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To assess the prevalence and potential risk factors for polypharmacy and prescribing of the potentially inappropriate medications, opioids and benzodiazepines/Z-drugs, in older adults with systemic lupus erythematosus (SLE).The study population comprised adults age ≥50 years meeting American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria followed at a tertiary care rheumatology clinic. Information on prescriptions filled in the 4 months preceding chart review was obtained from the Manitoba Drug Program Information Network. Clinical data, including age, sex, Charlson Comorbidity Index (CCI) score, Systemic Lupus Erythematosus Disease Activity Index 2000 score, prednisone use, SLE duration, and rural residence were abstracted from electronic medical records. Logistic regression analyses were performed to assess any association between polypharmacy (using 2 definitions: ≥5 and ≥10 medications), potentially inappropriate medication use, and clinical features.A total of 206 patients (mean age 62 years, 91% female, 36% rural) were included: 148 (72%) filled ≥5 medications, 71 (35%) filled ≥10 medications, 63 (31%) used benzodiazepines/Z-drugs, and 50 (24%) used opioids. Among the 77 patients age ≥65 years, 57 (74%) filled ≥5 medications, and 26 (34%) filled ≥10 medications, compared to 30% and 4%, respectively, of Manitobans age ≥65 years (National Prescription Drug Utilization Information System, 2016). The odds of polypharmacy were greater with prednisone use (adjusted odds ratio [OR] 3.70 [95% confidence interval (95% CI) 1.40-9.79] for ≥5 medications), CCI score (adjusted OR 1.62 [95% CI 1.20-2.17]), and rural residence (adjusted OR 2.05 [95% CI 1.01-4.18]). Odds of benzodiazepine/Z-drug use were increased with polypharmacy (adjusted OR 4.35 [95% CI 1.69-11.22]), and odds of opioid use were increased with polypharmacy (adjusted OR 6.75 [95% CI 1.93-23.69]) and CCI score (adjusted OR 1.29 [95% CI 1.08-1.54]).The prevalence of polypharmacy in this SLE cohort was higher than in the general Manitoban population. Polypharmacy is a strong marker for use of prescription benzodiazepines/Z-drugs and opioids.

Introduction: As the therapeutic options in the management of type 2 diabetes increase, there is an increase confusion among health care professionals, thus leading to the phenomenon of therapeutic inertia. This is the failure to escalate or de-escalate treatment when the clinical need for this is required. It has been studied extensively in various settings, however, it has never been reported in any studies focusing solely on primary care physicians with an interest in diabetes. This group is increasingly becoming the focus of managing complex diabetes care in the community, albeit with the support from specialists. Methods: In this retrospective audit, we assessed the prevalence of the phenomenon of therapeutic inertia amongst primary care physicians with an interest in diabetes in UK. We also assessed the predictive abilities of various patient level characteristics on therapeutic inertia amongst this group of clinicians. Results: Out of the 240 patients reported on, therapeutic inertia was judged to have occurred in 53 (22.1%) of patients. The full model containing all the selected variables was not statistically significant, p = 0.59. So the model was not able to distinguish between situations in which therapeutic inertia occurred and when it did not occur. None of the patient level characteristics on its own was predictive of therapeutic inertia. Conclusion: Therapeutic inertia was present only in about a fifth of patient patients with diabetes being managed by primary care physicians with an interest in diabetes.

Long-term treatment with warfarin is recommended for patients with atrial fibrillation at risk of stroke and those with recurrent venous thrombosis or prosthetic heart valves. Patient education before commencing warfarin − regarding signs and symptoms of bleeding, the impact of diet, potential drug interactions and the actions to take if a dose is missed − is pivotal to successful use. Scoring systems such as the CHADS2 score are used to determine if patients with atrial fibrillation are suitable for warfarin treatment. To rapidly achieve stable anticoagulation, use an age-adjusted protocol for starting warfarin. Regular monitoring of the anticoagulant effect is required. Evidence suggests that patients who self-monitor using point-of-care testing have better outcomes than other patients.

Purpose: This study provides a contemporary assessment of the treatment patterns, health care resource utilization (HRU) and costs among metastatic castration-sensitive prostate cancer (mCSPC) patients in the U.S. Materials and Methods: Adults with mCSPC were selected from Optum's de-identified Clinformatics® Data Mart Database (Commercial insurance/Medicare Advantage [COM/MA]; January 1, 2014–July 31, 2019) or Medicare Fee-for-Service (FFS; January 1, 2014–December 31, 2017). The index date was the first metastatic disease diagnosis date on/after the first prostate cancer diagnosis (without prior evidence of castration resistance). Patients were observed for 12 months pre-index (baseline) through their mCSPC period (from index until castration resistance or followup end). First-line (1L) mCSPC therapy was assessed during the mCSPC period; all-cause HRU and health plan-paid costs per-patient-per-year (PPPY) were measured during baseline and mCSPC periods. Results: Among 6,517 COM/MA and 13,324 Medicare-FFS mCSPC patients over ∼10 months (median mCSPC period), 38% and 48% remained untreated/deferred treatment, and 45% and 46% received 1L androgen deprivation therapy (ADT) monotherapy, respectively. 1L abiraterone acetate and docetaxel were used among 7% and 6% of COM/MA and 1% and 2% of Medicare-FFS patients, respectively. HRU increased from baseline to mCSPC period, resulting in increased health plan-paid costs from $21,201 to $108,767 in COM/MA and from $16,819 to $69,639 PPPY in Medicare-FFS. Conclusions: This study highlights the limited use of newer therapies that improve survival in men with mCSPC in the U.S. HRU and costs increased substantially after onset of metastasis. Given the emergence of newer effective mCSPC therapies, further evaluation of future real-world mCSPC treatment patterns and outcomes is warranted.

BACKGROUND More patients are turning to the internet for their health information than ever before. This is a growing problem as it is well recognized that medical information on the internet is highly variable. We assessed the quality of information on the internet regarding the anti-reflux procedure, Nissen Fundoplication. Three commonly used measures of website quality are the Health On the Net code, the Journal of the American Medical Association Benchmark criteria, and the DISCERN tool. The HON code is a seal of approval awarded by an independent organization where the JAMA Benchmark and DISCERN Tool are a set of standards that can be utilized by an internet user or webpage creator. METHODS We performed a Google search using the term "Nissen Fundoplication", where we analyzed the top 75 websites. We included English language websites and excluded advertisements, websites for medical professionals, duplicates, and requiring a login. Each website included was evaluated for presence of the HON seal and scored with the JAMA Benchmark and DISCERN criteria to determine quality. RESULTS Only 16.28% of websites were found to be HON code certified. The average JAMA benchmark score was 1.23, with 9.3% websites scoring the maximum 4 points and 39.53% receiving a score of 0. The average DISCERN score was 34.65 out of a total possible score of 75, where the mean score for the overall quality of the website (question 16) was 2.19 out of a maximal score of 5. CONCLUSION This study, using 3 commonly used validated measures, has found that the quality of online information pertaining to Nissen Fundoplication is sorely lacking. The implications of these results are twofold as an important reference for institutions to update their source material and a guide when providing patients with adequate resources.

