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BACKGROUND: This proof-of-concept trial examined a 6-month Prevention Plus (PP) intervention implemented in a federally qualified health center on child standardized BMI (ZBMI), using a planned clinical effect threshold of −0.16 ZBMI. The relationship between food security status and PP delivered with caregiver goals (PP+) and without caregiver goals (PP−) on energy balance behaviors (i.e., fruits and vegetables, physical activity) and child ZBMI was explored. METHODS: Seventy-three, underserved children, 4–10 years of age with a BMI ≥85th percentile, were randomized to one of two interventions, PP+ and PP−, both providing 2.5 hours of contact time, implemented in five clinics by behavioral health consultants (BHCs). Outcomes were child anthropometrics (included 9-month follow-up), implementation data collected from electronic health records, and caregiver and BHC evaluations. RESULTS: Children were 57.5% female and 78.1% Hispanic, with 32.9% from food-insecure households and 58.9% from households with an annual income of less than $20,000. Child ZBMI significantly (p

Background: The use of virtual care, defined as providing healthcare in ways other than in-person visits, dramatically increased during the COVID-19 pandemic to minimize infection risk and maintain care provision. However, the majority of studies evaluating the use of virtual care in oncology have focused on patients with solid tumor malignancies. Patients with hematologic malignancies represent a unique population related to their underlying malignancy and treatment, but the extent to which virtual care has been successfully integrated into clinical practice is unknown. As the demand for incorporating virtual care into routine clinical practice grows, understanding how to safely and effectively use virtual care in this specific patient population is essential. Methods: A scoping review was conducted to describe the use of virtual care in the management of patients with hematologic malignancies and to examine physician- and patient-reported outcomes based on its use. A comprehensive search strategy was used to identify articles on the use of virtual modalities (digital applications, phone visits, or video visits) to deliver routine clinical care to patients with hematologic malignancies published in English between January 2000 and April 2021 in the following databases: PubMed, Medline, EMBASE, CINAHL and Scopus. No restrictions were applied to the phase of care (surveillance, active treatment, and or survivorship). A combination of search terms to encompass hematologic malignancies and virtual care was used. Screening and data abstraction were performed by two independent reviewers (AS, AV) and conflicts were adjudicated by two additional reviewers (DR, AP). Data were extracted to assess the study design, population, setting, patient characteristics, virtual care methodology and study results. Results: A total of 350 abstracts were screened and 60 studies underwent full-text review. Of these, 15 studies met inclusion criteria (13 retrospective studies, 1 prospective pilot study, and 1 randomized controlled trial). The majority of papers were published from 2020 onward (Figure 1). Three studies found that app-based tools were effective in monitoring patient symptoms and triggering alerts which resulting in sooner follow-up if indicated. One app-based tool was also used in a resource limited country during the COVID-19 pandemic to allow for communication between hematologists and their patients. Four studies described the use of phone-based interventions for new consults and follow-up visits. Phone visits for used even in high-risk patients (for example, in 29 out of 50 patients with chronic graft-versus-host disease after allogeneic stem cell transplant). Five studies found that videoconferencing, with both physicians and oncology nurses, was highly rated by patients. Emerging themes included high levels of patient satisfaction across all domains of virtual care. Provider satisfaction scores were rated lower than patient scores, with concerns about technical issues leading to challenges with virtual care. Four studies found that virtual care allowed providers to promptly respond to patient concerns, specifically when patients were experiencing side-effects or had questions about their treatment. One study also suggested a decreased risk of death when telemedicine was used to monitor symptoms in patients with diffuse large B-cell lymphoma. There were no data addressing the impact of virtual care on costs or resource utilization. Conclusion: The use of virtual care in patients with hematologic malignancies appears to be feasible, even in high-risk populations. Patients were highly satisfied with virtual care, although providers had some challenges related to the specific technologies. More research is needed to evaluate the optimal method of integrating virtual care, informed by a wider range of patient-related outcomes, as well as the downstream consequences of this integration for patient, providers, and health systems. Figure 1 Figure 1. Disclosures Prica: Astra-Zeneca: Honoraria; Kite Gilead: Honoraria.

OBJECTIVE Youth with craniopharyngioma experience weight gain, fragmented sleep, excessive daytime sleepiness (EDS), fatigue, and psychosocial problems that negatively impact their overall health-related quality of life (HRQoL). Greater hypothalamic tumor involvement (HI) may be associated with higher rates or severity of these impairments; however, the direct and indirect impact of HI on the physical and psychosocial consequences associated with pediatric craniopharyngioma remain unclear. The purpose of the current study was to examine relations between HI, body mass index (BMI), fragmented sleep, EDS, fatigue, psychosocial problems, and HRQoL among youth with craniopharyngioma. METHODS Eighty-four youth with craniopharyngioma (Mage = 10.27 ± 4.3 years, 53.6% female, 64.3% White) were assessed with actigraphy, nocturnal polysomnography, and multiple sleep latency tests prior to proton therapy, when indicated. Caregivers completed measures of fatigue, psychosocial functioning, and HRQoL. RESULTS Hypothalamic tumor involvement was associated with greater BMI (Est. = 2.97, p = 0.003) and daytime sleepiness (Est. = 2.53, p = 0.01). Greater fatigue predicted more psychosocial problems (Est. = 0.29, p

Purpose: PARP inhibitors synergize with topoisomerase inhibitors, and veliparib plus modified (m) FOLFIRI (no 5-FU bolus) had preliminary activity in metastatic pancreatic cancers. This study evaluated the safety and efficacy of second-line treatment with veliparib and mFOLFIRI versus FOLFIRI (control) for metastatic pancreatic cancer. Patients and Methods: This randomized phase II clinical trial led by the SWOG Cancer Research Network enrolled patients between September 1, 2016 and December 13, 2017. The median follow-up was 9 months (IQR 1–27). BRCA1/2 and homologous recombination DNA damage repair (HR-DDR) genetic defects were tested in blood and tumor biopsies. Patients received veliparib 200 mg twice daily, days 1–7 with mFOLFIRI days 3–5, or FOLFIRI in 14-day cycles. Results: After 123 of planned 143 patients were accrued, an interim futility analysis indicated that the veliparib arm was unlikely to be superior to control, and the study was halted. Median overall survival (OS) was 5.4 versus 6.5 months (HR, 1.23; P = 0.28), and median progression-free survival (PFS) was 2.1 versus 2.9 months (HR, 1.39; P = 0.09) with veliparib versus control. Grade 3/4 toxicities were more common with veliparib (69% vs. 58%, P = 0.23). For cancers with HR-DDR defects versus wild-type, median PFS and OS were 7.3 versus 2.5 months (P = 0.05) and 10.1 versus 5.9 months (P = 0.17), respectively, with FOLFIRI, and 2.0 versus 2.1 months (P = 0.62) and 7.4 versus 5.1 months (P = 0.10), respectively, with veliparib plus mFOLFIRI. Conclusions: Veliparib plus mFOLFIRI did not improve survival for metastatic pancreatic cancer. FOLFIRI should be further studied in pancreatic cancers with HR-DDR defects.

Background Extensive intestinal resection may lead to short bowel syndrome resulting in intestinal insufficiency or intestinal failure (IF). Intestinal insufficiency and IF involve deficiency of the proglucagon-derived hormones, GLP-1 and GLP-2. Two major problems of short bowel (SB) are epithelial surface loss and accelerated transit. Standard treatment now targets intestinal adaptation with a GLP-2 analogue, to enlarge absorptive surface area. It is possible that additional benefit can be gained from combination of GLP-1 and GLP-2 activity, with the aim to enlarge intestinal surface area and also slow intestinal transit. Methods The GLP-1 and GLP-2 specific effects of the novel dual GLP-1 and GLP-2 receptor agonist dapiglutide (rINN) were characterized in rodents. Furthermore, in a murine SB model of intestinal insufficiency with 40% ileocecal resection, the influence of dapiglutide on intestinal growth, body weight, food intake, volume status and stool water content was tested against vehicle and sham operated male mice. Results Dapiglutide significantly improves oral glucose tolerance, reduces intestinal transit time and promotes intestinal growth. In the SB mouse model, dapiglutide promotes body weight recovery, despite unchanged liquid diet intake. Dapiglutide promotes significant intestinal growth, as indicated by significantly increased villus height, as well as intestinal length. Furthermore, dapiglutide reduces stool water losses, resulting in reduced plasma aldosterone. Conclusion Dapiglutide possesses specific and potent GLP-1 and GLP-2 receptor agonist effects in rodents. In the murine SB model, combined unimolecular GLP-1R and GLP-2R stimulation with dapiglutide potently attenuates intestinal insufficiency and potentially also IF. This article is protected by copyright. All rights reserved.

