Large-scale Observational Studies Research Articles

Community access to rectal artesunate for malaria (CARAMAL): A large-scale observational implementation study in the Democratic Republic of the Congo, Nigeria and Uganda.

The key to reducing malaria deaths in highly endemic areas is prompt access to quality case management. Given that many severe cases occur at peripheral level, rectal artesunate (RAS) in the form of suppositories was developed in the 1990s, allowing for rapid initiation of life-saving antimalarial treatment before referral to a health facility with full case management capabilities. One randomized controlled trial published in 2009 showed a protective effect of RAS pre-referral treatment against overall mortality of 26%, but with significant differences according to study sites and length of referral. Two important issues remained unaddressed: (1) whether the mortality impact of RAS observed under controlled trial conditions could be replicated under real-world circumstances; and (2) clear operational guidance for the wide-scale implementation of RAS, including essential health system determinants for optimal impact. From 2018 to 2020, the Community Access to Rectal Artesunate for Malaria (CARAMAL) project was conducted as a large-scale observational implementation study in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda (registered on ClinicalTrials.gov as NCT03568344). CARAMAL aimed to provide high-quality field evidence on the two issues above, in three remote settings with high malaria endemicity. A number of complementary study components were implemented. The core of the CARAMAL study was the Patient Surveillance System (PSS), which allowed tracking of cases of severe febrile illness from first contact at the periphery to a referral health facility, and then on to a Day 28 visit at the home of the patient. Community and provider cross-sectional surveys complemented the PSS. Here we describe in some detail RAS implementation, as well as the key CARAMAL study components and basic implementation experience. This manuscript does not intend to present key study results, but provides an extensive reference document for the companion papers describing the impact, referral process, post-referral treatment and costing of the RAS intervention.

Productivity Loss and Indirect Costs for Patients Newly Diagnosed with Early- versus Late-Stage Cancer in the USA: A Large-Scale Observational Research Study.

BackgroundThe total economic burden of cancer reflects direct and indirect costs, including productivity loss due to employment change, absenteeism, and presenteeism of patients and caregivers.ObjectiveThis study estimated the magnitude of employment decrease, work absence (WA), short-term disability (STD), long-term disability (LTD), and associated indirect costs among employees newly diagnosed with metastatic versus non-metastatic cancer in the USA.MethodsIBM® MarketScan® Commercial Claims and Encounters and Health and Productivity Management databases were used to identify employees aged 18–64 years and newly diagnosed with any cancer from 2009 to 2019. Proportions of patients with employment decrease, WA, STD, and LTD claims, and number of days missing from work were summarized by metastatic status during the first 12 months after diagnosis and the entire follow-up period. Subgroup analyses were conducted by age (< 50 years, ≥ 50 years) and cancer type (breast, lung, colon, pancreatic, and liver cancer).ResultsDuring the first year after diagnosis, compared to patients without metastases, significantly higher proportions of patients with metastases had employment decrease and STD or LTD claims (p < 0.001). The mean total number of days missing from work for patients with versus without metastases was 33.39 versus 14.91 (ratio = 2.40), 64.05 versus 27.15 (ratio = 2.36), and 105.93 versus 46.29 (ratio = 2.29) days within 3, 6, and 12 months after diagnosis, respectively. Estimates of indirect cost differences between the two groups ranged from $6,877 to $22,283 in the first year.ConclusionEarlier detection of cancer may reduce productivity loss of patients and indirect costs by initiating treatment before cancer progresses to late stage.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40258-022-00753-w.

Influence of obesity on incidence of thrombosis and disease severity in patients with COVID-19: From the CLOT-COVID study

BackgroundThe influence of obesity on the development of thrombosis and severity of coronavirus disease 2019 (COVID-19) remains unclear. MethodThe CLOT-COVID study was a retrospective multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 between April 2021 and September 2021 among 16 centers in Japan. The present study consisted of 2690 patients aged over 18 years with available body mass index (BMI), who were divided into an obesity group (BMI ≥30) (N = 457) and a non-obesity group (BMI <30) (N = 2233). ResultsThe obesity group showed more severe status of COVID-19 at admission compared with the non-obesity group. The incidence of thrombosis was not significantly different between the groups (obesity group: 2.6 % versus non-obesity group: 1.9 %, p = 0.39), while the incidence of a composite outcome of all-cause death, or requirement of mechanical ventilation or extracorporeal membrane oxygenation during hospitalization was significantly higher in the obesity group (20.1 % versus 15.0 %, p < 0.01). After adjusting confounders in the multivariable logistic regression model, the risk of obesity relative to non-obesity for thrombosis was not significant (adjusted OR, 1.39; 95 % CI, 0.68–2.84, p = 0.37), while the adjusted risk of obesity relative to non-obesity for the composite outcome was significant (adjusted OR, 1.85; 95 % CI, 1.39–2.47, p < 0.001). ConclusionsIn the present large-scale observational study, obesity was not significantly associated with the development of thrombosis during hospitalization; however, it was associated with severity of COVID-19.