Background Calciphylaxis is a rare disorder characterized by skin necrosis caused by calcium deposition within vessels, thrombosis, and subsequent tissue ischemia. Penile involvement may rarely occur. Objective To identify risk factors, diagnosis, management, and mortality of patients with penile calciphylaxis. Methods A retrospective medical record review was conducted of 16 patients with penile calciphylaxis treated at 2 large urban tertiary care centers between January 2001 and December 2019. A control group of 44 male patients with nonpenile calciphylaxis at the same institution was included. Results The median survival of patients with penile calciphylaxis was 3.8 months (interquartile range, 27.0 months). Mortality was 50% at 3 months and 62.5% at 6 months for penile calciphylaxis, and 13.6% at 3 months and 29.5% at 6 months for controls (P = .008). Patients with penile calciphylaxis were less likely to be obese (P = .04) but more likely to have hyperparathyroidism (P = .0003) and end-stage renal disease (P = .049). Limitations Retrospective study design and small sample size. Conclusions This study further defines the disease course of penile calciphylaxis, which has high mortality. Imaging may be used to aid diagnosis. Risk factors include end-stage renal disease, hyperparathyroidism, and normal body mass index.

Infant vocalizations are early-emerging communicative markers shown to be atypical in autism spectrum disorder (ASD), but few longitudinal, prospective studies exist. In this study, 23,850 infant vocalizations from infants at low (LR)- and high (HR)-risk for ASD (HR-ASD = 23, female = 3; HR-Neg = 35, female = 13; LR = 32, female = 10; 80% White; collected from 2007 to 2017 near Philadelphia) were analyzed at 6, 12, and 24 months. At 12 months, HR-ASD infants produced fewer vocalizations than HR-Neg infants. From 6 to 24 months, HR-Neg infants demonstrated steeper vocalization growth compared to HR-ASD and LR infants. Finally, among HR infants, vocalizing at 12 months was associated with language, social phenotype, and diagnosis at age 2. Infant vocalizing is an objective behavioral marker that could facilitate earlier detection of ASD.

Comprehensive education regarding human papillomavirus (HPV) pathogenesis, vaccination, and patient counseling are not routinely included in the medical school curriculum; consequently, student and provider knowledge, especially concerning head and neck pathology, remains low. The objective of this study was to demonstrate long-term retention of HPV knowledge and positive attitudes towards HPV vaccination after attending our novel HPV workshop, with a focus on knowledge of oropharyngeal cancer. A follow-up survey was administered to medical students 1.5 years after the initial completion of the workshop. HPV vaccination records from the student-led clinic were collected from the immunization information system. Awareness that HPV causes oropharyngeal cancer was present in 33% of medical students pre-curriculum; immediate and long-term post-curricular awareness of this association remained at 90% or higher (p

OBJECTIVE/HYPOTHESIS Utilization of flaps for reconstruction of large head and neck cancer (HNCA) defects has become more prevalent. The present study aimed to assess the impact of center experience as measured by annual hospital caseload on mortality, major complications, resource utilization, and 90-day readmissions following HNCA resection with flap reconstruction. STUDY DESIGN Non-Randomized Controlled Cohort Study. METHODS All adult patients undergoing elective HNCA resection with flap reconstruction were identified utilizing the 2010 to 2018 Nationwide Readmissions Database. Hospitals were subsequently classified as low-, medium-, or high-volume based on annual institutional surgical caseload tertiles. Multivariable regression models were implemented to assess the independent association of hospital volume with the outcomes of interest. RESULTS Over the nine-year study period, the proportion of HNCA resection with flap reconstruction gradually increased (12.8% in 2010 vs. 17.3% in 2018, P

The Radiation Therapy Oncology Group 91-11 trial and US Veterans Affairs trial revolutionized the way locally advanced laryngeal cancers are treated. Adjuvant therapies exist aimed toward laryngeal preservation using docetaxel, cisplatin, and fluorouracil. Cetuximab is a cornerstone of treatment due to the large role of epidermal growth factor receptor in laryngeal and hypopharyngeal carcinomas. In addition, the immune system is vital in the prevention of recurrence, and various immunomodulators against programmed cell death receptor 1 are being investigated. Multidisciplinary management of the patient with laryngeal and hypopharyngeal is key, as many vital functions are affected by this devastating disease.

RATIONALE, AIMS AND OBJECTIVES: The primary purpose of this study was to test both classic and novel FM pain and non-pain symptoms to determine their practical efficacy in aiding clinicians to distinguish FM pain from other chronic pain disorders. METHODS: 158 pain patients from two primary care clinics were evaluated with history, physical exam, chart review, and a questionnaire containing 26 exploratory symptoms (10 from the Symptom Impact Questionnaire (SIQR) and 16 from the FM literature)). The symptoms were rated on a 0-10 VAS for severity by those patients reporting pain over the past week. Somers' D and mean severity differences between FM and chronic pain patients without FM were used to rank the discriminatory and diagnostic contributions of symptoms. RESULTS: Fifty patients (14.2%) carried a chart diagnosis of FM, 108 (30.7%) had pain but not FM, and 192 (54.5%) who had neither pain nor FM. Comparing means between the two pain groups, the 5 best differentiating symptoms (all, P < .0001) were: a persistent deep aching over most of my body, poor balance (7.4 vs 3.1), environmental sensitivity (6.8 vs 3.0), tenderness to touch (6.8 vs 3.6) and pain after exercise (8.1 vs 4.1). Notably, VAS pain though significantly higher for FM was least discriminatory (6.5 vs 5.1, P < .001). The five best symptoms generated a ROC = 0.85 and Somers' D = 0.69, an accuracy of 81%, and an odd's ratio of 14.4. CONCLUSIONS: Our results herein suggest that clinicians may be well-served to consider symptoms in addition to those contained in current diagnostic criteria when recognizing FM in their chronic pain patients.

Background Patients with SARS-CoV-2 infection could develop severe disease requiring critical care admission. Case reports indicated high incidence of hypertriglyceridemia (HTG) in critically ill patients infected with SARS-CoV-2, which might be related to the drugs. Objective We sought to determine the risk factors associated with HTG in this population and to investigate the relationship between HTG and lipase. Methods A retrospective observational study was conducted at our hospital between March 1 and June 30, 2020. Patients were included if they were ≥18 years old, admitted to the intensive care unit (ICU), tested positive for SARS-CoV-2, and had triglycerides (TG) checked during their hospital stay. Results Of the 111 critically ill patients, 103 patients were included. Males comprised 88.3% of the sample. The median TG at baseline was 197.4 (IQR: 139.8-283) mg/dL. The lipase median level at baseline was 23.00 (IQR: 0.00-69.50) IU/L. The results of the mixed-effects logistic regression analysis indicated that patient-level variables, favipiravir use, blood glucose level, and propofol use were significantly associated with HTG. There was no relationship between lipase and TG levels over time. Furthermore, TG concentrations over time showed a similar trend to inflammatory markers. Conclusion and Relevance The incidence of clinically significant HTG was high and was associated with propofol and favipiravir use. HTG might reflect the high inflammatory state in these patients. Clinicians should look at the full picture before changing therapies based only on HTG. Our findings need to be replicated in a larger prospective study.

