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This article provides a current review of the literature examining caffeine use in older adults. Caffeine use is prevalent among older adults; thus, providers need to be aware of the prevalence and diagnostic criteria of caffeine use disorder versus nonproblematic use. The relationship between caffeine and various neuropsychiatric disorders, including Parkinson's disease, Alzheimer's disease, insomnia, and late-life depression, is reviewed. The neurobiological effects of caffeine are described, along with clinically relevant interactions between caffeine and common psychotropic medications.

Objective Spinal metastases occur primarily in the thoracic spine (50%–60%), less commonly in the lumbar (30%–35%), and, infrequently, in the cervical spine (10%–15%). There has been only 1 study with a limited population comparing the postoperative outcome among cervical, thoracic, and lumbar spine metastasis. The aim of this study is to identify whether the region of surgically treated spinal metastasis affects postoperative outcomes. Methods A retrospective study of patients with spinal metastasis was performed. The collected data were as follows: age, gender, smoking history, tumor histology, revised Tokuhashi score, preoperative and postoperative American Spinal Injury Association score, region of spinal metastasis, ambulatory status, surgical approach, surgery time, blood loss, complications, length of hospital stay, postoperative pain relief, postoperative adjuvant therapy, and survival. Data were analyzed to identify the factors affecting the survival and postoperative functional outcome. Results We studied 191 patients with spinal metastasis including 47 cervical spine metastases, 96 thoracic spine metastases, and 48 lumbar spine metastases, with a mean age of 60.91 ± 9.72 years. The overall median survival was 7 months (95% confidence interval, 2.9–20.63 months). Univariate analysis showed that region of the spine involved with metastasis did not significantly affect the survival and postoperative motor function improvement. Multivariate analysis showed that revised Tokuhashi score, postoperative radiotherapy, and postoperative chemotherapy were independent factors affecting survival. The rate of 30-day complications among patients with different regions of spine metastasis did not reach significance. Conclusions The postoperative outcomes of patients undergoing surgery for metastases are not affected by the region of the spine.

Malnutrition, muscle loss, and cachexia are prevalent in cancer and remain key challenges in oncology today. These conditions are frequently underrecognized and undertreated and have devastating consequences for patients. Early nutrition screening/assessment and intervention are associated with improved patient outcomes. As a multifaceted disease, cancer requires multimodal care that integrates supportive interventions, specifically nutrition and exercise, to improve nutrient intake, muscle mass, physical functioning, quality of life, and treatment outcomes. An integrated team of healthcare providers that incorporates societies’ recommendations into clinical practice can help achieve the best possible outcomes. A multidisciplinary panel of experts in oncology, nutrition, exercise, and medicine participated in a 2-day virtual roundtable in October 2020 to discuss gaps and opportunities in oncology nutrition, alone and in combination with exercise, relative to current evidence and international societies’ recommendations. The panel recommended five principles to optimize clinical oncology practice: (1) position oncology nutrition at the center of multidisciplinary care; (2) partner with colleagues and administrators to integrate a nutrition care process into the multidisciplinary cancer care approach; (3) screen all patients for malnutrition risk at diagnosis and regularly throughout treatment; (4) combine exercise and nutrition interventions before (e.g., prehabilitation), during, and after treatment as oncology standard of care to optimize nutrition status and muscle mass; and (5) incorporate a patient-centered approach into multidisciplinary care.

The COVID-19 pandemic prompted widespread closures of primary and secondary schools. Routine testing of asymptomatic students and staff members, as part of a comprehensive mitigation program, can help schools open safely. “Pooling in a pod” is a public health surveillance strategy whereby testing cohorts (pods) are based on social relationships and physical proximity. Pooled testing provides a single laboratory test result for the entire pod, rather than a separate result for each person in the pod. During the 2020-2021 school year, an independent preschool–grade 12 school in Washington, DC, used pooling in a pod for weekly on-site point-of-care testing of all staff members and students. Staff members and older students self-collected anterior nares samples, and trained staff members collected samples from younger students. Overall, 12 885 samples were tested in 1737 pools for 863 students and 264 staff members from November 30, 2020, through April 30, 2021. The average pool size was 7.4 people. The average time from sample collection to pool test result was 40 minutes. The direct testing cost per person per week was $24.24, including swabs. During the study period, 4 surveillance test pools received positive test results for COVID-19. A post-launch survey found most parents (90.3%), students (93.4%), and staff members (98.8%) were willing to participate in pooled testing with confirmatory tests for pool members who received a positive test result. The proportion of students in remote learning decreased by 62.2% for students in grades 6-12 ( P < .001) and by 92.4% for students in preschool to grade 5 after program initiation ( P < .001). Pooling in a pod is a feasible, cost-effective surveillance strategy that may facilitate safe, sustainable, in-person schooling during a pandemic.

Increased body mass may predispose children to a greater risk for radial head subluxation (RHS). Recent studies in the literature have reported a plateau in obesity prevalence among infants and toddlers. This study sought to examine recent epidemiological trends in RHS incidence from 2004 to 2018 using the National Electronic Injury Surveillance System database to determine how obesity patterns may affect RHS incidence. The National Electronic Injury Surveillance System (NEISS) database was queried for patients 6 years of age or younger presenting with radial head subluxation between January 1, 2004 and December 31, 2018. Patient demographics, mechanisms of injury, and location of injury were recorded. An estimated total 253,578 children 6 years or younger were treated for RHS with 14,204 (95% CI = 8124–20,284) in 2004 to 21,408 (95% CI = 12,882–29,934) in 2018. The overall annual rate of RHS per 10,000 children ≤ 6 years was 6.03 (95% CI = 4.85–7.58). The annual rate of RHS per 10,000 children ≤ 6 years increased (m = 0.200, s = 0.802, p

Heterogeneous disease manifestations are now recognized among some persons after initial recovery from SARS-CoV-2 infection. The National Institute of Allergy and Infectious Diseases convened a virtual workshop to summarize existing knowledge and to identify key knowledge gaps regarding this condition., Over the past year, the SARS-CoV-2 pandemic has swept the globe, resulting in an enormous worldwide burden of infection and mortality. However, the additional toll resulting from long-term consequences of the pandemic has yet to be tallied. Heterogeneous disease manifestations and syndromes are now recognized among some persons after their initial recovery from SARS-CoV-2 infection, representing in the broadest sense a failure to return to a baseline state of health after acute SARS-CoV-2 infection. On 3 to 4 December 2020, the National Institute of Allergy and Infectious Diseases, in collaboration with other Institutes and Centers of the National Institutes of Health, convened a virtual workshop to summarize existing knowledge on postacute COVID-19 and to identify key knowledge gaps regarding this condition.

Background Azithromycin and doxycycline are both recommended treatments for rectal Chlamydia trachomatis (CT) infection, but observational studies suggest that doxycycline may be more effective. Methods This randomized, double-blind, placebo-controlled trial compared azithromycin (single 1-g dose) versus doxycycline (100 mg twice daily for 7 days) for the treatment of rectal CT in men who have sex with men (MSM) in Seattle and Boston. Participants were enrolled after a diagnosis of rectal CT in clinical care and underwent repeated collection of rectal swabs for nucleic acid amplification testing (NAAT) at study enrollment and 2 weeks and 4 weeks postenrollment. The primary outcome was microbiologic cure (CT-negative NAAT) at 4 weeks. The complete case (CC) population included participants with a CT-positive NAAT at enrollment and a follow-up NAAT result; the intention-to-treat (ITT) population included all randomized participants. Results Among 177 participants enrolled, 135 (76%) met CC population criteria for the 4-week follow-up visit. Thirty-three participants (19%) were excluded because the CT NAAT repeated at enrollment was negative. Microbiologic cure was higher with doxycycline than azithromycin in both the CC population (100% [70 of 70] vs 74% [48 of 65]; absolute difference, 26%; 95% confidence interval [CI], 16–36%; P < .001) and the ITT population (91% [80 of 88] vs 71% [63 of 89]; absolute difference, 20%; 95% CI, 9–31%; P < .001). Conclusions A 1-week course of doxycycline was significantly more effective than a single dose of azithromycin for the treatment of rectal CT in MSM. Clinical Trials Registration NCT03608774.

