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OBJECTIVE The primary objective of this trial was to determine if shunt entry site affects the risk of shunt failure. METHODS The authors performed a parallel-design randomized controlled trial with an equal allocation of patients who received shunt placement via the anterior entry site and patients who received shunt placement via the posterior entry site. All patients were children with symptoms or signs of hydrocephalus and ventriculomegaly. Patients were ineligible if they had a prior history of shunt insertion. Patients received a ventriculoperitoneal shunt after randomization; randomization was stratified by surgeon. The primary outcome was shunt failure. The planned minimum follow-up was 18 months. The trial was designed to achieve high power to detect a 10% or greater absolute difference in the shunt failure rate at 1 year. An independent, blinded adjudication committee determined eligibility and the primary outcome. The study was conducted by the Hydrocephalus Clinical Research Network. RESULTS The study randomized 467 pediatric patients at 14 tertiary care pediatric hospitals in North America from April 2015 to January 2019. The adjudication committee, blinded to intervention, excluded 7 patients in each group for not meeting the study inclusion criteria. For the primary analysis, there were 229 patients in the posterior group and 224 patients in the anterior group. The median patient age was 1.3 months, and the most common etiologies of hydrocephalus were postintraventricular hemorrhage secondary to prematurity (32.7%), myelomeningocele (16.8%), and aqueductal stenosis (10.8%). There was no significant difference in the time to shunt failure between the entry sites (log-rank test, stratified by age < 6 months and ≥ 6 months; p = 0.061). The hazard ratio (HR) of a posterior shunt relative to an anterior shunt was calculated using a univariable Cox regression model and was nonsignificant (HR 1.35, 95% CI, 0.98–1.85; p = 0.062). No significant difference was found between entry sites for the surgery duration, number of ventricular catheter passes, ventricular catheter location, and hospital length of stay. There were no significant differences between entry sites for intraoperative complications, postoperative CSF leaks, pseudomeningoceles, shunt infections, skull fractures, postoperative seizures, new-onset epilepsy, or intracranial hemorrhages. CONCLUSIONS This randomized controlled trial comparing the anterior and posterior shunt entry sites has demonstrated no significant difference in the time to shunt failure. Anterior and posterior entry site surgeries were found to have similar outcomes and similar complication rates.

Attention deficit hyperactivity disorder (ADHD) symptomatology, comorbid diseases, and pharmacological treatment with antidepressants can have a negative impact on sexual function, which in turn increases the likelihood of sexual dysfunction in people with ADHD. The objective of this pilot study was to differentiate and delineate possible sexual dysfunction in adults with ADHD. Adult ADHD patients (n = 32, cisgender / heterosexual) and healthy controls (n = 32, cisgender / heterosexual) filled out the DÄS-Zuf questionnaire with 59 items (Krieger, 2013). This questionnaire is divided into the scales “general contentment with life,” “anxiety/depression,” “sexual dysfunction” and “sexual satisfaction.” Patients with ADHD had significantly higher scores on single items measuring various aspects of sexual dysfunction as well as higher scores on the “anxiety/depression” scale and lower scores on the “general contentment with life” scale. Following repeated measures analyses of covariance in which the scale “anxiety/depression” was controlled as covariate, none of the previously differences for single items between ADHD patients and controls remained significant. ADHD patients with methylphenidate showed stronger physical sexual arousal compared to those without methylphenidate. The results of this pilot study suggest several explanations for sexual dysfunction among adults with ADHD and offer tentative routes for practical treatment approaches.

Purpose: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA+), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA+ mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2. Patients and Methods: Patients had progressed after next-generation androgen receptor–directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized. Results: TRITON2 enrolled 115 patients with BRCA+ identified by central plasma (n = 34), central tissue (n = 37), or local (n = 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA+ by tissue testing. Conclusions: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA+ mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.

AIMS: To study the relationship between subclinical atrial fibrillation (AF) and changes in cognitive function in a large cohort of individuals with stroke risk factors.METHODS: Individuals with no prior AF diagnosis but with risk factors for stroke were recruited to undergo annual cognitive assessment with the Montreal Cognitive Assessment (MoCA) along with implantable loop recorder (ILR) monitoring for AF for 3 years. If AF episodes lasting ≥6 minutes were detected, oral anticoagulation (OAC) treatment was initiated.RESULTS: A total of 1194 participants (55.2 % men, mean age 74.5 (±3.9)) had a combined duration of heart rhythm monitoring of ≈1.3 million days. Among these, 339 participants (28.3%) had adjudicated AF, with a median AF burden of 0.072% (0.02, 0.39), and 324 (96%) initiated OAC. When stratifying the participants into AF burden groups (No AF, AFlow (AF burden 0.25%)), only participants in the AFlow group had a decrease in MoCA score over time (p = 0.03), although this was not significant after adjustment for stroke risk factors. A subgroup analysis of 175 participants (14.6%) with a MoCA CONCLUSIONS: In a high-risk population, subclinical AF detected by continuous monitoring and subsequently treated with OAC was not associated with a significant change in MoCA score over a three-year period.

Targeted public education may offer an approach to achieving more effective treatment in countries like Bangladesh, where breast cancer is a leading cause of cancer death in women. Effective cancer education interventions address the target population’s cultural and contextual needs. However, there is little published literature to guide the development of educational cancer interventions in a region where lack of resources combined with cultural stigma about cancer contribute to poor breast health outcomes for women. The goal of the current study was to design, test, and evaluate a culturally grounded intervention to promote breast problem care among women in rural Bangladesh. The current manuscript first describes the process of formative evaluation that led to the development of the intervention, including decisions about the audience, message construction, and mode of intervention delivery. Second, we describe the testing process, including process and outcome evaluation. Finally, we describe the lessons learned from the process. We conclude with recommendations related to cultural grounding for message development, questionnaire design, data collection procedures, and analysis.

Purpose: Percutaneous transluminal angioplasty (PTA) with conventional plain old balloon (POBA) and/or drug-coated balloon (DCB) is the primary intervention to treat peripheral artery stenoses. However, acute dissections during the procedure and potential for future target lesion revascularization remain procedural complications. The purpose of this study was to assess the acute and 12-month outcomes in patients who underwent novel vessel preparation with longitudinal, controlled-depth micro-incisions prior to PTA. Materials and Methods: Patients with symptomatic lower extremity peripheral arterial disease with a Rutherford class of 2 to 6 and >70% de novo stenosis of the superficial femoral or popliteal arteries were included in this retrospective study. Patients with thrombotic or embolic lesions, restenosis, or in-stent restenosis were excluded. The FLEX Vessel Prep System (FLEX VP) was used to prepare the vessel prior to PTA by creating micro-incisions at the target lesion. The FLEX VP was followed by POBA or paclitaxel DCB. Results: The study included 65 patients. Lesion characteristics were 90% median stenosis (range = 70%–100%), 75.4% mild-to-severe calcifications, and 33.8% occlusion rate, and median lesion length was 196 (range = 10–480) mm. Following vessel preparation, 82.1% of the patients had low severity dissection or no flow-limiting dissection. The provisional stent rate postprocedure was 16.9%, with a median stent length of 60 mm. The freedom from target lesion revascularization (FFTLR) in 63 evaluable patients at 6 and 12 months was 98.4% and 93.7%, respectively. Freedom from amputation was 100%. Conclusion: In this real-world/all-comers patient population with long, stenotic lesions across the calcification spectrum, vessel preparation with longitudinal micro-incisions prior to PTA was associated with low dissection rate, low dissection severity, low stent implantation, and high FFTLR with the absence of amputation at 12 months relative to published reports in long-lesion cohorts. These results support vessel preparation via micro-incisions.