Background In human immunodeficiency virus (HIV)–positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. Methods Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children Results Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P ≤ .03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P < .001). Conclusions One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders.

In most women ≥ 70 years old with hormone-receptor-positive breast cancer, axillary staging and adjuvant radiotherapy provide no survival advantage over surgery and hormone therapy alone. Despite recommendations for their omission, sentinel lymph node biopsy (SLNB) and adjuvant radiotherapy rates remain high. While treatment side effects are well documented, less is known about the incremental spending associated with SLNB and adjuvant radiotherapy. Using a statewide multipayer claims registry, we examined spending associated with breast cancer treatment in a retrospective cohort of women ≥ 70 years old undergoing surgery. 9074 women ≥70 years old underwent breast cancer resection between 2012 and 2019, with 78% (n = 7122) receiving SLNB and/or adjuvant radiotherapy within 90 days of surgery. Women undergoing SLNB were more likely to receive radiation (51% vs. 28%; p < 0.001 and OR = 2.68). Average 90-day spending varied substantially based upon treatment received, ranging from US$10,367 (breast-conserving surgery alone) to US$27,370 (mastectomy with SLNB and adjuvant radiotherapy). The relative increases in 90-day treatment spending in the breast-conserving surgery cohort was 65% for SLNB, 82% for adjuvant radiotherapy, and 120% for both treatments. SLNB and adjuvant radiotherapy have significant spending implications in older women with breast cancer, even though they are unlikely to improve survival.

A retrospective single center cohort study with prospective collected data from an institutional spine registry.To determine whether restoration of lordosis L5/S1 is possible with both anterior lumbar interbody fusion (ALIF) and transforaminal lumbar interbody fusion (TLIF) and to find out which technique is superior to recreate lordosis in L5/S1.Seventy-seven patients with ALIF and seventy-nine with TLIF L5/S1 were included. Operation time, estimated blood loss), and complications were evaluated. Segmental lordosis L5/S1 and L4/5, overall lordosis, and proximal lordosis (L1 to L4) were measured in X-rays before and after surgery. Oswesery disability index and EQ-5D were assessed before surgery, and 3 and 12 months after surgery.Mean operation time was 176.9 minutes for ALIF and 195.7 minutes for TLIF (p = 0.048). Estimated blood loss was 249.2 cc for ALIF and 362.9 cc for TLIF (p = 0.005). In terms of complications, only a difference in dural tears were found (TLIF 6, ALIF none; p = 0.014). Lordosis L5/S1 increased in the ALIF group (15.8 to 24.6°; p 0.001), whereas no difference was noted in the TLIF group (18.4 to 19.4°; p = 0.360). Clinical results showed significant improvement in the Oswesery disability index (ALIF: 43 to 21.9, TLIF: 45.2 to 23.0) and EQ-5D (ALIF: 0.494 to 0.732, TLIF: 0.393 to 0.764) after 12 months in both groups, without differences between the groups.ALIF and TLIF are comparable methods for performing fusion at L5/S1, with good clinical outcomes and comparable rates of complications. However, there is only a limited potential for recreating lordosis at L5/S1 with a TLIF.Eine retrospektive Single-Center-Kohortenstudie mit prospektiv erhobenen Daten eines institutionellen Wirbelsäulenregisters.Es wurde untersucht, ob eine Wiederherstellung der Lordose L5/S1 sowohl mit ALIF als auch mit TLIF möglich ist und welche Technik zur Wiederherstellung der Lordose bei L5/S1 überlegen ist.77 Patienten mit ALIF und 79 mit TLIF L5/S1 wurden eingeschlossen. Operationszeit (OT), geschätzter Blutverlust (EBL) und Komplikationen wurden ausgewertet. Die segmentale Lordose L5/S1 und L4/5, die Gesamtlordose (LL) und die proximale Lordose (L1 bis L4) wurden in Röntgenbildern vor und nach der Operation ermittelt. Oswesery disability index (ODI) und EQ 5D wurden vor der Operation, 3 und 12 Monate nach der Operation ausgewertet.Die mittlere OT betrug 176,9 min für ALIF und 195,7 min für TLIF (p = 0,048). Die EBL betrug 249,2cc für ALIF und 362,9 cc für TLIF (p = 0,005). In Bezug auf Komplikationen wurde nur ein Unterschied bei den Duraläsionen gefunden (TLIF 6, ALIF keine, p = 0,014). Die Lordose L5/S1 nahm in der ALIF-Gruppe postoperativ zu (15,8 bis 24,6°, p 0,001), während in der TLIF-Gruppe kein signifikanter Unterschied festgestellt wurde (18,4° bis 19,4°, p = 0,360). Die klinischen Ergebnisse zeigten eine signifikante Verbesserung des ODI (ALIF: 43 auf 21,9, TLIF: 45,2 auf 23,0) und des EQ 5D (ALIF: 0,494 auf 0,732, TLIF: 0,393 auf 0,764) nach 12 Monaten in beiden Gruppen, ohne Unterschiede zwischen den Gruppen.Sowohl ALIF als auch TLIF sind vergleichbare Methoden zur Durchführung einer Fusion an L5/S1, mit guten klinischen Ergebnissen und vergleichbaren Komplikationsraten. Allerdings besteht bei Durchführung eines TLIF nur ein begrenztes Potenzial zur Wiederherstellung der Lordose bei L5/S1.

Background The hypothesis of a curable oligometastatic prostate cancer (PCa) state remains to be clinically-proven. Conventional imaging often fails to localize early recurrences, hampering the potential for radical approaches. Objective We hypothesize that prostate-specific membrane antigen (PSMA)-targeted PET-MR/CT allows for earlier detection and localization of oligorecurrent-PCa, unveiling a molecularly-defined state amenable to curative-intent metastasis-directed treatment (MDT). Design/setting/participants Single-institution single-arm phase-two study. Patients with rising PSA (0.4-3.0 ng/mL) after maximal local therapy (radical prostatectomy and post-operative radiotherapy), negative conventional staging, and no prior salvage hormonal therapy (HT) were eligible. Interventions All patients underwent [18F]DCFPyL PET-MR/CT. Patients with molecularly-defined oligorecurrent-PCa had MDT (stereotactic ablative body radiotherapy [SABR] or surgery) without HT. Outcome measurements/statistical analysis Primary endpoint was biochemical response (complete, i.e. biochemical ‘no evidence of disease’ [bNED], or partial response [100% or ≥50% PSA decline from baseline, respectively]) after MDT. Simon’s two-stage design was employed (null and alternate hypotheses 20% response rate, respectively), with α and β of 0.1. Results Seventy-two patients were enrolled (May/2017-July/2019). Thirty-eight (53%) had PSMA-detected oligorecurrent-PCa amenable for MDT. Thirty-seven (51%) agreed to MDT: 10 and 27 underwent surgery and SABR, respectively. Median follow-up was 15.9 months (IQR 9.8-19.1). Of patients receiving MDT, the overall response rate was 60%, including 22% rendered bNED. One (2.7%) grade 3 toxicity (intra-operative ureteric injury) was observed. Conclusions PSMA-defined oligorecurrent-PCa can be rendered bNED, a necessary step towards cure, in 1 of 5 patients receiving MDT alone. Randomized trials are justified to determine if MDT +/− systemic agents can expand the curative therapeutic armamentarium for PCa. Patient summary We studied men treated for prostate cancer with rising PSA. We found PSMA imaging detected recurrent cancer in three-quarters of patients, and targeted treatment to these areas significantly decreased PSA in half of patients.

