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OBJECTIVES: This study was conducted to assess poultry farmers’ knowledge and practices regarding antibiotics, antimicrobial usage (AMU), and antimicrobial resistance (AMR), and to identify the sociodemographic factors of inappropriate use of antibiotics in commercial poultry farms in Bangladesh. METHODS: A qualitative survey of 140 farmers in Bangladesh was conducted from March to May 2019. A logistic regression model was used to identify factors associated with the inappropriate use of antibiotics. RESULTS: 47.1% of farmers were unable to explain antibiotics, 42.9% used antibiotics for preventive purposes, 4.3% used them as growth promoters, 25.7% used them as suggested by veterinarians, 42.9% used leftover antibiotics, 50% did not maintain antibiotics residual withdrawal period, and 98.6% did not know about AMR. In bivariable regression analysis, sex and primary occupation of poultry farmers, their knowledge about withdrawal periods for antibiotics, and no contact with veterinary surgeons (VS) were found to be significantly associated with the inappropriate use of antibiotics, while only ‘no contact with VS’ was identified in multivariable regression analysis. CONCLUSIONS: The findings suggest an urgent need to improve understanding of antibiotics and AMR. Adequate supervision by veterinarians would ensure adherence to appropriate AMU patterns, and would limit the misuse of antibiotics and associated AMR development in farms.

BACKGROUND: Antibacterial resistance is an ongoing global issue, threatening the lives of millions and affecting the quality of health systems, resulting in high costs to the worldwide economy. Syria is one of many countries with a high rate of antibiotic prescription or consumption, even before the war. METHODS: A retrospective cross-sectional study was conducted to assess the pattern of antibiotic prescribing with regard to acute upper respiratory tract infection (AURTI) cases throughout the year 2019; data were collected from GlobeMed Syria (now Modern Healthcare Claims Management Company) following ethical approval. RESULTS: The study comprised 14 913 cases, of which 13 382 (90%) had received an antibiotic prescription. All age groups showed high prescribing rates, with the 46–55 years age group having the highest (95.0%). Acute tonsillitis had the most significant percentage of antibiotics prescribed (98.7%). Cephalosporins were the most commonly prescribed antibiotic class. Family physicians were more inclined to prescribe antibiotics than those in other specialism groups. CONCLUSION: Syria has a high rate of prescribing antibiotics for AURTIs, which may contribute to the evolution of resistant bacteria. The rate is higher than those reported in other Arab countries. Physicians need to commit to following the official guidelines, taking the appropriate prescribing of antibiotics more seriously, and should take more care in distinguishing viral origins of AURTIs.

OBJECTIVE: To investigate the prevalence, intensity, clinical aspects and factors associated with tungiasis infection among primary school children in Northeastern Tanzania. METHODS: A quantitative school-based cross-sectional study was conducted among 401 primary school children. Participants were assessed through clinical examination to look for embedded Tunga penetrans in their hands, feet, arms and legs. A structured questionnaire was used to enquire about factors associated with tungiasis infection. The data were analysed using descriptive statistics, Chi-squared test and logistic regression, with p

Atopic dermatitis (AD) is an inflammatory skin disease associated with increased systemic and vascular inflammation. Although dupilumab has been proven to be effective against severe AD, imaging studies analysing its inflammation-reducing effect have rarely been reported. The aim of this study was to evaluate the effect of dupilumab on systemic and vascular inflammation in adult patients with severe AD, using (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET/CT). A total of 33 adult patients with severe AD and 25 healthy controls underwent (18)F-FDG PET/CT at baseline. Patients on dupilumab treatment underwent 18F-FDG PET/CT again after achieving a 75% reduction from baseline on the Eczema Area and Severity Index (EASI-75). Patients with AD exhibited increased (18)F-FDG uptake values in the liver, spleen, pancreas, and carotid artery compared with healthy controls. However, compared with baseline, there was no statistically significant difference in (18)F-FDG uptake in major organs and arteries after achieving EASI-75 with dupilumab treatment. In conclusion, while dupilumab treatment resulted in a significant clinical improvement and reduced serum inflammatory markers in adult patients with severe AD, no changes in systemic and vascular inflammation were observed on (18)F-FDG PET/CT imaging. SIGNIFICANCE Dupilumab is an effective treatment for atopic dermatitis; however, data on its systemic effects are limited. Patients with atopic dermatitis have increased vascular inflammation according to clinical severity. However, this study found that the changes in systemic and vascular inflammation after dupilumab treatment were not significant. Special attention is required to determine whether atopic dermatitis treatment not only improves skin symptoms, but also improves systemic and vascular inflammation.

OBJECTIVES: Trichomonas vaginalis is the most prevalent sexually transmitted parasite worldwide. However, no surveillance system exists to monitor T. vaginalis cases and drug resistance in Japan. METHODS: Cervical cytology vaginal swabs were collected from women with and without suspected symptoms of T. vaginalis infection; these swabs were used for the detection of T. vaginalis, human papillomavirus (HPV), and Candida albicans using specific polymerase chain reaction. Clinical isolates of T. vaginalis were subjected to metronidazole susceptibility tests using the previously reported minimal lethal concentration (MLC) and newly established half-maximal inhibitory concentration (IC(50)) values. RESULTS: The prevalence of T. vaginalis in the study population was 4.2% (5/119; 95% confidence interval [Cl], 1.5–9.7). Additionally, asymptomatic infection constituted 60% (3/5) of all cases of T. vaginalis infection. All T. vaginalis-positive patients were coinfected with HPV but not C. albicans. Five clinical T. vaginalis isolates showed metronidazole susceptibility, which was evaluated using MLC values. The quantitative IC(50) values revealed that two of these clinical isolates exhibited a decreased metronidazole susceptibility. CONCLUSION: This is the first study to demonstrate the prevalence of T. vaginalis in Japanese women. The IC(50) values of metronidazole against T. vaginalis enabled the precise and quantitative evaluation of metronidazole-susceptible T. vaginalis.

Objective The aim of this study was to examine the effect of coronavirus disease 2019 (COVID-19) on the malignancy-related clinical course and overall survival, and to determine the factors affecting mortality. Methods This retrospective study included 77 patients with hematological cancer and COVID-19. Patients were sub-grouped for analysis as survivors and non-survivors. Results COVID-19 was seen more frequently in myeloproliferative neoplasms (MPN), non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) patients. Mortality rate due to COVID-19 was 20.8%. No statistically significant difference was determined between the survivor and non-survivor groups with respect to age and gender, presence of any comorbidity, leukocyte, neutrophil, lymphocyte, and monocyte values. Platelet count and hemoglobin count were significantly lower in the group with mortality than in the group with recovery. Conclusion It should be kept in mind that low hemoglobin and platelet levels contribute to mortality. In addition, it is important to protect patients with hematological cancer from COVID-19 and undertake effective vaccination due to its mortal course.

Objective Transplantation of minor salivary glands (MSGs) to the conjunctiva is a treatment option for patients suffering from dry eye disease. As there is not enough information about labial and buccal MSGs in dogs, the aim of this study was to provide evidence of the presence of these glands and to investigate their spatial arrangement and excretory ducts. Methods The oral mucosa of the lower lip of 4 dogs and the whole lower jaw of 1 dog were used for histological and microCT analysis. Presence, number, volumes and the tissue depth of MSGs were assessed. Results Histological analysis showed that compact tubulo‐acinar glands were located in the submucosal connective tissue. MicroCT images revealed that 9 to 21 MSGs were arranged in a single row at the level of the dental alveolae. The volume of the MSGs increased from rostral to caudal and the total volume of glandular tissue per animal ranged from 35.01 mm3 to 549.43 mm3. The mean tissue depth of MSGs ranged from 0.57 mm to 1.37 mm (upper surface of glands) and between 1.43 mm and 3.09 mm (lower surface of the glands). Excretory ducts left the dorsal part of the glands and ran in dorso‐rostral direction. Conclusions The location, number and volume of the labial and buccal MSGs in the dog could be detected and described using microCT scans and histology. The present results can provide valuable information for future transplantation of labial MSGs as therapeutic measure against keratoconjunctivitis sicca.