Background: Successful bariatric surgery involves expertise from a multidisciplinary team. However, compliance with postoperative follow-up is often suboptimal and may impact weight loss. This stud...

OBJECTIVES/HYPOTHESIS To identify prognosticators and determine the efficacies of surgery with adjuvant radiotherapy (SR) and surgery with immunotherapy (SI) of head and neck mucosal melanoma (HNMM). STUDY DESIGN Retrospective database study. METHODS The 2004 to 2017 National Cancer Database was queried for HNMM patients. Cox proportional hazards and Kaplan-Meier analyses evaluated prognosticators of mortality and survival benefits conferred by SR, SI, or surgery with adjuvant radiotherapy and immunotherapy (SRI). Logistic regression identified predictors of adjuvant radiotherapy or immunotherapy use. RESULTS Overall, 1,910 cases (845 surgery, 802 SR, 51 SI, 101 SRI) were analyzed, with 50.3% females and an average age of 68.6 ± 13.8 years. SI was associated with greater overall survival (OS) than surgery (hazard ratio [HR] 0.672; P = .036). SI (HR 0.425; P = .024) and SRI (HR 0.594; P = .045) were associated with superior OS than SR. Older age (HR 1.607; P

Objective This study aimed to develop a classifier for infants at 12 months of age based on a parent-report measure (the First Year Inventory 2.0 [FYI]), for the following reasons: (1) to classify infants at elevated risk, above and beyond that attributable to familial risk status for ASD; and (2) to serve as a starting point to refine an approach for risk estimation in population samples. Method A total of 54 high−familial risk (HR) infants later diagnosed with ASD (HR-ASD), 183 HR infants not diagnosed with ASD at 24 months of age (HR-Neg), and 72 low-risk controls participated in the study. All infants contributed FYI data at 12 months of age and had a diagnostic assessment for ASD at age 24 months. A data-driven, cross-validated analytic approach was used to develop a classifier to determine screening accuracy (eg, sensitivity) of the FYI to classify HR-ASD and HR-Neg. Results The newly developed FYI classifier had an estimated sensitivity of 0.71 (95% CI: 0.50, 0.91) and specificity of 0.72 (95% CI: 0.49, 0.91). Conclusion This classifier demonstrates the potential to improve current screening for ASD risk at 12 months of age in infants already at elevated familial risk for ASD, increasing opportunities for detection of autism risk in infancy. Findings from this study highlight the utility of combining parent-report measures with machine learning approaches.

Background: The optimal treatment for coronavirus disease 2019 (COVID-19) remains unclear. Favipiravir, an RNA polymerase inhibitor, has been used for COVID-19 but its clinical role and safety have not been established. Methods: We evaluated the outcomes of hospitalized adults with COVID-19 on favipiravir as part of combination therapy between March 1 and June 1, 2020. Favipiravir was given at a loading dose of 1600 mg orally every 12 hours for 2 doses, followed by a maintenance dose of 600 mg orally every eight hours. We performed a retrospective assessment of virologic clearance, improvement in oxygenation, clinical improvement and possible adverse effects. Results: One hundred and nine patients received favipiravir for a mean duration of 5.32 days. Mean time from symptom onset to initiation of favipiravir (day 0) was 4.89 days. Quick Sequential Organ Failure Assessment score was 7 days and those receiving Conclusion: Early use of favipiravir as part of combination therapy was associated with improved outcomes, a low mortality rate and a high rate of clinical and oxygenation improvement in patients with mild, moderate, and severe COVID-19. There was no impact on virologic clearance. No severe adverse effects were recorded. The effect of favipiravir as monotherapy and as part of early combination therapy need to be elucidated further in randomized clinical trials.

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is an uncommon skin eruption characterized by fever, leukocytosis, and tender erythematous papules, nodules, and plaques. Histopathologically, SS lesions are characterized by marked superficial papillary edema with a dense neutrophilic infiltrate. SS is known to demonstrate both the Koebner phenomenon and pathergy. The majority of reported cases of these phenomena occur following significant cutaneous injury (e.g., biopsies, burns) rather than minor trauma such as pressure and friction. Here, we present the first known reported case of SS koebnerization secondary to minor grooming-related hair plucking. In addition, this is also the first reported case to our knowledge of SS with perifollicular involvement on histopathology.

BACKGROUND Management of sinonasal malignancy (SNM) often includes surgical resection as part of the multimodality treatment. Treatment-related surgical morbidity can occur, yet risk factors associated with complications in this population have not been sufficiently investigated. METHODS Adult patients with histologically confirmed SNM whose primary treatment included surgical resection were prospectively enrolled into an observational, multi-institutional cohort study from 2015 to 2020. Sociodemographic, disease, and treatment data were collected. Complications assessed included cerebrospinal fluid leak, orbital injury, intracranial injury, diplopia, meningitis, osteoradionecrosis, hospitalization for neutropenia, and subsequent chronic rhinosinusitis. The surgical approach was categorized as endoscopic resection (ER) or open/combined resection (O/CR). Associations between factors and complications were analyzed using Student's t test, Fisher's exact test, and logistic regression modeling. RESULTS Overall, 142 patients met the inclusion criteria. Twenty-three subjects had at least 1 complication (16.2%). On unadjusted analysis, adjuvant radiation therapy was associated with developing a complication (91.3% vs 65.5%, p = 0.013). Compared with the ER group (n = 98), the O/CR group (n = 44) had a greater percentage of higher T-stage lesions (p = 0.004) and more frequently received adjuvant radiation (84.1% vs 64.4%, p = 0.017) and chemotherapy (50.0% vs 30.6%, p = 0.038). Complication rates were similar between the ER and O/CR groups without controlling for other factors. Regression analysis that retained certain factors showed O/CR was associated with increased odds of experiencing a complication (odds ratio, 3.34; 95% confidence interval, 1.06-11.19). CONCLUSIONS Prospective, multicenter evaluation of SNM treatment outcomes is feasible. Undergoing O/CR was associated with increased odds of developing a complication after accounting for radiation therapy. Further studies are warranted to build upon these findings.

Background: ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms. Methods: This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18–75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (2:1; stratified by previous exacerbation count [two, or three or more], maintenance oral corticosteroid use, and region), using an integrated web-based response system, to receive benralizumab at 30 mg every 8 weeks (first three doses given 4 weeks apart) or matched placebo for 24 weeks. Primary efficacy measure was annualised asthma exacerbation rate, with rate ratio (RR) calculated over the approximate 24-week follow-up. Secondary efficacy measures included change from baseline to end of treatment (week 24) in St George's Respiratory Questionnaire (SGRQ) total score (key secondary endpoint), FEV1, peak expiratory flow (PEF), ACQ-6, Predominant Symptom and Impairment Assessment (PSIA), Clinician Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and Sino-Nasal Outcome Test-22 (SNOT-22). All efficacy analyses, except for SNOT-22, were summarised and analysed using the full analysis set on an intention-to-treat population (all randomly assigned patients receiving investigational product, regardless of protocol adherence or continued participation in the study). SNOT-22 was summarised for the subgroup of patients with physician-diagnosed nasal polyposis with informed consent. This study is registered with ClinicalTrials.gov, NCT03170271. Findings: Between July 7, 2017, and Sept 25, 2019, 656 patients received benralizumab (n=427) or placebo (n=229). Baseline characteristics were consistent with severe eosinophilic asthma. Benralizumab significantly reduced exacerbation risk by 49% compared with placebo (RR estimate 0·51, 95% CI 0·39–0·65; p5%) were nasopharyngitis (30 [7%]), headache (37 [9%]), sinusitis (28 [7%]), bronchitis (22 [5%]), and pyrexia (26 [6%]). Fewer serious adverse events were reported for benralizumab (23 [5%]) versus placebo (25 [11%]), and the only common serious adverse event (experienced by >1% of patients) was worsening of asthma, which was reported for nine (2%) patients in the benralizumab group and nine (4%) patients in the placebo group. Interpretation: Our results extend the efficacy profile of benralizumab for patients with severe eosinophilic asthma, showing early clinical benefits in patient-reported outcomes, HRQOL, lung function, and nasal polyposis symptoms. Funding: AstraZeneca.

