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Clinical trials conducted with incarcerated populations are rare. We present a case example of one such jail-based cancer prevention clinical trial to demonstrate the importance of including a theory-driven approach to intervention framing, novel experimental designs to boost access to low-risk trials, and retention strategies for long-term follow-up of hard-to-reach populations. As such we offer a social determinant of health framework to ensure cancer prevention research is conducted through the lenses of health promotion and health equity. Deviations from the gold-standard randomized control design, transparent systematic allotment, and street-based outreach retention strategies contribute to the feasibility of conducting clinical trials in carceral settings and after people leave jail. Best practices presented can be used in design and conduct of future clinical trials with criminal legal system-involved populations.
The White Sands dune field is the largest gypsum dune system in the world, derived from deflation of paleo-Lake Otero deposits. Understanding the timing of initial dune construction, and therefore lake deflation, is critical for understanding regional landscape evolution, including the history of lake desiccation. The onset of dune construction is currently estimated at ~8000 to 6500 cal yr BP, but numerical age control is limited. Archaeological evidence reported here indicates two older phases of gypsum dune construction. An archaeological site draped over a parabolic dune south of the main dune body contains artifacts dating to >12,200 cal yr BP, providing an upper age limit for the landform. Another site buried within a remnant of the main dune field yielded six statistically identical radiocarbon dates averaging ~8770 cal yr BP. The initial phase of terminal Pleistocene deflation and parabolic dune construction was perhaps localized but correlates with a period of regional aridity. Barchans and crescentic ridges comprising the main dune body developed in the Early Holocene in response to elevated salinity in local ground water and extensive exposures of gypsum available for deflation, likely due to aridity.
To describe patterns of inappropriate antibiotic prescribing at US children’s hospitals and how these patterns vary by clinical service.
Serial, cross-sectional study using quarterly surveys.
Surveys were completed in quarter 1 2019–quarter 3 2020 across 28 children’s hospitals in the United States.
Patients at children’s hospitals with ≥1 antibiotic order at 8:00 a.m. on institution-selected quarterly survey days.
Antimicrobial stewardship physicians and pharmacists collected data on antibiotic orders and evaluated appropriateness of prescribing. The primary outcome was percentage of inappropriate antibiotics, stratified by clinical service and antibiotic class. Secondary outcomes included reasons for inappropriate use and association of infectious diseases (ID) consultation with appropriateness.
Of 13,344 orders, 1,847 (13.8%) were inappropriate; 17.5% of patients receiving antibiotics had ≥1 inappropriate order. Pediatric intensive care units (PICU) and hospitalists contributed the most inappropriate orders (n = 384 and n = 314, respectively). Surgical subspecialists had the highest percentage of inappropriate orders (22.5%), and 56.8% of these were for prolonged or unnecessary surgical prophylaxis. ID consultation in the previous 7 days was associated with fewer inappropriate orders (15% vs 10%; P < .001); this association was most pronounced for hospitalist, PICU, and surgical and medical subspecialty services.
Inappropriate antibiotic use for hospitalized children persists and varies by clinical service. Across 28 children’s hospitals, PICUs and hospitalists contributed the most inappropriate antibiotic orders, and surgical subspecialists’ orders were most often judged inappropriate. Understanding service-specific prescribing patterns will enable antimicrobial stewardship programs to better design interventions to optimize antibiotic use.
To characterize antifungal prescribing patterns, including the indication for antifungal use, in hospitalized children across the United States.
We analyzed antifungal prescribing data from 32 hospitals that participated in the SHARPS Antibiotic Resistance, Prescribing, and Efficacy among Children (SHARPEC) study, a cross-sectional point-prevalence survey conducted between June 2016 and December 2017.
Inpatients aged <18 years with an active systemic antifungal order were included in the analysis. We classified antifungal prescribing by indication (ie, prophylaxis, empiric, targeted), and we compared the proportion of patients in each category based on patient and antifungal characteristics.
