Unknown Outcomes Research Articles

Unintentional trazodone overdoses in children ≤6 years of age: data from poison center over a period of 16 years

Context: Trazodone is an atypical antidepressant with no established safety in children. Previous case reports showed no complications at doses 50–500 mg in children. Our study objective is to characterize the clinical effects, dose-related toxicity, and establish triage dose for acute trazodone ingestions in children ≤6 years of age.Methods: Cases with acute trazodone ingestions in children ≤6 years of age between 2000 and 2015 were retrospectively reviewed. Data were analyzed for dose (mg/kg), clinical effects, management site, treatment, and outcome. Cases with coingestions, unknown outcome, or unknown dose were excluded.Results: A total of 84 patients (mean age 26.7 months, 35 females, 49 males) were included. Of those, 52 (61.9%) had no clinical effects; 29 (34.5%) had minor effects (vomiting, dizziness, headache); and three (3.6%) had moderate effects (ataxia, slurred speech, priapism). No major effects or deaths were observed. Moderate effects were manifested at doses ≥6.9 mg/kg. Priapism occurred in a 2-year-old child at a dose of 6.9 mg/kg. Sixteen (19%) patients were managed at home and 68 (81%) patients were referred to a HCF. Among those referred to a HCF, three (4.4%) patients had moderate effects with ingested dose ≥6.9 mg/kg. However, 27 (39.7%) patients of those referred to a HCF had an ingested dose <6 mg/kg and none of them manifested symptoms beyond minor effects. All referred patients had uneventful recovery and no sequela.Conclusions: Children should be referred for further evaluation in acute unintentional trazodone ingestions with doses ≥6 mg/kg.

Tolerance to ambiguous uncertainty predicts prosocial behavior

Uncertainty is a fundamental feature of human life that can be fractioned into two distinct psychological constructs: risk (known probabilistic outcomes) and ambiguity (unknown probabilistic outcomes). Although risk and ambiguity are known to powerfully bias nonsocial decision-making, their influence on prosocial behavior remains largely unexplored. Here we show that ambiguity attitudes, but not risk attitudes, predict prosocial behavior: the greater an individual’s ambiguity tolerance, the more they engage in costly prosocial behaviors, both during decisions to cooperate (experiments 1 and 3) and choices to trust (experiment 2). Once the ambiguity associated with another’s actions is sufficiently resolved, this relationship between ambiguity tolerance and prosocial choice is eliminated (experiment 3). Taken together, these results provide converging evidence that attitudes toward ambiguity are a robust predictor of one’s willingness to engage in costly social behavior, which suggests a mechanism for the underlying motivations of prosocial action.

Can improved diagnostics reduce mortality from Tuberculous meningitis? Findings from a 6.5-year cohort in Uganda

Background: Tuberculous meningitis (TBM) is the second most common cause of meningitis in sub-Saharan Africa and is notoriously difficult to diagnose. We describe the impact of improved TBM diagnostics over 6.5 years at two Ugandan referral hospitals. Methods: Cohort one received cerebrospinal fluid (CSF) smear microscopy only (2010-2013). Cohort two received smear microscopy and Xpert MTB/Rif (Xpert) on 1ml unprocessed CSF at physician discretion (2011-2013). Cohort three received smear microscopy, routine liquid-media culture and Xpert on large volume centrifuged CSF (2013-2017) for all meningitis suspects with a negative CSF cryptococcal antigen. We compared rates of microbiologically confirmed TBM and hospital outcomes over time. Results: 1672 HIV-infected adults presenting with suspected meningitis underwent lumbar puncture, of which 33% (558/1672) had negative CSF cryptococcal antigen and 12% (195/1672) were treated for TB meningitis. Over the study period, microbiological confirmation of TBM increased from 3% to 41% (P&lt;0.01) and there was a decline in in-hospital mortality from 57% to 41% (P=0.27) amongst those with a known outcome. Adjusting for definite TBM diagnosis and antiretroviral therapy use, and using imputed data, assuming 50% of those with an unknown outcome died, the odds of dying were nearly twice as high in cohort one (adjusted odds ratio 1.7, 95% CI 0.7 to 4.4) compared to cohort three. Sensitivity of Xpert was 63% (38/60) and culture was 65% (39/60) against a composite reference standard. Conclusions: As TBM diagnostics have improved, microbiologically-confirmed TBM diagnoses have increased and in-hospital mortality has declined. Yet, mortality due to TB meningitis remains unacceptably high and further measures are needed to improve outcomes from TBM in Uganda.