Background Large interindividual variations have been reported in chemotherapy‐induced toxicities. Little is known whether racial disparities exist in neutropenia associated with taxanes. Methods Patients with a diagnosis of primary cancer who underwent chemotherapy with taxanes were identified from Vanderbilt University Medical Center's Synthetic Derivative. Multinomial regression models were applied to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) of neutropenia associated with race, with adjustments for demographic variables, baseline neutrophil count, chemotherapy‐related information, prior treatments, and cancer site. Results A total of 3492 patients were included in the study. Compared with White patients, grade 2 or higher neutropenia was more frequently recorded among Black patients who received taxanes overall (42.2% vs. 32.7%, p, After accounting for baseline neutropenia count, patient characteristics and other treatments received, Black patients who received chemotherapy with taxanes had a greater risk for neutropenia compared with their White counterparts, especially for those who received paclitaxel. This is critically important for treatment planning and dose adjustments, expectation setting, and physician awareness for the potential for increased infections or febrile episodes during periods of neutropenia in Black patients. Our findings call for further investigations on this disparity, particularly in clinical trial settings, as well as on the underlying mechanisms.

Purpose: Blunt thoracic injuries are common among elderly patients and may be a common cause of morbidity and death from blunt trauma injuries. We aimed to examine the impact of chest CT on the diagnosis and change of management plan in elderly patients with stable blunt chest trauma. We hypothesized that chest CT may play an important role in providing optimal management to this subgroup of trauma patients. Methods: A retrospective analysis was performed on all the admitted adult blunt trauma patients between January 2014 and December 2018. Stable blunt chest trauma patients with abbreviated injury severity (AIS)

Purpose: To describe the initial experience of an academic center using 18F-DCFPyL PET in managing men with recurrent prostate cancer. Materials &amp, Methods: This prospective, single-arm IRB-approved study included men with biochemical failure after primary therapy for prostate cancer and negative/equivocal CT and bone scintigraphy who were candidates for salvage therapy, as determined by a multidisciplinary panel of experts. 18F-DCFPyL PET was assessed for the presence and extent of recurrence: local, oligometastatic (≤4), or extensive. Post-PET management and clinical outcome, including PSA response, was documented. For patients who received PET-directed ablative therapies, response was categorized as “complete” if PSA became undetectable or “favorable” if PSA decreased ≥50%. Results: Forty-seven men with biochemical failure after radical prostatectomy (n = 29), primary radiotherapy (n = 15) or focal tumor ablation (n = 3) were included. PET was positive in (43/47) 91.5%, including local recurrence in (9/47) 19.2%, oligometastatic disease in (16/47) 34%, and extensive metastatic disease in (18/47) 38.3%. PET-directed focal ablative therapies without systemic therapy were given to (13/29) 44.8% of patients without extensive metastases on PET with a mean PSA response of 69% (median, 74.5%, range: 35–100). Favorable biochemical response was observed in (10/13) 76.9% of patients with limited recurrence on PET, and in 23.1% (3/13), there was complete response. Conclusion: 18F-DCFPyL PET was positive in &gt, 90% of patients with biochemical failure. For those with limited recurrence, PSMA PET-directed local ablative therapies resulted in favorable outcome in more than 3 in 4 patients, and in nearly a quarter of them, there was complete biochemical response.

External beam radiotherapy is an effective curative treatment option for localized prostate cancer, the most common cancer in men worldwide. However, conventionally fractionated courses of curative external beam radiotherapy are usually 8–9 weeks long, resulting in a substantial burden to patients and the health-care system. This problem is exacerbated in low-income and middle-income countries where health-care resources might be scarce and patient funds limited. Trials have shown a clinical equipoise between hypofractionated schedules of radiotherapy and conventionally fractionated treatments, with the advantage of drastically shortening treatment durations with the use of hypofractionation. The hypofractionated schedules are supported by modern consensus guidelines for implementation in clinical practice. Furthermore, several economic evaluations have shown improved cost effectiveness of hypofractionated therapy compared with conventional schedules. However, these techniques demand complex infrastructure and advanced personnel training. Thus, a number of practical considerations must be borne in mind when implementing hypofractionation in low-income and middle-income countries, but the potential gain in the treatment of this patient population is substantial., Conventionally fractionated external beam radiotherapy is an effective treatment for localized prostate cancer, but long treatment programmes result in a substantial burden to patients and the health-care system, which is particularly problematic in low-income and middle-income countries (LMICs) where health-care resources might be scarce and patient funds limited. Here, the authors discuss the outcomes and benefits of hypofractionation — in terms of both oncology and economics — and how it could be used to improve prostate cancer care in LMICs., Key points The global burden of prostate cancer is increasing and prostate cancer is becoming a major source of health-care burden in low-income and middle-income countries (LMICs).Radiotherapy is an essential treatment modality in the management of prostate cancer. However, radiotherapy resources are lacking in LMICs, resulting in excess morbidity and mortality.Hypofractionated radiotherapy schedules offer an opportunity to maintain excellent treatment outcomes while shortening curative radiotherapy courses. This approach expands the treatment capacity and could improve crucial access in communities with limited radiotherapy resources.Initial investments are required for technological upgrades, such as intensity-modulated radiotherapy and image-guided radiotherapy, as well as in specialized training in order to optimally provide hypofractionated treatment. Discussion amongst government agencies and device manufacturers is essential to lower these costs.Personnel training and access to external consultation are critical resources for developing radiotherapy centres. Information and communication technologies enable remote guidance between developing and developed radiotherapy centres.In the long term, hypofractionation programmes result in long-term cost savings and simultaneously expand patient access to a curative modality in the management of prostate cancer.

Increased interest in real-world evidence (RWE) for clinical and regulatory decision making and the need to evaluate long-term benefits and risks of pharmaceutical products raise the importance of understanding the use of external controls (ECs) for uncontrolled extensions of randomized controlled trials (RCTs). We searched clinicaltrials.gov from 2009 to 2019 for uncontrolled extensions and assessed the use of ECs in the trial protocol registry and PubMed. We present characteristics of identified uncontrolled extensions, their adoption of ECs, and a qualitative appraisal of published uncontrolled extensions with ECs according to good pharmacoepidemiologic practice. The number of uncontrolled extensions increased slightly across the study period, resulting in a total of 1,115 studies. Most originated from phase III RCTs (62.2%) and specified safety outcomes (61.9% among those with specified outcomes). Most uncontrolled extensions incorporated no control group with only 7 out of 1,115 (0.6%) employing ECs. For those studies with ECs, all involved treatments for rare conditions and assessment of effectiveness. Attempts to balance comparison groups varied from none mentioned to propensity score matching. We noted consistent deficiencies in outcome ascertainment methods and approaches to address attrition bias. The contrast of the large and growing number of uncontrolled extensions with the small number of studies that utilized ECs showed clear opportunities for enhancement in design, measurement, and analysis of uncontrolled extensions to allow causal inferences on long-term treatment effects. As extensions continue to expand within RWE regulatory frameworks, development of guidelines for use of EC with uncontrolled extensions is needed.

Introduction: Verrucous carcinoma is a non-metastatic variant of squamous cell carcinoma. It was first reported by Ackerman in 1948. It is a verrucous exophytic tumor and, although it is a rare lesion, it mainly affects the oral cavity, with slow growth and can be locally invasive. Objective: To report a case and present an observational and retrospective analysis of medical records containing biopsy data from patients diagnosed with oral verrucous carcinoma (OVC) in an oral diagnostic referral service for a period of 24 years. Material and methods: The following data were collected: age, sex, ethnicity, anatomical location and management. Result: Eight cases of OVC were found, all in Caucasian patients (n = 8, 100%), aged between 57 and 102 years. 62% of the injuries affected women. The most affected region was the jugal mucosa (n = 4, 50%). In addition, Smoking patients were not found. In all cases, incisional biopsy was performed and referral to the head and neck surgeon. Conclusion: Caucasian women in the sixth and seventh decades of life were the most affected by OVC. The absence of smoking patients corroborates the literature, which reports that cigarettes appear to be unrelated to this injury. The dentist's role is to recognize the disease early, diagnose it and refer it for medical treatment.

