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Abstract Introduction Migraine‐related stigma (MiRS) and social burden is increasingly recognized. We assessed perspectives and attitudes toward migraine in people with and without migraine in Japan. Methods OVERCOME (Japan) was a cross‐sectional, population‐based web survey of people with and without migraine (July−September 2020). People with migraine were individuals who met the modified International Classification of Headache Disorders criteria or had self‐reported physician‐diagnosed migraine. People without migraine were selected per quota sampling to represent the Japanese adult population. People with migraine reported their experiences on stigma and social burden and answered how frequently they experienced stigma using the MiRS questionnaire. Associations between MiRS and disability and MiRS and interictal burden were examined using the migraine disability assessment and Migraine Interictal Burden Scale‐4. People without migraine reported their experiences and attitudes toward people with migraine by answering an 11‐item attitudinal migraine questionnaire. Results A total of 17,071 and 2008 people with and without migraine, respectively, completed the survey. Overall, 11,228 (65.8%) respondents with migraine reported that they have never experienced stigma or burden; however, of the 12,383 employed respondents, 5841 (47.2%) reported that their current employers are not “extremely” or “very” understanding about their conditions. Moreover, ∼30%−40% of respondents “sometimes,” “often,” or “very often” hid their migraine from others. The proportion of respondents who experienced stigma often or very often, as assessed by MiRS, was 16.5%; this increased with the increasing number of monthly migraine headache days. The proportion of respondents with moderate‐to‐severe disability and interictal burden increased with increasing stigma. Among respondents without migraine, the proportion holding a stigmatizing attitude toward those with migraine was low (

Abstract Background Gaucher disease (GD) is a rare autosomal recessive lysosomal storage disorder. GD types 2 and 3 are known as neuronopathic Gaucher disease (nGD) because they have brain involvement that progresses over time. Implementing a systematic approach to the collection of real-world clinical and patient-relevant outcomes data in nGD presents an opportunity to fill critical knowledge gaps and ultimately help healthcare providers in the management of this patient population. This paper summarizes the development of a patient-initiated Gaucher Registry for Development Innovation and Analysis of Neuronopathic Disease (GARDIAN). Methods The International Gaucher Alliance led the GARDIAN planning, including governance, scope, stakeholder involvement, platform, and reporting. Registry element input was determined in a series of meetings with clinical experts, patients, and caregivers, who identified key clinical variables and the draft content of nGD patient-reported outcomes (PRO) and observer-reported outcomes (ObsRO) focusing on symptoms, patient physical and emotional functioning. These were then tested in cognitive interviews with patients with nGD (> 12 years of age) and caregivers. Results Core registry data elements (n = 138) were identified by seven global clinical experts from Egypt, Germany, Israel, Japan, United Kingdom (UK), and United State (US) and reviewed via online Delphi method by 14 additional clinicians with experience of nGD from six countries and three pharmaceutical representatives. The elements were consistent with those identified via interviews with 10 patients/caregivers with nGD from Japan, Sweden, UK, and US. Key domains identified were demographics, diagnostic information, health status, clinical symptomatology, laboratory testing, treatment, healthcare resource utilization, aids/home improvements, and patient/caregiver burden and quality of life, specifically physical functioning, self-care, daily and social activities, emotional impacts, support services, and caregiver-specific impacts. Nine caregivers and six patients from the US, UK, China, Mexico, Egypt, and Japan participated in the cognitive interviews that informed revisions to ensure that all items are understandable and interpreted as intended. Conclusions The comprehensive set of clinical and patient relevant outcomes data, developed collaboratively among all stakeholders, to be reported using GARDIAN will bridge the many gaps in the understanding of nGD and align with regulatory frameworks on real-world data needs.