Objectives: Health studies of structural racism/discrimination have been animated through the deployment of neighborhood effects frameworks that engage institutional­ist concerns about sociopolitical resources and mobility structures. This study high­lights the acute illness risks of place-based inequalities and neighborhood-varying race-based inequalities by focusing on access to and the regulation of mortgage markets. Design: By merging neighborhood data on lending processes from the Home Mortgage Disclosure Act with individual health from the Project on Human Development in Chicago Neighborhoods, this article evalu­ates the acute childhood illness risks of four mutually inclusive, political economies using multilevel generalized linear models. Setting: Chicago, IL, USA Participants: Youth aged 0 to 17 years Methods: Multilevel logistic regression Main Outcome Measures: The prevalence of 11 acute illnesses (cold/flu, sinus trouble, sore throat/tonsils, headache, upset stom­ach, bronchitis, skin infection, pneumonia, UTI, fungal disease, mononucleosis) and the past-year frequencies of 6 acute illnesses (cold/flu, sinus trouble, sore throat/tonsils, headache, upset stomach, bronchitis) are evaluated. Results: The most theoretically consistent predictor of illness is a measure identifying neighborhoods with above-city-median levels of racial disparities in the regulation of loans – a mesolevel measure of structural racism. In areas with high levels of Minority- White differences in less regulated credit, youth are more likely to have a range of acute illnesses and experience them at more frequent intervals in the past year. Conclusions: This article highlights the substantive and methodological importance of focusing on multidimensional representa­tions of institutionalized political economic inequalities circumscribed and traversed by the power relations established by institu­tions and the state. Ethn Dis. 2021;31(Suppl1):319-332; doi:10.18865/ed.31.S1.319

Implementation science (IS) has emerged in response to a striking research-to-practice gap, with the goal of accelerating and addressing the development, translation, and widespread uptake of evidence-based interventions (EBIs). Despite the promise of IS, critical gaps and opportunities remain within the field to explicitly facilitate health equity, particularly as they relate to the role of social determinants of health and structural racism. In this commentary, we propose recommendations for the field of IS to include structural racism as a more explicit focus of our work. First, we make the case for including structural racism as a construct and promote its measure­ment as a determinant within existing IS frameworks/models, laying the foundation for an empirical evidence base on mecha­nisms through which such factors influence inequitable adoption, implementation, and sustainability of EBIs. Second, we suggest considerations for both EBIs and implemen­tation strategies that directly or indirectly address structural racism and impact health equity. Finally, we call for use of methods and approaches within IS that may be more appropriate for addressing structural racism at multiple ecological levels and clinical and community settings in which we conduct IS, including community-based participatory research and stakeholder engagement. We see these as opportunities to advance the focus on health equity within IS and con­clude with a charge to the field to consider making structural racism and the disman­tling of racism an explicit part of the IS research agenda.Ethn Dis. 2021;31(Suppl 1):357-364; doi:10.18865/ed.31.S1.357

Introduction: Limited existing research suggests that immigration climate and enforcement practices represent a social determinant of health for immigrants, their families, and communities. However, national research on the impact of specific policies is limited. The goal of this article is to estimate the effect of county-level participation in a 287(g) immigration enforcement agreement on very preterm birth (VPTB

Background: Although wage theft has been discussed primarily as a labor and human rights issue, it can be conceptualized as an issue of structural racism with important consequences for immigrant health. Objectives: The objectives of this study were to: 1) identify sociodemographic, employment, and stress-related characteris­tics that increase LDLs’ odds of experiencing wage theft; 2) assess the association be­tween wage theft and serious work-related injury; 3) assess the association between wage theft and three indicators of mental health—depression, social isolation, and alcohol use—as a function of wage theft; and 4) assess serious work-related injury as a function of wage theft controlling for mental health. Methods: Secondary data analyses were based on survey data collected from 331 Latino day laborers between November 2013 and July 2014. Regression analyses were conducted to test the relationships described above. Results: Approximately 25% of participants reported experiencing wage theft and 20% reported serious work-related injury. Wage theft was associated with working in construction and was initially associated with work-related injury. Wage theft was not significantly associated with mental health indicators. The association between wage theft and injury became non-significant when controlling for the mental health variables. Conclusions: The hardship and stress associated with wage theft incidents may ultimately lead to more frequent injury. Al­though we expected an association of wage theft with mental health, we found vulner­ability to physical health as indicated by in­jury incidents. Thus, our basic premise was partially supported: wage theft may act as a stressor that stems from conditions, in part, reflecting structural racism, making work­ers vulnerable to poorer health. Ethn Dis. 2021;31(Suppl 1):345-356; doi:10.18865/ed.31.S1.345

Purpose: The Bureau of Communicable Disease (BCD) at the New York City De­partment of Health and Mental Hygiene developed and implemented a multi-level intervention to: 1) establish bureau-wide race consciousness; 2) provide opportunities to examine the contemporary manifesta­tions of racism impacting institutions and communities; 3) develop praxis applying a racial equity and social justice lens to communicable disease surveillance; and 4) center the experiences of Black, Indigenous, People of Color (BIPOC) staff. Methods: A staff committee designed and implemented a multipronged initiative grounded in Public Health Critical Race (PHCR) praxis. The findings from a qualita­tive report focused on the experiences of POC staff formed the basis of the initiative. Results: Three major themes were identi­fied in the report (Microaggressions Report) as fac­tors that resulted in institutional inequities within the workplace: race-based biases in promotion of staff; lack of opportunity shar­ing for professional growth; and dominant power relations silencing the voices of POC staff. Based on findings from the Microag­gressions Report, BCD designed and implemented seven interventions including: 1) Racial Identity Caucusing; 2) Multimedia Learning; 3) All-staff Workshops; 4) Social Breakout Committee; 5) Surveillance and Data Equity; 6) Core Values Development; and 7) Committee for Hiring, Retention and Promotion. Conclusion: We describe the rationale, de­sign, and implementation of a multipronged intervention at a local health department as a strategy to address institutional racism. The creation of a Microaggressions Report and the PHCR methodology framed our ongoing effort to improve workplace culture and promote equitable opportunities for POC staff. Ethn Dis . 2021;31(Suppl 1):365-374; doi:10.18865/ed.31.S1.365

Objectives : To use the Consolidated Framework for Implementation Research (CFIR) adapted to a race-conscious frame to understand ways that structural racism interacts with intervention implementation and uptake within an equity-oriented trial designed to enhance student-school con­nectedness. Design: Secondary analysis of qualitative implementation data from Project TRUST (Training for Resiliency in Urban Students and Teachers), a hybrid effectiveness-imple­mentation, community-based participatory intervention. Setting: Ten schools across one urban school district. Methods: We analyzed qualitative ob­servational field notes, youth and parent researcher reflections, and semi-structured interviews with community-academic re­searchers and school-based partners within CFIR constructs based on framing questions using a Public Health Critical Race Praxis approach. Results: Within most CFIR constructs and sub-constructs, we identified barriers to implementation uptake not previously recognized using standard race-neutral definitions. Themes that crossed constructs included: 1) Leaders’ willingness to examine Black, Indigenous, People of Color (BIPOC) student and parent experiences of school discrimination and marginalization had a cascading influence on multiple factors related to implementation uptake; 2) The race/ethnicity of the principals was related to intervention engagement and interven­tion uptake, particularly at the extremes, but the relationship was complex; 3) External change agents from BIPOC communities facilitated intervention uptake in indirect but significant ways; 4) Highly networked implementation champions had the ability to enhance commitment to intervention uptake; however, perceptions of these indi­viduals and the degree to which they were networked was highly racialized. Conclusions: Equity-oriented interventions should consider structural racism within the CFIR model to better understand inter­vention uptake. Ethn Dis . 2021;31(Suppl 1):375-388; doi:10.18865/ed.31.S1.375

Objective: The aim of the study was to retrospectively evaluate the prevalence of reported and unreported potentially important incidental findings (PIFs) in consecutive nonenhanced abdominal CTs performed specifically for renal colic in the urgent setting. Methods: One radiologist, blinded to the finalized report, retrospectively re-evaluated nonenhanced abdominal CTs performed from January to December 2017 on adult patients from the emergency department with the specific request of urgent evaluation for renal colic, searching for PIFs. Results: The CTs of 312 patients were included in the study. Thirty-eight findings were reported in 38 different CTs, whereas the re-evaluation added 47 unreported findings in 47 different CTs, adding to total of 85 findings (27%). The difference in the proportion of reported and unreported PIFs between the original report and re-evaluation was significant (p < 0.001). No significant difference was found between the age of patients with and without reported findings. The proportion of potentially important findings did not vary significantly among the 3 shifts in the original report and in re-evaluation. The most frequent findings, both reported and unreported, were pleural effusion, lymphadenopathies, and liver nodules. Conclusions: Potentially important additional findings are frequently present in urgent nonenhanced abdominal CTs performed for renal colic, and many are not described in the finalized reports. Radiologists should take care not to underreport PIFs even in the urgent setting because of the possible consequences on the patient’s health and in order to avoid legal issues, while at the same time satisfying the need for timely and efficient reporting.

