Search

Objectives In 2012, onetime hepatitis C virus (HCV) screening was recommended for all baby boomers (people born during 1945-1965) in the United States, but only 4.0%-12.9% of baby boomers have ever had a screening ordered by a health care provider. This study examined the HCV screening prevalence among adult patients in a large academic health care system and assessed factors associated with the completion of screening when ordered for baby boomers. Methods We defined HCV screening completion as the completion of an HCV antibody test when it was ordered. We used electronic health records to examine HCV screening completion rates among adults (N = 106 630) from August 1, 2015, through July 31, 2020, by birth cohort. Among baby boomers whose health care provider ordered HCV screening, we examined frequency and percentages of HCV screening completion by sociodemographic and clinical characteristics. We conducted univariate and multivariable logistic regression analyses to assess factors associated with HCV screening completion among baby boomers. Results During the study period, 73.0% of baby boomers completed HCV screening when it was ordered. HCV completion did not differ by sex or race and ethnicity among baby boomers. Baby boomers with Medicare supplemental health insurance compared with commercial health insurance (adjusted odds ratio [aOR] = 1.87) and those seeing only advanced practice professionals compared with specialty care physicians (aOR = 2.24) were more likely to complete HCV screening when it was ordered. Conclusions Noncompletion of HCV screening is one of many barriers along the HCV treatment continuum. Our findings suggest a need for interventions targeting systems, health care providers, and patients to increase HCV screening rates in the United States.

Objectives Chronic hepatitis C virus (HCV) infection is one of the main causes of hepatocellular carcinoma. Before initiating a multilevel HCV screening intervention, we sought to (1) describe concordance between the electronic health record (EHR) data warehouse and manual medical record review in recording aspects of HCV testing and treatment and (2) estimate the percentage of patients with chronic HCV infection who initiated and completed HCV treatment using manual medical record review. Methods We examined the medical records for 177 patients (100 randomly selected patients born during 1945-1965 without evidence of HCV testing and 77 adult patients of any birth cohort who had completed HCV testing) with a primary care or relevant specialist visit at an academic health care system in Tampa, Florida, from 2015 through 2018. We used the Cohen κ coefficient to examine the degree of concordance between the searchable data warehouse and the medical record review abstractions. Descriptive statistics characterized referral to and receipt of treatment among patients with chronic HCV infection from medical record review. Results We found generally good concordance between the data warehouse abstraction and medical record review for HCV testing data (κ ranged from 0.66 to 0.87). However, the data warehouse failed to capture data on HCV treatment variables. According to medical record review, 28 patients had chronic HCV infection; 16 patients were prescribed treatment, 14 initiated treatment, and 9 achieved and had a reported posttreatment undetected HCV viral load. Conclusions Using data warehouse data provides generally reliable HCV testing information. However, without the use of natural language processing and purposeful EHR design, manual medical record reviews will likely be required to characterize treatment initiation and completion.

Summary Background The quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in a randomised, placebo-controlled study in men aged 16–26 years. We assessed the incidences of external genital warts related to HPV6 or 11, and external genital lesions and anal dysplasia related to HPV6, 11, 16, or 18, over 10 years of follow-up. Methods The 3-year base study was an international, multicentre, double-blind, randomised, placebo-controlled trial done at 71 sites in 18 countries. Eligible participants were heterosexual men (aged 16–23 years) or men who have sex with men (MSM; aged 16–26 years). Men who had clinically detectable anogenital warts or genital lesions at screening that were suggestive of infection with non-HPV sexually transmitted diseases, or who had a history of such findings, were excluded. Eligible participants were randomly assigned (1:1) to receive three doses of either quadrivalent HPV vaccine or placebo on day 1, month 2, and month 6, administered as a 0·5-mL injection into the deltoid muscle. The 7-year, open-label, long-term follow-up extension study was done at 46 centres in 16 countries. Participants who received one or more doses of the quadrivalent HPV vaccine in the base study were eligible for enrolment into the long-term follow-up study (early vaccination group). Placebo recipients were offered the three-dose quadrivalent HPV vaccine at the end of the base study; those who received one or more quadrivalent HPV vaccine doses were eligible for enrolment into the long-term follow-up study (catch-up vaccination group). The primary efficacy endpoints were the incidence of external genital warts related to HPV6 or 11 and the incidence of external genital lesions related to HPV6, 11, 16, or 18 in all participants and the incidence of anal intraepithelial neoplasia (including anal warts and flat lesions) or anal cancer related to HPV6, 11, 16, or 18 in MSM only. The primary efficacy analysis was done in the per-protocol population for the early vaccination group, which included participants who received all three vaccine doses, were seronegative at day 1 and PCR-negative from day 1 through month 7 of the base study for the HPV type being analysed, had no protocol violations that could affect evaluation of vaccine efficacy, and had attended at least one visit during the long-term follow-up study. For the catch-up vaccination group, efficacy was assessed in the modified intention-to-treat population, which included participants who had received at least one vaccine dose, were seronegative and PCR-negative for HPV types analysed from day 1 of the base study to the final follow-up visit before receiving the quadrivalent HPV vaccine, and had at least one long-term follow-up visit. Safety was assessed in all randomised participants who received at least one vaccine dose. This study is registered with ClinicalTrials.gov , NCT00090285 . Findings Between Aug 10, 2010, and April 3, 2017, 1803 participants were enrolled in the long-term follow-up study, of whom 936 (827 heterosexual men and 109 MSM) were included in the early vaccination group and 867 (739 heterosexual men and 128 MSM) were included in the catch-up vaccination group. Participants in the early vaccination group were followed up for a median of 9·5 years (range 0·1–11·5) after receiving the third dose of the quadrivalent HPV vaccine, and participants in the catch-up vaccination group were followed up for a median of 4·7 years (0·0–6·6) after receiving the third dose. In early vaccine group participants during long-term follow-up compared with the placebo group in the base study, the incidence per 10 000 person-years of external genital warts related to HPV6 or 11 was 0·0 (95% CI 0·0–8·7) versus 137·3 (83·9–212·1), of external genital lesions related to HPV6, 11, 16, or 18 was 0·0 (0·0–7·7) versus 140·4 (89·0–210·7), and of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 in MSM only was 20·5 (0·5–114·4) versus 906·2 (553·5–1399·5). Compared with during the base study (ie, before quadrivalent HPV vaccine administration), during the long-term follow-up period, participants in the catch-up vaccination group had no new reported cases of external genital warts related to HPV6 or 11 (149·6 cases per 10 000 person-years [95% CI 101·6–212·3] vs 0 cases per 10 000 person-years [0·0–13·5]) or external genital lesions related to HPV6, 11, 16, or 18 (155·1 cases per 10 000 person-years [108·0–215·7] vs 0 cases per 10 000 person-years [0·0–10·2]), and a lower incidence of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 (886·0 cases per 10 000 person-years [583·9–1289·1] vs 101·3 cases per 10 000 person-years [32·9–236·3]). No vaccine-related serious adverse events were reported. Interpretation The quadrivalent HPV vaccine provides durable protection against anogenital disease related to HPV6, 11, 16, and 18. The results support quadrivalent HPV vaccination in men, including catch-up vaccination. Funding Merck Sharp & Dohme.

A 1.5-year-old, female-spayed mix breed dog was presented with recurrent episodes of shaking and excessive panting attributed to drug-refractory ventricular arrhythmia (VA) characterized predominantly by incessant periods of ventricular bigeminy. The VA had a narrow QRS morphology, suggestive of an origin near the His-bundle or fascicular system. Diagnostic evaluation found no structural heart disease or underlying etiology. Three-dimensional electroanatomic mapping and radiofrequency catheter ablation were pursued. Voltage mapping demonstrated normal bi-ventricular voltage (≥1.5 mV) without any fractionated or multi-component electrograms, indicating absence of ventricular myocardial scar. Pace mapping identified an endocardial origin of the VA at the basal anterior-septum of the left ventricle, distal to the His-bundle and near the left bundle branch. Two ablation lesions were delivered to this site, and a left bundle branch block was temporarily induced. The dog recovered uneventfully. One month later, the owners reported a remarkable improvement in clinical signs and follow up 48-hour Holter monitor found complete resolution of VA.