Past, present and future of haemophilia gene therapy: From vectors and transgenes to known and unknown outcomes.

Since the 1960s, the pace of innovation in haemophilia treatment has been fast and furious and occasionally with unintended consequences. As newer technologies are harnessed to better treat, and potentially cure, haemophilias A and B, an understanding of their underlying scientific principles and their benefits and risks are essential for all stakeholders. This review summarizes the starts and stops of introducing FVIII and FIX transgenes clinically, beginning 20years ago. Lessons from earlier nonclinical and clinical experiments have been utilized to improve vector selection, vector design, promoter/enhancer cis control regions and codon-optimized transgenes to trigger in vivo clinical FVIII and FIX levels in the near-normal to normal ranges. Many known and unknown questions remain, and some, based upon benefit and risk, should be answered during larger phase 3 clinical trials. Prior clinical outcomes in haemophilia trials have not been standardized, making between-trial comparisons difficult. Going forward, haemophilia gene therapy clinical trials should utilize a standard set of core outcomes, to facilitate comparisons to other gene- and protein-based therapies. These outcomes will be more important as the field moves beyond the first-generation gene therapies into more complex vectors that may address the shortcomings of first-generation vectors and offer greater benefits to the patient.

P070: Excluding ectopic pregnancy in patients presenting to a community emergency department with first trimester bleeding

Introduction: Current guidelines recommend patients with first trimester bleeding without previously documented intrauterine pregnancy undergo urgent transvaginal ultrasound (TVUS) to exclude ectopic pregnancy. However, in Canadian practice to receive urgent TVUS, particularly out of daytime hours is difficult, if not impossible. Thus, when TVUS is not available to exclude ectopic pregnancy, providers use point of care ultrasound (POCUS) or their best clinical judgment to determine if the patient can be safely discharged home while awaiting outpatient follow-up. The objective of this study was to determine what proportion of first trimester patients presenting to a community hospital emergency department (ED) with vaginal bleeding undergo either TVUS or POCUS to exclude ectopic pregnancy. Methods: This is an ongoing retrospective chart review of pregnant women gestational age (GA) less than 20 weeks presenting to a community hospital ED (103,000 visits/year) with a discharge diagnosis of vaginal bleed, first trimester bleed, threatened abortion, spontaneous abortion, missed abortion, rule out ectopic pregnancy, and ectopic pregnancy from January 2016 - January 2017. Patients are excluded if they are diagnosed with a ruptured ectopic pregnancy during their index ED visit. To date, 98 patient charts have been reviewed. Results: Of the 98 included patients, 13 (13.3%) had a viable pregnancy, 37 (37.8%) had a spontaneous or missed abortion, 4 (4.1%) had an ectopic pregnancy, and 45 (45.9%) had unknown outcomes. Of included patients, 4 (4.1%) only had POCUS, 66 (67.4%) only had a radiologist-interpreted TVUS, and 3 (3.1%) had both POCUS and radiologist-interpreted TVUS during their ED index visits. Thus, 73 (74.5%) had either a radiologist-interpreted TVUS or ED provider-performed POCUS during their index ED visit. After their index ED visits, 2 (2.0%) patients returned with ruptured ectopic pregnancies, 1 of whom had not undergone initial US investigations. Conclusion: Although TVUS is standard of care to exclude ectopic pregnancy in patients presenting with first trimester bleeding or abdominal pain, our preliminary results show some patients are not receiving this diagnostic modality nor POCUS during their index ED visit. Particularly in a setting, such as this ED, without rapid access to an early pregnancy clinic, patients should be counselled about their risk of ectopic pregnancy at the time of ED discharge.