BACKGROUND: In response to the COVID-19 pandemic, elective surgical procedures have been delayed. Even with the implementation of surgical societies' recommendations, patient safety remains a concern. This study evaluates the postoperative outcomes in patients undergoing bariatric surgery after reopening (RO) elective surgery during the COVID-19 pandemic. METHODS: All patients who underwent bariatric surgery from September 2015 to July 2020 were included. Patients were divided into two cohorts: the pre-COVID-19 (PC) cohort and the RO cohort. Propensity score weighting was used to evaluate postoperative outcomes. RESULTS: Our study included 1076 patients, 1015 patients were in the PC and 61 patients in the RO. Sixty-four percent were female with a mean age of 37 years and median body mass index of 41 kg/m(2). There were no statistically significant differences in 30 days perioperative outcomes, including emergency department visits 24.8% PC versus 19.7% RO (p = 0.492), readmission 4.2% PC versus 8.2% RO (p = 0.361), reoperation 2.6% PC versus 0% RO (p = 0.996), and major complications 4.0% PC versus 4.9% RO (p = 0.812). No patients in the RO contracted COVID-19. CONCLUSIONS: With the appropriate policies and precautionary measures, there appear to be no differences in the 30-day postoperative outcomes before and during the COVID-19 pandemic.

Background Future innovations in science and technology with an impact on multimodal breast cancer management from a surgical perspective are discussed in this narrative review. The work was undertaken in response to the Commission on the Future of Surgery project initiated by the Royal College of Surgeons of England. Methods Expert opinion was sought around themes of surgical de-escalation, reduction in treatment morbidities, and improving the accuracy of breast-conserving surgery in terms of margin status. There was emphasis on how the primacy of surgical excision in an era of oncoplastic and reconstructive surgery is increasingly being challenged, with more effective systemic therapies that target residual disease burden, and permit response-adapted approaches to both breast and axillary surgery. Results Technologies for intraoperative margin assessment can potentially half re-excision rates after breast-conserving surgery, and sentinel lymph node biopsy will become a therapeutic procedure for many patients with node-positive disease treated either with surgery or chemotherapy as the primary modality. Genomic profiling of tumours can aid in the selection of patients for neoadjuvant and adjuvant therapies as well as prevention strategies. Molecular subtypes are predictive of response to induction therapies and reductive approaches to surgery in the breast or axilla. Conclusion Treatments are increasingly being tailored and based on improved understanding of tumour biology and relevant biomarkers to determine absolute benefit and permit delivery of cost-effective healthcare. Patient involvement is crucial for breast cancer studies to ensure relevance and outcome measures that are objective, meaningful, and patient-centred.

OBJECTIVES/HYPOTHESIS Identification of parathyroid glands and adjacent tissues intraoperatively can be quite challenging because of their small size, variable locations, and indistinct external features. The objective of this study is to test the efficacy of the dynamic optical contrast imaging (DOCI) technique as a tool in specifically differentiating parathyroid tissue and adjacent structures, facilitating efficient and reliable tissue differentiation. STUDY DESIGN Prospective study. METHODS Both animal and human tissues were included in this study. Fresh specimens were imaged with DOCI and subsequently processed for hematoxylin and eosin (H&E) stain. The DOCI images were analyzed and compared to the H&E results as ground truth. RESULTS In both animal and human experiments, significant DOCI contrast was observed between parathyroid glands and adjacent tissue of all types. Region of interest analysis revealed most distinct DOCI values for each tissue when using 494 and 572 nm-specific band pass filter for signal detection (P

Difficulty listening in noisy environments is a common complaint of individuals with autism spectrum disorder (ASD). However, the mechanisms underlying such auditory processing challenges are unknown. This preliminary study investigated auditory attention deployment in adults with ASD. Participants were instructed to maintain or switch attention between two simultaneous speech streams in three conditions: location (co-located versus ± 30° separation), voice (same voice versus male–female contrast), and both cues together. Results showed that individuals with ASD can selectively direct attention using location or voice cues, but performance was best when both cues were present. In comparison to neurotypical adults, overall performance was less accurate across all conditions. These findings warrant further investigation into auditory attention deployment differences in individuals with ASD.

To assess knowledge regarding head and neck cancers (HNCs) in 2020, factors associated with knowledge of the role of human papillomavirus (HPV) in HNCs, and factors associated with exposure to Oral, Head and Neck Cancer Awareness Week (OHANCAW).Cross-sectional survey.Online.The survey was distributed to 517 participants via a paid panel and utilized US Census-built quotas to represent the US population.Participants surpassed 50% awareness rates in only 5 of 10 (50.0%), 2 of 6 (33.3%), and 5 of 9 (55.5%) preselected answer choices for subsites, risk factors, and signs/symptoms of HNCs, respectively. Knowledge of HPV's role in oropharyngeal cancer was also low, at 30.6%. However, of the controlled variables, exposure to OHANCAW was closely associated with knowledge of HPV's role in HNC (odds ratio, 10.25; 95% CI, 5.36-19.62). Women and elderly individuals were less likely to be exposed to OHANCAW, while those with higher education, those who drink heavily (4 drinks/d), and current but not former tobacco users were more likely to be exposed.Knowledge of HNCs and the causal role of HPV remains suboptimal, though our results suggest that OHANCAW remains a viable educational pathway. However, certain at-risk populations, such as former smokers and older individuals, whom we may not be effectively reaching and screening, represent a priority for future outreach efforts.

Background Diagnostic shifts at early ages may provide invaluable insights into the nature of separation between autism spectrum disorder (ASD) and typical development. Recent conceptualizations of ASD suggest the condition is only fuzzily separated from non-ASD, with intermediate cases between the two. These intermediate cases may shift along a transition region over time, leading to apparent instability of diagnosis. Methods We used a cohort of children with high ASD risk, by virtue of having an older sibling with ASD, assessed at 24 months (N = 212) and 36 months (N = 191). We applied machine learning to empirically characterize the classification boundary between ASD and non-ASD, using variables quantifying developmental and adaptive skills. We computed the distance of children to the classification boundary. Results Children who switched diagnostic labels from 24 to 36 months, in both directions, (dynamic group) had intermediate phenotypic profiles. They were closer to the classification boundary compared to children who had stable diagnoses, both at 24 months (Cohen's d = .52) and at 36 months (d = .75). The magnitude of change in distance between the two time points was similar for the dynamic and stable groups (Cohen's d = .06), and diagnostic shifts were not associated with a large change. At the individual level, a few children in the dynamic group showed substantial change. Conclusions Our results suggested that a diagnostic shift was largely due to a slight movement within a transition region between ASD and non-ASD. This fact highlights the need for more vigilant surveillance and intervention strategies. Young children with intermediate phenotypes may have an increased susceptibility to gain or lose their diagnosis at later ages, calling attention to the inherently dynamic nature of early ASD diagnoses.

