COVID-19 and long-term impact on symptoms and Health-Related Quality of Life in Costa Rica: the RESPIRA cohort study.

BACKGROUND: Evidence continues to accumulate regarding the potential long-term health consequences of COVID-19 in the population. To distinguish between COVID-19-related symptoms and health limitations from those caused by other conditions, it is essential to compare cases with community controls using prospective data ensuring case-control status. The RESPIRA study addresses this need by investigating the lasting impact of COVID-19 on Health-related Quality of Life (HRQoL) and symptomatology in a population-based cohort in Costa Rica, thereby providing a robust framework for controlling HRQoL and symptoms. METHODS: The study comprised 641 PCR-confirmed, unvaccinated cases of COVID-19 and 947 matched population-based controls. Infection was confirmed using antibody tests on enrollment serum samples and symptoms were monitored monthly for 6 months post-enrolment. Administered at the 6-month visit (occurring between 6- and 2-months post-diagnosis for cases and 6 months after enrollment for controls), HRQoL and Self-Perceived Health Change were assessed using the SF-36, while brain fog, using three items from the Mental Health Inventory (MHI). Regression models were utilized to analyze SF-36, MHI scores, and Self-Perceived Health Change, adjusted for case/control status, severity (mild case, moderate case, hospitalized) and additional independent variables. Sensitivity analyses confirmed the robustness of the findings. RESULTS: Cases showed significantly higher prevalences of joint pain, chest tightness, and skin manifestations, that stabilized at higher frequencies from the fourth month post-diagnosis onwards (2.0%, 1.2%, and 0.8% respectively) compared to controls (0.9%, 0.4%, 0.2% respectively). Cases also exhibited significantly lower HRQoL than controls across all dimensions in the fully adjusted model, with a 12.4 percentage-point difference [95%CI: 9.4-14.6], in self-reported health compared to one year prior. Cases reported 8.0% [95%CI: 4.2, 11.5] more physical limitations, 7.3% [95%CI: 3.5, 10.5] increased lack of vitality, and 6.0% [95%CI: 2.4, 9.0] more brain fog compared to controls with similar characteristics. Undiagnosed cases detected with antibody tests among controls had HRQoL comparable to antibody negative controls. Differences were more pronounced in individuals with moderate or severe disease and among women. CONCLUSIONS: PCR-confirmed unvaccinated cases experienced prolonged HRQoL reductions 6 months to 2 years after diagnosis, this was particularly the case in severe cases and among women. Mildly symptomatic cases showed no significant long-term sequelae.

Development and external validation of a machine learning model for the prediction of persistent acute kidney injury stage 3 in multi-centric, multi-national intensive care cohorts.

BACKGROUND: The aim of this retrospective cohort study was to develop and validate on multiple international datasets a real-time machine learning model able to accurately predict persistent acute kidney injury (AKI) in the intensive care unit (ICU). METHODS: We selected adult patients admitted to ICU classified as AKI stage 2 or 3 as defined by the "Kidney Disease: Improving Global Outcomes" criteria. The primary endpoint was the ability to predict AKI stage 3 lasting for at least 72 h while in the ICU. An explainable tree regressor was trained and calibrated on two tertiary, urban, academic, single-center databases and externally validated on two multi-centers databases. RESULTS: A total of 7759 ICU patients were enrolled for analysis. The incidence of persistent stage 3 AKI varied from 11 to 6% in the development and internal validation cohorts, respectively and 19% in external validation cohorts. The model achieved area under the receiver operating characteristic curve of 0.94 (95% CI 0.92-0.95) in the US external validation cohort and 0.85 (95% CI 0.83-0.88) in the Italian external validation cohort. CONCLUSIONS: A machine learning approach fed with the proper data pipeline can accurately predict onset of Persistent AKI Stage 3 during ICU patient stay in retrospective, multi-centric and international datasets. This model has the potential to improve management of AKI episodes in ICU if implemented in clinical practice.

Time-dependent association between the economic activity restriction due to health condition and mental illness: Finding from 15-year prospective cohort study

Background and Objectives The Economic Activity Restriction (EAR) due to health conditions is being utilized as a foundational measure for the European indicator Healthy Life Years (HLY). The EAR group is experiencing limitations not only in economic activities but also in overall activities, and it is a population with a high likelihood of transitioning to mental illness due to health condition. However, few studies have investigated the relationship between EAR and mental illness. Therefore, the purpose of this study was to identify the association between EAR due to health conditions and mental illness for those aged 45 and older in South Korea. Methods We obtained data from the 2006–2020 Korean Longitudinal Study of Aging. EAR was assessed using self-reported questionnaires based on the Global Activity Limitation Indicator. mental illness was assessed based on the diagnosis data for participants who had been diagnosed. After excluding missing values, the data of 9,574 participants were analyzed using the chi-square test, log-rank tests, and time-dependent Cox proportional hazard model to evaluate the association between EAR and mental illness. Results Out of the 9,574 participants gathered at baseline, the mental illness rate was 4.8 %. The hazard ratio (HR) of mental illness in those in the “very probable” of EAR was 2.351 times higher (p-value <0.0001) compared with “not at all” of EAR. In model 1 which includes under 64 years, HR of mental illness in “very probable” of EAR was 3.679 times higher (p-value: 0.000) and in “probable” of EAR was 2.535 time higher (p-value: 0.001) compared with “not at all” of EAR. Conclusion If we provide opportunities to participate in community activities or provide the mental health promotion programs for middle-aged population who are experiencing EAR due to health condition... (AU)