The American Heart Association and American College of Cardiology published practice guidelines for the management of adult congenital heart disease in 2018 and the European Society of Cardiology published analogous guidelines in 2020. Although there are broad areas of consensus between the 2 documents, there are important differences that impact patient management. This review discusses key areas of agreement and disagreement between the 2 guidelines, with discussion of possible reasons for disagreement and potential implications.

BACKGROUND: The novel coronavirus 2019 (COVID-19) pandemic has transformed health care. With the need to limit COVID-19 exposures, telemedicine has become an increasingly important format for clinical care. Compared with other fields, neuro-ophthalmology faces unique challenges, given its dependence on physical examination signs that are difficult to elicit outside the office setting. As such, it is imperative to understand both patient and provider experiences to continue to adapt the technology and tailor its application. The purpose of this study is to analyze both neuro-ophthalmology physician and patient satisfaction with virtual health visits during the time of the COVID-19 pandemic. METHODS: Across three institutions (NYU Langone Health, Indiana University Health, and Columbia University Medical Center), telemedicine surveys were administered to 159 patients. Neuro-ophthalmologists completed 157 surveys; each of these were linked to a single patient visit. Patient surveys consisted of 5 questions regarding visit preparation, satisfaction, challenges, and comfort. The physician survey included 4 questions that focused on ability to gather specific clinical information by history and examination. RESULTS: Among 159 patients, 104 (65.4%) reported that they were satisfied with the visit, and 149 (93.7%) indicated that they were comfortable asking questions. Sixty-eight (73.9%) patients found the instructions provided before the visit easy to understand. Potential areas for improvement noted by patients included more detailed preparation instructions and better technology (phone positioning, Internet connection, and software). More than 87% (137/157) of neuro-ophthalmologists surveyed reported having performed an examination that provided enough information for medical decision-making. Some areas of the neuro-ophthalmologic examination were reported to be easy to conduct (range of eye movements, visual acuity, Amsler grids, Ishihara color plates, and pupillary examination). Other components were more difficult (saccades, red desaturation, visual fields, convergence, oscillations, ocular alignment, and smooth pursuit); some were especially challenging (vestibulo-ocular reflex [VOR], VOR suppression, and optokinetic nystagmus). Clinicians noted that virtual health visits were limited by patient preparation, inability to perform certain parts of the examination (funduscopy and pupils), and technological issues. CONCLUSIONS: Among virtual neuro-ophthalmology visits evaluated, most offer patients with appointments that satisfy their needs. Most physicians in this cohort obtained adequate clinical information for decision-making. Even better technology and instructions may help improve aspects of virtual health visits.

People with low incomes have a disproportionate prevalence of diabetes and its complications and experience many barriers to self-management, which community health workers (CHWs) may help address. We sought to examine the effects of an in-home CHW-led intervention for adults with diabetes and incomes

Undiagnosed and untreated obstructive sleep apnea (OSA) is associated with health comorbidities and negatively affects quality of life. Alternative treatments should be considered in patients who are unable to tolerate or benefit from positive airway pressure treatment. When properly indicated, positional devices, oral appliances, airway surgery, and hypoglossal nerve stimulation have been shown to be effective in treating OSA. Hypoglossal nerve stimulation is a successful second-line treatment with low associated morbidity and complication rate.

Case Presentation A 57-year-old man who had been intubated and placed on venovenous extracorporeal membrane oxygenation for hypoxemic respiratory failure due to COVID-19 pneumonia was transferred to our facility. He underwent anticoagulation with IV heparin titrated to an anti-Factor Xa goal of 0.1 to 0.3 international unit/mL. Over extracorporeal membrane oxygenation days 13 to 17, his WBC count rose from 17,500 to 47,000 cells/μL. He simultaneously experienced the development of fluid-refractory shock that required multiple vasopressors and received stress-dose hydrocortisone when his WBC was 30,000 cells/μL. He remained afebrile and was started on broad-spectrum antimicrobials that included antifungal and anthelminthic therapy.

Chagas disease (CD) serological screening at blood banks is usually performed by a single highly sensitive serological assay, with chemiluminescent immunoassays (CLIAs) being the method of choice. CLIAs employ recombinant, fusion peptides and/or chimeric antigens that selectively capture anti-Trypanosoma cruzi antibodies. However, despite high sensitivity, the ability of these tests to identify CD-positive cases should be evaluated against T. cruzi strains circulating in specific locales. Herein, we used a latent class analysis (LCA) approach employing an array of four chimeric antigens to assess the diagnostic performance of the Liaison XL Murex Chagas CLIA for the detection of anti-T. cruzi IgG in serum samples. The study included a panel of 5014 serum samples collected from volunteer blood donors at the Hematology and Hemotherapy Foundation of the State of Bahia, submitted to anti-T. cruzi antibody detection using Liaison Chagas CLIA and LCA as a reference test in the absence of a gold standard. LCA classified 4993 samples as negative, while positivity for T. cruzi antibodies was predicted in 21 samples. Compared with LCA, CLIA demonstrated sensitivity and specificity of 76.2% and 99.5%, respectively, providing an overall accuracy of 99.4%. In blood banks lacking a de facto highly sensitive screening immunoassay, the low sensitivity offered by Liaison Chagas CLIA renders it unsuitable for standalone use in serological screening procedures for CD. Moreover, blood banks are encouraged to carefully assess the ability of diagnostic methods to identify local T. cruzi strains in circulation.

In this study we aimed to assess whether individuals with ASD are prone to higher infection rates, or to severe COVID-19 illness. Individuals with ASD and age- and gender-matched controlled counterparts (total n = 32,812) were assessed for COVID-19 infection rates and hospitalizations. Results indicated higher infection rates among individuals with ASD, with the largest effect among individuals aged 40–60 (OR = 2.05, 95%CI 1.33–3.15, p

