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In many different fields, social scientists desire to understand temporal variation associated with age, time period, and cohort membership. Among methods proposed to address the identification problem in age-period-cohort analysis, the intrinsic estimator (IE) is reputed to impose few assumptions and to yield good estimates of the independent effects of age, period, and cohort groups. This article assesses the validity and application scope of IE theoretically and illustrates its properties with simulations. It shows that IE implicitly assumes a constraint on the linear age, period, and cohort effects. This constraint not only depends on the number of age, period, and cohort categories but also has nontrivial implications for estimation. Because this assumption is extremely difficult, if not impossible, to verify in empirical research, IE cannot and should not be used to estimate age, period, and cohort effects.

Early-life severe respiratory syncytial virus (RSV) infection has been associated with the onset of childhood wheezing illnesses. However, the relationship between RSV infection during infancy and the development of childhood asthma is unclear. We aimed to assess the association between RSV infection during infancy and childhood asthma. INSPIRE is a large, population-based, birth cohort of healthy infants with non-low birthweight born at term between June and December, 2012, or between June and December, 2013. Infants were recruited from 11 paediatric practices across middle Tennessee, USA. We ascertained RSV infection status (no infection vs infection) in the first year of life using a combination of passive and active surveillance with viral identification through molecular and serological techniques. Children were then followed up prospectively for the primary outcome of 5-year current asthma, which we analysed in all participants who completed 5-year follow-up. Statistical models, which were done for children with available data, were adjusted for child's sex, race and ethnicity, any breastfeeding, day-care attendance during infancy, exposure to second-hand smoke in utero or during early infancy, and maternal asthma. Of 1946 eligible children who were enrolled in the study, 1741 (89%) had available data to assess RSV infection status in the first year of life. The proportion of children with RSV infection during infancy was 944 (54%; 95% CI 52–57) of 1741 children. The proportion of children with 5-year current asthma was lower among those without RSV infection during infancy (91 [16%] of 587) than those with RSV infection during infancy (139 [21%] of 670; p=0·016). Not being infected with RSV during infancy was associated with a 26% lower risk of 5-year current asthma than being infected with RSV during infancy (adjusted RR 0·74, 95% CI 0·58–0·94, p=0·014). The estimated proportion of 5-year current asthma cases that could be prevented by avoiding RSV infection during infancy was 15% (95% CI 2·2–26·8). Among healthy children born at term, not being infected with RSV in the first year of life was associated with a substantially reduced risk of developing childhood asthma. Our findings show an age-dependent association between RSV infection during infancy and childhood asthma. However, to definitively establish causality, the effect of interventions that prevent, delay, or decrease the severity of the initial RSV infection on childhood asthma will need to be studied. US National Institutes of Health.

INTRODUCTION About a quarter of patients with ulcerative colitis (UC) who undergo a total proctocolectomy with ileal pouch–anal anastomosis (IPAA) experience chronic pouchitis. Many such patients require frequent or long-term antibiotics hypothesized to target the microbiome. While advance therapies (AT) targeting the immune response are effective in some patients with chronic pouchitis, the impact of AT initiation on antibiotic dependence has not been robustly examined in this population. METHODS In this multicenter retrospective study, we identified adults with a diagnosis of UC who had undergone IPAA with endoscopic evidence of pouchitis either before or after AT initiation. Individuals with endoscopic findings concerning for Crohn’s-like-disease of the pouch (pre-pouch ileal inflammation or stricture, abscess, fistula, pouch stricture) or isolated cuffitis were excluded. The proportion of time on antibiotics prior to and after AT initiation was calculated over a follow-up of at least 1 year in the cohort of new AT initiators (incidence cohort). In an additional subset of prevalent AT users with chronic pouchitis, we examined frequency of antibiotic use over the first two years of follow-up. RESULTS We identified 58 individuals in the incident AT cohort and 22 individuals in the prevalent AT user cohort. Among the ATs, 38 were on TNF antagonists, 25 were on vedolizumab, and 19 were on ustekinumab. Over at least 1 year of follow-up, among those newly initiating AT, over half (59%) experienced a reduction in percentage of time on antibiotics, while 41% observed no change or higher usage (26%). The reduction group saw an absolute difference of 20% reduction in time on antibiotics. The reduction group also had a higher proportion on ustekinumab compared to the no reduction group (38% vs 8%, p = 0.014); there were no differences noted by other advanced therapies. This remained significant on multivariable analysis (aOR 8.4, p = 0.015). Other factors like history of primary sclerosing cholangitis, age at UC diagnosis or IPAA creation, and time from IPAA to initiation of AT did not predict reduction in antibiotic use after AT initiation, though male sex demonstrated a non-significant trend (aOR: 0.28, p = 0.081). DISCUSSION Almost half of patients who were started on AT for chronic pouchitis had a reduction in antibiotic use over the first 1-2 years of treatment. Disease-related parameters did not predict which patients may experience this reduction in use. Further prospective studies are needed to identify impact of AT on antibiotic use in chronic pouchitis, and to define which patients may benefit from immune-mediated versus microbiome-directed therapy.

Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. However, initial reports of ECMO use in patients with COVID-19 described very high mortality and there have been no large, international cohort studies of ECMO for COVID-19 reported to date. We used data from the Extracorporeal Life Support Organization (ELSO) Registry to characterise the epidemiology, hospital course, and outcomes of patients aged 16 years or older with confirmed COVID-19 who had ECMO support initiated between Jan 16 and May 1, 2020, at 213 hospitals in 36 countries. The primary outcome was in-hospital death in a time-to-event analysis assessed at 90 days after ECMO initiation. We applied a multivariable Cox model to examine whether patient and hospital factors were associated with in-hospital mortality. Data for 1035 patients with COVID-19 who received ECMO support were included in this study. Of these, 67 (6%) remained hospitalised, 311 (30%) were discharged home or to an acute rehabilitation centre, 101 (10%) were discharged to a long-term acute care centre or unspecified location, 176 (17%) were discharged to another hospital, and 380 (37%) died. The estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 37·4% (95% CI 34·4–40·4). Mortality was 39% (380 of 968) in patients with a final disposition of death or hospital discharge. The use of ECMO for circulatory support was independently associated with higher in-hospital mortality (hazard ratio 1·89, 95% CI 1·20–2·97). In the subset of patients with COVID-19 receiving respiratory (venovenous) ECMO and characterised as having acute respiratory distress syndrome, the estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 38·0% (95% CI 34·6–41·5). In patients with COVID-19 who received ECMO, both estimated mortality 90 days after ECMO and mortality in those with a final disposition of death or discharge were less than 40%. These data from 213 hospitals worldwide provide a generalisable estimate of ECMO mortality in the setting of COVID-19. None.

Background: We established a community-based cohort study to assess the long-term impact of the Great East Japan Earthquake on disaster victims and gene-environment interactions on the incidence of major diseases, such as cancer and cardiovascular diseases. Methods: We asked participants to join our cohort in the health check-up settings and assessment center based settings. Inclusion criteria were aged 20 years or over and living in Miyagi or Iwate Prefecture. We obtained information on lifestyle, effect of disaster, blood, and urine information (Type 1 survey), and some detailed measurements (Type 2 survey), such as carotid echography and calcaneal ultrasound bone mineral density. All participants agreed to measure genome information and to distribute their information widely. Results: As a result, 87,865 gave their informed consent to join our study. Participation rate at health check-up site was about 70%. The participants in the Type 1 survey were more likely to have psychological distress than those in the Type 2 survey, and women were more likely to have psychological distress than men. Additionally, coastal residents were more likely to have higher degrees of psychological distress than inland residents, regardless of sex. Conclusion: This cohort comprised a large sample size and it contains information on the natural disaster, genome information, and metabolome information. This cohort also had several detailed measurements. Using this cohort enabled us to clarify the long-term effect of the disaster and also to establish personalized prevention based on genome, metabolome, and other omics information.

Systemic inflammation markers have been linked to increased cancer risk and mortality in a number of studies. However, few studies have estimated pre-diagnostic associations of systemic inflammation markers and cancer risk. Such markers could serve as biomarkers of cancer risk and aid in earlier identification of the disease. This study estimated associations between pre-diagnostic systemic inflammation markers and cancer risk in the prospective UK Biobank cohort of approximately 440,000 participants recruited between 2006 and 2010. We assessed associations between four immune-related markers based on blood cell counts: systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-tolymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and risk for 17 cancer sites by estimating hazard ratios (HR) using flexible parametric survival models. We observed positive associations with risk for seven out of 17 cancers with SII, NLR, PLR, and negative associations with LMR. The strongest associations were observed for SII for colorectal and lung cancer risk, with associations increasing in magnitude for cases diagnosed within one year of recruitment. For instance, the HR for colorectal cancer per standard deviation increment in SII was estimated at 1.09 (95% CI 1.02–1.16) in blood drawn five years prior to diagnosis and 1.50 (95% CI 1.24–1.80) in blood drawn one month prior to diagnosis. We observed associations between systemic inflammation markers and risk for several cancers. The increase in risk the last year prior to diagnosis may reflect a systemic immune response to an already present, yet clinically undetected cancer. Blood cell ratios could serve as biomarkers of cancer incidence risk with potential for early identification of disease in the last year prior to clinical diagnosis.