The Role of Biomarkers in Predicting Cognitive Impairment in Elderly Patients with Heart Failure.

OBJECTIVE: This study explores the impact of sST2, Growth Differentiation Factor 15 (GDF-15), and clinical factors on cognitive dysfunction in elderly patients with heart failure with reduced ejection fraction (HFrEF). METHODS: A cohort of 101 chronic stable HFrEF patients aged over 65 years old participated in the study. Cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) test and the Mini Mental State Examination (MMSE). Levels of sST2, GDF-15, and N-terminal pro b-type natriuretic peptide (NT-proBNP) were also measured. RESULTS: Notably higher levels of NT-proBNP and GDF-15 were observed in the group with cognitive dysfunction, whereas sST2 levels were similar between the groups. The cognitive dysfunction group consisted of older patients. A higher proportion of patients with normal cognitive function had received influenza vaccinations. Furthermore, GDF-15 levels inversely correlated with MMSE score. Right ventricular diameter was negatively correlated, while hemoglobin levels were positively correlated with both MoCA and MMSE scores. Logistic regression analysis identified increased GDF-15 levels, older age, and advanced New York Heart Association (NYHA) classes as predictors of higher cognitive dysfunction risk, whereas influenza vaccination was linked to a reduced risk of cognitive dysfunction. CONCLUSION: Cognitive dysfunction in elderly patients with heart failure may be influenced by factors such as age, right ventricular enlargement, anemia, NYHA functional class, and levels of GDF-15 and NT-proBNP.

Development and validation of a prognostic model for assessing long COVID risk following Omicron wave-a large population-based cohort study.

BACKGROUND: Long coronavirus disease (COVID) after COVID-19 infection is continuously threatening the health of people all over the world. Early prediction of the risk of Long COVID in hospitalized patients will help clinical management of COVID-19, but there is still no reliable and effective prediction model. METHODS: A total of 1905 hospitalized patients with COVID-19 infection were included in this study, and their Long COVID status was followed up 4-8 weeks after discharge. Univariable and multivariable logistic regression analysis were used to determine the risk factors for Long COVID. Patients were randomly divided into a training cohort (70%) and a validation cohort (30%), and factors for constructing the model were screened using Lasso regression in the training cohort. Visualize the Long COVID risk prediction model using nomogram. Evaluate the performance of the model in the training and validation cohort using the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: A total of 657 patients (34.5%) reported that they had symptoms of long COVID. The most common symptoms were fatigue or muscle weakness (16.8%), followed by sleep difficulties (11.1%) and cough (9.5%). The risk prediction nomogram of age, diabetes, chronic kidney disease, vaccination status, procalcitonin, leukocytes, lymphocytes, interleukin-6 and D-dimer were included for early identification of high-risk patients with Long COVID. AUCs of the model in the training cohort and validation cohort are 0.762 and 0.713, respectively, demonstrating relatively high discrimination of the model. The calibration curve further substantiated the proximity of the nomogram's predicted outcomes to the ideal curve, the consistency between the predicted outcomes and the actual outcomes, and the potential benefits for all patients as indicated by DCA. This observation was further validated in the validation cohort. CONCLUSIONS: We established a nomogram model to predict the long COVID risk of hospitalized patients with COVID-19, and proved its relatively good predictive performance. This model is helpful for the clinical management of long COVID.

Productivity loss by cancer stage in patients newly diagnosed with hepatocellular carcinoma: A claims database analysis.