Summary Background Multiple myeloma (MM) is a cytogenetically heterogeneous and incurable plasma cell disease with unknown etiology. It is thought that the ABO blood groups may play a role in the etiology of many diseases. The purpose of this study is to determine whether there is a relationship between the ABO blood groups and the development of MM, clinical findings and overall survival. Methods In this single-center, retrospective and observational study, 198 patients with known blood types who diagnosed with MM between January 2012 and June 2020 were included. Results It was shown that individuals with blood group 0 had a significantly lower risk of MM (OR = 0.575, 95% confidence interval 0.416–0.794, P = 0.001). The incidence of extramedullary lesion was significantly higher in those with 0 blood group compared to other blood groups (P = 0.000). Overall survival was significantly shorter in patients with 0 blood group than those without 0 blood group (P = 0.007). Conclusion Individuals with 0 blood group had a lower risk of developing MM. It was determined that having 0 blood group is a predisposing factor for the development of extramedullary lesion in MM patients. However, it was shown that having a blood group of 0 was a very significant prognostic factor for MM patients and was associated with short OS.

PURPOSE: In 2009 a Dutch guideline was published containing recommendations to reduce Hospital Admissions Related to Medications (HARMs). This study aims to examine time-trends of HARMs and their potential preventability between 2008 and 2013 in The Netherlands.METHODS: A retrospective prevalence study was conducted using the Dutch PHARMO Database Network. A semi-automated pre-selection was used to make a crude identification of possible HARMs of which four samples were selected. These were independently assessed with respect to causality and potential preventability by a physician and pharmacist. The results were stratified by age into 18-64 years and 65 years and older. For these groups the net prevalences and incidence rates of HARMs and potentially preventable HARMs were calculated for the years 2008, 2009, 2011 and 2013.RESULTS: Four samples of 467 (2008), 447 (2009), 446 (2011) and 408 (2013) admissions were assessed. The net prevalence of HARMs in the 18-64 years group was approximately four times smaller compared to the older group with a mean prevalence of 2.7% (95% confidence interval [CI]:2.4%-3.0%) and 10.2% (95%CI: 9.7%-10.7%) respectively. The potential preventability was 25.1% (18.4%-31.8%) and 48.3% (95%CI: 44.8%-51.8%), respectively. The prevalence of HARMs in both groups did not change significantly between 2008 and 2013 with 2.4% (95%CI: 1.9%-3.0%) and 10.0% (95%CI: 9.0%-11.0%) in 2008 and 3.1% (2.7%-3.5%) and 10.4% (95%CI: 9.4%-11.4%) in 2013, respectively.CONCLUSION: Despite efforts to reduce HARMs, the prevalence did not decrease over time. Additional measures are therefore necessary, especially in the elderly population.

Purpose This study evaluated the effectiveness of risk minimisation measures (RMMs) implemented following the 2014 referral for valproate in Europe. Methods Cross‐sectional survey was conducted over 2‐month period in 2016 among physicians who prescribed valproate in France, Germany, the United Kingdom, Spain and Sweden. The web‐based questionnaire included five endpoints to evaluate physicians' knowledge on (a) prescribing valproate only for epilepsy and bipolar disorder in women if other treatments were ineffective or not tolerated; (b) ensuring supervision by experienced physicians while treating these conditions; (c) considering alternative treatments for women planning pregnancy, regular review of treatment needs and re‐assessing the benefit–risk balance in women and girls reaching puberty; (d) informing patients about the risks of taking valproate during pregnancy and (e) advising women on effective contraception during their treatment. Results Among 1153 physicians, 95.5% responded prescribing valproate for epilepsy and bipolar disorder in women only if other treatments are ineffective/not tolerated; 66.5% supervised while treatment; 76.6% considered alternative treatments for women planning pregnancy; 92.1% informed patients about the risks of taking valproate during pregnancy and 94.4% advised patients on the use of effective contraception during its treatment. Overall, 25.8% physicians recalled receiving both educational material (EM) and Dear Healthcare Professional Communication (DHPC). All endpoint rates were higher for physicians who acknowledged receipt of both DHPC and EM compared to physicians who did not receive them. Conclusions Although results varied across geography and physician speciality, majority of physicians had good knowledge about the indication and safety aspects of prescribing and using valproate.

CK2α is a ubiquitous, well-studied protein kinase that is a target for small molecule inhibition, for treatment of cancers. While many different classes of ATP-competitive inhibitors have been described for CK2α, they tend to suffer from significant off-target activity and new approaches are needed. A series of inhibitors of CK2α has recently been described as allosteric, acting at a previously unidentified binding site. Given the similarity of these inhibitors to known ATP-competitive inhibitors, we have investigated these further. In our thorough structural and biophysical analyses, we have found no evidence that these inhibitors bind to the proposed allosteric site. Rather, we report crystal structures, competitive ITC and NMR, HDX mass spectrometry and chemoinformatic analyses that all point to these compounds binding in the ATP pocket. Our crystal structures however do show that the proposed allosteric site can bind ligands, just not those in the previously described series. Comparison of our results and experimental details with the data presented in the original report suggest several reasons for the disparity in our conclusions, the primary reason being non-specific inhibition by aggregation.Table of Content graphics

Purpose To describe the effect that validation of venous thromboembolism (VTE) coded entries in the health improvement network (THIN) has on incidence rates of VTE among a cohort of rivaroxaban/warfarin users. Methods Among 36 701 individuals with a first prescription for rivaroxaban/warfarin between 2012 and 2015, we performed a two‐step VTE case identification process followed by a two‐step case validation process involving manual review of patient records. A valid case required a coded entry for VTE at some point after their first rivaroxaban/warfarin prescription with evidence of referral/hospitalization either as a coded entry or entered as free text. Positive predictive values (PPVs) with 95% confidence intervals (CIs) were calculated using validated cases as the gold standard. Incidence rates were calculated per 1000 person‐years with 95% CIs. Results We identified 2166 patients with a coded entry of VTE after their initial rivaroxaban/warfarin prescription; incidence rate of 45.31 per 1000 person‐years (95% CI: 43.49‐47.22). After manual review of patient records including the free text, there were 712 incident VTE cases; incidence rate of 14.90 per 1000 person‐years (95% CI: 13.85‐16.02). The PPV for coded entries of VTE alone was 32.9%, and the PPV for coded entries of VTE with a coded entry of referral/hospitalization was 39.8%; this increased to 69.6% after manual review of coded clinical entries in patient records. Conclusions Among rivaroxaban/warfarin users in THIN, valid VTE case identification requires manual review of patient records including the free text to prevent outcome misclassification and substantial overestimation of VTE incidence rates.

Purpose Strategies to identify and validate acute myocardial infarction (AMI) and stroke in primary‐care electronic records may impact effect measures, but to an unknown extent. Additionally, the validity of cardiovascular risk factors that could act as confounders in studies on those endpoints has not been thoroughly assessed in the United Kingdom Clinical Practice Research Datalink's (CPRD's) GOLD database. We explored the validity of algorithms to identify cardiovascular outcomes and risk factors and evaluated different outcome‐identification strategies using these algorithms for estimation of adjusted incidence rate ratios (IRRs). Methods First, we identified AMI, stroke, smoking, obesity, and menopausal status in a cohort treated for overactive bladder by applying computerized algorithms to primary care medical records (2004–2012). We validated these cardiovascular outcomes and risk factors with physician questionnaires (gold standard for this analysis). Second, we estimated IRRs for AMI and stroke using algorithm–identified and questionnaire–confirmed cases, comparing these with IRRs from cases identified through linkage with hospitalization/mortality data (best estimate). Results For AMI, the algorithm's positive predictive value (PPV) was >90%. Initial algorithms for stroke performed less well because of inclusion of codes for prevalent stroke; algorithm refinement increased PPV to 80% but decreased sensitivity by 20%. Algorithms for smoking and obesity were considered valid. IRRs based on questionnaire‐confirmed cases only were closer to IRRs estimated from hospitalization/mortality data than IRRs from algorithm‐identified cases. Conclusions AMI, stroke, smoking, obesity, and postmenopausal status can be accurately identified in CPRD. Physician questionnaire–validated AMI and stroke cases yield IRRs closest to the best estimate.