Abstract Background Knowledge of patient outcomes and treatment effectiveness associated with acute migraine treatments in Japan is lacking. Objective To describe patient-reported outcomes (PROs) and treatment effectiveness in three acute treatment groups from OVERCOME (Japan): over-the-counter (OTC) only, prescription nonsteroidal anti-inflammatory drugs/acetaminophen (Rx-NSAIDs/ACE) only, and triptans. Methods OVERCOME (Japan) was an observational, cross-sectional, population-based web survey of people with migraine (July–September 2020). PROs, including the Migraine-Specific Quality of Life Questionnaire (MSQ), Migraine Interictal Burden Scale (MIBS-4), Migraine Disability Assessment (MIDAS), and Work Productivity and Activity Impairment Questionnaire: Migraine (WPAI-M), were compared pairwise between treatment groups. Logistic regression was used to examine treatment effectiveness. Results The analysis included 9075 survey respondents (OTC only: n = 5791; Rx-NSAIDs/ACE only: n = 751; triptans: n = 2533). Triptan users reported the lowest MSQ scores, most severe disability (MIDAS: 20.7% versus 6.3% and 11.6%) and severe interictal burden (MIBS-4: 50.1% versus 21.2% and 19.8%), and greatest work impairment (WPAI-M: 50.4% versus 32.2% and 30.8%) compared with the OTC and Rx-NSAIDs/ACE groups, respectively. Treatment effectiveness was very poor-to-poor for 60.9%, 43.1%, and 47.6% of the triptan, OTC, and Rx-NSAIDs/ACE groups, respectively. Severe interictal burden was significantly associated with insufficient treatment effectiveness (odds ratios, severe versus no burden: 0.47 [95% confidence interval: 0.40–0.54], 0.56 [0.35–0.89], and 0.41 [0.32–0.52], for the OTC, Rx-NSAIDs/ACE, and triptan groups, respectively). Conclusion People with high migraine burden used triptans for acute treatment, but many reported poor treatment effectiveness. Education may be required to promote better treatments, including earlier introduction of migraine-specific acute and preventive medications.

Stenotrophomonas maltophilia and Achromobacter xylosoxidans are emerging nosocomial, non-glucose fermenting, Gram-negative pathogens. In this nested case-control trial, independent predictors for S. maltophilia infections were hemodialysis and recent antibiotic usage (overall), while recent usage of fluoroquinolones, was independently associated with A. xylosoxidans infections. Infections were independently associated with multiple worse outcomes.

Abstract Frailty, as measured by the modified frailty index-5 (mFI-5), and older age are associated with increased mortality in the setting of spinal cord injury (SCI). However, there is limited evidence demonstrating an incremental prognostic value derived from patient mFI-5. We conducted a retrospective cohort study to evaluate in-hospital mortality among adult complete cervical SCI patients at participating centers of the Trauma Quality Improvement Program from 2010 to 2018. Logistic regression was used to model in-hospital mortality, and the area under the receiver operating characteristic curve (AUROC) of regression models with age, mFI-5, or age with mFI-5 was used to compare the prognostic value of each model. 4733 patients were eligible. We found that both age (80 y versus 60 y: OR 3.59 95% CI [2.82 4.56], P

Abstract Odontoid fractures are increasingly prevalent in older adults and associated with high morbidity and mortality. Optimal management remains controversial. Our study aims to investigate the association between surgical management of odontoid fractures and in-hospital mortality in a multi-center geriatric cohort. We identified patients 65 years or older with C2 odontoid fractures from the Trauma Quality Improvement Program database. The primary study outcome was in-hospital mortality. Secondary outcomes were in-hospital complications and hospital length of stay. Generalized estimating equation models were used to compare outcomes between operative and non-operative cohorts. Among the 13,218 eligible patients, 1100 (8.3%) were treated surgically. The risk of in-hospital mortality did not differ between surgical and non-surgical groups, after patient and hospital-level adjustment (OR: 0.94, 95%CI: 0.55–1.60). The risks of major complications and immobility-related complications were higher in the operative cohort (adjusted OR: 2.12, 95%CI: 1.53–2.94; and OR: 2.24, 95%CI: 1.38–3.63, respectively). Patients undergoing surgery had extended in-hospital length of stay compared to the non-operative group (9 days, IQR: 6–12 days vs. 4 days, IQR: 3–7 days). These findings were supported by secondary analyses that considered between-center differences in rates of surgery. Among geriatric patients with odontoid fractures surgical management was associated with similar in-hospital mortality, but higher in-hospital complication rates compared to non-operative management. Surgical management of geriatric patients with odontoid fractures requires careful patient selection and consideration of pre-existing comorbidities.

