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Objectives Racial and socioeconomic disparities in the incidence of Legionnaires’ disease have been documented for the past 2 decades; however, the social determinants of health (SDH) that contribute to these disparities are not well studied. The objective of this narrative review was to characterize SDH to inform efforts to reduce disparities in the incidence of Legionnaires’ disease. Methods We conducted a narrative review of articles published from January 1979 through October 2019 that focused on disparities in the incidence of Legionnaires’ disease and pneumonia (inclusive of bacterial pneumonia and/or community-acquired pneumonia) among adults and children (excluding articles that were limited to people aged Results Of the 19 articles reviewed, multiple articles examined disparities in incidence of Legionnaires’ disease and pneumonia related to economic stability/income (n = 13) and comorbidities (n = 10), and fewer articles incorporated SDH variables related to education (n = 3), social support (none), health care access (n = 1), and neighborhood and built environment (n = 6) in their analyses. Conclusions Neighborhood and built-environment factors such as housing, drinking water infrastructure, and pollutant exposures represent critical partnership and research opportunities. More research that incorporates SDH and multilevel, cross-sector interventions is needed to address disparities in Legionnaires’ disease incidence.

Environmental remediation of polluted sites in developing communities often faces difficulties due to the misalignment of project objectives with the needs and interests of local communities, establishment of unrealistic expectations for the outcome of the project, and failure to account for the available resources in the community itself. Remediation decisions favor technical data and technical solutions as the main means of determining remediation options, requiring significant investment and local capacity that are often not found in developing communities. Often these systems fail to account for the social aspects in environmental management and remediation. In contrast, new approaches in local knowledge-based solutions focus on pre-existing environmental management initiatives to establish objectives that are meaningful to the community itself. “Positive deviance” – or the idea that there are solutions already in communities that are successful at addressing challenges despite the barriers that a community faces – are often overlooked during project design and implementation. Identifying examples of positive deviance and working with community members who are well versed in local challenges, available resources, and local capacity presents opportunities for community members to establish project objectives and provides the foundation for future environmental management projects in the area. We present a case study of artisanal and small-scale gold mining (ASGM) in the Andes municipality, Antioquia, Colombia and local initiatives to overcome community-identified environmental pollutants. Through a series of semi-structured interviews, surveys, and site visits, we identified community perception of environmental pollutants, management techniques for mining waste, and grassroots initiatives that were locally developed to address them. Through key communication and interaction between innovators with identified positive deviance projects, technical experts, and other miners facing similar challenges, innovative projects that account for the social, political, and economic realities of a developing community can become widespread, leading to improved environmental and social conditions.

Highlights • Our study investigated the safety and tolerability of palliative radiation therapy (RT) with concurrent Dabrafenib and Trametinib in patients with metastatic BRAF mutant melanoma, and we found that none of the patients enrolled in this study experienced grade 3 or 4 RT related toxicities. • We suggest that Dabrafenib and Trametinib may be safely used concurrently with common palliative RT doses to extracranial sites., Background Concurrent treatment with BRAF inhibitors and palliative radiation therapy (RT) could be associated with increased toxicity, especially skin toxicity. Current Eastern Cooperative Oncology Group (ECOG) consensus guideline recommend ceasing BRAF inhibitors during RT. There is a lack of data regarding concurrent RT with combined BRAF and MEK inhibitors. This single-arm phase I/II trial was designed to assess the safety and tolerability of palliative RT with concurrent Dabrafenib and Trametinib in patients with BRAF-mutant metastatic melanoma. Materials and methods Patients received Dabrafenib and Trametinib before and during palliative RT to soft tissue, nodal or bony metastases. The RT dose was escalated stepwise during the study period. Toxicity data including clinical photographs of the irradiated area was collected for up to 12 months following completion of RT. Results Between June 2016 to October 2019, ten patients were enrolled before the study was stopped early due to low accrual rate. Six patients were treated at level 1 (20 Gy in 5 fractions, any location) and 4 patients at level 2a (30 Gy in 10 fractions with no abdominal viscera exposed). All alive patients completed one year of post-RT follow-up. Of the 82 adverse events (AEs) documented, the majority (90%) were grade 1 and 2. Eight grade 3 events (10%) occurred in five patients, only one was treatment-related (grade 3 fever due to Dabrafenib and Trametinib). No patients experienced grade 3 or 4 RT related toxicities, including skin toxicities. One serious AE was documented in relation to a grade 3 fever due to Dabrafenib and Trametinib requiring hospitalisation. Conclusions The lack of grade 3 and 4 RT-related toxicities in our study suggests that Dabrafenib and Trametinib may be continued concurrently during fractionated non-visceral palliative RT to extracranial sites.

Autosomal dominant polycystic kidney disease (ADPKD), primarily due to PKD1 or PKD2 mutations, causes progressive kidney cyst development and kidney failure. There is significant intrafamilial variability likely due to the genetic background and environmental/lifestyle factors; variability that can be modeled in PKD mice. Here, we characterized mice homozygous for the PKD1 hypomorphic allele, p.Arg3277Cys (Pkd1(RC/RC)), inbred into the BALB/cJ (BC) or the 129S6/SvEvTac (129) strains, plus F1 progeny bred with the previously characterized C57BL/6J (B6) model; F1(BC/B6) or F1(129/B6). By one-month cystic disease in both the BC and 129 Pkd1(RC/RC) mice was more severe than in B6 and continued with more rapid progression to six to nine months. Thereafter, the expansive disease stage plateaued/declined, coinciding with increased fibrosis and a clear decline in kidney function. Greater severity correlated with more inter-animal and inter-kidney disease variability, especially in the 129-line. Both F1 combinations had intermediate disease severity, more similar to B6 but progressive from one-month of age. Mild biliary dysgenesis, and an early switch from proximal tubule to collecting duct cysts, was seen in all backgrounds. Preclinical testing with a positive control, tolvaptan, employed the F1(129/B6)-Pkd1(RC/RC) line, which has moderately progressive disease and limited isogenic variability. Magnetic resonance imaging was utilized to randomize animals and provide total kidney volume endpoints; complementing more traditional data. Thus, we show how genetic background can tailor the Pkd1(RC/RC) model to address different aspects of pathogenesis and disease modification, and describe a possible standardized protocol for preclinical testing.

OBJECTIVEInhibition of platelet aggregation is universally used to prevent thromboembolic complications related to stent placement in endovascular neurosurgery, but excessive inhibition potentiates hemorrhagic complications. Previously, the authors demonstrated that two different commercially available measures of adenosine diphosphate (ADP)–dependent platelet inhibition—the VerifyNow P2Y12 clopidogrel assay (measured in platelet reactivity units [PRU]) and maximal amplitude (MA) attributable to ADP activity (MA-ADP) derived from thromboelastography (TEG) with platelet mapping (PM)—yielded wildly different results. This study sought to analyze observed complications to quantify the ideal therapeutic windows for both tests.METHODSNinety-one patients with simultaneous or near-simultaneous PRU and TEG-PM results who underwent craniocervical endovascular stenting at the authors’ institution between September 2015 and November 2017 were identified and retrospectively enrolled. From November 2017 until June 2019, 109 additional patients were prospectively enrolled. For this study, in-hospital thrombotic and hemorrhagic complications (both CNS and non-CNS) were tabulated, and receiver operating characteristic (ROC) curve analysis was used to identify threshold values of the PRU and MA-ADP for predicting each type of complication.RESULTSOf the 200 patients enrolled, 7 were excluded because of anemia or thrombocytopenia outside of the test manufacturer’s specified ranges and 1 was excluded because they did not have a TEG-PM result. Including complications of all severities, there were a total of 15 CNS thrombotic complications, 1 access-site thrombotic complication, 3 CNS hemorrhages, 8 access-site hemorrhagic complications, and 3 hemorrhagic complications not affecting either the CNS or the access site. ROC curve analysis yielded therapeutic threshold values of 118–144 PRU. The results demonstrated PRU has a significant dose-dependent effect on the rates of thrombosis and hemorrhage. Logistic regression models did not demonstrate statistically significant relationships between the MA-ADP and either thrombosis or hemorrhage. ROC analysis based on these models is of little value and did not identify significant threshold values for MA-ADP.CONCLUSIONSThere continues to be poor correlation between the results of TEG-PM and PRU. PRU accurately predicted complications, with a relatively narrow ideal value range of 118–144. The MA-ADP alone does not appear able to accurately predict either hemorrhagic or thrombotic complications in this group.

