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Key Points Question Are results of universal and selective screening for suicide risk implemented in a pediatric emergency department associated with future suicidal behaviors? Findings In this cohort study of 15 003 youths aged 8 to 18 years, positive screens were significantly associated with subsequent suicide-related hospital visits compared with standard emergency department procedures. Screening also more than doubled the detection of suicide risk compared with treatment as usual. Meaning These findings suggest that screening for suicide risk in pediatric emergency departments is an effective approach to identify risk for subsequent suicide-related emergency department visits., This cohort study examines the association between results of universal and selective screening for suicide risk in a pediatric emergency department using the Ask Suicide-Screening Questions (ASQ) instrument and subsequent suicide-related outcomes., Importance According to National Patient Safety Goal 15.01.01, all individuals being treated or evaluated for behavioral health conditions as their primary reason for care in hospitals and behavioral health care organizations accredited by The Joint Commission should be screened for suicide risk using a validated tool. Existing suicide risk screens have minimal or no high-quality evidence of association with future suicide-related outcomes. Objective To test the association between results of the Ask Suicide-Screening Questions (ASQ) instrument in a pediatric emergency department (ED), implemented through selective and universal screening approaches, and subsequent suicide-related outcomes. Design, Setting, and Participants In this retrospective cohort study at an urban pediatric ED in the United States, the ASQ was administered to youths aged 8 to 18 years with behavioral and psychiatric presenting problems from March 18, 2013, to December 31, 2016 (selective condition), and then to youths aged 10 to 18 years with medical presenting problems (in addition to those aged 8-18 years with behavioral and psychiatric presenting problems) from January 1, 2017, to December 31, 2018 (universal condition). Exposure Positive ASQ screen at baseline ED visit. Main Outcomes and Measures The main outcomes were subsequent ED visits with suicide-related presenting problems (ie, ideation or attempts) based on electronic health records and death by suicide identified through state medical examiner records. Association with suicide-related outcomes was calculated over the entire study period using survival analyses and at 3-month follow-up for both conditions using relative risk. Results The complete sample was 15 003 youths (7044 [47.0%] male; 10 209 [68.0%] black; mean [SD] age, 14.5 [3.1] years at baseline). The follow-up for the selective condition was a mean (SD) of 1133.7 (433.3) days; for the universal condition, it was 366.2 (209.2) days. In the selective condition, there were 275 suicide-related ED visits and 3 deaths by suicide. In the universal condition, there were 118 suicide-related ED visits and no deaths during the follow-up period. Adjusting for demographic characteristics and baseline presenting problem, positive ASQ screens were associated with greater risk of suicide-related outcomes among both the universal sample (hazard ratio, 6.8 [95% CI, 4.2-11.1]) and the selective sample (hazard ratio, 4.8 [95% CI, 3.5-6.5]). Conclusions and Relevance Positive results of both selective and universal screening for suicide risk in pediatric EDs appear to be associated with subsequent suicidal behavior. Screening may be a particularly effective way to detect suicide risk among those who did not present with ideation or attempt. Future studies should examine the impact of screening in combination with other policies and procedures aimed at reducing suicide risk.

Objectives Chronic exposure to arsenic has been reported as a risk factor for nonmelanoma skin cancer, notably squamous cell carcinoma. However, current knowledge is limited about the association between arsenic exposure and melanoma. Our objectives were to (1) measure the association between total urinary arsenic levels and melanoma compared with nonmelanoma skin cancer and no cancer and (2) analyze the association between water source and melanoma and nonmelanoma skin cancer. Methods We collected cross-sectional data from the 2003-2016 cycles of the National Health and Nutrition Examination Survey. We conducted univariate and multivariate logistic regressions. To evaluate the possible association of skin cancer with source of tap water, we calculated odds ratios for participants with melanoma and nonmelanoma skin cancer, compared with participants with no cancer. Results White race, higher education, higher socioeconomic status, and smoking history were associated with melanoma and nonmelanoma skin cancer in the full study population. After adjusting for age and race/ethnicity, the adjusted odds ratio of participants with >50 μg/L of total urinary arsenic for melanoma or nonmelanoma skin cancer was 1.87 (95% CI, 0.58-6.05) and 2.23 (95% CI, 1.12-4.45) times higher compared with no cancer, respectively. Participants with nonmelanoma skin cancer had 2.06 increased odds of reporting a nonmunicipal water source compared with participants without cancer. Conclusions We did not find a relationship between the incidence of melanoma and exposure to arsenic among US adults. Nonmunicipal water sources were associated with nonmelanoma skin cancer and should be further investigated.

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.

Purpose Information regarding the views of patients, on visual field testing is limited, and no information exists regarding their preferences for test developments. This study aimed to increase knowledge of patients’ experiences of visual field assessment and to explore their opinions and priorities regarding current areas of research and development. Design Online questionnaire with purposive sampling design. Participants Adults who regularly undergo visual field tests in Australia who report having glaucoma or being at glaucomatous risk. Methods An anonymous survey, implemented using the Qualtrics webtool, with both closed- and-open ended questions designed to explore opinions regarding visual field testing, visit attendance for perimetry, as well as priorities for developments. Main Outcome Measures The survey assessed 3 domains: (1) opinions regarding test duration and visit frequency, (2) subjective experience, and (3) perspectives on future developments. Results One hundred fifty-two complete survey responses were obtained. The median age of participants was 66 years (interquartile range [IQR], 60–72 years). Most participants (70%) had experience of undergoing more than 11 visual field tests. Participants recalled that they completed visual field tests in median of 6 minutes (IQR, 5–8 minutes) and were willing to accept additional time (median, 5 minutes; IQR, 3–6 minutes) to obtain more information. Participants were prepared to increase both the number of visual field tests per eye and the frequency of visual field tests (median, 3 visits per year; IQR, 2–4 visits per year) to gain more information about their visual status. Regarding future developments, the most preferred option was “similar test times but an increase in the level of information about my visual field,” which ranked significantly higher than all other options, including “shorter test times that maintain the currently available level of information about my visual field.” Conclusions Our study confirms, in a different population and health care system, previous research reporting patient perspectives on visual field assessment. We further revealed that health care consumers show a strong preference for accurate information about their vision and report being prepared to undergo longer visual field tests or more visual field tests to achieve that outcome.

Setting Nonoptimized medication therapies (NOMTs) are associated with likely avoidable illnesses and mortality affecting millions of people and costing an estimated $528 billion per year in excess health spending in the United States. The coronavirus disease 2019 (COVID-19) pandemic brought into focus barriers limiting the ability of U.S. pharmacists and pharmacies to provide services that can reduce NOMTs and improve U.S. population health. Objectives This National Science Foundation Center for Health Organization Transformation study explored potential strategies that U.S. pharmacists, pharmacies, and their partners could implement to reduce NOMTs while also delivering other forms of value to U.S. populations from 2021 to 2025 (during and after the COVID-19 pandemic). Design A panel of senior leaders representing the U.S. pharmacist and pharmacy sector participated in a 4-round Delphi process to identify unmet needs, barriers, change drivers, and priority strategies for meeting those needs. Data were gathered and analyzed by public health researchers, most of whom are outside the pharmacist and pharmacy sector. Results A comprehensive set of evidence-based strategies with potential to reduce NOMTs, protect and improve population health and well-being, and strengthen the sector were identified. Four transformational strategies were recommended: comprehensive payment and practice transformation, strengthening pharmacy data interoperability infrastructure, development of unifying measurement and management mechanisms, and development of a more robust national research infrastructure. Strengthening health equity was a cross-cutting strategy affecting all areas. Conclusion The results may be of interest to policy makers, pharmacists, pharmacies, physicians, nurses and other clinicians, pharmaceutical firms, plan sponsors, plans, health systems, clinics, aging care, digital technology companies, and others interested in optimizing outcomes from medications and related therapies for U.S. populations.

Background Despite a better understanding of the epidemiology, pathogenesis, and management of patients with anaphylaxis, there remain knowledge gaps. Enumerating and prioritizing these gaps would allow limited scientific resources to be directed more effectively. Objective We sought to systematically describe and appraise anaphylaxis knowledge gaps and future research priorities based on their potential impact and feasibility. Methods We convened a 25-member multidisciplinary panel of anaphylaxis experts. Panelists formulated knowledge gaps/research priority statements in an anonymous electronic survey. Four anaphylaxis themed writing groups were formed to refine statements: (1) Population Science, (2) Basic and Translational Sciences, (3) Emergency Department Care/Acute Management, and (4) Long-Term Management Strategies and Prevention. Revised statements were incorporated into an anonymous electronic survey, and panelists were asked to rate the impact and feasibility of addressing statements on a continuous 0 to 100 scale. Results The panel generated 98 statements across the 4 anaphylaxis themes: Population Science (29), Basic and Translational Sciences (27), Emergency Department Care/Acute Management (24), and Long-Term Management Strategies and Prevention (18). Median scores for impact and feasibility ranged from 50.0 to 95.0 and from 40.0 to 90.0, respectively. Key statements based on median rating for impact/feasibility included the need to refine anaphylaxis diagnostic criteria, identify reliable diagnostic, predictive, and prognostic anaphylaxis bioassays, develop clinical prediction models to standardize postanaphylaxis observation periods and hospitalization criteria, and determine immunotherapy best practices. Conclusions We identified and systematically appraised anaphylaxis knowledge gaps and future research priorities. This study reinforces the need to harmonize scientific pursuits to optimize the outcomes of patients with and at risk of anaphylaxis.

