Age Strata Research Articles

Waning of Antibody Response Among Vaccinees who Received Two Doses of Covishield Vaccine.

There are limited data available on the long-term presence of SARS-CoV-2-specific binding antibodies and neutralizing antibodies in circulation among the elderly population. This study aims to examine levels of anti-SARS-CoV-2 antibodies in vaccines who have completed at least 6 months since the second vaccine dose. A cross-sectional study was conducted from November 2021 to January 2022 among 199 vaccines aged 60 years and above residing in Belagavi city, who received two doses of the Covishield vaccine. Antibody response to SARS-COV-2 virus whole cell antigen was measured by a kit COVID KAWACH IgG Micro LISA (J Mitra and Company, India) in 199 participants who had completed at least 6 months after receiving the second dose of Covishield vaccine. The antibody response was measured as a ratio of optical density (OD) in the participant's sample to the mean OD in negative control test by normal (T/N). Independent Kruskal-Wallis test was applied to test the difference between the T/N ratio by months of vaccination since the second dose and by the age group strata. The median T/N values among participants who completed 6, 7, 8, and 9 months since the second vaccine dose were 14.17, 10.46, 7.93, and 5.11, respectively, and this decline in T/N values was statistically significant. Antibody response values showed a decline with increasing age for participants in the age strata 60-69, 70-79, and 80 and above, respectively. A significant decline was observed in antibody response over 9 months supporting the administration of booster dose of vaccine.

Frailty is a stronger predictor of death in younger intensive care patients than in older patients: a prospective observational study

BackgroundWhile frailty is a known predictor of adverse outcomes in older patients, its effect in younger populations is unknown. This prospective observational study was conducted in a tertiary-level mixed ICU to assess the impact of frailty on long-term survival in intensive care patients of different ages.MethodsData on premorbid frailty (Clinical Frailty Score; CFS), severity of illness (the Simplified Acute Physiology Score, third version; SAPS3), limitations of care and outcome were collected in 817 adult ICU patients. Hazard ratios (HR) for death within 180 days after ICU admission were calculated. Unadjusted and adjusted analyses were used to evaluate the association of frailty with outcome in different age groups.ResultsPatients were classified into predefined age groups (18–49 years (n = 241), 50–64 (n = 188), 65–79 (n = 311) and 80 years or older (n = 77)). The proportion of frail (CFS ≥ 5) patients was 41% (n = 333) in the overall population and increased with each age strata (n = 46 (19%) vs. n = 67 (36%) vs. n = 174 (56%) vs. n = 46 (60%), P < 0.05). Frail patients had higher SAPS3, more treatment restrictions and higher ICU mortality. Frailty was associated with an increased risk of 180-day mortality in all age groups (HR 5.7 (95% CI 2.8–11.4), P < 0.05; 8.0 (4.0–16.2), P < 0.05; 4.1 (2.2–6.6), P < 0.05; 2.4 (1.1–5.0), P = 0.02). The effect remained significant after adjustment for SAPS3, comorbidity and limitations of treatment only in patients aged 50–64 (2.1 (1.1–3.1), P < 0.05).ConclusionsPremorbid frailty is common in ICU patients of all ages and was found in 55% of patients aged under 64 years. Frailty was independently associated with mortality only among middle-aged patients, where the risk of death was increased twofold. Our study supports the use of frailty assessment in identifying younger ICU patients at a higher risk of death.

Hierarchical Bayesian bootstrap for heterogeneous treatment effect estimation.

A major focus of causal inference is the estimation of heterogeneous average treatment effects (HTE) - average treatment effects within strata of another variable of interest such as levels of a biomarker, education, or age strata. Inference involves estimating a stratum-specific regression and integrating it over the distribution of confounders in that stratum - which itself must be estimated. Standard practice involves estimating these stratum-specific confounder distributions independently (e.g. via the empirical distribution or Rubin's Bayesian bootstrap), which becomes problematic for sparsely populated strata with few observed confounder vectors. In this paper, we develop a nonparametric hierarchical Bayesian bootstrap (HBB) prior over the stratum-specific confounder distributions for HTE estimation. The HBB partially pools the stratum-specific distributions, thereby allowing principled borrowing of confounder information across strata when sparsity is a concern. We show that posterior inference under the HBB can yield efficiency gains over standard marginalization approaches while avoiding strong parametric assumptions about the confounder distribution. We use our approach to estimate the adverse event risk of proton versus photon chemoradiotherapy across various cancer types.