Summary Background Standard treatment for high-risk non-muscle-invasive bladder cancer is transurethral resection of bladder tumour followed by intravesical BCG immunotherapy. However, despite high initial responses rates, up to 50% of patients have recurrence or become BCG-unresponsive. PD-1 pathway activation is implicated in BCG resistance. In the KEYNOTE-057 study, we evaluated pembrolizumab, a PD-1 inhibitor, in BCG-unresponsive non-muscle-invasive bladder cancer. Methods We did this open-label, single-arm, multicentre, phase 2 study in 54 sites (hospitals and cancer centres) in 14 countries. In cohort A of the trial, adults aged 18 years or older with histologically confirmed BCG-unresponsive carcinoma in situ of the bladder, with or without papillary tumours, with an Eastern Cooperative Oncology Group performance status of 0–2, and who were ineligible for or declined radical cystectomy were enrolled. All enrolled patients were assigned to receive pembrolizumab 200 mg intravenously every 3 weeks for up to 24 months or until centrally confirmed disease persistence, recurrence, or progression; unacceptable toxic effects; or withdrawal of consent. The primary endpoint was clinical complete response rate (absence of high-risk non-muscle-invasive bladder cancer or progressive disease), assessed by cystoscopy and urine cytology approximately 3 months after the first dose of study drug. Patient follow-ups were done every 3 months for the first 2 years and every 6 months thereafter for up to 5 years. Efficacy was assessed in all patients who received at least one dose of the study drug and met BCG-unresponsive criteria. Safety was assessed in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov number, NCT02625961 , and is ongoing. Findings Between Dec 9, 2015, and April 1, 2018, we screened 334 patients for inclusion. 186 patients did not meet inclusion criteria, and 47 patients were assigned to cohort B (patients with BCG-unresponsive high grade Ta or any grade T1 papillary disease without carcinoma in situ; results will be reported separately). 101 eligible patients were enrolled and assigned to receive pembrolizumab. All 101 patients received at least one dose of the study drug and were included in the safety analysis. Five patients had disease that did not meet the US Food and Drug Administration definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore not included in the efficacy analysis (n=96). Median follow-up was 36·4 months (IQR 32·0–40·7). 39 (41%; 95% CI 30·7–51·1) of 96 patients with BCG-unresponsive carcinoma in situ of the bladder with or without papillary tumours had a complete response at 3 months. Grade 3 or 4 treatment-related adverse events occurred in 13 (13%) patients; the most common were arthralgia (in two [2%] patients) and hyponatraemia (in three [3%] patients). Serious treatment-related adverse events occurred in eight (8%) patients. There were no deaths that were considered treatment related. Interpretation Pembrolizumab monotherapy was tolerable and showed promising antitumour activity in patients with BCG-unresponsive non-muscle-invasive bladder cancer who declined or were ineligible for radical cystectomy and should be considered a a clinically active non-surgical treatment option in this difficult-to-treat population. Funding Merck Sharp & Dohme.

Undisturbed sleep has been shown to be important for both health and quality of life (Medic et al. [7]). The World Health Organization estimates that nearly 25% of the population suffers from disturbed sleep due to environmental noise (Health TWECfEa, [2]). Sleep disturbance associated with elevated noise levels is particularly prevalent in metropolitan areas. Our study tested the hypothesis that white noise would improve sleep in New Yorkers complaining of sleep difficulty due to elevated sound levels.Ten adult participants were included in this study. All participants were recruited from a New York City based sleep clinic. Inclusion criteria was based on the presence of sleep disturbance and the reporting of high levels of environmental noise in participants' sleep location. The study was conducted using a within-subject, ABA design, with baseline, treatment phase, followed by another baseline (washout) period. Each phase lasted one-week, during which noise level and sleep were assessed. The treatment consisted of the application of a white noise device (Dohm Classic by Marpac, LLC) in the participants' bedroom. Sleep parameters were measured subjectively using the Consensus Sleep Diary (Carney et al. [15]), and objectively using a Motionlogger Actigraph.Paired sample t-tests were conducted to evaluate the hypothesis that white noise improves sleep in a high noise environment. Significance was found on the variables WASO, as measured by actigraphy, t(9) = 3.438, p = 0.007 and sleep latency as measured by sleep diary, t(9) = 2.947, p = 0.016. There was a trend toward significance on the number of awakenings during the night, as measured by sleep diary, t(9) = 2.622, p = 0.028 (Holm's sequential correction of p-value required a value of0.01 to find significance on this comparison) and sleep efficiency (actigraph), t(9) = -2.121, p = 0.063.Our data show that white noise significantly improved sleep based on subjective and objective measurements in subjects complaining of difficulty sleeping due to high levels of environmental noise. This suggests that the application of white noise may be an effective tool in helping to improve sleep in those settings.

Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases. Findings Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53.6%] women) from 56 countries were included in the study. Of these, 31 798 (75.4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84.2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46.2 years (IQR 34.3-58.0); median age at diagnosis of familial hypercholesterolaemia was 44.4 years (32.5-56.5), with 40.2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17.4% (2.1% for stroke and 5.2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81.1%) were receiving statins and 3691 (21.2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5.43 mmol/L (IQR 4.32-6.72) among patients not taking lipid-lowering medications and 4.23 mmol/L (3.20-5.66) among those taking them. Among patients taking lipid-lowering medications, 2.7% had LDL cholesterol lower than 1.8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin-kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1.8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p, Pfizer Independent Grant for Learning Change [16157823]; Amgen; Merck Sharp Dohme; Sanofi-Aventis; Daiichi Sankyo; Regeneron; National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK; NIHR; Czech Ministry of Health [NU20-02-00261]; Canadian Institutes of Health Research; Austrian Heart Foundation; Tyrolean Regional Government; Gulf Heart Association, The EAS FHSC is an academic initiative that has received funding from a Pfizer Independent Grant for Learning & Change 2014 (16157823) and from investigator-initiated research grants to the European Atherosclerosis Society-Imperial College London from Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron. KKR acknowledges support from the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK. KID acknowledges support from a PhD Studentship from NIHR under the Applied Health Research programme for Northwest London, UK (the views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health). TF was supported by a grant from the Czech Ministry of Health (NU20-02-00261). JG receives support from the Canadian Institutes of Health Research. The Austrian Familial Hypercholesterolaemia registry has been supported by funds from the Austrian Heart Foundation and the Tyrolean Regional Government. The Gulf Familial Hypercholesterolaemia registry was done under the auspices of the Gulf Heart Association.

The rate of the remodeling of the arterialized saphenous vein conduit limits the outcomes of coronary artery bypass graft surgery (CABG), which may be influenced by endothelial dysfunction. We tested the hypothesis that high stretch (HS) induces human saphenous vein endothelial cell (hSVEC) dysfunction and examined candidate underlying mechanisms. Our results showed that in vitro HS reduces NO bioavailability, increases inflammatory adhesion molecule expression (E-selectin and VCAM1) and THP-1 cell adhesion. HS decreases F-actin in hSVECs, but not in human arterial endothelial cells, and is accompanied by G-actin and cofilin’s nuclear shuttling and increased reactive oxidative species (ROS). Pre-treatment with the broad-acting antioxidant N-acetylcysteine (NAC) supported this observation and diminished stretch-induced actin remodeling and inflammatory adhesive molecule expression. Altogether, we provide evidence that increased oxidative stress and actin cytoskeleton remodeling play a role in HS-induced saphenous vein endothelial cell dysfunction, which may contribute to predisposing saphenous vein graft to failure.

Testing is an essential part of containment of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic. This review summarizes studies for SARS‐CoV‐2 infection and testing. Nasopharyngeal samples are best at sensitivity detection, especially in early stages of disease and in asymptomatic individuals. Current swab processing involves a 100‐ to 1000‐fold dilution of the patient sample. Future optimization of testing should focus on using smaller volumes of viral transport media and swab designs to increase comfort and increased viral adhesion.