Background: Epidemiological data on anticoagulation for venous thromboembolism (VTE) in prostate cancer are sparse. We aimed to investigate associations between anticoagulation duration and risks of VTE recurrence after treatment cessation and major on-treatment bleeding in men with prostate cancer in Sweden. Methods: Using nationwide prostate cancer registry and prescribing data, we followed 1413 men with VTE and an outpatient anticoagulant prescription following prostate cancer diagnosis. Men were followed to identify cases of recurrent VTE, and hospitalized major bleeding. We calculated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) to quantify the association between anticoagulation duration (reference ≤3 months) and recurrent VTE using Cox regression. We estimated 1-year cumulative incidences of major bleedings from anticoagulation initiation.Results: The outpatient anticoagulation prescribed was parenteral (64%), direct oral anticoagulant (31%), and vitamin K antagonist (20%). Median duration of anticoagulation was 7 months. Adjusted HRs (95% CI) for off-treatment recurrent pulmonary embolism (PE) were 0.32 (0.09–1.15) for >3–6 months’ duration, 0.21 (0.06–0.69) for >6–9 months and 0.16 (0.05–0.55) for >9 months; corresponding HRs for deep vein thrombosis (DVT) were 0.67 (0.27–1.66), 0.80 (0.31–2.07), and 1.19 (0.47–3.02). One-year cumulative incidences of intracranial, gastrointestinal and urogenital bleeding were 0.9%, 1.7%, 3.0% during treatment, and 1.2%, 0.9%, 1.6% after treatment cessation.Conclusion: The greatest benefit in reducing recurrent VTE risk was with >9 months anticoagulation for PE and >3–6 months for DVT. Risks of major bleeding were low not being substantially different to the risks after treatment cessation.

Background Respiratory motion may introduce errors during radiotherapy. This study aims to assess and validate internal gross tumour volume (IGTV) margins in proximal and distal borders of gastroesophageal junction (GEJ) tumours during simultaneous integrated boost radiotherapy. Methods We enrolled 10 patients in group A and 9 patients in group B. For all patients, two markers were placed at the upper and lower borders of the tumour before treatment. In group A, within the simulation and every 5 fractions of radiotherapy, we used 4-dimensional computed tomography (4DCT) to record the intrafractional displacement of the proximal and distal markers. By fusing the average image of each repeated 4DCT with the simulation image based on the lumbar vertebra, the interfractional displacement could be obtained. We calculated the IGTV margin in the proximal and distal borders of the GEJ tumour. In group B, by referring to the simulation images and cone-beam computed tomography (CBCT) images, the range of tumour displacement in proximal and distal borders of GEJ tumour was estimated. We calculated the proportion of marker displacement range in group B lay within the IGTV margin calculated based on the data obtained in group A to estimate the accuracy of the IGTV margin. Results The intrafractional displacement in the cranial–caudal (CC) direction was significantly larger than that in the anterior–posterior (AP) and left–right (LR) directions for both the proximal and distal markers of the tumour. The interfractional displacement in the AP and LR directions was larger than that in the CC direction (p = 0.001, p = 0.017) based on the distal marker. The IGTV margins in the LR, AP and CC directions were 9 mm, 8.5 mm and 12.1 mm for the proximal marker and 15.8 mm, 12.7 mm and 11.5 mm for the distal marker, respectively. In group B, the proportions of markers that located within the IGTV margin in the LR, AP and CC directions were 96.5%, 91.3% and 96.5% for the proximal marker and 100%, 96.5%, 93.1% for the distal marker, respectively. Conclusions Our study proposed individualized IGTV margins for proximal and distal borders of GEJ tumours during neoadjuvant radiotherapy. The IGTV margin determined in this study was acceptable. This margin could be a reference in clinical practice.

Global rates of obesity and type 2 diabetes mellitus (T2DM) are increasing globally concomitant with a rising prevalence of sleep deprivation and sleep disorders. Understanding the links between sleep, obesity and T2DM might offer an opportunity to develop better prevention and treatment strategies for these epidemics. Experimental studies have shown that sleep restriction is associated with changes in energy homeostasis, insulin resistance and β-cell function. Epidemiological cohort studies established short sleep duration as a risk factor for developing obesity and T2DM. In addition, small studies suggested that short sleep duration was associated with less weight loss following lifestyle interventions or bariatric surgery. In this article, we review the epidemiological evidence linking sleep duration to obesity and T2DM and plausible mechanisms. In addition, we review the impact of changes in sleep duration on obesity and T2DM.

Background Fractures are a great health issue associated with morbidity, quality of life, life span, and health care expenditure. Fractures are correlated with cardiovascular disease, type 2 diabetes mellitus, cerebrovascular disease, and some psychiatric disorders. However, representative national data are few, and longitudinal cohort studies on the association between schizophrenia and the subsequent fracture risk are scant. We designed a nationwide population-based cohort study to investigate the association of schizophrenia with hip, vertebral, and wrist fractures over a 10-year follow-up. Methods Data of patients with schizophrenia (International Classification of Diseases, Ninth Revision, Clinical Modification code 295) and matched over January 2000–December 2009) were extracted from Taiwan National Health Insurance Research Database. A Cox proportional-hazards regression model was constructed to calculate hazard ratios (HRs) for fractures between the schizophrenia and control cohorts. Results Of 2028 people with schizophrenia (mean age: 36.3 years, 49.4% female), 89 (4.4%) reported newly diagnosed fractures—significantly higher than the proportion in the control population (257, 3.2%; P = 0.007). The incidences of hip (1.2%, P = 0.009) and vertebral (2.6%, P = 0.011) fractures were significantly higher in the schizophrenia cohort than in the control cohort. In Cox regression analysis, hip (adjusted HR: 1.78, 95% confidence interval [CI]: 1.08–2.93) and vertebral (adjusted HR: 1.40, 95% CI: 1.01–1.95) fracture risks were significantly higher in patients with schizophrenia. Furthermore, a sex-based subgroup analysis revealed that the risk of hip fracture remained significantly higher in female patients with schizophrenia (HR: 2.68, 95% CI: 1.32–5.44) than in female controls. On the other hand, there was no significant interaction between effects of sex and schizophrenia on the risk of fractures. Conclusions Over a 10-year follow-up, hip and vertebral fracture risks were higher in the people with schizophrenia than in the controls. The risk of fractures in patients with schizophrenia does not differ between female and male.

Background Lactation consultants frequently advise adjustments to fit and hold (or positioning and attachment) with the aim of optimising intra-oral nipple placement. However, approaches to fit and hold vary widely, with limited evidence of benefits, and effects of fit and hold on infant tongue movement have not been examined. The aim of this preliminary study was to investigate whether a gestalt breastfeeding intervention alters tongue movement, using measurements from ultrasound imaging to determine nipple placement and intra-oral nipple and breast tissue dimensions. Methods Ultrasound measurements were conducted in five breastfeeding dyads, infants aged 4–20 weeks, while feeding in their usual or ‘standard’ position and again after brief application of gestalt principles of fit and hold. Four of the mother-baby pairs, who had received comprehensive lactation support, reported persisting nipple pain. Three of these infants had difficulty latching and fussed at the breast; three had been diagnosed with oral ties. A fifth pair was breastfeeding successfully. Results Ultrasound demonstrated that the distance from nipple tip to junction of the hard and soft palate decreased, intra-oral nipple and breast tissue dimensions increased, and nipple slide decreased after a brief gestalt intervention. Conclusion These preliminary findings suggest that changes in fit and hold impact on infant tongue movement and contour. Further research investigating short- and long-term outcomes of a gestalt breastfeeding intervention in larger cohorts is required.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The majority of FMD patients are women. Although a variety of genetic, mechanical, and hormonal factors play a role in the pathogenesis of FMD, overall, its cause remains poorly understood. It is probable that the pathogenesis of FMD is linked to a combination of genetic and environmental factors. Extensive studies have correlated the arterial lesions of FMD to histopathological findings of arterial fibrosis, cellular hyperplasia, and distortion of the abnormal architecture of the arterial wall. More recently, the vascular phenotype of lesions associated with FMD has been expanded to include arterial aneurysms, dissections, and tortuosity. However, in the absence of a string-of-beads or focal stenosis, these lesions do not suffice to establish the diagnosis. While FMD most commonly involves renal and cerebrovascular arteries, involvement of most arteries throughout the body has been reported. Increasing evidence highlights that FMD is a systemic arterial disease and that subclinical alterations can be found in non-affected arterial segments. Recent significant progress in FMD-related research has led to improve our understanding of the disease’s clinical manifestations, natural history, epidemiology, and genetics. Ongoing work continues to focus on FMD genetics and proteomics, physiological effects of FMD on cardiovascular structure and function, and novel imaging modalities and blood-based biomarkers that can be used to identify subclinical FMD. It is also hoped that the next decade will bring the development of multi-centred and potentially international clinical trials to provide comparative effectiveness data to inform the optimal management of patients with FMD.