Background The ACGME mandates that residency programs provide training related to high value care (HVC). The purpose of this study was to explore HVC education in general surgery residency programs. Methods An electronic survey was distributed to general surgery residents in geographically diverse programs. Results The response rate was 29% (181/619). Residents reported various HVC components in their curricula. Less than half felt HVC is very important for their future practice (44%) and only 15% felt confident they could lead a QI initiative in practice. Only 20% of residents reported participating in a root cause analysis and less than one-third of residents (30%) were frequently exposed to cost considerations. Conclusion Few residents feel prepared to lead quality improvement initiatives, have participated in patient safety processes, or are aware of patients’ costs of care. This underscores the need for improved scope and quality of HVC education and establishment of formal curricula.

There is little evidence on the role of diet in childhood/adolescence and multiple sclerosis (MS) in adulthood. The MS Sunshine Study recruited adults with recent-onset MS ( n = 602) and matched controls ( n = 653). Of these, 84% provided dietary recall for specific ages between childhood and young adulthood (6–10, 11–15 and 16–20 years). We used logistic regression to test associations between age-specific diet and case-control status. Consumption of fruit (all ages), yoghurt (all ages) and legumes (11–15 years) was associated with lower probability of adult-onset MS (all p

While health care for people with an intellectual disability in Australia has transitioned from institutional specialisation to a mainstream primary care model, access and quality of health care in...

The opioid crisis has continued to progress in the United States and the rest of the world. As this crisis continues, there is a pressing need for a rapid and cost-effective method for detecting fentanyl. Recent studies have suggested that lateral flow immunoassays (LFIs) could fill this technology gap. These qualitative paper-based assays contain antibodies designed to react with fentanyl and provide positive or negative results within a matter of minutes. In this study, two different LFI configurations for the detection of fentanyl were examined (dipsticks and cassettes) for effectiveness of detection using seized drug samples and postmortem urine samples. In the current study, 44 seized drug samples (32 fentanyl-positive, 12 fentanyl-negative) and 14 postmortem urine samples (10 fentanyl-positive, 4 fentanyl-negative) were analyzed. All 32 fentanyl-containing seized drug samples and 10 postmortem fentanyl-positive urine samples displayed positive LFI results with both LFI configurations. The fentanyl dipsticks displayed a sensitivity of 100%, a specificity of 75%, and an efficiency of 93.2% for seized drug samples and a sensitivity, specificity, and efficiency of 100% for postmortem urine. Analysis of the fentanyl cassettes displayed a sensitivity, specificity, and efficiency of 100% for seized drug samples and a sensitivity of 100%, a specificity of 75%, and an efficiency of 92.9% for postmortem urine samples. These data point to the utility of LFIs as a quick and low resource-dependent option for presumptive detection of fentanyl in real-world situations.

To identify evidence related to association between the nurse work environment and severe maternal morbidity in high-income countries.Quantitative Systematic review.Cumulative Index of Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, PubMed/Medline, and Scopus were systematically searched for studies published in English from January 1990-December 2019. Studies were selected based on a priori eligibility criteria.Two independent reviewers used a two-phase screening process. First, the reviewers assessed the eligibility of studies based on titles and abstracts; followed by assessing the full text of all remaining studies based on the eligibility criteria. An adapted version of the Joanna Briggs Institute data extraction tool was created to extract relevant information from studies reviewed during the second screening phase.Of the 535 de-duplicated articles examined by two independent reviewers, there were no eligible empirical studies that assessed the association between nurse work environment and severe maternal morbidity.There is a critical gap in knowledge regarding how characteristics of the nurse work environment may influence severe maternal morbidity in high-income countries. Future directions for nursing research include using available maternal health surveillance hospital-level data, conducting high-quality studies, and using evidence-based frameworks to guide future studies. Future directions for nursing practice include leveraging professional learning communities for nursing education and training and leveraging quality improvement initiatives.As the first known systematic review of its kind, this 'empty review' provides evidence of a lacking body of literature on the association between nurse work environment, as a modifiable organizational characteristic and preventable severe maternal morbidity in high-income countries. This article provides a call to action in the form of five recommendations for future nursing research and practice, which could serve to elucidate research, practice, and policy opportunities to reduce preventable severe maternal morbidity in high-income countries.目的: 确定高收入国家护士工作环境与严重孕产妇发病率之间关系的相关证据。 设计: 定量系统评估。 数据来源: 对护理学及医疗相关文献累计索引、Cochrane系统评估数据库、PubMed/Medline和Scopus中1990年1月至2019年12月期间以英文形式发表的研究进行了系统检索。根据先验的资格标准进行研究选择。 评估方法: 两名独立评估员采用了二阶段筛选过程。首先, 评估员根据标题和摘要评估研究的资格条件; 然后根据资格标准评估所有剩余研究的全文内容。创建了Joanna Briggs Institute数据提取工具的改编版, 以便从第二个筛选阶段审查的研究中提取相关信息。 结果: 在两名独立评估员审查的535篇去重文章中, 没有符合条件的实证研究评估护士工作环境与严重孕产妇发病率之间的关系。 结论: 在高收入国家, 关于护士工作环境的特点如何影响严重孕产妇发病率的问题, 目前存在关键知识空白。护理研究的未来方向包括利用现有的孕产妇健康监测医院层面的数据, 开展高质量的研究, 并利用循证框架来指导未来的研究。护理实践的未来方向包括利用专业学习社区进行护理教育和培训, 以及利用质量改进举措。 影响: 作为第一项已知的系统性评估,这种‘空洞的评估’提供了证据, 证明在高收入国家, 作为一种可改变的组织特征的护士工作环境与可预防的严重孕产妇发病率之间缺乏文献参考。本文以对未来护理研究和实践提出五项建议的形式发出行动呼吁, 这些建议可有助于阐明研究、实践和政策机会, 以降低高收入国家可预防的严重孕产妇发病率。.

Highlights • Targeted anti-cytokine agents, tocilizumab and anakinra, used to treat COVID-19 related cytokine storm yield mixed results. • Early identification of cytokine storm using laboratory abnormalities can detect patients prior to mechanical ventilation. • Early identification and treatment of cytokine storm with anakinra and corticosteroids led to improved outcomes compared to initiating tocilizumab shortly after mechanical ventilation. • Early identification and treatment of cytokine storm may be more important than which anti-inflammatory treatment is chosen. • Our results provide additional support for the use of corticosteroid treatment of COVID19 cytokine storm., Objective To examine outcomes among patients who were treated with the targeted anti-cytokine agents, anakinra or tocilizumab, for COVID-19 -related cytokine storm (COVID19-CS). Methods We conducted a retrospective cohort study of all SARS-coV2-RNA-positive patients treated with tocilizumab or anakinra in Kaiser Permanente Southern California. Local experts developed and implemented criteria to define COVID19-CS. All variables were extracted from the electronic health record. Results At tocilizumab initiation (n = 52), 50 (96.2%) were intubated, and only 7 (13.5%) received concomitant corticosteroids. At anakinra initiation (n = 41), 23 (56.1%) were intubated, and all received concomitant corticosteroids. Fewer anakinra-treated patients died (n = 9, 22%) and more were extubated/never intubated (n = 26, 63.4%) compared to tocilizumab-treated patients (n = 24, 46.2% dead, n = 22, 42.3% extubated/never intubated). Patients who died had more severe sepsis and respiratory failure and met COVID-CS laboratory criteria longer (median = 3 days) compared to those extubated/never intubated (median = 1 day). After accounting for differences in disease severity at treatment initiation, this apparent superiority of anakinra over tocilizumab was no longer statistically significant (propensity score-adjusted hazards ratio 0.46, 95% confidence interval 0.18–1.20). Conclusions Prompt identification and treatment of COVID19-CS prior to intubation may be more important than the specific type of anti-inflammatory treatment. Randomized controlled trials of targeted anti-cytokine treatments and corticosteroids should report duration of cytokine storm in addition to clinical severity at randomization.