Traumatic cyclodialysis clefts, a rare diagnosis after blunt injury to the eye, are typically amenable to closure with either medical therapy or direct surgical cyclopexy. However, when cyclodialysis clefts cannot be closed through these methods, unorthodox techniques may be required. We describe a method to close a traumatic cyclodialysis cleft involving simultaneous vitrectomy, capsular tension ring placement, and insertion of an intraocular lens.

Background: Until the advent of T cell check point inhibitors standard second-line therapy for patients with metastatic urothelial cancer (mUC) was undefined. Histone deacetylase inhibitors (HDACi) have anti-cancer activity in a variety of tumor models including modulation of apoptosis in bladder cancer cell lines. We evaluated the efficacy and toxicity of the HDACi vorinostat in patients with mUC failing first-line platinum-based therapy either in the adjuvant/neoadjuvant setting or for recurrent/advanced disease. Methods: Vorinostat was given orally 200 mg twice daily continuously until progression or unacceptable toxicity. The primary end point was RECIST response rate (RR); a RR > 20% was deemed interesting in a 2-stage design requiring one response in the first 12 patients to proceed to 2nd stage for a total of 37 subjects. CT or MRI scan imaging occurred every 6 weeks. Results: Fourteen patients were accrued characterized by: median age 66 years (43–84); Caucasian (79%); males (86%); and Karnofsky performance status ≥90 (50%). Accrual was terminated in the first stage as no responses were observed. Best response was stable disease (3 patients). Progression was observed in 8 patients. Two patients came off therapy prior to re-imaging and a 3rd patient died while on treatment and was not assessed for response. Median number of cycles was 2 (range 1–11). Median disease-free survival and overall survival times were 1.1 (0.8, 2.1) & 3.2 (2.1, 14.5) months, respectively. Toxicities were predominantly cytopenias and thrombocytopenic bleeding. Two pts. had grade 5 toxicity unlikely related to treatment. Two pts. had grade 4 and 6 had grade 3 toxicities observed. Two patients with stable disease remained on therapy for 6+ cycles. Conclusions: Vorinostat on this dose-schedule had limited efficacy and significant toxicity resulting in a unfavorable risk:benefit ratio in patients with mUC. NCT00363883.

Introduction There are currently no approved targeted therapies for lung squamous-cell carcinoma (LSCC) and KRAS-mutant lung adenocarcinoma (LUAD). About 30% of LSCC and 25% of KRAS-mutant LUAD exhibit hyperactive NRF2 pathway activation through mutations in NFE2L2 (the gene encoding NRF2) or its negative regulator, KEAP1. Preclinical data demonstrate that these tumors are uniquely sensitive to dual inhibition of glycolysis and glutaminolysis via mammalian target of rapamycin (mTOR) and glutaminase inhibitors. This phase 1 study was designed to assess safety and preliminary activity of the mTOR inhibitor MLN0128 (sapanisertib) in combination with the glutaminase inhibitor CB-839 HCl. Methods Phase 1 dose finding will use the queue-based variation of the 3 + 3 dose escalation scheme with the primary endpoint of identifying the recommended expansion dose. To confirm the acceptable tolerability of the recommended expansion dose, patients will subsequently enroll onto 1 of 4 expansion cohorts (n = 14 per cohort): (1) LSCC harboring NFE2L2 or (2) KEAP1 mutations, or (3) LUAD harboring KRAS/(KEAP1 or NFE2L2) coalterations, or (4) LSCC wild type for NFE2L2 and KEAP1. The primary endpoint of the dose expansion is to determine the preliminary efficacy of MLN0128/CB-839 combination therapy. Conclusion This phase 1 study will determine the recommended expansion dose and preliminary efficacy of MLN0128 and CB-839 in advanced non–small-cell lung cancer with a focus on subsets of LSCC and KRAS-mutant LUAD harboring NFE2L2 or KEAP1 mutations.

Summary Background Puerto Rico began screening blood donations for Zika virus RNA with nucleic acid amplification tests (NAATs) on April 3, 2016, because of an emerging Zika virus outbreak. We followed up positive donors to assess the dynamics of viral and serological markers during the early stages of Zika virus infection and update the estimate of infection incidence in the Puerto Rican population during the outbreak. Methods Blood donations from volunteer donors in Puerto Rico were screened for the presence of Zika virus RNA using the cobas Zika NAAT. Positive donations were further tested to confirm infection, estimate viral load, and identify Zika virus-specific IgM antibodies. Individuals with positive blood donations were invited to attend follow-up visits. Donations with confirmed infection (defined as detection of Zika virus RNA or IgM on additional testing of index or follow-up samples) were assessed for stage of infection according to Zika virus RNA detectability in simulated minipools, viral load, and Zika virus IgM status. A three-step process was used to estimate the mean duration of NAAT reactivity of Zika virus in human plasma from individuals identified pre-seroconversion with at least one follow up visit and to update the 2016 incidence estimate of Zika virus infection. Findings Between April 3 and Dec 31, 2016, 53 112 blood donations were screened for Zika virus, of which 351 tested positive, 339 had confirmed infections, and 319 could be staged. Compared with IgM-positive index donations (n=110), IgM-negative index donations (n=209) had higher mean viral loads (1·1 × 106 vs 8·3 × 104 international units per mL) and were more likely to be detected in simulated minipools (93% [n=194] vs 26% [n=29]). The proportions of donations with confirmed infections that had viral RNA detected only in individual-donation NAATs (ie, not in simulated minipools) and were IgM positive increased as the epidemic evolved. The estimated mean duration of NAAT detectability in the 140 donors included in the follow-up study was 11·70 days (95% CI 10·06–14·36). Applying this detection period to the observed proportion of donations that were confirmed NAAT positive yielded a Zika virus seasonal incidence estimate of 21·1% (95% CI 18·1–24·1); 768 101 infections in a population of 3 638 773 in 2016. Interpretation Characterisation of early Zika virus infection has implications for blood safety because infectivity of blood donations and utility of screening methods likely correlate with viral load and serological stage of infection. Our findings also have implications for diagnostic testing, public health surveillance, and epidemiology, and we estimate that around 21% of the Puerto Rican population was infected during the 2016 outbreak. Funding Biomedical Advanced Research and Development Authority, National Heart, Lung, and Blood Institute.