Distracted driving indiscriminately kills nearly 3500 people each year with young adults having greater risks associated with this phenomenon. Prevention programs targeting the distracted driving habits of young adults are necessary to ameliorate the high costs, both in dollars and in lives, associated with this behavior. Few health education and prevention programs have been assessed for their effectiveness in changing knowledge, attitudes, and behaviors related to distracted driving. This study explores a distracted driving intervention among undergraduate students enrolled in an introductory public health course. A quasi-experimental study design was used to compare the pre- and post-data of the group receiving 5-weeks of a distracted driving intervention to a control group. Questionnaires were administered to both groups prior to and 2 weeks following the intervention to assess changes in knowledge, attitudes, and behaviors related to distracted driving. A Difference-in-Difference technique showed significant changes in knowledge (β = 0.40, p = 0.03) and total scores (β = 2.48, p = 0.04) in the intervention (n = 97) compared to the control (n = 131). T-tests examining pre- and post-scores for individual behaviors showed the intervention group displayed positive changes for some behaviors (talking, texting, cellphone use, grooming) compared to the control. The results support the impact that a classroom-based distracted driving intervention can have on undergraduate college students. Implications for this type of health education program may lead to improvements in distracted driving attitudes and behavior among this age-group.

Aims In breastfeeding women, anti-epileptic therapy can lead to infant toxicities, even with newer anti-epileptic drugs such as levetiracetam. This study assessed levetiracetam breastmilk excretion and its correlation with the maternal oral dose and serum concentrations. Methods Women with epilepsy treated with levetiracetam were recruited to this study and completed a questionnaire. Levetiracetam concentrations were determined in serial breastmilk samples (pre-dose to 12 h post-dose period) and in a single pre-dose maternal serum sample. Results Twenty breastfeeding women and 21 infants (one woman with twins; 16 fully and five partially breastfed infants) participated in this study. The trough breastmilk/serum ratio of levetiracetam was 0.98 ± 0.20. The infant levetiracetam daily dose was 5.39 ± 1.96 and 2.70 ± 0.98 mg. kg-1. d-1 , and the relative infant dose (RID) was 13.8 ± 3.1% and 6.9 ± 1.6% in the fully and partially breastfed infants, respectively. Substantial correlations between the levetiracetam dose, maternal serum and breastmilk trough concentrations, and breastmilk AUC values were found. Three women reported somnolence in their fully breastfed infants, which resolved shortly after switching to partial breastfeeding. All the infants gained weight according to their age. Conclusions Infant levetiracetam exposure via the breastmilk was close to the safety thresholds (trough breastmilk/serum ratio slightly below 1, RID > 10% in fully breastfed infants), and infant somnolescence reports could be related to exposure of the infants to levetiracetam via breastmilk. Further studies are warranted to reveal the short- and long-term safety of levetiracetam in breastfeeding.

The purpose of this review is to describe the Southeastern Kidney Transplant Coalition’s mission, vision, goals, and Early Transplant Access Registry as an example of a community/academic collaboration dedicated to improving access to transplantation and reducing inequities in transplant access. The barriers and facilitators to referral and evaluation for kidney transplantation are not necessarily the same as for waitlisting and transplantation. Recent findings suggest that inequities in transplant access are multilevel and multifactorial and require continued community engagement to improve access to kidney transplantation across patients, health systems, and populations. Community-engaged approaches are critical to ensuring that inequities in transplant access — which may vary across regions — are not only described but are addressed in practice in a sustainable manner.

Objectives The aim of this study was to identify the patterns of medication load, its medication burden, coordination of healthcare and patient’s understanding of their conventional cardiac medications and related herbal-derived preparations. Methods The study is a mixed-method both, quantitative and qualitative approach, which involved Filipino elderly patients (n=69) enrolled in the outpatient service of the National Center for Geriatric Health, Manila. Data were gathered through face-to-face surveys and interviews using a semi-structured questionnaire. Descriptive statistics were used during data analysis. Thematic analysis was also used to emphasize patterns in the responses of the participants. Results Respondents were knowledgeable on the name (86.9%), visual characteristics (78.3%), and indication and administration of their medicine (88.4%). The frequency of their doctor’s information on the possible side effects of the medicines was noted. The almost negligible difference in the proportions of those who asserted during the information dissemination on the medication side effect by their doctors was observed ( Conclusions The majority of the elderly patients recognized the purpose and extent of medication. It was noted that pharmacists play a limited role in understanding selected Filipino elderly patients on their medication. Lack of communication between the patient and the pharmacist was noted as preliminary findings in the study. Respondents were not yet informed of the responsibility of the pharmacist to provide information regarding their medication. Integration of pharmacists’ care for geriatric health must be strengthened and highly recommended. Supervision by the healthcare professionals, particularly by the pharmacists, must be fully established.

Lumbar punctures (LPs) are commonly performed procedures, serving diagnostic and therapeutic purposes. They are generally safe, and serious, life-threatening complications are rare. We report a case of a patient who underwent an LP and subsequently developed shock. Imaging studies revealed a retroperitoneal hematoma with an active bleed. Interrogation of the lumbar branches in the interventional radiology suite revealed an active arterial bleed at the level of L3-L4 which was successfully embolized. We present this case to highlight the possibility of a rare complication of an LP and to emphasize the importance of early detection and resuscitative intervention.

Context Translational research in uro-oncology depends on the availability of high-quality biospecimens and associated data to advance precision medicine and improve clinical outcomes. Procurement, storage, and annotation of these specimens represent critical steps towards this end. Objective To review best-practice experiences gained via the McCain GU BioBank, a repository of more than 750 000 biospecimens obtained from more than 16 000 patients attending clinics at the University Health Network in Toronto, Canada. Evidence acquisition The review summarizes our experiences at a large single-institution genitourinary oncology biorepository. Evidence synthesis Key findings are placed in the context of emerging trends in genitourinary oncology, with a focus on integration of molecular profiling and clinical data with traditional biorepository management. Proposed approaches provide high-quality biospecimens with comprehensive and reliable clinical data that can fuel innovation and discovery in research. Conclusions Biorepositories are vital for improving clinical outcomes and advancing personalized medicine. High-quality biospecimens and their associated clinical data are crucial for validation of biomarkers in oncology. Efforts to procure, store, and annotate clinical specimens represent critical steps in translational research. Elements such as biobank size, biospecimen types, disease cohorts, predetermined collection protocols, broad informed consent, sample handling and storage protocols, and available infrastructure directly influence the effectiveness and capacity of a biobank. Patient summary Biorepositories, or biobanks, are facilities that store biospecimens such as blood, urine, or tissue (usually collected from humans) for use in research. Biobanks have become an important resource in medical research, as they provide high-quality specimens to support different types of contemporary research such as genomics, biomarker discovery, and personalized medicine. Clinical management and treatment of genitourinary cancers, such as prostate, kidney, and bladder cancers, are particularly suited for biomarker research. The provision of biospecimens and their associated clinical data have become crucial for validation of biomarkers in these cancers.

Prospectively designed studies that make use of real-world data (RWD) are increasingly being used for studies with regulatory implications, including both premarket and post-market studies, aided b...

Background Immune checkpoint inhibitor (ICI) therapy is highly effective in metastatic mismatch repair-deficient (MMR-D) colorectal cancer (CRC). In this study, we evaluated molecular and clinical predictors of ICI response in MMR-D CRC. Materials and Methods Patient databases at four cancer institutions were queried. The Fisher exact test was performed to test the association of clinical and molecular markers. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and compared by the log-rank test. Twelve- and 24-month PFS rates were compared by the Z test. Results A total of 60 patients with CRC with MMR-D/microsatellite instability-high who previously received ICIs were identified. Patients with liver metastasis had a lower overall response rate as compared with other sites of metastasis (36.4% vs. 68.7%; p = .081). Patients with MLH1/PMS2 loss had worse 1-year and 2-year PFS rates compared with patients with MSH2/MSH6 loss (84.2% vs. 57.8% and 78.2% vs. 54.2%, respectively; p < .001). There were improved 1-year and 2-year PFS rates in patients with wild-type BRAF when compared with patients with BRAF V600E mutation (73.3% vs. 40%, and 73.3% vs. 26.7%; respectively; p < .001). Patients aged >65 had significantly worse PFS rates as compared with patients aged ≤65 (p < .001). Conclusion BRAF V600E mutation, MLH1 and/or PMS2 loss, as well as age >65 years and liver metastasis, may be predictive of duration of ICI response in patients with MMR-D CRC. Larger cohorts are needed to confirm our findings. Implications for Practice The results of this study reveal clinically important biomarkers that potentially predict immune checkpoint inhibitor response in patients with mismatch repair-deficient colorectal cancer.