Inference in cosmology often starts with noisy observations of random fields on the celestial sphere, such as maps of the microwave background radiation, continuous maps of cosmic structure in different wavelengths, or maps of point tracers of the cosmological fields. Almanac uses Hamiltonian Monte Carlo sampling to infer the underlying all-sky noiseless maps of cosmic structures, in multiple redshift bins, together with their auto- and cross-power spectra. It can sample many millions of parameters, handling the highly variable signal-to-noise of typical cosmological signals, and it provides science-ready posterior data products. In the case of spin-weight 2 fields, Almanac infers $E$- and $B$-mode power spectra and parity-violating $EB$ power, and, by sampling the full posteriors rather than point estimates, it avoids the problem of $EB$-leakage. For theories with no $B$-mode signal, inferred non-zero $B$-mode power may be a useful diagnostic of systematic errors or an indication of new physics. Almanac's aim is to characterise the statistical properties of the maps, with outputs that are completely independent of the cosmological model, beyond an assumption of statistical isotropy. Inference of parameters of any particular cosmological model follows in a separate analysis stage. We demonstrate our signal extraction on a CMB-like experiment.

IntroductionThe objective of this study was to investigate the effect of a novel screw type on stiffness and failure characteristics of a tibial plateau leveling osteotomy (TPLO) construct under cyclic loading conditions. The authors hypothesized that bone-screw-fasteners (BSF) would result in superior biomechanical stability compared with locking buttress screws (LBS).Materials and MethodsTwelve pairs of canine cadaveric pelvic limbs were included in this ex vivo biomechanical study. A TPLO was performed using a 3.5mm locking TPLO plate and stabilized using either LBS or BSF. Cyclic loading was performed for 30,000 cycles at 4Hz with a peak-load of 1000N (50N valley). The cyclic test was then continued by stepwise incremental increase of peak-load at a rate of 75N per 500 cycles until failure.ResultsCycles to failure for LBS (44,260 ± 5,770) and BSF (41,540 ± 7,686) were not significantly different (p = 0.36). Maximum force for LBS (3,134 ± 797N) and BSF (2,940 ± 831N) was not significantly different either (p = 0.58). Dynamic stiffness for LBS (1,778 ± 932 N/mm) and BSF (1,574 ± 677 N/mm) was not significantly different (p = 0.58).DiscussionStabilization of the TPLO with BSF provided similar biomechanical stability under cyclic axial loading conditions as the LBS. BSF may be an acceptable alternative to traditional locking screws for TPLO.

We use time-domain simulations of Jupiter observations to test and develop a beam reconstruction pipeline for the Simons Observatory Small Aperture Telescopes. The method relies on a mapmaker that estimates and subtracts correlated atmospheric noise and a beam fitting code designed to compensate for the bias caused by the mapmaker. We test our reconstruction performance for four different frequency bands against various algorithmic parameters, atmospheric conditions, and input beams. We additionally show the reconstruction quality as a function of the number of available observations and investigate how different calibration strategies affect the beam uncertainty. For all of the cases considered, we find good agreement between the fitted results and the input beam model within an ∼1.5% error for a multipole range ℓ = 30–700 and an ∼0.5% error for a multipole range ℓ = 50–200. We conclude by using a harmonic-domain component separation algorithm to verify that the beam reconstruction errors and biases observed in our analysis do not significantly bias the Simons Observatory r -measurement