BACKGROUND: New cancer diagnoses are associated with employment decrease, workplace absenteeism, and attributable costs to employers. OBJECTIVE: To estimate the workplace productivity loss in the year following a new diagnosis of early-, intermediate-, or advanced-stage hepatocellular carcinoma (HCC) in commercially insured US adults. METHODS: We conducted a retrospective cohort study using Merative MarketScan commercial claims to identify incident HCC diagnoses from 2010 to 2020. Patients were stratified into early-, intermediate-, or advanced-stage cohorts based on presence of secondary malignancy codes or first treatment received. Mean workdays lost and attributable cost in the year following a new diagnosis were calculated using the Kaplan-Meier sample averages to account for censoring. An exploratory analysis was conducted on subgroups in the early and advanced cohorts to assess productivity loss in patients with and without treatment. RESULTS: Mean workdays lost in the year following a new HCC diagnosis among the early, intermediate, and advanced cohorts was 22.6 days (95% CI = 16.0-29.8), 17.4 days (95% CI = 11.9-23.2), and 19.5 days (95% CI = 15.6-23.6), respectively. Corresponding indirect costs were $6,031(95% CI = $4,270-$7,953), $4,644 (95% CI = $3,176-$6,192), and $5,204 (95% CI = $4,163-$6,298). Early-stage patients without a liver transplant and advanced-stage patients who received systemic therapy had 19.7 (95% CI = 12.7-27.4) and 22.0 (95% CI = 16.6-27.7) mean workdays lost, respectively. CONCLUSIONS: Productivity loss varies by stage and appears to be higher in early-stage patients who receive more intensive treatments in the first year following a new HCC diagnosis.

Health care resource utilization and costs associated with psychiatric comorbidities in adult patients with attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous condition with extensive psychiatric comorbidities. ADHD has been associated with substantial clinical and economic burden; however, little is known about the incremental burden specifically attributable to psychiatric comorbidities of ADHD in adults. OBJECTIVE: To assess the impact of psychiatric comorbidities, specifically anxiety and depression, on health care resource utilization (HRU) and costs in treated adults with ADHD in the United States. METHODS: A retrospective case-cohort study was conducted. Adults with ADHD were identified in the IQVIA PharMetrics Plus database (10/01/2015-09/30/2021). The index date was defined as the date of initiation of a randomly selected ADHD treatment. The baseline period was defined as the 6 months prior to the index date, and the study period as the 12 months following the index date. Patients with at least 1 diagnosis for anxiety and/or depression during both the baseline and study periods were classified in the ADHD+anxiety/depression cohort, whereas those without diagnoses for anxiety or depression at any time were classified in the ADHD-only cohort. Entropy balancing was used to create reweighted cohorts with similar baseline characteristics. All-cause HRU and health care costs were assessed during the study period and compared between cohorts using regression analyses. Cost analyses were also conducted in subgroups stratified by comorbid conditions. RESULTS: After reweighting, patients in the ADHD-only cohort (N = 276,906) and ADHD+anxiety/depression cohort (N = 217,944) had similar characteristics (mean age 34.1 years; 54.8% male). All-cause HRU was higher in the ADHD+anxiety/depression cohort than the ADHD-only cohort (incidence rate ratios for inpatient admissions: 4.5, emergency department visits: 1.8, outpatient visits: 2.0, and psychotherapy visits: 6.4; all P < 0.01). All-cause health care costs were more than 2 times higher in the ADHD+anxiety/depression cohort than the ADHD-only cohort (mean per-patient per-year [PPPY] costs in ADHD-only vs ADHD+anxiety/depression cohort: $5,335 vs $11,315; P < 0.01). Among the ADHD+anxiety/depression cohort, average all-cause health care costs were $9,233, $10,651, and $15,610 PPPY among subgroup of patients with ADHD and only anxiety, only depression, and both anxiety and depression, respectively. CONCLUSIONS: Comorbid anxiety and depression is associated with additional HRU and costs burden in patients with ADHD. Comanagement of these conditions is important and has the potential to alleviate the burden experienced by patients and the health care system.

Incidence of tuberculous infection in a TB-endemic city.

Current metrics for TB transmission include TB notifications, disease mortality, and prevalence surveys. These metrics are helpful to national TB programs to assess the burden of disease, but they do not directly measure incident infection in the community.To estimate incidence of Mycobacterium tuberculosis infection in Kampala, Uganda, we performed a prospective cohort study between 2014 and 2017 which enrolled of 1,275 adult residents without signs of tuberculous infection (tuberculin skin test [TST] <5 mm and no signs of TB disease) and followed them for conversion of TST at 1 year.During follow-up, 194 participants converted the TST and 158 converted by one year. The incidence density of TST conversion was 13.2 conversions/100 person-year (95% CI 11.6-15.1), which corresponds to an annual cumulative incidence of tuberculous infection of 12.4% (95% CI 10.7-14.3). Cumulative incidence was greater among older participants and among men. Among participants who reported prior exposure to TB cases, the cumulative risk was highest among those reporting exposure during follow-up.The high annual incidence of infection suggests that residents of Kampala have adequate contact for infection with undetected, infectious cases of TB as they go about their daily lives..

Spinal catheter revision in pediatric intrathecal baclofen pumps: risk factors and postoperative outcomes.