AIMS Papaverine is indicated for abdominal pain of various aetiologies. However, data on maternal and foetal safety following gestational exposure are lacking. The aim was to examine whether first trimester exposure to papaverine is associated with increased risk for major malformation and whether gestational exposure at any stage is associated with increased risk for preterm delivery, lower birthweight, small for gestational age, caesarean section (CS), lower Apgar score and perinatal death. METHODS A retrospective comparative study consisted of pregnant women treated with papaverine between February 2010 and October 2019 at a large tertiary center. The control group comprised of livebirth deliveries randomly selected from the institutional obstetric database. RESULTS The study group consisted of 498 pregnancies, which resulted in 537/544 (98.7%) live births, of whom 46/537 (8.6%) were exposed during the first trimester. The control group consisted of 498 pregnancies and 514 live births. Rate of major malformations did not differ between study group (2/46, 4.3%) and control (25/315, 4.9%, P = .67). Papaverine exposure was associated with higher rate of preterm delivery (22.3 vs. 10.3%, P

Postoperative shoulder imbalance is a common complication in adolescent idiopathic scoliosis and may impair patient satisfaction. The little data in the literature on the prediction and treatment of postoperative shoulder imbalance is incongruous. According to some studies, postoperative shoulder imbalance depends on the superior instrumented vertebral bodies, skeletal maturity, extent of correction and flexibility of the major curve.Can preoperative radiological parameters from X-ray and traction films as well as correction of the curves be used to identify a factor impacting on postoperative shoulder imbalance?Prospective data in adolescent idiopathic scoliosis with thoracic curve (Lenke type 1), operated on between 2015 and 2018 at a scoliosis centre, were analysed retrospectively based on full-length X-rays of the spine (pre-/postOP and follow-up (FU)) and preoperative-traction films: age; correction of proximal, main and lumbar curve; shoulder height [mm]; clavicle angle [°]; T1 tilt [°]; coronal plumb line deviation [mm]. The findings were expressed as means with standard deviation. Changes in parameters over time (postOP-FU) were compared by t test (significance level α = 0.05). The correlation between preOP parameters and extent of correction with postoperative shoulder imbalance (≥ 15 mm) was determined by Pearson correlation and regression classification analysis.55 patients with adolescent idiopathic scoliosis, mean age of 15 ± 1.4 years. The FU-rate after a mean of 15 months was 80% (n = 44). Correction of proximal, main and lumbar curve: 47.0%, 75.8% and 68.8%, respectively, without statistically significant change (Δ) in FU (p 0.05). Shoulder height was - 11.0 ± 12.7 mm (preOP), 15.5 ± 13.4 mm (postOP), 10.1 ± 10.6 mm (FU) (p 0.05). 38% of those with adolescent idiopathic scoliosis had preOP right shoulder elevation; 55% (postOP) and 32% (FU) respectively had postoperative shoulder imbalance (left shoulder elevation). Strong statistical correlation was found for Δshoulder position (FU-preOP) with pre-OP shoulder position (r = - 0.7), and Δshoulder position (pre-OP traction films) (r = 0.5) with pre-OP clavicle angle (r = - 0.5). On regression classification analysis, 81.8% of cases did display postoperative shoulder imbalance if proximal curve correction was ≤ 64.4%; main and lumbar curve correction, Δshoulder elevation (preOP traction films) played a secondary role.One common complication even in Lenke type 1 adolescent idiopathic scoliosis is postoperative shoulder imbalance. Preoperative planning should include traction films, preoperative shoulder position and clavicle angle to avoid postoperative shoulder imbalance. Moderate correction of proximal curve is critical for postoperative shoulder balance.Die postoperative Schulterimbalance ist eine häufige und für die Patientenzufriedenheit relevante Komplikation bei der adoleszenten idiopathischen Skoliose. Die Datenlage in der Literatur ist gering und inkongruent in Bezug auf die Vorhersage und Behandlung der postoperativen Schulterimbalance. Einige Studien kommen zu dem Schluss, dass die postoperative Schulterimbalance von den oberen instrumentierten Wirbelkörpern, der Skelettreife, dem Ausmaß der Korrektur oder Flexibilität der Hauptkrümmung abhängig ist.Können durch präoperative radiologische Parameter anhand konventioneller Röntgenbilder und Traktionsaufnahmen sowie der Korrektur der Krümmungen Einflussfaktoren auf die postoperative Schulterimbalance bestimmt werden?Prospektiv erfasste Daten von adoleszenten idiopathischen Skoliosen mit thorakaler Krümmung (Typ 1 nach Lenke), operiert 2015 – 2018 an einem Skoliosezentrum, wurden anhand von Röntgenaufnahmen der gesamten Wirbelsäule (prä-, postOP und Follow-up [FU]) und präOP-Traktionsaufnahmen retrospektiv analysiert: Alter, Korrektur der proximalen, Haupt- und lumbalen Krümmung, Schulterhöhe (mm), Klavikulawinkel (°), T1-Winkel (°), koronare Lotabweichung (mm). Die Ergebnisse wurden als Mittelwerte mit Standardabweichung angegeben. Die Veränderung der Parameter im Verlauf (postOP-FU) wurden mithilfe des t-Tests verglichen (Signifikanzniveau α = 0,05). Der Zusammenhang der präOP-Parameter sowie des Ausmaßes der Korrektur mit der postoperativen Schulterimbalance (|≥|15 mm) wurde durch die Korrelationsanalyse nach Pearson und Regressions-Klassifikations-Analyse statistisch analysiert.Es wurden 55 adoleszente idiopathische Skoliosen im Alter von durchschnittlich 15 ± 1,4 Jahren untersucht. Die FU-Rate betrug 80% (n = 44) nach durchschnittlich 15 Monaten. Korrektur der proximalen Krümmung: 47,0%, Hauptkrümmung: 75,8%; lumbale Krümmung: 68,8%, ohne statistisch signifikante Veränderung (Δ) im FU (p 0,05). Die Schulterhöhe betrug − 11,0 ± 12,7 mm (präOP), 15,5 ± 13,4 mm (postOP), 10,1 ± 10,6 mm (FU; p 0,05). 38% der adoleszenten idiopathischen Skoliosen hatten einen präOP Schulterhochstand rechts; 55% (postOP) und 32% (FU) hatten eine postoperative Schulterimbalance (Hochstand links). Mit einem statistisch starken Effekt ergaben sich Korrelationen für ΔSchulterstand (FU-präOP) mit jeweils dem präOP Schulterstand (r = − 0,7), der ΔSchulterstand (Traktionsaufnahmen-präOP; r = 0,5) und dem präOP Klavikulawinkel (r = − 0,5). Bei einer Korrektur der proximalen Krümmung von ≤ 64,4% hatten 81,8% der Fälle keine postoperative Schulterimbalance in der Regressions-Klassifikations-Analyse, einen nachgeordneten Einfluss hatte die Korrektur der Haupt- und der lumbalen Krümmung, ΔSchulterstand (Traktionsaufnahmen-präOP).Die postoperative Schulterimbalance ist auch bei adoleszenten idiopathischen Skoliosen vom Typ 1 nach Lenke eine häufige Komplikation. Bei der präoperativen Planung sollten Traktionsaufnahmen, der präoperative Schulterstand und Klavikulawinkel zu Vermeidung einer postoperativen Schulterimbalance berücksichtigt werden. Eine moderate Korrektur der proximalen Krümmung ist essenziell für eine postoperative Schulterbalance.

Background Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) mutations are a genetic risk factor for Crohn disease. Ileocecal resection is the most often performed surgery in Crohn disease. We investigated the effect of Nod2 knockout (KO) status on anastomotic healing after extended ileocecal resection (ICR) in mice. Methods Male C57BL6/J wild-type and Nod2 KO mice underwent an 11 cm resection of the terminal ileum including the cecum. An end-to-end jejuno-colostomy was performed. Animals were killed after 5 days investigating bursting pressure, hydroxyproline content, and expression of matrix metabolism genes, key cytokines, and histology of the anastomosis. Results Mortality was higher in the Nod2 KO group but not because of local or septic complications. Bursting pressure was significantly reduced in the Nod2 KO mice (32.5 vs 78.0 mmHg, P < 0.0024), whereas hydroxyprolin content was equal. The amount of granulation tissue at the anastomosis was similar but more unstructured in the Nod2 KO mice. Gene expression measured by real-time polymerase chain reaction showed significantly increased expression for Collagen 1alpha and for collagen degradation as measured by matrix metalloproteinase-2, -9, and -13 in the Nod2 KO mice. Gelatinase activity from anastomotic tissue was enhanced by Nod2 status. Gene expression of arginase I, tumor necrosis factor-α, and transforming growth factor-ß but not inducible nitric oxide synthase were also increased at the anastomosis in the Nod2 KO mice compared with the control mice. Conclusions We found that Nod2 deficiency results in significantly reduced bursting pressure after ileocecal resection. This effect is mediated via an increased matrix turnover. Patients with genetic NOD2 variations may be prone to anastomotic failure after bowel resection.