Healthcare-workers are at risk of contact with measles patients and disease transmission. Measles-infected employees of healthcare facilities may contribute to the nosocomial measles spread and serve as a source of infection for most susceptible cohorts such as pregnant women, neonates, and immunocompromised patients. In order to study the humoral immunity against measles in healthcare workers and reveal factors associated with seronegative status, we performed a cross-sectional study by enrolling 847 healthcare workers of the Arkhangelsk Regional Clinical Hospital. Anti-measles virus serum immunoglobulin G antibodies were quantified by using VectorMeasles-IgG ELISA kit (Vector-Best, Russia). According to the manufacturer's recommendations specific IgG anti-measles titer cut-off value higher than 0.18 IU/ml, equal to 0.12—0.17 IU/ml, or lower than 0.12 IU/ml was considered as positive (protective), equivocal, or negative, respectively. Assessing an impact of employee's gender, age, affiliation (department), current position was carried out by using binary logistic regression analysis while analyzing seronegative status of healthcare workers. Study participants dominated by females (92.1%). The median age was 48 (39; 57) years. The employees of somatic departments prevailed (26.7%). It was found that 93.7% of medical workers had concentration of anti-measles antibodies exceeding magnitude of protective titer (above 0.18 IU/ml), 4.4% and 1.9% were measles seronegative and equivocal, respectively. The level of antibodies against measles was associated with age of healthcare workers, but not with gender. All employees older than 60 years were measles seropositive, whereas those younger than 35 or within range 35 to 60 years of age had protective antibody titer in 77% and 95.5% of cases, respectively. The proportion of subjects with seronegative results did not depend on employee's position (doctor, nurse, cleaning worker), but varied a lot between different hospital departments. According to the data of logistic regression, the odds to have a seronegative test result among employees from somatic and remaining departments were 4.4-fold higher. Importantly, the rate of seronegative results was by 10-fold lower in employees born between 1968 and 1984 than those found in subjects born after 1985. On the other hand, subjects older than 60 years of age were seronegative at 50-fold lower rate than those who were under 35. The median concentration of measles immunoglobulin G among vaccinated healthcare workers vs. subjects recovered after natural infection was significantly lower reaching 0.56 IU/ml and 4.2 IU/ml (p 0.001), respectively. Five-year monitoring showed that titer of measles IgG antibodies decreased by 1.2-1.9-fold (average — 1.5). Thus, a cohort of healthcare workers from multidisciplinary healthcare facility demonstrated that the proportion measles-susceptible subjects was 6.3%. Importantly, age of examined subjects mainly affected seronegative status. Taking into consideration age-related lowered serum antibody level in vaccinated healthcare workers, seroprevalence studies and subsequent revaccination of seronegative people should be performed at least once every 5 years to prevent measles spread in healthcare facilities.

Although the co-occurrence of autistic spectrum disorder (ASD) and schizophrenia have been previously reported, the scope and magnitude of this comorbidity across large samples have not been sufficiently established. This study was aimed to assess the co-occurrence between schizophrenia and ASD in a large dataset, and to examine its predominance across different age and sex groups. Schizophrenia patients and age and sex frequency controls (n = 49,334) were assessed for the prevalence of autism spectrum disorder. The sample was stratified by age and sex, and co-occurrence was assessed using univariate and multivariate logistic regressions. Results indicated that schizophrenia was associated with ASD (OR = 7.01, 95%CI 2.98-16.43, p .0001) across all age groups aside from 50 to 70 years. This association was significant among male participants (OR = 11.69, 95%CI 3.59-38.01, p .0001) but not among female participants (OR = 2.33, 95%CI 0.60-9.03, p = .21). These findings indicate a large overlap between schizophrenia and ASD, and point to the need to expand the understanding of the potential mediating mechanisms of this co-occurrence.

Familial Hypercholesterolemia (FH) is characterized by elevated LDL-cholesterol (LDL-C) and high atherosclerosis risk. The impact of different dietary patterns on atherosclerosis biomarkers has been poorly studied in FH. This study verified the association of adherence to a Mediterranean diet with biomarkers of dyslipidemia and low-grade inflammation in molecularly proven FH adults from Brazil (BR) and Spain (SP).In this cross-sectional study adherence to the Mediterranean diet was assessed by a validated score and generalized estimating equations were used to evaluate its association with plasma LDL-C, apolipoprotein-B (ApoB) and high sensitivity C-reactive protein (hs-CRP) concentrations. We included 92 (mean age 45 years, 58.7% females) and 98 FH individuals (mean age 46.8 years, 60.2% females) respectively from BR and SP. FH causing variants did not differ between countries. LDL-C, ApoB and hs-CRP concentrations were higher in BR than in SP: 179 (135-250) and 161 (133-193) mg/dL; 141 (109-181) and 103 (88-134) mg/dL; and 1.6 (0.8-4.0) and 0.8 (0.4-1.5) mg/L respectively (all p 0.001). Most of BR had low adherence (n = 77, 83.7%), while the majority of SP were divided into moderate (n = 35, 35.7%) and strong adherence to the Mediterranean diet (n = 37, 37.8%), p 0.001. There was a significant inverse association of adherence to the Mediterranean diet score with higher LDL-C, ApoB, and hs-CRP after adjusting for socio economic parameters, caloric and fatty acid intakes as well as pharmacological lipid lowering therapies.Higher adherence to a Mediterranean diet was associated with better dyslipidemia and low-grade inflammation profiles in FH.

The Covid-19 pandemic highly impacts mental health worldwide. Patients with psychiatric disorders are a vulnerable risk population for worsening of their condition and relapse of symptoms. This study investigates the pandemic-related course of psychosocial burden in patients with pre-existing mental disorders. With the newly developed Goettingen psychosocial Burden and Symptom Inventory (Goe-BSI) psychosocial burden has been traced retrospectively (1) before the pandemic (beginning of 2020), (2) at its beginning under maximum lockdown conditions (March 2020), and (3) for the current state after maximum lockdown conditions (April/May 2020). The Goe-BSI also integrates the Adjustment Disorder New Module (ADNM-20), assesses general psychiatric symptoms, and resilience. A total of 213 patients covering all major psychiatric disorders (ICD-10 F0-F9) were interviewed once in the time range from April, 24th until May 11th, 2020. Across all diagnoses patients exhibited a distinct pattern with an initial rise followed by a decline of psychosocial burden (p 2 = 0.09; Bonferroni-corrected pairwise comparisons between all three time-points: p

OBJECTIVE Facial palsy can be caused by masses within the posterior fossa and is a known risk of surgery for tumor resection. Although well documented in the adult literature, postoperative facial weakness after posterior fossa tumor resection in pediatric patients has not been well studied. The objective of this work was to determine the incidence of postoperative facial palsy after tumor surgery, and to investigate clinical and radiographic risk factors. METHODS A retrospective analysis was conducted at a single large pediatric hospital. Clinical, radiographic, and histological data were examined in children who were surgically treated for posterior fossa tumors between May 1, 1994, and June 1, 2011. The incidence of postoperative facial weakness was documented. A multivariate logistic regression model was used to analyze the predictive ability of clinicoradiological variables for facial weakness. RESULTS A total of 163 patients were included in this study. The average age at surgery was 7.4 ± 4.7 years, and tumor pathologies included astrocytoma (44%), medulloblastoma (36%), and ependymoma (20%). The lesions of 27 patients (17%) were considered high grade in nature. Thirteen patients (8%) exhibited preoperative symptoms of facial palsy. The overall incidence of postoperative facial palsy was 26% (43 patients), and the incidence of new postoperative facial palsy in patients without preoperative facial weakness was 20% (30 patients). The presence of a preoperative facial palsy had a large and significant effect in univariate analysis (OR 11.82, 95% CI 3.07–45.44, p < 0.01). Multivariate logistic regression identified recurrent operation (OR 4.45, 95% CI 1.49–13.30, p = 0.01) and other preoperative cranial nerve palsy (CNP; OR 3.01, 95% CI 1.24–7.29, p = 0.02) as significant risk factors for postoperative facial weakness. CONCLUSIONS Facial palsy is a risk during surgical resection of posterior fossa brain tumors in the pediatric population. The study results suggest that the incidence of new postoperative facial palsy can be as high as 20%. The presence of preoperative facial palsy, an operation for recurrent tumor, and the presence of other preoperative CNPs were found to be significant risk factors for postoperative facial weakness.