OBJECTIVE: Intrathecal baclofen (ITB) pumps are commonly used in pediatric patients with cerebral palsy (CP) and medically refractory spasticity. However, catheter malfunction and associated risk factors are not well understood. The aim of this study was to examine potential risk factors for spinal catheter malfunction and characterize postoperative follow-up to understand the clinical consequences. METHODS: Patients who received ITB pump replacement or revision at Boston Children's Hospital between 2010 and 2023 were retrospectively reviewed. The spinal catheter revision cohort (SCRC) included patients whose spinal catheter was occluded requiring lumbar catheter revision. The second cohort included abdominal pump replacements only (APRC). Between-group comparisons and multivariable regression identified factors associated with catheter revision and postoperative outcomes. RESULTS: Forty-one (33.6%) patients underwent spinal catheter revision and were compared with 81 patients (66.4%) who underwent abdominal pump replacement only. Younger age at surgery and an elevated preoperative lower-extremity modified Ashworth scale grade were associated with spinal catheter revision (p < 0.05). Catheter model type, tip location, and history of spinal fusion were not associated with obstruction. Postoperatively, SCRC patients experienced a higher rate of infection (17.1%) relative to APRC patients (0%) within 30 days from their ITB pump replacement procedure (p < 0.05) and greater likelihood of subsequent ITB system removal compared with the APRC (24.4% vs 7.4%, p < 0.05). Although not differing preoperatively, SCRC patients had lower postoperative ITB doses when compared with the APRC group (median dose 143 vs 350 µg/day, p < 0.05) at hospital discharge and remained statistically different at the 6-month and 1-year follow-ups (p < 0.05). There were no postoperative differences in baclofen overdose, withdrawal, or median number of hospital readmissions within 30 days. Overall, 31.7% of spinal catheter revisions were unanticipated by the clinical team at time of surgery. CONCLUSIONS: Younger age at surgery and increased preoperative lower-extremity tone may be risk factors for catheter obstruction, resulting in a higher rate of postoperative infection and subsequent ITB pump removal compared with pump replacement alone. Spinal catheter occlusion can complicate revision or replacement procedures, especially when unanticipated. Routine clinical assessment may be inadequate for diagnosing insidious catheter malfunction. Catheter occlusion deserves further study, and routine assessment of catheter patency may be warranted to prevent suboptimal tone therapy.

The role of dementia in the association between APOE4 and all-cause mortality: pooled analyses of two population-based cohort studies.

BACKGROUND: The ε4 allele of the apolipoprotein E gene (APOE4) plays a role in neurodegeneration and in cardiovascular disease, but findings on its association with mortality are inconsistent. We aimed to examine the association between APOE4 and mortality, and the role of dementia in this association. METHODS: In this pooled analysis, data on White participants aged 45-90 years who underwent APOE genotyping were drawn from two population-based cohorts: the Whitehall II study (UK), which began in 1985 and is ongoing, and the Three-City study (France), initiated in 1999 and ended in 2012. In the Three-City study, vital status was ascertained through linkage to the national registry of death Institut National de la Statistique des Études économiques, and dementia was ascertained via a neuropsychological evaluation and validation of diagnoses by an independent committee of neurologists and geriatricians. In the Whitehall II study, vital status was ascertained through linkage to the UK national mortality register, and dementia cases were ascertained by linkage to three national registers. Participants with prevalent dementia at baseline and participants missing an APOE genotype were excluded from analyses. Cox regression proportional hazard models were used to examine the association of APOE4 with all-cause, cardiovascular, and cancer mortality. The role of dementia in the association between APOE4 status and mortality was examined by excluding participants who developed dementia during follow-up from the analyses. An illness-death model was then used to examine the role of incident dementia in these associations. FINDINGS: 14 091 participants (8492 from the Three-City study and 5599 from the Whitehall II study; 6668 [47%] of participants were women and 7423 [53%] were men), with a median follow-up of 15·4 years (IQR 10·6-21·2), were included in the analyses. Of these participants, APOE4 carriers (3264 [23%] of the cohort carried at least one ε4 allele) had a higher risk of all-cause mortality compared with non-carriers, with hazard ratios (HR) of 1·16 (95% CI 1·07-1·26) for heterozygotes and 1·59 (1·24-2·06) for homozygotes. Compared with APOE3 homozygotes, higher cardiovascular mortality was observed in APOE4 carriers, with a HR of 1·23 (1·01-1·50) for heterozygotes, and no association was found between APOE4 and cancer mortality. Excluding cases of incident dementia over the follow-up resulted in attenuated associations with mortality in homozygotes but not in heterozygotes. The illness-death model indicated that the higher mortality risk in APOE4 carriers was not solely attributable to dementia. INTERPRETATION: We found a robust association between APOE4 and all-cause and cardiovascular mortality but not cancer mortality. Dementia explained a significant proportion of the association with all-cause mortality for APOE4 homozygotes, while non-dementia factors, such as cardiovascular disease mortality, are likely to play a role in shaping mortality outcomes in APOE4 heterozygotes. FUNDING: National Institutes of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Subtrochanteric Femur Fractures: The Association Between Obesity and Perioperative, Clinical, and Radiographic Outcomes.