P067: Ectopic pregnancy outcomes in patients discharged from the emergency department

Introduction: The objective of this study was to determine the proportion of women who had a ruptured ectopic pregnancy after being discharged from the ED where ectopic pregnancy had not yet been excluded. Methods: This was a retrospective chart review of pregnant (&lt;12 week gestational age) women discharged home from an academic tertiary care ED with a diagnosis of ectopic pregnancy, rule out ectopic pregnancy, or pregnancy of unknown location (PUL) over a 7 year period. Results: Of the 550 included patients, 83 (15.1%) had a viable pregnancy, 94 (17.1%) had a spontaneous or missed abortion, 230 (41.8%) had an ectopic pregnancy, 72 (13.1%) had unknown outcomes and 71 (12.9%) had other outcomes which included therapeutic abortion, molar pregnancy or resolution of HCG with no location documented. Of the 230 ectopic pregnancies, 42 (7.6%) underwent expectant management, 131 (23.8%) were managed medically with methotrexate, 29 (5.3%) were managed with surgical intervention, and 28 (5.1%) patients had a ruptured ectopic pregnancy after their index ED visit. Of the 550 included patients, 221 (40.2%) did not have a transvaginal US during their index ED visit, 73 (33.0%) were subsequently diagnosed with an ectopic pregnancy. Conclusion: These results may be useful for ED physicians counselling women with symptomatic early pregnancies about the risk of ectopic pregnancy after they are discharged from the ED.

Painful Arm Mass-Weight Lifting

HISTORY: A 29 year old male reports acute onset of pain and palpable mass in his right distal bicep while weight lifting 2 weeks prior to presentation. He reports a dull ache that has persisted despite heat and ibuprofen. He developed bruising which resolved. He has continued lifting. He has no paresthesia, weakness, or radiculopathy. He has no exertional pain. He has a known history of multiple aneurysms diagnosed at the age of 7 with negative genetic testing. PHYSICAL EXAMINATION: There are no overlying skin changes or deformity. There is a tender, non-pulsatile 2cm mass within the medial distal bicep with firmness of the surrounding soft tissues. Active range of motion at the shoulder and elbow are full and symmetric. Pain cannot be recreated with manual muscle testing. Brachial and radial pulses are symmetric and equal. Right ulnar pulse is difficult to palpate. Allen’s test reveals reduced right ulnar blood flow. Lower extremity pulses are symmetric and equal. Cervical spine motion is normal. Spurling’s test is negative bilaterally. DIFFERENTIAL DIAGNOSIS: Superficial phlebitis Intramuscular hemorrhage Biceps or brachioradialis muscle tear Neoplasm (vascular, sarcoma, nerve sheath) Brachial artery aneurysm or pseudoaneurysm TEST AND RESULTS: Bilateral extremity angiogram - Right arm: multiple aneurysms proximal to the antecubital fossa, the largest measures over 1.5 cm. Aneurysms at the origin of the ulnar and radial arteries without distal abnormality. Left arm: 1.5 cm aneurysm proximal to the antecubital fossa. Right mid vertebral artery aneurysm (1.4 cm); prior coil embolization of the left vertebral artery. Lower extremities: 33 discrete aneurysms. Pseudoaneurysm at the proximal anastomosis of the aorto-bi-iliac graft that measures 4 cm proximally and 2.2 cm on the right iliac limb. FINAL WORKING DIAGNOSIS: Multiple aneurysmal disease of unknown origin TREATMENT AND OUTCOMES: This case highlights provocative issues of a rare vascular disorder with no literature related to physical activity recommendations. Increased intravascular pressure related to heavy resistance likely accelerates disease progression, and as such, the athlete was advised to refrain from weightlifting. Vascular surgery was consulted for evaluation of abdominal aortic pseudoaneurysm and right vertebral artery aneurysm.

Dengue vaccination during pregnancy – An overview of clinical trials data

BackgroundThe live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in several endemic countries and contraindicated during pregnancy. Inadvertent vaccination during pregnancy may occur during clinical trials that include women of childbearing age. The potential risk associated with dengue vaccination in pregnancy remains unknown. We describe pregnancy outcomes following inadvertent dengue vaccination in pregnancy from CYD-TDV trial data. MethodsData were collected from trials conducted as part of the CYD-TDV clinical development. Women who received CYD-TDV or placebo during the pre-specified pregnancy risk window (from 30 days before the date of their last menstrual period to end of pregnancy) were considered as exposed; pregnancies occurring in non-risk periods during the trials were considered to be non-exposed. Pregnancy losses were defined as abortion (spontaneous or unspecified), death in utero, and stillbirth. Results615 pregnancies were reported from 19 CYD-TDV trials: 404 in the CYD-TDV arm, and 211 in the placebo arm. Exposure could not be determined for 7 pregnancies (5, CYD-TDV; 2, placebo). In the CYD-TDV arm, 58 pregnancies were considered as exposed. Most of these (n = 47, 81%) had healthy live births; 6 (10.3%) had pregnancy losses; 3 underwent elective termination and 2 had unknown outcome. In the placebo group, 30 pregnancies were considered exposed. Most of these (n = 25, 83%) had healthy births; 4 (13.3%) had pregnancy losses; and 1 had elective termination. Among non-exposed pregnancies, most resulted in healthy live births; 23/341 (6.7%) in the CYD-TDV group and 17/179 (9.5%) in the placebo group had pregnancy losses. Most reported pregnancy losses were in women considered high-risk for adverse pregnancy outcome, primarily due to young age. ConclusionIn the small dataset assessed, no evidence of increased adverse pregnancy outcomes has been identified from inadvertent immunization of women in early pregnancy with CYD-TDV compared with the control group.