Background Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. Objectives This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. Methods Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. Results From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. Conclusions COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity., Central Illustration

OBJECTIVE Posterior fossa decompression with duraplasty (PFDD) is commonly performed for Chiari I malformation (CM-I) with syringomyelia (SM). However, complication rates associated with various dural graft types are not well established. The objective of this study was to elucidate complication rates within 6 months of surgery among autograft and commonly used nonautologous grafts for pediatric patients who underwent PFDD for CM-I/SM. METHODS The Park-Reeves Syringomyelia Research Consortium database was queried for pediatric patients who had undergone PFDD for CM-I with SM. All patients had tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and ≥ 6 months of postoperative follow-up after PFDD. Complications (e.g., pseudomeningocele, CSF leak, meningitis, and hydrocephalus) and postoperative changes in syrinx size, headaches, and neck pain were compared for autograft versus nonautologous graft. RESULTS A total of 781 PFDD cases were analyzed (359 autograft, 422 nonautologous graft). Nonautologous grafts included bovine pericardium (n = 63), bovine collagen (n = 225), synthetic (n = 99), and human cadaveric allograft (n = 35). Autograft (103/359, 28.7%) had a similar overall complication rate compared to nonautologous graft (143/422, 33.9%) (p = 0.12). However, nonautologous graft was associated with significantly higher rates of pseudomeningocele (p = 0.04) and meningitis (p < 0.001). The higher rate of meningitis was influenced particularly by the higher rate of chemical meningitis (p = 0.002) versus infectious meningitis (p = 0.132). Among 4 types of nonautologous grafts, there were differences in complication rates (p = 0.02), including chemical meningitis (p = 0.01) and postoperative nausea/vomiting (p = 0.03). Allograft demonstrated the lowest complication rates overall (14.3%) and yielded significantly fewer complications compared to bovine collagen (p = 0.02) and synthetic (p = 0.003) grafts. Synthetic graft yielded higher complication rates than autograft (p = 0.01). Autograft and nonautologous graft resulted in equal improvements in syrinx size (p < 0.0001). No differences were found for postoperative changes in headaches or neck pain. CONCLUSIONS In the largest multicenter cohort to date, complication rates for dural autograft and nonautologous graft are similar after PFDD for CM-I/SM, although nonautologous graft results in higher rates of pseudomeningocele and meningitis. Rates of meningitis differ among nonautologous graft types. Autograft and nonautologous graft are equivalent for reducing syrinx size, headaches, and neck pain.

Maternal morbidity and mortality continue to rise in the United States, with cardiovascular disease as the leading cause of maternal deaths. Congenital heart disease is now the most common cardiovascular condition encountered during pregnancy, and its prevalence will continue to grow. In tandem with these trends, maternal cardiovascular health is becoming increasingly complex. The identification of women at highest risk for cardiovascular complications is essential, and a team-based approach is recommended to optimize maternal and fetal outcomes. This document, the second of a 5-part series, will provide practical guidance from pre-conception through postpartum for cardiovascular conditions that are predominantly congenital or heritable in nature, including aortopathies, congenital heart disease, pulmonary hypertension, and valvular heart disease.

Background and purpose Risk prediction with the Global Registry of Acute Coronary Events (GRACE) risk model is guideline-recommended in acute coronary syndrome (ACS) patients. However, the performance of more contemporary scores derived from ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and National Cardiovascular Data (NCDR) registries remains incompletely understood. We aimed to compare these models in German ACS patients. Methods and results A total of 1567 patients with (Non-)ST-segment elevation myocardial infarction (NSTEMI: 1002 patients, STEMI: 565 patients) undergoing invasive management at University Hospital Dusseldorf (Germany) from 2014 to 2018 were included. Overall in-hospital mortality was 7.5% (NSTEMI 3.7%, STEMI 14.5%). Parameters for calculation of GRACE 1.0, GRACE 2.0, ACTION and NCDR risk models and in-hospital mortality were assessed and risk model performance was compared. The GRACE 1.0 risk model for prediction of in-hospital mortality discriminated risk superior (c-index 0.84) to its successor GRACE 2.0 (c-index 0.79, pGRACE1.0vsGRACE2.0 = 0.0008). The NCDR model performed best in discrimination of risk in ACS overall (c-index 0.89; pACTIONvsNCDR Conclusions In a contemporary German patient population with ACS, modern NCDR and ACTION risk models showed superior performance in prediction of in-hospital mortality compared to the gold-standard GRACE model.

Background: Behavioral lifestyle interventions are the foundation of adolescent obesity treatment. Tailoring an intervention using adolescent stakeholder engagement during the development process could improve intervention effectiveness. Methods: Adolescents with overweight/obesity ages 14–19 (n = 41) participated in 11 sex-specific focus groups (girls = 6, boys = 5) and were asked their preferences regarding who should lead the intervention and be involved, what the messaging of the program should be, how to make the program engaging and maintain participation, and how to best measure nutrition intake and activity. Transcripts were coded and analyzed for emergent themes. Results: Mean age was 16.0 ± 1.8 years and participants were racially/ethnically diverse. Adolescents preferred interventions that avoid a focus on “weight loss,” and instead emphasize “healthy lifestyle,” which represents a more comprehensive goal of targeting physical and mental well-being. Most participants indicated preferences for a relatable instructor with prior weight loss experience. Both sexes preferred optional parental involvement, as some parents were described as helpful, while others were perceived as a hindrance to success. Boys and girls identified incentives, engaging activities, and electronic communication as core components for engagement and retention, with girls emphasizing socialization and building relationships. Sex differences in preferences were observed. Girls had more concerns about intervention participation and preferred interventions to be sex stratified. Conclusions: Behavioral interventions to treat adolescent obesity should focus messaging/content on healthy lifestyles, rather than weight loss, and be sex stratified. Development and implementation of future behavioral interventions for adolescent obesity should consider tailoring to adolescent preferences when possible to improve feasibility, acceptability, and effectiveness.

Paracoccidioidomycosis (PCM), or blastomycosis in South America, is a systemic granulomatous mycosis related to activities associated with soil management, especially agriculture. PCM restricted to tracheobronchial tree region has not yet been reported.