Summary Background Young survivors of cancer are at increased risk for cancers that are related to human papillomavirus (HPV), primarily caused by oncogenic HPV types 16 and 18. We aimed to examine the immunogenicity and safety of the three-dose series of HPV vaccine in young survivors of cancer. Methods We conducted an investigator-initiated, phase 2, single-arm, open-label, non-inferiority trial at five National Cancer Institute-designated comprehensive cancer centres in the USA. Eligible participants were survivors of cancer who were HPV vaccine-naive, were aged 9–26 years, in remission, and had completed cancer therapy between 1 and 5 years previously. Participants received three intramuscular doses of either quadrivalent HPV vaccine (HPV4; enrolments on or before March 1, 2016) or nonavalent HPV vaccine (HPV9; enrolments after March 1, 2016) over 6 months (on day 1, at month 2, and at month 6). We also obtained data from published clinical trials assessing safety and immunogenicity of HPV4 and HPV9 in 9–26-year-olds from the general population, as a comparator group. The primary endpoint was antibody response against HPV types 16 and 18 at month 7 in the per-protocol population. A response was deemed non-inferior if the lower bound of the multiplicity-adjusted 95% CI was greater than 0·5 for the ratio of anti-HPV-16 and anti-HPV-18 geometric mean titres (GMTs) in survivors of cancer versus the general population. Responses were examined separately in male and female participants by age group (ie, 9–15 years and 16–26 years). Safety was assessed in all participants who received at least one vaccine dose and for whom safety data were available. This study is registered with ClinicalTrials.gov, NCT01492582. This trial is now completed. Findings Between Feb 18, 2013, and June 22, 2018, we enrolled 453 survivors of cancer, of whom 436 received one or more vaccine doses: 203 (47%) participants had survived leukaemia, 185 (42%) were female, and 280 (64%) were non-Hispanic white. Mean age at first dose was 15·6 years (SD 4·6). 378 (83%) of 453 participants had evaluable immunogenicity data; main reasons for exclusion from per-protocol analysis were to loss to follow-up, patient reasons, and medical reasons. Data were also obtained from 26 486 general population controls. The ratio of mean GMT for anti-HPV types 16 and 18 in survivors of cancer versus the general population was more than 1 for all subgroups (ie, aged 9–15 years, aged 16–26 years, male, and female groups) in both vaccine cohorts (ranging from 1·64 [95% CI 1·12–2·18] for anti-HPV type 16 in female participants aged 9–15 years who received HPV9, to 4·77 [2·48–7·18] for anti-HPV type 18 in male participants aged 16–26 years who received HPV4). Non-inferiority criteria were met within each age and sex subgroup, except against HPV type 18 in female participants aged 16–26 years receiving HPV9 (4·30 [0·00–9·05]). Adverse events were reported by 237 (54%) of 435 participants; injection site pain was most common (174 [40%] participants). One serious adverse event (ie, erythema nodosum) was possibly related to vaccine (HPV9; 16–26 year female cohort). Interpretation Immunogenicity and safety of HPV vaccine three-dose series in survivors of cancer is similar to that in the general population, providing evidence for use in this clinically vulnerable population. Funding US National Cancer Institute, Merck, Sharp & Dohme, and American Lebanese Syrian Associated Charities.

OBJECTIVE Children with multiple prematurely fused cranial sutures and those undergoing surgical correction later in life appear to experience worse neurocognitive outcomes, but it is unclear whether higher intracranial pressure (ICP) is implicated in this process. The purpose of this study was to elucidate the effect of age at intervention and number of involved cranial sutures on ICP, as well as to assess which cranial suture closure may be more associated with elevated ICP. METHODS The prospective craniofacial database at the authors’ institution was queried for patients undergoing initial corrective surgery for craniosynostosis in whom intraoperative measurement of ICP was obtained prior to craniectomy. Age, involved sutures, and syndromic status were analyzed in the context of measured ICP by using multiple linear regression. RESULTS Fifty patients met the inclusion criteria. Age at procedure (p = 0.028, β = +0.060 mm Hg/month) and multiple-suture involvement (p = 0.010, β = +4.175 mm Hg if multisuture) were both significantly implicated in elevated ICP. The actual number of major sutures involved was significantly correlated to ICP (p = 0.001; β = +1.687 mm Hg/suture). Among patients with single-suture involvement, there was an overall significant difference of median ICP across the suture types (p = 0.008), with metopic having the lowest (12.5 mm Hg) and sagittal having the highest (16.0 mm Hg). Patients with multiple-suture involvement had significantly higher ICP (p = 0.003; 18.5 mm Hg). Patients with craniofacial syndromes were 79.3 times more likely to have multiple-suture involvement (p < 0.001). Corrective surgery for craniosynostosis demonstrated significant intraoperative reduction of elevated ICP (all p < 0.050). CONCLUSIONS Syndromic status, older age at intervention for craniosynostosis, and multiple premature fusion of cranial sutures were associated with significantly higher ICP.

A 14-year-old, 5.8 kg (12.7 lb) male castrated Jack Russell Terrier was referred for investigation of syncope and an arrhythmia. Electrocardiogram showed pronounced variation in the sinus rate including long periods of sinus arrest and an inconsistent escape rhythm. Sick sinus syndrome was the presumptive diagnosis. A single lead permanent transvenous pacemaker was implanted and was programmed to perform ventricular-demand pacing. Postoperative pacemaker interrogation revealed undersensing and asynchronous pacing during episodes of supraventricular tachycardia (SVT). This intermittent pacemaker malfunction was attributed to a specific pacemaker programming feature called quiet timer blanking. Adjustment of pacemaker parameters did not restore normal function. Treatment with sotalol (5 mg per os q 12 h) was used to medically treat the SVT, and asynchronous pacing was not observed during follow-up visits. To the authors’ knowledge, this is the first documented case of quiet timer blanking causing paroxysmal undersensing and asynchronous pacing in a dog with a permanent pacemaker.

Purpose: The prevalence of high-risk human papillomavirus (hrHPV) infection among transgender women has been reported to be very high and sexually transmitted infection (STI) prevention strategies have focused on transgender women who engage in sex work. The purpose of our study was to describe hrHPV infection prevalence among a group of transgender women and to explore the differences according to sex work history (SW). Methods: The Condesa Study, an HPV vaccine, and screening study, recruited 207 transgender women without previous HPV vaccination, ages 18–60, from two clinics in Mexico City that provide HIV and transgender health care (May 2018–December 2019). At enrollment, they completed a questionnaire on sociodemographic and sexual behavior data. The hrHPV DNA genotyping was done on self-collected anal samples. Factors associated with hrHPV, stratified by presence or absence of SW, were assessed with multiple logistic regression. Results: A total of 43.5% of participants reported a history of SW. Anal hrHPV prevalence was 62.0% among participants with a history of SW and 52.0% among those without. Overall, 1 in 4 (26.6%) participants were living with HIV. Independent risk factors associated with hrHPV among transgender women with a history of SW were younger age, younger age at first anal intercourse (15–17 years), and greater number of sexual partners in the last 3 months. Among transgender women who had not done SW, greater number of sexual partners in the last 3 months and self-reported STIs were associated with hrHPV. Conclusions: Prevalence of anal infection with hrHPV was high among transgender women. Our results support that other sexual behaviors different from participating in SW contribute to the high prevalence of HPV and that there is an urgent need to include all transgender women in prevention programs for HPV and associated cancers, regardless of SW.

After initial reports of anaphylaxis to the messenger RNA (mRNA) COVID-19 vaccines, the Centers for Disease Control and Prevention (CDC) put forth guidance stating that patients with a history of anaphylaxis to vaccine components like polyethylene glycol (PEG) should not receive the mRNA COVID-19 vaccines.1 To address this clinical challenge and decrease vaccine hesitancy, we published an approach to guide COVID-19 vaccination in high-risk allergy individuals.2-4 While the etiology of anaphylaxis to mRNA COVID-19 vaccines remains unclear, PEG continues to be an important focus.5,6 Paclitaxel contains polyoxyl-35 castor oil --a PEG derivative and structurally similar to the excipient in Pfizer-BioNTech and Moderna COVID-19 vaccines-- and docetaxel contains polysorbate 80 --the excipient in Janssen COVID-19 vaccine. Given this, we sought to assess the utility of pre-vaccine excipient skin testing (ST), risk stratification and COVID-19 vaccine tolerability in oncology patients with a history of paclitaxel or docetaxel hypersensitivity reaction (HSR).