Purpose To determine risk of respiratory tract infections, urinary tract infections and candidiasis in secukinumab users compared to ustekinumab users among individuals with psoriasis in Sweden. Methods This was a Swedish population‐based register‐linked new‐user cohort study on individuals with psoriasis and psoriasis arthritis treated with secukinumab (2015‐2017) and ustekinumab (2009‐2017). Ever‐never exposure definition was used, that is, each individual's follow‐up time was attributed to the drug they were first exposed to. Risk of severe respiratory and urinary tract infections and candidiasis (diagnosis codes from out‐patient specialist visits and in‐patient hospitalisations) and respiratory and urinary tract infections treated in primary care (proxied by dispensation of antibiotics) was determined by adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox regression. We also give crude incidence rates and rate ratios. Results In total, 1955 new users of secukinumab (n = 848) and ustekinumab (n = 1107) were identified. There was a slightly increased risk of respiratory and urinary tract infections treated in primary care among secukinumab users compared to ustekinumab users (HR: 1.22, 95% CI: 1.03‐1.43). Non‐significant differences in estimated risk of severe respiratory and urinary tract infections (HR: 0.96, 95% CI: 0.57‐1.61) and candidiasis (HR: 1.80, 95% CI: 0.84‐3.84) treated in the hospital setting were observed. Conclusion We observed a slightly increased risk of respiratory and urinary tract infections treated in primary care among secukinumab users compared to ustekinumab users. Larger studies with longer follow‐up are needed to draw conclusions on relative safety.

Neuropathies in Myoclonic Epilepsy with Ragged Red Fibers (MERRF) syndrome are frequent but ganglionopathies have never been reported. We retrospectively identified 24 patients with MERRF mutations in the neuromuscular center Nord/Est/Ile de France (Pitié-Salpêtrière, Paris, France). Seventeen nerve conduction studies (NCS) were available. Five patients had MERRF syndrome and ganglionopathy, a pure sensory neuropathy. All of them displayed ataxia and mild clinical sensory abnormalities. Ganglionopathies have been reported in mitochondrial diseases but never in MERRF syndrome. We suggest that patients presenting with ganglionopathy, especially if associated with myopathy, lipomatosis or epilepsy, should be screened for MERRF mutations.

Purpose During preclinical testing, teriparatide caused a dose‐dependent increase in the incidence of osteosarcoma in rats. This study compared the incidence rate of osteosarcoma among patients aged ≥65 years treated with teriparatide vs a matched‐comparator cohort. Methods This population‐based comparative‐cohort study matched exposure details for each teriparatide user, identified via Medicare Part D prescription claims, and up to four comparators based on age, sex, zip code, date of claim for filled prescription, and number of unique therapeutic classes dispensed. Outcomes were identified via linkage with participating cancer registries. All US state cancer registries were invited to participate. Results Overall, 153 316 patients in the teriparatide cohort and 613 247 in the comparator cohort were linked to 811 osteosarcoma cases from 26 participating state cancer registries (68% of US patients aged ≥65 years diagnosed 2007‐2014). Analysis on a subset of cohorts revealed they were balanced for known osteosarcoma risk factors and Charlson comorbidity index. Mean duration of teriparatide treatment was 10 months. No osteosarcoma cases were observed in the teriparatide cohort; the incidence rate in the comparator cohort was consistent with the background incidence rate among adults aged ≥65 years. The incidence rate ratio was 0.0 (95% confidence interval, 0.0‐3.2). Conclusions For US patients aged ≥65 years, incidence of osteosarcoma among those treated with teriparatide ranges from 0 to 3.2 times the incidence of osteosarcoma in those treated with other medications. Given low incidence of osteosarcoma, this range of effect is inconsistent with a large absolute increase in osteosarcoma risk.

Background To ensure successful integration and implementation of evidence into practice, validation of measures and interventions should be performed in the population and setting in which they will be used. Purpose This article provides a method for evaluating the predictive performance of a risk tool using the Hester Davis fall risk tool as an example. Methods A retrospective matched-pairs sample of fallers and nonfallers was created. Psychometric properties were calculated using 2 × 2 contingency tables and compared to data in the original report. Results In this study sample, the risk tool showed minimal ability to distinguish patients at risk for falling from those not at risk. Conclusions Organizations are urged to assess the performance of risk tools in their own patient population. This article provides a practical approach for the validation of evidence into the practice setting.

Purpose To compare the effectiveness and safety of a drug in daily practice with the outcomes of a target non‐inferiority trial by rigorously mimickingin an observational study the trial's design features. Methods This cohort study was conducted using the British Clinical Practice Research Datalink (CPRD) to emulate the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial. Patients with atrial fibrillation who were newly prescribed (>=12 months of no use) either rivaroxaban or warfarinfrom October 2008 to December 2017 were included. Non‐inferiority of rivaroxaban to warfarin in the prevention of stroke or systemic embolism was assessed in different analysis populations (intention‐to‐treat [ITT], per‐protocol [PP], and as‐treated populations) using a hazardratio (HR) of 1.46 as the non‐inferiority margin. Major bleeding (safety outcome) was also assessed and compared to that of the target trial. All outcomes were analyzed using Cox‐proportional hazard analyses. Results We included 25,473 incident users of rivaroxaban (n=4,008) or warfarin(n=21,465). Similar to the trial, non‐inferiority in the primary out come was demonstrated in all three analysis populations: HR=1.04 (95%CI 0.84 to 1.30) (ITT), HR=0.98 (95%CI 0.70 to 1.38) (PP), and HR=1.11 (95%CI 0.86 to 1.42) (as‐treated). Risk of major bleeding was also similar to the target trial. Conclusion The results of this study provide supportive evidence to the effectiveness of rivaroxaban and adds knowledge on the usefulness of emulating a non‐inferiority trial to assess drug effectiveness.

OBJECTIVES Self-ratings seem to be the most effortless strategy for assessment of patients' chemical senses. Notably, although flavor perception strongly relies on olfaction, the relationship between self-reported flavor perception and orthonasal olfactory tests have hitherto not been considered. The aim of this study was to investigate the relationship between self-perceived olfactory function (SO), taste (ST), and flavor perception (SF) and smell test results in patients with olfactory dysfunction (OD). METHODS We included 203 patients with quantitative OD. Group comparison, bivariate correlation, and ordinal logistic regression were employed to quantify the relationships between predictor variables (age, gender, reason for OD, and orthonasal olfaction-summed scores of threshold, discrimination, and identification [TDI]) and outcomes of SO and SF ("impaired," "average," or "good"). RESULTS Group comparison revealed significant differences between SO and SF (P

Purpose The purpose of this paper is to present the Part 2 of CES Conference review. Design/methodology/approach This paper is a conference review. Findings Focus is on new innovative products on display. Originality/value This paper is an original report.

Objectives This study examined the effectiveness of injection laryngoplasty (IL) in muscle tension dysphonia (MTD) patients who did not fully respond to voice therapy. It was hypothesized that IL would improve voice quality and voice-related quality of life measures in MTD. Methods A retrospective review was conducted on 37 patients with a primary diagnosis of MTD who underwent IL following a suboptimal response to voice therapy (mean age = 43.0 years; standard deviation [SD] = 13.4; range = 23 to 71). Outcome measures included laryngoscopic signs of supraglottic constriction, Voice Handicap Index-10 (VHI-10) scores, maximal phonation time, vowel fundamental frequency (F0), standard deviation of F0 (F0SD), harmonics-to-noise ratio (HNR), and smoothed cepstral peak prominence. These were compared between baseline and within 3 months following the IL procedure. Results There was significant decrease in supraglottic constriction. Mean (SD) of VHI-10 scores decreased from 25.4 (5.7) at baseline to 15.3 (9.3) following IL. This improvement in VHI-10 was observed in patients with and without baseline glottal insufficiency (GI). Mean (SD) of HNR (decibels) increased from 21.1 (5.4) at baseline to 22.8 (4.3) after IL. Only patients with GI demonstrated a significant improvement in HNR from baseline to post-IL. No statistically significant differences in other acoustic measures were observed. Conclusions IL resulted in positive changes in voice-related quality of life in MTD patients with and without GI. Acoustically, only those with GI demonstrated an increase in HNR following IL. Further studies are needed to examine the effects of IL in MTD. Level of evidence 4 Laryngoscope, 130:980-985, 2020.