Incidence and risk of herpes zoster in patients with ulcerative colitis and Crohn's disease in the USA.

Patients with inflammatory bowel disease (IBD) are at increased risk of herpes zoster (HZ). We evaluated the incidence of HZ in ulcerative colitis (UC) and Crohn's disease (CD) patients and compared this with HZ incidence in a non-IBD population. We conducted a retrospective cohort study (GSK study identifier: VEO-000043) of adults aged ≥18 years with UC and CD and without IBD who were identified from claims recorded in a US healthcare database between October 2015 and February 2020. Crude HZ incidence rates/1,000 person-years (PY) were calculated, and comparisons of HZ incidence rates between UC or CD and non-IBD cohorts were made using adjusted generalized linear models. The study population comprised a total of 29,928 UC, 25,959 CD, and 11,839,329 non-IBD patients. Crude overall HZ incidence rates were 13.64/1,000 PY (UC), 15.94/1,000 PY (CD), and 7.95/1,000 PY (non-IBD). UC and CD patients had increased HZ incidence rates, with adjusted incidence rate ratios of 1.35 (95% confidence interval [CI], 1.26-1.44) and 1.66 (95% CI, 1.56-1.77), respectively, compared with non-IBD patients. Stratified analysis indicated increased relative rates of HZ in progressively younger age strata in the UC and CD patients compared with non-IBD patients. HZ incidence rates were higher in UC and CD patients who had previously received thiopurines or methotrexate, TNF-inhibitors, or corticosteroids than in UC and CD patients who did not take those medicines. UC and CD patients had increased HZ incidence rates compared with patients without IBD, demonstrating the importance of HZ prevention in IBD patients.

New reference values for maximum respiratory pressures in healthy Brazilian children following guidelines recommendations: A regional study.

To determine reference values for maximum static respiratory pressures in healthy children from a Brazilian region, following recommendations of the European Respiratory Society (ERS) and the Brazilian Society of Pneumology and Tisiology (SBPT). A cross-sectional observational study was conducted with healthy children (6 to 11 years) of both sexes. The maximum inspiratory and expiratory pressures (PImax and PEmax, respectively) were measured using a digital manometer. Each child performed a minimum of three and a maximum of five maneuvers; three acceptable and reproducible maneuvers were considered for analysis. Minimum time for each maneuver was 1.5 seconds, with a one-second plateau, and one minute of rest between them. A stepwise multiple linear regression analysis was conducted for PImax and PEmax, considering correlations between independent variables: age, weight, and sex. We included 121 children (62 girls [51%]). Boys reached higher values for maximum respiratory pressures than girls. Respiratory pressures increased with age showing moderate effect sizes (PImax: f = 0.36; PEmax: f = 0.30) between the stratified age groups (6-7, 8-9, and 10-11 years). Age and sex were included in the PImax equation (PImax = 24.630 + 7.044 x age (years) + 13.161 x sex; R2 = 0.189). PEmax equations were built considering age for girls and weight for boys [PEmax (girls) = 55.623 + 4.698 x age (years) and PEmax (boys) = 82.617 + 0.612 x weight (kg); R2 = 0.068]. This study determined new reference equations for maximal respiratory pressures in healthy Brazilian children, following ERS and SBPT recommendations.

The associations of total testosterone with probable nonalcoholic steatohepatitis and nonalcoholic fatty liver disease fibrotic progression in men with type 2 diabetes: a cross-sectional study