Background Pneumocystis jirovecii pneumonia (PCP) with acute respiratory failure can result in development of pneumothorax during treatment. This study aimed to identify the incidence and related factors of pneumothorax in patients with PCP and acute respiratory failure and to analyze their prognosis. Methods We retrospectively reviewed the occurrence of pneumothorax, including clinical characteristics and results of other examinations, in 119 non-human immunodeficiency virus patients with PCP and respiratory failure requiring mechanical ventilator treatment in a medical intensive care unit (ICU) at a tertiary-care center between July 2016 and April 2019. Results During follow up duration, twenty-two patients (18.5%) developed pneumothorax during ventilator treatment, with 45 (37.8%) eventually requiring a tracheostomy due to weaning failure. Cytomegalovirus co-infection (odds ratio 13.9; p = 0.013) was related with occurrence of pneumothorax in multivariate analysis. And development of pneumothorax was not associated with need for tracheostomy and mortality. Furthermore, analysis of survivor after 28 days in ICU, patients without pneumothorax were significantly more successful in weaning from mechanical ventilator than the patients with pneumothorax (44% vs. 13.3%, p = 0.037). PCP patients without pneumothorax showed successful home discharges compared to those who without pneumothorax (p = 0.010). Conclusions The development of pneumothorax increased in PCP patient with cytomegalovirus co-infection, pneumothorax might have difficulty in and prolonged weaning from mechanical ventilators, which clinicians should be aware of when planning treatment for such patients.

Background Arthroscopy is a minimally invasive diagnostic tool and treatment strategy in patients suffering from temporomandibular disorders (TMD) when conservative treatment fails. This study aimed to find specific variables on pre-operative MRI or during arthroscopy that could predict success of arthroscopic lysis and lavage. Methods This retrospective analysis compared pre-operative maximum interincisal opening (MIO), pain and main complaint (pain, limited MIO or joint sounds) with results at short-term and medium-term follow-up (ST and MT respectively). Different variables scored on MRI or arthroscopy were used to make a stepwise regression model, subsequently a combined analysis was conducted using variables from both MRI and arthroscopy. Results A total of 47 patients (50 joints) met the inclusion criteria. The main complaint improved by 62 and 53% at ST and MT respectively. The absolute or probable absence of a crumpled disc scored on MRI predicted success at ST and MT (p = 0.0112 and p = 0.0054), and remained significant at MT in the combined analysis (p = 0.0078). Arthroscopic findings of degenerative joint disease predicted success at ST (p = 0.0178), absolute or probable absence of discal reduction scored during arthroscopy significantly predicted success in the combined analysis at ST (p = 0.0474). Conclusion To improve selection criteria for patients undergoing an arthroscopic lysis and lavage of the TMJ, future research might focus on variables visualized on MRI. Although more research is needed, disc shape and in particular the absolute or probable absence of a crumpled disc might be used as predictive variable for success.

Background Serum lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA) and CYFRA21-1 are the commonly used biomarkers to identify patients with autoimmune pulmonary alveolar proteinosis (APAP). However, it is not clear which of the biomarkers is more sensitive to the severity of the patient’s condition. Methods APAP patients numbering 151 were enrolled in this study. All patients’ severity was assessed through the severity and prognosis score of PAP (SPSP). According to the respective laboratory upper limits of serum levels of LDH, CEA and CYFRA21-1, APAP patients were divided into higher and lower-level groups. Patients were divided into five groups based on SPSP. 88 patients had completed six months of follow-up. We calculated sensitivity, specificity, and critical point of LDH, CEA and CYFRA21-1 between APAP patients and normal control group, and between grade 1–2 and 3–5 through receiving operating characteristics (ROC) curve. Results Serum LDH, CEA and CYFRA21-1 levels of patients with PAP were higher and distinctly related to PaO2, FVC, FEV1, DLCO, HRCT scores and SPSP. The SPSP of patients in higher-level LDH, CEA and CYFRA21-1 groups were higher than those of corresponding lower-level groups. Based on SPSP results, the patients were divided into five groups (grade I, 20; grade II, 37; grade III, 40; grade IV, 38; grade V, 16). The serum level of CYFRA21-1 of patients with APAP in grade II was higher than that of patients in grade I and lower than that of patients in grade III. Serum CYFRA21-1 of patients with APAP after six months were higher than the baseline among the aggravated group. Serum LDH, CEA and CYFRA21-1 levels after six months among patients in the relieved group of patients with APAP were lower than the baseline. ROC correlating LDH, CEA and CYFRA21-1 values with APAP severity (between grade 1–2 and 3–5) showed an optimal cutoff of LDH of over 203 U/L ( 3.3 ng/ml) (AUC: 0.815, 95% CI [0.748–0.882], sensitivity: 0.606, specificity: 0.877). Conclusion Serum CYFRA21-1 level was more sensitive in revealing the severity of APAP than LDH and CEA levels among mild to moderate forms of disease.

Background Hepatocellular carcinoma (HCC) is the sixth most common form of cancer worldwide. Although surgical treatments have an acceptable cure rate, tumor recurrence is still a challenging issue. In this meta-analysis, we investigated whether statins prevent HCC recurrence following liver surgery. Methods PubMed, Web of Science, EMBASE and Cochrane Central were searched. The Outcome of interest was the HCC recurrence after hepatic surgery. Pooled estimates were represented as hazard ratios (HRs) and odds ratios (ORs) using a random-effects model. Summary effect measures are presented together with their corresponding 95% confidence intervals (CI). The certainty of evidence was evaluated using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach. Results The literature search retrieved 1362 studies excluding duplicates. Nine retrospective studies including 44,219 patients (2243 in the statin group and 41,976 in the non-statin group) were included in the qualitative analysis. Patients who received statins had a lower rate of recurrence after liver surgery (HR: 0.53; 95% CI: 0.44–0.63; p P P P Conclusion Statins increase the disease-free survival of patients with HCC after liver surgery. These drugs seem to have chemoprevention effects that decrease the probability of HCC recurrence after liver transplantation or liver resection.

Background We have here assessed the impact of demographic, clinical, and treatment compliance characteristics on health-related quality of life (HRQoL) of Venezuelan patients with systemic lupus erythematosus (SLE). We have used a disease-specific questionnaire, the Lupus Quality of Life (LupusQoL), validated in our patient population, to measure HRQoL. Methods A cross-sectional study was conducted among 100 patients with SLE from outpatient clinics. Patients completed a form with demographic, clinical, and treatment compliance data, and the LupusQoL questionnaire. HRQoL was classified as better or worse according to previously established cut-off points for this patient population. Spearman’s r test was used to determine the correlations between age, years of education, disease duration, SLEDAI, and SLICC-DI with the eight domains of the LupusQoL. Mann–Whitney U test was used to compare the HRQoL between the two groups of patients according to treatment compliance. Binomial logistic regression using the backward stepwise selection method was performed to identify the risk factors associated with each of the eight domains of the LupusQoL among patients with inactive (SLEDAI Results HRQoL of our patients was classified as better in all domains of the LupusQoL. Age correlated negatively with all domains of the LupusQoL, except with “burden to others”, and disease activity correlated negatively with all domains of the LupusQoL, except with “intimate relationships” and “burden to others” (p p worse “planning” and “intimate relationships” was advanced age, while having had SLE flare-ups in the previous six months was a risk factor associated with worse “physical health” (p Conclusion Age and disease activity were negatively correlated with almost all domains of the LupusQoL, and treatment compliance was associated with higher score in the “physical health” domain. Disease control and treatment compliance should be the main goals for a better HRQoL in our patients with SLE.

Background Bacteraemia is associated with high morbidity and mortality, with delayed antibiotic treatment associated with poorer outcomes. Early identification is challenging, but clinically important. Multiple scoring systems have been developed to identify individuals in the broader categories of sepsis. We designed this study to assess the performance of existing scoring systems and pathways—CEC SEPSIS KILLS pathway (an Australian sepsis care package), quick sequential organ failure score (qSOFA), systemic inflammatory response syndrome (SIRS) and the Shapiro criteria. Methods This was a retrospective cohort study performed in two metropolitan hospitals in NSW, consisting of adult patients (> 18 years) with positive blood cultures containing a true pathogen and patients matched by age without positive blood cultures. Performance (sensitivity, specificity, and mortality prediction) of recognised sepsis and bacteraemia criteria and pathways—qSOFA, SIRS, Shapiro criteria and CEC SEPSIS KILLS pathway in the first 4 h following ED triage was assessed. Results There were 251 patients in each cohort. Sepsis-related mortality was higher in the bacteraemic group (OR 0.4, p = 0.03). Of the criteria studied, the modified Shapiro criteria had the highest sensitivity (88%) with modest specificity (37.85%), and qSOFA had the highest specificity (83.67%) with poor sensitivity (19.82%). SIRS had reasonable sensitivity (82.07%), with poor sensitivity (20.72%). The CEC SEPSIS pathway sensitivity of 70.1% and specificity of 71.1%. The SEPSIS KILLS was activated on only 14% of bacteraemic patients. Conclusion The performance of all scoring systems and pathways was suboptimal in the identification of patients at risk of bacteraemia presenting to the emergency department.

Background Although acute hepatitis E is not fatal in healthy individuals, it is unclear whether hepatitis E superinfection increases the mortality in patients with pre-existing liver disease. Thus, we investigated the prognosis of patients with acute hepatitis E according to their cirrhosis diagnosis, and the prognosis according to the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis and chronic liver disease (CLD). Methods This study included 74 consecutive patients who were diagnosed with acute viral hepatitis E between January 2007 and December 2019. Of them, 39 patients without CLD, 13 patients with non-cirrhotic CLD, and 22 patients with cirrhotic CLD were analyzed. Results Among the 74 patients with HEV infection, 7 (9.5%) died within 180 days: 5 with underlying cirrhosis (71.4%) and 2 without cirrhosis (28.6%). The 180-day mortality was significant higher for patients with cirrhosis than for patients without cirrhosis (22.7% vs. 3.8%, P = 0.013). The age- and sex-adjusted proportional-hazard model revealed an approximately eightfold increase in the 180-day mortality risk in patients with cirrhosis compared to patients without cirrhosis. In addition, development of hepatitis E virus-related ACLF due to acute liver function deterioration in patients with pre-existing CLD or cirrhosis worsened the 180-day mortality rate. Conclusions Our findings suggest that the acute hepatitis E mortality rate was low in healthy individuals but higher in patients with cirrhosis, and especially high in those with ACLF.