Safety of acupotomy in a real-world setting: A prospective pilot and feasibility study

ObjectiveAcupotomy is a modern acupuncture method that includes modern surgical methods. Since acupotomy is relatively more invasive than filiform acupuncture treatment, it is important to establish the safety profile of this practice. To justify further large-scale prospective observational studies, this preliminary study was performed to assess the feasibility of the approach and investigate the safety profile and factors potentially associated with adverse events (AEs). MethodsThis was a prospective pilot study that assessed the feasibility of a large-scale forthcoming safety study on acupotomy treatment in a real-world setting. The feasibility (call response rate, drop-out rate, response rate for each variable and recruitment per month) and safety profile (incidence, type, severity and causality of AEs, and factors potentially associated with AEs) were measured. ResultsA total of 28 participants joined the study from January to May 2018. A follow-up assessment was achieved in 258 (1185 treatment points) out of 261 sessions (1214 treatment points). The response rate via telephone on the day after treatment was 87.3%. There were 8 systemic AEs in all the sessions (8/258; 3.11%) and 27 local AEs on the total points treated (27/1185; 2.28%). Severe AEs did not occur. Total AE and local AE occurrence were associated with blade width and the number of needle stimulations per treatment point. ConclusionThe findings suggest that it could be feasible to analyze the safety of acupotomy in a real-world setting. Moreover, the primary data on some relevant AEs could be determined. We are planning large-scale prospective studies based on these findings. Trial registrationClinical Research Information Service (CRIS) KCT0002849 (https://cris.nih.go.kr/cris/search/detailSearch.do/11487).

Cross-sectional and longitudinal associations between lipid accumulation product and hyperuricemia

Background and aimsLipid accumulation product (LAP) is a novel, sex-specific, index-describing lipid over accumulation. Previous studies used baseline LAP for predicting hyperuricaemia; however, the relationship between them is unclear. We aimed to investigate the relationship between LAP and the risk of hyperuricaemia in the Central Chinese population. Methods and resultsThis large-scale observational study comprised a cross-sectional population sample and a prospective cohort of 44,294 healthy subjects. This study examined the association between LAP and the risk of hyperuricaemia in the total sample and subgroups using multiple logistic regression analysis and multivariate cox proportional hazards model analysis. As a result, there was a dose-response relationship between LAP and the risk of hyperuricaemia. The prevalence of hyperuricaemia was 13.4% in the cross-sectional study. During 9 years of follow-up, hyperuricaemia occurred in 928 (19.8%) participants. The corresponding hazard ratios after multiple adjustments of hyperuricaemia in the second, third and fourth quartile were 1.34 (95% confidence interval [CI], 1.04–1.72), 2.01 (95% CI, 1.54–2.63), and 2.44 (95% CI, 1.80–3.30)-fold higher vs. the first quartile, respectively. Subgroup analyses showed that the association between LAP and the risk of hyperuricaemia was more pronounced in females, individuals≤49 years old and subjects with eGFR ≥60 ml/min/1.73 m2. ConclusionLAP was positively related to the risk of hyperuricaemia in the Central Chinese population, particularly in women, individuals≤49 years old and adults with relatively normal renal function. These findings suggested the potential of LAP as an independent risk indicator in preventing hyperuricaemia.

Bidirectional Longitudinal Relationships Between Arterial Stiffness and Hypertension Are Independent of Those Between Arterial Stiffness and Diabetes: A Large-Scale Prospective Observational Study in Employees of a Japanese Company.