Purpose To estimate the risk of dyskinesia and impulse control disorders (ICDs) in patients with Parkinson's disease (PD) prescribed ropinirole prolonged‐release (R‐PR) compared to those prescribed immediate‐release dopamine agonists (IR‐DA) as monotherapy. Methods PD patients initiating R‐PR or IR‐DA as monotherapy between 2008 and 2013 were identified on the Clinical Practice Research Datalink. The cohorts were propensity score matched on a 1:1 basis. The incidence of dyskinesia and ICD in each treatment cohort and the incidence rate ratios were calculated. Adherence to medication and time to levodopa initiation were also evaluated. Results We identified 341 patients in each treatment cohort after propensity score matching. The baseline characteristics were generally comparable. Dyskinesia incidence in R‐PR and IR‐DA cohorts was 2.98 (95% CI: 0.74‐11.9) and 3.93 (95% CI: 0.98‐15.7) per 1000 person‐years, respectively (incidence rate ratio of R‐PR vs ID‐DA: 0.76, 95% CI: 0.11‐5.38). Less than five cases of ICD were identified and all occurred in the IR‐DA cohort. The patients in the R‐PR cohort remained on treatment for a significantly longer duration than those in the IR‐DA cohort (682 days vs 444 days; P

Randomized clinical trials (RCTs) are the gold standard in producing clinical evidence of efficacy and safety of medical interventions. More recently, a new paradigm is emerging—specifically within the context of preauthorization regulatory decision‐making—for some novel uses of real‐world evidence (RWE) from a variety of real‐world data (RWD) sources to answer certain clinical questions. Traditionally reserved for rare diseases and other special circumstances, external controls (eg, historical controls) are recognized as a possible type of control arm for single‐arm trials. However, creating and analyzing an external control arm using RWD can be challenging since design and analytics may not fully control for all systematic differences (biases). Nonetheless, certain biases can be attenuated using appropriate design and analytical approaches. The main objective of this paper is to improve the scientific rigor in the generation of external control arms using RWD. Here we (a) discuss the rationale and regulatory circumstances appropriate for external control arms, (b) define different types of external control arms, and (c) describe study design elements and approaches to mitigate certain biases in external control arms. This manuscript received endorsement from the International Society for Pharmacoepidemiology (ISPE).

Purpose Investigate effectiveness by gender and age and equity implications of treatment with renin‐angiotensin system blockade (RASb) in heart failure (HF) patients. Methods In this population‐based register study, we used inpatient data from 2006 to 2010 for patients age 20 years or older with no HF hospitalisation for minimum of 1 year before an index hospitalisation. A wash‐out period for RASb of 6 months preceding admission was used. Hospital data were linked with drug dispensation data and cause of death data. The associations between time‐dependent RASb exposure and all‐cause death and HF death, respectively, were examined by Cox regression models. Interactions by gender and age were also investigated on the multiplicative and additive scales. Results Thirty thousand seven hundred twenty‐one patients were analysed. Fifty‐one percent were women. Median age was 83. Fifty‐three percent of women and 64% of men received RASb after the index hospitalisation. Younger patients were more likely to receive RASb than older ones. One‐year mortality was 28%. RASb was associated with an overall hazard ratio (HR) for all‐cause death of 0.72 (95% confidence interval 0.69‐0.75), and an HR of 0.85 (0.77‐0.93) for HF death. Interaction analyses showed HRs for all‐cause death associated with RASb between 0.12 (0.10‐0.13) in the youngest, and 0.80 (0.76‐0.84) in the oldest patients. Conclusions RASb appeared effective for women and men and for patients of all ages in this hospitalised HF cohort. No gender difference in effectiveness was found. RASb exposure was low overall, indicating a need for improved adherence to treatment guidelines. Treatment with RASb may be inequitable for women and older patients.

This article reports the first verified cases of infection by Trichophyton bullosum in Africa since the description of the fungus, isolated in 1933 from the coat of horses in Tunisia and Mali. We found the fungus in cutaneous samples obtained from donkeys suffering from severe dermatitis with areas of alopecia and scaling in the surroundings of Cairo (Egypt). Fungal elements (arthroconidia and hyphae) were seen at the microscopy of material collected by skin scraping and digested in NaOH. Fungal colonies grown on various culture media were identified through PCR and sequencing of the ITS rDNA region. Since the original report in Africa and the Middle East, only a few cases have been reported thus far in humans in France and two cases in horses in the Czech Republic and Japan. Trichophyton bullosum seems thus an infrequent cause of dermatophytosis. However, the actual prevalence of this pathogen may be underestimated due to the similarity with T. verrucosum, a predominant cause of infection in cattle, occasionally found on horses and donkeys. Indeed, the two fungi can be distinguished only via molecular methods, which are poorly employed in epidemiological studies on equine and bovine dermatophytosis. The present study results add to our knowledge on the ecology of this poorly explored dermatophyte, supporting the concept that equines are the primary hosts of T. bullosum and confirming the presence of this pathogen in Africa. At the same time, these are the first unequivocally documented infections in donkeys due to T. bullosum.

PURPOSE Tobacco use is the leading cause of premature death worldwide. One aspect of tobacco control is convincing farmers to stop tobacco production. We assessed the willingness of tobacco farmers in Uganda to stop growing tobacco. METHODS We conducted a cross-sectional interview survey with an interviewer-administered questionnaire. Participants were active tobacco farmers in 12 villages of Kanungu district (N = 528) and were interviewed in 2013 to assess their willingness to stop growing tobacco. RESULTS Most farmers (61.7%) grew tobacco only as a cash crop with no supplemental income. A total of 198 farmers (37.5%) were willing to stop growing tobacco. Ninety-two respondents cited coffee as a potential replacement crop for tobacco and 106 mentioned rice. Barriers to growing replacement crops were that tobacco is highly profitable (n = 172) and that the soil (n = 175) and/or weather (n = 22) cannot sustain any crops other than tobacco. Willingness to stop growing tobacco was 1.32 times as likely among farmers who said that tobacco use causes respiratory diseases and 1.16 times as likely among farmers who received less than less than $300 USD from tobacco sales in the previous season. Agreeing that tobacco is profitable decreased the likelihood of willingness to stop growing tobacco by 36%. CONCLUSION Only one in three farmers were willing to stop growing tobacco. To increase their willingness to stop growing tobacco, farmers must be educated on the health consequences of tobacco and we must demonstrate to farmers that other crops may be more profitable than tobacco.

PURPOSE Although cancer is uncommon, it is a significant cause of pediatric morbidity and mortality in the developing world. The need for intensive care in pediatric oncology has increased with more intense chemotherapeutic interventions. It is important to identify patients who will benefit from management in the intensive care unit (ICU), given the resource limitation in developing countries. In this review, we examine our institutional experience with pediatric patients with cancer needing ICU care. METHODS A retrospective chart review from December 2015 to June 2017 was performed with institutional review board approval for all pediatric oncology patients admitted to the ICU. Data collection included age, diagnosis, disease stage, Pediatric Risk of Mortality (PRISM III) score, and therapeutic interventions. RESULTS We reviewed 59 pediatric oncology ICU medical records. There were 36 boys (61%) and 23 girls (39%). The median age was 4 years. Average stay in the ICU was 4.6 days. Three significant reasons for ICU referral were respiratory distress, sepsis, and circulatory collapse. There were 34 ICU survivors (57.6%). Among those who survived the ICU, 20 patients (58.8%) later died of therapy-related complications. Factors related to increased ICU mortality included the need for mechanical ventilation, the need for inotropic support, the number of failing organs, and a high PRISM III score. CONCLUSION The mortality rate for pediatric oncology patients admitted to the ICU in developing countries is higher than in developed countries. Mortality was significantly related to the need for mechanical ventilation. PRISM III scoring can help identify patients who can benefit from ICU treatment, which is expensive in resource-limited low- and middle-income countries such as Pakistan.