BackgroundFamotidine has been posited as a potential treatment for COVID-19. We compared the incidence of COVID-19 outcomes (i.e., death; and death or intensive services use) among hospitalized famotidine users vs. proton pump inhibitors (PPIs) users, hydroxychloroquine users or famotidine non-users separately.MethodsWe constructed a retrospective cohort study using data from COVID-19 Premier Hospital electronic health records. Study population were COVID-19 hospitalized patients aged 18 years or older. Famotidine, PPI and hydroxychloroquine exposure groups were defined as patients dispensed any medication containing one of the three drugs on the day of admission. The famotidine non-user group was derived from the same source population with no history of exposure to any drug with famotidine as an active ingredient prior to or on the day of admission. Time-at-risk was defined based on the intention-to-treat principle starting 1 day after admission to 30 days after admission. For each study comparison group, we fit a propensity score (PS) model through large-scale regularized B logistic regression. The outcome was modeled using a survival model.ResultsWe identified 2193 users of PPI, 5950 users of the hydroxychloroquine, 1816 users of famotidine and 26,820 non-famotidine users. After PS stratification, the hazard ratios for death were as follows: famotidine vs no famotidine HR 1.03 (0.89-1.18); vs PPIs: HR 1.14 (0.94-1.39); vs hydroxychloroquine:1.03 (0.85-1.24). Similar results were observed for the risk of death or intensive services use.ConclusionWe found no evidence of a reduced risk of COVID-19 outcomes among hospitalized COVID-19 patients who used famotidine compared to those who did not or compared to PPI or hydroxychloroquine users.

Introduction: Extrapulmonary small-cell cancer (EPSCC) is a relatively rare malignancy. The management of EPSCC is usually extrapolated from small-cell lung cancer (SCLC). In spite of the morphological similarity of the 2 malignancies, there are many differences in clinical features, prognosis, and recommendations of treatment of these disorders. The data on the correlation of clinical-pathological characteristics of EPSCC and treatment results is scarce. Materials and Methods: This retrospective analysis of 41 consecutively treated patients diagnosed with EPSCC in 2015–2018 was performed in a tertiary medical center. The correlation between the clinical and pathological characteristics and the treatment outcome (response rate, disease-free interval, and overall medial survival) was done using the standard statistics, Kaplan-Meier method, and multivariate analyses. The stratification was done on the stage of the disease, Ki-67 proliferative index, the location of the tumor, and smoking. Results: Forty-one patients were included with a median age of 66.3 years. The most common primary site was the gastrointestinal tract (28, 68.3%) including the pancreas. The most common distant metastasis site was the liver (23, 56.1%). Only 2 patients (4.9%) had brain metastases. Unlike in SCLC, most patients did not have any history of smoking (23, 56.1%). Nineteen patients with metastatic disease received systemic treatment, mostly cisplatin-based chemotherapy, with a response rate of 57.9%. The results of treatment were significantly better in patients with disseminated EPSCC with Ki-67 Discussion: The results of our study show the unique entity of EPSCC. The rarity of brain metastases proves that prophylactic brain irradiation should not be recommended in practice. The provocative idea of prophylactic liver irradiation in limited-stage EPSCC of gastrointestinal origin can be evaluated in future studies. The predictive role of Ki-67 is important in metastatic EPSCC. There is probably no role of smoking in developing EPSCC.

Hepatic metastases are a major cause of morbidity and mortality for patients with cancer. Apart from curative resection, which offers patients the potential for long-term survival, an array of locoregional therapies, with limited evidence of improving survival, are used to treat them. The authors use examples from the realm of gastrointestinal cancer, largely focusing on the experience of patients with neuroendocrine cancer, hepatobiliary cancer, and colorectal cancer, to suggest that current systemic therapies offer, at minimum, similar survival outcomes for patients compared with these locoregional approaches.

Summary Background Although acellular dermal matrix (ADM) is widely used in expander-implant-based breast reconstructions, previous analyses have been unable to demonstrate improvements in patient-reported outcomes (PROs) with this approach over non-ADM procedures. This study aims to develop a more selective, evidence-based approach to the use of ADM in expander-implant-based breast reconstruction by identifying patient subgroups in which ADM improved clinical outcomes and PROs. Study design The Mastectomy Reconstruction Outcomes Consortium Study prospectively evaluated immediate expander-implant reconstructions at 11 centers from 2012 to 2015. Complications (any/overall and major), and PROs (satisfaction, physical, psychosocial, and sexual well-being) were assessed two years postoperatively using medical records and the BREAST-Q, respectively. Using mixed-models accounting for centers and with interaction terms, we analyzed for differential ADM effects across various clinical subgroups, including age, body mass index, radiation timing, and chemotherapy. Results Expander-implant-based breast reconstruction was performed in 1451 patients, 738 with and 713 without ADM. Major complication risk was higher in ADM users vs. nonusers (22.9% vs. 16.4% and p = 0.04). Major complication risk with ADM increased with higher BMI (BMI=30, OR=1.70; BMI=35, OR=2.29, interaction p = 0.02). No significant ADM effects were observed for breast satisfaction, psychosocial, sexual, and physical well-being within any subgroups. Conclusion In immediate expander-implant-based breast reconstruction, ADM was associated with a greater risk of major complications, particularly in high-BMI patients. We were unable to identify patient subgroups where ADM was associated with significant improvements in PROs. Given these findings and the financial costs of ADM, a more critical approach to the use of ADM in expander-implant reconstruction may be warranted.

There is no standardized curriculum for teaching interventional spine procedures during residency. The objective of this protocol was to share a curriculum using a cadaver laboratory for teaching Physical Medicine and Rehabilitation residents interventional spine procedures, which can be an effective and safe medium to train residents. This protocol provides a checklist that can guide the residents while they are in the cadaver laboratory with a focus on some of the most common lumbar procedures. Twelve physical medicine and rehabilitation resident's confidence in their ability to maneuver the x-ray image intensifier (C-arm), identify spine anatomy under fluoroscopy, and drive the needle improved after the training curriculum (P0.005). Although the cadaver laboratory curriculum is not a replacement for the required Accreditation Council for Graduate Medical Education training, it may serve as a tool to improve resident preparedness for spine procedures.

Objective: To explore the impact of the Covid-19 pandemic on the stress levels and experience of academic surgeons by training status (eg, housestaff or faculty). Background: Covid-19 has uniquely challenged and changed the United States healthcare system. A better understanding of the surgeon experience is necessary to inform proactive workforce management and support. Methods: A multi-institutional, cross-sectional telephone survey of surgeons was conducted across 5 academic medical centers from May 15 to June 5, 2020. The exposure of interest was training status. The primary outcome was maximum stress level, measured using the validated Stress Numerical Rating Scale-11 (range 0–10). Results: A total of 335 surveys were completed (49.3% housestaff, 50.7% faculty; response rate 63.7%). The mean maximum stress level of faculty was 7.21 (SD 1.81) and of housestaff was 6.86 (SD 2.06) (P = 0.102). Mean stress levels at the time of the survey trended lower amongst housestaff (4.17, SD 1.89) than faculty (4.56, SD 2.15) (P = 0.076). More housestaff (63.6%) than faculty (40.0%) reported exposure to individuals with Covid-19 (P < 0.001). Subjects reported inadequate personal protective equipment in approximately a third of professional exposures, with no difference by training status (P = 0.557). Conclusions: During the early months of the Covid-19 pandemic, the personal and professional experiences of housestaff and faculty differed, in part due to a difference in exposure as well as non-work-related stressors. Workforce safety, including adequate personal protective equipment, expanded benefits (eg, emergency childcare), and deliberate staffing models may help to alleviate the stress associated with disease resurgence or future disasters.