BackgroundHypertension and diabetes frequently coexist; however, it has not yet been clarified if the bidirectional longitudinal relationships between arterial stiffness and hypertension are independent of those between arterial stiffness and diabetes.Methods and ResultsIn this 16‐year prospective observational study, 3960 middle‐aged employees of a Japanese company without hypertension/diabetes at the study baseline underwent annual repeated measurements of blood pressure, serum glycosylated hemoglobin A1c levels, and brachial‐ankle pulse wave velocity. By the end of the study period, 664, 779, 154, and 406 subjects developed hypertension, prehypertension, diabetes, and prediabetes, respectively. Increased brachial‐ankle pulse wave velocity at the baseline was associated with a significant odds ratio (per 1 SD increase) for new onset of prehypertension/hypertension with (2.45/3.28; P<0.001) or without (2.49/2.76; P<0.001) coexisting prediabetes/diabetes, but not for new onset of prediabetes/diabetes without coexisting hypertension. Analyses using the latent growth curve model confirmed the bidirectional relationships between brachial‐ankle pulse wave velocity and hypertension, but no such relationship was observed between brachial‐ankle pulse wave velocity and abnormal glucose metabolism.ConclusionsIn middle‐aged employees of a Japanese company, while bidirectional relationships were found to exist between increased arterial stiffness and hypertension, such a relationship was not found between increased arterial stiffness and diabetes. Therefore, it appears that increased arterial stiffness may be associated with the development of hypertension but not with that of diabetes.

Can diatom motility indices reflect excess fine sediment condition in streams?

The diatom motility trait is widely used in bioassessment studies, however, there is no strong consensus as to what environmental conditions diatom motility reflects. We used random forest models to explore the behavior of several diatom-based motility indices and examined whether stronger diatom motility-environmental relationships could be developed by controlling for environmental factors that influence natural sediment loads and factors that co-occur with anthropogenic sediment loading. Across the study area, median values of most stressors were low; streambed fine sediments ranged from 0 to 100% (median: 6.7%) and total phosphorus concentrations ranged from 0 to 2587 µg L−1 (median: 17 µg L−1). Depending on the index, median abundance of motile taxa ranged between 8 and 47%, and was highest in the plains ecoregion. Few sites were dominated by motile taxa, with only 9 sites having a relative abundance of highly motile taxa >50%. Refinement of the motility trait did result in improved model performance; the RF model developed for highly motile taxa had the lowest RMSE (0.11) with environmental variables explaining 34.9% of the variability in the index. Variables indicative of streambed and water column sediments were not important predictors in the RF models for any motility index and motility trait refinement did not improve the relationship between motility index and streambed fine sediments. Variables related to water quality (e.g., total phosphorus, conductivity), flow (e.g., runoff, % of channel as fast moving water), and watershed characteristics (e.g., watershed slope) were the most important environmental predictors for the RF models for all motility indices, while variables indicative of streambed and water column sediments had lower importance values. Stratifying sites by ecoregion resulted in slight improvement of model performance for the mountain ecoregion (RMSE = 0.09) but did not result in stronger relationships between diatom-motility indices and instream sediments. Stratifying sites by instream total phosphorus concentrations also resulted in slight improvements in RF model performance (RMSE = 0.10), but did not result in stronger relationships between diatom motility indices and instream sediment conditions. Stratifying sites by geomorphic features had no effect on how diatom motility indices responded to instream sediments. Our results show that the relationship between the diatom motility trait and fine sediment is complex. Strong relationships between fine sediments and diatom motility may be difficult to detect in large-scale observational studies covering complex landscapes with multiple interacting factors.

Examining the impact of sharing COVID-19 misinformation online on mental health

Misinformation about the COVID-19 pandemic proliferated widely on social media platforms during the course of the health crisis. Experts have speculated that consuming misinformation online can potentially worsen the mental health of individuals, by causing heightened anxiety, stress, and even suicidal ideation. The present study aims to quantify the causal relationship between sharing misinformation, a strong indicator of consuming misinformation, and experiencing exacerbated anxiety. We conduct a large-scale observational study spanning over 80 million Twitter posts made by 76,985 Twitter users during an 18.5 month period. The results from this study demonstrate that users who shared COVID-19 misinformation experienced approximately two times additional increase in anxiety when compared to similar users who did not share misinformation. Socio-demographic analysis reveals that women, racial minorities, and individuals with lower levels of education in the United States experienced a disproportionately higher increase in anxiety when compared to the other users. These findings shed light on the mental health costs of consuming online misinformation. The work bears practical implications for social media platforms in curbing the adverse psychological impacts of misinformation, while also upholding the ethos of an online public sphere.