Metabolic acidosis induces osteoclastic bone resorption and inhibits osteoblastic bone formation. Previously we found that mice with a global deletion of the proton receptor OGR1 had increased bone density although both osteoblast and osteoclast activity were increased. To test whether direct effects on osteoclast OGR1 are critical for metabolic acidosis stimulated bone resorption, we generated knockout mice with an osteoclast-specific deletion of OGR1 (knockout mice). We studied bones from three-month old female mice and the differentiated osteoclasts derived from bone marrow of femurs from these knockout and wild type mice. MicroCT demonstrated increased density in tibiae and femurs but not in vertebrae of the knockout mice. Tartrate resistant acid phosphatase staining of tibia indicated a decrease in osteoclast number and surface area/bone surface from knockout compared to wild type mice. Osteoclasts derived from the marrow of knockout mice demonstrated decreased pit formation, osteoclast staining and osteoclast-specific gene expression compared to those from wild type mice. In response to metabolic acidosis, osteoclasts from knockout mice had decreased nuclear translocation of NFATc1, a transcriptional regulator of differentiation, and no increase in size or number compared to osteoclasts from wild type mice. Thus, loss of osteoclast OGR1 decreased both basal and metabolic acidosis-induced osteoclast activity indicating osteoclast OGR1 is important in mediating metabolic acidosis-induced bone resorption. Understanding the role of OGR1 in metabolic acidosis-induced bone resorption will provide insight into bone loss in acidotic patients with chronic kidney disease.

OBJECTIVEThe primary objective of this study was to use the prospective Hydrocephalus Clinical Research Network (HCRN) registry to determine clinical predictors of fast time to shunt failure (≤ 30 days from last revision) and ultrafast time to failure (≤ 7 days from last revision).METHODSRevisions (including those due to infection) to permanent shunt placements that occurred between April 2008 and November 2017 for patients whose entire shunt experience was recorded in the registry were analyzed. All registry data provided at the time of initial shunt placement and subsequent revision were reviewed. Key variables analyzed included etiology of hydrocephalus, age at time of initial shunt placement, presence of slit ventricles on imaging at revision, whether the ventricles were enlarged at the time of revision, and presence of prior fast failure events. Univariable and multivariable analyses were performed to find key predictors of fast and ultrafast failure events.RESULTSA cohort of 1030 patients with initial shunt insertions experienced a total of 1995 revisions. Of the 1978 revision events with complete records, 1216 (61.5%) shunts remained functional for more than 1 year, and 762 (38.5%) failed within 1 year of the procedure date. Of those that failed within 1 year, 423 (55.5%) failed slowly (31–365 days) and 339 (44.5%) failed fast (≤ 30 days). Of the fast failures, 131 (38.6%) were ultrafast (≤ 7 days). In the multivariable analysis specified a priori, etiology of hydrocephalus (p = 0.005) and previous failure history (p = 0.011) were independently associated with fast failure. Age at time of procedure (p = 0.042) and etiology of hydrocephalus (p = 0.004) were independently associated with ultrafast failure. These relationships in both a priori models were supported by the data-driven multivariable models as well.CONCLUSIONSNeither the presence of slit ventricle syndrome nor ventricular enlargement at the time of shunt failure appears to be a significant predictor of repeated, rapid shunt revisions. Age at the time of procedure, etiology of hydrocephalus, and the history of previous failure events seem to be important predictors of fast and ultrafast shunt failure. Further work is required to understand the mechanisms of these risk factors as well as mitigation strategies.

Despite high level of vaccination coverage, pertussis remains a serious problem of modern medicine. Pertussis cases are registered among infants, adolescents, and adults. Infants younger than three months of age have the highest rate of serious clinical pertussis course. Transplacental transfer of pertussis-specific antibodies induce protection against infection. The available data regarding anti-pertussis antibody level in pregnant women in Russia remain sparce. To evaluate the humoral immunity to Bordetella pertussis in pregnant women and factors associated with seronegative status, we performed a cross-sectional study with 388 participants. SeroPertussis IgG (Israel) ELISA kit was used to quantitate antibodies against pertussis toxin/hemagglutinin. Binary logistic regression analysis was performed to assess factors associated with seronegative status. The median age of the subjects was 30 years old, more than half of which (51.3%) provided no verified pertussis vaccination data so that their children will not receive transplacental anti-infectious immunity. Gestational age was significantly associated with seronegative status. Compared to women tested during the first trimester, participants in the third trimester of pregnancy were more likely to be seronegative against pertussis. The odds of being susceptible rose with increased gestational period (p 0.01 for linear trend). Age, number of pregnancies and vaccination status revealed no impact on significant differences between seropositive and seronegative subjects. Pertussis booster vaccinations for preschool children, adolescents and healthcare workers dealing with pregnant women and neonates as well as cocoon vaccination strategy and vaccination during pregnancy were necessary to be implemented to protect infants against pertussis.

COVID-19 is a highly contagious disease that can cause severe pneumonia. Patients with pneumonia undergo chest X-rays (XR) to assess infiltrates that identify the infection. However, the radiographic characteristics of COVID-19 are similar to the other acute respiratory syndromes, hindering the imaging diagnosis. In this work, we proposed identifying quantitative/radiomic biomarkers for COVID-19 to support XR assessment of acute respiratory diseases. This retrospective study used different cohorts of 227 patients diagnosed with pneumonia; 49 of them had COVID-19. Automatically segmented images were characterized by 558 quantitative features, including gray-level histogram and matrices of co-occurrence, run-length, size zone, dependence, and neighboring gray-tone difference. Higher-order features were also calculated after applying square and wavelet transforms. Mann–Whitney U test assessed the diagnostic performance of the features, and the log-rank test assessed the prognostic value to predict Kaplan–Meier curves of overall and deterioration-free survival. Statistical analysis identified 51 independently validated radiomic features associated with COVID-19. Most of them were wavelet-transformed features; the highest performance was the small dependence matrix feature of “low gray-level emphasis” (area under the curve of 0.87, sensitivity of 0.85, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p

Introduction Can intermittent energy restriction (IER) improve fat loss and fat-free mass retention compared with continuous energy restriction (CER) in resistance-trained adults? Methods Sixty-one adults (32 women) with mean (SD) age 28.7 (6.5) years, body weight 77.2 (16.1) kg and body fat 25.5 (6.1)% were randomized to 12 weeks of (1) 4 x 3-weeks of moderate (m) energy restriction interspersed with 3 x 1-weeks of energy balance (mIER; n=30; 15 weeks total), or (2) 12 weeks of continuous moderate energy restriction (mCER; n=31). Analyses of all outcome measures were by intention-to-treat. Results After accounting for baseline differences, mIER did not result in lower fat mass or body weight, or greater fat-free mass, compared to mCER after energy restriction. Mean (and 97.5% confidence interval, CI) for fat mass at the end of mIER versus mCER was 15.3 (12.5 to 18.0) kg versus 18.0 (14.3 to 21.7) kg (P=0.321), for fat-free mass was 56.7 (51.5 to 61.9) kg versus 56.7 (51.4 to 62.0) kg (P=0.309), and for body weight (with 95% CI) was 72.1 (66.4 to 77.9) versus 74.6 (69.3 to 80.0) (P=0.283). There were no differences between interventions in muscle strength or endurance or in resting energy expenditure, leptin, testosterone, insulin like growth factor-1, free 3,3',5-triiodothyronine or active ghrelin, nor in sleep, muscle dysmorphia or eating disorder behaviours. However, participants in mIER exhibited lower hunger (P=0.002) and desire to eat (P=0.014) compared to those in mCER, and greater satisfaction (P=0.016) and peptide YY (P=0.034). Conclusions Similar fat loss and fat-free mass retention are achieved with mIER and mCER during 12 weeks of energy restriction; however, mIER is associated with reduced appetite. Trial registration ACTRN12618000638235p.