BackgroundTestosterone has an impact on metabolic disorders and men with type 2 diabetes mellitus (T2DM) are predisposed to hypogonadism; meanwhile, patients with T2DM have higher risk of NAFLD. Therefore, we speculate that testosterone may affect the progression of NAFLD in T2DM patients and we aim to investigate whether total testosterone is associated with NAFLD progression in men with T2DM.MethodsA cross-sectional study. A total of 1782 male participants with T2DM were enrolled from seven communities in Shanghai. Probable nonalcoholic steatohepatitis (NASH) was defined by the concurrence of NAFLD and metabolic syndrome (MetS). NAFLD fibrosis score was used to identify patients with probable advanced fibrosis. Multinomial logistic regression and ordinal logistic regression was used to measure the association of total testosterone (independent variable) and the progression category of NAFLD (dependent variable).ResultsIn male, TT quartiles were negatively associated with probable NASH (Q1 vs. Q4 OR 2.07 95% CI 1.31–3.28, P for trend = 0.001) and inflammatory progression of NAFLD with OR of 1 SD increment of ln (TT) 0.81 (95% CI 0.72–0.92, P for trend < 0.001), but positively with fibrotic progression (Q1 vs. Q4 OR 0.45, 95% CI 0.29–0.72, P for trend = 0.001) with OR of 1 SD increment of ln (TT) 1.24 (95% CI 1.07–1.45). According to stratified analyses, for inflammatory progression, the interactions of age strata, duration of diabetes strata, and dyslipidemia status with 1 SD increment of ln (TT) were significant (P for interaction 0.007, 0.003, and 0.012, respectively); as for fibrotic progression, we found no interactions (all P for interaction ≥ 0.05).ConclusionsDifferent associations between TT and inflammatory and fibrotic progression of NAFLD in male were observed, suggesting different roles of TT in inflammatory and fibrotic stages of NAFLD.

Elderly Patients with Hepatocellular Carcinoma Benefit from Liver Transplantation as Much as Younger Ones

Introduction: The literature on liver transplantation (LT) for cirrhosis-associated hepatocellular carcinoma (cirr-HCC) in elderly patients (≥65 years of age) is scarce. The aim of this study was therefore to analyze the outcome after LT for cirr-HCC in elderly patients in our single-center experience. Methods: All consecutive patients who underwent LT for cirr-HCC at our center were identified from our prospectively collected LT database and stratified into an elderly (≥65 years) and a younger (<65 years) cohort. Perioperative mortality as well as Kaplan-Meier estimations of overall (OS) and recurrence-free survival (RFS) were compared between age strata. A subgroup analysis was performed for patients with HCC only inside Milan criteria. For further oncological comparison, outcome in the subgroup of elderly LT recipients with HCC inside Milan was also compared to a group of elderly patients undergoing liver resection for cirr-HCC inside Milan extracted from our institutional liver resection database. Results: Out of 369 consecutive patients with cirr-HCC who underwent LT between 1998 and 2022 at our center, we identified 97 elderly (with a subgroup of 14 septuagenarians) and 272 younger LT patients. 5- and 10-year OS in elderly compared to younger LT patients was 63% and 52% versus 63% and 46% (p = 0.67), respectively, while 5- and 10-year RFS was 58% and 49% versus 58% and 44% (p = 0.69). 5-/10-year OS and RFS in 50 elderly LT recipients with HCC inside Milan were 68%/55% and 62%/54%, respectively, which compared to 46%/38% (p = 0.07) and 26%/14% (p < 0.0001) in elderly patients after liver resection for cirr-HCC inside Milan. Conclusion: Our results in almost 100 elderly patients after LT for cirr-HCC show that older age per se should not be considered a contraindication to LT and that selected elderly patients older than 65 and even 70 years benefit from LT as much as younger ones.

RESILIENCE AND MULTIFACTORIAL STRESSORS AMONG OLDER ADULTS DURING THE COVID-19 PANDEMIC: A QUALITATIVE STUDY

Abstract The COVID-19 pandemic represents a complex stressor that is experienced differently across individuals and age strata. The present study explored perceptions and experiences of older adults within the domains of health, social interactions, finances and care of existing chronic medical conditions; and strategies used to cope with these stressors. We recruited 30 people (mean age 81.4 years) stratified by frailty status to complete semi-structured interviews about what changes to the above domains had occurred and what coping strategies were utilized. Using inductive and deductive coding techniques, thematic analysis revealed three overarching themes. The first was Pandemic Experience, which was perceived as stressful, especially in the domains of social isolation from friends and family and concern for others’ well-being. The second domain was Resilience where participants reported highly adaptable and creative ways to connect with others and viewed the pandemic from a lens of lifetime experience, which acted as a stress buffer. The third theme was Silver Linings where participants reported unexpected renewal like reconnecting with family and friends in more meaningful ways and reconnecting with nature. We found no meaningful distinction in experience by frailty status and explore reasons for this. Policy implications including internet access and training and societal aging biases are discussed in the context of aging and coping theories.