" The Worst Thing Was…": Prostate Cancer Patients' Evaluations of Their Diagnosis and Treatment Experiences.

The objective of the current study was to identify the patient-perceived “worst aspects” of their diagnostic and treatment processes for prostate cancer (PCa) so as to inform targeted interventions aimed at reducing patient anxiety and depression. Two hundred and fifty-two patients who had received their diagnoses less than 8 years ago answered a postal survey about (a) background information, (b) their own descriptions of the worst aspects of their diagnosis and treatment, and (c) their ratings of 13 aspects of that process for (i) how these aspects made them feel stressed, anxious, and depressed and (ii) how they affected their relationships with significant others. They also answered standardized scales of anxiety and depression. The worst aspects reported by patients were receiving the initial diagnosis of PCa, plus the unknown outcome of that diagnosis, because of the possibility of death, loss of quality of life and/or partner, and the shock of the diagnosis. The most common coping strategy was to “just deal with it,” but participants also thought that more information would help. Principal contributors to feeling stressed, anxious, and depressed were also the diagnosis itself, followed by surgery treatment effects. The aspects that most affected relationships were receiving the diagnosis and the side effects of hormone therapy. The identification of these specific worst aspects of the PCa experience provides a set of potential treatment and prevention “targets” for psychosocial care in PCa patients.

The California Multidrug-Resistant Tuberculosis Consult Service: a partnership of state and local programs.

Background: The US Centers for Disease Control and Prevention recommend expert consultation for multi-drug-resistant tuberculosis (MDR-TB) cases. In 2002, the California MDR-TB Service was created to provide expert MDR-TB consultations. We describe the characteristics, treatment outcomes and management of patients referred to the Service. Methods: Surveillance data were used for descriptive analysis of cases, with consultation during July 2002-December 2012. Clinical consultation data and modified World Health Organization indicators were used to assess the care and management of cases, with consultation from January 2009 to December 2012. Results: Of 339 MDR-TB patients, 140 received a consultation. The proportion of patients receiving a consultation increased from 12% in 2002 to 63% in 2012. There were 24 pre-extensively drug-resistant TB and 5 patients with extensively drug-resistant TB. The majority (n = 123, 88%) completed treatment, 5 (4%) died, 7 (5%) moved before treatment completion, 4 (3%) stopped treatment due to an adverse event and 1 (1%) had an unknown outcome. Indicator data showed that 86% underwent rapid molecular drug susceptibility testing, 98% received at least four drugs to which they had known or presumed susceptibility, and 93% culture converted within 6 months. Conclusions: Consultations with the MDR-TB Service increased over time. Results highlight successful treatment and indicator outcomes.

Quantum Mechanics Requires an Observer Context Distinguishing Between Reality and its Mental Representation

When phenomena in quantum mechanics are interpreted from the perspective of bio-psychology, wave function collapse from several to a single eigenstate must be plausibly explained. Quantum mechanics requires a context, yet the context of an observer is rarely considered. On the other hand, in bio-psychology, the observer context is examined to explain superposition and collapse by different mental functions used in everyday life. Three mental functions are described, one of which is responsible for observation, and the others for conservation and treatment of information in mental representation. Whereas observation produces information with certainty, the subsequent processes result in information that remains uncertain potentiality. In order to encompass uncertainty, multiple possibilities are simultaneously considered in mental superposition, one of which should represent the unknown future outcome in observable reality. During verification by new observation, all suggested potentialities necessarily collapse to one real outcome. The collapse of superposition does not occur in observable physical reality, but in its mental representation. Some physical principles—such as superposition, infinity and nothingness before the Big Bang—are pure phenomena of mental representation, which will always remain unverifiable by observation. This argument proves that mental representation brought about by the observer context participates in the production of mental models for the best approximation of physical reality.