Background This study was performed to identify the association between the total magnetic resonance imaging burden of small vessel disease and the occurrence of post-stroke dysphagia in patients with a single recent small subcortical infarct (RSSI). Methods We retrospectively identified all patients with a magnetic resonance imaging-confirmed single RSSI. The water-swallowing test and volume-viscosity swallow test were performed within the first 24 h following admission to assess swallowing. Demographic and clinical data were extracted from our stroke database. Based on brain magnetic resonance imaging, we independently rated the presence of cerebral microbleeds, lacunes, white matter hyperintensities and enlarged perivascular spaces. The presence of each small vessel disease feature was summed to determine the total small vessel disease burden, ranging from 0 to 4. Results In total, 308 patients with a single RSSI were enrolled. Overall, 54 (17.5%) were diagnosed with post-stroke dysphagia. The risk factors related to post-stroke dysphagia included the following: older age, higher National Institute of Health Stroke Scale scores, higher C-reactive protein level and higher fibrinogen level. Based on multiple logistic regression, National Institute of Health Stroke Scale scores and total small vessel disease burden were independent risk factors of post-stroke dysphagia in patients with a single RSSI, after adjusting for age, gender, history of hypertension, C-reactive protein level and fibrinogen level. Conclusions Dysphagia in patients with a single RSSI was associated with a more severe total small vessel disease burden as reflected by MRI. Total MRI of cerebral small vessel disease burden may predict dysphagia in these patients. Furthermore, more severe total small vessel disease burden was associated with systemic inflammation.

Background Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children Methods An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. Results 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13–5.19; p = 0.024). Moreover, children Conclusion The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.

BackgroundHip fracture is highly associated with disability and consequently, mortality in the elderly population. Postoperative acute kidney injury (AKI) is not unusual and is associated with considerable morbidity and mortality. We aimed to determine the incidences and potential risk factors for postoperative AKI in elderly patients with femoral neck fracture.MethodsWe retrospectively evaluated patients over 65 years of age who had been subjected to surgery for femoral neck fracture at Peking University People's Hospital from January 2015 to December 2019. Demographic characteristics and potential risk factors were collected. AKI was defined according to the Kidney Disease Improving Global Outcomes Guidelines (KDIGO).ResultsA total of 308 elderly patients with femoral neck fracture were included in the study. The overall incidence of postoperative AKI was 12% (37 cases). Through binary logistic regression analysis, adjusted for age, intraoperative blood loss and BMI, we identified that early postoperative albumin levels, hemoglobin changes and intraoperative hypotension are independent risk factors for postoperative AKI. The model considering the three factors can improve accuracy of predicting the possibility of developing AKI. The patients with AKI had a significantly higher mortality of 40.5% than those without AKI (24.0%,p< 0.001)ConclusionThe incidence of postoperative AKI in elderly patients with femoral neck fracture was 12%. Independent risk factors for postoperative AKI included hemoglobin changes, early postoperative hypoalbuminemia and intraoperative hypotension. At the same time, postoperative AKI significantly increased mortality in elderly patients with femoral neck fracture. Taking multiple possible factors into consideration can better predict the possibility of elderly patients developing AKI after surgery.

In September of 2020, the Iowa Department of Public Health released guidance stating that persons exposed to someone with coronavirus disease (COVID-19) need not quarantine if the case-patient and the contact wore face masks at the time of exposure. This guidance differed from that issued by the Centers for Disease Control and Prevention. To determine the best action, we matched exposure information from COVID-19 case investigations with reported test results and calculated the secondary attack rates (SARs) after masked and unmasked exposures. Mask use by both parties reduced the SAR by half, from 25.6% to 12.5%. Longer exposure duration significantly increased SARs. Masks significantly reduced virus transmission when worn by both the case-patient and the contact, but SARs for each group were higher than anticipated. This finding suggests that quarantine after COVID-19 exposure is beneficial even if parties wore masks.

Background The COVID-19 pandemic remains a public health priority, and vaccination is important for ending the pandemic. Racial and ethnic minorities are disproportionally affected by COVID-19 yet report high levels of vaccination hesitancy. Objective We conducted virtual Town Halls to address vaccine hesitancy among racial and ethnic minorities in South Florida. Methods Our approach used social influence and persuasion models. A formative phase gathered meeting preferences from our communities and developed and tested our approach. An implementation phase conducted six virtual Town Halls in partnership with minority community-based organizations. Results The Town Halls reached 383 participants (mean age 37.5 years; 63.4% female, 33.9% male, 2.7% nonbinary; 59% racial/ethnic minority), who completed pre- and post-meeting assessments. Among non-vaccinated participants, at the pre poll, 58% reported a high likelihood of seeking vaccination, rising to 63% at post-assessment. Unvaccinated “non-hesitant” and “hesitant” groups were compared on trusted information sources, and reasons and barriers for vaccination. Non-hesitant participants reported significantly greater trust in the COVID-19 Task Force (97.3% vs. 83.3%) as a source of vaccine information than did hesitant participants. Non-hesitant participants were significantly more likely to endorse family safety (82.5% vs. 63.2%), community safety (72.5% vs. 26.3%), personal safety (85% vs. 36.8%), and wanting to return to a normal life (70% vs. 31.6%), as reasons for vaccination than were hesitant participants. Hesitant participants were significantly more likely to endorse concerns about vaccine safety doubts (63.2% vs. 17.5%) and not believing the pandemic is as bad as people say it is (21.1% vs. 5%) as barriers to vaccination than were non-hesitant participants. Qualitative data revealed high consumer satisfaction with the Town Halls. Conclusion This study supports the feasibility, acceptability, and potential impact of virtual Town Halls for addressing vaccine hesitancy among racial/ethnic minorities; however, our approach was very resource intensive, required an extensive community-university collaborative infrastructure, and yielded a small effect.

Background The evidence-base underpinning treatment efficacy and effectiveness for hidradenitis suppurativa (HS) is limited, as has been highlighted in the wide-ranging research priorities established by a James Lind Alliance priority-setting partnership (PSP). Understanding the landscape of surgical practice is a key step towards tackling undesired variation in care and resolving treatment uncertainties. This survey of current surgical practice aimed to describe care pathways involving surgeons for the management of HS and surgical approaches to management. Methods In the development of the prospective cohort Treatment of Hidradenitis Suppurativa Evaluation Study (THESEUS), a bespoke electronic surgeon survey was conducted to describe variation in care pathways and surgical preferences in the management of HS. This was disseminated to a pre-defined denominator list of surgeons using local collaborators through the reconstructive surgery trials network (RSTN). Results Key results were small numbers of surgeons working in formal multidisciplinary teams (MDTs) (8/198, 4%), heterogeneity of first-line intervention, low rates of guideline endorsed treatments (laser and deroofing in particular), variation in wound closure methods and follow-up length, and that over half of respondents do not use well-validated outcome instruments to determine treatment success/failure (110/198, 56%). Conclusions This survey demonstrated variation in care, which is likely to be undesirable. Surgeons treating HS patients might consider developing MDTs or referring patients to those with an interest in HS and considering routine outcome measurement. Such steps might reduce variation, increase standardisation of care and improve access to specific treatments.

Background: The Asian Working Group for Sarcopenia 2019 (AWGS 2019) is the gold standard diagnostic criteria for sarcopenia in Asian populations. The calf circumference (CalF), the strength, assistance in walking, rising from a chair, climbing stairs, and falls (SARC-F) and the SARC-CalF questionnaires for sarcopenia screening have been used by AWGS 2019. The aim of this study was to assess accuracy of these three sarcopenia screening tools in patients with interstitial lung disease. Methods: In this cross-sectional study, stable patients with interstitial lung disease were enrolled. The SARC-F, SARC-CalF, and CalF, used in patients with interstitial lung disease, were compared to the diagnostic criteria proposed by AWGS 2019. The accuracy of screening tools was compared using sensitivity and specificity. Moreover, areas under the receiver operating characteristic curves (AUC) were computed. Results: Seventy eight patients were analyzed, and sarcopenia was identified in 25 (32.1%) patients with interstitial lung disease by the AWGS 2019 criteria. The sensitivity of the CalF was highest (96%) of the three screening tools, while the specificity was 60%. The sensitivity of SARC-F and SARC-CalF were 24% and 68%, while the specificity were 92% and 66%, respectively. The AUCs of CalF, SARC-F, and SARC-CalF in all patients were 0.78, 0.58, and 0.67, respectively. Conclusions: The CalF is most suitable for screening sarcopenia in patients with interstitial lung disease, while SARC-F and SARC-CalF are not., BMC Pulmonary Medicine, 22, art. no. 45; 2022

Objective The aim of this study was to evaluate the incidence and duration of delayed hyponatremia and to assess the factors influencing the development of delayed hyponatremia after transsphenoidal surgery (TSS) in pituitary adenomas. Methods We retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. Univariable and multivariable statistics were carried out to identify factors independently associated with the occurrence of delayed hyponatremia. Results Of the 285 patients with pituitary adenoma who underwent microscopic TSS, 44 (15.4%) developed postoperative-delayed hyponatremia and 241 (84.6%) did not. The onset of delayed hyponatremia occurred an average of 5.84 days post-surgery and persisted for an average of 5.36 days. Logistic regression analysis showed the highest risk of delayed hyponatremia in patients with significant change in tumor cavity height (odds ratio (OR), 1.158; 95% CI, 1.062, 1.262; P = 0.001), preoperative hypothalamus–pituitary–thyroid axis hypofunction (OR, 3.112; 95% CI, 1.481, 6.539; P = 0.003), and significant difference in blood sodium levels before and 2 days after TSS (OR, 1.101; 95% CI, 1.005, 1.206; P = 0.039). Conclusions Preoperative hypothyroidism, difference in blood sodium levels before and 2 days after TSS, and the change in tumor cavity height after TSS played important roles in predicting postoperative-delayed hyponatremia onset in patients with pituitary adenomas.