OBJECTIVES: To evaluate the association between obesity and treatment approaches, perioperative factors, and clinical and radiographic outcomes following subtrochanteric fracture fixation. DESIGN: Retrospective Cohort. SETTING: Academic Medical Center. PATIENT SELECTION CRITERIA: Patients operatively treated for an AO/OTA 32Axa, 32Bxa, or 32Cxa subtrochanteric femur fracture. OUTCOME MEASURES AND COMPARISONS: Injury characteristics, perioperative parameters, fixation information, postoperative complications, and clinical and radiographic outcomes. Univariate analyses were conducted between the obese (BMI ≥30 kg/m2) and the nonobese (BMI <30 kg/m2) cohorts. Regression analyses were performed to assess BMI as a continuous variable. RESULTS: Of 230 operatively treated subtrochanteric fracture patients identified, 49 (21%) were obese and 181 (79%) were nonobese. The average age of the obese cohort was 69.6 ± 17.2 years, with 16 (33%) male and 33 (77%) female. The average age of the nonobese cohort was 71.8 ± 19.2 years, with 60 (33%) male and 121 (77%) female. Aside from BMI, there were no significant differences in demographics between the obese and nonobese (age [P = 0.465], sex [P = 0.948], American Society of Anesthesiology Score [P = 0.739]). Both cohorts demonstrated similar injury characteristics including mechanism of injury, atypical fracture type, and AO/OTA fracture pattern (32A, 32B, 32C). Obese patients underwent more open reduction procedures (59% open obese, 11% open nonobese, P < 0.001), a finding further quantified by a 24% increased likelihood of open reduction for every 1 unit increase in BMI (OR: 1.2, 95% CI, 1.2-1.3, P < 0.001). There was no difference in average nail diameter, 1 versus 2-screw nail design, or number of locking screws placed. The obese cohort was operated more frequently on a fracture table (P < 0.001) when compared with the nonobese cohort that was operated more frequently on a flat table (P < 0.001). There were no significant differences (P > 0.050) in postoperative complications, mortality/readmission rates, hospital quality measures, fixation failure, or time to bone healing. CONCLUSIONS: The treatment of subtrochanteric fractures in obese patients is associated with a higher likelihood of surgeons opting for open fracture reduction and the use of different operating room table types, but no difference was observed in postoperative complications, mortality or readmission rates, or healing timeline when compared with nonobese patients. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Trends in the burden and determinants of HIV in the Asia-Pacific region (1990-2019): An age-period-cohort analysis of the 2019 Global Burden of Disease Study.

Although the burden of the human immunodeficiency virus (HIV) in the Asia-Pacific region is increasingly severe, comprehensive evidence of the burden of HIV is scarce. We aimed to report the burden of HIV in people aged 15-79 years from 1990 to 2019 using data from the Global Burden of Disease Study (GBD) 2019. We analyzed rates of age-standardized disability-adjusted life years (ASDR), age-standardized mortality (ASMR), and age-standardized incidence (ASIR) in our age-period-cohort analysis by sociodemographic index (SDI). According to HIV reports in 2019 from 29 countries in the Asia-Pacific region, the low SDI group in Papua New Guinea had the highest ASDR, ASMR, and ASIR. From 1990 to 2019, the ASDR, ASIR, and ASMR of persons with acquired immune deficiency syndrome (AIDS) increased in 21 (72%) of the 29 countries in the Asia-Pacific region. During the same period, the disability-adjusted life years (DALYs) of AIDS patients in the low SDI group in the region grew the fastest, particularly in Nepal. The incidence of HIV among individuals aged 20-30 years in the low-middle SDI group was higher than that of those in the other age groups. In 2019, unsafe sex was the main cause of HIV-related ASDR in the region's 29 countries, followed by drug use. The severity of the burden of HIV/AIDS in the Asia-Pacific region is increasing, especially among low SDI groups. Specific public health policies should be formulated based on the socioeconomic development level of each country to alleviate the burden of HIV/AIDS.

Nonoperative Versus Operative Treatment of Z-Type Comminuted Clavicle Fractures in Adolescents: A Prospective Substratified Cohort Analysis.