Objectives: Previous studies assessing the outcomes of hip arthroscopy in patients with global acetabular overcoverage and focal superolateral acetabular overcoverage have been limited by short and intermediate-term follow-up periods and inconsistent radiographic criteria in defining these specific subpopulations of femoroacetabular impingement syndrome (FAIS) patients. The objective of this study is to evaluate the long-term postoperative outcomes for patients with FAIS in the setting of global acetabular overcoverage, lateral acetabular overcoverage, and normal acetabular coverage over a 10-year period. Methods: Patients undergoing hip arthroscopy for FAIS were enrolled in a prospective cohort study, and those with a minimum follow-up of 10 years were included in this analysis. The patients were categorized based on the type of acetabular coverage: global overcoverage (lateral center-edge angle [LCEA] >40° with coxa profunda), lateral overcoverage (LCEA >40° without coxa profunda), and no overcoverage (LCEA <40°). Functional outcomes, measured by the modified Harris Hip Score (MHHS) and Nonarthritic Hip Score (NAHS), as well as survivorship rates, including revision arthroscopy and conversion to total hip arthroplasty (THA), were compared across these groups. All statistical analyses were considered significant at P < 0.05. Results: A total of 162 patients were included in this analysis. The cohort had a mean age of 38.90 ± 12.61 years and a mean BMI of 24.86 ± 4.03, with an average follow-up duration of 11.63 ± 1.07 years. Among these patients, 73.5% (119/162) had no acetabular overcoverage, 17.3% (28/162) had lateral overcoverage, and 9.3% (15/162) had global overcoverage. Revision rates were 0% for the global overcoverage group, 7.7% for the lateral overcoverage group, and 5.3% for the no overcoverage group (P = 0.6786). THA rates were 0% for the global overcoverage group, 12% for the lateral overcoverage group, and 8.1% for the no overcoverage group (P = 0.5854). Functional outcome scores revealed significant differences among the groups, with the global overcoverage group exhibiting lower MHHS and NAHS scores compared to the other groups (MHHS: P = 0.0061, NAHS: P = 0.0057) (Table 1). Additionally, female sex (P = 0.04) and higher BMI (P < 0.0001) were associated with worse long-term hip function. Conclusions: At a minimum of 10 years postoperatively, there was no significant difference in the rate of reoperation or conversion to THA between patients with global acetabular overcoverage, lateral overcoverage, and no overcoverage. However, patients with global overcoverage demonstrated worse functional outcomes compared to those with lateral or no overcoverage. Appropriate acetabuloplasty remains critical in managing these patients, and global acetabular overcoverage may portend worse long term functional outcomes compared to other FAIS subtypes.

Objectives: The rate of recurrent shoulder instability following return to sport (RTS) after Bankart repair remains unsatisfactory. Criteria-based return to sport (CBRTS) protocols have been developed to determine if athletes are ready to return to their previous activity levels. However, there is a lack of evidence supporting passing thresholds for CBRTS protocols. This study aims to evaluate whether healthy volunteers can pass a previously published CBRTS protocol. Methods: This was a single-institution prospective single cohort study. Conducted in March 2024, this study included 26 volunteers with no history of upper extremity injury or surgery. Volunteers were assessed according to a published CBRTS protocol: (i) isometric testing of external rotation (ER) and internal rotation (IR) in the supine and prone position assessed by hand–held dynamometry; (ii) isokinetic strength testing of ER and IR assessed by isokinetic dynamometry; (iii) endurance testing of side lying ER, prone ER, and prone Y test; and (iv) functional testing via closed kinetic chain upper extremity (CKCUE) stability test and unilateral shot put test. A limb symmetry index (LSI) and proportion of volunteers that passed each test were calculated.  A passing LSI value was defined as LSI within 10% of the contralateral side, except for the shot put test, for which a passing value was defined as 80% ≤ LSI ≤ 110%. A passing score for the CKCUE stability test was ≥ 21. Results: The proportion of the 26 participants (average age 24.8 years (23-25); 14 males, 12 females) that passed isokinetic testing ranged from 30.8% to 57.7%. For isometric testing, passing ranged from 46.2% to 69.2%. For endurance testing, passing ranged from 19.2% to 30.8%.  50% of participants passed the CKCUE stability test, while 96.2% passed the unilateral shot put test. A non-dominant arm deficit was apparent in 10 of the 12 bilateral arm tests. Conclusions: A high percentage of healthy individuals are unable to pass post-Bankart repair CBRTS protocol tests. Clinicians should consider these findings when using CBRTS testing for athletes after Bankart repair. The benchmark LSI should be practical while still protecting against recurrent instability.