Primary midline hernias arising in the linea alba are common. While mesh repair has been shown to reduce recurrence rates even in small hernias, many surgeons still use a suture repair for defects of less than 2 cm. The recent European and Americas Hernia Societies Guidelines recommended suture repair only for hernias smaller than 1 cm. A suture repair implies edge-to-edge or overlapping fascial margins, which necessarily involves tension on the repair. A darn is a tension-free repair where, in effect, a “mesh” is hand-woven across the defect in situ. The darn repair is a modification of the darn techniques for inguinal hernia repair. Eligible patients undergoing this repair at the Royal Infirmary of Edinburgh between 1 January 2008 and 31 December 2017 were identified from a prospective computer-based medical record system and their case notes reviewed. Inclusion criteria were adult patients with a primary midline abdominal wall defect smaller than 2 cm in the widest diameter of the hernia defect measured intra-operatively. Patients were followed up by telephone in 2019. Those who reported possible recurrence or other symptoms in the region of their hernia repair were reviewed in the outpatient clinic. 47 suture-darn repairs were undertaken over the 10-year period. Fifteen of the darn repair operations (32%) were performed under local anaesthesia. Forty-one patients were followed up with a mean of 80 ± 35 and median of 87 months after surgery. Six patients (13%) were lost to follow-up. Recurrence was found in two cases (5%) and one patient has since been diagnosed with a new epigastric hernia some 5 cm cranial to the previous repair. The darn repair for small primary midline hernias is quick and inexpensive with promising long-term results. It can be performed under local anaesthesia. It can serve as an alternative to mesh repair for defects less than 2 cm in maximum dimension.

The prevalence of multidrug-resistant organisms is increasing worldwide, posing a unique challenge to global health care systems. Novel approaches are needed to combat the spread of infection with these organisms. The enteric microbiome, and in particular the resistome, offers a unique target in both the prevention of infection with these organisms and the acquisition and spread within the community. We highlight a novel approach to combat multidrug-resistant organisms: the use of prebiotics, probiotics, and synbiotics to manipulate the microbiome and resistome. This review summarizes the published literature and clinical trials related to these products to date, with a focus on efficacious trials. It highlights the probable mechanism of action for each product, as well as its safety profile in selective populations. Ultimately, although further research is needed before a definitive statement can be made on the efficacy of any of these 3 interventions, the literature to date offers new hope and a new tool in the arsenal in the fight against bacterial drug resistance.

Introduction Despite growth in hand/upper extremity investigation, impactful studies have not been thoroughly identified. Previous studies have been limited in scope. This study sought to identify and characterize the most impactful orthopaedic papers in hand/upper extremity over the past 25 years. Materials and Methods The top 1,000 hand/upper extremity orthopaedic studies published from 1992 to 2017 were identified with Web of Science. After screening for relevance in order of decreasing citation number, the top 100 articles were identified for bibliometric analysis. Results The mean number of authors and citations were 4.51 (range, 1–21) and 169.4 (range, 105–863). Common study types included, case series (n = 52), randomized controlled trial (n = 17), and prospective cohort (n = 16), which predominantly covered topics related to shoulder (n = 34), wrist/forearm (n = 21), and hand (n = 17). Among wrist/forearm and hand studies, distal radius fractures (n = 12) and nerve-related topics (n = 10) were most frequently analyzed. Most studies were of level IV (n = 51) and level II (n = 16) evidence. Recent studies had greater impact (mean citations/year: 2011, 82.7/year vs. 1992, 16.1/year). Conclusion Most of the 100 top orthopaedic articles in hand/upper extremity were of level IV or II evidence, retrospective, and nonrandomized. Despite an observed recent increase in level I studies, a lack of prospective, randomized trials is apparent.

A greater number of medically complex patients with multiple comorbidities are now more readily considered for total knee arthroplasty (TKA). Therefore, the purpose of this study was to determine whether comorbidity burden, measured with the Elixhauser Comorbidity Index (ECI), correlated with 90-day medical complications and longer in-hospital lengths-of-stay (LOS) in TKA patients. The PearlDiver supercomputer was queried for all primary TKA patients in the Medicare Standard Analytic Files from 2005 to 2014 using International Classification of Disease, 9th edition codes. Patients were included based on ECI scores, ranging from 1 to 5. ECI 1 patients served as the control cohort, while ECI 2, 3, 4, and 5 patients were considered study cohorts. Each study cohort was matched based on age and gender to the control cohort, resulting in a total of 715,398 patients included for analysis (ECI 1, n = 144,072; ECI 2, n = 144,072; ECI 3, n = 144,072; ECI 4, n = 144,072; ECI 5, n = 139,110). Logistic regression analyses were performed to compare 90-day medical complications and Welch's t-tests were performed to compare LOS between the cohorts. Patients with higher ECI scores were more likely to develop medical complications and have longer LOS compared with matched patients in the control cohort. Compared with matched ECI 1 patients, patients with ECI scores of 2 (odds ratio [OR]: 1.19, 95% confidence interval [CI]: 1.14–1.24), 3 (OR: 1.27, 95% CI: 1.21–1.32), 4 (OR: 1.32, 95% CI: 1.27–1.38), and 5 (OR: 1.33, 95% CI: 1.27–1.39) were significantly more likely to develop 90-day medical complications. Additionally, the mean LOS of patients in the ECI 2 (2.59 ± 1.49 vs. 2.73 ± 1.52 days), ECI 3 (2.59 ± 1.49 vs. 2.88 ± 1.51 days; p

Background Antimicrobial resistance in Mycoplasma genitalium (MG), a cause of urethritis, is a growing concern. Yet little is known about the geographic distribution of MG resistance in the United States or about its associated clinical outcomes. We evaluated the frequency of MG among men with urethritis, resistance mutations, and posttreatment symptom persistence. Methods We enrolled men presenting with urethritis symptoms to 6 US sexually transmitted disease (STD) clinics during June 2017–July 2018; men with urethritis were eligible for follow-up contact and, if they had persistent symptoms or MG, a chart review. Urethral specimens were tested for MG and other bacterial STDs. Mutations in 23S ribosomal ribonucleic acid (rRNA) loci (macrolide resistance–associated mutations [MRMs]) and in parC and gyrA (quinolone-associated mutations) were detected by targeted amplification/Sanger sequencing. Results Among 914 evaluable participants, 28.7% (95% confidence interval [CI], 23.8–33.6) had MG. Men with MG were more often Black (79.8% vs 66%, respectively), Conclusions MG infection was common among men with urethritis; the MRM prevalence was high among men with MG. Persistent symptoms following treatment were frequent among men both with and without MG.

Context: The Dynamic Leap Balance Test (DLBT) is a new dynamic balance task that requires serial changes in base of support with alternating limb support and recovery of dynamic stability, as compared with the Y modification of the Star Excursion Balance Test (Y-SEBT), which assesses dynamic stability over an unchanging base of support. Objectives: To assess the dynamic balance performance in 2 different types of dynamic balance tasks, the DLBT and the SEBT, in subjects with unilateral chronic ankle instability (CAI) when compared with matched controls. The authors hypothesized that the DLBT score would significantly differ between the CAI involved and uninvolved limbs (contralateral and healthy matched) and demonstrate a modest (r = .50) association with the SEBT scores. Design: Case-control. Setting: Controlled laboratory. Participants: A total of 36 physically active adults, 18 with history of unilateral CAI and 18 without history of ankle injury, were enrolled in the study. CAI subjects were identified using the Identification of Functional Ankle Instability questionnaire. Interventions: The DLBT and the SEBT were performed in a randomized order on a randomly selected limb in CAI and healthy subjects. Main Outcome Measures: Time taken to complete the DLBT and the reach distances performed on the SEBT were compared between the CAI and the healthy subjects. Results: There were no statistically significant differences (P P .01) for unstable ankles compared with the stable ankle. The authors found no correlation (P > .05) between DLBT time and any of the SEBT reach distances suggesting that the DLBT provides unique information in the assessment of patients with CAI. Conclusion: The DLBT challenges the ability to maintain postural control in CAI subjects differently than the SEBT. There is a need of more dynamic balance assessment tools that are functional and clinically relevant.

Institutional Problems, Individual Solutions Positioning Black physicians and investigators at the forefront of vaccine-rollout efforts in an attempt to boost vaccine uptake in Black American commu...