Among 34,927 surveyed patients, 2,095 (6%) received at least 1 systemic antifungal and there were 2,207 antifungal prescriptions. Most patients had an underlying oncology or bone marrow transplant diagnosis (57%) or were premature (13%). The most prescribed antifungal was fluconazole (48%) and the most common indication for antifungal use was prophylaxis (64%). Of 2,095 patients receiving antifungals, 79 (4%) were prescribed >1 antifungal, most often as targeted therapy (48%). The antifungal prescribing rate ranged from 13.6 to 131.2 antifungals per 1,000 patients across hospitals (P < .001).
Most antifungal use in hospitalized children was for prophylaxis, and the rate of antifungal prescribing varied significantly across hospitals. Potential targets for antifungal stewardship efforts include high-risk, high-utilization populations, such as oncology and bone marrow transplant patients, and specific patterns of utilization, including prophylactic and combination antifungal therapy.
Binge eating disorder (BED) is a pernicious psychiatric disorder which is linked with broad medical and psychiatric morbidity, and obesity. While BED may be characterized by altered cortical morphometry, no evidence to date examined possible sex-differences in regional gray matter characteristics among those with BED. This is especially important to consider in children, where BED symptoms often emerge coincident with rapid gray matter maturation.
Pre-adolescent, 9–10-year old boys (N = 38) and girls (N = 33) with BED were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development Study. We investigated sex differences in gray matter density (GMD) via voxel-based morphometry. Control sex differences were also assessed in age and body mass index and developmentally matched control children (boys N = 36; girls N = 38). Among children with BED, we additionally assessed the association between dorsolateral prefrontal (dlPFC) GMD and parent-reported behavioral approach and inhibition tendencies.
Girls with BED uniquely demonstrate diffuse clusters of greater GMD (p < 0.05, Threshold Free Cluster Enhancement corrected) in the (i) left dlPFC (p = 0.003), (ii) bilateral dmPFC (p = 0.004), (iii) bilateral primary motor and somatosensory cortex (p = 0.0003) and (iv) bilateral precuneus (p = 0.007). Brain-behavioral associations suggest a unique negative correlation between GMD in the left dlPFC and behavioral approach tendencies among girls with BED.
Early-onset BED may be characterized by regional sex differences in terms of its underlying gray matter morphometry.
This chapter examines the work of Woody Allen in the context of the accusations of child abuse paedophilia made against him. Many of his best-known works have the central character played by Allen in a relationship with a much younger woman. In these roles, he self-consciously asks questions about the legitimacy of such relationships, publicly engaging with these questions through artistic methods. The chapter deals with a number of key questions crossing aesthetics, ethics, biography, autobiography, memory studies, trauma studies, gender studies, sexuality studies and reception studies. How does the private and public life of a filmmaker change our reception of his work, if at all?
Keywords: youth, monstrous men, autobiography
Fiction v Reality
Public opinion on Woody Allen and his films has shifted since the #MeToo era. Allen and his films were at the heart of the American establishment and at the centre of film criticism since the 1970s (Monaco 1981: 299). We only have to consider two of his comedies in the early part of that decade – Bananas (1971) and Sleeper (1973) – to acknowledge his standing, and then there is also Annie Hall (1977) and Manhattan (1979). These films created this era along with the mythic elements of New York (ibid.). From the 1950s to 1970s, professional opinion did not consider sexual abuse to be a danger or significant social problem (Jenkins 1996: 84–85). Perpetrators, especially those in positions of power, were protected by the press (Lee 2005). The late 1980s and early 1990s witnessed a media storm in the United States and Britain concerning sexual abuse allegations (Davies and Dalgleish 2001). Since 1992, Woody Allen's life and work, often indistinguishable as argued here, have been inseparable from the media attention given to the child sexual abuse allegations made against him. His influence is ‘characterised by a compulsion to repeat and a desire to separate, underpinned, no doubt, by Allen's biographical scandals’ (Hannington 2020).
Concern over sexual abuse led to what Allen's supporters would call a new censorship and witch-hunt. Witch-hunt was a term also used in the late 1980s and early 1990s regarding some claims of child sexual abuse, including claimed satanic ritual abuse.
We examined ampicillin dosing in pediatric patients across 3 conditions: (1) bacterial lower respiratory tract infections (LRTIs) in infants and children >3 months, (2) neonates with suspected or proven sepsis, and (3) neonates with suspected central nervous system (CNS) infections. We compared our findings to dosing guidance for these specific indications.
Retrospective cohort study.