Reference ranges for functional and structural echocardiographic parameters in asian athletes: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Physiologic cardiac remodelling is common in elite athletes, including changes such as increased left ventricle size and left ventricular wall thickness. These changes often overlap with those from pathological cardiac conditions - for instance dilated cardiomyopathy and hypertrophic cardiomyopathy - leading to diagnostic uncertainty. The availability of reference ranges specific to elite athletes, particularly Caucasian and Black ethnicities, facilitates accurate differentiation between physiology and pathology. However, there remains a paucity of Asian data despite an increased representation in global sport. Purpose To perform a systematic review and meta-analysis of cardiac imaging studies in Asian elite athletes and obtain reference values for commonly utilised parameters in this population. Methods We searched MEDLINE via PubMed, Embase, and the Cochrane Database for relevant studies from inception till 27th July 2021. We included observational studies that reported relevant cardiac imaging parameters in Asian elite athletes. We excluded studies that did not report gender-specific cardiac imaging parameters. After study selection and data extraction, we performed random effects meta-analysis of means to obtain the weighted mean of each relevant cardiac imaging parameter stratified by gender. Results We included a total of eight studies with relevant echocardiographic data from East Asia, South Asia and West Asia which comprised a total of 799 male and 206 female elite athletes participating in endurance and mixed sport disciplines. We excluded data pertaining to athletes participating in skill and power disciplines in a post-hoc manner due to paucity of data and extreme data ranges. The weighted mean left ventricular mass (g) was 211.5 (95% CI 202.6 - 220.3, I2 = 85.8%) for males, and 139.3 (95% CI 132 - 146.7, I2 = 88.2%) for females. The weighted mean left ventricular mass indexed to body surface area (g/m2) was 103.1 (95% CI 99.2 - 106.9, I2 = 79.4%) for males, and 75.1 (95% CI 71.5 - 78.6, I2 = 86.1%) for females. For left ventricular end diastolic diameter (mm), the weighted mean was 54.4 (95% CI 53.1 - 55.7, I2 = 97.3%) for males, and 47.2 (95% CI 46.2 - 48.3, I2 = 89.3%) for females. Lastly, the weighted mean left ventricular wall thickness (mm) was 9.9 (95% CI 9.6 - 10.2, I2 = 91.3%) for males, and 8.7 (95% CI 8.5 - 9, I2 = 80.7%) for females. Conclusions This is the first meta-analysis that provides preliminary echocardiographic reference ranges for Asian elite athletes. Statistical heterogeneity, however, is high in most outcome measures. This is likely due to the presence of confounders such as study demographics. Due to a paucity of studies, further subgroup or stratified analyses could not be performed meaningfully. More large-scale observational studies are required such that more sport, gender or region-specific data could be generated.

CE-543-03 EARLY RHYTHM CONTROL IN PATIENTS WITH INCIDENT ATRIAL FIBRILLATION WHO HAD A PRIOR HISTORY OF STROKE: A NATIONWIDE POPULATION-BASED COHORT STUDY

Early rhythm control therapy has been demonstrated to be associated with a lower risk of stroke compared to usual care in patients with atrial fibrillation (AF). However, there are limited data regarding the benefit of early rhythm control therapy for secondary prevention for stroke in patients with AF. To compare the risk of recurrent stroke between early rhythm control therapy and usual care in patients with new-onset AF and a history of prior stroke. Using the Korean nationwide claims database, we identified patients who were newly diagnosed as AF and had a history of prior stroke. Patients who received rhythm control therapy, including antiarrhythmic drug (AAD), direct current cardioversion (DCC), or AF catheter ablation, within 1 year after incident AF were defined as the early rhythm control group, otherwise as the usual care group. The propensity score weighting method was used to balance baseline characteristics between the two groups. Incident stroke was evaluated as a primary outcome. A total of 53,509 patients were included (mean age 72±11 years, 53% men; mean CHA2DS2-VASc score 5.5±1.6). All patients were prescribed oral anticoagulants. Among the total study population, 12,455 patients were assigned to the early rhythm control group (AAD, DCC, and AF catheter ablation in 99.4%, 8.6%, and 3.9%, respectively), and 41,054 patients were in the usual care group. During a median 2.6 years (IQR 1.5 to 4.5 years) of follow-up, 4382 patients had an incident stroke (IR, 2.6 per 100 person-years). Early rhythm control was associated with a lower risk of recurrent stroke compared to usual care (hazard ratio, 0.720, 95% confidence interval, 0.666-0.779, p<0.001) (Figure). Early rhythm control consistently showed a lower risk of stroke than usual care regardless of the characteristics of prior stroke, whether recent, severe, and disabling stroke or not. In this large-scale observational cohort study, early rhythm control within 1 year after AF diagnosis might be beneficial to prevent recurrent stroke in patients with incident AF and a history of prior stroke. Integrated care, including optimal rhythm control with appropriate anticoagulation, should be considered for patients who had incident AF and a history of stroke to reduce the risk of recurrent stroke.

Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.

Stimulants can cause psychotic symptoms at high doses and with parenteral use, but it remains uncertain whether the clinical use of prescription stimulants (PS) at therapeutic doses precipitates psychosis or influences long-term psychosis risk. Although serious, psychosis is a relatively uncommon event that is difficult to detect in brief randomized controlled trials. There have been several large-scale observational studies of PS and psychosis risk, which have not been reviewed; therefore, we conducted a systematic review of observational studies of PS and psychosis risk in adults and children. We conducted a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered with International Prospective Register of Systematic Reviews (CRD42021243484). Eligible studies were longitudinal observational studies, either cohort or case-control, published in English that reported on PS exposure and risk of psychotic events or disorders. Risk of bias assessments were performed with the ROBINS-I instrument. There were 10,736 reports screened, and 8 were ultimately included (n = 232,567 patients): 4 retrospective cohort studies, 1 nested case-control study, 2 self-controlled case series, and 1 prospective cohort study. Exposure to methylphenidate (MPH) was more commonly studied than amphetamine (AMPH). In the 3 studies with lowest risk of bias, there was no effect of MPH exposure on psychosis risk, but there was evidence for increased risk with AMPH in 1 study. We conclude that observational studies do not support a clear-cut effect of prescribed MPH on psychosis risk but that AMPH has been less well studied and may increase psychosis risk.

Liver resection for a solitary huge hepatocellular carcinoma (≥ 10 cm): A large-scale multicenter observational study

Liver resection for a solitary huge hepatocellular carcinoma (≥ 10 cm): A large-scale multicenter observational study

Low levels of vitamin D and coronary artery disease: Is it time for therapy?

The association between vitamin D and the prevalence and severity of coronary artery disease (CAD), major established cardiovascular risk factors, and acute ischemic events has been consistently demonstrated in large-scale observational studies and meta-analyses, with relevant prognostic implications. The rise in prevalence of hypovitaminosis D in recent years, reaching pandemic pro-portions, has pointed to the importance of the identification and optimization of the indications and strategies for the therapeutic use of vitamin D, with particular relevance for cardiovascular health. However, vitamin D supplementation has provided so far inconsistent results in primary prevention, with even fewer data reported in patients with established CAD. The present review aims to provide an updated overview of the available evidence and potential therapeutic applications of vitaminD in patients with CAD.

P104 Comparative risk of infection for first-line csDMARD therapy in rheumatoid arthritis: a multinational cohort analysis of real world data

Abstract Background/Aims Infections on conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) are an important concern for rheumatoid arthritis (RA) patients, especially during the COVID-19 pandemic. However comparative safety data between csDMARDs have been conflicting and limited in power. The objective was to assess the comparative safety of serious, opportunistic and all infections (including non-serious) of first-line csDMARDs in RA through a large multinational observational study. Methods We evaluated first-line new users of methotrexate (MTX), hydroxychloroquine (HCQ), sulfasalazine (SZ) and leflunomide (LEF) monotherapy. Data was obtained from four US databases (IQVIA US Ambulatory EMR (AMBER), Optum® De-identified Clinformatics® Datamart (Optum), IBM MarketScan® Medicare Supplemental Database (MDCR), and IBM MarketScan Commercial Database (CCAE)), one from Germany (IQVIA Disease Analyser Germany EMR (Germany)), and another from the UK (IQVIA UK The Health Improvement Network). Patients included were ≥18 years with a RA diagnosis between 2005-2019, without prior inflammatory arthritis, cancer or infection (in the preceding 30 days). Serious infections were defined as those requiring hospitalisation or resulting in death within 30 days; opportunistic infections were defined as per published EULAR consensus. Patients were followed from 1-day following treatment initiation to the earliest of treatment discontinuation, switching, or add-on plus 14 days, or loss to follow-up. Cox proportional-hazards models for MTX against each csDMARD with large-scale propensity score stratification were performed. A large set of negative control outcomes were used to calibrate hazard ratios (cHR) to account for potential residual confounding. Estimates were pooled where homogeneity across sources was adequate (I2&amp;lt;0.4). Results A total of 247,511 patients were included (MTX: 141,647; HCQ: 73,286, SSZ: 16,521, LEF: 16,057), with pooled incidence rates of serious, opportunistic and all infections across sources for MTX users of 33.7, 20.1 and 311.8 per 1,000 pyrs, respectively. With MTX as the referent, for all infections, the pooled cHR (with 95% Confidence Intervals) for SSZ was 0.73 (0.62, 0.86); HCQ, 0.96 (0.89, 1.04); and LEF, 0.74 (0.50, 1.08). The serious infection pooled cHR for SSZ was 0.75 (0.58, 0.97) and for LEF, 0.93 (0.61, 1.40). For opportunistic infections, pooled cHR for HCQ was 1.04 (0.92, 1.19). Conclusion SSZ, LEF and less consistently HCQ had a lower risk of all (including non-serious) infections, compared to MTX. SSZ and LEF were associated with a 25% reduction in the expected risk of all infections. SSZ was associated with a 25% lower risk of serious infections relative to MTX. In the first large scale observational network study assessing comparative risk of infection with csDMARDs there were differences between drugs in risk for all infections, with potential implications for clinical care. Disclosure M. Jani: None. E. Burn: None. J. Weaver: Corporate appointments; Janssen. L. Carmona: None. K. Chatzidionysiou: None. B. Illigen: None. D. Vizcaya: Corporate appointments; Bayer. T. Duarte-Salles: None. P. Ryan: Corporate appointments; Janssen. D. Prieto-Alhambra: None.