OBJECTIVES: To compare the clinical, radiographic, and patient-reported outcomes of nonoperative and operative treatment of adolescents with comminuted "Z-type" midshaft clavicle fractures. DESIGN: Prospective observational cohort. SETTING: Eight tertiary care pediatric centers. PATIENT SELECTION CRITERIA: Patients aged 10-18 years who were treated either operatively or nonoperatively for a diaphyseal clavicle fracture between 2013 and 2017 were screened/enrolled at the time of injury. The current subcohort analysis was derived from a larger adolescent clavicle study population of 907 patients. OUTCOME MEASUREMENTS AND COMPARISONS: Complications and validated patient-reported outcome measures (PROs):(ASES, QuickDASH, Marx Shoulder Activity Score, EQ-5D, EQ-VAS, and patient satisfaction score) were compared between operative and nonoperative cohorts. RESULTS: Eighty-one patients (69 male [85.2%], 12 female; average age 15 years [11.1-18.7]; 78 with sports participation [96.2%]) were followed through bony healing and return to sports, while 59 patients (73%) completed 2-year follow-up with PROs, 26 of whom were treated nonoperatively and 33 treated operatively. All demographic and fracture characteristics were similar (P > 0.05) between the 2-year follow-up cohorts except for fracture shortening, which was greater in the operative cohort (23 vs. 29 mm, P = 0.01). After controlling for this potential confounder through both regression and propensity matched subgroup analysis, nonoperative versus operative cohorts showed no difference in rates of nonunion (0%), delayed union (0% vs. 2.3%, P = 1.0), symptomatic malunion (2.7% vs. 0%, P = 0.4), refracture (2.7% vs. 2.2%, P = 1.0), unexpected subsequent surgery (5.4% vs. 11.4%, P = 0.45), or clinically significant complications (5.4% vs. 16%, P = 0.17). There were no differences in any PROs between cohorts, both before and after controlling for the difference in fracture shortening (all P-values >0.05). CONCLUSIONS: In this prospective comparison of complications and 2-year PROs in adolescents with comminuted Z-type clavicle fractures, nonoperative and operative treatment yielded similar outcomes. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Risk of Seizure Recurrence Due to Autoimmune Encephalitis With NMDAR, LGI1, CASPR2, and GABABR Antibodies: Implications for Return to Driving.

BACKGROUND AND OBJECTIVES: Patients with ongoing seizures are usually not allowed to drive. The prognosis for seizure freedom is favorable in patients with autoimmune encephalitis (AIE) with antibodies against NMDA receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and the gamma-aminobutyric-acid B receptor (GABABR). We hypothesized that after a seizure-free period of 3 months, patients with AIE have a seizure recurrence risk of <20% during the subsequent 12 months. This would render them eligible for noncommercial driving according to driving regulations in several countries. METHODS: This retrospective multicenter cohort study analyzed follow-up data from patients aged 15 years or older with seizures resulting from NMDAR-, LGI1-, CASPR2-, or GABABR-AIE, who had been seizure-free for ≥3 months. We used Kaplan-Meier (KM) estimates for the seizure recurrence risk at 12 months for each antibody group and tested for the effects of potential covariates with regression models. RESULTS: We included 383 patients with NMDAR-, 440 with LGI1-, 114 with CASPR2-, and 44 with GABABR-AIE from 14 international centers. After being seizure-free for 3 months after an initial seizure period, we calculated the probability of remaining seizure-free for another 12 months (KM estimate) as 0.89 (95% confidence interval [CI] 0.85-0.92) for NMDAR, 0.84 (CI 0.80-0.88) for LGI1, 0.82 (CI 0.75-0.90) for CASPR2, and 0.76 (CI 0.62-0.93) for GABABR. DISCUSSION: Taking a <20% recurrence risk within 12 months as sufficient, patients with NMDAR-AIE and LGI1-AIE could be considered eligible for noncommercial driving after having been seizure-free for 3 months.

Genome Sequencing for Diagnosing Rare Diseases.

BACKGROUND: Genetic variants that cause rare disorders may remain elusive even after expansive testing, such as exome sequencing. The diagnostic yield of genome sequencing, particularly after a negative evaluation, remains poorly defined. METHODS: We sequenced and analyzed the genomes of families with diverse phenotypes who were suspected to have a rare monogenic disease and for whom genetic testing had not revealed a diagnosis, as well as the genomes of a replication cohort at an independent clinical center. RESULTS: We sequenced the genomes of 822 families (744 in the initial cohort and 78 in the replication cohort) and made a molecular diagnosis in 218 of 744 families (29.3%). Of the 218 families, 61 (28.0%) - 8.2% of families in the initial cohort - had variants that required genome sequencing for identification, including coding variants, intronic variants, small structural variants, copy-neutral inversions, complex rearrangements, and tandem repeat expansions. Most families in which a molecular diagnosis was made after previous nondiagnostic exome sequencing (63.5%) had variants that could be detected by reanalysis of the exome-sequence data (53.4%) or by additional analytic methods, such as copy-number variant calling, to exome-sequence data (10.8%). We obtained similar results in the replication cohort: in 33% of the families in which a molecular diagnosis was made, or 8% of the cohort, genome sequencing was required, which showed the applicability of these findings to both research and clinical environments. CONCLUSIONS: The diagnostic yield of genome sequencing in a large, diverse research cohort and in a small clinical cohort of persons who had previously undergone genetic testing was approximately 8% and included several types of pathogenic variation that had not previously been detected by means of exome sequencing or other techniques. (Funded by the National Human Genome Research Institute and others.).