Schizophrenia has a multifactorial etiology, involving a polygenic architecture. The potential benefit of whole genome sequencing (WGS) in schizophrenia and other psychotic disorders is not well studied. We investigated the yield of clinical WGS analysis in 251 families with a proband diagnosed with schizophrenia (N = 190), schizoaffective disorder (N = 49), or other conditions involving psychosis (N = 48). Participants were recruited in Israel and USA, mainly of Jewish, Arab, and other European ancestries. Trio (parents and proband) WGS was performed for 228 families (90.8%); in the other families, WGS included parents and at least two affected siblings. In the secondary analyses, we evaluated the contribution of rare variant enrichment in particular gene sets, and calculated polygenic risk score (PRS) for schizophrenia. For the primary outcome, diagnostic rate was 6.4%; we found clinically significant, single nucleotide variants (SNVs) or small insertions or deletions (indels) in 14 probands (5.6%), and copy number variants (CNVs) in 2 (0.8%). Significant enrichment of rare loss-of-function variants was observed in a gene set of top schizophrenia candidate genes in affected individuals, compared with population controls (N = 6,840). The PRS for schizophrenia was significantly increased in the affected individuals group, compared to their unaffected relatives. Last, we were also able to provide pharmacogenomics information based on CYP2D6 genotype data for most participants, and determine their antipsychotic metabolizer status. In conclusion, our findings suggest that WGS may have a role in the setting of both research and genetic counseling for individuals with schizophrenia and other psychotic disorders and their families.

Arrhythmogenic cardiomyopathy (ACM) is a primary disease of the myocardium, predominantly caused by genetic defects in proteins of the cardiac intercalated disc, particularly, desmosomes. Transmission is mostly autosomal dominant with incomplete penetrance. ACM also has wide phenotype variability, ranging from premature ventricular contractions to sudden cardiac death and heart failure. Among other drivers and modulators of phenotype, inflammation in response to viral infection and immune triggers have been postulated to be an aggravator of cardiac myocyte damage and necrosis. This theory is supported by multiple pieces of evidence, including the presence of inflammatory infiltrates in more than two-thirds of ACM hearts, detection of different cardiotropic viruses in sporadic cases of ACM, the fact that patients with ACM often fulfill the histological criteria of active myocarditis, and the abundance of anti–desmoglein-2, antiheart, and anti-intercalated disk autoantibodies in patients with arrhythmogenic right ventricular cardiomyopathy. In keeping with the frequent familial occurrence of ACM, it has been proposed that, in addition to genetic predisposition to progressive myocardial damage, a heritable susceptibility to viral infections and immune reactions may explain familial clustering of ACM. Moreover, considerable in vitro and in vivo evidence implicates activated inflammatory signaling in ACM. Although the role of inflammation/immune response in ACM is not entirely clear, inflammation as a driver of phenotype and a potential target for mechanism-based therapy warrants further research. This review discusses the present evidence supporting the role of inflammatory and immune responses in ACM pathogenesis and proposes opportunities for translational and clinical investigation.

Objective To evaluate the timing and safety of cleft palate (CP) repair in patients with Robin sequence (RS) treated with mandibular distraction osteogenesis (MDO) or tongue-lip adhesion (TLA) for airway obstruction. Design Retrospective cohort study. Setting Tertiary Pediatric Hospital during 2004-2020. Patients 148 patients with RS underwent MDO, 66 met inclusion by having MDO and followed by palatoplasty. 26 patients with RS underwent TLA, 14 met inclusion by having TLA and followed by palatoplasty. Main Outcome Measures Patient characteristics, hospital/operative details, postoperative complications, and polysomnographic (PSG) data were compared. Results Groups were well-matched except more patients with syndromes underwent MDO (N = 27, 41%, P ≤ .002). In the MDO and TLA cohorts, mean CP repair age was 12.8 ± 1.9 months and 14.6 ± 1.6 months, respectively ( P ≤ .002). Despite the earlier CP repair in the MDO group, there were no differences in peri-operative complication rates after palatoplasty in either group. All sleep respiratory parameters improved after MDO/TLA prior to palatoplasty P ≤ .050. All PSG parameters remained significantly improved after palatoplasty compared to preoperative values, P ≤ .043. Obstructive apnea hypopnea index and Oxygen saturation nadir further improved after palatoplasty within the MDO group, P ≤ .050, while no changes in the TLA group, P ≥ .500. Conclusions MDO was associated with earlier age at palatoplasty than TLA with a similar perioperative risk profile. In those patients with pre- and post-palatoplasty PSG data, palatoplasty was not associated with a deterioration in PSG parameters, and in fact in the MDO group, PSG data improved.

Background The risk of severe COVID-19 varies significantly among persons of similar age and is higher in males. Age-independent, sex-biased differences in susceptibility to severe COVID-19 may be ascribable to deficits in a sexually dimorphic protective attribute that we termed immunologic resilience (IR). Objective To examine whether deficits in IR that antedate or are induced by SARS-CoV-2 infection independently predict COVID-19 mortality. Methods IR levels were quantified with two novel metrics: immune health grades (IHG-I [best] to IHG-IV) to gauge CD8+ and CD4+ T-cell count equilibrium, and blood gene expression signatures. IR metrics were examined in a prospective COVID-19 cohort (n=522); primary outcome was 30-day mortality. Associations of IR metrics with outcomes in non-COVID-19 cohorts (n=13,461) provided the framework for linking pre-COVID-19 IR status to IR during COVID-19, as well as to clinical outcomes. Results IHG-I, tracking high-grade equilibrium between CD8+ and CD4+ T-cell counts, was the most common grade (73%) among healthy adults, particularly in females. SARS-CoV-2 infection associated with underrepresentation of IHG-I (21%) vs. overrepresentation (77%) of IHG-II or IHG-IV, especially in males vs. females (P Conclusion Preservation of immunocompetence with controlled inflammation during antigenic challenges is a hallmark of IR and associates with longevity and AIDS resistance. Independent of age, a male-biased proclivity to degrade IR before and/or during SARS-CoV-2 infection predisposes to severe COVID-19. Clinical implications Biomarkers tracking immunologic resilience may have broad prognostic utility, as they associated with longevity, as well as resistance to a progressive disease course during SARS-CoV-2, influenza, or HIV infection.

Purpose Adjuvant chemotherapy reduces recurrence in early-stage triple-negative breast cancer (TNBC). However, data are lacking evaluating anthracycline + taxane (ATAX) versus taxane-based (TAX) chemotherapy in older women with node-negative TNBC, as they are often excluded from trials. The purpose of this study was to evaluate the effect of adjuvant ATAX versus TAX on cancer-specific (CSS) and overall survival (OS) in older patients with node-negative TNBC. Patients and methods Using the SEER-Medicare database, we selected patients aged ≥ 66 years diagnosed with Stage T1-4N0M0 TNBC between 2010 and 2015 (N = 3348). Kaplan–Meier survival curves and adjusted Cox proportional hazards models were used to estimate 3-year OS and CSS. Multivariant Cox regression analysis was used to identify independent factors associated with use of ATAX compared to TAX. Results Approximately half (N = 1679) of patients identified received chemotherapy and of these, 58.6% (N = 984) received TAX, 25.0% (N = 420) received ATAX, and 16.4% (N = 275) received another regimen. Three-year CSS and OS was improved with any adjuvant chemotherapy from 88.9 to 92.2% (p = 0.0018) for CSS and 77.2% to 88.6% for OS (p p = 0.048) for ATAX and OS was 91.0% for TAX and 86.4% for ATAX (p = 0.032). Conclusion While adjuvant chemotherapy was associated with improved clinical outcomes, the administration of ATAX compared to TAX was associated with inferior 3-year OS and CSS in older women with node-negative TNBC. The use of adjuvant ATAX should be considered carefully in this patient population.