Upadacitinib is an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA) and recently approved by the European Medicines Agency for the treatment of psoriatic arthritis (PsA). The efficacy and safety profile of upadacitinib in PsA have been established in the SELECT‐PsA program in two global phase III studies, which evaluated upadacitinib 15 and 30 mg q.d. The analyses described here characterized upadacitinib pharmacokinetics and exposure‐response relationships for efficacy and safety endpoints using data from the SELECT‐PsA studies. Upadacitinib pharmacokinetics in patients with PsA were characterized through a Bayesian population analysis approach and were comparable to pharmacokinetics in patients with RA. Exposure‐response relationships for key efficacy and safety endpoints were characterized using data from 1916 patients with PsA. The percentage of patients achieving efficacy endpoints at week 12 (American College of Rheumatology [ACR]50 and ACR70), 16 and 24 (sIGA0/1) increased with increasing upadacitinib average plasma concentration over a dosing interval, whereas no clear exposure‐response trend was observed for ACR20 at week 12 or ACR20/50/70 at week 24 within the range of plasma exposures evaluated in the phase III PsA studies. No clear trends for exposure‐response relationships were identified for experiencing pneumonia, herpes zoster infection, hemoglobin less than 8 g/dl, lymphopenia (grade ≥ 3), or neutropenia (grade ≥ 3) after 24 weeks of treatment. Shallow relationships with plasma exposures were observed for serious infections and hemoglobin decrease greater than 2 g/dl from baseline at week 24. Based on exposure‐response analyses, the upadacitinib 15 mg q.d. regimen is predicted to achieve robust efficacy in patients with PsA and to be associated with limited incidences of reductions in hemoglobin or occurrence of serious infections.

Structural racism-the ways that institutional policies, practices, and other norms operate to create and sustain race-based inequities1-has historically been foundational to the operations of academic medical centers and research institutions. Since its inception, academic medicine has depended on the exploitation of vulnerable communities to achieve medical, educational, and research goals.2 Research practices have long ignored or taken advantage of the individuals purportedly benefiting from the research, a dynamic most manifestly true for Black, Indigenous, and People of Color (BIPOC) communities in the United States. Reflecting current practices in racial justice work, we intentionally use the term "BIPOC" to highlight shared experiences within racially and ethnically minoritized communities, given the history of white supremacy in the United States. We acknowledge limitations of this term, which collapses myriad unique communities and histories into 1 construct. Specifically, child and adolescent psychiatry has historically been driven by Eurocentric approaches, paradigms, and methodology. These nonparticipatory dominant research practices have contributed to a lack of culturally responsive interventions for BIPOC communities, a paucity of evidence-based practices with demonstrated effectiveness within BIPOC communities, and disparities in access and quality of care.3 Mental health research involving BIPOC communities has been replete with exploitation and inequality.2.

Funder: Alzheimer's Research UK, Funder: Alzheimer's Society, Funder: Brain Research UK, Funder: the Wolfson Foundation, Funder: NIHR UCL/H Biomedical Research Centre, Funder: Leonard Wolfson Experimental Neurology Centre Clinical Research Facility, Funder: UK Dementia Research Institute, Funder: UK Medical Research Council, Funder: Bluefield project, Funder: the Association for Frontotemporal Dementias Research Grant 2009, BACKGROUND: Clinical endpoints for upcoming therapeutic trials in frontotemporal dementia (FTD) are increasingly urgent. Cognitive composite scores are often used as endpoints but are lacking in genetic FTD. We aimed to create cognitive composite scores for genetic frontotemporal dementia (FTD) as well as recommendations for recruitment and duration in clinical trial design. METHODS: A standardized neuropsychological test battery covering six cognitive domains was completed by 69 C9orf72, 41 GRN, and 28 MAPT mutation carriers with CDR�� plus NACC-FTLD ��� 0.5 and 275 controls. Logistic regression was used to identify the combination of tests that distinguished best between each mutation carrier group and controls. The composite scores were calculated from the weighted averages of test scores in the models based on the regression coefficients. Sample size estimates were calculated for individual cognitive tests and composites in a theoretical trial aimed at preventing progression from a prodromal stage (CDR�� plus NACC-FTLD 0.5) to a fully symptomatic stage (CDR�� plus NACC-FTLD ��� 1). Time-to-event analysis was performed to determine how quickly mutation carriers progressed from CDR�� plus NACC-FTLD = 0.5 to ��� 1 (and therefore how long a trial would need to be). RESULTS: The results from the logistic regression analyses resulted in different composite scores for each mutation carrier group (i.e. C9orf72, GRN, and MAPT). The estimated sample size to detect a treatment effect was lower for composite scores than for most individual tests. A Kaplan-Meier curve showed that after 3 years, ~ 50% of individuals had converted from CDR�� plus NACC-FTLD 0.5 to ��� 1, which means that the estimated effect size needs to be halved in sample size calculations as only half of the mutation carriers would be expected to progress from CDR�� plus NACC FTLD 0.5 to ��� 1 without treatment over that time period. DISCUSSION: We created gene-specific cognitive composite scores for C9orf72, GRN, and MAPT mutation carriers, which resulted in substantially lower estimated sample sizes to detect a treatment effect than the individual cognitive tests. The GENFI-Cog composites have potential as cognitive endpoints for upcoming clinical trials. The results from this study provide recommendations for estimating sample size and trial duration.

High‐dose methotrexate (HDMTX) pharmacokinetics (PKs), including the best estimated glomerular filtration rate (eGFR) equation that reflects methotrexate (MTX) clearance, requires investigation. This prospective, observational, single‐center study evaluated adult patients with lymphoma treated with HDMTX. Samples were collected at predefined time points up to 96 h postinfusion. MTX and 7‐hydroxy‐MTX PKs were estimated by standard noncompartmental analysis. Linear regression determined which serum creatinine‐ or cystatin C‐based eGFR equation best predicted MTX clearance. The 80 included patients had a median (interquartile range [IQR]) age of 68.6 years (IQR 59.2–75.6), 54 (67.5%) were men, and 74 (92.5%) were White. The median (IQR) dose of MTX was 7.6 (IQR 4.8–11.3) grams. Median clearance was similar across three dosing levels at 4.5–5.6 L/h and was consistent with linear PKs. Liver function, weight, age, sex, concomitant chemotherapy, and number of previous MTX doses did not impact clearance. MTX area under the curve (AUC) values varied over a fourfold range and appeared to increase in proportion to the dose. The eGFRcys (ml/min) equation most closely correlated with MTX clearance in both the entire cohort and after excluding outlier MTX clearance values (r = 0.31 and 0.51, respectively). HDMTX as a 4‐h infusion displays high interpatient pharmacokinetic variability. Population PK modeling to optimize MTX AUC attainment requires further evaluation. The cystatin C‐based eGFR equation most closely estimated MTX clearance and should be investigated for dosing and monitoring in adults requiring MTX as part of lymphoma management.

