Accurate, comprehensive, and timely detection of drug-resistant tuberculosis (TB) is essential to inform patient treatment and enable public health surveillance. This is crucial for effective control ...of TB globally. Whole-genome sequencing (WGS) and targeted next-generation sequencing (NGS) approaches have potential as rapid in vitro diagnostics (IVDs), but the complexity of workflows, interpretation of results, high costs, and vulnerability of instrumentation have been barriers to broad uptake outside of reference laboratories, especially in low- and middle-income countries. A new, solid-state, tabletop sequencing instrument, Illumina iSeq100, has the potential to decentralize NGS for individual patient care.
In this study, we evaluated WGS and targeted NGS for TB on both the new iSeq100 and the widely used MiSeq (both manufactured by Illumina) and compared sequencing performance, costs, and usability. We utilized DNA libraries produced from Mycobacterium tuberculosis clinical isolates for the evaluation. We conducted WGS on three strains and observed equivalent uniform genome coverage with both platforms and found the depth of coverage obtained was consistent with the expected data output. Utilizing the standardized, cloud-based ReSeqTB bioinformatics pipeline for variant analysis, we found the two platforms to have 94.0% (CI 93.1%-94.8%) agreement, in comparison to 97.6% (CI 97%-98.1%) agreement for the same libraries on two MiSeq instruments. For the targeted NGS approach, 46 M. tuberculosis-specific amplicon libraries had 99.6% (CI 98.0%-99.9%) agreement between the iSeq100 and MiSeq data sets in drug resistance-associated SNPs. The upfront capital costs are almost 5-fold lower for the iSeq100 ($19,900 USD) platform in comparison to the MiSeq ($99,000 USD); however, because of difference in the batching capabilities, the price per sample for WGS was higher on the iSeq100. For WGS of M. tuberculosis at the minimum depth of coverage of 30x, the cost per sample on the iSeq100 was $69.44 USD versus $28.21 USD on the MiSeq, assuming a 2 × 150 bp run on a v3 kit. In terms of ease of use, the sequencing workflow of iSeq100 has been optimized to only require 27 minutes total of hands-on time pre- and post-run, and the maintenance is simplified by a single-use cartridge-based fluidic system. As these are the first sequencing attempts on the iSeq100 for M. tuberculosis, the sequencing pool loading concentration still needs optimization, which will affect sequencing error and depth of coverage. Additionally, the costs are based on current equipment and reagent costs, which are subject to change.
The iSeq100 instrument is capable of running existing TB WGS and targeted NGS library preparations with comparable accuracy to the MiSeq. The iSeq100 has reduced sequencing workflow hands-on time and is able to deliver sequencing results in <24 hours. Reduced capital and maintenance costs and lower-throughput capabilities also give the iSeq100 an advantage over MiSeq in settings of individualized care but not in high-throughput settings such as reference laboratories, where sample batching can be optimized to minimize cost at the expense of workflow complexity and time.
Work-related factors have been found to be influential in shaping a number of return-to-work outcomes including return-to-work expectations. Based on the idea that work-related factors have the ...potential for modification through workplace-based initiatives, this study involved a detailed examination of work-related factors referenced by workers as being taken into consideration when estimating timeframes for returning to work.
Focus groups were conducted with 30 employees, currently off work (≤ 3 months) due to a musculoskeletal condition. During the focus groups, participants wrote and spoke about the factors that they considered when forming their expectations for returning to work. Data were subjected to thematic content analysis.
Discussions revealed that participants' considerations tended to differ depending on whether or not they had a job to return to. Those with jobs (n = 23) referenced specific influences such as working relationships, accommodations, physical and practical limitations, as well as concerns about their ability to do their job. Those without a job to return to (n = 7) talked about the ways they would go about finding work, and how long they thought this would take. Both groups mentioned the influence of wanting to find the "right" job, retraining and being limited due to the need for income.
Findings indicate that employees reference numerous work-related factors when estimating their timeframes for returning to work, and that many of these have been previously identified as relating to other return-to-work outcomes. Findings suggest the potential to improve return-to-work expectation through addressing work-related influences, and helping people work through the tasks they need to complete in order to move forward in the return-to-work process.