Introduction Metastatic triple-negative breast cancer (TNBC) is an aggressive cancer with poor survival that is difficult to treat due to a lack of targeted options. Conventional therapies targeting hormone receptors (HR) and human epidermal growth factor 2 (HER2) are ineffective and often chemotherapy is standard-of-care. Sacituzumab govitecan is an antibody drug conjugate (ADC) comprised of an active metabolite of irinotecan, SN-38, bound to a humanized monoclonal antibody targeting trophoblastic cell-surface antigen 2 (Trop-2). Trop-2 is highly expressed on the surface of TNBC cells, making it an attractive target. Areas covered We explore the mechanism, pharmacology, efficacy, safety, and tolerability of sacituzumab govitecan. A literature search was conducted via PubMed using keywords such as 'sacituzumab govitecan,' and 'metastatic TNBC.' Expert opinion Sacituzumab govitecan has promising survival benefits in patients with previously treated mTNBC based on data from the ASCENT trial. Common adverse effects were neutropenia, diarrhea, and nausea, however these effects were manageable with supportive care. Sacituzumab govitecan has shown promise in cancers outside of TNBC, such as urothelial and lung and is being evaluated in HR-positive breast cancers. It is likely we will see this therapy used in combination with other novel targeted agents as current clinical trials mature.

To establish the effectiveness of cooled radiofrequency ablation in managing hip pain from osteoarthritis at 6 months after receiving treatment in patients who failed conservative treatments and are not surgical candidates due to comorbidities or unwillingness to undergo arthroplasty surgery by targeting the femoral and obturator branches and assessing the degree of hip pain relief and change of function. This prospective pilot study includes a total of 11 consecutive patients experiencing persistent chronic hip pain in the setting of advanced osteoarthritis. Patients initially underwent anesthetic blocks of the obturator and femoral nerve branches to determine cooled radiofrequency ablation candidacy. After adequate response to the anesthetic blocks (> 50% immediate pain relief), patients were subjected to the procedures 2–3 weeks later. Treatment response was evaluated utilizing clinically validated questionnaires and visual analog score in order to assess impact on pain severity, stiffness, and functional activities of daily living. Follow-up outcome scores were collected up to 6 months after cooled radiofrequency ablation procedure. A total of 11 hips were treated consecutively between August 2019 and March 2020 (mean patient age 61.4 years; 8 M:3F). The mean total HOOS score improved significantly from baseline at 17.0 ± 6.0 to 52.9 ± 5.4 at a mean of 6.2 months after treatment (p

Onboarding is the process in which new employees are introduced to an organization and its vision, mission, and values. Library literature reflects the importance of onboarding in welcoming new emp...

Aims Orthopaedic surgeries are complex, frequently performed procedures associated with significant haemorrhage and perioperative blood transfusion. Given refinements in surgical techniques and changes to transfusion practices, we aim to describe contemporary transfusion practices in orthopaedic surgery in order to inform perioperative planning and blood banking requirements. Methods We performed a retrospective cohort study of adult patients who underwent orthopaedic surgery at four Canadian hospitals between 2014 and 2016. We studied all patients admitted to hospital for nonarthroscopic joint surgeries, amputations, and fracture surgeries. For each surgery and surgical subgroup, we characterized the proportion of patients who received red blood cell (RBC) transfusion, the mean/median number of RBC units transfused, and exposure to platelets and plasma. Results Of the 14,584 included patients, the most commonly performed surgeries were knee arthroplasty (24.8%), hip arthroplasty (24.6%), and hip fracture surgery (17.4%). A total of 10.3% of patients received RBC transfusion; the proportion of patients receiving RBC transfusions varied widely based on the surgical subgroup (0.0% to 33.1%). Primary knee arthroplasty and hip arthroplasty, the two most common surgeries, were associated with in-hospital transfusion frequencies of 2.8% and 4.5%, respectively. RBC transfusion occurred in 25.0% of hip fracture surgeries, accounting for the greatest total number of RBC units transfused in our cohort (38.0% of all transfused RBC units). Platelet and plasma transfusions were uncommon. Conclusion Orthopaedic surgeries were associated with variable rates of transfusion. The rate of RBC transfusion is highly dependent on the surgery type. Identifying surgeries with the highest transfusion rates, and further evaluation of factors that contribute to transfusion in identified at-risk populations, can serve to inform perioperative planning and blood bank requirements, and facilitate pre-emptive transfusion mitigation strategies. Cite this article: Bone Jt Open 2021;2(10):850–857.

Background Racial/ethnic health inequities have been well-documented among youth and young adults with type 1 diabetes (T1D), yet little is known about how socioeconomic position (SEP) intersects with the risk marker of race/ethnicity to predict inequities in longitudinal glycemic control. Purpose To identify patterns of SEP, race/ethnicity, and clinical characteristics that differentiate hemoglobin A1c (HbA1c) trajectories among youth and young adults after T1D diagnosis. Methods The SEARCH for Diabetes in Youth cohort includes youth with diabetes diagnosed from 2002 to 2006 and 2008 who were followed through 2015. We analyzed data from 1,313 youth and young adults with T1D with ≥3 HbA1c measures. Classification tree analysis identified patterns of baseline demographic, SEP, and clinical characteristic that best predicted HbA1c trajectories over an average of 8.3 years using group-based trajectory modeling. Results Two HbA1c trajectories were identified: Trajectory 1 (77%) with lower baseline HbA1c and mild increases (from mean 7.4% to 8.4%) and Trajectory 2 (23%) with higher baseline HbA1c and major increases (from 8.5% to 11.2%). Race/ethnicity intersected with different SEP characteristics among non-Hispanic white (NHW) than in non-whites. Public health insurance predicted high-risk Trajectory 2 membership in non-whites, whereas parental education, household structure, diagnosis age and glucose checking frequency predicted membership for NHW youth and young adults. Two characteristics, race/ethnicity and parental education alone identified 80% of the Trajectory 2 members. Conclusions Race/ethnicity intersects with multiple SEP and clinical characteristics among youth and young adults with T1D, which is associated with particularly high risk of poor long-term glycemic control.

Approximately 5% of individuals with schizophrenia die from suicide. However, suicide in psychosis is still poorly characterized, partly due to a lack of adequate population-based clinical or genetic data on suicide death. The Utah Suicide Genetics Research Study (USGRS) provides a large population-based cohort of suicide deaths with medical record and genome-wide data (N = 4380). Examination of this cohort identified medical and genetic risks associated with type of suicide death and investigated the relative contributions of psychotic and affective symptoms to method of suicide. Key differences in method of suicide (common vs. atypical methods) were tested in relation to lifetime psychosis and genome-wide genetic risk for schizophrenia, major depressive disorder, and neuroticism. Consistent with previous studies, psychosis-spectrum disorders were observed to be common in suicide (15% of the cohort). Individuals with psychosis more frequently died from atypical methods, with rates of atypical suicide increasing across the schizophrenia spectrum. Genetic risk for schizophrenia was also associated with atypical suicide, regardless of clinical diagnosis, though this association weakened when filtering individuals with schizophrenia from the analysis. Follow-up examination indicated that high rates of atypical suicide observed in schizophrenia are not likely accounted for by restricted access to firearms. Overall, better accounting for the increased risk of atypical suicide methods in psychosis could lead to improved prevention strategies in a large portion of the suicide risk population.

Diabetes is a common disease among pediatric populations in the United States and worldwide. The incidence of type 1 and type 2 diabetes is increasing, with disproportional increases in racial/ethnic subpopulations. As the prevalence of obesity continue to increase, type 2 diabetes now represents a major form of pediatric diabetes. The management of diabetes in youth centers on maintaining glycemic control to prevent acute and chronic complications. This article summarizes the epidemiology, etiology, management, and complications of type 1 and type 2 diabetes in youth, as well as future directions and opportunities.

OBJECTIVE Newborn skincare influences levels of beneficial factors from vernix and vaginal secretions but also the emergence of potential skin pathogens. However, evidence-based national guidelines for newborn skincare do not exist, and actual hospital practices for newborn skincare have not been described. In this study, we test the hypothesis that US maternity hospitals follow differing policies with regard to newborn skincare. METHODS A 16-question survey querying skin care practices was distributed to nursery medical directors at the 109 US hospital members of the Better Outcomes through Research for Newborns network. Data from free text responses were coded by 2 study personnel. Survey responses were analyzed by using descriptive statistics and compared by region of the United States. RESULTS Delaying the first newborn bath by at least 6 hours is a practice followed by 87% of US hospitals surveyed. Discharging newborns without a bath was reported in 10% of hospitals and was more common for newborns born in nonacademic centers and on the West Coast. Procedures and products used for newborn skincare varied significantly. Parental education on tub immersion and soap use was also inconsistent and potentially contradictory between providers. Evidence cited by hospitals in forming their policies is scant. CONCLUSION In this study, we identify similar and strikingly different newborn skincare policies across a national network of US maternity hospitals. Research is needed to identify effects of differing skincare routines on skin integrity, infection rates, and childhood health outcomes to improve the evidence base for the care of newborn skin.