We examined whether Medicaid-enrolled women in CenteringPregnancy group prenatal care had higher rates of (1) postpartum visit attendance and (2) postpartum uptake of contraceptives, compared to women in individual prenatal care.We linked birth certificates and Medicaid claims for women receiving group prenatal care in 18 healthcare practices and applied preferential-within cluster propensity score methods to identify a comparison group, accounting for the nested data structure by practice. We examined five standardized, claims-based outcomes: postpartum visit attendance; contraception within 3 days; and any contraception, long-acting reversible contraception (LARC), and permanent contraception within eight weeks. We assessed outcomes using logistic regression for two treatment levels: (1) any group attendance compared to no group attendance and (2) attendance at five or more group sessions to at least five prenatal care visits, including crossovers attending fewer than five group sessions (minimum threshold analysis).Women attending at least five group sessions had higher rates of postpartum visit attendance (71.5% vs. 67.5%, p .05). Women with any group attendance (N = 2834) were more likely than women with individual care only (N = 13,088) to receive contraception within 3 days (19.8% vs. 16.9%, p .001) and to receive a LARC within eight weeks' postpartum (18.0% vs. 15.2%, p .001). At both treatment levels, group participants were less likely to elect permanent contraception (5.9% vs. 7.8%, p 0.001). Women meeting the five-visit group threshold were not more likely to initiate contraception or LARCs within 8 weeks' postpartum.Participation in at least five group compared to five individual prenatal care visits is associated with greater rates of postpartum visit attendance. Additional engagement and education in group prenatal care may influence postpartum visit attendance.Planning for postpartum care and contraception during prenatal care is an important strategy for connecting women to postpartum healthcare. Regardless of prenatal care model, women have low uptake of contraception in the postpartum period. Increased use of group prenatal care with its scheduled family planning discussion may help to increase postpartum contraceptive uptake. This benefit is dependent on availability of postpartum contraception options.

Recently, states have enacted teacher-carry laws. While controversial, little scholarship has tapped public attitudes toward such reforms. Because public opinion shapes policy, the public is an imp...

Objectives: This community-based participatory research focused on physical and social barriers to healthcare for refugee women in Melbourne, Australia.Design: Women from non-English speaking backg...

Green stormwater infrastructure mirrors natural hydrologic processes and is presented as an alternative or complement to traditional gray stormwater infrastructure, which uses concrete chan...

Objectives Group prenatal care models were initially designed for women with medically low-risk pregnancies, and early outcome data focused on these patient populations. Pregnancy outcome data for women with medically high-risk pregnancies participating in group prenatal care is needed to guide clinical practice. This study compares rates of preterm birth, low birth weight, and neonatal intensive care unit admissions among women with medical risk for poor birth outcomes who receive group versus individual prenatal care. Study Design This retrospective cohort study uses vital statistics data to compare pregnancy outcomes for women from 21 obstetric practices participating in a statewide expansion project of group prenatal care. The study population for this paper included women with pregestational or gestational hypertension, pregestational or gestational diabetes, and high body mass index (BMI > 45 kg/m2). Patients were matched using propensity scoring, and outcomes were compared using logistic regression. Two levels of treatment exposure based on group visit attendance were evaluated for women in group care: any exposure (one or more groups) or minimum threshold (five or more groups). Results Participation in group prenatal care at either treatment exposure level was associated with a lower risk of neonatal intensive care unit (NICU) admissions (10.2 group vs. 13.8% individual care, odds ratio [OR] = 0.708, p Conclusion This study provides preliminary evidence that women who have or develop common medical conditions during pregnancy are not at greater risk for preterm birth, low birth weight, or NICU admissions if they participate in group prenatal care. Practices who routinely exclude patients with these conditions from group participation should reconsider increasing inclusivity of their groups. Key Points

Supplemental Digital Content is available in the text., OBJECTIVES: To compare the performance of Sequential Organ Failure Assessment, systemic inflammatory response syndrome, Red Flag Sepsis, and National Institute of Clinical Excellence sepsis risk stratification tools in the identification of patients at greatest risk of mortality from sepsis in nonintensive care environments. DESIGN: Secondary analysis of three annual 24-hour point-prevalence study periods. SETTING: The general wards and emergency departments of 14 acute hospitals across Wales. Studies were conducted on the third Wednesday of October in 2017, 2018, and 2019. PATIENTS: We screened all patients presenting to the emergency department and on the general wards. MEASUREMENTS AND MAIN RESULTS: We recruited 1,271 patients, of which 724 (56.9%) had systemic inflammatory response syndrome greater than or equal to 2, 679 (53.4%) had Sequential Organ Failure Assessment greater than or equal to 2, and 977 (76.9%) had Red Flag Sepsis. When stratified according to National Institute of Clinical Excellence guidelines, 450 patients (35.4%) were in the “High risk” category in comparison with 665 (52.3%) in “Moderate to High risk” and 156 (12.3%) in “Low risk” category. In a planned sensitivity analysis, we found that none of the tools accurately predicted mortality at 90 days, and Sequential Organ Failure Assessment and National Institute of Clinical Excellence tools showed only moderate discriminatory power for mortality at 7 and 14 days. Furthermore, we could not find any significant correlation with any of the tools at any of the mortality time points. CONCLUSIONS: Our data suggest that the sepsis risk stratification tools currently utilized in emergency departments and on the general wards do not predict mortality adequately. This is illustrated by the disparity in mortality risk of the populations captured by each instrument, as well as the weak concordance between them. We propose that future studies on the development of sepsis identification tools should focus on identifying predicator values of both the short- and long-term outcomes of sepsis.

Objectives To assess whether head CT with 3D reconstruction can replace skull radiographs (SXR) in the imaging investigation of suspected physical abuse (SPA)/abusive head trauma (AHT). Methods PACS was interrogated for antemortem skeletal surveys performed for SPA, patients younger than 2 years, SXR and CT performed within 4 days of each other. Paired SXR and CT were independently reviewed. One reviewer analysed CT without and (3 months later) with 3D reconstructions. SXR and CT expert consensus review formed the gold standard. Observer reliability was calculated. Results A total of 104 SXR/CT examination pairs were identified, mean age 6.75 months (range 4 days to 2 years); 21 (20%) had skull fractures; two fractures on CT were missed on SXR. There were no fractures on SXR that were not seen on CT. For SXR and CT, respectively: PPV reviewer 1, 95% confidence interval (CI) 48–82% and 85–100%; reviewer 2, 67–98% and 82–100%; and NPV reviewer 1, 95%, CI 88–98% and 96–100%; reviewer 2, 88–97% and 88–98%. Inter- and intra-observer reliability were respectively the following: SXR, excellent (kappa = 0.831) and good (kappa = 0.694); CT, excellent (kappa = 0.831) and perfect (kappa = 1). All results were statistically significant (p Conclusions CT has greater diagnostic accuracy than SXR in detecting skull fractures which is increased on concurrent review of 3D reconstructions and should be performed in every case of SPA/AHT. SXR does not add further diagnostic information and can be omitted from the skeletal survey when CT with 3D reconstruction is going to be, or has been, performed. Key Points • Head CT with 3D reconstruction is more sensitive and specific for the diagnosis of skull fractures. • Skull radiographs can be safely omitted from the initial skeletal survey performed for suspected physical abuse when head CT with 3D reconstruction is going to be, or has been, performed.