P135 Lower limb muscle strength and balance in older adults with distal radius fracture: a systematic review

Abstract Background/Aims Distal radius fractures (DRF) are common fall-related fragility fractures disproportionately affecting older females. After a DRF, there is an increased risk of future fragility fractures and functional decline. Systematic review evidence shows balance and muscle strengthening exercises reduce falls in older adults. Despite this, existing DRF rehabilitation trials have mainly focused on upper limb impairments. To inform rehabilitation requirements, we aimed to 1.) compare lower limb muscle strength and balance between older adults with a DRF with age- and sex-matched controls, and 2.) synthesise lower limb muscle strength and balance outcomes in older adults with a DRF. Methods We searched Embase, MEDLINE and CINAHL (1990 to August 2021). We included randomised and non-randomised controlled trials, and observational studies, that assessed lower limb strength and/or balance in adults aged ≥50 years enrolled within one year after a DRF. Strength and balance had to be assessed using validated instrumented or physical performance measures. Two reviewers independently screened titles and abstracts, and full-text reports of potentially eligible studies. One reviewer extracted data, then checked by another. Two reviewers independently appraised studies using the Cochrane risk-of-bias tool or Newcastle-Ottawa scale. We synthesised results narratively due to heterogeneity. PROSPERO registration: CRD42020196274. Results Seventeen studies (10 case-control studies, three RCTs and four case-series) including 1112 participants (95% women) with a DRF were included. Participants’ mean age ranged from 56 to 73 years; median sample size was 80 (IQR 54-106). Eleven (65%) studies assessed lower limb muscle strength using 10 different methods. Knee extensor strength assessment was most common (5/11 studies) followed by the 30-second and five times sit-to-stand tests (3/11 studies). All studies assessed balance, using 14 different methods. Single leg balance assessment was most common (6/17 studies) followed by functional reach and postural sway (3/17 studies). 5/10 case-control studies assessed lower limb muscle strength. Two studies found cases performed worse than controls during sit-to-stand tests; three studies assessed knee extensor strength with conflicting findings. All case-control studies assessed balance, with cases demonstrating impaired balance compared to controls on some measures. 4/17 studies assessed strength and 6/17 studies assessed balance at multiple timepoints. Over time, strength progressively improved in 3/4 studies but changes in balance were inconsistent across studies. Conclusion There is some evidence that older adults with a DRF have impaired lower limb muscle strength and balance compared to age- and sex-matched controls, but findings are inconsistent. Synthesis of results was limited by heterogeneity in the design, quality, and assessment methods used in included studies. Large-scale robust case-control and/or prospective observational studies are needed to better establish the rehabilitation requirements for this population. Disclosure C. Forde: Grants/research support; CF is supported by the NIHR Biomedical Research Centre, based at Oxford University Hospitals Trust, Oxford. P.J.A. Nicolson: Grants/research support; PN is supported by a Versus Arthritis Foundation Fellowship (ref. 22428). C. Vye: None. J.C.H. Pun: Grants/research support; JP received financial support from the NMAHPs Internship Versus Arthritis (Grant reference 22082). W. Sheehan: None. M. Costa: Grants/research support; MC receives grants from NIHR and related health charities. S.E. Lamb: Grants/research support; SL receives grants from NIHR and related health charities. D.J. Keene: Grants/research support; DK is supported by a National Institute of Health Research (NIHR) Postdoctoral Fellowship (ref. PDF-2016-09-056) and by the NIHR Biomedical Research Centre, based at Oxford University Hospitals Trust.