The study included data from 32 children’s hospitals in the United States.
We reviewed prescriptions from the SHARPS study of antimicrobials, a survey of antibiotic prescribing from July 2016 to December 2017. Prescriptions were analyzed for indication, total daily dose per kilogram, and presence of antimicrobial stewardship program (ASP) review. LRTI prescriptions were compared to IDSA recommendations for community-acquired pneumonia. Neonatal prescriptions were compared to recommendations from the American Academy of Pediatrics (AAP). Prescriptions were categorized as “optimal” (80%–120% of recommended dosing), “suboptimal” (<80% of recommended dosing), or “excessive” (>120% of recommended dosing).
Among 1,038 ampicillin prescriptions, we analyzed 88 prescriptions for LRTI, 499 prescriptions for neonatal sepsis, and 27 prescriptions for neonatal CNS infection. Of the LRTI prescriptions, 77.3%were optimal. Of prescriptions for neonatal sepsis, 81.6% were excessive compared to AAP bacteremia recommendations but 78.8% were suboptimal compared to AAP meningitis guidelines. Also, 48.1% of prescriptions for neonatal CNS infection were suboptimal, and 50.6% of prescriptions were not reviewed by the ASP.
LRTI dosing is generally within the IDSA-recommended range. However, dosing for neonatal sepsis often exceeds the recommendation for bacteremia but is below the recommendation for meningitis. This variability points to an important opportunity for future antimicrobial stewardship efforts.
Behavioral features of binge eating disorder (BED) suggest abnormalities in reward and inhibitory control. Studies of adult populations suggest functional abnormalities in reward and inhibitory control networks. Despite behavioral markers often developing in children, the neurobiology of pediatric BED remains unstudied.
58 pre-adolescent children (aged 9–10-years) with BED (mBMI = 25.05; s.d. = 5.40) and 66 age, BMI and developmentally matched control children (mBMI = 25.78; s.d. = 0.33) were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development (ABCD) Study. We investigated group differences in resting-state functional MRI functional connectivity (FC) within and between reward and inhibitory control networks. A seed-based approach was employed to assess nodes in the reward [orbitofrontal cortex (OFC), nucleus accumbens, amygdala] and inhibitory control [dorsolateral prefrontal cortex, anterior cingulate cortex (ACC)] networks via hypothesis-driven seed-to-seed analyses, and secondary seed-to-voxel analyses.
Findings revealed reduced FC between the dlPFC and amygdala, and between the ACC and OFC in pre-adolescent children with BED, relative to controls. These findings indicating aberrant connectivity between nodes of inhibitory control and reward networks were corroborated by the whole-brain FC analyses.
Early-onset BED may be characterized by diffuse abnormalities in the functional synergy between reward and cognitive control networks, without perturbations within reward and inhibitory control networks, respectively. The decreased capacity to regulate a reward-driven pursuit of hedonic foods, which is characteristic of BED, may in part, rest on this dysconnectivity between reward and inhibitory control networks.
Electrical injury (EI) is a significant, multifaceted trauma often with multi-domain cognitive sequelae, even when the expected current path does not pass through the brain. Chronic pain (CP) research suggests pain may affect cognition directly and indirectly by influencing emotional distress which then impacts cognitive functioning. As chronic pain may be critical to understanding EI-related cognitive difficulties, the aims of the current study were: examine the direct and indirect effects of pain on cognition following EI and compare the relationship between pain and cognition in EI and CP populations.
This cross-sectional study used data from a clinical sample of 50 patients with EI (84.0% male; Mage = 43.7 years) administered standardized measures of pain (Pain Patient Profile), depression, and neurocognitive functioning. A CP comparison sample of 93 patients was also included.
Higher pain levels were associated with poorer attention/processing speed and executive functioning performance among patients with EI. Depression was significantly correlated with pain and mediated the relationship between pain and attention/processing speed in patients with EI. When comparing the patients with EI and CP, the relationship between pain and cognition was similar for both clinical groups.
Findings indicate that pain impacts mood and cognition in patients with EI, and the influence of pain and its effect on cognition should be considered in the assessment and treatment of patients who have experienced an electrical injury.