Key Points Question What are the characteristics of amyloid-related imaging abnormalities (ARIA) during aducanumab treatment in individuals with early Alzheimer disease? Findings In an integrated safety data set of 2 phase 3 clinical trials (EMERGE and ENGAGE) including 3285 participants, 425 patients (41.3%) in the combined 10 mg/kg aducanumab group (n = 1029) experienced ARIA; ARIA-edema occurred in 362 patients (35.2%), and 94 of these patients (26.0%) experienced associated symptoms (eg, headache, confusion, dizziness, and nausea). ARIA-microhemorrhage and ARIA–superficial siderosis occurred in 197 patients (19.1%) and 151 patients (14.7%), respectively. Meaning Amyloid-related imaging abnormalities occurred in approximately 40% of participants in the phase 3 studies of aducanumab, and approximately one-quarter of these patients experienced symptoms., This secondary analysis of 2 phase 3 randomized clinical trials describes the radiographic and clinical characteristics of amyloid-related imaging abnormalities that occurred in the EMERGE and ENGAGE trials., Importance The EMERGE and ENGAGE phase 3 randomized clinical trials of aducanumab provide a robust data set to characterize amyloid-related imaging abnormalities (ARIA) that occur with treatment with aducanumab, an amyloid-β (Aβ)–targeting monoclonal antibody, in patients with mild cognitive impairment due to Alzheimer disease or mild Alzheimer disease dementia. Objective To describe the radiographic and clinical characteristics of ARIA that occurred in EMERGE and ENGAGE. Design, Setting, and Participants Secondary analysis of data from the EMERGE and ENGAGE trials, which were 2 double-blind, placebo-controlled, parallel-group, phase 3 randomized clinical trials that compared low-dose and high-dose aducanumab treatment with placebo among participants at 348 sites across 20 countries. Enrollment occurred from August 2015 to July 2018, and the trials were terminated early (March 21, 2019) based on a futility analysis. The combined studies consisted of a total of 3285 participants with Alzheimer disease who received 1 or more doses of placebo (n = 1087) or aducanumab (n = 2198; 2752 total person-years of exposure) during the placebo-controlled period. Primary data analyses were performed from November 2019 to July 2020, with additional analyses performed through July 2021. Interventions Participants were randomly assigned 1:1:1 to high-dose or low-dose intravenous aducanumab or placebo once every 4 weeks. Dose titration was used as a risk-minimization strategy. Main Outcomes and Measures Brain magnetic resonance imaging was used to monitor patients for ARIA; associated symptoms were reported as adverse events. Results Of 3285 included participants, the mean (SD) age was 70.4 (7.45) years; 1706 participants (52%) were female, 2661 (81%) had mild cognitive impairment due to Alzheimer disease, and 1777 (54%) used symptomatic medications for Alzheimer disease. A total of 764 participants from EMERGE and 709 participants from ENGAGE were categorized as withdrawn before study completion, most often owing to early termination of the study by the sponsor. Unless otherwise specified, all results represent analyses from the 10-mg/kg group. During the placebo-controlled period, 425 of 1029 patients (41.3%) experienced ARIA, with serious cases occurring in 14 patients (1.4%). ARIA-edema (ARIA-E) was the most common adverse event (362 of 1029 [35.2%]), and 263 initial events (72.7%) occurred within the first 8 doses of aducanumab; 94 participants (26.0%) with an event exhibited symptoms. Common associated symptoms among 103 patients with symptomatic ARIA-E or ARIA-H were headache (48 [46.6%]), confusion (15 [14.6%]), dizziness (11 [10.7%]), and nausea (8 [7.8%]). Incidence of ARIA-E was highest in aducanumab-treated participants who were apolipoprotein E ε4 allele carriers. Most events (479 of 488 [98.2%]) among those with ARIA-E resolved radiographically; 404 of 488 (82.8%) resolved within 16 weeks. In the placebo group, 29 of 1076 participants (2.7%) had ARIA-E (apolipoprotein E ε4 carriers: 16 of 742 [2.2%]; noncarriers, 13 of 334 [3.9%]). ARIA-microhemorrhage and ARIA–superficial siderosis occurred in 197 participants (19.1%) and 151 participants (14.7%), respectively. Conclusions and Relevance In this integrated safety data set from EMERGE and ENGAGE, the most common adverse event in the 10-mg/kg group was ARIA-E, which occurred in 362 of the 1029 patients (35.2%) in the 10-mg/kg group with at least 1 postbaseline MRI scan, with 94 patients (26.0%) experiencing associated symptoms. The most common associated symptom was headache. Trial Registrations ClinicalTrials.gov Identifiers: NCT02484547, NCT02477800

Background Intrauterine insemination (IUI) treatment is recommended in subfertile women with AFS/ASRM stage I/II endometriosis. However, the efficacy of IUI in women with ovarian endometriomas with tubal patency is uncertain. We explored the efficacy of IUI for the treatment of endometrioma-associated subfertility. Methods We performed a retrospective matched cohort study using propensity matching (PSM) analysis. Subfertile couples undergoing IUI with and without ovarian stimulation between January 1, 2015, and May 30, 2020 were reviewed. Results After PSM, 56 women with endometrioma alone were matched to 173 patients with unexplained subfertility. The per-cycle pregnancy rate (PR) was comparable between women with endometrioma-associated subfertility (n = 56, 87 cycles) and women with unexplained subfertility (n = 173, 280 cycles) (9.2% vs. 17.9%, OR 0.47; 95% CI, 0.21–1.03). Subgroup analyses based on IUI with or without stimulation also resulted in comparable results. A trend toward a lower cumulative pregnancy rates (CPRs) was seen in women with endometrioma (14.3%, 8/56) compared with women with unexplained subfertility (28.9%, 50/173), but the differences were not significant (HR 0.49; 95% CI, 0.23–1.15). However, patients with endometrioma were nearly twice as likely to converse to IVF treatment compared with those without the disease (60.7% versus 43.9%; OR 1.97; 95% CI, 1.07–3.65). Conclusion IUI may be a viable approach for subfertile women with endometrioma and no other identifiable infertility factor. More studies are needed to reassure the findings.

Background Patients with gastric cancer are aging in Japan. It is not clear which patients and which surgical procedures have survival benefits after gastrectomy. A multivariate analysis was performed. Methods The medical records of 166 patients aged ≥ 80 years who underwent gastrectomy without macroscopic residual tumors were retrospectively reviewed. Univariate and multivariate analyses using Cox proportional hazard models were performed to detect prognostic factors for overall survival. Results In univariate analyses, age (≥ 90 vs. ≥ 80, Conclusions ASA-PS was a useful predictor for postoperative mortality. Gastrectomy including cardia is best avoided.

Objective To describe the clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy in children. Method Data from 11 pediatric patients with autoimmune GFAP astrocytopathy were retrospectively analyzed. Results All of the patients showed encephalitis and meningoencephalitis or meningoencephalomyelitis with or without myelitis. 45.4% of the patients had fever, 27.3% headaches, 18.2% dizziness, 18.2% drowsiness, and 18.2% mental disorders. Cerebrospinal fluid (CSF) was detected in all patients. The white blood cell counts (WBC) (90.9%), lactic dehydrogenase levels (72.7%), protein level (36.4%), and adenosine deaminase activity (ADA) level (27.3%) were elevated, and the CSF glucose levels (72.7%) were slightly reduced. Nine patients (90%) were found to have brain abnormalities, of which five (50.0%) patients had abnormal symmetrical laminar patterns or line patterns hyperintensity lesions on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images in the basal ganglia, hypothalamus, subcortical white matter and periventricular white matter. The linear radial enhancement pattern of the cerebral white matter was only seen in two patients, with the most common being abnormal enhancement of leptomeninges (50%). Five patients had longitudinally extensive spinal cord lesions. Conclusion The findings of pediatric patients with autoimmune GFAP astrocytopathy are different from previous reports.

Background Rural India has a severe shortage of human resources for health (HRH). The National Rural Health Mission (NRHM) deploys HRH in the rural public health system to tackle shortages. Sanctioning under NRHM does not account for workload resulting in inadequate and inequitable HRH allocation. The Workforce Indicators of Staffing Needs (WISN) approach can identify shortages and inform appropriate sanctioning norms. India currently lacks nationally relevant WISN estimates. We used existing data and modelling techniques to synthesize such estimates. Methods We conducted a retrospective analysis of existing survey data for 93 facilities from 5 states over 8 years to create WISN calculations for HRH cadres at primary and community health centres (PHCs and CHCs) in rural areas. We modelled nationally representative average WISN-based requirements for specialist doctors at CHCs, general doctors and nurses at PHCs and CHCs. For 2019, we calculated national and state-level overall and per-centre WISN differences and ratios to depict shortage and workload pressure. We checked correlations between WISN ratios for cadres at a given centre-type to assess joint workload pressure. We evaluated the gaps between WISN-based requirements and sanctioned posts to investigate suboptimal sanctioning through concordance analysis and difference comparisons. Results In 2019, at the national-level, WISN differences depicted workforce shortages for all considered HRH cadres. WISN ratios showed that nurses at PHCs and CHCs, and all specialist doctors at CHCs had very high workload pressure. States with more workload on PHC-doctors also had more workload on PHC-nurses depicting an augmenting or compounding effect on workload pressure across cadres. A similar result was seen for CHC-specialist pairs—physicians and surgeons, physicians and paediatricians, and paediatricians and obstetricians–gynaecologists. We found poor concordance between current sanctioning norms and WISN-based requirements with all cadres facing under-sanctioning. We also present across-state variations in workforce problems, workload pressure and sanctioning problems. Conclusion We demonstrate the use of WISN calculations based on available data and modelling techniques for national-level estimation. Our findings suggest prioritising nurses and specialists in the rural public health system and updating the existing sanctioning norms based on workload assessments. Workload-based rural HRH deployment can ensure adequate availability and optimal distribution.

Background People with COPD have been reported to bear a distinct airway microbiota from healthy individuals based on bronchoalveolar lavage (BAL) and sputum samples. Unfortunately, the collection of these samples involves relatively invasive procedures and is resource-demanding, limiting its regular use. Non-invasive samples from the upper airways could constitute an interesting alternative, but its relationship with COPD is still underexplored. We examined the merits of saliva to identify the typical profile of COPD oral bacteria and test its association with the disease. Methods Outpatients with COPD and age-sex matched healthy controls were recruited and characterised based on clinical parameters and 16S rRNA profiling of oral bacteria. A clustering analysis based on patients’ oral bacteria beta-diversity and logistic regressions were performed to evaluate the association between oral bacteria composition and COPD. Results 128 individuals participated (70 patients and 58 controls). Differential abundance analyses showed differences in patients comparable to the ones previously observed in samples from the lower respiratory tract, i.e., an increase in Proteobacteria (particularly Haemophilus) and loss of microbiota diversity. An unsupervised clustering analysis separated patients in two groups based on microbiota composition differing significantly in the frequency of patients hospitalized due to severe acute exacerbation of COPD (AECOPD) and in the frequency of GOLD D patients. Furthermore, a low frequency of Prevotella was associated with a significantly higher risk of recent severe AECOPD and of being GOLD D. Conclusion Salivary bacteria showed an association with COPD, particularly with severe exacerbations, supporting the use of this non-invasive specimen for future studies of heterogeneous respiratory diseases like COPD.