Comparison between the homologous BNT162b2 and the heterologous Gam-COVID-Vac/BNT162b2 vaccine regimen in republic of North Macedonia

The medical and socio-economic consequences that stemmed from the COVID-19 pandemic, forced the healthcare policymakers in Republic of North Macedonia to rely on five different vaccines against the SARS-CoV-2 virus, in order to reach a satisfactory level of herd immunity. It is here where we got the idea to compare the heterologous Gam-COVID-Vac/BNT162b2 regimen to the homologous BNT162b2 regimen, with our main focus being the immunogenicity differences between the two of them. Additionally, we researched the variation in humoral immune response relative to age strata; the reactogenicity differences; and discrepancies in SARS-CoV-2 infection incidence between the two regimens. To achieve this, antibody titers in sera samples from fifty-three (53) healthcare workers, divided in heterologous and homologous group, were analysed at six different time checkpoints. Our results showed robust immunogenic response after the administration of the booster dose (4. 2-fold increase in antibody titers), followed by a slower-waning humoral immune protection in the heterologous regimen, compared to the homologous BNT162b2 schedule, furthermore confirmed by non-inferiority testing (Geometric Mean Ratio=0,98) at the final checkpoint. That, coupled with the similar reactogenicity (p=0,767) of both regimens, imply that the Gam-COVID-Vac/BNT162b2 combination might be a feasible approach in the effort to contain the COVID-19 pandemic.

298 MPACT OF GUIDELINES-ORIENTED AGE CUT-OFF IN INTERMEDIATE TO LOWVRISK PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT WITH NEWEST GENERATION SELF-EXPANDING VALVES: A COMBINED ANALYSIS FROM NEOPRO AND NEOPRO-2 REGISTRIES

Abstract Introduction While randomized controlled trials have widely shown superiority or non-inferiority of transcatheter aortic valve replacement (TAVR) across the whole spectrum of surgical risks, 2021 ESC guidelines on valvular heart disease provide a class Ia indication for TAVR for patients at high surgical risk or, alternatively, aging &amp;gt;=75 years, irrespective of their surgical risk. Conversely, for patients aging &amp;lt;75 y and at low risk, surgical aortic valve replacement is recommended. Thus, in intermediate-low (IL) risk patients, the 75 y age cut-off is pivotal to guide the choice of intervention. The aim of the present study was to explore the impact on such cut-off on clinical outcomes in a real-world setting. Methods Consecutive IL surgical risk patients enrolled in the NEOPRO and NEOPRO-2 registries were included. A 1:1 propensity score matching (PSM) was used to match patients aged &amp;gt;= vs. &amp;lt;75 years old. The primary endpoint was the composite of all-cause death or cardiovascular hospitalizations. Results A total of 3642 patients undergoing TAVR with self-expanding transcatheter heart valves (THVs) from 2012 to 2021 were enrolled. After PSM, 484 patients (N=242 in both groups) were included in the final analysis. Mean age was 70.1±5.2 in patients aged &amp;lt;75 y and 81.56±4.18 in those aged &amp;gt;=75 y (p&amp;lt;0.001), while mean Society of Thoracic Surgeon (STS) score was 3.6±2.5%. Implanted THVs were Acurate Neo, Evolut Pro, Acurate Neo 2 and Evolut Pro+ in 199 (41.1%), 188 (38.8%), 73 (15.1%) and 24 (5%) patients respectively, with no between-groups differences. Rates of in-hospital complications were comparable across the two age categories. At 1-year follow-up, the cumulative incidence of all-cause death was 11% in patients aged &amp;gt;=75 y and 13% in those aged &amp;lt;75y (Log-Rank p=0.627); similarly, the composite of all-cause death or cardiovascular hospitalizations occurred in 14% vs. 16% of patients (Log-Rank p=0.554). Conclusions TAVI has comparable benefit across age strata in IL risk patients. The age cut-off suggested by current guidelines is not predictive of adverse events during hospital stay, neither of all-cause mortality through a mid-term follow-up. This opens the question to future studies focusing on lifetime management and not age cut-off.