Background: The association between Helicobacter pylori (H. pylori) infection and pancreatic cancer (PC) risk remains inconclusive. We examined the association between H. pylori antibodies and PC r...

BACKGROUND: Supervised exercise training improves outcomes in patients with pulmonary arterial hypertension (PAH). The effect of an unsupervised activity intervention has not been tested. RESEARCH QUESTION: Can a text-based mobile health intervention increase step counts in patients with PAH? STUDY DESIGN AND METHODS: We performed a randomized, parallel arm, single-blind clinical trial. We randomized patients to usual care or a text message-based intervention for 12 weeks. The intervention arm received three automated text messages per day with real-time step count updates and encouraging messages rooted in behavioral change theory. Individual step targets increased by 20% every 4 weeks. The primary end point was mean week 12 step counts. Secondary end points included the 6-min walk test, quality of life, right ventricular function, and body composition. RESULTS: Among 42 randomized participants, the change in raw steps between baseline and week 12 was higher in the intervention group (1,409 steps [interquartile range, –32 to 2,220] vs –149 steps [interquartile range, –1,010 to 735]; P = .02), which persisted after adjustment for age, sex, baseline step counts, and functional class (model estimated difference, 1,250 steps; P = .03). The intervention arm took a higher average number of steps on all days between days 9 and 84 (P < .05, all days). There was no difference in week 12 six-minute walk distance. Analysis of secondary end points suggested improvements in the emPHasis-10 score (adjusted change, –4.2; P = .046), a reduction in visceral fat volume (adjusted change, –170 mL; P = .023), and nearly significant improvement in tricuspid annular plane systolic excursion (model estimated difference, 1.2 mm; P = .051). INTERPRETATION: This study demonstrated the feasibility of an automated text message-based intervention to increase physical activity in patients with PAH. Additional studies are warranted to examine the effect of the intervention on clinical outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No. NCT03069716; URL: www.clinicaltrials.gov

Summary Background There is currently a lack of patient-reported outcome measures for ear reconstruction. We developed the EAR-Q to measure ear appearance and post-operative adverse effects from the patient perspective. Methods Field-test data were collected from children and young adults in eight countries between 13 May 2016 and 12 December 2019. Rasch measurement theory (RMT) analysis was used to refine the scales and to examine their psychometric properties. Results Participants had microtia (n = 607), prominent ears (n = 145) or another ear condition (n = 111), and provided 960 assessments for the Appearance scale (e.g., size, shape, photos), and 137 assessments for the Adverse Effects scale (e.g., itchy, painful, numb). RMT analysis led to the reduction of each scale to 10-items. Data fit the Rasch model for the Appearance (X2(80) = 90.9, p = 0.19) and Adverse Effects (X2(20) = 24.5, p = 0.22) scales. All items in each scale had ordered thresholds and good item fit. There was no evidence of differential item function for the Appearance scale by age, gender, language, or type of ear condition. Reliability was high for the Appearance scale, with person separation index (PSI) and Cronbach alpha values with and without extremes ≥0.92. Reliability for the Adverse Effects scale was adequate (i.e., PSI and Cronbach alpha values ≥0.71). Higher scores (liked appearance more) correlated with higher scores (better) on Psychological, Social and School scales. Interpretation The EAR-Q can be used in those 8–29 years of age to understand the patient perspective in clinical practice and research, and in addition, can be used to benchmark outcomes for ear reconstruction internationally.

PURPOSE: The aim was to investigate the effect of dietary nitrate supplementation (in the form of beetroot juice, BRJ) for 20 days on salivary nitrite (a potential precursor of bioactive nitric oxide), exercise performance and high altitude (HA) acclimatisation in field conditions (hypobaric hypoxia). METHODS: This was a single-blinded randomised control study of 22 healthy adult participants (12 men, 10 women, mean age 28 ± 12 years) across a HA military expedition. Participants were randomised pre-ascent to receive two 70 ml dose per day of either BRJ (~12.5 mmol nitrate per day; n = 11) or non-nitrate calorie matched control (n = 11). Participants ingested supplement doses daily, beginning 3 days prior to departure and continued until the highest sleeping altitude (4800 m) reached on day 17 of the expedition. Data were collected at baseline (44 m altitude), at 2350 m (day 9), 3400 m (day 12) and 4800 m (day 17). RESULTS: BRJ enhanced the salivary levels of nitrite (p = 0.007). There was a significant decrease in peripheral oxygen saturation and there were increases in heart rate, diastolic blood pressure, and rating of perceived exertion with increasing altitude (p=

BACKGROUND Low-cost, automated interventions that increase knowledge and skills around diet and lifestyle modifications are recommended for cardiovascular disease risk reduction. METHODS We initiated a quality improvement program to assess the impact of a web-based diet and lifestyle intervention utilizing short animated videos in adults with high blood pressure (BP) at a primary care clinic in Saudi Arabia. We enrolled adults with elevated BP, not on BP medications, who were identified using the electronic medical record. We delivered a web-linked diet and lifestyle intervention using animated videos covering diet and lifestyle topics. Videos and reminders were sent weekly for 5 weeks. Outcomes were proportion who engaged in the program, returned for a repeat BP within 3 months, and change in BP. RESULTS We enrolled 269 adult participants, with a mean (SD) age of 41.6 (12.4) years; 77% were male. At the conclusion of the pilot, we demonstrated a high level of engagement: overall, 69% of materials were viewed and 67% of patients returned for BP. Patients who returned had a mean (SD) baseline systolic BP of 138.0 (7.2) mm Hg and a large mean reduction in systolic BP from baseline, −10.5 mm Hg (12.4; P < 0.001). CONCLUSIONS Overall, the feasibility of a video-assisted, web-based, diet and lifestyle intervention as a support tool for hypertension management demonstrated a high participation rate and a high return rate for reassessment of BP. These findings suggest that this low-cost, automated intervention may have a great potential as a scalable tool for blood pressure management. However, randomized trials to understanding the effectiveness of the support tools are needed.

SUMMARY The relationship between wound irrigation and healing has been recognized for centuries. However, there is little evidence and no official recommendations from any health care organization regarding best wound irrigation practices. This is the first review of wound irrigation that systematically summarizes the literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and distills the evidence into a practical format. In this comprehensive review, the authors outline the irrigation fluids and delivery methods used in the identified studies, analyze reported treatment outcomes, summarize irrigation effectiveness, and propose evidence-based guidelines to improve wound healing outcomes and enhance the consistency of wound irrigation. Thirty-one high-quality studies with a combined total of 61,808 patients were included. Based on the current evidence provided by this review, the authors propose the following guidelines: (1) acute soft-tissue wounds should receive continuous gravity flow irrigation with polyhexanide; (2) complex wounds should receive continuous negative-pressure wound therapy with instillation with polyhexanide; (3) infected wounds should receive continuous negative-pressure wound therapy with instillation with silver nitrate, polyhexanide, acetic acid, or povidone-iodine; (4) breast implant wounds should receive gravity lavage with povidone-iodine or antibiotics; and (5) surgical-site infection rates can be reduced with intraoperative povidone-iodine irrigation.

OBJECTIVE To review cases of canine conjunctival hemangioma (HA) and hemangiosarcoma (HSA) treated surgically at a referral center to establish success of surgical management, recurrence rates, and long-term outcomes for patients. ANIMALS STUDIED Retrospective record review of dogs that underwent surgery to remove histologically diagnosed conjunctival HA or HSA between April 2004 and April 2020 to collect data on signalment, tumor location, interval between initial presentation and surgery, tumor diagnosis, surgical dose, surgical margins, tumor size, recurrence and survival times. RESULTS A total of 52 dogs (60 tumors) were included. The mean age of affected dogs was 8.69 years; the most affected breed was the Border collie (n = 13, 25%). 28 tumors were HA (46.67%) and 32 HSA (53.33%). Tumors occurred in three locations: the lateral bulbar conjunctiva (n = 37, 61.67%), the third eyelid margin (n = 19, 31.67%), and the ventral conjunctival fornix (n = 4, 6.67%). There was no site predilection for HA versus HSA. 97% of tumors occurred in non-pigmented tissue. Corneal invasion was more likely to be a feature of malignant tumors. Five tumors were incompletely excised, one of which recurred. There was no statistical difference in likelihood of incomplete excision between HSA and HA. Six tumors (10%) recurred. HSA was not statistically more likely to recur than HA. Recurrence times ranged from 5 weeks to 1 year. CONCLUSION Surgical treatment of conjunctival HA and HSA is likely to be curative. There is a recurrence rate of 10% regardless of tumor type, and recurrence may be late in the course of the disease.