Abstract Background Esophageal cancer is a highly prevalent cancer associated with low survival, especially among those with advanced disease. Second‐line (2L) treatment patterns and related clinical outcomes of patients with advanced esophageal squamous cell carcinoma (advESCC) treated in routine clinical care were examined globally and regionally. Methods A retrospective, noninterventional study collected physician‐provided chart data of patients aged ≥20 years receiving either 2L active systemic therapy or BSC following first‐line active therapy for advESCC from 11 countries in Asian and Western regions (September–October 2018). Bivariate analyses examined treatment and outcomes by region. Results AdvESCC patients (Asia = 192; West = 195) were examined, of which 58.1% (Asia n = 101; West n = 124) received active systemic therapy. While regional differences in tumor classification and staging at diagnosis were observed with less advanced tumors in Asia, no regional differences for these characteristics at 2L initiation were reported. Both taxane‐ and nontaxane‐based therapies were used as 2L therapy among Asian and Western patients, although more western than Asian patients received immuno‐ or targeted therapies (17.0% vs. 3.0%; p = 0.001). Alopecia (10.7%), neutropenia (9.3%), and fatigue (9.3%) were the most‐commonly reported adverse events (AEs) in both regions. Significantly higher 2L AE‐related emergency room visits (Asia = 22.5% vs. West = 8.0%; p

We present a field-based signal extraction of weak lensing from noisy observations on the curved and masked sky. We test the analysis on a simulated Euclid-like survey, using a Euclid-like mask and noise level. To make optimal use of the information available in such a galaxy survey, we present a Bayesian method for inferring the angular power spectra of the weak lensing fields, together with an inference of the noise-cleaned tomographic weak lensing shear and convergence (projected mass) maps. The latter can be used for field-level inference with the aim of extracting cosmological parameter information including non-gaussianity of cosmic fields. We jointly infer all-sky $E$-mode and $B$-mode tomographic auto- and cross-power spectra from the masked sky, and potentially parity-violating $EB$-mode power spectra, up to a maximum multipole of $\ell_{\rm max}=2048$. We use Hamiltonian Monte Carlo sampling, inferring simultaneously the power spectra and denoised maps with a total of $\sim 16.8$ million free parameters. The main output and natural outcome is the set of samples of the posterior, which does not suffer from leakage of power from $E$ to $B$ unless reduced to point estimates. However, such point estimates of the power spectra, the mean and most likely maps, and their variances and covariances, can be computed if desired.

Abstract Background Suicidal ideation (SI) affects approximately 30–40% of those with major depressive disorder (MDD). To date, studies have examined the substantial humanistic and economic burden to caregivers of persons with MDD, however little is known of the impact of caring for persons with MDD when SI is present. This study examined the additional burden imposed on caregivers for persons with unipolar depression and SI in five major European countries. Methods A retrospective, cross-sectional analysis was conducted in five European countries using 2020 Europe National Health Wellness Survey (France, Germany, Italy, Spain and the United Kingdom) to compare differences in health and economic outcomes between caregivers of adults with unipolar depression and SI (CAUD-SI) and caregivers of adults with unipolar depression without SI (CAUD-nSI). The outcomes assessed included health-related quality of life (HRQoL; Medical Outcomes Study Short Form [SF-12v2]), health status (Short-Form 6 Dimension [SF-6D], EuroQol 5-Dimension 5-Level [EQ-5D-5L]), Work productivity and activity impairment (WPAI) and healthcare resource utilization (HRU). Linear mixed models and generalized linear mixed models adjusted for covariates were used to compare the two groups on outcomes of interest. Results Of 62,319 respondents, 0.89% (n = 554) were CAUD-SI and 1.34% (n = 837) were CAUD-nSI. In adjusted models, CAUD-SI reported greater humanistic burden than CAUD-nSI, with lower HRQoL (PCS: 42.7 vs. 45.0, p