Introduction. Infants younger than 3 months old are at high risk of severe pertussis, complications and pertussis-associated mortality. Newborns receive protection against pertussis from maternal antibodies transferred predominantly during late pregnancy. Neither disease, nor vaccination provides lifelong immunity against pertussis. So most of women have low antibody concentrations, leaving their newborn infant at a higher risk for disease in the first months of life.The aim of this study was to assess the concentration of antibodies against Вordetella pertussis among mother-baby dyads.Methods. We performed a cross-sectional study including 119 mother-baby dyads. Maternal antibodies were measured in venous blood specimens during the last trimester of pregnancy for women and in cord blood for newborn infants.Results. The median age was 30 (25; 34) years. The half of participants had unknown vaccination status (49,6%). Only 12,6% had a protective level (>18 U/mL) of anti-pertussis antibodies, 74,8% of participants had a nonprotective (Conclusion. We revealed a huge proportion of pregnant women (87,4%) and newborns (77,3%) susceptible to pertussis. Maternal antibody level against pertussis was the major predictor of the antibody level in the infant.

Over 390 million people worldwide are infected with dengue fever each year. In the absence of an effective vaccine for general use, national control programs must rely on hospital readiness and targeted vector control to prepare for epidemics, so accurate forecasting remains an important goal. Many dengue forecasting approaches have used environmental data linked to mosquito ecology to predict when epidemics will occur, but these have had mixed results. Conversely, human mobility, an important driver in the spatial spread of infection, is often ignored. Here we compare time-series forecasts of dengue fever in Thailand, integrating epidemiological data with mobility models generated from mobile phone data. We show that geographically-distant provinces strongly connected by human travel have more highly correlated dengue incidence than weakly connected provinces of the same distance, and that incorporating mobility data improves traditional time-series forecasting approaches. Notably, no single model or class of model always outperformed others. We propose an adaptive, mosaic forecasting approach for early warning systems.

Using a multi-institutional EMR registry, we extracted housing status and evaluated the presence of several important comorbidities in order to describe the demographics and comorbidity burden of persons experiencing homelessness in northeast Ohio and compare this to non-homeless individuals of varying socioeconomic position. Of 1,974,766 patients in the EMR registry, we identified 15,920 (0.8%) as homeless, 351,279 (17.8%) as non-homeless and in the top quintile of area deprivation index (ADI), and 1,607,567 (81.4%) as non-homeless and in the lower four quintiles of area deprivation. The comorbidity burden was highest in the homeless population with depression (48.1%), anxiety (45.8%), hypertension (44.2%), cardiovascular disease (18.4%), and hepatitis (18.1%) among the most prevalent conditions. We conclude that it is possible to identify homeless individuals and document their comorbidity burden using a multi-institutional EMR registry, in order to guide future interventions to address the health of the homeless at the health-system and community level.

Complex public health programmes may suffer from 'teething problems' during their implementation in practice, especially when programmes are developed top-down without the participation of end-users and service providers. Trying out and optimising a new concept in practice with stakeholder ' s participation may enhance the programme ' s chance of success. In this article we describe the participatory optimisation process of a German primary prevention programme for stroke caregivers, performed before its full-scale implementation. A Participatory Action Research (PAR) approach was applied immediately after the development of the preliminary programme that was led by the professional research team. Iterative PAR-cycles were composed of: observe, reflect, plan and act. Through PAR a matured concept, containing eight Conceptual Building Blocks, was obtained. The five preliminary building blocks: `Content ', `Human resources ', `Personalised approach ', `Timing ', and `Setting ', were prioritised to be the core blocks, providing the base for individual caregiver support. Three new building blocks: `Network building ', `Communication ', and `Social safety-net ' were designated as facilitating blocks, interconnecting and safeguarding the programme. PAR was found to be vital in systematically detecting the conceptual weaknesses of the preliminary concept and in adjusting its components to the needs of the key stakeholders, before full-scale implementation.

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P, Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.

BACKGROUND: Occipital-cervical fusion (OCF) and ventral decompression (VD) may be used in the treatment of pediatric Chiari-1 malformation (CM-1) with syringomyelia (SM) as adjuncts to posterior fossa decompression (PFD) for complex craniovertebral junction pathology. OBJECTIVE: To examine factors influencing the use of OCF and OCF/VD in a multicenter cohort of pediatric CM-1 and SM subjects treated with PFD. METHODS: The Park-Reeves Syringomyelia Research Consortium registry was used to examine 637 subjects with cerebellar tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and at least 1 yr of follow-up after their index PFD. Comparisons were made between subjects who received PFD alone and those with PFD + OCF or PFD + OCF/VD. RESULTS: All 637 patients underwent PFD, 505 (79.2%) with and 132 (20.8%) without duraplasty. A total of 12 subjects went on to have OCF at some point in their management (PFD + OCF), whereas 4 had OCF and VD (PFD + OCF/VD). Of those with complete data, a history of platybasia (3/10, P = .011), Klippel-Feil (2/10, P = .015), and basilar invagination (3/12, P

A low FODMAP diet (LFD) has become a standard treatment in irritable bowel syndrome (IBS) patients. Compliant adherence to a LFD is challenging. We investigated the effect of a LFD compared to a less restrictive low lactose diet (LLD) in a randomized cross-over trial with IBS patients.Twenty-nine IBS patients were randomly assigned to two groups. After a run-in phase of 14 days, patients received 21 days of either a LFD or LLD. This intervention was followed by a washout period of 21 days before crossing over to the alternate diet. Dietician led diet instruction was given continuously. An IBS Severity Scoring System (IBS-SSS) was filled in at the end of each study period. To enhance study adherence, daily symptoms were assessed using a Visual Analog Scale (VAS).IBS patients, irrespective of lactase deficiency, had a significantly reduced IBS-SSS score after both diets (LFD p = 0.002, LLD p = 0.007) without significant difference. On both diets, patients reported that IBS had less impact on their daily life compared to the time before the study (p 0.01). On daily assessment, IBS patients on LFD reported significantly less abdominal pain (median VAS difference to baseline -0.8 (-2.8 to 2.7, p = 0.03) and less bloating (-0.5 (-4.1 to 3.4, p = 0.02) than patients on the LLD.Both diets improved the overall IBS severity significantly and patients' preference of the two diets was similar. LFD but not LLD effectively reduced pain and bloating in patients with IBS.

Background: Persons with multiple sclerosis (MS) and depression symptoms report real-world cognitive difficulties that may be missed by laboratory cognitive tests. Objective: To examine the relationship of depressive symptoms to cognitive monotasking versus multitasking in early MS. Method: Persons with early MS ( n = 185; ⩽5 years diagnosed) reported mood, completed monotasking and multitasking cognitive tests, and received high-resolution 3.0 T magnetic resonance imaging (MRI). Partial correlations analyzed associations between mood and cognition, controlling for age, sex, estimated premorbid IQ, T2 lesion volume, and normalized gray matter volume. Results: Depression symptoms were more related to worse cognitive multitasking (−0.353, p 0.50). Findings were replicated with a second depression measure. Multitasking was worse in patients with at least mild depression than both patients with no/minimal depression and healthy controls. Multitasking was not related to mood in healthy controls. Conclusions: Depression symptoms are linked to cognitive multitasking in early MS; standard monotasking cognitive assessments appear less sensitive to depression-related cognition. Further investigation should determine directionality and mechanisms of this relationship, with the goal of enhancing treatment for cognitive dysfunction and depression in MS.