Zoliflodacin is a novel spiropyrimidinetrione antibiotic being developed as single oral dose treatment to address the growing global threat of Neisseria gonorrhoeae. To evaluate the cardiac safety of zoliflodacin, a thorough QT/QTc (TQT) study was performed in healthy subjects. In this randomized, double-blind, placebo-controlled, 4-period crossover study, 72 subjects in a fasted state received a single dose of zoliflodacin at 2 g (therapeutic), zoliflodacin at 4 g (supratherapeutic), placebo, and moxifloxacin at 400 mg as a positive comparator. Cardiac repolarization was measured by duration of the corrected QT interval by Fridericia's formula (QTcF). At each time point up to 24 h after zoliflodacin administration, the upper limit of the one-sided 95% confidence interval (CI) for the placebo-corrected change from the predose baseline in QTcF (ΔΔQTcF) was less than 10 ms, indicating an absence of a clinically meaningful increase in QT prolongation. The lower limit of the one-sided multiplicity-adjusted 95% CI of ΔΔQTcF for moxifloxacin was longer than 5 ms at four time points from 1 to 4 h after dosing, demonstrating adequate sensitivity of the QTc measurement. There were no clinically significant effects on heart rate, PR and QRS intervals, electrocardiogram (ECG) morphology, or laboratory values. Treatment-emergent adverse events (AEs) were mild or moderate in severity and transient. This was a negative TQT study according to regulatory guidelines (E14) and confirms that a single oral dose of zoliflodacin is safe and well tolerated. These findings suggest that zoliflodacin is not proarrhythmic and contribute to the favorable assessment of cardiac safety for a single oral dose of zoliflodacin. (This study has been registered at ClinicalTrials.gov under registration no. NCT03613649.).

Background The COVID-19 pandemic has meant a significant decline in the activities of the paediatric spinal services in Scotland. Method All referrals to the Scottish paediatrics spinal service from 1st January 2020 to 30th June 2020 were analysed. Comparison was made to the same period in 2019. All orthotist initial consultations and all paediatrics spinal theatre activity in Scotland from 1st March 2020 to 30th June 2020 was analysed and compared to the previous year. Results There was a 64.3% decline in referrals during the first wave of the pandemic in Scotland to the paediatric spinal service. The mean wait time to be seen in 1st clinic for a new referral was 6.56 weeks in 2020 compared to 10.94 in 2019. There were however 60 patients still waiting to be seen. The number of paediatric spinal operations declined by 34% during March to June 2020 when compared to the same months in 2019 There was a reduction of 50% of new paediatric patients seen by orthotists from March – June 2020 when compared to 2019 Conclusions COVID-19 has had a significant effect on paediatric spinal services in Scotland. This is likely due to a combination of service delivery factors and patient factors. This is likely to result in delays to children getting the care they require for their spinal condition. There will also be a back-log of patients requiring to be seen when services start to re-establish themselves. There are several options available to department to optimise efficiency, such as video consultants and streamlining referral systems.

IMPORTANCE: Preclinical studies suggest that inhibition of single-stranded DNA repair by ataxia telangiectasia and Rad3 (ATR) may enhance the cytotoxicity of cisplatin, gemcitabine, and other chemotherapeutic agents. Cisplatin with gemcitabine remains the standard up-front therapy for treatment in patients with metastatic urothelial cancer. OBJECTIVE: To determine whether the use of the selective ATR inhibitor, berzosertib, could augment the activity of cisplatin with gemcitabine. DESIGN, SETTING, AND PARTICIPANTS: In a phase 2 randomized clinical trial, 87 patients across 23 centers in the National Cancer Institute Experimental Therapeutics Clinical Trials Network were randomized to receive either cisplatin with gemcitabine alone (control arm) or cisplatin with gemcitabine plus berzosertib (experimental arm). Key eligibility criteria included confirmed metastatic urothelial cancer, no prior cytotoxic therapy for metastatic disease, 12 months or more since perioperative therapy, and eligibility for cisplatin receipt based on standard criteria. The study was conducted from January 27, 2017, to December 15, 2020. INTERVENTIONS: In the control arm, cisplatin, 70 mg/m(2), was given on day 1 and gemcitabine, 1000 mg/m(2), was given on days 1 and 8 of a 21-day cycle. In the experimental arm, cisplatin, 60 mg/m(2), was given on day 1; gemcitabine, 875 mg/m(2), on days 1 and 8; and berzosertib, 90 mg/m(2), on days 2 and 9 of a 21-day cycle. MAIN OUTCOMES AND MEASURES: The primary end point of the study was progression-free survival. The analysis was on all patients who started therapy. RESULTS: Of the total of 87 patients randomized, 41 patients received cisplatin with gemcitabine alone and 46 received cisplatin with gemcitabine plus berzosertib. Median age was 67 (range, 32-84) years, and 68 patients (78%) were men. Median progression-free survival was 8.0 months for both arms (Bajorin risk-adjusted hazard ratio, 1.22; 95% CI, 0.72-2.08). Median overall survival was shorter with cisplatin with gemcitabine plus berzosertib compared with cisplatin with gemcitabine alone (14.4 vs 19.8 months; Bajorin risk-adjusted hazard ratio, 1.42; 95% CI, 0.76-2.68). Higher rates of grade 3 vs grade 4 thrombocytopenia (59% vs 39%) and neutropenia (37% vs 27%) were observed with cisplatin with gemcitabine and berzosertib compared with cisplatin with gemcitabine alone; consequently, more dose reductions were needed in the experimental arm. Patients in the experimental arm received a median cisplatin dose of 250 mg/m(2), which was significantly lower than the median dose of 370 mg/m(2) in the control arm (P

Introduction Distal radius fractures (DRFs) are increasingly managed surgically among fragility fractures due to prolonged life expectancy and surgical advancements. Yet, malnutrition can impact postoperative outcomes and complications. We sought to determine the impact of malnutrition on open reduction and internal fixation (ORIF) of DRFs during the perioperative and 30-day postoperative periods.Materials and Methods Using the National Surgical Quality Improvement Program database, all patients who underwent ORIF of a DRF between January 1, 2008, and December 31, 2016, were identified and stratified by preoperative serum albumin levels: normal (≥3.5 g/dL; n = 2,546) or hypoalbuminemia (Results Compared with patients with normal levels, a higher proportion of hypoalbuminemia patients had ASA scores > 3 (9.1 vs. 2%) and a longer mean length of stay (3.16 vs. 0.83 days). Hypoalbuminemia patients also had 625% greater odds for developing major complications during the 30-day postoperative period (odds ratio = 7.25; 95% confidence interval: 1.91–27.49).Conclusion Malnutrition significantly affected outcomes and complications of distal radius ORIF. This study highlights the importance of prevention and treatment of malnutrition in the setting of fragility fractures.

INTRODUCTION Outcomes after anterior cervical diskectomy and fusion (ACDF) and cervical total disk arthroplasty (TDA) are satisfactory, but related morbidity and revision surgery rates are notable. This study sought to determine complication variations among ACDF, TDA, and combined ACDF-TDA as well as predictors of postoperative complications. METHODS Patients undergoing 1- to 2-level ACDF and/or TDA with at least a 2-year follow-up from 2009 to 2011 were identified from the Statewide Planning and Research Cooperative System database. Patient demographics, hospital-related parameters, mortality, and postoperative outcomes were compared, and their predictors were identified using multivariate logistic regression. RESULTS A total of 16,510 and 449 individuals underwent ACDF and cervical TDA, respectively, and 201 underwent ACDF-TDA. ACDF-TDA patients had the highest rates of cardiac complications and pulmonary embolism (PE) (P ≤ 0.006), whereas TDA patients had higher individual surgical and device/implant/internal fixation complications (P ≤ 0.025). ACDF-TDA patients experienced the lowest rate of revisions. Cervical TDA increased the odds of any surgical complications (OR = 2.5, P = 0.002), overall complications (OR = 1.57, P = 0.034), and revisions (OR = 2.29, P < 0.001). Deyo index predicted any medical/surgical complications (OR = 1.43 and 1.19, respectively). Female sex was associated with increased odds of readmission (OR 1.30, P < 0.001) but was protective against medical complications (OR = 0.81, P = 0.013). DISCUSSION Combined ACDF-TDA procedures were not associated with increases in 2-year individual or overall complications, readmissions, or revisions. LEVEL OF EVIDENCE Level 3-Therapeutic study.