Sutureless Closure Versus Conventional Technique in the Primary Surgery of Total Anomalous Pulmonary Venous Connection: A Systematic Review and Meta-analysis.

Sutureless closure has been used for primary repair of total anomalous pulmonary venous connection (TAPVC) for over 20years but its superiority over conventional technique is still uncertain. This systematic review was conducted to compare the effectiveness of sutureless closure and conventional surgery as the primary repair for TAPVC. Systematic search was performed in June 2021 on 12 databases. All studies comparing sutureless and conventional surgery for TAPVC were included. The primary endpoints were early mortality, overall mortality, postoperative pulmonary venous stenosis (PVS), and reoperation. Meta-analysis of two-arm studies was performed with several sensitivity and subgroup analyses. Six retrospective studies with 767 patients were included in meta-analyses. Sutureless closure significantly reduced the risk of early mortality, overall mortality, postoperative PVS, and reoperation by 53%, 45%, 77%, and 67% compared to conventional technique, respectively. No heterogeneity was found and presence of publication bias was non-significant. The results were consistent in all sensitivity analyses. Subgroup analyses revealed that sutureless closure was superior to conventional technique in patients with and without preoperative pulmonary venous obstruction, and neonates and non-neonates. Sutureless closure is better than conventional closure as the primary surgery for TAPVC patients. We advocate using sutureless closure for patients with TAPVC. Future large-scale observational studies or clinical trials are required to confirm our findings.

The current status of thrombosis and anticoagulation therapy in patients with COVID-19 in Japan: From the CLOT-COVID study

BackgroundData on thrombosis and current real-world management strategies for anticoagulation therapy are scarce but important for understanding current issues and unmet needs of an optimal management of patients with coronavirus disease 2019 (COVID-19). MethodThe CLOT-COVID Study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study: UMIN000045800) was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021, and we tried to capture the status of the patients in the fourth and fifth waves of the COVID-19 infections in Japan. We enrolled consecutive hospitalized patients who were diagnosed with COVID-19 and had a positive polymerase chain reaction test obtained from the hospital databases. ResultsAmong 2894 patients with COVID-19, 1245 (43%) received pharmacological thromboprophylaxis. The proportion of pharmacological thromboprophylaxis increased according to the severity of the COVID-19 in 9.8% with mild COVID-19, 61% with moderate COVID-19, and 97% with severe COVID-19. The types and doses of anticoagulants varied widely across the participating centers. During the hospitalization, 38 patients (1.3%) and 126 (4.4%) underwent ultrasound examinations for the lower extremities and contrast-enhanced computed tomography examinations, respectively, and 55 (1.9%) developed thrombosis, mostly venous thromboembolism (71%). The incidence of thrombosis increased according to the severity of the COVID-19 in 0.2% with mild COVID-19, 1.4% with moderate COVID-19, and 9.5% with severe COVID-19. Major bleeding occurred in 57 patients (2.0%) and 158 (5.5%) died, and 81% of them were due to respiratory failure from COVID-19 pneumonia. ConclusionsIn the present large-scale observational study, pharmacological thromboprophylaxis for hospitalized patients with COVID-19 was common especially in patients with severe COVID-19, and management strategies varied widely across the participating centers. The overall incidence of thrombosis was substantially low with an increased incidence according to the severity of the COVID-19.