This study investigates associations of several dimensions of childhood adversities (CAs) with lifetime mental disorders, 12-month disorder persistence, and impairment among incoming college students.
Data come from the World Mental Health International College Student Initiative (WMH-ICS). Web-based surveys conducted in nine countries (n = 20 427) assessed lifetime and 12-month mental disorders, 12-month role impairment, and seven types of CAs occurring before the age of 18: parental psychopathology, emotional, physical, and sexual abuse, neglect, bullying victimization, and dating violence. Poisson regressions estimated associations using three dimensions of CA exposure: type, number, and frequency.
Overall, 75.8% of students reported exposure to at least one CA. In multivariate regression models, lifetime onset and 12-month mood, anxiety, and substance use disorders were all associated with either the type, number, or frequency of CAs. In contrast, none of these associations was significant when predicting disorder persistence. Of the three CA dimensions examined, only frequency was associated with severe role impairment among students with 12-month disorders. Population-attributable risk simulations suggest that 18.7–57.5% of 12-month disorders and 16.3% of severe role impairment among those with disorders were associated with these CAs.
CAs are associated with an elevated risk of onset and impairment among 12-month cases of diverse mental disorders but are not involved in disorder persistence. Future research on the associations of CAs with psychopathology should include fine-grained assessments of CA exposure and attempt to trace out modifiable intervention targets linked to mechanisms of associations with lifetime psychopathology and burden of 12-month mental disorders.
To achieve the elimination of the hepatitis C virus (HCV), sustained and sufficient levels of HCV testing is critical. The purpose of this study was to assess trends in testing and evaluate the effectiveness of strategies to diagnose people living with HCV. Data were from 12 primary care clinics in Victoria, Australia, that provide targeted services to people who inject drugs (PWID), alongside general health care. This ecological study spanned 2009–2019 and included analyses of trends in annual numbers of HCV antibody tests among individuals with no previous positive HCV antibody test recorded and annual test yield (positive HCV antibody tests/all HCV antibody tests). Generalised linear models estimated the association between count outcomes (HCV antibody tests and positive HCV antibody tests) and time, and χ2 test assessed the trend in test yield. A total of 44 889 HCV antibody tests were conducted 2009–2019; test numbers increased 6% annually on average [95% confidence interval (CI) 4–9]. Test yield declined from 2009 (21%) to 2019 (9%) (χ2P = <0.01). In more recent years (2013–2019) annual test yield remained relatively stable. Modest increases in HCV antibody testing and stable but high test yield within clinics delivering services to PWID highlights testing strategies are resulting in people are being diagnosed however further increases in the testing of people at risk of HCV or living with HCV may be needed to reach Australia's HCV elimination goals.
To assess current resources, interventions, and obstacles of pediatric outpatient antimicrobial stewardship programs (ASP).
Institutions from the Sharing Antimicrobial Reports for Pediatric Stewardship OutPatient collaborative (SHARPS-OP).
Antimicrobial stewardship leaders from the above institutions.
An investigator-developed survey was deployed online in September 2020 to antimicrobial stewardship leaders in SHARPS-OP institutions. The survey was divided into 4 sections: (1) basic information, (2) status of pediatric outpatient ASP in the institutions including financial support, (3) outpatient ASP interventions undertaken by the institutions, and (4) needs and SHARPS-OP collaborative goals.
Of 56 invited institutions, 45 participated, achieving an 80% response rate. Only 5 sites (11%) had allocated financial support for an outpatient ASP, compared to 42 (95.6%) for their inpatient ASP. The most widely used outpatient ASP interventions included antimicrobial guidance (57.8%), education (46.7%), and quality improvement projects (37.8%). Time was identified as the biggest barrier to expanding outpatient ASPs (91.1%), followed by financial support (53.3%), development of meaningful reports (51.1%), and administrative support (44.4%). Important goals of the collaborative included seeking learning opportunities and developing clear metrics for pediatric outpatient ASP benchmarking. Program needs included securing operational support (35.8%) and strengthening data analysis (31.6%).
Very few pediatric institutions with robust inpatient ASPs have devoted time and financial support to advance outpatient efforts. To promote appropriate antibiotic prescribing in the outpatient arena, time and resource funding by administrative leaders are necessary to develop a robust, sustainable stewardship infrastructure.