Key Clinical Points Evaluation and Management of Severe Covid-19 Patients with severe coronavirus disease 2019 (Covid-19) may become critically ill with acute respiratory distress syndrome that typ...

Aims: The first year after childbirth involves a major transition for women, which can accentuate inadequacies and feelings of powerlessness, making them vulnerable to depression. The aim of this study was to investigate the prevalence and frequency of maternal postpartum depressive symptoms at different times after giving birth (0–21 months). Methods: Data were collected cross-sectionally using a web questionnaire containing the Edinburgh Postnatal Depression Scale (EPDS). A total of 888 mothers with children in the age range 0–21 months responded. Results: The results showed different levels of depression over the range of months included in the study. The overall prevalence using EPDS ⩾ 12 was 27.8%. There were higher levels at 9–12 months and 17–21 months. The highest levels of symptoms of depression were found at nine, 12, and 17 months after birth, and the lowest levels at two and 16 months. Conclusions: Many mothers experience symptoms of depression after giving birth that can continue well beyond the child’s first year. We have identified different levels of depression at different points in time after giving birth, with highs and lows throughout the first 21 months. This highlights a need to screen for depression more than once during the first years, as well as a closer cooperation between midwives and child healthcare nurses in supporting mothers in the transition to motherhood. This is an important aspect of public health, which not only involves mothers with symptoms of depression, but also their ability to care for their child and a possible negative impact on the child’s development.

National data on patient characteristics, treatment, and outcomes of critically ill coronavirus disease 2019 (COVID-19) solid organ transplant (SOT) patients are limited. We analyzed data from a multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units (ICUs) at 68 hospitals across the United States from March 4 to May 8, 2020. From 4153 patients, we created a propensity score matched cohort of 386 patients, including 98 SOT patients and 288 non-SOT patients. We used a binomial generalized linear model (log-binomial model) to examine the association of SOT status with death and other clinical outcomes. Among the 386 patients, the median age was 60 years, 72% were male, and 41% were black. Death within 28 days of ICU admission was similar in SOT and non-SOT patients (40% and 43%, respectively; relative risk [RR] 0.92; 95% confidence interval [CI]: 0.70-1.22). Other outcomes and requirement for organ support including receipt of mechanical ventilation, development of acute respiratory distress syndrome, and receipt of vasopressors were also similar between groups. There was a trend toward higher risk of acute kidney injury requiring renal replacement therapy in SOT vs. non-SOT patients (37% vs. 27%; RR [95% CI]: 1.34 [0.97-1.85]). Death and organ support requirement were similar between SOT and non-SOT critically ill patients with COVID-19.

Maternal sensitivity to infant distress is a key predictor of infant attachment security and social-emotional development. Preventive interventions that support mothers' sensitive responses to infant distress are crucial, as are rigorous evaluations that test

Ovarian cancer survival and recurrence rate are drastically affected by the amount of tumor that can be surgically removed prior to chemotherapy. Surgeons are currently limited to visual inspection, making smaller tumors difficult to remove surgically. Enhancing the surgeon’s ability to selectively remove cancerous tissue would have a positive effect on a patient’s prognosis. One approach to aid in surgical tumor removal involves using targeted fluorescent probes to selectively label cancerous tissue. To date, there has been a trade off in balancing two requirements for the surgeon: the ability to see maximal tumors and the ability to identify these tumors by eye while performing the surgery. The ability to see maximal tumors has been prioritized and this has led to the use of fluorophores activated by near-infrared (NIR) light as NIR penetrates most deeply in this surgical setting, but the light emitted by traditional NIR fluorophores is invisible to the naked eye. This has necessitated the use of specialty detectors and monitors that the surgeon must consult while performing the surgery. In this study, we develop nanoparticles that selectively label ovarian tumors and are activated by NIR light but emit visible light. This potentially allows for maximal tumor observation and real time detection by eye during surgery. We designed two generations of up-converting nanoparticles (UCNPs) that emit green light when illuminated with NIR light. These particles specifically label ovarian tumors most likely via tumor-associated macrophages (TAMs), which are prominent in the tumor microenvironment. Our results demonstrate that this approach is viable means of visualizing tumors during surgery without the need for complicated, expensive, and bulky detection equipment. Continued improvement and experimentation could expand our approach into a much needed surgical technique to aid ovarian tumor removal.

To examine cancer prevalence in men with and without military service history, using national-level self-reported outcomes. A cross-sectional survey-based US study, including men aged 18 and above from the Health Information National Trends Survey database between 2011 and 2014. The primary endpoint was self-reported cancer prevalence. Multivariable logistic regression analyses assessed the association of various covariates with the prevalence of cancer. A total of 4,527 men were analyzed, with 1,352 (29.9%) reporting a history of military service. Compared to men with no military service history, men with a military service history were older (median of 65 [IQR 56, 74] vs. 53 [IQR 41, 62] years, p

Previous research suggests that young adults from out-of-home care (OHC) are at high risk of low education and unemployment. However, there are no studies on their risk of long-term NEET (Not in Employment, Education or Training). This study compared the risk of NEET at age 21-23 among OHC youth across Denmark, Finland and Sweden, using register data for an entire birth cohort born in 1987. The Nordic countries share many features, but there are differences in the provision of after-care support and in the linkage between the educational system and the labour market. The results show that about a fourth in Denmark and Sweden and a third in Finland were NEET, suggesting that the welfare systems were not able to compensate for the OHC youth's childhood disadvantages. To a significant extent, the excess risk of NEET was attributed to poor school performance. Implications for research, policy and practice are discussed.

Purpose Clinical trials compare outcomes among patients receiving study treatment with comparators drawn from the same source. These internal controls are missing in single arm trials and from long‐term extensions (LTE) of trials including only the treatment arm. An external control group derived from a different setting is then required to assess safety or effectiveness. Methods We present examples of external control groups that demonstrate some of the issues that arise and make recommendations to address them through careful assessment of the data source fitness for use, design, and analysis steps. Results Inclusion and exclusion criteria and context that produce a trial population may result in trial patients with different clinical characteristics than are present in an external comparison group. If these differences affect the risk of outcomes, then a comparison of outcome occurrence will be confounded. Further, patients who continue into LTE may differ from those initially entering the trial due to treatment effects. Application of appropriate methods is needed to make valid inferences when such treatment or selection effects are present. Outcome measures in a trial may be ascertained and defined differently from what can be obtained in an external comparison group. Differences in sensitivity and specificity for identification or measurement of study outcomes leads to information bias that can also invalidate inferences. Conclusion This review concentrates on threats to the valid use of external control groups both in the scenarios of single arm trials and LTE of randomized controlled trials, along with methodological approaches to mitigate them.

OBJECTIVES To assess whether free PSA ratio (FPSAR) at biochemical recurrence (BCR) can predict metastasis, castrate-resistant prostate cancer (CRPC), and cancer-specific survival (CSS), following therapy for localised disease. PATIENTS AND METHODS A single-centre retrospective cohort study (NCT03927287) including a discovery cohort composed of patients with an FPSAR after radical prostatectomy (RP) or radiotherapy (RT) between 2000 and 2017. For validation, an independent Biobank cohort of patients with BCR after RP was tested. Using a defined FPSAR cut-off, the metastasis-free-survival (MFS), CRPC-free survival, and CSS were compared. Multivariable Cox models determined the association between post-treatment FPSAR, metastases, and CRPC. RESULTS Overall, 822 patients (305 RP- and 363 RT-treated patients and 154 Biobank patients) were analysed. In the RP cohort, a total of 272/305 (89.1%) and 33/305 (10.9%) had a FPSAR test incidentally and reflexively, respectively. In the RT cohort, 155/363 (42.7%) and 208/263 (57.3%) had a FPSAR test incidentally and reflexively, respectively. However, in the prospective Biobank RP cohort, FPSAR testing was done on all samples of patients diagnosed with BCR. A FPSAR cut-off of 0.10 was determined using receiver operating characteristic analyses in both the RP and RT cohorts. A FPSAR of

Fur das pathologische Verstandnis retinaler Veranderungen sind direkte Vergleiche von hochaufgeloster In-vivo-Bildgebung und histologischer Darstellung wunschenswert. Dargestellt wird der methodische Aufbau zur multimodalen In-vivo- und Ex-vivo-Bildgebung eines Spenderauges mit sekundaren Veranderungen nach einem retinalen Zentralarterienverschluss. Die sich anschliesende Korrelation mit der Histologie erfolgt an identischen Gewebelokalisationen. Mit entsprechenden Vorrichtungen lassen sich In-vivo- und Ex-vivo-Bildgebung korrelieren und an den herkommlichen Geraten zur retinalen Bildgebung – wie am Beispiel des SD-OCTs („spectral domain“ optische Koharenztomographie) gezeigt – aufnehmen. Die prazise Ausrichtung des Gewebes ermoglicht eine histologische Analyse an identischen Aufnahmeorten. Durch die direkte Korrelation von klinischer Bildgebung mit Ex-vivo-Darstellung und Histologie lassen sich Erkenntnisse zur Pathogenese unterschiedlicher ophthalmologischer Krankheiten gewinnen. Die groste Herausforderung ist derzeit die eingeschrankte Verfugbarkeit von Spendergewebe.