Few studies adequately evaluate the impact of wound location on patient outcomes after lower extremity revascularization. Consequently, we evaluated the relationship between lower extremity wound location and long-term outcomes.We reviewed all patients at our institution undergoing any first-time open surgical bypass or percutaneous transluminal angioplasty with or without stenting for tissue loss between 2005 and 2014. We categorized wounds into three distinct groups: forefoot (ie, toes and metatarsal heads), midfoot (ie, dorsal, plantar, lateral, medial surfaces excluding toes, metatarsal heads, or heel), and heel. Limbs with multiple wounds were excluded from analyses. We compared rates of perioperative complications, wound healing, reintervention, limb salvage, amputation-free survival, and survival using χOf 2869 infrainguinal revascularizations from 2005 to 2014, 1126 underwent a first-time revascularization for tissue loss, of which 253 patients had multiple wounds, 197 had wounds proximal to the ankle, 100 had unreliable wound information, and 576 (forefoot, n = 397; midfoot, n = 61; heel, n = 118) fit our criteria and had a single foot wound with reliable information regarding wound specifics. Patients with forefoot, midfoot, and heel wounds had similar rates of coronary artery disease, hypertension, diabetes, and smoking history (all P.05). Conversely, there were significant differences in patient age (71 vs 69 vs 70 years), prevalence of gangrene (41% vs 5% vs 21%), and dialysis dependence (18% vs 17% vs 30%) (all P .05). There were no statistically significant differences in perioperative mortality (1.3% vs 4.9% vs 4.2%; P = .06) or postoperative complications among the three groups. Between forefoot, midfoot, and heel wounds, there were significant differences in unadjusted 6-month rates of complete wound healing (69% vs 64% vs 53%), 3-year rates of amputation-free survival (54% vs 57% vs 35%), and survival (61% vs 72% vs 41%) (all P .05). After adjustment, compared with forefoot wounds, heel wounds were associated with higher rates of incomplete 6-month wound healing (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.1-2.]), major amputation or mortality (HR, 1.7; 95% CI, 1.1-2.7), and all-cause mortality (HR, 1.8; 95% CI, 1.1-3.0), but not major amputation alone (HR, 2.1; 95% CI, 0.9-4.5). In open surgical bypass-first patients, heel wounds were solely associated with an increased risk of all-cause mortality (HR, 1.7; 95% CI, 1.1-2.8), whereas heel wounds in percutaneous transluminal angioplasty-first patients were associated with an increased risk of incomplete wound healing (HR, 2.2; 95% CI, 1.3-3.7), major amputation or mortality (HR, 2.3; 95% CI, 1.1-5.4), and all-cause mortality (HR, 2.8; 95% CI, 1.1-7.2).Heel wounds confer considerably higher short- and long-term morbidity and mortality compared with midfoot or forefoot wounds in patients undergoing any first-time lower extremity revascularization.

There has been a drastic increase in the incidence of nonmelanoma (NMSC), including squamous, basal cell, and melanoma skin cancers worldwide. Most cases of skin cancer can be treated effectively with surgery; fewer than 10% of cases are advanced and may require additional therapies. A better understanding of the biology of skin cancer will help contribute to better prognostic information and identification of possible new therapeutic targets. Herein, the authors review the biology and pathogenesis of both NMSC and melanoma, focusing on critical cell signaling pathways mediating the disease and current therapeutic strategies targeted to underlying genetic pathways.

In this study, paper-based surgical consent is demonstrated to have significant errors of omission and legibility. These errors were improved by the introduction of a procedure-specific, patient-bespoke, semi-digital consent form application. Patient-reported experience of their involvement in shared decision-making is described for paper-based consent and the implications of future digital consent are discussed.

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

Knee joint trauma can cause an osteochondral defect (OD), a risk factor for osteoarthritis and cause of debilitating pain in patients. Rodent OD models are less translatable due to their smaller joint size and open growth plate. This study proposes sheep as a translationally relevant model to understand the neuronal basis of OD pain. Unilateral 6 mm deep OD was induced in adult female sheep. 2-6 weeks post-operation, lumbar dorsal root ganglia (DRG) neurons were collected from the contralateral and OD side of operated sheep. Functional assessment of neuronal excitability and activity of the pain-related ion channels TRPV1 and P2X3 was carried out using electrophysiology and Ca2+-imaging. Immunohistochemistry was utilized to verify expression of pain-related proteins. We observed that an increased proportion of OD DRG neurons (sheep, N = 3; Ctrl neurons, n =15, OD neurons, n = 16) showed spontaneous electrical excitability (Ctrl: 20.33 ± 4.5%; OD: 50 ± 10%; p = 0.009, unpaired t-test) and an increased proportion fired a greater number of spikes above baseline in response to application of a TRPV1 agonist (capsaicin) application (Ctrl: 40%; OD: 75%; p = 0.04, chi-sq test). Capsaicin also produced Ca2+ influx in an increased proportion of OD DRG neurons isolated (Ctrl: 25%; OD: 44%; p = 0.001, chi-sq test). Neither protein expression, nor functionality of the P2X3 ion channel were altered in OD neurons. Overall, we provide evidence of increased excitability of DRG neurons (an important neural correlate of pain) and TRPV1 function in an OD sheep model. Our data show that functional assessment of sheep DRG neurons can provide important insights into the neural basis of OD pain and thus potentially prevent its progression into arthritic pain. Significance statement Pain is the primary symptom of osteoarthritis (OA) and often the main reason for patients seeking medical care. Understanding pain mechanisms in OA can boost the development of disease specific pain relief. While small animals such as mouse and rat have been widely used in OA pain studies, the genetic and anatomical differences between rodents and humans can hinder clinical translation. Here, we studied pain in an early osteochondral defect (OD) model in sheep, a commonly used large animal model in OA research. We found increased excitability and TRPV1 function in dorsal root ganglia (DRG) neurons innervating the site of OD. This study thus demonstrates the utility of using a large animal, such as sheep, for studying mechanisms of joint pain.