IntroductionBrain metastases are a significant source of morbidity and mortality for patients with lung cancer. Lung cancer can induce local and systemic immunosuppression, promoting tumor growth and dissemination. One mechanism of immunosuppression is tumor-induced expansion of programmed death-ligand 1 (PD-L1) expressing myeloid cells. Here, we investigate peripheral blood immune phenotype in NSCLC patients with or without brain metastasis.MethodsPeripheral blood was collected from patients with lung metastatic brain tumors and pre-metastatic lung cancer. Immunosuppressive monocytes, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs) were quantified through flow cytometry. T cell reactivity was analyzed via ELISpot. Brain metastasis conditioned media was collected from tumor-derived cell cultures and analyzed for cytokines by ELISA. Naïve monocytes were stimulated with brain metastasis conditioned media to evaluate PD-L1 stimulation.ResultsPatients with brain metastatic lung carcinoma demonstrated increased peripheral monocyte PD-L1, MDSC abundance, and Treg percentage compared to early stage pre-metastatic patients and healthy controls. Patients with elevated peripheral monocyte PD-L1 had less reactive T cells and worse survival. Brain metastasis conditioned media stimulation increased monocyte PD-L1, and conditioned media IL-6 levels correlated with PD-L1 induction. Treatment with anti-IL-6 or anti-IL-6 receptor antibodies reduced PD-L1 expression. In summary, patients with lung cancer and brain metastases exhibit multiple markers of peripheral immunosuppression.ConclusionsThe frequency of PD-L1+ myeloid cells correlated with the presence of brain metastases.Tumor-derived IL-6 was capable of inducing PD-L1+ myeloid cellsin vitro, suggesting thatmonitoring of immunosuppressive factors in peripheral blood may identify new targets for therapeutic intervention in selected patients.

ZIKV infection during pregnancy causes microcephaly, but not all neonates are affected. This study shows that features of the maternal antibodies correlate with the risk of ZIKV-associated microcephaly., Zika virus (ZIKV) infection during pregnancy causes congenital abnormalities, including microcephaly. However, rates vary widely, and the contributing risk factors remain unclear. We examined the serum antibody response to ZIKV and other flaviviruses in Brazilian women giving birth during the 2015–2016 outbreak. Infected pregnancies with intermediate or higher ZIKV antibody enhancement titers were at increased risk to give birth to microcephalic infants compared with those with lower titers (P < 0.0001). Similarly, analysis of ZIKV-infected pregnant macaques revealed that fetal brain damage was more frequent in mothers with higher enhancement titers. Thus, features of the maternal antibodies are associated with and may contribute to the genesis of ZIKV-associated microcephaly.

The Roux-en-Y gastric bypass (RYGB) isuery ID="Q1" Text="Author:Kindly check the edit made in the article title." -->the most efficacious procedure of choice for obese patients with gastroesophageal reflux disease (GERD). The laparoscopic sleeve gastrectomy (LSG) has high rates of worsening GERD post operatively. Little evidence exists as to whether the use of objective foregut investigations has a meaningful impact on surgical procedure selection. This study examined whether a standard preoperative foregut evaluation protocol effected procedure selection in bariatric patients presenting for surgical evaluation with subjective symptoms of GERD. Patients presenting for bariatric surgery evaluation with subjective symptoms of GERD entered into a predetermined protocol of foregut evaluation. Patients initially underwent upper endoscopy and esophagram. If the patient desired a LSG, further testing with esophageal pH testing and high-resolution manometry was ordered. If significant pathology was discovered on any of these investigations RYGB was recommended, if investigations were normal LSG was felt to be permissible. Data were collected prospectively from July 2016 to December 2018 and reviewed. One hundred and thirty-three patients were identified as being eligible to have progressed through the protocol. Pathology was commonly discovered on preoperative evaluations. On EGD Barrett’s esophagus was discovered in 4%, grade C or D esophagitis in 18% and hiatal hernia in 36% of patients. On esophagram, hiatal hernia was discovered in 42.3% of patients. Abnormal esophageal motility was discovered in 41% and abnormal DeMeester scores in 83% of tested patients. Of the 133 patients evaluated, the final procedure the patient ultimately underwent was primarily determined based on protocol test results in 24.8% of cases. Foregut pathology is common in bariatric patients with subjective symptoms of GERD. Implementing a comprehensive protocol to objectively assess these patients leads to a significant clinical impact on which procedure these patients ultimately undergo.

Survival outcomes for patients with glioblastoma (GBM) are universally poor with only a small percentage of patients surviving five years beyond initial diagnosis. Activation of the immune system against tumor cells is the basis of immunotherapy and aims to facilitate long-term immune surveillance and tumor suppression. Cytomegalovirus (CMV) has emerged as an immunologic target in GBM given that tumor cells have been shown to express the CMV-associated proteins IE1 and pp65. Moreover, vaccine therapy targeting CMV antigens has promoted improved survival outcomes with long-term survivors. In this report, we present the case of a 69 year-old woman with GBM who survived seven years post-diagnosis. Following tumor resection, the patient underwent concomitant radiation and temozolomide therapy that was complicated by CMV colitis and abdominal abscesses. Despite not receiving adjuvant temozolomide, the patient demonstrated a five year progression-free survival before requiring re-resection for radiation necrosis. Following re-resection, the patient survived for two additional years. As the patient's tumor stained positive for CMV antigens IE1 and pp65, it is hypothesized that she developed an immune response against CMV during recovery that contributed to anti-tumor surveillance and prolonged survival. Overall, this case supports further investigation into the role of CMV and immunotherapy in GBM.

BACKGROUND: Brain radiotherapy is used in the management of melanoma brain metastases (MBM) and can result in radionecrosis. Anti-PD-1 is active in the brain and may increase the risk of radionecrosis when combined with radiotherapy. We studied the incidence, associated factors and management of radionecrosis in longer-term survivors with MBM treated with this combination. METHODS: Patients with MBM treated with radiotherapy and anti-PD-1 who survived >1 year were identified to determine radionecrosis incidence (Cohort A, n = 135). Cohort A plus additional radionecrosis cases were examined for factors associated with radionecrosis and management (Cohort B, n = 148). RESULTS: From Cohort A, 17% developed radionecrosis, with a cumulative incidence at 2 years of 18%. Using Cohort B, multivariable analysis confirmed an association between radionecrosis and elevated lactate dehydrogenase (p = 0.0496) and prior treatment with ipilimumab (p = 0.0319). Radionecrosis was diagnosed based on MRI (100%), symptoms (69%) and pathology (56%). Treatment included corticosteroids, bevacizumab and neurosurgery. CONCLUSIONS: Radionecrosis is a significant toxicity in longer-term melanoma survivors with MBM treated with anti-PD-1 and radiotherapy. Identification of those at risk of radionecrosis who may avoid radiotherapy is required.