Background Matrix metalloproteinase 9 (MMP9) expression in the tumor microenvironment is implicated in multiple protumorigenic processes. Andecaliximab (GS-5745), a monoclonal antibody targeting MMP9 with high affinity and selectivity, was evaluated in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic adenocarcinoma. Patients and Methods This phase I study was completed in two parts: part A was a dose-finding, monotherapy phase that enrolled patients with advanced solid tumors, and part B examined andecaliximab in combination with chemotherapy in specific patient cohorts. In the cohort of patients with pancreatic adenocarcinoma (n = 36), andecaliximab 800 mg every 2 weeks was administered in combination with gemcitabine and nab-paclitaxel. Patients were treated until unacceptable toxicity, withdrawal of consent, disease progression, or death. Efficacy, safety, and biomarker assessments were performed. Results Andecaliximab combined with gemcitabine and nab-paclitaxel appeared to be well tolerated and did not demonstrate any unusual toxicities in patients with pancreatic adenocarcinoma. The most common treatment-emergent adverse events were fatigue (75.0%), alopecia (55.6%), peripheral edema (55.6%), and nausea (50.0%). Median progression-free survival was 7.8 months (90% confidence interval, 6.9−11.0) with an objective response rate of 44.4% and median duration of response of 7.6 months. Maximal andecaliximab target binding, defined as undetectable, andecaliximab-free MMP9 in plasma, was observed. Conclusion Andecaliximab in combination with gemcitabine and nab-paclitaxel demonstrates a favorable safety profile and clinical activity in patients with advanced pancreatic adenocarcinoma. Implications for Practice The combination of andecaliximab, a novel, first-in-class inhibitor of matrix metalloproteinase 9, with gemcitabine and nab-paclitaxel in patients with advanced pancreatic adenocarcinoma provided a median progression-free survival of 7.8 months and objective response rate of 44.4%. The majority of systemic biomarkers related to matrix metalloproteinase 9 activity and immune suppression increased at 2 months, whereas biomarkers related to tumor burden decreased. Although this study demonstrates promising results with andecaliximab plus chemotherapy in patients with advanced pancreatic adenocarcinoma, andecaliximab was not associated with a survival benefit in a phase III study in patients with advanced gastric/gastroesophageal junction carcinoma.

Aims/hypothesis Chronic stimulation of β2-adrenoceptors, opposite to acute treatment, was reported to reduce blood glucose levels, as well as to improve glucose and insulin tolerance in rodent models of diabetes by essentially unknown mechanisms. We recently described a novel pathway that mediates glucose uptake in skeletal muscle cells via stimulation of β2-adrenoceptors. In the current study we further explored the potential therapeutic relevance of β2-adrenoceptor stimulation to improve glucose homeostasis and the mechanisms responsible for the effect. Methods C57Bl/6N mice with diet-induced obesity were treated both acutely and for up to 42 days with a wide range of clenbuterol dosages and treatment durations. Glucose homeostasis was assessed by glucose tolerance test. We also measured in vivo glucose uptake in skeletal muscle, insulin sensitivity by insulin tolerance test, plasma insulin levels, hepatic lipids and glycogen. Results Consistent with previous findings, acute clenbuterol administration increased blood glucose and insulin levels. However, already after 4 days of treatment, beneficial effects of clenbuterol were manifested in glucose homeostasis (32% improvement of glucose tolerance after 4 days of treatment, p −1 day−1 (40 times lower than previously studied). Mechanistically, these effects were not due to increased insulin levels, but clenbuterol enhanced glucose uptake in skeletal muscle in vivo both acutely in lean mice (by 64%, p p p p p Conclusions/interpretation Clenbuterol improved glucose tolerance after 4 days of treatment and these effects were maintained for up to 42 days. Effects were achieved with doses in a clinically relevant microgram range. Mechanistically, prolonged treatment with a low dose of clenbuterol improved glucose homeostasis in insulin resistant mice, most likely by stimulating glucose uptake in skeletal muscle and improving whole-body insulin sensitivity as well as by reducing hepatic lipids and glycogen. We conclude that selective β2-adrenergic agonists might be an attractive potential treatment for type 2 diabetes. This remains to be confirmed in humans.

The role of percent free prostate specific antigen (%fPSA) in patients who have undergone radical prostatectomy and subsequently experienced disease relapse is unclear. We previously conducted 2 retrospective studies and found %fPSA 15 or greater in the setting of biochemical recurrence confers more aggressive disease. To validate that finding we used biobank specimens collected prospectively when patients were first diagnosed with biochemical recurrence.Biobank specimens of patients with undetectable prostate specific antigen after radical prostatectomy and subsequent biochemical recurrence (prostate specific antigen 0.1 ng/ml or greater) were analyzed for %fPSA. Patients were stratified according to the %fPSA cutoff of 15. Univariable and multivariable logistic regression analysis was performed to predict covariates associated with a higher %fPSA. Cox proportional hazard models were performed to evaluate the prognostic effect of %fPSA on androgen deprivation therapy-free survival, metastasis-free survival, castration resistant-free survival and cancer specific survival.A total of 154 men were included in the study, of whom 126 (82%) had %fPSA less than 15 and 28 (18%) had %fPSA 15 or greater. Median followup for %fPSA less than 15 and %fPSA 15 or greater was 75 and 69 months, respectively. Patients with %fPSA 15 or greater had increased hazard of receiving androgen deprivation therapy (43% vs 25%, adjusted HR 2.40, 95% CI 1.12-5.11), metastatic disease (21% vs 7.9%, adjusted HR 4.10, 95% CI 1.11-15.2) and castration resistant prostate cancer (14% vs 4.0%, unadjusted HR 4.14, 95% CI 1.11-15.5) vs %fPSA less than 15, respectively.Patients with %fPSA 15 or greater were started on androgen deprivation therapy earlier, and they had progression to castration resistant prostate cancer and metastatic stage earlier. %fPSA 15 or greater in the setting of biochemical recurrence after radical prostatectomy is an indicator of a more aggressive disease. Unlike in the diagnostic setting, a higher %fPSA portends a worse clinical outcome.

BACKGROUND: Multiple studies have demonstrated the safety of omitting therapies in older women with breast cancer. Despite de-implementation guidelines, up to 65% of older women continue to receive one or more of these low-value services. Previous work has investigated the role of both provider and patient attitudes as barriers to de-implementation; however, the importance of the patient’s maximizing-minimizing preferences within this context remains unclear. METHODS: In this qualitative study, we conducted thirty (n = 30) semi-structured interviews with women ≥ 70 years old without a previous diagnosis of breast cancer to elicit perspectives on breast cancer treatment in relation to their medical maximizing-minimizing preferences, as determined by the single-item maximizer-minimizer elicitation question (MM1). We used an interpretive description approach in analysis to produce a thematic survey. RESULTS: Participants were relatively evenly distributed across the MM1 (minimizer n = 8, neutral n = 13, maximizer n = 9). Despite being told of recommendations allowing for the safe omission of SLNB and post-lumpectomy radiotherapy, maximizers consistently stated preferences for more medical intervention and aggressive therapies over minimizers and neutral individuals. CONCLUSION: Medical maximizing-minimizing preferences in older women correspond with preferences for breast cancer treatment options that guidelines identify as potentially unnecessary. Increased awareness of patient-level variability in maximizing-minimizing preferences may be valuable in developing optimal intervention strategies to reduce utilization of low-value care.