Aim The aim of this study is to investigate the prevalence of asymptomatic hyperuricemia in Qatar and to examine its association with changes in markers of dyslipidemia, prediabetes and subclinical inflammation. Methods A cross-sectional study of young adult participants aged 18 - 40 years old devoid of comorbidities collected between 2012 and 2017. Exposure was defined as uric acid level, and outcomes were defined as levels of different blood markers. De-identified data were collected from Qatar Biobank. T-tests, correlation tests and multiple linear regression were all used to investigate the effects of hyperuricemia on blood markers. Statistical analyses were conducted using STATA 16. Results The prevalence of asymptomatic hyperuricemia is 21.2% among young adults in Qatar. Differences between hyperuricemic and normouricemic groups were observed using multiple linear regression analysis and found to be statistically and clinically significant after adjusting for age, gender, BMI, smoking and exercise. Significant associations were found between uric acid level and HDL-c p = 0.019 (correlation coefficient -0.07 (95% CI [-0.14, -0.01]); c-peptide p = 0.018 (correlation coefficient 0.38 (95% CI [0.06, 0.69]) and monocyte to HDL ratio (MHR) p = 0.026 (correlation coefficient 0.47 (95% CI [0.06, 0.89]). Conclusions Asymptomatic hyperuricemia is prevalent among young adults and associated with markers of prediabetes, dyslipidemia, and subclinical inflammation.

Acute ischemic stroke continues to devastate millions of individuals worldwide. Current treatments work to restore blood flow but not rescue affected tissue. Our goal was to develop a combination of neuroprotective agents administered intra‐arterially following recanalization to target ischemic tissue. Using C57Bl/6J male mice, we performed tandem transient ipsilateral middle cerebral/common carotid artery occlusion, followed by immediate intra‐arterial pharmacotherapy administration through a standardized protocol. Two pharmacotherapy agents, verapamil and lubeluzole, were selected based on their potential to modulate different aspects of the ischemic cascade; verapamil, a calcium channel blocker, works in an acute fashion blocking L‐type calcium channels, whereas lubeluzole, an N‐methyl‐D‐aspartate modulator, works in a delayed fashion blocking intracellular glutamate trafficking. We hypothesized that combination therapy would provide complimentary and potentially synergistic benefit treating brain tissue undergoing various stages of injury. Physiological measurements for heart rate and pulse distention (blood pressure) demonstrated no detrimental effects between groups, suggesting that the combination drug administration is safe. Tissue analysis demonstrated a significant difference between combination and control (saline) groups in infarct volume, neuronal health, and astrogliosis. Although a significant difference in functional outcome was not observed, we did note that the combination treatment group had a greater percent change from baseline in forced motor movement as compared with controls. This study demonstrates the safety and feasibility of intra‐arterial combination therapy following successful recanalization and warrants further study.

Background Congenital esophageal atresia postoperative anastomotic stricture occurs in 30–50% of cases. Patients with severe dysphagia are treated with endoscopic balloon dilatation (EBD) and/or local injection of steroids, but many patients continue to experience frequent stricture. In this study, we investigated the transplantation of autologous oral mucosa-derived cell sheets (epithelial cell sheets) as a prophylactic treatment for congenital esophageal atresia postoperative anastomotic stricture. Methods Epithelial cell sheets were fabricated from a patient’s oral epithelial tissue, and their safety was confirmed by quality control tests. The epithelial cell sheets were transported under controlled conditions from the fabrication facility to the transplantation facility and successfully transplanted onto the lacerations caused by EBD using a newly developed transplantation device for pediatric patients. The safety of the transplantation was confirmed by follow-up examinations over 48 weeks. Results The dates that EBD was performed were recorded for one year before and after epithelial cell sheet transplantation, and the intervals (in days) were evaluated. For about 6 months after transplantation, the intervals between EBDs were longer than in the year before transplantation. The patients were also aware of a reduction in dysphagia after transplantation. Conclusions These results suggest that cell sheet transplantation may be effective in preventing anastomotic stricture after surgery for congenital esophageal atresia, but the effect was temporary and limited in this case. Although we chose a very severe case for the first human clinical study, it may be possible to obtain a more definitive effect if the transplantation is performed before the disease becomes so severe. Future studies are needed to identify cases in which cell sheet transplantation is most effective and to determine the appropriate timeframes for transplantation. Trial registration: UMIN, UMIN000034566, registered 19 October 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393.

Background Oral mucositis (OM) associated with cancer treatment not only impairs patients’ quality of life but also causes treatment delays or changes. This prospective exploratory study was conducted to evaluate the efficacy of Episil® oral liquid, which is an approved protective formulation for the oral mucosa in patients with OM. The extent of the pain-relieving effect, feeling during use, and adverse events or problems were evaluated. Methods In total, 10 Japanese cancer patients with OM receiving chemotherapy, pretreatment therapy for hematopoietic stem cell transplantation, or radiation therapy for head and neck cancer were enrolled. Results A numerical rating scale (NRS) was used to assess oral pain intensity due to OM. Compared to baseline, the mean NRS began to decrease at 5 min after using Episil® (7.1 ± 1.4 to 4.6 ± 2.87; p = 0.264). A significant decrease was observed in the pain score after using Episil® compared with that before using Episil®, and this effect lasted up to 120 min. The protective effects of Episil® were observed 3–5 min after application. Some patients felt slight soreness or discomfort when applying Episil®. However, this discomfort due to Episil®’s stimulation was within the allowable range and transient. No adverse events were observed in any of the cases. Conclusions The results of this prospective study showed that Episil® could be an effective treatment to relieve oral pain in Japanese patients with moderate to severe OM, and this newly approved product might adequately support patients’ oral intake. Trial registration University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) (UMIN000031921).

Background After treatment of intrauterine adhesions, the rate of re-adhesion is high and the pregnancy outcome unpredictable and unsatisfactory. This study established and verified a decision tree predictive model of live birth in patients after surgery for moderate-to-severe intrauterine adhesions (IUAs). Methods A retrospective observational study initially comprised 394 patients with moderate-to-severe IUAs diagnosed via hysteroscopy. The patients underwent hysteroscopic adhesiolysis from January 2013 to January 2017, in a university-affiliated hospital. Follow-ups to determine the rate of live birth were conducted by telephone for at least the first postoperative year. A classification and regression tree algorithm was applied to establish a decision tree model of live birth after surgery. Results Within the final population of 374 patients, the total live birth rate after treatment was 29.7%. The accuracy of the model was 83.8%, and the area under the receiver operating characteristic curve (AUC) was 0.870 (95% CI 7.699–0.989). The root node variable was postoperative menstrual pattern. The predictive accuracy of the multivariate logistic regression model was 70.3%, and the AUC was 0.835 (95% CI 0.667–0.962). Conclusions The decision tree predictive model is useful for predicting live birth after surgery for IUAs; postoperative menstrual pattern is a key factor in the model. This model will help clinicians make appropriate clinical decisions during patient consultations.

To determine risk factors for coronavirus disease (COVID-19) among US healthcare personnel (HCP), we conducted a case–control analysis. We collected data about activities outside the workplace and COVID-19 patient care activities from HCP with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results (cases) and from HCP with negative test results (controls) in healthcare facilities in 5 US states. We used conditional logistic regression to calculate adjusted matched odds ratios and 95% CIs for exposures. Among 345 cases and 622 controls, factors associated with risk were having close contact with persons with COVID-19 outside the workplace, having close contact with COVID-19 patients in the workplace, and assisting COVID-19 patients with activities of daily living. Protecting HCP from COVID-19 may require interventions that reduce their exposures outside the workplace and improve their ability to more safely assist COVID-19 patients with activities of daily living.

Background Studies of the hospital volume-outcome relationship have highlighted that a greater volume activity improves patient outcomes. While this finding has been known for years, most studies to date have failed to delve into what underlies this relationship. Objective This study aimed to shed light on the basis of the hospital volume effect on patient outcomes by comparing treatment modalities for epithelial ovarian carcinoma patients. Data An exhaustive dataset of 355 patients in first-line treatment for Epithelial Ovarian Carcinoma (EOC) in 2012 in three regions of France was used. These regions account for 15% of the metropolitan French population. Methods In the presence of endogeneity induced by a reverse causality between hospital volume and patient outcomes, we used an instrumental variable approach. Hospital volume of activity was instrumented by the distance from patients’ homes to their hospital, the population density, and the median net income of patient municipalities. Results Based on our parameter estimates, we found that the rate of complete tumor resection would increase by 15.5 percentage points with centralized care, and by 8.3 percentage points if treatment decisions were coordinated by high-volume centers compared to decentralized care. Conclusion As volume alone is an imperfect correlate of quality, policy-makers need to know what volume is a proxy for in order to devise volume-based policies.