Objectives: Recent evidence has suggested that subcritical bone loss can result in a higher rate of recurrent instability as well as inferior outcomes following an arthroscopic soft tissue Bankart procedure.  Several options to manage subcritical bone loss exist including the addition of a Infraspinatus Remplissage or a bone transfer procedure.  The purpose of this study is to compare the outcomes between the arthroscopic Bankart repair plus Remplissage to an open Latarjet for the treatment of anterior shoulder instability in patients with glenoid bone loss from 13.5-20% in an active-duty military population. We hypothesize that there will be no difference in recurrence rate or patient reported outcomes between the two procedures.  Methods: A retrospective matched cohort comparison of patients who underwent anterior glenohumeral instability procedures with subcritical bone loss was performed. Inclusion criteria included symptomatic anterior shoulder instability, subcritical glenoid bone loss (13.5-20%), recurrent instability with at least two instability episodes, surgical treatment with arthroscopic Bankart repair plus Remplissage or open Latarjet, and minimum follow-up of 2 years. Outcomes assessed included recurrent instability (defined as postoperative dislocation or subjective subluxation), military physical restrictions, WOSI, and SANE scores. Results: Fifty patients were included, 25 of whom underwent an arthroscopic Bankart repair plus Remplissage and 25 patients treated with an open Latarjet. The average bone loss was 18.2% and 19.4%, respectively. Overall, five patients experienced recurrent instability, 3 in the arthroscopic Bankart group and 2 in the open Latarjet group.  The average post-operative SANE score for arthroscopic Bankart/Remplissage group was 86.1% and open Latarjet group was 84.2% (p<0.1). The average post-operative WOSI score for the arthroscopic Bankart plus Remplissage group was 66.2% and open Latarjet group was 67.5% (p=0.1).  There was no difference in the number patients placed on permanent physical restrictions in the arthroscopic Bankart plus Remplissage group (5) compared with open Latarjet (3) (p<0.1).  There were 4 complications other than recurrent instability in the Latarjet cohort compared to 0 in the arthroscopic Bankart plus Remplissage cohort (p=0.05). Conclusions: In patients with subcritical glenoid bone loss (defined as 13.5% to 24%), there was no difference in recurrent instability between an arthroscopic Bankart plus Remplissage compared to an open Latarjet.  Additionally, there was no difference in post-operative SANE or WOSI scores, complications, or the number of patients placed on permanent military restriction.

Objectives: To compare clinical and radiographic outcomes between patients undergoing glenoid reconstruction with frozen DTA and a matched cohort of patients with fresh DTA Methods: A retrospective review was performed of consecutive patients with a minimum of 5% anterior glenoid bone loss (GBL) associated with recurrent anterior shoulder instability who underwent stabilization with either open or arthroscopic DTA glenoid reconstruction and had a minimum of two-year follow up. Consecutive patients undergoing frozen DTA were matched in a 1-to-1 format to patients undergoing fresh DTA by age, body mass index and number of previous shoulder operations. Patients were evaluated postoperatively with the Western Ontario shoulder instability index (WOSI) score, pain relief, and for episodes of recurrent instability. All patients also underwent postoperative imaging evaluation with computed tomography (CT) in which graft incorporation and allograft angle were measured. Statistical analyses were performed using Mann-Whitney U tests and Chi-square tests, respectively, to compare continuous outcomes and categorical variables. Results: A total of 100 patients (50 fresh open DTA, 50 frozen arthroscopic DTA) with a median ± IQR age of 32.0 ± 6.7 and 27.9 ± 15.9 years respectively, were analyzed at minimum 2 years follow-up. There were significantly more males (98% vs 70%, p<0.01) in the fresh DTA group and also had significantly greater glenoid bone loss defects (25% ± 6% vs 21% ± 11, p<0.01). Patients in both groups experienced significant WOSI score improvement (p < 0.05) Both groups demonstrated similar clinical outcomes regarding improvement postoperatively (p=0.61), pain relief (p=0.09), and recurrence rates (p=0.31). There was only one case of recurrent instability among the groups in the open fresh DTA cohort. Analysis of CT data at an average of 15 months postoperatively showed no significant difference between fresh versus frozen DTA groups for average Graft-glenoid interface healing rate, allograft angle, and final anterior-posterior dimensions (graft + glenoid). Conclusions: Open fresh and arthroscopic frozen DTA for anatomic glenoid reconstruction in patients with recurrent anterior shoulder instability results in a clinically stable joint with comparable outcomes and solid allograft healing rates. Additional long-term studies are needed to determine if these results are maintained over time.