To develop algorithms to identify metastatic castration-sensitive prostate cancer (mCSPC) patients and castration-resistant prostate cancer (mCRPC) patients, using health claims data and laboratory test results.A targeted literature review summarized mCSPC and mCRPC patient selection criteria previously used in real-world retrospective studies. Novel algorithms to identify mCSPC and mCRPC were developed based on diagnosis codes indicating hormone sensitivity/resistance, prostate-specific antigen (PSA) test results, and claims for castration and mCRPC-specific treatments. These algorithms were applied to claims data from Optum Clinformatics Extended DataMart (Date of Death) Databases (commercial insurance/Medicare Advantage [COM/MA]; 01 January 2014-31 July 2019) and Medicare Fee-for-Service (Medicare-FFS; 01 January 2014-31 December 2017).Previous real-world studies identified mCSPC primarily based on metastasis diagnosis codes, and mCRPC based on mCRPC-specific drugs. Using the current study's algorithms, 7034 COM/MA and 19,981 Medicare-FFS patients were identified as having mCSPC, and 2578 COM/MA and 11,554 Medicare-FFS as having mCRPC. Most mCSPC patients were identified based on evidence of being hormone/castration-naive. Patients were identified as having mCRPC most commonly based on rising PSA (COM/MA), or at the metastasis diagnosis date if it occurred after castration (Medicare-FFS). Among patients with mCSPC, 14-17% had evidence of progression to castration resistance during a median 1-year follow-up period, mostly based on use of mCRPC-specific drugs.Comprehensive algorithms based on claims and laboratory data were developed to identify and distinguish patients with mCSPC and mCRPC. This will facilitate appropriate identification of mCSPC and mCRPC patients based on health claims data and better understanding of patient unmet needs in real-world settings.

We evaluated interleukin-6 (IL-6) receptor-α subunit (IL-6Rα) signaling inhibition with sarilumab and tocilizumab, the association between IL-6Rα receptor occupancy (RO) and C-reactive protein (CRP), and the potential clinical relevance of any differences. For this, we measured IL-6Rα binding and signaling inhibition with sarilumab and tocilizumab in vitro, simulated soluble IL-6Rα RO over time for approved sarilumab subcutaneous (SC) and tocilizumab intravenous (IV) and SC doses, and assessed associations between calculated RO and CRP reduction, 28-joint Disease Activity Score based on CRP, and 20%/50%/70% improvement in American College of Rheumatology responses from clinical data. Sarilumab binds IL-6Rα in vitro with 15- to 22-fold higher affinity than tocilizumab, and inhibits IL-6–mediated classical and trans signaling via membrane-bound and soluble IL-6Rα. Sarilumab 200 and 150 mg SC every 2 weeks achieved >90% RO after first and second doses, respectively, maintained throughout the treatment period. At steady-state trough, RO was greater with sarilumab 200 mg (98%) and 150 mg SC every 2 weeks (94%), and tocilizumab 162 mg SC weekly (>99%) and 8 mg/kg IV every 4 weeks (99%), vs tocilizumab 162 mg SC every 2 weeks (84%) and 4 mg/kg IV every 4 weeks (60%). Higher RO was associated with greater CRP reduction and 28-joint Disease Activity Score based on CRP reduction, and more sarilumab patients achieving 20%/50%/70% improvement in American College of Rheumatology responses. The greatest reduction in CRP levels was observed with sarilumab (both doses) and tocilizumab 8 mg/kg IV every 4 weeks (reductions proportionally smaller with 4 mg/kg IV every 4 weeks). Higher IL-6Rα binding affinity translated into higher RO with sarilumab vs tocilizumab 4 mg/kg every 4 weeks or 162 mg every 2 weeks; tocilizumab required the higher dose or increased frequency to maintain the same degree of RO and CRP reduction. Higher RO was associated with clinical parameter improvements.

Background and Aim: We have previously shown in a retrospective analysis that the plasma thyroid-stimulating hormone (TSH) rises significantly post-Ramadan in levothyroxine-treated hypothyroid patients, possibly as a result of lifestyle alterations and time restrictions during the nonfasting period from dusk until dawn. The aim of this study is to determine the best time to instruct patients to take levothyroxine during Ramadan so as to minimize changes in thyroid function tests during this period. Methods: In a randomized prospective design, hypothyroid patients taking levothyroxine were randomized to receive instructions to take levothyroxine at one of the following 3 times during Ramadan: (group 1) at dusk 30-min before Iftar meal, (group 2) 3 or more hours after Iftar meal, or (group 3) at dawn 30-min before Suhur meal. Thyroid function tests were performed within 3 months before Ramadan and within 6 weeks post-Ramadan. Data from patients with at least 1 blood test before or after Ramadan were analyzed using mixed-effects regression models. Results: Plasma TSH levels were available at one or more time points for 148 patients, group 1 (n = 50), group 2 (n = 46), and group 3 (n = 52). A statistically significant within-patient increase in plasma TSH was seen in patients at the 25th percentile pre-Ramadan in groups 2 and 3 (p values Conclusions: Our data suggest that instructing patients to take levothyroxine at the time of breaking the fast 30 min before the Iftar meal minimizes unfavorable changes in plasma TSH post-Ramadan. In contrast, instructing patients to take levothyroxine 3 h post-Iftar or 30 min before Suhur led to a greater rise in post-Ramadan TSH.

Bacterial biofilms are often found in chronically infected wounds. Biofilms protect bacteria from antibiotics and impair wound healing. Surgical debridement is often needed to remove the biofilm from an infected wound. Laser-generated shockwave (LGS) treatment is a novel tissue-sparing treatment for biofilm disruption. Previous studies have demonstrated that LGS is effective in disrupting biofilms in vitro. In this study, we aim to determine the safety threshold of the LGS technology in an in vivo rodent model. To understand the in vivo effects of LGS on healthy cutaneous tissue, the de-haired dorsal skin of Sprague-Dawley rats were treated with LGS at three different peak pressures (118, 296, 227 MPa). These pressures were generated using a 1064 nm Nd/YAG laser (pulse duration 5 ns and laser fluence of 777.9 mJ) with laser spot size diameters of 2.2, 3.0, and 4.2 mm, respectively. Following treatment, the animals were observed for 72 h, and a small subset was euthanized at 1-h, 24-h, and 72-h post-treatment and assessed for tissue injury or inflammation under histology. Each treatment group consisted of 9 rats (n = 3/time point for 1-h, 24-h, 72-h post-treatment). An additional 4 control (untreated) rats were included in the analysis, for a total of 31 animals. Gross injuries occurred in 21 (77%) animals and consisted of minor erythema, with prevalence positively correlated with peak pressure (p < 0.05). Of injuries under gross observation, 94% resolved within 24 h. Under histological analysis, the injuries and tissue inflammation were found to be localized to the epidermis and superficial dermis. LGS appears to be well tolerated by cutaneous tissue for the laser energy settings shown to be effective against bacterial biofilm in vitro. All injuries incurred, at even the highest peak pressures, were clinically mild and resolved within 1 day. This lends further support to the overall safety of LGS and serves to translate LGS towards in vivo efficacy studies.

To outline our current neonatal resuscitation practices and discuss changes that have occurred in the field since the International Liaison Committee on Resuscitation (ILCOR) guidelines were published in 2015. There have been interesting developments in delayed cord clamping, heart rate assessments, and oxygen delivery. New developments continue to emerge in the field of neonatal resuscitation, some of which have been adopted into mainstream practice, while others still require more research to establish efficacy and safety.