PURPOSE Cervical cancer constitutes a public health problem in Cameroon where it represents 13.8% of cancers in women. We wanted to evaluate compliance with cervical cancer care with a focus on patients who are lost to follow-up from the time that symptoms suggestive of cervical cancer are clinically recognized to treatment. PATIENTS AND METHODS Sociodemographic data, attitude toward diagnosis and treatment, and reason for discontinuing care were recorded and analyzed for a period of 5 years from January 2010 to December 2015. RESULTS One hundred twenty-six patients had symptoms suggestive of cervical cancer, but only 110 (87.30%) could pay for biopsy, 29 (26.36%) of those did not collect their results, 17 (18.7%) denied their results, and 20 (19%) did not benefit from treatment. Only 44 of 110 patients were able to finish their cancer care treatment program. Reasons for discontinuing the cancer care included lack of financial means to pay for it, distance from the care center, and belief in alternative treatments. CONCLUSION This study highlights the magnitude of the difficulties of accessing and receiving cancer care in semiurban areas in Cameroon. Poverty, belief in alternative treatment options, and unequal distribution of care services determined which patients would be lost to follow-up. Redistribution of resources and cancer care providers is mandatory to improve this situation.

PURPOSE Biomarker—estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/ neu) —discordance plays an essential role in the management and prognosis of patients with metastatic breast cancer. Rates of discordance have been previously reported around 12% to 35%, 30% to 50%, and 5% to 15%, respectively, in Western literature. Data are sparse regarding the same from developing countries, such as India. METHODS We performed an ambispective review of paired biomarker status in patients with breast cancer—stage I, II, and III as per American Joint Committee on Cancer, 7th edition—who developed metastasis at recurrence (N = 103 patients). Biomarker status and clinical and radiologic parameters were documented at baseline and subsequent follow-up. RESULTS Discordance was present in 21.3% for ER, 29.1% for PR, and 15.5% for HER2/ neu receptor. In our cohort, 7.8% had positive to negative ER and 13.6% negative to positive. Whereas 21.4% had positive to negative PR, 7.8% had negative to positive PR. Approximately 6.8% had positive to negative HER2/ neu receptor and 8.7% negative to positive. In our cohort, 41 patients (40%) had single-site metastasis—bone, 15.5%; lung, 11.7%; nonregional lymph node, 7.8%; liver, 3.9%; and brain, 0.97%. More than one site of metastasis was present in 62 patients (60%). The most common sites of metastasis were visceral—lung and liver—followed by bone, nonregional lymph node, skin, and brain. CONCLUSION The current study demonstrated that metastatic disease evolution in breast cancer is characterized by change in the tumor biology, which leads to discordance in receptor status. Repeat biomarker studies at metastatic recurrence is warranted, especially if treatment plans include hormone and targeted therapy.

PURPOSE In the Middle East, incidence rate ratios (IRRs) of non-Hodgkin lymphoma (NHL) to Hodgkin lymphoma (HL) are more than 50% lower than the United States. MATERIALS AND METHODS Age-specific incidence rates (ASIRs), age-adjusted incidence rates (AAIRs), and IRRs of NHL:HL were compared using the cancer registries of Iraq, Jordan, Saudi Arabia, and US SEER. RESULTS The NHL AAIR (95% CI) per 100,000 population was 4.4 (4.1 to 4.7) for Iraq, 5.4 (4.6 to 6.2) for Jordan, 4.7 (4.4 to 5.1) for Saudi Arabia, and 13.2 (13.0 to 13.4) for the United States. The HL AAIR was 1.8 (1.6 to 2.0) for Iraq, 1.8 (1.4 to 2.2) for Jordan, 2.1 (1.9 to 2.2) for Saudi Arabia, and 2.3 (2.2 to 2.4) for the United States, with respective NHL:HL IRR of 2.4 (2.2 to 2.7), 3.0 (2.4 to 3.8), 2.2 (2.0 to 2.5), and 5.7 (5.5 to 6.0). NHL ASIRs for the Middle East and the United States were similar until 30 to 39 years of age. Thereafter, ASIR of NHL peaked at 20 to 33 per 100,000 at age 70 years in the Middle East regions, all much lower than the US age 70 years rate of greater than 100 per 100,000. Diffuse large B-cell lymphoma (DLBCL) represented 52% of NHL in Sulaimaniyah Province of Iraq and 51% of NHL in Saudi Arabia. Both regions had AAIR for DLBCL less than 42% of DLBCL in US SEER. Pediatric Epstein-Barr virus–related Burkitt’s lymphoma at 8% was the second most frequent NHL in Sulaimaniyah but made little contribution to overall NHL rates. CONCLUSION The incidence of HL was slightly lower than in the United States, but it was the markedly lower rates of adult NHL with advancing age, including the predominant DLBCL, that accounted for the low NHL:HL IRR in these Middle Eastern countries.

PURPOSE RNA editing is a post-transcriptional process that alters the nucleotide sequences of certain transcripts, in vertebrate most often converting adenosines to inosines. Multiple studies have recently implicated RNA editing in cancer development; however, most studies have focused on recoding RNA editing events. The function and clinical relevance of noncoding RNA (ncRNA) editing events in cancers have not been systematically examined. PATIENTS AND METHODS We improved our previously published pipeline to identify ncRNA editing sites from four human cancers: liver hepatocellular carcinoma, lung adenocarcinoma, kidney renal clear-cell carcinoma, and thyroid carcinoma. We then developed multiple advanced statistical models to identify significantly differential edited (DE) sites between tumor and normal samples and clinical relevance ncRNA editing sites, as well as to investigate the association between gene expression, ncRNA editing, and microRNAs. Finally, we validated computational results with experiments. RESULTS We identified 3,788 ncRNA editing sites of high confidence from the four cancers. We found thousands of DE sites which had distinct profiles across the four cancers. In kidney cancer, which had the largest uncensored survival data among the four cancers, 80 DE sites were significantly associated with patient survival. We identified 3′ untranslated region (UTR) RNA editing sites that can affect gene expression, either independent of or by working with microRNAs. We validated that the 3′UTR RNA editing sites in CWF19L1 and F11R genes resulted in increased protein levels and that alterations of the expression of the two genes affected the proliferation of human embryonic kidney cells. CONCLUSION On the basis of our computational and experimental results, we hypothesize that 3′UTR editing sites may affect their host gene expression, thereby affecting cell proliferation.

PURPOSE Hospitalizations are a common occurrence during chemotherapy for advanced cancer. Validated risk stratification tools could facilitate proactive approaches for reducing hospitalizations by identifying at-risk patients. PATIENTS AND METHODS We assembled two retrospective cohorts of patients receiving chemotherapy for advanced nonhematologic cancer; cohorts were drawn from three integrated health plans of the Cancer Research Network. We used these cohorts to develop and validate logistic regression models estimating 30-day hospitalization risk after chemotherapy initiation. The development cohort included patients in two health plans from 2005 to 2013. The validation cohort included patients in a third health plan from 2007 to 2016. Candidate predictor variables were derived from clinical data in institutional data warehouses. Models were validated based on the C-statistic, positive predictive value, and negative predictive value. Positive predictive value and negative predictive value were calculated in reference to a prespecified risk threshold (hospitalization risk ≥ 18.0%). RESULTS There were 3,606 patients in the development cohort (median age, 63 years) and 634 evaluable patients in the validation cohort (median age, 64 years). Lung cancer was the most common diagnosis in both cohorts (26% and 31%, respectively). The selected risk stratification model included two variables: albumin and sodium. The model C-statistic in the validation cohort was 0.69 (95% CI, 0.62 to 0.75); 39% of patients were classified as high risk according to the prespecified threshold; 30-day hospitalization risk was 24.2% (95% CI, 19.9% to 32.0%) in the high-risk group and 8.7% (95% CI, 6.1% to 12.0%) in the low-risk group. CONCLUSION A model based on data elements routinely collected during cancer treatment can reliably identify patients at high risk for hospitalization after chemotherapy initiation. Additional research is necessary to determine whether this model can be deployed to prevent chemotherapy-related hospitalizations.