Abstract Background Caregiving in depression imposes a complex health and economic burden. Moreover, there is a paucity of studies examining the impact of caregiving for adult relatives with unipolar depression (CG-UD). This study assessed the burden among CG-UD in five western European (EUR5) countries (France, Germany, Italy, Spain and the United Kingdom) compared with caregivers of adults with other chronic comorbidities (CG-OD) and general non-caregiving (non-CG) population. Methods A retrospective observational study was conducted using the 2016 National Health and Wellness Survey (NHWS) in EUR5. Differences in humanistic burden (health status and health-related quality of life [HRQoL]) and economic burden (work productivity and activity impairments, health care resource utilization [HRU]) were assessed between CG-UD and CG-OD respondents. Caregiver-specific burden (caregiving responsibilities and caregiver reaction assessment [CRA]) was assessed between caregiver groups. Generalized linear models were used to compare between the groups on the outcomes after adjusting for potential confounders. Results Of the 77,418 survey respondents examined, 1380 identified as CG-UD, 6470 as CG-OD and 69,334 as non-CG. Compared to CG-OD and non-CG, CG-UD, reported significantly lower health status (e.g., EuroQoL-5 Dimensions-5 Levels [EQ-5D-5L]: CG-UD = 0.63, CG-OD = 0.67, and non-CG = 0.73, p

Abstract Background A patient is considered to suffer from treatment resistant depression (TRD) when consecutive treatment with two products of different pharmacological classes, used for a sufficient length of time at an adequate dose, fail to induce a clinically meaningful effect (inadequate response). The primary aim of the current study was to examine the humanistic and economic burden of TRD in five European countries, France, Germany, Italy, Spain and the United Kingdom, by comparing with non-treatment resistant depression (nTRD) and general population respondents. Methods The sample for this retrospective observational study was taken from the 2017 National Health and Wellness Survey conducted in five European countries. Demographic and patient characteristics were examined for TRD patients compared to respondents with nTRD and to the general population using chi-square tests or one-way analysis of variance for categorical or continuous variables, respectively. Generalized linear models were performed to examine group differences after adjusting these estimates for confounders. Results A total 52,060 survey respondents were examined, of which 2686 and 622 were considered to have non-treatment resistant and treatment-resistant depression, respectively. Relative to the general population, nTRD and TRD respondents reported significant decrements in health-related quality of life, including lower adjusted mental (− 12.1 vs. -18.1) and physical (− 2.5 vs. -5.4) component scores of the SF-12v2 and increased adjusted relative risk for work (2.2 vs. 2.7) and activity (1.9 vs. 2.5) impairment (all p

Abstract Background Uncontrolled gout can cause significant joint and organ damage and has been associated with impairments in quality of life and high economic cost. Gout has also been associated with other comorbid diseases, such as chronic kidney disease. The current study explored if healthcare resource utilization (HRU) and survival differs between patients with incident gout in the presence or absence of chronic kidney disease (CKD). Methods Clalit Health Services (CHS) data were used to conduct a retrospective population-based cohort study of incident gout between 1/1/2006–31/12/2009. Incident cases of gout were identified and stratified by CKD status and by age group (

Abstract Background Osteoarthritis (OA) is one of the most common causes of health and work impairment; however, this relationship, especially in Japan, is not well characterized. This study examined work impairment and OA in Japanese workers, specifically the relationship with health-related quality of life (HRQoL) and health status. Methods This retrospective, cross-sectional observational study included the data of employed adults with a self-reported OA diagnosis from the 2014 Japan National Health and Wellness Survey. Presenteeism and absenteeism were classified using the Work Productivity and Activity Impairment (WPAI) questionnaire for impairment at work in the past week. Outcome variables included health-related quality of life, which was measured with the revised Medical Outcomes Study 36-Item Short Form Survey Instrument Health Survey (SF-36v2), and depression symptom severity, which was assessed using the Patient Health Questionnaire-9 (PHQ-9). Results The majority (71.2%) of respondents with OA reported presenteeism, and 11.1% reported absenteeism. Presenteeism and absenteeism were both associated with younger age; a lower proportion of respondents with than without presenteeism were married or living with a partner, and a greater proportion of those with absenteeism had comorbid conditions (for all, p