Pathogenic variants in methyl-CpG protein 2 (MECP2; OMIM 300005) result in an X-linked, severe, and progressive epigenetic disorder, Rett syndrome (RTT, OMIM: 312750), that predominantly affects females (Rett, 1966). Using Neul's revised diagnostic criteria, affected individuals can be clinically classified as classic or atypical RTT (Neul et al., 2010). After 6–18 months of apparently normal development, girls with the classic form of RTT gradually start losing their previously acquired skills including spoken language and other communication, coordination, and social interaction. Along with acquired microcephaly, affected girls lose purposeful use of their hands and develop midline stereotypic hand movements, breathing irregularities, seizures, scoliosis, and disturbed sleeping patterns. The partial/complete loss of spoken language is one of the core diagnostic criteria which is essential to be present for an affected individual to be classified as an individual with classic RTT. However, it is not necessarily a required criterion when classifying individuals with atypical RTT (Neul et al., 2010; Schonewolf-Greulich et al., 2019). As per the definitions adopted in the article by Neul et al. (2010) “… an individual who had learned to babble but then loses this ability is considered to have a loss of acquired language …” Owing to the broad variability of the phenotype in individuals with RTT, a proportion of them satisfy some, but not all, of the necessary revised diagnostic criteria and are classified as atypical RTT. Furthermore, individuals may be classified as RTT-like, exhibiting some clinical features associated with RTT, but not enough to be classified as either classic or atypical RTT (Ip et al., 2018). Approximately 97% of individuals with classic RTT and 86% of individuals with atypical RTT have pathogenic variants in MECP2 (Neul et al., 2014). A small proportion of individuals with clinical features overlapping with RTT have been reported with pathogenic variants in cyclin-dependent kinase-like 5 (CDKL5, OMIM: 300203) and forkhead box G1 (FOXG1, OMIM: 164874); however, a significant proportion of individuals clinically classified as RTT remain without a definite genetic diagnosis (Armani et al., 2012).

Background Diabetes is common in patients with rheumatoid arthritis (RA). Interleukin (IL)-6 is implicated in both the pathogenesis of RA and in glucose homeostasis; this post hoc analysis investigated the effects of IL-6 receptor vs. tumour necrosis factor inhibition on glycosylated haemoglobin (HbA1c) in patients with RA with or without diabetes. Methods Data were from two placebo-controlled phase III studies of subcutaneous sarilumab 150/200 mg q2w + methotrexate or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and a phase III monotherapy study of sarilumab 200 mg q2w vs. adalimumab 40 mg q2w. Patients with diabetes were identified by medical history or use of antidiabetic medication (patients with HbA1c ≥ 9% were excluded from all three studies). HbA1c was measured at baseline and weeks 12/24. Safety and efficacy were assessed in RA patients with or without diabetes. Results Patients with diabetes (n = 184) were older, weighed more and exhibited higher RA disease activity than patients without diabetes (n = 1928). Regardless of diabetes status, in patients on background csDMARDs, least squares (LS) mean difference (95% CI) in change from baseline in HbA1c for sarilumab 150 mg/200 mg vs. placebo at week 24 was − 0.28 (− 0.40, − 0.16; nominal p p p = 0.0043). Greater reduction in HbA1c than placebo or adalimumab was observed at week 24 with sarilumab in patients with diabetes and/or baseline HbA1c ≥ 7%. There was no correlation between baseline/change from baseline in HbA1c and baseline/change from baseline in C-reactive protein, 28-joint Disease Activity Score, or haemoglobin, nor between HbA1c change from baseline and baseline glucocorticoid use. Medical history of diabetes or use of diabetes treatments had limited impact on safety and efficacy of sarilumab and was consistent with overall phase III findings in patients with RA. Conclusions In post hoc analyses, sarilumab was associated with a greater reduction in HbA1c than csDMARDs or adalimumab, independent of sarilumab anti-inflammatory effects. Prospective studies are required to further assess these preliminary findings. Trial registration ClinTrials.gov NCT01061736: date of registration February 03, 2010; ClinTrials.gov NCT01709578: date of registration October 18, 2012; ClinTrials.gov NCT02332590: date of registration January 07, 2015.

Background. This study aimed to assess the validity of 2 microsimulation models of colorectal cancer (CRC), Policy1-Bowel and ASCCA. Methods. The model-estimated CRC risk in population subgroups with different health statuses, “dwell time” (time from incident precancerous polyp to symptomatically detected CRC), and reduction in symptomatically detected CRC incidence after a one-time complete removal of polyps and/or undetected CRC were compared with published findings from 3 well-established models ( MISCAN, CRC-SPIN, and SimCRC). Furthermore, 6 randomized controlled trials (RCTs) that provided screening using a guaiac fecal occult blood test (Funen trial, Burgundy trial, and Minnesota Colon Cancer Control Study [MCCCS]) or flexible sigmoidoscopy (NORCCAP, SCORE, and UKFSST) with long-term follow-up were simulated. Model-estimated long-term relative reductions of CRC incidence (RR inc) and mortality (RR mort) were compared with the RCTs’ findings. Results. The Policy1-Bowel and ASCCA estimates showed more similarities to CRC-SPIN and SimCRC. For example, overall dwell times estimated by Policy1-Bowel (24.0 years) and ASCCA (25.3) were comparable to CRC-SPIN (25.8) and SimCRC (25.2) but higher than MISCAN (10.6). In addition, ∼86% of Policy1-Bowel’s and ∼74% of ASCCA’s estimated RR inc and RR mort were consistent with the RCTs’ long-term follow-up findings. For example, at 17 to 18 years of follow-up, the MCCCS reported RR mort of 0.67 (95% confidence interval [CI], 0.51–0.83) and 0.79 (95% CI, 0.62–0.97) for the annual and biennial screening arm, respectively, and the UKFSST reported RR mort of 0.70 (95% CI, 0.62–0.79) for CRC at all sites and 0.54 (95% CI, 0.46–0.65) for distal CRC. The corresponding model estimates were 0.65, 0.74, 0.81, and 0.61, respectively, for Policy1-Bowel and 0.65, 0.70, 0.75, and 0.58, respectively, for ASCCA. Conclusion. Policy1-Bowel and ASCCA’s estimates are largely consistent with the data included for comparisons, which indicates good model validity.

Dengue virus infects several million people each year. Although usually a self-limiting disease, some patients can develop life-threatening severe complications, characterized by plasma leakage, hemorrhaging, and shock. The signs and symptoms of severe disease usually arise late in the disease course when patients are recovering and fever has subsided, making it difficult to predict. Efforts are underway to identify risk factors and biomarkers that can accurately predict disease severity in the acute febrile phase of the disease, facilitating early intervention and treatment strategies for those at greatest risk. In this review we discuss recent advancements in identifying risk factors and biomarkers for the prognosis of severe dengue.

An 8-y-old Labrador Retriever was presented to a small animal practice in northern Virginia with a history of recent lethargy. Physical examination findings were unremarkable. Ultrasound revealed several large hepatic masses and multiple smaller masses involving the pancreas. Cytologic findings on fine-needle aspirates of the hepatic masses included inflammation and necrosis with eosinophilic, membranous oval structures consistent with cestode infection. Histopathologic findings for biopsies of these masses included extensive necrosis, inflammation, and PAS-positive hyaline-like membranous material interpreted as metacestode cyst wall. A PCR product was generated from aspirate material using primers specific for Echinococcus multilocularis. Subsequent sequence data were 100% homologous to E. multilocularis NADH dehydrogenase subunit I gene sequences. The dog received daily oral albendazole (10 mg/kg) treatment, but its condition deteriorated, and the dog was euthanized. The dog, born in Mississippi, was brought as a puppy to Virginia with no other travel history. To our knowledge, alveolar echinococcosis has not been reported previously in a dog in the United States; E. multilocularis infection was apparently acquired in the mid-Atlantic region of the United States.