Ectopic pregnancy outcomes in patients discharged from the emergency department.

The objective of this study was to determine the proportion of women who had a ruptured ectopic pregnancy after being discharged from the emergency department (ED) where ectopic pregnancy had not yet been excluded. This was a retrospective chart review of pregnant (<12-week gestational age) women discharged home from an academic tertiary care ED with a diagnosis of ectopic pregnancy, rule-out ectopic pregnancy, or pregnancy of unknown location over a 7-year period. Of the 550 included patients, 83 (15.1%) had a viable pregnancy, 94 (17.1%) had a spontaneous or missed abortion, 230 (41.8%) had an ectopic pregnancy, 72 (13.1%) had unknown outcomes, and 71 (12.9%) had other outcomes that included therapeutic abortion, molar pregnancy, or resolution of βHCG with no location documented. Of the 230 ectopic pregnancies, 42 (7.6%) underwent expectant management, 131 (23.8%) were managed medically with methotrexate, 29 (5.3%) were managed with surgical intervention, and 28 (5.1%) patients had a ruptured ectopic pregnancy after their index ED visit. Of the 550 included patients, 221 (40.2%) did not have a transvaginal ultrasound during their index ED visit, and 73 (33.0%) were subsequently diagnosed with an ectopic pregnancy. These results may be useful for ED physicians counselling women with symptomatic early pregnancies about the risk of ectopic pregnancy after they are discharged from the ED.

Survival factors of hospitalized out-of-hospital cardiac arrest patients in Taiwan: A retrospective study.

The chain of survival has been shown to improve the chances of survival for victims of cardiac arrest. Post-cardiac arrest care has been demonstrated to significantly impact the survival of out-of-hospital cardiac arrest (OHCA). How post-cardiac arrest care influences the survival of OHCA patients has been a main concern in recent years. The objective of this study was to assess the survival outcome of hospitalized OHCA patients and determine the factors associated with improved survival in terms of survival to discharge. We conducted a retrospective observational study by analyzing records from the National Health Insurance Research Database of Taiwan from 2007 to 2013. We collected cases with an International Classification of Disease Clinical Modification, 9th revision primary diagnosis codes of 427.41 (ventricular fibrillation, VF) or 427.5 (cardiac arrest) and excluded patients less than 18 years old, as well as cases with an unknown outcome or a combination of traumatic comorbidities. We then calculated the proportion of survival to discharge among hospitalized OHCA patients. Factors associated with the dependent variable were examined by logistic regression. Statistical analysis was conducted using SPSS 22 (IBM, Armonk, NY). Of the 11,000 cases, 2,499 patients (22.7%) survived to hospital discharge. The mean age of subjects who survived to hospital discharge and those who did not was 66.7±16.7 and 71.7±15.2 years, respectively. After adjusting for covariates, neurological failure, cardiac comorbidities, hospital level, intensive care unit beds, transfer to another hospital, and length of hospital stay were independent predictors of improved survival. Cardiac rhythm on admission was a strong factor associated with survival to discharge (VF vs. non-VF: adjusted odds ratio: 3.51; 95% confidence interval: 3.06–4.01). In conclusion, cardiac comorbidities, hospital volume, cardiac rhythm on admission, transfer to another hospital and length of hospital stay had a significant positive association with survival to discharge in hospitalized OHCA patients in Taiwan.