Background Challenging emerging entities with distinctive molecular signatures may benefit from algorithms for diagnostic work-up. Methods Fusion sarcomas (2020–2021, during pandemic) were diagnosed by clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS). Results Six fusion sarcomas in two males and four females involved the chest-wall, neck, or extremities; ages ranged 2-73, median 18 years. Sizes ranged 5.3-25.0, median 9.1 cm. These include high grade 1) TPR-NTRK1 of proximal femur with a larger rounded soft tissue mass, previously considered osteosarcoma yet without convincing tumor matrix. A pathologic fracture necessitated emergency hemipelvectomy (NED) and 2) novel KANK1-NTRK2 sarcoma of bone and soft tissue with spindled pleomorphic to epithelioid features (AWD metastases). 3) Novel ERC1-ALK unaligned fusion, a low grade infiltrative deep soft tissue hand sarcoma with prominent-vascularity, myopericytoid/lipofibromatosis-like ovoid cells, and collagenized stroma, was successfully treated with ALK-inhibitor (Crizotinib), avoiding amputation. These NTRK and ALK tumors variably express S100 and CD34 and were negative for SOX10. 4) and 5) CIC-DUX4 round cell tumors (rapid metastases/demise), one with COVID superinfection, were previously treated as Ewing sarcoma. These demonstrated mild pleomorphism and necrosis, variable myxoid change and CD99 reactivity, and a distinctive dot-like-Golgi WT1 immunostaining pattern. 6) A chest wall/thoracic round cell sarcoma, focal CD34/ keratins/CK7, revealed nuclear-STAT6, STAT6-NAB2 by NGS, confirming malignant solitary fibrous tumor, intermediate-risk-stratification (AWD metastases). Conclusions Recent fusion sarcomas include new KANK1-NTRK2 and ERC1-ALK, the latter successfully treated by targeted-therapy. ALK/NTRK fusion partners TPR and KANK1 suggest unusual high-grade morphology/behavior. Clinicoradiologic, morphologic, and phenotypic algorithms can prompt molecular-targeted immunostains or NGS for final classification and promising inhibitor therapy.

The primary objectives were to determine the prevalence of and identify variables associated with respiratory bacterial co-infection in COVID-19 inpatients. Secondary outcomes included length of stay and in-hospital mortality. Eighty-two (11.2%) of 735 COVID-19 inpatients had respiratory bacterial co-infection. Fifty-seven patients met inclusion criteria and were matched to three patients lacking co-infection (N = 228 patients). Patients with co-infection were more likely to receive antibiotics [57 (100%) vs. 130 (76%), p < 0.0001] and for a longer duration [19 (13-33) vs. 8 (4-13) days, p

There has been praise of how female leaders have handled the Coronavirus pandemic relative to their male counterparts by presenting a more "caring" leadership. Of similar coverage has been the role of public trust for how successful governments have been in containing outbreaks. In this paper, we build on these two literatures to understand different determinants of trust during the pandemic between men and women. Following social role theory, we argue that female citizens' trust judgements are more likely to be driven by the perception that leaders are more caring than are men, whilst men's judgements are more likely to be driven by competence judgements than women's. We test this argument using original survey data from three countries. We find that this relationship holds in the United States, but not the United Kingdom or Italy. This adds to variation in gender gaps in the USA and Europe;at the same time, it also suggests that the propensity for women to be less trusting than men is not down to (perceived) leadership traits. [ABSTRACT FROM AUTHOR] Copyright of Journal of Elections, Public Opinion & Parties is the property of Routledge and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We conducted a retrospective cohort study in Kaiser Permanente Southern California from 1 January 2020 to 30 September 2020. We found that rituximab‐treated persons with multiple sclerosis (pwMS, n = 1895) were more likely be hospitalized (n = 8, 33.3%), but not die (n = 0) from COVID‐19, compared to the 4.81 million non‐MS population (5.8% and 1.4%, respectively). Time in months (adjusted OR = 0.32, 95% CI = 0.15–0.69, p = 0.0033) and receiving 1000 mg compared to lower doses at last infusion (adjusted OR = 6.28, 95% CI = 1.38–28.5, p = 0.0173) were independent predictors of COVID‐19 severity. Rituximab‐treated pwMS should be counseled to take extra precautions in the 5 months following each infusion. Using extended dosing intervals and lower doses could be considered.

Background Australian women from migrant and refugee communities experience reduced access to sexual and reproductive healthcare. Human-centred design can be a more ethical and effective approach to developing health solutions with underserved populations that are more likely to experience significant disadvantage or social marginalisation. This study aimed to evaluate how well Shifra, a small Australian-based not-for-profit, applied human-centred design when developing a web-based application that delivers local, evidence-based and culturally relevant health information to its non-English speaking users. Methods This study undertook a document review, survey, and semi-structured interviews to evaluate how well Shifra was able to achieve its objectives using a human-centred design approach. Results A co-design process successfully led to the development of a web-based health app for refugee and migrant women. This evaluation also yielded several important recommendations for improving Shifra’s human-centred design approach moving forward. Conclusions Improving refugees’ access to sexual and reproductive health is complex and requires innovative and thoughtful problem solving. This evaluation of Shifra’s human-centred design approach provides a helpful and rigorous guide in reporting that may encourage other organisations undertaking human-centred design work to evaluate their own implementation., Plain English summary Australian women from non-English speaking migrant and refugee communities face reduced access to sexual and reproductive healthcare and many then go on to experience poor health outcomes as a result. There is an urgent need for new approach to improve access to healthcare for underserved communities, one that centres these women in the process of finding, developing and disseminating the solutions themselves. Human-centred design can be a more ethical and effective methodology in working with communities to develop these health solutions. This study aimed to evaluate how well Shifra, a small Australian-based not-for-profit focused on improving access to healthcare for refugees and new migrants, undertook human-centred design approach when developing a Smartphone app that delivers local, safe and culturally relevant health information to non-English speaking Australians. The authors interviewed refugees, health and social sector experts and computer programmers involved in creating Shifra to evaluate how well they used human-centred design to achieve its goals. This evaluation found that Shifra’s approach was successful whilst also highlighting several important recommendations for improving collaborative efforts with refugee communities. These findings could help other projects also seeking to undertake an authentic community co-design process.

Bilateral ligation of the anterior division of the internal iliac arteries can be a lifesaving intervention for severe pelvic hemorrhage. The procedure results in decreased pelvic perfusion and promotes coagulation. The classical method of internal iliac artery ligation involved extensive retroperitoneal dissection with complete circumferential isolation of the vessel to allow the passage of a suture around the artery. This can be surgically challenging and fraught with risks of inadvertent injury to the surrounding iliac veins. We propose a contemporary technique that requires limited dissection of the anterior division of the internal iliac artery. A few millimeters of space is created on either side of the artery by spreading right-angle forceps parallel to the vessel. The artery is occluded by 2 large vascular clips. Because circumferential vessel dissection is not necessary with this technique, there is limited disruption of the delicate underlying internal iliac vein. In addition, this approach may decrease the risk of inadvertent injury to the adjacent external iliac vein. By showcasing the ease of our approach to internal iliac artery ligation, we hope to empower surgeons with an alternative approach to this lifesaving procedure.