BackgroundThe degree to which suicide risk aggregates in US families is unknown. The authors aimed to determine the familial risk of suicide in Utah, and tested whether familial risk varies based on the characteristics of the suicides and their relatives.MethodsA population-based sample of 12 160 suicides from 1904 to 2014 were identified from the Utah Population Database and matched 1:5 to controls based on sex and age using at-risk sampling. All first through third- and fifth-degree relatives of suicide probands and controls were identified (N = 13 480 122). The familial risk of suicide was estimated based on hazard ratios (HR) from an unsupervised Cox regression model in a unified framework. Moderation by sex of the proband or relative and age of the proband at time of suicide (v. ⩾25 years) was examined.ResultsSignificantly elevated HRs were observed in first- (HR 3.45; 95% CI 3.12–3.82) through fifth-degree relatives (HR 1.07; 95% CI 1.02–1.12) of suicide probands. Among first-degree relatives of female suicide probands, the HR of suicide was 6.99 (95% CI 3.99–12.25) in mothers, 6.39 in sisters (95% CI 3.78–10.82), and 5.65 (95% CI 3.38–9.44) in daughters. The HR in first-degree relatives of suicide probands under 25 years at death was 4.29 (95% CI 3.49–5.26).ConclusionsElevated familial suicide risk in relatives of female and younger suicide probands suggests that there are unique risk groups to which prevention efforts should be directed – namely suicidal young adults and women with a strong family history of suicide.

Strong quantitative and functional antibody responses to the quadrivalent human papillomavirus (HPV) vaccine were reported in mid-adult aged men, but there are limited data on the avidity of the antibody response and the memory B-cell response following vaccination. Although circulating antibodies induced by vaccination are believed to be the main mediators of protection against infection, evaluation of avidity of antibodies and memory B cell responses are critical for a better understanding of the vaccine immunogenicity mechanisms. Both the modified enzyme-linked immunosorbent assay (ELISA) and the enzyme-linked immunosorbent spot (ELISpot) assay are tools to measure the humoral and cellular immune responses post vaccination to characterize vaccine immunogenicity. The avidity of HPV-16 and HPV-18 specific IgG in the serum of mid-adult aged men (N = 126) who received three quadrivalent HPV vaccine doses was examined using a modified ELISA. HPV-16 memory B-cell responses were assessed via ELISpot at month 0 (prior to vaccination) and 1-month post-dose three of the vaccine (month 7). The quadrivalent vaccine induced an increase in HPV-16 and HPV-18 antibody avidity at month 7. HPV-18 avidity levels moderately correlated with anti-HPV-18 antibody titers, but no association was observed for HPV-16 antibody titers and avidity levels. The HPV-16-specific memory B-cell response was induced following three vaccine doses, however, no association with anti-HPV-16 antibody avidity was observed. Three doses of quadrivalent HPV vaccine increased antibody affinity maturation for HPV-16/18 and increased the frequency of anti-HPV-16 memory B-cells in mid-adult aged men.

PURPOSE The goal of this study was to investigate patient specific factors and surgical techniques that affect occipital step-off deformity in children undergoing posterior vault distraction osteogenesis (PVDO). METHODS Patients who underwent PVDO were retrospectively reviewed and included if a high resolution three-dimensional computed tomography scan was available 1-year post-distractor removal. Two craniofacial surgeons were blinded to individual subjects and presented with 3 still images of three-dimensional bone reconstructions and asked to rate the degree of step off: none, mild, moderate, or severe. The data were analyzed with multinomial logistic regressions and other appropriate statistics. RESULTS Forty-one patients met inclusion criteria. All patients had multisuture or bicoronal craniosynostosis. Multinomial logistic regression identified age at PVDO (Cox and Snell = 0.487, P

Background In men, the incidence of human papillomavirus (HPV)–related cancer is rising, but data regarding male HPV infection and seroprevalence are available from only a few countries. Methods This analysis of a global HPV vaccine trial evaluated baseline data from 1399 human immunodeficiency virus–negative heterosexual men (HM) and men who have sex with men (MSM). Key objectives included assessment of HPV prevalence and risk factors for seropositivity to 9-valent HPV (9vHPV) vaccine types (6, 11, 16, 18, 31, 33, 45, 52, and 58), and concordance between seropositivity and prevalent HPV type. Results Overall, 455 of 3463 HM (13.1%) and 228 of 602 MSM (37.9%) were HPV DNA positive for any 9vHPV vaccine type at baseline. Infection prevalence and seroprevalence (≥1 9vHPV vaccine type) were 13.2% and 8.1%, respectively, among 333 HM from Europe, and 37.9% and 29.9%, respectively, among 335 MSM from Europe or North America. Among men with baseline infection, MSM had higher seroprevalence for concordant HPV types (39.5% vs 10.8% in HM). The seropositivity risk (irrespective of baseline infection status) was higher among MSM versus HM (age-adjusted odds ratio, 3.0 [95% confidence interval, 2.4–6.4]). Among MSM, statistically significant seropositivity risk factors included younger age at sexual debut, higher number of receptive anal sex partners, and less frequent condom use. No factors assessed were associated with seropositivity in HM. Conclusions Higher proportions of MSM than HM were HPV DNA positive and seropositive, and concordance between HPV DNA positivity and seropositivity, a potential marker of true infection versus carriage, was higher in MSM. Most MSM and HM were seronegative for all 9vHPV vaccine types, suggesting the potential benefit of catch-up vaccination after sexual debut. Clinical Trials Registration. NCT00090285.

Oral human papillomavirus (HPV) is associated with increasing rates of HPV-associated oropharyngeal cancer (OPC) in men. Sequential infection from one site to another has been demonstrated at the cervix and anus. Thus, risk of an oral HPV infection following a genital infection of the same type in the HPV Infection in Men study was investigated. Samples from 3,140 men enrolled in a longitudinal cohort were assessed for sequential genital to oral infection with one of nine HPV types (HPV 6, 11, 16, 18, 31, 33, 45, 52, 58); and then also sequential, same-type oral to genital infection. Incidence rate ratios (IRRs) compared rates of oral HPV among men with and without prior genital infection of the same type. Risk of sequential HPV infections were assessed using Cox proportional hazards model. Incidence of an oral HPV infection was significantly higher among men with a prior genital infection of the same type for any of the 9 HPV types (IRR: 2.3; 95% CI: 1.7–3.0). Hazard ratio of a sequential genital to oral HPV infection was 2.3 (95% CI: 1.7–3.1) and 3.5 (95% CI: 1.9–6.4) for oral to genital infection. Both changed minimally after adjustment for age, country, circumcision, alcohol use, lifetime sexual partners and recent oral sex partners. HPV infections at one site could elevate risk of a subsequent genital or oral HPV infection of the same type in men, emphasizing the importance of vaccination to prevent all HPV infections.

