hydroxy- and desmethyl dabrafenib could not be identified, whereas carboxy-dabrafenib was a substrate of several OATPs. Dabrafenib, hydroxy-, and desmethyl-dabrafenib were substrates of P-gp and BCRP, whereas carboxy-dabrafenib was not. Although a small increase in exposure to carboxy-dabrafenib upon inhibition of OATPs and an increase in exposure to desmethyl-dabrafenib upon inhibition of P-gp or BCRP cannot be excluded, the clinical significance of such increases is likely to be low.

Prioritizing Patient-Reported Outcomes in Breast Cancer Surgery Quality Improvement.

Breast-cancer-specific tools that measure health-related quality of life (HRQOL) were developed for use in research or clinical practice, and little is known about these tools' performance ability for quality improvement. Furthermore, existing tools may not fully reflect all issues that contribute to quality care as seen by patients. Work is needed to identify and validate patient-reported outcome measures for use in quality improvement in breast cancer surgical care. We conducted an exploratory qualitative study in order to better understand what HRQOL domains and processes of care define high quality surgical care for women undergoing mastectomy for breast cancer from both the patient and clinician perspective. We conducted focus groups and one-on-one interviews with 15 women and administered a prioritization questionnaire to participants. We also conducted a prioritization questionnaire among surgical oncologists, general surgeons, and reconstructive surgeons who are members of the Washington State Medical Association. Both the patient and surgeon prioritization questionnaire asked participants to prioritize HRQOL and treatment satisfaction-related aspects of their breast cancer surgical care at key time points before and after mastectomy. A Stakeholder Advisory Panel was convened to review focus group, interview, and prioritization questionnaire results and make recommendations as to patient-reported outcome domains to focus on and existing instruments to use for quality improvement. Patients and clinicians largely agreed on important HRQOL domains, including emotional well-being, education, communication, and process of care. The Stakeholder Advisory Panel, composed of 12 clinicians and five patients, reviewed study findings and existing patient-reported outcomes measurement tools. The panel recommended that the BREAST-Q, a flexible tool with independently validated modules designed for research and clinical care, is an ideal tool to begin developing novel quality improvement benchmarks focused on patient-reported outcomes.

The Promise and Pitfalls of Using Crowdsourcing in Research Prioritization for Back Pain: Cross-Sectional Surveys.

BACKGROUND: The involvement of patients in research better aligns evidence generation to the gaps that patients themselves face when making decisions about health care. However, obtaining patients' perspectives is challenging. Amazon's Mechanical Turk (MTurk) has gained popularity over the past decade as a crowdsourcing platform to reach large numbers of individuals to perform tasks for a small reward for the respondent, at small cost to the investigator. The appropriateness of such crowdsourcing methods in medical research has yet to be clarified. OBJECTIVE: The goals of this study were to (1) understand how those on MTurk who screen positive for back pain prioritize research topics compared with those who screen negative for back pain, and (2) determine the qualitative differences in open-ended comments between groups. METHODS: We conducted cross-sectional surveys on MTurk to assess participants' back pain and allow them to prioritize research topics. We paid respondents US $0.10 to complete the 24-point Roland Morris Disability Questionnaire (RMDQ) to categorize participants as those "with back pain" and those "without back pain," then offered both those with (RMDQ score ≥7) and those without back pain (RMDQ <7) an opportunity to rank their top 5 (of 18) research topics for an additional US $0.75. We compared demographic information and research priorities between the 2 groups and performed qualitative analyses on free-text commentary that participants provided. RESULTS: We conducted 2 screening waves. We first screened 2189 individuals for back pain over 33 days and invited 480 (21.93%) who screened positive to complete the prioritization, of whom 350 (72.9% of eligible) did. We later screened 664 individuals over 7 days and invited 474 (71.4%) without back pain to complete the prioritization, of whom 397 (83.7% of eligible) did. Those with back pain who prioritized were comparable with those without in terms of age, education, marital status, and employment. The group with back pain had a higher proportion of women (234, 67.2% vs 229, 57.8%, P=.02). The groups' rank lists of research priorities were highly correlated: Spearman correlation coefficient was .88 when considering topics ranked in the top 5. The 2 groups agreed on 4 of the top 5 and 9 of the top 10 research priorities. CONCLUSIONS: Crowdsourcing platforms such as MTurk support efforts to efficiently reach large groups of individuals to obtain input on research activities. In the context of back pain, a prevalent and easily understood condition, the rank list of those with back pain was highly correlated with that of those without back pain. However, subtle differences in the content and quality of free-text comments suggest supplemental efforts may be needed to augment the reach of crowdsourcing in obtaining perspectives from patients, especially from specific populations.

Disseminated intravascular coagulation in an under-recognised zoonotic infection.

A 51 year old man presented with severe sepsis, disseminated intravascular coagulation (DIC) and multiorgan dysfunction after a 24 hour history of diarrhoea and malaise. Despite fluid resuscitation and receiving a platelet transfusion, freshfrozen plasma and intravenous broad-spectrum antibiotics, he remained anuric with a worsening metabolic acidosis. He was transferred to critical care for organ support including renal replacement therapy. He subsequently developed purpura fulminans. Blood cultures were positive for Captocytophaga carnimorsis, a gram-negative canine zoonosis that is an underdiagnosed cause of severe sepsis, for which DIC at presentation is characteristic. Treatment is with penicillins and fluoroquinolones. Identification of risk factors for unusual organisms and recognition of DIC allowing prompt treatment is critical for the acute physician.