Aim: To validate mobile-based funduscope for diabetic retinopathy screening in Estonia. Methods: Quality validation comparison of HEINE® iC2 funduscope and Zeiss Visucam camera with image scoring and diagnostic test accuracy measurement by sensitivity and specificity. Study took place from January 2020 until March 2020 in East-Tallinn Central Hospital’s eye clinic. Results: Based on 90 patients, the Zeiss Visucam showed 35.6% DR prevalence while iC2 had 18.9% for images and 17.8% for videos. The average Likert score was 4.7 for Zeiss Visucam and 2.4 for both iC2 images and iC2 videos. The sensitivity of iC2 images was 72.7% (95%CI 49.6–88.4) for grader 1 and 61.9% (95%CI 38.7–81.0) for grader 2, iC2 video sensitivity was 57.1% (95%CI 37.4–75.0) and 65.4% (95%CI 44.4–82.1), respectively. The grader-based specificity for iC2 images was 96.7% (95%CI 80.9–99.8) and 93.5% (95%CI 77.2–98.9). iC2 videos had a 100% (95%CI 91.7–1.0; 92.0–1.0) specificity by both graders. Cohen’s kappa agreement was 0.82 and 0.96 for images and videos. Conclusion: Mobile-based funduscope iC2 is not valid for DR screening with non-dilated pupils and thus not suitable for clinics that do not have experienced specialist present. Moreover, the screening specialist needs to be experienced fundus photographer with extra multiple day training for funduscope use. As main resolution, mobile-based funduscope was not validated for DR screening in Estonia based on pre-set study criteria. Additional research and development of funduscope algorithm for image stripping from videos is needed for validation as iC2 benefits do not offset the gold standard at the moment.

Antibiotics can alter the gut microbiome (GMB), which may be associated with stone disease. We sought to determine the effect that antibiotics have on the GMB, urine ion excretion and stone formation in genetic hypercalciuric stone-forming (GHS) rats. 116th generation GHS rats were fed a fixed amount of a normal calcium (1.2%) and phosphate (0.65%) diet, and divided into three groups (n = 10): control (CTL) diet, or supplemented with ciprofloxacin (Cipro, 5 mg/day) or Bactrim (250 mg/day). Urine and fecal pellets were collected over 6, 12 and 18 weeks. Fecal DNA was amplified across the 16S rRNA V4 region. At 18 weeks, kidney stone formation was visualized by Faxitron and blindly assessed by three investigators. After 18 weeks, urine calcium and oxalate decreased with Bactrim compared to CTL and Cipro. Urine pH increased with Bactrim compared to CTL and Cipro. Urine citrate increased with Cipro compared to CTL and decreased by half with Bactrim. Calcification increased with Bactrim compared to CTL and Cipro. Increased microbial diversity correlated with decreased urinary oxalate in all animals (R = − 0.46, p = 0.006). A potential microbial network emerged as significantly associated with shifts in urinary pH. Bactrim and Cipro differentially altered the GMB of GHS rats. The Bactrim group experienced a decrease in urine calcium, increased CaP supersaturation and increased calcification. The GMB is likely a contributing factor to changes in urine chemistry, supersaturation and stone risk. Further investigation is required to fully understand the association between antibiotics, the GMB and kidney stone formation.

Purpose Diet is one of the most important modifiable risk factors for the development of type 2 diabetes. Here, we aim to identify dietary patterns and to investigate their association with prediabetes, undetected diabetes and prevalent diabetes. Methods The present study included 1305 participants of the cross-sectional population-based KORA FF4 study. Oral glucose tolerance test (OGTT) measurements together with a physician-confirmed diagnosis allowed for an accurate categorization of the participants according to their glucose tolerance status into normal glucose tolerance (n = 698), prediabetes (n = 459), undetected diabetes (n = 49), and prevalent diabetes (n = 99). Dietary patterns were identified through principal component analysis followed by hierarchical clustering. The association between dietary patterns and glucose tolerance status was investigated using multinomial logistic regression models. Results A Prudent pattern, characterized by high consumption of vegetables, fruits, wholegrains and dairy products, and a Western pattern, characterized by high consumption of red and processed meat, alcoholic beverages, refined grains and sugar-sweetened beverages, were identified. Participants following the Western pattern had significantly higher chances of having prediabetes (odds ratio [OR] 1.92; 95% confidence interval [CI] 1.35, 2.73), undetected diabetes (OR 10.12; 95% CI 4.19, 24.43) or prevalent diabetes (OR 3.51; 95% CI 1.85, 6.67), compared to participants following the Prudent pattern. Conclusion To our knowledge, the present study is one of the few investigating the association between dietary patterns and prediabetes or undetected diabetes. The use of a reference group exclusively including participants with normal glucose tolerance might explain the strong associations observed in our study. These results suggest a very important role of dietary habits in the prevention of prediabetes and type 2 diabetes.

BACKGROUND AND PURPOSE: Various patterns of leukoencephalopathy have been described in coronavirus disease 2019 (COVID-19). In this article, we aimed to describe the clinical and imaging features of acute disseminated leukoencephalopathy in critically ill patients with COVID-19 and the imaging evolution during a short-term follow-up. MATERIALS AND METHODS: We identified and reviewed the clinical data, laboratory results, imaging findings, and outcomes for 8 critically ill patients with COVID-19 with acute disseminated leukoencephalopathy. RESULTS: All patients demonstrated multiple areas of white matter changes in both cerebral hemispheres; 87.5% (7/8) of patients had a posterior predilection. Four patients (50%) had short-term follow-up imaging within a median of 17 days after the first MR imaging; they developed brain atrophy, and their white matter lesions evolved into necrotizing cystic cavitations. All (8/8) patients had inflammatory cytokine release syndrome as demonstrated by elevated interleukin-6, D-dimer, lactate dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, and ferritin levels. Most (7/8; 87.5%) patients were on prolonged ventilator support (median, 44.5 days; interquartile range, 20.5 days). These patients had poor functional outcomes (6/8 [75%] patients were discharged with mRS 5) and high mortality (2/8, 25%). CONCLUSIONS: Critically ill patients with COVID-19 can develop acute disseminated leukoencephalopathy that evolves into cystic degeneration of white matter lesions with brain atrophy during a short period, which we dubbed virus-associated necrotizing disseminated acute leukoencephalopathy. This may be the result of COVID-19-related endothelial injury, cytokine storm, or thrombotic microangiopathy.

ObjectiveTo determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–positive patients and recorded new neurologic disorders and hospital outcomes.MethodsWe conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders.ResultsOf 4,491 patients with COVID-19 hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were reverse transcriptase PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all p < 0.05). After adjusting for age, sex, SOFA scores, intubation, history, medical complications, medications, and comfort care status, patients with COVID-19 with neurologic disorders had increased risk of in-hospital mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.17–1.62, p < 0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63–0.85, p < 0.001).ConclusionsNeurologic disorders were detected in 13.5% of patients with COVID-19 and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.