BACKGROUND Orthognathic surgery has traditionally been performed after skeletal maturity. Although these procedures are also being performed in children, the implications of earlier intervention and specific risk factors in this younger population remain unknown. METHODS The American College of Surgeons National Surgical Quality Improvement Program Pediatric dataset was queried for orthognathic procedures performed in 2018. Complications, readmissions, and reoperations were analyzed with appropriate statistics. RESULTS Overall adverse event rate after orthognathic surgery in pediatric patients was 7.8% (n = 22 of 281), which were associated with having any comorbidity (P

Bipolar disorder (BP) suicide death rates are 10–30 times greater than the general population, likely arising from environmental and genetic risk factors. Though suicidal behavior in BP has been investigated, studies have not addressed combined clinical and genetic factors specific to suicide death. To address this gap, a large, harmonized BP cohort was assessed to identify clinical risk factors for suicide death and attempt which then directed testing of underlying polygenic risks. 5901 individuals of European ancestry were assessed: 353 individuals with BP and 2498 without BP who died from suicide (BPS and NBPS, respectively) from a population-derived sample along with a volunteer-derived sample of 799 individuals with BP and a history of suicide attempt (BPSA), 824 individuals with BP and no prior attempts (BPNSA), and 1427 individuals without several common psychiatric illnesses per self-report (C). Clinical and subsequent directed genetic analyses utilized multivariable logistic models accounting for critical covariates and multiple testing. There was overrepresentation of diagnosis of PTSD (OR = 4.9, 95%CI: 3.1–7.6) in BPS versus BPSA, driven by female subjects. PRS assessments showed elevations in BPS including PTSD (OR = 1.3, 95%CI:1.1–1.5, versus C), female-derived ADHD (OR = 1.2, 95%CI:1.1–1.4, versus C), and male insomnia (OR = 1.4, 95%CI: 1.1–1.7, versus BPSA). The results provide support from genetic and clinical standpoints for dysregulated traumatic response particularly increasing risk of suicide death among individuals with BP of Northern European ancestry. Such findings may direct more aggressive treatment and prevention of trauma sequelae within at-risk bipolar individuals.

Fronto-orbital advancement (FOA) of the anterior skull and orbital bandeau is standard of care for craniosynostosis with anterior morphology. Fronto-orbital retrusion, temporal hollowing, and bony contour irregularities are commonly seen in long-term follow-up. In this study, we report several technical adaptations of a new FOA technique described in Fearon et al that help facilitate adaptation of the single-segment neo-bandeau FOA technique in preparation of use in younger patients, and perform a craniometric analysis of the technique. Five consecutive patients who underwent the single-segment neo-bandeau FOA in 2020 with available pre- and post-operative three-dimensional head computed tomography scans were studied. Using Materialise Mimics (Materialise, Ghent, Belgium), cranial length, cranial height, cranial widths, and intracranial volume were measured. Two (40%) patients were male and all were non-Hispanic White with a median age at surgery of 18.6 months (interquartile range 10.4-45.7). Three patients (60%) had bicoronal or other multi-suture craniosynostosis, and 1 each had metopic and sagittal craniosynostosis. Intraoperatively measured intracranial pressure decreased from 17.8 mmHg (R 13.0-20.0) before craniectomy to 4.8 mmHg (R 2.0-11.0; P = 0.038) after craniectomy. Anterior cranial width increased postoperatively (mean 92.6 mm; R 74.9-111.5 versus 117.6 mm; R 109.8-135.2, P = 0.005). Intracranial volume increased from preoperative (mean 1211 cm3; R 782-1949 cm3) to postoperative (1387 cm3; R 1022-2108 cm3; P = 0.009). The authors find in this small sample that a single-segment neo-bandeau FOA demonstrates volumetric expansion similar to conventional FOA techniques and is feasible in infants under 1 year of age.

PURPOSE The purpose of this study is to quantitatively establish the volumetric changes observed with posterior vault distraction osteogenesis in the anterior, middle, and posterior thirds of the cranial vault; characterize change in cranial length, width, and height, correlating these changes to demographic variables that may help identify why younger kids gain more volume; and describe the short-term position of the transport segment. METHODS Multisuture craniosynostosis patients who underwent posterior vault distraction osteogenesis were retrospectively reviewed. Pediatric, dose-reduced, thin cut helically acquired head computed tomography scans were analyzed on Materialise Mimics v22 (Materialise, Ghent, Belgium). Pre and post-PVDO and "old" and "young" cohort were compared. RESULTS Twenty-one patients met inclusion criteria. The change in cranial length was significantly less at a median of 14.9 mm [Interquartile range (IQR) 11.8, 31.6] compared to the X-ray measured AP distraction distance (30 mm [IQR 24, 33]; P

Background: A positive association between Merkel cell polyomavirus (MCPyV) infection and cutaneous squamous cell carcinoma (cuSCC) has been observed in at least one previous case–control study. To evaluate this association in a prospective context, we investigated infections with human polyomaviruses (HPyV), including MCPyV, as predictors of keratinocyte carcinomas, including cuSCC and basal cell carcinoma (BCC), among a cohort of immunocompetent individuals enrolled in the Viruses in Skin Cancer (VIRUSCAN) Study. Methods: Associations between markers of baseline HPyV infection (serum antibodies and viral DNA in eyebrow hairs and skin swabs) and incident keratinocyte carcinomas were modeled using Cox proportional hazards regression. Proportions of baseline HPyV infections that were concordant with a subsequent tumor positive for the same HPyV type were assessed. Results: No significant associations were observed between baseline markers of MCPyV or other HPyV infections and cuSCC or BCC. Less than 4.5% of baseline MCPyV infections were also detected in subsequently developed keratinocyte carcinoma tumors. Conclusions: HPyV infection was not a predictor of keratinocyte carcinoma risk in this prospective cohort. Impact: Cancer-associated infections represent attractive targets for cancer prevention; however, HPyV infections have limited potential as novel targets for cuSCC prevention.

Background Vioptix is a near-infrared spectroscopy tissue oximetry technology that allows for noninvasive monitoring of flap perfusion. Despite the reported benefits of Vioptix, the cost-effectiveness of this flap monitoring technology has not been compared to clinical examination alone. Methods A cost-effectiveness model, from the patient perspective, was constructed with two treatment arms: clinical examination versus clinical examination combined with Vioptix for flap monitoring after autologous, free flap breast reconstruction. Costs, utilities, and other model inputs were identified from the literature. One-way and probabilistic sensitivity analyses were performed. Gamma distributions were created for cost variables, and beta distributions were created for probability variables. An incremental cost-effectiveness ratio under $50,000 per quality-adjusted life-year (QALY) was considered cost-effective. All analyses were performed using TreeAge Pro (Williamstown, Mass.). Results Mean cost of autologous free tissue transfer breast reconstruction with clinical examination-based flap monitoring was found to be $37,561 with an effectiveness of 0.79, whereas the mean cost of clinical examination with Vioptix for flap monitoring was $39,361 with effectiveness of 0.82. This yielded an incremental cost-effectiveness ratio of $60,507 for clinical examination combined with Vioptix for flap monitoring. One-way sensitivity analysis revealed that clinical examination with Vioptix became cost-effective when the cost of Vioptix was less than $1487. Probabilistic sensitivity analysis found that clinical examination was cost-effective in 86.5 percent of cases. Conclusion Although clinical examination combined with Vioptix is minimally more effective for flap monitoring after autologous, free flap breast reconstruction, clinical examination alone is the more cost-effective flap monitoring option.

Purpose of the review While there has been a longstanding interest in metabolic disease in pulmonary hypertension, publications in the last several years have translated basic science findings to human disease and even led to recently published studies of metabolic therapy in pulmonary arterial hypertension that are discussed here. Recent findings Progress has been made in four key areas including mechanisms of insulin resistance in pulmonary arterial hypertension, the role of obesity in pulmonary vascular disease, novel clinical trials targeting metabolism in pulmonary hypertension, and the role of metabolism in chronic thromboembolic pulmonary hypertension. Summary : Insulin resistance in pulmonary arterial hypertension is primarily in the lipid axis. There are systemic manifestations of insulin resistance including right ventricular lipotoxicity. Obesity is associated with elevation of right ventricular systolic pressure even in a healthy population and therapies in pulmonary arterial hypertension that target metabolism hold promise for improving exercise, right ventricular function, and visceral adiposity. Finally, there are emerging data that chronic thromboembolic pulmonary hypertension is similarly characterized by metabolic alterations, though the specific metabolites may be different from pulmonary arterial hypertension.