PURPOSE Matching patients to investigational therapies requires new tools to support physician decision making. We designed and implemented Precision Insight Support Engine (PRECISE), an automated, just-in-time, clinical-grade informatics platform to identify and dynamically track patients on the basis of molecular and clinical criteria. Real-world use of this tool was analyzed to determine whether PRECISE facilitated enrollment to early-phase, genome-driven trials. MATERIALS AND METHODS We analyzed patients who were enrolled in genome-driven, early-phase trials using PRECISE at Memorial Sloan Kettering Cancer Center between April 2014 and January 2018. Primary end point was the proportion of enrolled patients who were successfully identified using PRECISE before enrollment. Secondary end points included time from sequencing and PRECISE identification to enrollment. Reasons for a failure to identify genomically matched patients were also explored. RESULTS Data were analyzed from 41 therapeutic trials led by 19 principal investigators. In total, 755 patients were accrued to these studies during the period that PRECISE was used. PRECISE successfully identified 327 patients (43%) before enrollment. Patients were diagnosed with 29 tumor types and harbored alterations in 43 oncogenes, most commonly ERBB2 (21.3%), PIK3CA (14.1%), and BRAF (8.7%). Median time from sequencing to enrollment was 163 days (interquartile range, 66 to 357 days), and from PRECISE identification to enrollment 87 days (interquartile range, 37 to 180 days). Common reasons for failing to identify patients before enrollment included accrual on the basis of molecular alterations that did not match pre-established PRECISE genomic eligibility (140 [33%] of 428) and external sequencing not available for parsing (127 [30%] of 428). CONCLUSION PRECISE identified 43% of all patients accrued to a diverse cohort of early-phase, genome-matched studies. Purpose-built informatics platforms represent a novel and potentially effective method for matching patients to molecularly selected studies.

PURPOSE Cancer is a growing public health concern in low-income countries (LICs). From 14 million new patient cases identified worldwide each year, 8 million are diagnosed in LICs. The fatality rate is 75% in LICs compared with 46% in high-income countries. Causes are low literacy levels, lack of awareness and knowledge about cancer, and limited education of health care professionals that leads to late detection and diagnosis. In Tanzania, cancer incidence will double to 60,000 in 2030. The referral hospital of Northern Tanzania established a new cancer unit in December 2016 to meet these needs. However, there is limited knowledge about perceptions of health care professionals toward cancer care in LICs. This study aims to understand attitudes and perspectives of those professionals and the treatment-related challenges in a newly established center to assist future efforts in this field. METHODS A qualitative method approach using in-depth interviews was chosen to achieve inductive conceptualization. Analysis of data was performed according to qualitative content analysis. RESULTS Eleven interviews were conducted. Five main categories were found: training and education of staff, availability of financial support, challenges in management, interests in future developments, and job satisfaction. Subcategories elaborated in more detail within the main categories. CONCLUSION Limitations in staffing, training, and education were major concerns. The importance of sustainable funding and the needed cooperation of the government with international aid were identified as key points. The involvement of different stakeholders requires guidance by health care management. Health care professionals expressed their satisfaction with the possibilities of treating cancer and the rewarding feedback from patients. Misconceptions and poor knowledge by patients were mentioned as reasons for delayed health-seeking behavior. Screening and awareness programs were seen as useful interventions.

PURPOSE Molecular cancer subtyping is an important tool in predicting prognosis and developing novel precision medicine approaches. We developed a novel platform-independent gene expression–based classification system for molecular subtyping of patients with high-grade serous ovarian carcinoma (HGSOC). METHODS Unprocessed exon array (569 tumor and nine normal) and RNA sequencing (RNA-seq; 376 tumor) HGSOC data sets, with clinical annotations, were downloaded from the Genomic Data Commons portal. Sample clustering was performed by non-negative matrix factorization by using isoform-level expression estimates. The association between the subtypes and overall survival was evaluated by Cox proportional hazards regression model after adjusting for the covariates. A novel classification system was developed for HGSOC molecular subtyping. Robustness and generalizability of the gene signatures were validated using independent microarray and RNA-seq data sets. RESULTS Sample clustering recaptured the four known The Cancer Genome Atlas molecular subtypes but switched the subtype for 22% of the cases, which resulted in significant ( P = .006) survival differences among the refined subgroups. After adjusting for covariate effects, the mesenchymal subgroup was found to be at an increased hazard for death compared with the immunoreactive subgroup. Both gene- and isoform-level signatures achieved more than 92% prediction accuracy when tested on independent samples profiled on the exon array platform. When the classifier was applied to RNA-seq data, the subtyping calls agreed with the predictions made from exon array data for 95% of the 279 samples profiled by both platforms. CONCLUSION Isoform-level expression analysis successfully stratifies patients with HGSOC into groups with differing prognosis and has led to the development of robust, platform-independent gene signatures for HGSOC molecular subtyping. The association of the refined The Cancer Genome Atlas HGSOC subtypes with overall survival, independent of covariates, enhances the clinical annotation of the HGSOC cohort.

PURPOSE Although the bulk of patient-generated health data are increasing exponentially, their use is impeded because most data come in unstructured format, namely as free-text clinical reports. A variety of natural language processing (NLP) methods have emerged to automate the processing of free text ranging from statistical to deep learning–based models; however, the optimal approach for medical text analysis remains to be determined. The aim of this study was to provide a head-to-head comparison of novel NLP techniques and inform future studies about their utility for automated medical text analysis. PATIENTS AND METHODS Magnetic resonance imaging reports of patients with brain metastases treated in two tertiary centers were retrieved and manually annotated using a binary classification (single metastasis v two or more metastases). Multiple bag-of-words and sequence-based NLP models were developed and compared after randomly splitting the annotated reports into training and test sets in an 80:20 ratio. RESULTS A total of 1,479 radiology reports of patients diagnosed with brain metastases were retrieved. The least absolute shrinkage and selection operator (LASSO) regression model demonstrated the best overall performance on the hold-out test set with an area under the receiver operating characteristic curve of 0.92 (95% CI, 0.89 to 0.94), accuracy of 83% (95% CI, 80% to 87%), calibration intercept of –0.06 (95% CI, –0.14 to 0.01), and calibration slope of 1.06 (95% CI, 0.95 to 1.17). CONCLUSION Among various NLP techniques, the bag-of-words approach combined with a LASSO regression model demonstrated the best overall performance in extracting binary outcomes from free-text clinical reports. This study provides a framework for the development of machine learning-based NLP models as well as a clinical vignette of patients diagnosed with brain metastases.

Purpose BRAF mutation in papillary thyroid carcinoma (PTC) is associated with an aggressive phenotype, with varying incidence. We evaluated the prevalence of BRAF mutations in PTC among Filipino patients and their correlation with clinicopathologic characteristics. Patients and Methods Clinicopathologic data were retrieved from 64 sequential patients who underwent thyroidectomy from June 2016 to December 2016. BRAF mutation testing was performed using Sanger sequencing. Results Eighteen (28%) of 64 patients were diagnosed with PTC; 12 (70.59%) of 17 harbored a BRAF V600E mutation (no amplification in one patient). Demographics of patients with PTC were as follows: 13 women and five men, with median age of 46 years (range, 25 to 74 years). Fourteen patients had conventional subtype PTC; two, follicular variant; one, oncocytic variant; and one, tall-cell features. Tumor size ranged from 0.8 to 7.0 cm (median, 2.4 cm); extrathyroidal extension was present in seven (38.9%) of 18 patients, multifocality in six (33.33%) of eight, and lymph node involvement in eight (44.4%) of 18. Significant association between presence of a BRAF mutation and presence of extrathyroidal extension or lymph node involvement was not determined due to the limited sample size. Conclusion The high preponderance of BRAF mutation (70.59%) suggests some correlation with the previously reported lower 5-year survival among Filipinos. This warrants further investigation in a larger-cohort prospective study.

PURPOSE Multidisciplinary management of Wilms tumor has been defined through multicenter prospective studies and an average expected patient cure rate of 90%. In sub-Saharan Africa, such studies are uncommon. After the encouraging results of the first Groupe Franco-Africain d'Oncologie Pédiatrique (GFAOP) study, we report the results of the GFAOP-NEPHRO-02 study using an adaptation of the International Society of Paediatric Oncology 2001 protocol. PATIENTS AND METHODS From April 1, 2005, to March 31, 2011, seven African units participated in a nonrandomized prospective study. All patients who were referred with a clinical and radiologic diagnosis of renal tumor were screened. Those older than age 6 months and younger than 18 years with a unilateral tumor previously untreated were pre-included and received preoperative chemotherapy. Patients with unfavorable histology or with a tumor other than Wilms, or with a nonresponding stage IV tumor were excluded secondarily. RESULTS Three hundred thirteen patients were initially screened. Two hundred fifty-seven patients were pre-included and 169 with histologic confirmation of intermediate-risk nephroblastoma were registered in the study and administered postoperative treatment. Thirty-one percent of patients were classified as stage I, 38% stage II, 24% stage III, and 7% stage IV. Radiotherapy was not available for any stage III patients. Three-year overall survival rate was 72% for all study patients and 73% for those with localized disease. CONCLUSION It was possible to conduct sub-Saharan African multicenter therapeutic studies within the framework of GFAOP. Survival results were satisfactory. Improvements in procedure, data collection, and outcome are expected in a new study. Radiotherapy is needed to reduce the relapse rate in patients with stage III disease.