EVALUATION OF DRUG THERAPY PROBLEMS IN ASTHMA PATIENTS RECEIVING CARE IN TWO HOSPITALS IN SOUTH-EASTERN NIGERIA

Objective: To evaluate drug therapy problems in asthma patients visiting a secondary and tertiary hospital in South-Eastern Nigeria.Methods: This study was a retrospective, cross-sectional analyses of the medical records of adult asthmatic patients receiving care in two hospitals in Enugu State, within a 15-year period. The Pharmaceutical Network Care Europe (PCNE) tool version 6.2 was used to assess drug therapy problems. The IBM Statistical Product for Services Solution (SPSS) version 20.0 was used for analysis. For all results, P ≤ 0.05 was considered statistically significant.Results: Majority of the patients were below 60 y old (81.2%); female (68.8%) and were on more than two drugs (95.3%). Majority of the identified drug therapy problems (DTPs) were adverse reactions (65.7%). The inappropriate drug combination was the major cause of DTPs (65.6%). Only about 23.4% of the intervention outcomes were known. University of Nigeria Teaching Hospital (UNTH) had more interventions (35.9%) than Medical Centre (8.0%) (χ2 = 6.323; df = 1; **P = 0.012); and more of the outcomes of their interventions known (38.5%) compared to Medical Centre (0.0%) (χ2 = 12.559; df = 1; **P ˂ 0.001).Conclusion: Adverse reactions and inappropriate drug selection were the major identified DTPs and major cause of DTPs, respectively. Most DTPs had no interventions. The documented interventions included stopping of the drugs, change of drugs or dosage, change of instructions for use and starting of new drugs. Most interventions had unknown outcomes. UNTH had more interventions with known outcomes than the University of Nigeria Medical Centre.

"Fear of the Known and Unknown": Factors Affecting Participation Following Knee Replacement Among Persons With Participation Restriction.

Evidence suggests that more than 30% of patients post-total knee replacement (TKR) are living with participation restrictions, yet little is known about their perceptions of and factors contributing to these restrictions. The purpose of this study was to identify emergent or recurring themes behind participation restrictions after TKR. Nineteen participants between 50 and 85 years old reporting participation restrictions 1 to 5 years post-TKR completed semistructured qualitative interviews about their participation experience after TKR. Participants provided background information in written questionnaires. Data collected from in-person interviews were analyzed qualitatively using a grounded theory approach. Participants discussed 3 major themes with regard to participation post-TKR: (1) limiting activities requiring long-distance walking due to continued knee impairments, (2) avoiding activities with negative or unknown outcome expectancies, and (3) using problem solving to identify strategies to participate in important activities. An unknown or negative outcome expectancy, particularly with regard to activities requiring long-distance walking, may lead to participation restrictions in some patients post-TKR. As participants reported using self-efficacy and coping strategies to improve participation, further physical rehabilitation or interdisciplinary rehabilitation incorporating the identified strategies may be effective with some patients post-TKR.

What happens to patients discharged against medical advice?

Introduction:Discharge against medical advice (DAMA) when requested by family members of patients in Indian Critical Care Units (CCUs) leads to loss of follow-up and unknown patient outcomes. Exclusion of these patients from research analysis and quality audits confounds these results. We hence explored the proportion of patients leaving DAMA, reasons, and their outcomes at 30 and 90 days.Methods:This was a prospective study of CCU patients admitted from July 2013 to February 2014. All patients, who were DAMA during this period, were included in this study. Demographics, APACHE data, and outcomes were collected and compared to patients discharged regularly during the same period. Outcomes of DAMA patients at 30 and 90 days were gathered by telephone follow-up.Results:Among the 663 patients admitted to the CCU, 15.1% (100 patients) were DAMA. The baseline APACHE score of the DAMA group was higher than the regular discharge group (29.5 ± 8.6 vs. 26.1 ± 10.3; P = 0.002). During the 30-day follow-up, 23% were alive, 56% dead, and 21% could not be contacted. At 90 days, mortality was 62% and survivors decreased to 14%. Common reasons for DAMA were – wanting to take the patient to another hospital (21%), reluctance for further treatments (12%), financial constraints (9%), and overall poor prognosis (7%).Conclusion:A significant proportion of patients in the CCU get DAMA despite high severity of illness. Understanding the outcomes of these patients will help refine CCU quality audit reports and research study results.

Estimation of Area Under the ROC Curve under nonignorable verification bias.

The Area Under the Receiving Operating Characteristic Curve (AUC) is frequently used for assessing the overall accuracy of a diagnostic marker. However, estimation of AUC relies on knowledge of the true outcomes of subjects: diseased or non-diseased. Because disease verification based on a gold standard is often expensive and/or invasive, only a limited number of patients are sent to verification at doctors' discretion. Estimation of AUC is generally biased if only small verified samples are used and it is thus necessary to make corrections for such lack of information. However, correction based on the ignorable missingness assumption (or missing at random) is also biased if the missing mechanism indeed depends on the unknown disease outcome, which is called nonignorable missing. In this paper, we propose a propensity-score-adjustment method for estimating AUC based on the instrumental variable assumption when the missingness of disease status is nonignorable. The new method makes parametric assumptions on the verification probability, and the probability of being diseased for verified samples rather than for the whole sample. The proposed parametric assumption on the observed sample is easier to be verified than the parametric assumption on the full sample. We establish the asymptotic properties of the proposed estimators. A simulation study is performed to compare the proposed method with existing methods. The proposed method is also applied to an Alzheimer's disease data collected by National Alzheimer's Coordinating Center.