The primary objective is to determine which of two interventions: 1) an eight week, online, home-based, supervised, group rehabilitation programme (REGAIN); or 2) a single online session of advice (best-practice usual care); is the most clinically and cost-effective treatment for people with ongoing COVID-19 sequelae more than three months after hospital discharge. Multi-centre, 2-arm (1:1 ratio) parallel group, randomised controlled trial with embedded process evaluation and health economic evaluation. Adults with ongoing COVID-19 sequelae more than three months after hospital discharge Inclusion criteria: 1) Adults ≥18 years; 2) ≥ 3 months after any hospital discharge related to COVID-19 infection, regardless of need for critical care or ventilatory support; 3) substantial (as defined by the participant) COVID-19 related physical and/or mental health problems; 4) access to, and able/supported to use email and internet audio/video; 4) able to provide informed consent; 5) able to understand spoken and written English, Bengali, Gujarati, Urdu, Punjabi or Mandarin, themselves or supported by family/friends. Exclusion criteria: 1) exercise contraindicated; 2) severe mental health problems preventing engagement; 3) previous randomisation in the present study; 4) already engaged in, or planning to engage in an alternative NHS rehabilitation programme in the next 12 weeks; 5) a member of the same household previously randomised in the present study. Intervention 1: The Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) programme: an eight week, online, home-based, supervised, group rehabilitation programme. Intervention 2: A thirty-minute, on-line, one-to-one consultation with a REGAIN practitioner (best-practice usual care). The primary outcome is health-related quality of life (HRQoL) – PROMIS® 29+2 Profile v2.1 (PROPr) – measured at three months post-randomisation. Secondary outcomes include dyspnoea, cognitive function, health utility, physical activity participation, post-traumatic stress disorder (PTSD) symptom severity, depressive and anxiety symptoms, work status, health and social care resource use, death - measured at three, six and 12 months post-randomisation. Participants will be randomised to best practice usual care or the REGAIN programme on a 1:1.03 basis using a computer-generated randomisation sequence, performed by minimisation and stratified by age, level of hospital care, and case level mental health symptomatology. Once consent and baseline questionnaires have been completed by the participant online at home, randomisation will be performed automatically by a bespoke web-based system. To ensure allocation concealment from both participant and REGAIN practitioner at baseline, randomisation will be performed only after the baseline questionnaires have been completed online at home by the participant. After randomisation has been performed, participants and REGAIN practitioners cannot be blind to group allocation. Follow-up outcome assessments will be completed by participants online at home. A total of 535 participants will be randomised: 263 to the best-practice usual care arm, and 272 participants to the REGAIN programme arm. Current protocol: Version 3.0 (27th October 2020) Recruitment will begin in December 2020 and is anticipated to complete by September 2021. ISRCTN:11466448 , 23rd November 2020 The full protocol Version 3.0 (27th October 2020) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interests of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

What is known and objective The 2017 IDSA/SHEA Clinical Practice Guidelines for Clostridioides difficile infection (CDI) recommend treating recurrent episodes with fidaxomicin or oral vancomycin, but there is little evidence to support one strategy over another, particularly beyond the first recurrence. The aim of this study was to compare clinical outcomes in patients with recurrent CDI treated with vancomycin vs. fidaxomicin. Methods This retrospective study evaluated inpatients with recurrent CDI treated with vancomycin or fidaxomicin between 1 January 2013 and 1 May 2019. The primary outcome was CDI recurrence. Secondary outcomes included re-infection, treatment failure, infection-related length of stay (IRLOS) and in-hospital all-cause mortality (IHACM). The Wilcoxon rank-sum test, Pearson's chi-square test or Fisher's exact test was utilized, as appropriate. A multivariable logistic regression (MLR) model was used to estimate the adjusted odds ratio and 95% confidence interval assessing recurrence while adjusting for confounding variables. A survival analysis was also conducted. Results 135 patients met the inclusion criteria (35 fidaxomicin vs. 100 vancomycin). There was no difference in CDI recurrence [7 (20%) fidaxomicin vs. 11 (11%) vancomycin, p = 0.18]; this persisted in the MLR model (OR: 0.85 [95% CI 0.27-2.7]) and survival analysis (p = 0.1954). Additionally, there was no difference in re-infection rate (p = 0.73), treatment failure (p = 0.13), IRLOS (p = 0.19) or IHACM (p = 0.65). What is new and conclusion This represents the first analysis of CDI recurrence that included patients with >2 prior episodes of CDI. The study found no difference in additional recurrences when patients were treated with oral vancomycin vs fidaxomicin for recurrent CDI. However, the current study is limited by the small sample size available for inclusion. Prospective randomized studies with larger sample sizes are needed to confirm this study's conclusions.

We piloted a methodology for collecting and interpreting root cause—or environmental deficiency (ED)—information from Legionnaires’ disease (LD) outbreak investigation reports. The methodology included a classification framework to assess common failures observed in the implementation of water management programs (WMPs). We reviewed reports from fourteen CDC-led investigations between 1 January 2015 and 21 June 2019 to identify EDs associated with outbreaks of LD. We developed an abstraction guide to standardize data collection from outbreak reports and define relevant parameters. We categorized each ED according to three criteria: ED type, WMP-deficiency type, and source of deficiency. We calculated the prevalence of EDs among facilities and explored differences between facilities with and without WMPs. A majority of EDs identified (81%) were classified as process failures. Facilities with WMPs (n = 8) had lower prevalence of EDs attributed to plumbed devices (9.1%) and infrastructure design (0%) than facilities without WMPs (n = 6; 33.3% and 24.2%, respectively). About three quarters (72%) of LD cases and 81% of the fatalities in our sample originated at facilities without a WMP. This report highlights the importance of WMPs in preventing and mitigating outbreaks of LD. Building water system process management is a primary obstacle toward limiting the root causes of LD outbreaks. Greater emphasis on the documentation, verification, validation, and continuous program review steps will be important in maximizing the effectiveness of WMPs.

Objectives Staphylococcus aureus (S. aureus) is the leading cause of bacteraemia and infective endocarditis worldwide. The preferred management of patients with methicillin-susceptible S. aureus (MSSA) bacteraemia includes definitive therapy with intravenous anti-staphylococcal beta-lactam (ASBL) antibiotics. Daptomycin (DAP) has been targeted as a viable substitute for beta-lactam allergic or intolerant patients. Methods This single-center retrospective cohort study assessed clinical outcomes of DAP compared with ASBL antibiotics [nafcillin (NAF) or cefazolin (CFZ)] for the treatment of MSSA bacteraemia in patients hospitalised from 01 November 2011 to 31 October 2018. The primary outcome was a composite of the following: clinical failure, MSSA recurrence and MSSA persistence or inpatient infection-related mortality. Secondary outcomes included duration of MSSA bacteraemia, infection-related length of stay, infection-related 90-day readmission, 30-day all-cause mortality, and adverse events necessitating a change in therapy. Results Of 89 patients with MSSA bacteraemia who were included: 29 received DAP, 30 received NAF and 30 received CFZ. There was no difference in the composite primary outcome in patients treated with DAP compared with ASBL (10% vs. 5%, P = 0.39). The DAP cohort had a longer hospital length of stay compared with the ASBL group (20 days vs. 11.5 days, P = 0.0007). No differences were detected between other secondary outcomes. Conclusion This study suggests that DAP may serve as a comparable alternative to ASBLs for treatment of MSSA bacteraemia, as no differences in clinical outcomes were identified. Larger studies are needed to confirm these findings.

Background Recent travel is associated with ~20% of reported Legionnaires’ disease (LD) cases worldwide. Methods We analyzed LD cases reported to the Centers for Disease Control and Prevention (CDC) during 2015–2016. Travel-associated cases met case criteria for confirmed LD in someone who spent ≥1 night away from home during the 10 days before symptom onset. Most analyses were limited to travel-associated, public accommodation stay (TAPAS) cases. We used reported travel dates to estimate the number of TAPAS cases acquired during travel. Results Of 12,200 LD cases reported among U.S. residents, 12.3% were travel-associated; 8.7% were TAPAS. Median patient age for TAPAS cases was 61 years; 64.4% were male; 67.3% were white; 77.9% were non-Hispanic; 96.1% were hospitalized; 4.5% died. Among 887 TAPAS cases involving U.S. destinations, an estimated 29.8% were acquired during travel; 4.28 TAPAS cases were reported, and an estimated 1.10 TAPAS cases were acquired during travel, per 10,000,000 hotel room nights booked. Sixty-eight U.S. TAPAS clusters were detected. Conclusions While acquisition during travel accounted for a relatively small proportion of all LD cases, clusters of TAPAS cases were frequently detected. Prompt notification of these cases to CDC facilitates cluster detection and expedites intervention.