Objective: To evaluate the development process and clinical impact of implementing a standardized perioperative clinical care pathway for cleft palate repair. Design: Medical records of patients undergoing primary cleft palate repair prior to pathway implementation were retrospectively reviewed as a historical control group (N = 40). The historical cohort was compared to a prospectively collected group of patients who were treated according to the pathway (N = 40). Patients: Healthy, nonsyndromic infants undergoing primary cleft palate repair at a tertiary care pediatric hospital. Interventions: A novel, standardized pathway was created through an iterative process, combining literature review with expert opinion and discussions with institutional stakeholders. The pathway integrated multimodal analgesia throughout the perioperative course and included intraoperative bilateral maxillary nerve blocks. Perioperative protocols for preoperative fasting, case timing, antiemetics, intravenous fluid management, and postoperative diet advancement were standardized. Main Outcome Measures: Primary outcomes include: (1) length of hospital stay, (2) cumulative opioid consumption, (3) oral intake postoperatively. Results: Patients treated according to the pathway had shorter mean length of stay (31 vs 57 hours, P < .001), decreased cumulative morphine consumption (77 vs 727 μg/kg, P < .001), shorter time to initiate oral intake (9.3 vs 22 hours, P = .01), and greater volume of oral intake in first 24 hours postoperatively (379 vs 171 mL, P < .001). There were no differences in total anesthesia time, total surgical time, or complication rates between the control and treatment groups. Conclusions: Implementation of a standardized perioperative clinical care pathway for primary cleft palate repair is safe, feasible, and associated with reduced length of stay, reduced opioid consumption, and improved oral intake postoperatively.

The relationship between the level of glucagon-like peptide-1 and repeated weight gain was evaluated in 31 patients suffering from grade IIIII obesity and type 2 diabetes mellitus after bariatric interventions for 3 years. It was found that the level of stimulated glucagon-like peptide-1 significantly increased by the third day after sleeve gastroplasty and gastroschunt compared to the initial parameters (p = 0.001 for obese patients; p = 0.000 for obese patients and diabetes mellitus). In the plateau phase (body weight retention) after bariatric intervention, the level of stimulated glucagon-like peptide-1 in obese patients and patients suffering from obesity in combination with diabetes mellitus did not significantly differ from the indicators of healthy individuals. There was no association between the level of glucagon-like peptide-1 and repeated weight gain. This may be due to the limited contribution of glucagon-like peptide-1 to body weight dynamics after bariatric interventions and the predominance of patient compliance. Thus, the level of stimulated glucagon-like peptide-1 at baseline, on the third day and in the plateau phase after bariatric intervention was not associated with the value of repeated weight gain.

The National Heart, Lung, and Blood Institute and the Cardiovascular Medical Research and Education Fund held a workshop on the application of pulmonary vascular disease omics data to the understanding, prevention, and treatment of pulmonary vascular disease. Experts in pulmonary vascular disease, omics, and data analytics met to identify knowledge gaps and formulate ideas for future research priorities in pulmonary vascular disease in line with National Heart, Lung, and Blood Institute Strategic Vision goals. The group identified opportunities to develop analytic approaches to multiomic datasets, to identify molecular pathways in pulmonary vascular disease pathobiology, and to link novel phenotypes to meaningful clinical outcomes. The committee suggested support for interdisciplinary research teams to develop and validate analytic methods, a national effort to coordinate biosamples and data, a consortium of preclinical investigators to expedite target evaluation and drug development, longitudinal assessment of molecular biomarkers in clinical trials, and a task force to develop a master clinical trials protocol for pulmonary vascular disease.

Cranial vault remodeling (CVR) in patients with craniosynostosis serves to correct abnormal skull morphology and increase intracranial volume to prevent or treat pathologic increases in intracranial pressure (Taylor and Bartlett, Plast Reconstr Surg 140: 82e-93e, 2017). Distraction osteogenesis is a well-established technique for bony repositioning and growth stimulation in the facial and long bones, in which the gradual separation of bony segments at an osteotomy site results in generation of new bone and subsequent bone lengthening (Greene, 2018). While initially described in the orthopedic literature, the relevance and applicability of distraction osteogenesis to craniofacial surgery has been well-studied and is now well-established (Steinbacher et al., Plast Reconstr Surg 127: 792-801, 2011). Posterior cranial vault distraction osteogenesis (PVDO) was introduced as a treatment option for cranial vault expansion in patients with craniosynostosis in 2009 by White et al., based upon the premise that posterior vault distraction could provide greater intracranial volume expansion than fronto-orbital advancement and remodeling (FOAR), but that acute posterior cranial vault expansions were limited by the soft tissue envelope of the infant scalp and prone to relapse related to the supine positioning typical of infants (White et al., Childs Nerv Syst 25: 231-236, 2009). Since this introduction, significant evidence has accrued regarding the safety of, and outcomes after, PVDO. PVDO is now known to provide larger increases in intracranial volume in comparison to anterior cranial vault remodeling procedures (Derderian et al., Plast Reconstr Surg 135:1665-1672, 2015) and to provide morphologic improvements in both the posterior and anterior cranial vaults (Goldstein et al., Plast Reconstr Surg 131:1367-1375, 2013). Perioperative major morbidity is comparable to conventional vault remodeling (Taylor et al., Plast Reconstr Surg 129:674e-680e, 2012) and the procedure has been safely applied to patients of various ages with syndromic and non-syndromic craniosynostosis (Zhang et al., J Craniofac Surg 29:566-571, 2018; Li et al., J Craniofac Surg 27:1165-1169, 2016). Many high-volume craniofacial centers now consider PVDO the preferred first operation in infants with syndromic craniosynostosis, and indications for this procedure continue to expand as evidence accrues regarding its utility and safety (Steinbacher et al., Plast Reconstr Surg 127: 792-801, 2011; Swanson et al., Plast Reconstr Surg 137:829e-841e, 2016).

BACKGROUND: Individuals with diabetes require extensive self-management. Little is known about how Hurricane Matthew (Matthew) or Hurricane Florence (Florence) impacted diabetes self-management and outcomes in Robeson County, North Carolina. METHODS: Mixed methods were used to assess the impact of hurricanes on diabetes self-management and outcomes. Individuals with diabetes were recruited for focus groups to understand the perceived impact on diabetes self-management. Health care providers were recruited for parallel key informant interviews. Mean hemoglobin A1c (HbA1c) and frequency of diabetic ketoacidosis (DKA) from hospital data six months before and after Matthew were compared using Student t-tests. RESULTS: A demographic breakdown of 34.25% white, 21.70% Black or African American, and 21.38% American Indian or Alaska Native was observed from focus groups. Qualitative results highlight a limited access to a balanced diet and medications. No significant differences were found between mean HbA1c values before and after Matthew (before Matthew: mean HbA1c 8.34 ± 1.87%; after Matthew: mean HbA1c 8.31 ± 1.93 %; P = .366). The period prevalence (PP) of DKA was higher after Matthew than before (before Matthew: 39 cases out of 4,025 visits, PP = .010; after Matthew: 87 cases out of 3,779 visits, PP = .023; P

Background Penicillin and other beta-lactam antibiotics are recommended for group B Streptococcus and cesarean section prophylaxis, but approximately 10% of pregnant patients report a penicillin allergy. Objective To assess the safety and impact of penicillin allergy evaluation in pregnant patients. Methods In this retrospective study of obstetrician-ordered Allergy/Immunology (AI) electronic consultations (e-consults) from September 20, 2017 through December 31, 2019, we reviewed the electronic health record for e-consult recommendation; patient demographic, obstetric, and allergy histories; and peripartum antibiotic utilization with indication. For patients whose electronic consultation recommended an in-person AI evaluation, testing outcomes were determined, and multivariable logistic regression models were used to compare antibiotic use between patients who did and did not receive an in-person AI evaluation. Results Of 389 obstetrician-ordered e-consults, 363 (93%) recommended an in-person AI evaluation; of these, 222 (61%) patients received an in-person AI evaluation. Of 220 (99%) patients skin tested, 209 (95%) had their penicillin allergy label safely removed. Compared with patients who did not receive an in-person AI evaluation despite it being recommended (n = 141), patients with in-person AI evaluation (n = 222) had reduced peripartum vancomycin (adjusted odds ratio [aOR], 0.07; 95% CI, 0.01-0.33), clindamycin (aOR, 0.17; 95% CI, 0.08-0.34), and gentamicin (aOR, 0.39; 95% CI, 0.19-0.78) use and increased penicillin (aOR, 18.0; 95% CI, 6.30-51.2) use. The fully AI evaluated patients had increased first-line antibiotic prophylaxis for group B Streptococcus (aOR, 26.9; 95% CI, 6.32-114) and cesarean section (aOR, 1.94; 95% CI, 1.06-3.52). Conclusions In a sample of 220 pregnant patients with penicillin allergy histories and in-person AI evaluation, penicillin allergy testing was safe and associated with significantly reduced broad-spectrum antibiotic use and increased first-line beta-lactam antibiotic use.