PURPOSE Cancer is in the process of changing to become a chronic disease; therefore, an increasing number of oncologic patients (OPs) are being admitted to intensive care units (ICUs) for supportive care of disease or therapy-related complications. We compare the short- and long-term outcomes of critically ill mechanically ventilated OPs with those of their nononcologic counterparts. PATIENTS AND METHODS We performed a prospective study of patients admitted to our ICU between October 2017 and February 2019. Demographic, physiologic, laboratory, clinical, and treatment data were obtained. The primary outcome was survival at 28 days and at the end of the follow-up period. Secondary outcomes were survival according to acute severity scoring (Acute Physiology and Chronic Health Evaluation II score), Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson comorbidity index. RESULTS A total of 1,490 patients were admitted during the study period; 358 patients (24%) were OPs, and 100 of these OPs were supported with mechanical ventilation. Seventy-three percent of OPs had an ECOG performances status of 0 or 1, and 90% had solid tumors. Reason for admission to the ICU was postoperative admission in 44 patients and neutropenic infection in 10 patients. The follow-up period was 148 days (range, 42 to 363 days). Survival at 28 days was similar between OPs and nononcologic patients and associated with the Acute Physiology and Chronic Health Evaluation II score. However, long-term survival was lower in OPs compared with nononcologic patients (52% v 76%, respectively; P < .001) and associated with poor ECOG performance status. CONCLUSION Short-term survival of critically ill, mechanically ventilated OPs is similar to that of their nononcologic counterparts and is determined by the severity of the critical illness.

PURPOSE The overall survival (OS) results in patients with ALK-positive metastatic non–small-cell lung cancer (NSCLC) have rarely been reported. The aim of this prospective-retrospective cohort study was to obtain real-world data on the use of crizotinib or chemotherapy in patients with ALK-positive metastatic NSCLC in Russia. PATIENTS AND METHODS Patients with epidermal growth factor receptor–negative metastatic NSCLC were screened in 23 cancer centers. To be eligible, patients were required to have confirmation of ALK rearrangement. Patients were treated with crizotinib (250 mg twice daily; n = 96) or the investigator’s choice of platinum-based chemotherapy (n = 53). The primary end point was OS. RESULTS A total of 149 ALK-positive patients were included. Mean age was 53 years in both groups. Patients were predominately women (59%) and never-smokers (74%), and most patients had adenocarcinoma histology (95%). At a median follow-up time of 15 months, 79 of the 149 patients included in the analysis had died. Median OS from the start of treatment was 31 months (95% CI, 28.5 to 33.5 months) in the crizotinib group and 15.0 months (95% CI, 9.0 to 21.0 months) in the chemotherapy group ( P < .001). The objective response rate was 34% in the crizotinib group. Among patients with brain metastasis, one complete response (6%) and five partial responses (31%) were achieved. Grade 3 adverse events were observed in three patients (3%) in the crizotinib group. CONCLUSION The improved OS observed in crizotinib clinical trials in ALK-positive NSCLC was also observed in the less selective patient populations treated in daily practice in Russia. The use of standard chemotherapy in these patients remains common but seems inappropriate as a result of the effectiveness of newer treatments, such as crizotinib.

PURPOSE Cervical cancer is the leading cause of mortality by cancer in sub-Saharan Africa. The human papillomavirus (HPV) infection is recognized as a necessary and sufficient cause for cervical cancer. Population-specific estimates of HPV prevalence in the Democratic Republic of the Congo (DRC) are unknown. This study aims to estimate the prevalence of HPV and identify predominant genotypes circulating in Kinshasa, DRC. METHODS Between July 2015 and July 2017, women were invited to attend a screening program at Mont-Amba Health Centre in Kinshasa. Cervical specimens were collected using the Preservcyt medium. HPV DNA testing was performed for all specimens using real-time polymerase chain reaction. RESULTS During the 2-year period, a total of 1,870 women age 25 to 82 years were screened. The mean age was 46 years (± 11.4 years). The overall HPV prevalence was 28.2% (95% CI, 26.1% to 30.3%). High-risk HPV prevalence was 24.8% (95% CI, 22.8% to 26.8%). Women younger than 30 years had the highest overall HPV prevalence (42.2%; 95% CI, 34.7% to 49.9%). A second peak of prevalence was observed in women age 60 years and older. HPV68 (5.5%; 95% CI, 4.5% to 6.6%) was the most prevalent HPV type. CONCLUSION The distribution of HPV genotypes among women in our population was different compared with other world regions. A key finding was that HPV68 was the most prevalent high-risk HPV genotype. These findings highlight the need for the determination in our population of the etiologic fraction of different HPV types in invasive cervical cancers.

PURPOSE Non–clear-cell renal cell carcinoma (nccRCC) encompasses approximately 20% of renal cell carcinomas and includes subtypes that vary in clinical and molecular biology. Compared with clear cell renal cell carcinoma, nccRCC demonstrates limited sensitivity to conventional vascular endothelial growth factor– and mammalian target of rapamycin–directed agents, indicating a need for better therapies. Characterizing the genomic landscape of metastatic nccRCC variants may help define novel therapeutic strategies. PATIENTS AND METHODS We retrospectively analyzed tumor tissue from patients with metastatic nccRCC who consented to genomic analysis of their tumor and germline DNA. A hybridization capture–based assay was used to identify single nucleotide variants and small insertions and deletions across more than 340 cancer-associated genes with germline comparison. Clinical actionability of somatic mutations was assessed using OncoKB levels of evidence. Microsatellite instability (MSI) in the tumor was investigated. RESULTS Of 116 patients included in the analysis, 57 (49%) presented with de novo metastatic disease, and 59 (51%) presented with localized disease that later metastasized. Subtype classifications included unclassified (n = 41; 35%), papillary (n = 26; 22%), chromophobe (n = 17; 15%), translocation associated (n = 13; 11%), and other (n = 19; 16%). Of all tumors, 15 (13%) had putative driver somatic alterations amenable to targeted therapies, including alterations in MET, TSC1/2, and an ALK translocation. Of 45 patients who had germline testing, 11 (24%) harbored mutations, seven of which could potentially guide therapy. Of 115 available tumors for analysis, two (1.7%) had high and six (5%) had intermediate MSI status. CONCLUSION The mutation profiles of metastatic nccRCC vary by subtype. Comprehensive analysis of somatic mutations, germline mutations, and MSI, interpreted via an annotated precision oncology knowledge base, identified potentially targetable alterations in 22% of patients, which merits additional investigation.

PURPOSE There is limited knowledge of the long-term health effects of the Chernobyl nuclear power plant accident that occurred more than 30 years ago in Ukraine. This study describes trends in the incidence of solid organ malignancy in Ukraine and the five regions most affected by the radioactive fallout. METHODS The National Cancer Registry of Ukraine was queried for age-standardized incidence rates (ASIRs) of solid organ malignancy in Ukraine and the regions of Kyiv, Chernihiv, Zhytomyr, Rivne, and Volyn covering the period of 1999 to 2016. Joinpoint analysis was used to calculate the average annual percentage of change. RESULTS The highest burdens of cancer incidence in Ukraine were seen in the lung, stomach, breast, and prostate. We observed significant increases in the ASIRs of colon (average annual percentage of change, 1.5 [95% CI, 1.3 to 1.7]), rectal (0.9 [95% CI, 0.6 to 1.2]), kidney (2.3 [95% CI, 1.8 to 2.9]), thyroid (4.2 [95% CI, 3.1 to 5.3]), breast (1 [95% CI, 0.6 to 1.4]), cervical (0.7 [95% CI, 0.3 to 1.2]), and prostate (3.9 [95% CI, 3.6 to 4.2]) cancers, with decreases in stomach (−2.4 [95% CI, −2.5 to −2.3]) and lung (−1.8 [95% CI, −2.1 to −1.5]) cancers. ASIRs in the affected regions were similar to nationwide rates, with the exception of those for Kyiv. CONCLUSION The incidence rates of many solid organ malignancies in Ukraine are rising. However, the rates of solid organ malignancy in the five regions most affected by fallout did not substantially differ from national patterns, with the exception of those for Kyiv. Ongoing monitoring of cancer incidence in Ukraine is necessary to understand how best to decrease disease burden nationwide and to elucidate the causes of regional variations in ASIRs, such as access to diagnostics and environmental exposures.