Study objective Trauma victims are frequently triaged to a trauma center according to the patient’s calculated Glasgow Coma Scale (GCS) score despite its known inconsistencies. The substitution of a ...simpler binary assessment of GCS-motor (GCS-m) score less than 6 (ie, “patient does not follow commands”) would simplify field triage. We compare total GCS score to this binary assessment for predicting trauma outcomes. Methods This retrospective analysis of a statewide trauma registry includes records from 393,877 patients from 1999 to 2013. Patients with initial GCS score less than or equal to 13 were compared with those with GCS-m score less than 6 for outcomes of Injury Severity Score (ISS) greater than 15, ISS greater than 24, death, ICU admission, need for surgery, or need for craniotomy. We judged a priori that differences less than 5% lack clinical importance. Results The relative differences between GCS and GCS-m scores less than 6 were less than 5% and thus clinically unimportant for all outcomes tested, even when statistically significant. For the 6 outcomes, the differences in areas under receiver operating characteristic curves ranged from 0.014 to 0.048. Total GCS score less than or equal to 13 was slightly more sensitive (difference 3.3%; 95% confidence interval 3.2% to 3.4%) and slightly less specific (difference –1.5%; 95% confidence interval –1.6% to –1.5%) than GCS-m score less than 6 for predicting ISS greater than 15, with similar overall accuracy (74.1% versus 74.2%). Conclusion Replacement of the total GCS score with a simple binary decision point of GCS-m score less than 6, or a patient who “does not follow commands,” predicts serious injury, as well as the total GCS score, and would simplify out-of-hospital trauma triage.
To determine the optimal glucose challenge test (GCT) cutoff value for the screening of gestational diabetes mellitus (GDM) based on pre-pregnancy BMI.
An-IRB approved retrospective cohort analysis ...of singleton pregnancies at a large tertiary healthcare center from January 2004 to December 2020 was performed. The first GCT value completed between 20 and 32 weeks was used. Using a receiver operator curve (ROC), we sought to determine the optimal GCT cutoff value for each BMI category that would predict the development of GDM. Youden Index was used to determine optimal cut-point of GCT values for each BMI class.
A total of 23,550 patients with a GCT value were identified. Of those, 1,676 (7.1%) were diagnosed with GDM. 513 (30.6%) with normal BMI, 449 (26.8%) overweight, 347 (20.7%) class I obese, 210 (12.5%) class II obese, and 157 (9.4%) class III obese patients were diagnosed with GDM. Gestational diabetes was predicted at GCT cutoff value of 130 mg/dL with an area under the curve (AUC) of 0.92 (BMI <25), 131 mg/dL with an AUC of 0.92 (overweight BMI), 131 mg/dL with an AUC of 0.89 (class I BMI), 133 mg/dL with an AUC of 0.88 (class II BMI), and 131 mg/dL with an AUC of 0.88 (class III BMI).
AUC ranged from 0.88 to 0.92 with 93% or greater sensitivity for GCT cutoff value across each of the BMI categories. The findings support a GCT cutoff value of 130 mg/dL for GDM screening regardless of BMI.
We describe age, multiple chronic condition profiles and health system contact in patients with urological cancer.
Using Geisinger Health System electronic health records we identified adult primary ...care patients and a subset with at least 1 urology encounter between 2001 and 2015. The Agency for Health Care Research and Quality Chronic Condition Indicator and Clinical Classifications Software tools were applied to ICD-9 codes to identify chronic conditions. Multiple chronic conditions were defined as 2 or more chronic conditions. Patients with urological cancer were identified using ICD-9 codes for prostate, bladder, kidney, testis and penile cancer. Inpatient and outpatient visits in the year prior to the most recent encounter were counted to document health system contact.
We identified 357,100 primary care and 33,079 urology patients, of whom 4,023 had urological cancer. Patients with urological cancer were older than primary care patients (71 vs 46 years) and they had more median chronic conditions (7 vs 4). Kidney and bladder cancer were the most common chronic conditions (median 8 patients each). Coronary artery disease and chronic kidney disease were common in urological cancer cases compared to mental health conditions in primary care cases. Patients with urological cancer who had multiple chronic conditions had the most health system contact, including 32% with at least 1 hospitalization and 68% with more than 5 outpatient visits during 1 year.
Urology patients are older and more medically complex, especially those with urological cancer than primary care patients. These data may inform care redesign to reduce the treatment burden and improve care coordination in urological cancer cases.