Background Anxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country’s mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment resistance, relapse, or substantial side effects. Further, due to the COVID-19 pandemic and stay-at-home order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. Previously, we have demonstrated dihydromyricetin (DHM), the major bioactive flavonoid extracted from Ampelopsis grossedentata, exhibits anxiolytic properties in a mouse model of social isolation-induced anxiety. Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigated the effects of short-term social isolation on the neuroimmune system. Methods Eight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. The anxiety-like behaviors after DHM treatment were examined using elevated plus-maze and open field behavioral tests. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured. Results Socially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Also, a dynamic alteration in hippocampal microglia were detected illustrated as a decline in microglia number and overactivation as determined by significant morphological changes including decreases in lacunarity, perimeter, and cell size and increase in cell density. Moreover, social isolation induced an increase in serum corticosterone level and activation in NF-κB pathway. Notably, DHM treatment counteracted these changes. Conclusion The results suggest that social isolation contributes to neuroinflammation, while DHM has the ability to improve neuroinflammation induced by anxiety.

Background Functional neurological disorder is defined by symptoms not explained by the current model of disease and its pathophysiology. It is found in 8.4% of patients presenting as acute stroke. Treatment is difficult and recurrence rates are high. We introduced hypnotherapy as a therapeutic option in addition to standard stroke unit care. Methods This is an observational study of successive patients with functional neurological disorder presenting as acute stroke treated with hypnotherapy between 1 April 2014 and 1 February 2018. The diagnosis of functional neurological disorder was confirmed by clinical examination and computed tomography/magnetic resonance imaging. Hypnosis was delivered by a hypnotherapy trained stroke physician using imagery for induction. A positive response was defined as a National Institutes of Health Stroke score reduction to 0 or by ≥4 points posthypnotherapy. Costs were calculated as therapist time and benefits as reduction in disability/bed days. Results Sixty-eight patients (mean age 36.4 years, 52 (76%) females, mean baseline National Institutes of Health Stroke 5.0 (range 1–9)) were included. Two patients (3%) could not be hypnotized. Fifty-eight 58 (85%) responded, 47 (81%) required one treatment session, while 19% needed up to three sessions for symptomatic improvement. No adverse events were observed. Disability (modified Rankin Scale) reduced from a mean of 2.3 to 0.5 resulting in an average cost saving of £1,658 per patient. Most (n = 50, 86%) remained well without recurrence at six-month follow-up. Conclusions In this case series, hypnotherapy was associated with rapid and sustained recovery of symptoms. A prospective randomized controlled study is required to confirm the findings and establish generalizability of the results.

Background: The costs associated with the treatment of sickle cell disease (SCD) are understudied in low and middle-income countries (LMIC), where resources are scarcer and policy decisions about resource allocation rely on detailed cost data. Few studies have investigated the cost-savings of disease-modifying therapies in SCD in real-world setting. We evaluated the cost of treating SCD-related acute complications and the potential cost-savings of hydroxyurea therapy at HEMORIO, a specialized tertiary hematology center in Brazil. Methods: The costs (US dollars) of emergency department (ED) and hospitalizations from SCD-related complications between 01.01.2018 and 06.30.2018 were ascertained using absorption and micro-costing approaches. ED costs are presented as cost per each ED event and hospital admission costs are presented as cost per each admission event. ED and admission costs (separated and combined) were determined and compartmentalized into several inputs by fixed and variable categories for all patients over the period of the study [Falk JA et al, Atlas 2001]. The cause of ED or hospital admission visit was verified by a physician and abstracted via medical record review. All hospital admissions were evaluated in the ED. If an ED encounter resulted in an admission, the encounter was counted as an admission event only. The causes related to SCD were grouped and classified according to the discharge diagnosis: 1) VOC (acute pain crisis, priapism or dactylitis); 2) Infection (fever, sepsis, or acute chest syndrome); 3) Anemia exacerbation (acute hemolytic crisis, transient aplastic crisis, or acute splenic sequestration); 4) Chronic organ damage (overt stroke, chronic kidney disease, chronic liver disease or organ failure. Hydroxyurea adherence was estimated by medication possession ratio (MPR) during the study period [Shah N, et al. Health and quality of life outcomes. 2019]. The one-sample proportions test with continuity correction compared the differences in frequency of ED or admissions across discharge diagnoses and the Wilcoxon rank sum test with continuity correction was used to compare cost differences across the groups. Results: In total, 1144 patients, median age 17 years (range 0-70), 903 (78.9%) with HbSS/HbSβ 0-thalassemia, 441 (38.5%) prescribed hydroxyurea, visited the ED, of whom 381 (33%) were admitted. VOC accounted for 64% of all ED visits and 60% of all admissions (Table 1). Anemia exacerbation was the most expensive reason for ED visit ($321.87/visit), while chronic organ damage carried the highest admission cost ($2,176.40/visit) (Figure 1). Compared with other genotypes, individuals with HbSS/HbSβ 0-thalassemia were admitted more often (79% versus 21%, p Discussion: It is estimated that between 60,000 to 100,000 individuals live with SCD in Brazil today [Lobo CL, et al. Pediatric blood & cancer. 2014]. In a LMIC hematology-specialized center, VOCs accounted for most acute visits from patients with SCD, but costs were highest due to anemia exacerbation. Analgesics, antibiotics, and housing drove most expenses. Our results confirm the lower acute health care resource utilization with hydroxyurea therapy (fewer ED visits and admissions among those prescribed this medication). Hydroxyurea therapy reduced ED costs among individuals with HbSS/HbSβ 0-thalassemia, however, was dependent on adherence level. A cost analysis of individuals with SCD has never been performed in Brazil previously. Our study will facilitate appropriate planning of allocation of funds and development of health policies for individuals with SCD and may serve as the benchmark against which new SCD disease-modifying therapies may be compared for cost-effectiveness and cost-savings estimation in LMIC, such as Brazil. Figure 1 Figure 1. Disclosures Lobo: Novartis: Consultancy. Hankins: Global Blood Therapeutics: Consultancy; UpToDate: Consultancy; Vindico Medical Education: Consultancy; Bluebird Bio: Consultancy.

Background Multimorbidity poses a challenge for high quality primary care provision for nursing care-dependent people with (PWD) and without (PWOD) dementia. Evidence on the association of primary care quality of multimorbid PWD and PWOD with the event of a nursing home admission (NHA) is missing. This study aimed to investigate the contribution of individual quality of primary care for chronic diseases in multimorbid care-dependent PWD and PWOD on the duration of ongoing residence at home before the occurrence of NHA. Methods We conducted a retrospective cohort study among elderly care-dependent PWD and PWOD in Germany for six combinations of chronic diseases using statutory health insurance claims data (2007–2016). Primary care quality was measured by 21 process and outcome indicators for hypertension, diabetes, depression, chronic obstructive pulmonary disease and heart failure. The primary outcome was time to NHA after initial onset of care-dependency. Multivariable Cox proportional hazard models were used to compare the time-to-event between PWD and PWOD. Results Among 5876 PWD and 12,837 PWOD 5130 NHA occurred. With the highest proportion of NHA for PWD with hypertension and depression and for PWOD with hypertension, diabetes and depression. Average duration until NHA ranged from 6.5 to 8.9 quarters for PWD and from 9.6 to 13.5 quarters for PWOD. Adjusted analyses show consistent associations of the quality of diabetes care with the duration of remaining in one’s own home regardless of the presence of dementia. Process indicators assessing guideline-fidelity are associated with remaining in one’s home longer, while indicators assessing complications, such as emergency inpatient treatment (HR = 2.67, 95% CI 1.99–3.60 PWD; HR = 2.81, 95% CI 2.28–3.47 PWOD) or lower-limb amputation (HR = 3.10, 95% CI 1.78–5.55 PWD; HR = 2.81, 95% CI 1.94–4.08 PWOD) in PWD and PWOD with hypertension and diabetes, increase the risk of NHA. Conclusions The quality of primary care provided to care-dependent multimorbid PWD and POWD, influences the time individuals spend living in their own homes after onset of care-dependency before a NHA. Health care professionals should consider possibilities and barriers of guideline-based, coordinated care for multimorbid care-dependent people. Further research on quality indicator sets that acknowledge the complexity of care for multimorbid elderly populations is needed.

Background Diabetes is one of the major public health concerns. Prediabetes can increase the risk of developing some non-communicable diseases such as type 2 diabetes. Given the increasing trend of prediabetes, it is critical to control it and prevent its complications. Curcumin is a major bioactive component of turmeric. Zinc is an antioxidant nutrient. The present trial aimed to evaluate the effect of curcumin and zinc co-supplementation along with a loss-weight diet on serum lipid profiles in overweight or obese patients with prediabetes. Methods Eighty-four participants were randomized to four groups (curcumin (500 mg/day), zinc (30 mg/day), “curcumin and zinc”, and placebo) for 90 days. Serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), non-HDL, HDL/LDL ratio, weight, BMI, waist circumstance (WC), hip circumstance (HC), physical activity (PA) and dietary intake were determined pre and post-intervention. This study will be conducted at Yazd Diabetes Research Clinic, Shahid Sadoughi University of Medical Sciences. Results Totally, 82 participants were included in the final analysis. After the adjusted PA effect, changes in serum TG (adjusted p = 0.001), LDL (adjusted p = 0.035), non-HDL (adjusted p = 0.003), HDL/LDL ratio (adjusted p = 0.002), and HDL (adjusted p Conclusion The beneficial effects of “curcumin and zinc” co-supplementation was reported for the changes of some lipid profiles (TG, LDL, HDL, non-HDL, and HDL to LDL ratio), BMI, and weight with no positive effects on TC, dietary intake, PA, WC, and HC. Therefore, it may play a potential role in the prevention of macro and microvascular complications. Trial registration The project is a registered clinical trial (Registration number: IRCT20190902044671N1, Iranian Registry of Clinical Trials (IRCT), registered October 11, 2019.