Objectives Elbow flexion loss is a debilitating upper extremity injury. Surgical treatment options include nonfree muscle transfers (tendon transfers, nerve transfers, Steindler procedure, Oberlin transfers, and pedicled muscle transfers) or free muscle transfers. We sought to determine if free muscle transfers and nonfree muscle transfers have similar outcomes for elbow flexion reanimation. Materials and Methods A literature search for studies evaluating free and nonfree muscle transfers for elbow flexion reanimation was performed. Included studies reported on transfer failure (strength Results Six studies were included (n = 331 patients). Free muscle patients experienced lower failure rates than nonfree muscle patients. There was no significant difference in ROM. A nonsignificant trend toward better mean strength and DASH scores among free muscle patients was observed. Conclusion Free muscle transfers may be superior to nonfree muscle transfers for elbow flexion reanimation, given their lower failure rates. Well-powered future studies may reveal differences in strength and DASH scores between free and nonfree muscle transfers.

Acute appendicitis is one of the most common emergency surgical procedure, yet atypical presentation sometimes can be challenging for clinician. I present a case of 19-year-old gentleman that initially presented with 1day history of bilateral testicular pain and lower abdominal pain. His past history includes a positive sexual history. Initial ultrasound of the testis showed bilateral orchitis and an equivocal appendix. With a significantly raised inflammatory marker and highly suspicious for appendicitis, a CT scan was obtained which showed perforated appendicitis and the patient underwent laparoscopic appendicectomy with resolution of symptoms after that. We encourage clinician to be aware of this clinical pitfall as patient can sometimes be managed in other department to minimise any delayed diagnosis or any unnecessary procedure

PURPOSE Patients with metastatic urothelial carcinoma are often ineligible for cisplatin-based treatments. A National Cancer Institute Cancer Therapy Evaluation Program–sponsored trial assessed the tolerability and efficacy of a gemcitabine-eribulin combination in this population. METHODS Patients with treatment-naïve advanced or recurrent metastatic urothelial carcinoma of the bladder, ureter, or urethra not amenable to curative surgery and not candidates for cisplatin-based therapy were eligible. Cisplatin ineligibility was defined as creatinine clearance less than 60 mL/min (but ≥ 30 mL/min), grade 2 neuropathy, or grade 2 hearing loss. Treatment was gemcitabine 1,000 mg/m2 intravenously followed by eribulin 1.4 mg/m2, both on days 1 and 8, repeated in 21-day cycles until progression or unacceptable toxicity. A Simon two-stage phase II trial design was used to distinguish between Response Evaluation Criteria in Solid Tumors, version 1.1 objective response rates of 20% versus 50%. RESULTS Between June 2015 and March 2017, 24 eligible patients with a median age of 73 years (range, 62 to 88 years) underwent therapy. Performance status of 0, 1, or 2 was seen in 11, 11, and two patients, respectively. Sites of disease included: lymph nodes, 16; lungs, nine; liver, seven; bladder, five; bones, two. Median number of cycles received was four (range, one to 16). Of 24 patients, 12 were confirmed responders; the observed objective response rate was 50% (95% CI, 29% to 71%). Median overall survival was 11.9 months (95% CI, 5.6 to 20.4 months), and median progression-free survival was 5.3 months (95% CI, 4.5 to 6.7 months). The most common treatment-related any-grade toxicities were fatigue (83% of patients), neutropenia (79%), anemia (63%), alopecia (50%), elevated AST (50%), and constipation, nausea, and thrombocytopenia (42% each). CONCLUSION Gemcitabine-eribulin treatment response and survival for cisplatin-ineligible patients compare favorably to other regimens. Additional research is needed.

Gonorrhea remains a major public health challenge, and current recommendations for gonorrhea treatment are threatened by evolving antimicrobial resistance and a diminished pipeline for new antibiotics. Evaluations of potential new treatments for gonorrhea currently make limited use of new understanding of the pharmacokinetic and pharmacodynamic contributors to effective therapy, the prevention of antimicrobial resistance, and newer designs for clinical trials. They are hampered by the requirement to utilize combination ceftriaxone/azithromycin therapy as the comparator regimen in noninferiority trials designed to seek an indication for gonorrhea therapy. Evolving gonococcal epidemiology and clinical trial design constraints hinder the enrollment of those populations at the greatest risk for gonorrhea (adolescents, women, and persons infected with antibiotic-resistant Neisseria gonorrhoeae). This article summarizes a recent meeting on the evaluation process for antimicrobials for urogenital gonorrhea treatment and encourages the consideration of new designs for the evaluation of gonorrhea therapy.

PURPOSE: The reported maximum tolerated dose (MTD) of single agent belinostat is 1000 mg/m(2) given days 1-5, every 21 days. Pre-clinical evidence suggests histone deacetylase inhibitors enhance retinoic acid signaling in a variety of solid tumors. We conducted a phase I study of belinostat combined with 50-100 mg/m(2)/day 13-cis-retinoic acid (13-cRA) in patients with advanced solid tumors. METHODS: Belinostat was administered days 1-5 and 13-cRA days 1-14, every 21 days. Dose limiting toxicity (DLT) was defined as cycle 1 hematologic toxicity grade ≥3 not resolving to grade ≤1 within 1 week or non-hematologic toxicity grade ≥3 (except controlled nausea and vomiting and transient liver function abnormalities) attributable to belinostat. RESULTS: Among 51 patients, two DLTs were observed: grade 3 hypersensitivity with dizziness and hypoxia at 1700 mg/m(2)/day belinostat with 100 mg/m(2)/day 13-cRA, and grade 3 allergic reaction at 2000 mg/m(2)/day belinostat with 100 mg/m(2)/day 13-cRA. The MTD was not reached. Pharmacokinetics of belinostat may be non-linear at high doses. Ten patients had stable disease, including one with neuroendocrine pancreatic cancer for 56 cycles, one with breast cancer for 12 cycles, and one with lung cancer for 8 cycles. Partial responses included a patient with keratinizing squamous cell carcinoma of the tonsils, and a patient with lung cancer. CONCLUSIONS: The combination of belinostat 2000 mg/m(2) days 1-5 and 13-cRA 100 mg/m(2) days 1-14, every 21 days, was well-tolerated and an MTD was not reached despite doubling the established single agent MTD of belinostat.

Varicella zoster and herpes zoster are infections caused by the highly contagious varicella-zoster virus (VZV). Despite widespread availability of vaccines against VZV, as well as varicella vaccination rates >95%, VZV remains a public health concern because of several common myths and misconceptions. Because of the success of routine varicella vaccination programs, some people mistakenly believe that varicella and herpes zoster are now no longer a threat to public health. Another common misconception is that shingles is less infectious than varicella; however, clinical evidence indicates otherwise. Several knowledge gaps exist around VZV transmission and the availability and use of varicella zoster immune globulin (human) for postexposure prophylaxis against VZV. To help reduce the incidence of severe disease in high-risk individuals (eg, elderly people, pregnant women, unvaccinated persons, infants, and immunocompromised children and adults), this article addresses misbeliefs and broadens awareness of VZV exposure, infection risks, complications, and treatments.