Challenging behavior, such as aggression, is highly prevalent in children and adolescents on the autism spectrum and can have a devastating impact. Previous reviews of challenging behavior ...interventions did not include interventions targeting emotion dysregulation, a common cause of challenging behavior. We reviewed emotion dysregulation and challenging behavior interventions for preschoolers to adolescents to determine which evidence-based strategies have the most empirical support for reducing/preventing emotion dysregulation/challenging behavior. We reviewed 95 studies, including 29 group and 66 single case designs. We excluded non-behavioral/psychosocial interventions and those targeting internalizing symptoms only. We applied a coding system to identify discrete strategies based on autism practice guidelines with the addition of strategies common in childhood mental health disorders, and an evidence grading system. Strategies with the highest quality evidence (multiple randomized controlled trials with low bias risk) were Parent-Implemented Intervention, Emotion Regulation Training, Reinforcement, Visual Supports, Cognitive Behavioral/Instructional Strategies and Antecedent-Based Interventions. Regarding outcomes, most studies included challenging behavior measures, while few included emotion dysregulation measures. This review highlights the importance of teaching emotion regulation skills explicitly, positively reinforcing replacement/alternative behaviors, using visuals and metacognition, addressing stressors proactively, and involving parents. It also calls for more rigorously designed studies and for including emotion dysregulation as an outcome/mediator in future trials.
Since its bi‐cultural foundation with Te Tiriti o Waitangi (the Treaty of Waitangi, signed in 1840 by Māori, the indigenous Polynesian people of Aotearoa New Zealand (NZ), chiefs and representatives ...of the British Crown), cultural identities have expanded through immigration. While Aotearoa NZ's government seeks to encourage workplace diversity in public service agencies, developments are being disrupted by Covid‐19. Using a typology of equality approaches, this study appraises the “ambition” of equity progress in Aotearoa NZ public service agencies based on content analysis of interviews with sector experts, agency staff and managers. In terms of equity discourses, workplace inequities emerge as more pronounced for Māori and Pasifika (the indigenous peoples of the Pacific), indicating that more “ambitious” equality initiatives, including those which aim for intersectional inclusion, are needed. The study thereby contributes a more nuanced understanding of equity approaches that could meaningfully inform workplace initiatives designed to recognize, value and empower gender diversity. Its relevance for Aotearoa NZ, which has one of the most diverse working‐age populations in the world, is likely to resonate in other countries where workforce diversity is yet to translate into equitable engagement in and experiences of work organizations by all.
Workers' own expectations for returning to work following a period of sickness absence have been found to be one of the best predictors of future work status; however, there is a limited ...understanding of why people expect what they do. The current study was undertaken with the aim of determining what people take into consideration when forming their expectations for returning to work.
Thirty-four people (8 women, 26 men), who were off work due to a musculoskeletal condition, participated in one of 14 focus groups. Participants were aged 25 to 65 (M = 45, SD = 12.6), and all had been out of work for 3 months or less.
All participants reported expecting to return to work, with the most common timeframe being approximately 30 days (Range = 1 day-12 months). When explaining what they thought about when forming their expectations, participants referenced numerous considerations. Much of what was spoken about could be compartmentalized to reflect features of themselves, their condition, or their broader environmental contexts. Participant's subjective experience of these features influenced his or her expectations. Prominent themes included concerns about employability, a desire to get back to normal, no job to go back to, mixed emotions, re-injury concerns, the judgments of workplace stakeholders, being needed by their employer, waiting for input, until the money runs out, and working out what was in their best interest.
Indications are that many of the reported considerations are amenable to intervention, suggesting opportunities to assist workers in the process of returning to work.
To examine pregnancy complications in women with uncomplicated mild-moderate chronic hypertension (CHTN) treated with antihypertensives prior to 20 weeks compared to those not on antihypertensives.
...This retrospective cohort study examined singleton pregnancies of women with mild-moderate CHTN who delivered from 01/2014-3/2019. Pregnancies complicated by hypertension at ≥ 20 weeks, end organ damage, preexisting diabetes mellitus, early-onset gestational diabetes, multifetal gestation, and fetal anomalies were excluded. Adjusted logistic regression analyses were performed for each of the outcomes. Adjusted odds ratios (aOR) were reported along with associated 95% confidence intervals (CI) and p-values.
Primary outcome was superimposed preeclampsia with severe features. Additional maternal outcomes were superimposed preeclampsia without severe features, severe hypertension, indicated preterm delivery, placental abruption, and mode of delivery. Neonatal outcomes included composite perinatal outcomes (fetal growth restriction, intrauterine fetal demise, and small for gestational age neonate), low birth weight, very low birth weight, admission to the neonatal intensive care unit, and Apgar score <7 at 5-minutes.
345 women were identified: 232 (67.2%) were not taking antihypertensives and 113 (32.8%) were taking ≥1 antihypertensive. There was no significant difference in the primary outcome (p = 0.65; aOR = 0.88; 95% CI 0.51−1.52) among the group taking antihypertensive therapy as compared to those not taking antihypertensives. No statistically significant differences were seen for any of the other secondary maternal or neonatal outcomes.
Our data supports that the use of antihypertensive therapy in women with mild-moderate CHTN does not reduce the risk of developing superimposed preeclampsia.
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