“Ceux-là Qui Partent pour Partir”: Travel as Relinquishment in Charles Baudelaire's Le Voyage

This paper explores the desire for traveling infusing the final poem of Charles Baudelaire's collection Les Fleurs du mal, the poem Le Voyage (variously translated as Travel or The Voyage). I focus on the yearning of the speaker and the poet for the abandoning of the known world, on the desire for renouncing of the underwhelming earthly existence for the discovery of the Unknown and the New. This transgressive urge, the essay argues, lies at the heart of Baudelaire's poetic sensibility, and is a powerful harbinger of modernist aesthetics. I comment on the daring, defying excess of the poem, on its dreaming of and indulging into a journey that effaces and escapes the boundaries and limitations of reality. Le voyage thus becomes a vehicle of evasion, of radical abandonment to the unknown outcomes of a journey conceived as relinquishment. Among various travelers, it is those who embark on journey for the journey's sake who receive the poet's highest commendations. I characterize the paradoxical coexistence of the yearning for a metaphysical breakthrough, and full awareness of the existential void, of the futility of any travel whose purpose lies outside of itself, as crucial to Baudelaire's artistic temperament. I also proceed to comment on the far reaching consequences of Baudelaire's pessimistic and confrontational poetics. An argument is made that interpretation of Baudelaire needs to acknowledge at all times the fierce and irreconcilable attitude of the poet, an attitude which has all too often been downplayed by more tame and conformist readings of the Fleurs du mal.

Designing towards the Unknown: Engaging with Material and Aesthetic Uncertainty

New materials with new capabilities demand new ways of approaching design. Destabilising existing methods is crucial to develop new methods. Yet, radical destabilisation—where outcomes remain unknown long enough that new discoveries become possible—is not easy in technology design where complex interdisciplinary teams with time and resource constraints need to deliver concrete outcomes on schedule. The Poetic Kinaesthetic Interface project (PKI) engages with this problematic directly. In PKI we use unfolding processes—informed by participatory, speculative and critical design—in emergent actions, to design towards unknown outcomes, using unknown materials. The impossibility of this task is proving as useful as it is disruptive. At its most potent, it is destabilising expectations, aesthetics and processes. Keeping the researchers, collaborators and participants in a state of unknowing, is opening the research potential to far-ranging possibilities. In this article we unpack the motivations driving the PKI project. We present our mixed-methodology, which entangles textile crafts, design interactions and materiality to shape an embodied enquiry. Our research outcomes are procedural and methodological. PKI brings together diverse human, non-human, known and unknown actors to discover where the emergent assemblages might lead. Our approach is re-invigorating—as it demands re-envisioning of—the design process.

Risk factors for unfavourable treatment outcome among new smear-positive pulmonary tuberculosis cases in China.

Setting: Three projects of the Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB. Objectives: To assess unfavourable treatment outcomes (UTOs), including failure, died, loss to follow-up (LTFU), transferred out and unknown outcome, and to identify risk factors associated with UTOs. Design: This was a cross-sectional study using routine programme data. Results: Of 30 277 new smear-positive tuberculosis (TB) patients, 4261 (14.1%) had UTOs: 2048 (6.8%) LTFU, 1418 (4.7%) transferred out, 390 (1.3%) died, 340 (1.1%) failed and 65 (0.2%) had an unknown outcome. Risk factors for LTFU (including LTFU, transfer out and unknown outcome) were residing in Anhui, age > 55 years, service delay > 10 days, patient delay < 30 days, directly observed treatment (DOT) provided by a family member or others and unknown DOT provider. The outcome of 'died' was associated with residing in Shaanxi, age > 55 years, male sex, patient delay > 30 days and unknown DOT provider. 'Failed' was associated with having unlimited access to health services, patient delay of >30 days and unknown DOT provider. Conclusion: This study highlights the predominance of lost patients among UTOs. Patients with family members or other non-medical DOT providers or unknown DOT providers had a high risk of a UTO. There is an urgent need to address these service-related factors.