Background: The approved dosing of ertapenem in patients with chronic kidney disease stage 5 utilizing dialysis (CKD-5D) is 0.5 g intravenous daily. Several reports associated this dosing strategy with neurotoxicity. Objective: The purpose of this study is to identify the incidence of neurotoxicity in this population and the risk factors associated with this toxicity. The secondary objective was to review the literature and discuss a safer/cost-effective dosing strategy based on available data. Methods: A retrospective study was conducted screening all patients who received ertapenem and hemodialysis at our quaternary hospital between May 2015 and March 2019. Patients’ demographics, comorbidities, concomitant drugs (known to induce neurotoxicity), and seizure history were collected. Results: A total of 99 eligible patients were identified; 10 of them (10%) developed neurotoxicity. The patients who developed neurotoxicity were all male; mean age was 74 ± 9 years as compared with 68.9 ± 13 years in the sample. Bivariate relationships between all predictors and the seizures (dichotomously coded) were estimated to investigate the risk factors. The following were the significant predictors of seizures: male sex (17%; P = 0.014), dementia (27%; P = 0.012), and concomitant use of β-lactams, aminoglycosides, or fluoroquinolones (19.6%; P = 0.042). Conclusion and Relevance: The currently approved ertapenem dose imposes a risk of developing neurotoxicity in patients with CKD-5D. Utilizing the published data in this population, alternative post-dialysis dosing strategies administered through dialysis access such as 1 g loading dose, followed by either 0.5 g (for the 48 hours interdialytic time) or 1 g (for the 72 hours interdialytic time) might warrant further investigation for efficacy and safety.

Introduction Hemodialysis patients frequently suffer from anemia. Proper utilization of therapies such as iron and erythropoiesis-stimulating agents (ESAs) is crucial to attain symptom management and established hemoglobin targets. The purpose of this study was to evaluate the clinical and financial impact of nephrology-trained pharmacists on anemia management in these patients. Materials and methods A retrospective study of outpatient hemodialysis patients observed between January 2010 and December 2011. In December 2010, pharmacists were tasked to manage anemia under a medical directive. Primary endpoints were compared across years using a mixed-effects model strategy. An unstructured random effects correlation matrix was utilized to capture patient-level variation in 2010 and 2011, separately. Results Of 202 patients identified, 163 contributed in both years, 57% were males, aged 65.18 ± 16.3 years. Hemoglobin levels were 10.95 ± 0.95 and 10.83 ± 0.94 g/dL in 2010 vs. 2011, respectively (p = 0.158), while the transfusion rate was 1.3% and 1.8%, respectively (p = 0.196). Ferritin levels of 273.5 ± 22 and 317.1 ± 12 ng/mL (p = 0.0019), iron saturation 0.30 ± 0.11 and 0.30 ± 0.05 (p = 0.838), and parenteral iron dose of 215.4 ± 100.2 and 317.1 ± 123.7 mg, respectively (p = 0.996), were identified. Finally, the average weekly ESA dose in 2010 was higher and trending up as compared to 2011 where it significantly trended down. The amount of intravenous erythropoietin alfa was 12,315.6 ± 76 vs. 11,364.1 ± 52 units/week, respectively (p = 0.0556) with expenditure of 2.8 million Canadian dollars in 2010 vs. 2.3 million Canadian dollars in 2011. Conclusion The participation of a nephrology pharmacist resulted in favorable outcomes in dose optimization, decreased expenditure, and positive trends in therapeutic goal achievement.

ObjectivesThis study evaluated the comparative effectiveness of a tumour necrosis factor inhibitor (TNFi) versus a non-TNFi (biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs)) as the first-line treatment following conventional synthetic DMARDs, as well as potential modifiers of response, observed in US clinical practice.MethodsData were from a large US healthcare registry (Consortium of Rheumatology Researchers of North America Rheumatoid Arthritis Registry). The analysis included patients (aged ≥18 years) with a documented diagnosis of rheumatoid arthritis (RA), a valid baseline Clinical Disease Activity Index (CDAI) score of >2.8 and no prior bDMARD or tsDMARD use. Outcomes were captured at 1-year postinitiation of a TNFi (adalimumab, etanercept, certolizumab pegol, golimumab or infliximab) or a non-TNFi (abatacept, tocilizumab, rituximab, anakinra or tofacitinib) and included CDAI, 28-Joint Modified Disease Activity Score, patient-reported outcomes (including the Health Assessment Questionnaire Disability Index, EuroQol-5 Dimension score, sleep, anxiety, morning stiffness and fatigue) and rates of anaemia. Groups were propensity score-matched at baseline to account for potential confounding.ResultsThere were no statistically significant differences observed between the TNFi and non-TNFi treatment groups for outcomes assessed, except the incidence rate ratio for anaemia, which slightly favoured the TNFi group (19.04 per 100 person-years) versus the non-TNFi group (24.01 per 100 person-years, p=0.03). No potential effect modifiers were found to be statistically significant.ConclusionsThe findings of no significant differences in outcomes between first-line TNF versus first-line non-TNF groups support RA guidelines, which recommend individualised care based on clinical judgement and consideration of patient preferences.

Dengue induces a spectrum of severity in humans from the milder dengue fever to severe disease, or dengue hemorrhagic fever (DHF). Chymase is a candidate biomarker that may aid dengue prognosis. This prospective study aimed to identify whether warning signs of severe dengue, including hypovolemia and fluid accumulation, were associated with elevated chymase. Serum chymase levels were quantified prospectively and longitudinally in hospitalized pediatric dengue patients in Sri Lanka. Warning signs were determined based on daily clinical assessments, laboratory tests and ultrasound findings. Chymase was significantly elevated during the acute phase of disease in DHF or Severe dengue, defined by either the 1997 or 2009 WHO diagnosis guidelines, and persisted longer in the most severe patients. Chymase levels were higher in patients with narrow pulse pressure and clinical warning signs such as severe leakage, fluid accumulation, pleural effusion, gall-bladder wall thickening and rapid haematocrit rise concurrent with thrombocytopenia. No association between chymase and liver enlargement was observed. This study confirms that serum chymase levels are associated with DHF/Severe dengue disease in hospitalized pediatric patients. Chymase levels correlate with warning signs of vascular dysfunction highlighting the possible functional role of chymase in vascular leakage during dengue. Nanyang Technological University Singapore Infectious Diseases Initiative - National Medical Research Council Published version The clinical study was funded by the Lee Kong Chian School of Medicine (A. Wilder-Smith`s start-up grant), monitoring of the study was funded by a global health grant from the Singapore Infectious Diseases Initiative (to Wei-Yee Leong). The laboratory and data analyses were funded by Duke-NUS Start-up funding to Ashley St. John.