Backpack use and weight have been suggested as possible causes of back pain in adolescents. Current literature reviews show that evidence is lacking to link backpack use and backpack characteristics with the increasing rates of adolescent back pain (Yamato, Br J Sports Med 52:1241–1245, 2018). Any association is more likely related to fatigue and loss of core/trunk stabilization strength when carrying a backpack for extended periods of time. The American Academy of Pediatrics offers recommendations on the proper use, fit, and weight of backpacks as a means to decrease strain on the adolescent spine.

Tocilizumab, an interleukin-6 receptor antagonist, has been used to treat critically ill patients with coronavirus disease-2019. We present the case of a previously immunocompetent man with coronavirus disease-2019 who developed invasive pulmonary aspergillosis after treatment with tocilizumab, illustrating the importance of considering opportunistic infections when providing immune modulating therapy.

Background: Neonatal intensive care unit (NICU) patient satisfaction is measured as parent satisfaction. Parents are critical to the family-centered care model and can evaluate care. Several EMpowerment of PArents in THe Intensive Care (EMPATHIC) instruments were developed in the Netherlands to measure parent satisfaction with neonatal and pediatric intensive care. EMPATHIC instruments comprise five domains and a total score: information, care and treatment, organization, parental participation, and professional attitude. To our knowledge, the EMPATHIC has not been adapted for USA use. Objectives: (1) To select a relevant EMPATHIC instrument for our study. (2) To expand the content reflecting the role of nurses and the cultural heterogeneity of USA NICU infants. (3) To adapt the selected EMPATHIC instrument to USA English. (4) To establish psychometric properties of the linguistically adapted instrument. (5) To evaluate instrument performance with additional items. Methods: The EMPATHIC-30 was selected based on shortest length, high overlap with neonatal EMPATHIC-N, and availability of a validated Spanish-language version. Six items from the EMPATHIC-N were added, two of which were split into separate items, resulting in the EMPATHIC-38. A neonatal nurse practitioner adapted wording to USA English. Cognitive debriefing was performed with eight NICU parents to evaluate adapted wording. Parent survey data from a study about missed nursing care and NICU parent satisfaction were utilized. Internal consistency of the five domains and overall score was measured by Cronbach's alpha. Spearman's rank correlations were computed for domains and overall score with four validity measures. Differential validity was determined using 13 parent demographic subgroups. Results: Data were from 282 parents. Parent race was predominantly White (61%) or Black (22%). One fifth were Hispanic. The adapted wording was satisfactory. Four of the five EMPATHIC-30 and EMPATHIC-38 domains had Cronbach alphas at or above 0.70, indicating acceptable reliability. Correlations between the domain, total scores, and validity indicators ranged from 0.30 to 0.57, indicating positive, moderate associations. Results were replicated in demographic subgroups. Reliability and validity of the three domains with additional items were better than or equivalent to values for the original. Conclusion: The linguistically adapted EMPATHIC-30-NICU-USA and the expanded EMPATHIC-38-NICU-USA exhibit satisfactory psychometric properties and are suitable for use in USA NICUs.

Category: Basic Sciences/Biologics; Ankle; Diabetes; Midfoot/Forefoot Introduction/Purpose: Charcot neuropathic arthropathy (CNA) is a debilitating, rapidly destructive degenerative joint disease that occurs in diabetic, neuropathic midfoot. Clinicoradiologic assessment for CNA previously relied on Eichenholtz Stage. There is limited data on CNA histopathology. The goal of this study was to independently develop a histopathologic scoring system for Charcot neuropathic arthropathy. Methods: Retrieval of surgical pathology specimens from neuroarthropathic CNA patients (2012-2019) were analyzed to evaluate joint soft tissue and bone. Considering progression from large to small periarticular bone fragments to resolution, we devised and applied a CNA FEMASK-score (named after coauthors): 0= intraneural arteriolosclerosis; 1= large bone fragments without host histiocytic response; 2= mixed bone fragments with host histiocytic response; 3= small minute bone spicules resorption to fibrosis. Clinical modified Eichenholtz staging and outcome were then compared the CNA FEMASK-score to assess for associations between these three elements. Results: Forty-eight cases of CNA included 34 males and 14 females, mean age 60.3 and age range 28-83 years, with clinical diabetes mellitus (predominantly Type II) and longstanding neuropathy. Elevated HbA1C, Eichenholtz stage, American Society of Anesthesia score, and Charlson comorbidity index were predictive of amputation. Pathologic specimens varied from fixation tissue to amputation. In addition to neurotraumatic, neurovascular and inflammatory findings, a distinctive intraneural hyalinized arteriolosclerosis was observed. FEMASK-scores:1 = 10%, 2= 58%, and 3=32%. FEMASK-score comparisons were 98% accurate compared with the modified Eichenholtz criteria scores of each patient and 98% reproducible among pathologists. FEMASK 2 and 3 correlates strongly with amputation. Conclusion: Our novel CNA FEMASK-score classification, derived from the largest cohort of diabetic neuropathic specimens, is reproducible, explains pathophysiology, correlates with Eichenholtz, and predicts amputation. The unique intraneural vasculopathy observed contributes to CNA etiology.

Objective To characterize fellowship training experiences in the 11 Canadian minimally invasive gynaecologic surgery (MIGS) programs and compare the surgical exposure of fellows in these programs to that of the American Association of Gynecologic Laparoscopists (AAGL) accredited fellowship in MIGS (FMIGS). Methods In this cross-sectional study, 2017 and 2018 MIGS fellowship graduates across Canada were given a web-based survey via SurveyMonkey software to evaluate 5 key components of postgraduate fellowship curricula: 1) surgical exposure; 2) teaching and evaluation methods; 3) research experience; 4) clinical responsibilities; and 5) pursuit of other academic endeavours. Interest in creating a national standardized curriculum and seeking accreditation for MIGS fellowships were also examined. Results The survey attained a 91% (20/22) response rate of the target population. All Canadian MIGS programs met the minimum standards for at least 62% (8/13) of the surgical competencies listed by the AAGL, with office hysteroscopy being the procedure with the largest discordance. Half of respondents (10/20) attended a program with an established curriculum, and 75% (15/20) believed there would be a benefit to standardizing training nationwide. Seventy percent (14/20) had published at least one manuscript during their fellowship and 60% (12/20) pursued postgraduate degrees. The majority (55%; 11/20) felt certain that MIGS should become a credentialed fellowship in Canada. Conclusion Canada has made meaningful progress in MIGS training over the past decade with 11 well-established fellowship programs. Although this survey identifies a general interest in standardized training and accreditation for Canadian MIGS programs, more research is needed on how best to accomplish this.

What is known Daptomycin is associated with a number of adverse effects including eosinophilic pneumonia, hypersensitivity reaction, myopathy, rhabdomyolysis, headache and transaminitis. The adverse effects of high-dose daptomycin have not been fully evaluated in patients with end-stage renal disease (ESRD). Objective To determine the incidence and characteristics of significant adverse effects in patients receiving high-dose daptomycin with severe renal dysfunction. Methods A single-centre, retrospective study was conducted to assess safety outcomes of high-dose daptomycin in patients with an estimated creatinine clearance less than 30 mL/min. Adult patients aged 18 to 89 years admitted between 1 July 2015 and 1 July 2019 were eligible for inclusion. Patients must have received definitive daptomycin therapy with doses greater than or equal to 7.5 mg/kg based on actual body weight. The primary outcome was overall incidence of creatine phosphokinase (CK) elevation, myopathy and rhabdomyolysis. Results and discussion A total of 74 patients who received daptomycin therapy were screened with 50 included in the study. The population was well distributed in terms of gender (48% male, n = 24) with a median age of 61 (IQR, 48-67) years. The primary indication for daptomycin use was Gram-positive bacteremia. The median daptomycin dose was 750 (IQR, 600-875) mg, or 8.46 (IQR, 7.92-9.96) mg/kg based on actual body weight, with a median patient weight of 81 (IQR, 65-113) kg. The median duration of therapy was 27 (IQR, 14-42) days. One patient experienced significant CK elevation while on daptomycin therapy with rhabdomyolysis; however, daptomycin was continued as there was an alternative explanation for an elevated CK. One patient experienced daptomycin discontinuation due to CK elevation without meeting the definition for significant CK elevation. What is new and conclusion In a cohort of patients with severe renal dysfunction treated with daptomycin 7.5 mg/kg or greater, significant CK elevation on daptomycin therapy was infrequently observed. Future research should confirm these findings, with special consideration for higher mg/kg dosages and/or obese populations.