Waist-to-height ratio and body fat percentage as risk factors for ischemic cardiovascular disease: a prospective cohort study from UK Biobank.

BACKGROUND: The independent effect of waist-to-height ratio (WHtR) and body fat percentage (BF%) on ischemic cardiovascular disease (CVD) remains uncertain. OBJECTIVES: This study aimed to investigate the independent associations of WHtR and BF% with ischemic CVD. METHODS: This prospective cohort study used data from the UK Biobank. BF% was calculated as fat mass divided by body weight, measured by bioimpedance. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for overall and sex-specific associations of BF% and WHtR with risks of ischemic CVD and its main subtypes [myocardial infarction (MI) and ischemic stroke (IS)], adjusted for a range of potential confounders, including mutual adjustment for BF% and WHtR. RESULTS: In total, 468,333 participants without existing CVD were included in the analysis. During 12 y of follow-up, 20,151 ischemic CVD events, 13,604 MIs, and 6681 ISs were recorded. WHtR was linearly associated with ischemic CVD, MI, and IS, with an HR per 5% increase of 1.23 (95% CI: 1.20, 1.25), 1.24 (95% CI: 1.21, 1.27), and 1.22 (95% CI: 1.18, 1.26), respectively, independent of BF%. A stronger association between WHtR and MI was seen in females than in males. The association of BF% with these outcomes was substantially attenuated in both sexes after adjustment for WHtR. For example, in females, the HR (highest compared with lowest fifth) was reduced from 1.94 (95% CI: 1.76, 2.15) to 1.04 (95% CI: 0.90, 1.01) for ischemic CVD, from 2.04 (95% CI: 1.79, 2.32) to 0.97 (95% CI: 0.81, 1.16) for MI, and from 1.81 (95% CI: 1.54, 2.13) to 1.07 (95% CI: 0.85, 1.33) for IS. CONCLUSIONS: WHtR, when used as a proxy measure for central obesity, is linearly associated with ischemic CVD in both sexes, which is independent of BF%. In contrast, the relationship of BF% with these health outcomes is predominantly driven by its correlation with WHtR.

[Association between exposure to PM_(2.5) and chronic kidney disease in a population with metabolic syndrome].

OBJECTIVE: To investigate the association between long-term fine particulate matter(PM_(2.5)) exposure and the risk of chronic kidney disease(CKD) in people with abnormal metabolism syndrome(MS) components. METHODS: Based on health checkup data from a hospital in Beijing, a retrospective cohort study was used to collect annual checkup data from 2013-2019. A questionnaire was used to obtain information on demographic characteristics and lifestyle habits. We measured blood pressure, height, weight, waist circumference, concentrations of triglycerides(TG), fasting glucose, and high-density lipoprotein cholesterol(HDL-C). Longitude and latitude were also extracted from the addresses of the study subjects for pollutant exposure data estimation. Logistic regression models were used to explore the estimated effect of long-term PM_(2.5) exposure on the risk of CKD prevalence in people with abnormal MS components. Two-pollutant and multi-pollutant models were developed to test the stability of these result. Subgroup analysis was conducted based on age, the presence of MS, individual MS component abnormalities, and dual-component MS abnormalities. RESULTS: The study included 1540 study subjects with abnormal MS components at baseline, 206 with CKD during the study period. The association between long-term PM_(2.5) exposure and increased risk of CKD in people with abnormal MS fractions was statistically significant, with a 2.26-fold increase in risk of CKD for every 10 µg/m~3 increase in PM_(2.5) exposure(OR=3.26, 95% CI 2.72-3.90). The result in the dual-pollutant models and multi-pollutant models suggested that the association between long-term PM_(2.5) exposure and increased risk of CKD in people with abnormal MS fractions remained stable after controlling for contemporaneous confounding by other air pollutants. The result of subgroup analysis revealed that individuals aged 45 or older, without MS, with TG<1.7 mmol/L, HDL-C≥1.04 mmol/L, without hypertension, and with central obesity and high blood sugar had a stronger association between PM_(2.5) exposure and CKD-related health effects. CONCLUSION: Long-term exposure to PM_(2.5) may increase the risk of CKD in people with abnormal MS components. More attention should be paid to middle-aged and elderly people aged ≥45 years, people with central obesity and hyperglycemia.

[Effect of gestational weight gain on growth trajectory in children aged 0 to 3 years].