Introduction:This study sought to determine the effect that malnutrition, defined as hypoalbuminemia, has on hip fracture patients treated with total hip arthroplasty (THA). Specifically, we evaluated: (1) demographics and perioperative data; (2) postoperative complications; and (3) re-operation rates.Methods:The National Surgical Quality Improvement Program database was utilised to identify hip fracture patients who underwent THA from 2008 to 2015. Propensity scores were calculated for the likelihood of having a preoperative albumin measurement. Hip fracture patients who underwent THA and had preoperative hypoalbuminemia (Results:Compared to controls, hypoalbuminemia patients were older (p = 0.006), more likely male ( p = 0.024), had higher Charlson/Deyo scores ( p = 0.0001), more likely smokers ( p < 0.0001), more likely functionally dependent ( p < 0.0001), had ASA scores ⩾3 ( p < 0.0001) and had longer LOS ( p < 0.0001). Compared to controls, hypoalbuminemia patients had 80% higher risk for any complication (OR = 1.80; 95% CI, 1.43–2.26), 113% higher risk for major complications (OR = 2.13; 95% CI, 1.31–3.48), and 79% higher risk for minor complications (OR = 1.79; 95% CI, 1.42–2.26), and 97% increased risk for re-operation (OR = 1.97; 95% CI, 1.20–3.23).Conclusions:The findings in the present study indicate the need to develop better pre- and postoperative medical and nutritional care for malnourished hip fracture patients who undergo THA in order to potentially mitigate their increased risk.

Background: Emerging data suggest that some patients with TNBC could benefit from the addition of immune-based therapy. This observation is in part due to the significant association between distinct tumor-infiltrating lymphocytes (TILs) and prognosis in TNBC. Efforts to comprehensively characterize the immune microenvironment of TNBCs are critically important to gain a better understanding of the immune landscape and how it influences response to both standard chemotherapy and immunotherapy. We previously assessed both stromal TILs (sTILs) and intraepithelial TILs (iTILs) from pre-treatment tumor samples from patients enrolled on a phase II study of neoadjuvant gemcitabine, carboplatin and iniparib (PrECOG 0105; NCT00813956). We found that both iTILS and sTILS significantly associated with pathologic response. Furthermore, we assessed a novel 'in silico flow cytometry' gene expression-based method, CIBERSORT, designed to assess overall immune content and deconvolute the relative levels of distinct leukocyte subsets in tumors. Specific leukocyte subsets significantly associated with pCR included activated memory CD4+ T cells, CD8+ T cells and M1 macrophages (all p Methods: We performed SPARTA - Spatial Perception And Regional Tumor Analysis - a multiplexed immunohistochemistry-based technology with data visualization and analysis modules that is designed to capture clinically relevant information about the tumor microenvironment in 72 pre-treatment FFPE tumor sections from patients enrolled on PrECOG 0105. SPARTA was used to test and analyze the coordinated expression of PD-L1, PD-1, CD45RO, CD4, CD8 and HLA-DRA in the study cohort from whole slide scanned images. Pathologic response at the time of surgery was evaluated using the residual cancer burden index. Germline BRCA1 and BRCA2 status was known for all patients. Results: Of 72 samples, 67 were evaluable for SPARTA analysis. Within a subset of tumors separately profiled by both SPARTA (FFPE/IHC microscopy) and CIBERSORT (Frozen/RNA GEP), we found significant correlation for clinically relevant TIL subpopulations, including for CD8+ T cells (r=0.83, p Conclusions: Spatial mapping of the immune microenvironment in primary TNBC reveals distinct immune cell populations associated with response to neoadjuvant platinum-based therapy. Citation Format: Telli ML, Vinayak S, Khododoust MS, Gruber JJ, Ford JM, Sanchez P, Banayan N, Azimi S, Tumeh PC, Newman AM, Alizadeh AA. Spatial mapping of the immune microenvironment in primary triple-negative breast cancer (TNBC) and association with neoadjuvant therapy response [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD5-12.

The purpose of this meta-analysis was to assess the evidence supporting the use of cementless versus cemented total knee arthroplasties (TKAs). Specifically, we evaluated (1) all-cause survivorship, (2) aseptic survivorship, and (3) functional outcomes (Knee Society Scores [KSS], Oxford Knee Scores, Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] scores, and ranges of motion [ROMs]). A literature search was performed for studies that evaluated cementless versus cemented TKAs published between 2000 and 2017. Selected studies included three randomized controlled trials, three retrospective observational studies, and one prospective observational study that met the following criteria: (1) primary TKAs, (2) compared cementless and cemented TKAs, (3) implant survivorship that described the causes of failure, and (4) at least one functional outcome. To compare the two cohorts, pooled odds ratios (OR) and 95% confidence intervals (95% CI) were used to calculate tibial and femoral implant survivorship, and pooled mean differences (MD) and 95% CI calculated the functional scores and ROMs. Based on pooled data from the few number of studies, cementless TKAs had a better all-cause survivorship (OR = 0.37; 95% CI, 0.15–0.92) and tended to have a better aseptic survivorship (OR = 0.44; 95% CI, 0.17–1.14). However, this is likely due to the 83.3% weight of the single cementless study potentially influencing the analysis. There were no differences in terms of KSS knee (MD = 1.03; 95% CI, −1.13–3.20) or function scores (MD = 5.36; 95% CI, –3.75–14.51), Oxford knee scores (MD = 0.36; 95% CI, –3.84–4.56), or WOMAC scores (MD = 0.62; 95% CI, –0.87–2.11). Moreover, there was no difference in ROMs (MD = 1.47; 95% CI, –0.11–3.05). Cementless TKA had a better all-cause survivorship when compared with cemented fixation, and similar functional outcomes were demonstrated. However, these findings are based on only a few number of studies (n = 7). Therefore, additional prospective, randomized control trials need to be performed to best compare cementless versus cemented outcomes.

BackgroundFemale youth ice hockey players are an understudied population. This study documented injury types, rates and mechanisms for female youth ice hockey players reporting to US emergency departments to inform safety measures and sideline medical preparedness.MethodsThe National Electronic Injury Surveillance System (NEISS) database was queried for all ice hockey injuries (product code 1279) from January 1, 2002 to December 31, 2019. Cases involving players over the age of 18 years and males were excluded. Incidence rate ratios (IRR) were calculated using OpenEpi and compared between age divisions. Spearman's rank correlation was utilized to evaluate the correlation between age and injury incidence. USA Hockey membership statistics were used to establish the population at risk and calculate incidence rates (IR).ResultsAn estimated 20,384 ice hockey injuries presented to participating United States emergency departments. The number of female youth ice hockey players increased significantly from 36,258 in 2002 to 65,072 in 2019 (p

Background The WHO Surgical Safety Checklist has been shown to reduce perioperative morbidity and mortality worldwide. There is evidence to suggest that sign-out is the most poorly performed phase of the checklist as it coincides with a period of high workload for team members. This study aimed to see whether modification of this process might result in greater compliance. Methods A controlled longitudinal (before and after) study was performed to evaluate the effect of a modified checklist sign-out on compliance in a single surgical department. Checklist quality was evaluated by measurement of checklist completion, active participation, and team member presence. Workload assessment was performed to identify the optimal moment for the sign-out process. The sign-out process was modified through an iterative multidisciplinary approach, informed by results from the workload assessment. Feedback was obtained through staff surveys. Results A total of 185 operations were used, with an intervention group in vascular surgery and a control group in orthopaedics. The optimal timing for sign-out was identified as after final wound closure. The modified sign-out process improved active participation of team members (21 of 34 versus 31 of 34; P = 0.010). In the control group, complete compliance improved (48 of 76 versus 30 of 41; P = 0.041). However, active participation decreased (53 of 76 versus 19 of 41; P = 0.022). No differences were noted between groups in team member presence. Eighteen of 21 staff questioned viewed the modifications positively. Conclusion The optimal sign-out timing was identified as immediately after final wound closure prior to undraping the patient., In an analysis using a workload-based approach, it was found that the optimal WHO checklist sign-out timing was immediately after final wound closure. This finding was used to reiteratively modify the WHO checklist sign-out process, leading to improved active participation between team members.