Factors associated with aortic valve stenosis in Japanese patients with end-stage kidney disease

BackgroundAortic valve stenosis (AS) has a high prevalence and poor prognosis in patients who receive maintenance dialysis. However, few large-scale observational studies in Japan have investigated patients with AS who underwent dialysis. In this study, we investigated the prevalence and factors associated with AS in Japanese patients who underwent dialysis.MethodsIn this cross-sectional analysis, we enrolled patients who underwent dialysis and transthoracic echocardiography between July 1, 2017 and June 30, 2018. Patients with a maximum aortic jet velocity (Vmax) ≥ 2.0 m/s, pressure gradient (PG) between the left ventricle and ascending aorta (mean PG) ≥ 20 mmHg, or aortic valve area (AVA) ≤ 1.0 cm2 were categorized into the AS group (G1). Patients with Vmax ≥ 3.0 m/s, mean PG ≥ 20 mmHg, or AVA ≤ 1.0 cm2 were categorized into the moderate and severe AS groups (G2). We performed multivariate logistic regression analysis and compared G1 and G2 with the non-AS group to determine the risk factors for AS. We also investigated the risk factors for aortic valve calcification, which is a pre-stage for AS.ResultsOf the 2,786 patients investigated, 555 (20.0%) and 193 (6.9%) were categorized into G1 and G2, respectively. Multivariate logistic regression analysis revealed that age, long-term dialysis, and elevated serum phosphorus levels were associated with AS in both the groups (p < 0.05). These factors were converted into ordinal categories, and a multivariate logistic regression analysis was performed. Patients with serum phosphorus levels measuring 5.0–5.9 mg/dL and > 6.0 mg/dL showed a higher risk of AS than those with serum phosphorus levels measuring < 4.0 mg/dL (odds ratio 2.24, p = 0.01 and odds ratio 2.66, p = 0.005, respectively). Aortic valve calcification was associated with age, long-term dialysis, diabetes mellitus, administration of vitamin D receptor activators, elevated serum calcium levels, and anemia (p < 0.05 for all).ConclusionsPatients on dialysis showed a high prevalence of AS, which was associated with age, long-term dialysis, and elevated serum phosphorus levels.Trial registrationUMIN000026756, registered on March 29, 2017.

Prior-Preconditioned Conjugate Gradient Method for Accelerated Gibbs Sampling in “Large n, Large p” Bayesian Sparse Regression

In a modern observational study based on healthcare databases, the number of observations and of predictors typically range in the order of 105–106 and of 104–105. Despite the large sample size, data rarely provide sufficient information to reliably estimate such a large number of parameters. Sparse regression techniques provide potential solutions, one notable approach being the Bayesian method based on shrinkage priors. In the “large n and large p” setting, however, the required posterior computation encounters a bottleneck at repeated sampling from a high-dimensional Gaussian distribution, whose precision matrix Φ is expensive to compute and factorize. In this article, we present a novel algorithm to speed up this bottleneck based on the following observation: We can cheaply generate a random vector b such that the solution to the linear system Φ β = b has the desired Gaussian distribution. We can then solve the linear system by the conjugate gradient (CG) algorithm through matrix-vector multiplications by Φ ; this involves no explicit factorization or calculation of Φ itself. Rapid convergence of CG in this context is guaranteed by the theory of prior-preconditioning we develop. We apply our algorithm to a clinically relevant large-scale observational study with n = 72 , 489 patients and p = 22 , 175 clinical covariates, designed to assess the relative risk of adverse events from two alternative blood anti-coagulants. Our algorithm demonstrates an order of magnitude speed-up in posterior inference, in our case cutting the computation time from two weeks to less than a day. Supplementary materials for this article are available online.

Genetic and observational evidence: No independent role for cholesterol efflux over static high-density lipoprotein concentration measures in coronary heart disease risk assessment.

BackgroundObservational findings for high‐density lipoprotein (HDL)‐mediated cholesterol efflux capacity (HDL‐CEC) and coronary heart disease (CHD) appear inconsistent, and knowledge of the genetic architecture of HDL‐CEC is limited.ObjectivesA large‐scale observational study on the associations of HDL‐CEC and other HDL‐related measures with CHD and the largest genome‐wide association study (GWAS) of HDL‐CEC.Participants/methodsSix independent cohorts were included with follow‐up data for 14,438 participants to investigate the associations of HDL‐related measures with incident CHD (1,570 events). The GWAS of HDL‐CEC was carried out in 20,372 participants.ResultsHDL‐CEC did not associate with CHD when adjusted for traditional risk factors and HDL cholesterol (HDL‐C). In contradiction, almost all HDL‐related concentration measures associated consistently with CHD after corresponding adjustments. There were no genetic loci associated with HDL‐CEC independent of HDL‐C and triglycerides.ConclusionHDL‐CEC is not unequivocally associated with CHD in contrast to HDL‐C, apolipoprotein A‐I, and most of the HDL subclass particle concentrations.