OBJECTIVE: To describe the growth trajectory of body mass index for age Z score(BAZ) in children aged 0 to 3 years and to explore the association between gestational weight gain and BAZ growth trajectory. METHODS: Based on a prospective cohort study, we recruited pregnant women in their early pregnancy into this study from 2013 to 2017 in Taicang of Jiangsu Province, tracked their weight changes until they gave birth, and calculated and evaluated their gestational weight gain(GWG) as appropriate, inadequate or excessive GWG based on Chinese GWG standard. Children's height/length and weight were measured at birth, 1, 3, 6, 8, 12, 18, 24, 30 and 36 months of age, and their BAZ scores were calculated. Group-based trajectory modeling(GBTM) was used for fitting BAZ trajectories. Multilevel Logistic regression was used to analyze the association between the level of GWG and BAZ growth trajectories. RESULTS: There were 1864 mother-child pairs in the study, and three groups of BAZ trajectories were fitted including slow growth trajectory(34.07%), appropriate growth trajectory(48.23%), and fast growth trajectory(17.70%). In univariate analysis, compared with children whose mothers had appropriate GWG, the children whose mothers had inadequate GWG were more likely in the group of slow growth trajectory(OR = 1.95, 95%CI 1.28-2.96), and the children whose mothers had excessive GWG were more likely in the group of fast growth trajectory(OR = 1.57, 95% CI 1.19-2.07). After adjusting for maternal pre-pregnancy body mass index(BMI) and parity, and the child's gender and birth weight, the children whose mothers gained in adequate GWG were more likely in the group of slow growth trajectory(OR = 1.84, 95%CI 1.19-2.84), while the association between excessive GWG and fast growth trajectory was not statistically significant(OR = 1.26, 95%CI 0.94-1.68). CONCLUSION: The BAZ trajectories of children aged 0-3 years can be categorized into slow, appropriate, and fast growth groups, and children's slow growth was associated with maternal inadequate GWG.

Hepatic steatosis, metabolic dysfunction and risk of mortality: findings from a multinational prospective cohort study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are implicated in the aetiology of non-communicable diseases. Our study aimed to evaluate associations between NAFLD and MetS with overall and cause-specific mortality. METHODS: We used dietary, lifestyle, anthropometric and metabolic biomarker data from a random subsample of 15,784 EPIC cohort participants. NAFLD was assessed using the fatty liver index (FLI) and MetS using the revised definition. Indices for metabolic dysfunction-associated fatty liver disease (MAFLD) were calculated. The individual associations of these indices with overall and cause-specific mortality were assessed using multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs). As a subobjective, risk associations with adaptations of new classifications of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic and alcohol-related liver disease (MetALD) were also assessed. RESULTS: Among the 15,784 sub-cohort participants, a total of 1997 deaths occurred (835 due to cancer, 520 to CVD, 642 to other causes) over a median 15.6 (IQR, 12.3-17.1) years of follow-up. Compared to an FLI < 30, FLI ≥ 60 was associated with increased risks of overall mortality (HR = 1.44, 95%CI = 1.27-1.63), and deaths from cancer (HR = 1.32, 95%CI = 1.09-1.60), CVD (HR = 2.06, 95% CI = 1.61-2.63) or other causes (HR = 1.21, 95%CI = 0.97-1.51). Mortality risk associations were also elevated for individuals with MAFLD compared to those without. Individuals with MetS were at increased risk of all mortality endpoints, except cancer-specific mortality. MASLD and MetALD were associated with higher risk of overall mortality. CONCLUSIONS: Our findings based on a prospective cohort suggest that individuals with hepatic steatosis or metabolic dysfunction have a higher overall and cause-specific mortality risk.

Acute anterior cruciate ligament rupture: can repair become an alternative to reconstruction: a meta-analysis of randomized controlled trials and cohort studies.

PURPOSE: To perform a meta-analysis to compare clinical outcomes of anterior cruciate ligament (ACL) repair and ACL reconstruction for acute ACL rupture. METHOD: We searched Pubmed, Embase, the Cochrane Library, and Web of Science databases to seek relevant studies. Clinical outcomes included failure rate, hardware removal rate, anteroposterior (AP) knee laxity, and patient-reported outcomes. In addition, subgroup analysis was carried out according to repair techniques, rupture locations, and study designs. Funnel plots were used to detect publication bias. All statistical analysis was performed using STATA (version 14.2, StataCorp). RESULTS: A total of 10 articles were included in this study, comprising 5 randomized controlled trials (RCTs) and 5 cohort studies, involving a total of 549 patients. We found no statistical differences between the ACL repair and ACL reconstruction in the following outcomes: failure rate, AP knee laxity, International Knee Documentation Committee (IKDC) score, Lysholm score, Knee Injury and Osteoarthritis Outcome (KOOS) Score, and Tegner score. However, the ACL repair group had a higher hardware removal rate. Except for AP knee laxity results on different repair techniques, there was no statistical difference in other subgroup analyses. CONCLUSION: Compared with ACL reconstruction, ACL repair shows similar results in clinical outcomes, and it is promising to be an effective alternative treatment for acute ACL rupture. Larger samples and higher-quality studies are needed to support our results and further explore the advantages of ACL repair in other aspects. LEVEL OF EVIDENCE: Level III.