The COVID-19 pandemic has prompted widespread primary and secondary school closures. Routine testing of asymptomatic students and staff, as part of a comprehensive program, can help schools open safely. “Pooling-in-a-pod” is a public health surveillance strategy whereby testing cohorts are composed based on social relationships and physical proximity. Pooling-in-a-pod allowed for weekly on-site point-of-care testing of all staff and students at an independent preschool to grade 12 school in Washington, D.C. Staff and older students self-collected anterior nares samples, and trained staff collected samples from younger students. Overall, 6,746 samples were tested for 815 students and 276 staff between November 30, 2020, and March 3, 2021. The average pool size was 7.3 people. Sample collection to pool result time averaged 40 minutes. The direct testing cost per person per week was $24.77, including swabs. One surveillance test pool was positive. During the study period, daily new cases in Washington, D.C., ranged from 24 – 46 per 100,000 population. A post-launch survey found most parents (90.3%), students (93.4%), and staff (98.8%) were willing to participate in pooled testing with confirmatory tests for positive pool members. The school reported a 32.6% decrease in virtual learning after initiation of the program. Pooling-in-a-pod is feasible, cost-effective, and an acceptable COVID-19 surveillance strategy for schools. School officials and policymakers can leverage this strategy to facilitate safe, sustainable, in-person schooling. SUMMARY 1) What is the current understanding of this subject? Routine COVID-19 testing as part of a comprehensive strategy to operate schools safely is currently not widely implemented. 2) What does this report add to the literature? “Pooling-in-a-pod,” is a public health surveillance strategy whereby cohorts are composed based on social relationships and physical proximity. 6,746 samples were tested in 969 pools (average pool size 7.3 people) in a Washington, D.C. school, thereby requiring fewer test kits and less expense. The program was widely acceptable. 3) What are the implications for public health practice? Pooling-in-a-pod allows for more accessible testing to facilitate safe in-person schooling and minimize the negative effects of distance learning.

Children with B-cell non-Hodgkin lymphoma (B-NHL) have an excellent chance of survival, however, current clinical risk stratification places as many as half of patients in a high-risk group receiving very intensive chemo-immunotherapy. TP53 alterations are associated with adverse outcome in many malignancies; however, whilst common in paediatric B-NHL, their utility as a risk classifier is unknown. We evaluated the clinical significance of TP53 abnormalities (mutations, deletion and/or copy number neutral loss of heterozygosity) in a large UK paediatric B-NHL cohort and determined their impact on survival. TP53 abnormalities were present in 54.7% of cases and were independently associated with a significantly inferior survival compared to those without a TP53 abnormality (PFS 70.0% vs 100%, p p = 0.002). Moreover, amongst patients clinically defined as high-risk (stage III with high LDH or stage IV), those without a TP53 abnormality have superior survival compared to those with TP53 abnormalities (PFS 100% vs 55.6%, p = 0.005, OS 100% vs 66.7%, p = 0.019). Biallelic TP53 abnormalities were either maintained from the presentation or acquired at progression in all paired diagnosis/progression Burkitt lymphoma cases. TP53 abnormalities thus define clinical risk groups within paediatric B-NHL and offer a novel molecular risk stratifier, allowing more personalised treatment protocols.

We present 4 pediatric patients with trisomy 21 (T21) and associated comorbidities who developed coronavirus disease 2019 requiring hospitalization. A review of the literature revealed that comorbidities associated with T21 may predispose patients to severe disease. Children with T21 should be considered high risk and monitored carefully if infected with severe acute respiratory syndrome coronavirus 2.

Introduction: Understanding the development of psychological symptoms post-arrest is a major research gap. In qualitative studies, cardiac arrest survivors report being poorly equipped to face the numerous sequelae upon returning home, which could in turn exacerbate acute psychological symptoms from the initial cardiac arrest event. In this study, we examined associations between illness perceptions (i.e. cognitive and emotional appraisals of illness and recovery), readiness for discharge, and provider-patient communication with psychological symptoms in cardiac arrest survivors with good neurologic recovery. Methods: We distributed an online survey to cardiac arrest survivors who were members of the Sudden Cardiac Arrest Foundation. Survivors completed the Brief Illness Perception Questionnaire (B-IPQ), Readiness for Hospital Discharge Scale (RHDS), Questionnaire for the Quality of Provider-Patient Interactions (QQPPI), PTSD Checklist-5 (PCL-5), and Patient Health Questionnaire-4 (PHQ-4) which has anxiety and depression subscales. Three multiple regression models examined associations between B-IPQ, RHDS, and QQPPI scores with PCL-5 and PHQ-4 anxiety and depression sores, adjusted for age, sex, time since arrest, self-reported understanding of cardiac arrest and post-arrest symptoms at discharge, self-reported memory at discharge, functional status via the Lawton Instrumental Activities of Daily Living scale, pre-arrest Charlson Comorbidity Index, and income. Results: We obtained full data from 163 survivors (mean age: 50.1 years, 50.3% women, 95.5% white, mean time since arrest: 63.9 months). More threatening illness perceptions (β: .57, p < .01) and lower readiness for discharge (β: -.22, p = .01) were associated with greater posttraumatic stress symptoms. More threatening illness perceptions was associated with greater anxiety (β: .53, p < .01) and depression (β: .5, p < .01) symptoms. Conclusions: Illness perceptions and readiness for discharge were associated with psychological symptoms in cardiac arrest survivors. Future studies should examine the feasibility of in-hospital assessment of survivors’ illness perceptions, readiness for discharge, and psychological symptoms.

Background Cytomegalovirus (CMV) is a significant source of morbidity and mortality among transplant recipients; the epidemiology is less understood in pediatric hematopoietic cell transplantation (HCT) cohorts. Furthermore, there is a paucity of data related to CMV prophylactic and preemptive strategies. Methods A single-center retrospective observational cohort of allogeneic HCT recipients at the Children’s Hospital of Philadelphia January 1, 2004–December 31, 2017 was constructed. Subjects were followed for 180 days after transplant to determine whether they had CMV infection or disease. Data on antiviral therapy were collected as were outcomes of CMV disease and adverse events (AEs) related to the antiviral therapy. Results Between January 2004 and March 2017, 345 allogeneic HCTs in 333 patients undergoing CMV surveillance testing were identified. CMV DNAemia was detected during the 180-day follow-up in 89 (25.8%) HCTs. CMV recipient-positive transplants were most likely to have CMV infection (47%). Infection rates were high for those receiving a CMV-specific prophylaxis regimen (50%). CMV DNAemia progressed to CMV disease 11.2% of the time. Of 224 subjects receiving CMV-specific prophylaxis, 19.2% experienced ≥1 AE. Of 53 receiving preemptive therapy during any CMV DNAemia episode, 32.1% experienced ≥1 AE. Conclusions CMV infection is common in pediatric allogeneic HCT recipients. The CMV-specific prophylaxis regimen employed in this cohort did not effectively prevent DNAemia, progression to CMV disease was uncommon, and AEs from prophylaxis and preemptive therapy were frequent. Novel approaches that reduce the impact of CMV on pediatric allogeneic HCT recipients are needed.

Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified the typical pregnancy outcomes of congenital ZIKV infection, with fetal demise and placental abnormalities. We estimated sample sizes needed to define differences between groups and demonstrated that future studies quantifying brain region volumes, retinal structure, hearing, and visual pathway function require a sample size of 14 animals per group (14 ZIKV, 14 control) to detect statistically significant differences in at least half of the infant exam parameters. Establishing the parameters for future studies of neurodevelopmental outcomes following congenital ZIKV exposure in macaques is essential for robust and rigorous experimental design.

Fungal spondylodiscitis is rare (0.5%–1.6% of spondylodiscitis) and mainly caused by Candida albicans. Surgical intervention in spondylodiscitis patients is indicated for compression of neural elements, spinal instability, severe kyphosis, failure of conservative management and intractable pain. However, there is no evidence-based optimal surgical approach for spondylodiscitis. There have been only case reports of surgical treatment for Candida spondylodiscitis. We evaluated the preliminary results of the efficacy and safety of one-stage debridement via oblique lateral corridor with interbody fusion (OLIF) using stand-alone cement reconstruction after debridement for the treatment of Candida spondylodiscitis in patients with major co-morbidities. Five patients (4 males, 1 female, mean age: 64.2 years) suffering from Candida albicans lumbar spondylodiscitis who underwent this procedure were studied. Their predominant symptoms were unremitting back and leg pain and all had pre and postoperative anti-fungal therapy under microbiologist supervision. The operative time ranged from 137 minutes to 260 minutes (mean: 213.4 minutes). The mean blood loss was 160 mL (range: 100–200 mL). There were no perioperative complications. At follow-up all showed major improvement in pain and ambulatory status. CT scan showed radiological stability for all patients at 6–12 months. Our preliminary results showed stand-alone anterior debridement and spinal re-construction with cement through mini-open OLIF approach might be a safe and effective option for patients with spinal fungal infection and major comorbidities.

While receiving treatment for COVID-19, Mr G, age 56, experiences an acute psychotic episode He has no known psychiatric history What could be causing his symptoms? © 2020 Quadrant Healthcom Inc All rights reserved

The purpose of this study was to compare the: 1) RVUs; 2) lengths-of-surgery; 3) RVU per minute between revision hip (THA) and knee (TKA) arthroplasties; and 4) perform an annualized surgeon cost analysis. Using the ACS-NSQIP from 2008 to 2015, 8081 revision TKAs, 7233 THAs were compared. Revision THA had greater mean RVUs (30.27 vs. 27.10 RVUs, p

ObjectivesThere is emerging interest and data supporting the effectiveness of community health workers (CHWs) in non-communicable diseases (NCDs) in low/middle-income countries (LMICs). This study aimed to determine whether a CHW-led intervention targeting diabetes and hypertension could improve markers of clinical disease control in rural Mexico.Design and settingA prospective observational stepped-wedge study was conducted across seven communities in rural Chiapas, Mexico from March 2014 to April 2018.Participants149 adults with hypertension and/or diabetes.InterventionThis study was conducted in the context of the programmatic roll-out of an accompaniment-based CHW-led intervention designed to complement comprehensive primary care for adults with diabetes and/or hypertension. Implementation occurred sequentially at 3-month intervals with point-of-care data collected at baseline and every 3 months thereafter for 12 months following roll-out in all communities.Outcome measuresPrimary outcomes were glycated haemoglobin (HbA1c) and systolic blood pressure (SBP), overall and stratified by baseline disease control. We conducted an individual-level analysis using mixed effects regression, adjusting for time, cohort and clustering at the individual and community levels.ResultsAmong patients with diabetes, the CHW-led intervention was associated with a decrease in HbA1c of 0.35%; however, CIs were wide (95% CI −0.90% to 0.20%). In patients with hypertension, there was a 4.7 mm Hg decrease in SBP (95% CI −8.9 to −0.6). In diabetic patients with HbA1c ≥9%, HbA1c decreased by 0.96% (95% CI −1.69% to −0.23%), and in patients with uncontrolled hypertension, SBP decreased by 10.2 mm Hg (95% CI −17.7 to −2.8).ConclusionsWe found that a CHW-led intervention resulted in clinically meaningful improvement in disease markers for patients with diabetes and hypertension, most apparent among patients with hypertension and patients with uncontrolled disease at baseline. These findings suggest that CHWs can play a valuable role in supporting NCD management in LMICs.Trial registration numberNCT02549495.

Summary The trial compared three physiotherapy approaches: manual or exercise therapy compared with a single session of physiotherapy education (SSPT) for people with osteoporotic vertebral fracture(s). At 1 year, there were no statistically significant differences between the groups meaning there is inadequate evidence to support manual or exercise therapy. Introduction To evaluate the clinical and cost-effectiveness of different physiotherapy approaches for people with osteoporotic vertebral fracture(s) (OVF). Methods >Prospective, multicentre, adaptive, three-arm randomised controlled trial. Six hundred fifteen adults with back pain, osteoporosis, and at least 1 OVF participated. Interventions: 7 individual physiotherapy sessions over 12 weeks focused on either manual therapy or home exercise compared with a single session of physiotherapy education (SSPT). The co-primary outcomes were quality of life and back muscle endurance measured by the QUALEFFO-41 and timed loaded standing (TLS) test at 12 months. Results At 12 months, there were no statistically significant differences between groups. Mean QUALEFFO-41: − 1.3 (exercise), − 0.15 (manual), and − 1.2 (SSPT), a mean difference of − 0.2 (95% CI, − 3.2 to 1.6) for exercise and 1.3 (95% CI, − 1.8 to 2.9) for manual therapy. Mean TLS: 9.8 s (exercise), 13.6 s (manual), and 4.2 s (SSPT), a mean increase of 5.8 s (95% CI, − 4.8 to 20.5) for exercise and 9.7 s (95% CI, 0.1 to 24.9) for manual therapy. Exercise provided more quality-adjusted life years than SSPT but was more expensive. At 4 months, significant changes above SSPT occurred in endurance and balance in manual therapy, and in endurance for those ≤ 70 years, in balance, mobility, and walking in exercise. Conclusions Adherence was problematic. Benefits at 4 months did not persist and at 12 months, we found no significant differences between treatments. There is inadequate evidence a short physiotherapy intervention of either manual therapy or home exercise provides long-term benefits, but arguably short-term benefits are valuable. Trial registration ISRCTN 49117867.

TB of the knee is often associated with marked morbidity because of its late and non-specific presentation. The use of TKA (total knee arthroplasty) in the face of a previous tuberculous knee infection has been criticized with multiple controversies. Therefore, the purpose of this review is to assess: (1) clinical outcomes, (2) radiographic outcomes, and (3) complications of TKA in the face of a previous healed TB infection. Our analysis has demonstrated that previous TB infection of the knee joint does not preclude TKA if indicated and suggests placing patients who have ESR or CRP results out of normal range on pre-operative anti-TB prophylactic antibiotic for a minimum of 2 weeks. In case of local recurrence following TKA, antibiotic therapy alone can be an effective treatment option.We examined reported outcomes of performing TKA in patients with previous TB infection of the knee. Different strategies recommended by different authors to maximize the success of TKA in this situation are also discussed.TKA has been proven to be effective in patients who are status post tuberculous arthritis when thoughtful patient selection and peri-operative planning is conducted. Tuberculosis continues to have a rising incidence and increasing spread of multi-drug resistant strains.