Perception of weight loss requirements before bariatric surgery varies among patients, physicians, and health insurance payers. Current clinical guidelines do not require preoperative weight loss because of a lack of scientific support regarding its benefits.To examine the association of preoperative body mass index (BMI) and weight loss with 30-day mortality after bariatric surgery.This cohort study used data from 480 075 patients who underwent bariatric surgery from 2015 to 2017 in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program, which covers more than 90% of all bariatric surgery programs in the United States and Canada. Clinical and demographic data were collected at all participating institutions using a standardized protocol. Data analysis was performed from December 2018 to November 2019.Preoperative BMI and weight loss.30-day mortality after bariatric surgery.Of the 480 075 patients (mean [SD] age 45.1 [12.0] years; 383 265 [79.8%] women), 511 deaths (0.1%) occurred within 30 days of bariatric surgery. Compared with patients with a preoperative BMI of 35.0 to 39.9, the multivariable-adjusted odds ratios for 30-day mortality for patients with preoperative BMI of 40.0 to 44.9, 45.0 to 49.9, 50.0 to 54.9, and 55.0 and greater were 1.37 (95% CI, 1.02-1.83), 2.19 (95% CI, 1.64-2.92), 2.61 (95% CI, 1.90-3.58), and 5.03 (95% CI, 3.78-6.68), respectively (P for trend .001). Moreover, compared with no preoperative weight loss, the multivariable-adjusted odds ratios for 30-day mortality for patients with weight loss of more than 0% to less than 5.0%, 5.0% to 9.9%, and 10.0% and greater were 0.76 (95% CI, 0.60-0.96), 0.69 (95% CI, 0.53-0.90), and 0.58 (95% CI, 0.41-0.82), respectively (P for trend = .003).In this study, even moderate weight loss (ie,0% to5%) before bariatric surgery was associated with a lower risk of 30-day mortality. These findings may help inform future updates of clinical guidelines regarding bariatric surgery.

ObjectiveTo describe the safety and efficacy of rituximab (RTX) in MS and pregnancy, we conducted a retrospective cohort study of 74 pregnancies among 55 women treated with RTX for MS and their offspring.MethodsWe used prospectively collected information from the electronic health record at Kaiser Permanente Southern California between 2012 and 2019 of mother and baby to identify treatment history, pregnancy outcomes, and relapses.ResultsLast RTX exposure before conception occurred between 1.8 and 5.2 months in 32 (49%) of 65 pregnancies and accidentally during the first trimester in 9 (12%). Among 38 live births, adverse pregnancy outcomes were as follows: 3 preterm deliveries (including 1 set of twins), 1 neonatal death (preterm twin), and 1 perinatal stroke (full-term). No stillbirths, chorioamnionitis, or major malformations were found. Fifteen (27%) women had at least one first-trimester miscarriage, of whom 8 (53%) had a history of infertility. Cumulative dose or timing of last RTX infusion was not associated with an increased risk of miscarriage. Only 2 (5.4%) women experienced relapses, one during pregnancy and the other postpartum.ConclusionWe observed no increase in adverse pregnancy outcomes compared with expected national incidence rates and remarkably little disease activity in RTX-treated women with MS, particularly when compared with periconceptional natalizumab-treated cohorts. However, larger studies are needed to fully assess the safety of RTX use before pregnancy, especially risks associated with prolonged B-cell depletion and hypogammaglobulinemia. Until these data are available, we recommend restricting RTX use before pregnancy to women who require highly effective MS treatments.Classification of evidenceThis study provides Class IV evidence that for pregnant women with MS, RTX controls disease activity and does not increase adverse pregnancy outcomes.

Author(s): Love, Jeff N.; Doty, Christopher I.; Smith, Jessica L.; Deiorio, Nicole M.; Jordan, Jaime; Van Meter, Michael W.; Edens, Mary Ann; Hegarty, Cullen B. | Abstract: Introduction: Interest is growing in specialty-specific assessments of student candidates based on clinical clerkship performance to assist in the selection process for postgraduate training. The most established and extensively used is the emergency medicine (EM) Standardized Letter of Evaluation (SLOE), serving as a substitute for the letter of recommendation. Typically developed by a program’s leadership, the group SLOE strives to provide a unified institutional perspective on performance. The group SLOE lacks guidelines to direct its development raising questions regarding the assessments, processes, and standardization programs employ. This study surveys EM programs to gather validity evidence regarding the inputs and processes involved in developing group SLOEs.Methods: A structured telephone interview was administered to assess the input data and processes employed by United States EM programs when generating group SLOEs.Results: With 156/178 (87.6%) of Accreditation Council of Graduate Medical Education-approved programs responding, 146 (93.6%) reported developing group SLOEs. Issues identified in development include the following: (1) 84.9% (124/146) of programs limit the consensus process by not employing rigorous methodology; (2) several stakeholder groups (nurses, patients) do not participate in candidate assessment placing final decisions at risk for construct under-representation; and (3) clinical shift assessments don’t reflect the task-specific expertise of each stakeholder group nor has the validity of each been assessed.Conclusion: Success of the group SLOE in its role as a summative workplace-based assessment is dependent upon valid input data and appropriate processes. This study of current program practices provides specific recommendations that would strengthen the validity arguments for the group SLOE.

Background: The satisfaction of parents of infants in neonatal intensive care is important to parent-infant bonding and parents' ability to care for their baby, including after discharge. Given the principal caregiver role of nurses in this setting, parent satisfaction is influenced by high quality nursing care. Nursing care that is required but missed, such as counseling and support, might influence parent satisfaction. How missed nursing care relates to parent satisfaction is unknown. Objective: To describe the satisfaction of parents of infants in neonatal intensive care and to determine how satisfaction relates to missed nursing care in a sample of USA nursing units. Methods: The design was cross-sectional and correlational. Thirty neonatal intensive care units that participate in the National Database of Nursing Quality Indicators were recruited. To maximize sample variation in missed care, the highest and lowest quartile hospitals on missed nursing care, measured by nurse survey, were eligible. Ten parents of infants who were to be discharged were recruited from each site to complete a survey. Parent satisfaction was measured by the EMPATHIC-38 instrument, comprising five subscales: information, care and treatment, organization, parental participation, and professional attitude, and a total satisfaction score. Multivariate regression models were estimated. Results: Parent satisfaction was high (5.70 out of 6.00). The prevalence of missed care was 25 and 51% for low and high missed care units, respectively, and 40% for all units. On average, nurses missed 1.06 care activities; in the low and high missed care units the averages were 0.46 and 1.32. Over 10% of nurses missed activities that involved the parent, e.g., teaching, helping breastfeeding mothers, and preparing families for discharge. One standard deviation decrease in missed care activities at the unit level was associated with a 0.08-point increase in parent satisfaction with care and treatment (p = 0.01). Conclusion: Parents in USA neonatal intensive care units are highly satisfied. Neonatal intensive care nurses routinely miss care. Parent satisfaction with care and treatment is related to missed nursing care. Nursing care that is missed relates primarily to the care of the baby by the parents, which could have long term health and developmental consequences.