Vitamin C deficiency has been a historical disease rarely seen nowadays. We illustrate a case of a boy with autism presenting with severe pulmonary hypertension and refusal to walk secondary to vitamin C deficiency. Initiating treatment with high-dose vitamin C reversed his symptoms and he regained full power of his lower limbs with total normalisation of his pulmonary pressures.
To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health.
The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification).
Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and antimicrobial stewardship. The multistep, 7-month process included a literature review, interactive teleconferences, web-based surveys, and 2 in-person meetings.
A final list of 12 high-priority research topics were generated in the 2 domains. High-priority healthcare-associated infection topics included judicious testing for Clostridioides difficile infection, chlorhexidine (CHG) bathing, measuring and preventing hospital-onset bloodstream infection rates, surgical site infection prevention, surveillance and prevention of multidrug resistant gram-negative rod infections. Antimicrobial stewardship topics included β-lactam allergy de-labeling, judicious use of perioperative antibiotics, intravenous to oral conversion of antimicrobial therapy, developing a patient-level “harm index” for antibiotic exposure, and benchmarking and or peer comparison of antibiotic use for common inpatient conditions.
We identified 6 healthcare-associated infection topics and 6 antimicrobial stewardship topics as potentially high-impact targets for pediatric research.
To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission.
Pilot prospective multicenter surveillance study.
The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals.
All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data.
In total, 408 isolates were collected from 358 patients; 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%), and ESBL-Kp (7.6%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure.
Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients).
Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.
Studies of the American public demonstrate that partisans often diverge not only on questions of opinion but also on matters of fact. However, little is known about partisan divergence in factual beliefs among the government officials who make real policy decisions, or how it compares to belief polarization among the public. This letter describes the first systematic comparison of factual belief polarization between the public and government officials, which we conducted using a paired survey approach. The results indicate that political elites are consistently more accurately informed than the public across a wide range of politically contentious facts. However, this increase in accuracy does not translate into reduced factual belief polarization. These findings demonstrate that a more informed political elite does not necessarily mitigate partisan factual disagreement in policy making.
Background: The medical device reprocessing department (MDRD) is a crucial patient safety area with checkpoints to ensure appropriate reprocessing. Objective: We report the application of molecular pathology in the investigation of potential blood and body fluid exposure (BBFE) during endoscopy. Methods: When there is a potential BBFE from a medical device, our hospital has a systematic process whereby the clinical area involves the MDRD and the infection prevention control (IPC) team. The MDRD provides reprocessing documentation, including detailed information regarding the prior use of the devices. The clinician and the IPC physician discuss the risk of BBFE. If patient disclosure occurs, the IPC physician provides follow-up as appropriate. This report illustrates the collaboration of clinicians, the IPC team, the MDRD, pathologists, and molecular pathologists in investigating the possibility of residual human tissue and BBFE during endoscopy. Case reports: Two independent but similar events occurred in September 2016 and September 2019 in the pediatric endoscopy suite at our site, a tertiary-care pediatric hospital with 163 beds in Edmonton, Canada. During both endoscopies, the pediatric gastroenterologists observed a piece of tissue ejected from the gastroscope into the intestinal lumen when the biopsy forceps were pushed out of the channel for the first time. This observation raised concerns of possible gaps in the reprocessing of the endoscope and residual tissue remaining in the working channel after its last use. Both gastroenterologists were able to retrieve the presumed foreign tissue; however, both patients had possible BBFE because the mucosal surface was breached by the biopsy forceps. The MDRD reprocessing of both endoscopes was reviewed, and no gap was identified. In discussion with the pathologists and molecular pathologists, human identity testing using genetic markers was performed on the biopsy blocks of the previous patient on whom the endoscope was used, the potentially exposed patient, and the presumed foreign tissue for each event. The test results indicated that the presumed foreign tissue was in fact from the potentially exposed patient and therefore there was no BBFE. It is presumed that the working channel itself captured a small amount of the patient’s tissue during scope insertion. The results were a relief to the patients and families. Conclusions: It is prudent to investigate residual foreign tissue in a medical device that is being used on patients with mucosal breaches. Molecular pathology involving human identity testing is a very useful tool in the investigation of these types of events.