Abstract Background Israel is one of the few countries that have a national program for quality assessment of community healthcare. We aimed to evaluate whether improved performance in diabetes care was associated with improved health of diabetic patients on a national level. Methods We conducted a nationwide ecological study estimating improvements in diabetes-related quality indicators and health outcomes. We estimated both correlations between composite measures of diabetes-related quality indicators and selected outcomes, and assessed through a joinpoint analysis whether trends in selected outcomes changed 4 years after the inception of the national program. Results Between 2002 and 2010, the prevalence of diabetes in Israeli adults increased from 4.8% to 7.4%. During these years, an improvement was noticed in most quality indicators (from 53% to 75% for the composite score). Declines were noted in rates of blindness, diabetes-related end-stage kidney disease, lower limbs amputations and diabetes-related mortality. Significant accelerations in decline were noted for amputations in men and diabetes-related mortality in both Arab men and women 4 years after the inception of the national program. Conclusion This study suggests that Israel’s national program for quality indicators in diabetes care in the community has probably had a significant impact on the health status of the whole population and may have contributed to narrowing gaps in life expectancy between Israeli Jews and Arabs. Future studies based on individual-level data are needed to confirm these results.

Pulsar-timing arrays (PTAs) are seeking gravitational waves from supermassive-black-hole binaries, and there are prospects to complement these searches with stellar-astrometry measurements. Theorists still disagree, however, as to whether the local gravitational-wave background will be statistically isotropic, as arises if it is the summed contributions from many SMBH binaries, or whether it exhibits the type of statistical anisotropy that arises if the local background is dominated by a handful (or even one) bright source. Here we derive, using bipolar spherical harmonics, the optimal PTA estimators for statistical anisotropy in the GW background and simple estimates of the detectability of this anisotropy. We provide results on the smallest detectable amplitude of a dipole anisotropy (and several other low-order multipole moments) and also the smallest detectable amplitude of a "beam'' of gravitational waves. Results are presented as a function of the signal-to-noise with which the GW signal is detected and as a function of the number of pulsars (assuming uniform distribution on the sky and equal sensitivity per pulsar). We provide results first for measurements with a single time-domain window function and then show how the results are augmented with the inclusion of time-domain information. The approach here is intended to be conceptually straightforward and to complement the results of more detailed (but correspondingly less intuitive) modeling of the actual measurements.

Out-patient treatment of community-acquired pneumonia (CAP) is a major challenge in an era of increasing prevalence of antimicrobial resistance. However, data describing the clinical impact of such resistance are scarce. A probability model was developed to estimate the impact of antimicrobial resistance on clinical outcomes for adults with CAP, eligible for out-patient care. The model assumed patients would be evaluated at 48-72 h, with those failing to improve being either hospitalized or switched to a different antibiotic. Two strategies were considered: amoxicillin followed by erythromycin (amoxicillin/erythromycin) and erythromycin followed by levofloxacin (erythromycin/levofloxacin). Analyses were conducted based on susceptibility of the major pathogens in France and the UK. Primary model-generated outcome measures were the proportion of patients successfully treated with first-line therapy and the proportion of patients subsequently hospitalized. The model estimated that in France, the amoxicillin/erythromycin strategy would lead to 67.8% improving within 48-72 h and 12.7% subsequently being hospitalized, compared with 48.6% and 13.7% for erythromycin/levofloxacin. For the UK, first-line success and hospitalization rates were, respectively, 71.7% and 8.1% for amoxicillin/erythromycin, and 65.3% and 9.3% for erythromycin/levofloxacin. The model estimated that antimicrobial resistance was responsible for >40% of hospitalizations in France and 15% in the UK. These data suggest that in areas with substantially reduced levels of susceptibility, antimicrobial resistance may be a significant contributor to subsequent hospitalization in adults initially treated as out-patients for CAP. Choice of out-patient treatment strategy should consider local resistance rates in order to maximize the likelihood of early cure, thereby minimizing hospitalizations. [ABSTRACT FROM AUTHOR]