Dietary Characteristics of Elders with Frailty and with Mild Cognitive Impairment: Cross-Sectional Findings and Implications from the Nutrition and Health Survey in Taiwan 2014-2017.

It is unclear whether low dietary intake accompanied with multiple nutrient deficiencies or specific nutrient inadequacy is associated with geriatric syndrome. This study aimed to examine the nutrition inadequacy profiles associated with frailty and cognitive impairment (CI). With information from the Nutrition and Health Survey in Taiwan, 2014-2017, sex-specific nutrient intakes and intake per kg of body weight (BW) were estimated from 24-hour recall data for two age groups (65-74 years; ≥75 years) regarding the three frailty and three CI subgroups. Total energy intakes were significantly lower with the severity of both frailty and CI in analysis combining both gender and age groups, and in both the 65-to-74-year-old women or the over-75-year-old women. These trends were observed but not significant in either of the two age groups in men. Significantly lower levels of energy intake have been observed when age, sex, and sampling strata were adjusted. Intake levels of multiple nutrients also decreased with the severity of frailty and CI. A greater number of nutrient inadequacies for the frail and the CI was found in the 65-to-74-year-old group than the over-75-year-old age group. However, most of the associations between micronutrients and the two geriatric syndromes disappeared after energy adjustment. The remaining few did not show consistency across age-sex subgroups. In conclusion, frailty or CI was associated with low amounts of food consumption accompanied by multiple nutrient insufficiencies. Dietary intervention to ensure adequate total energy and multiple nutrient intakes should be trialed in the geriatric population to address both the causal and efficacy issues.

Healthspan and chronic disease burden among young adult and middle-aged male former American-style professional football players

ObjectiveTo examine the relationships between age, healthspan and chronic illness among former professional American-style football (ASF) players.MethodsWe compared age-specific race-standardised and body mass index-standardised prevalence ratios of arthritis, dementia/Alzheimer’s disease,...

Outcomes with IV tenecteplase and IV alteplase for acute ischemic stroke with or without thrombectomy in real-world settings in the United States

Background and PurposeAlthough many stroke centers in United States are using intravenous (IV) tenecteplase (TNK) for acute ischemic stroke patients, there is paucity of comparative data between IV TNK and IV alteplase from real-world settings. Materials and MethodsWe analyzed the data from 122 healthcare facilities in Cerner Real World Data and included patients admitted between February 2016 to April 2022 to determine the effect of IV TNK (compared with IV alteplase) on occurrence of two outcomes in acute ischemic stroke patients stratified by use of thrombectomy: non-routine discharge or death, and intracranial hemorrhage after adjusting for potential confounders. ResultsAmong 30,643 acute ischemic stroke patients analyzed, 29,480 (96.2%) and 1,163 (3.8%) patients received IV alteplase and IV TNK, respectively. The proportion of patients who received thrombectomy was significantly higher among patients who received IV TNK compared with those who received IV alteplase (16.7% versus 11.0%, p<0.001). Occurrence of intracranial hemorrhage was more common among patients treated with IV TNK in acute ischemic stroke patients who did not receive thrombectomy (7.9% versus 5.1%, p<0.001) but not in those who received thrombectomy (20.1% versus 16.8%, p = 0.234). In the logistic regression analysis, patients treated with IV TNK who did not receive thrombectomy were at higher risk of intracranial hemorrhage (OR, 1.34, 95% CI 1.05-1.72, p = 0.02) after adjusting for age (age strata), gender, race/ethnicity, hypertension, diabetes mellitus, atrial fibrillation, hyperlipidemia, malignancy, nicotine dependence, previous ischemic stroke, previous transient ischemic attack, previous intracerebral hemorrhage, previous subarachnoid hemorrhage, previous acute myocardial infarction, atherosclerosis of aorta, previous AKI, congestive heart failure, peripheral vascular disease, and hospital type, aphasia, hemiplegia, neglect, somnolence, stupor and coma, dysphagia, and homonymous hemianopsia. There was no difference in the rate of non-routine discharge or death between patients treated with IV TNK and those treated with IV alteplase in the multivariate analyses. ConclusionsIn an analysis of real-world data, IV TNK was associated with higher rates of intracranial hemorrhage compared with IV alteplase in patients with acute ischemic stroke who did not undergo thrombectomy.

Mosaic Loss of Chromosome Y in Peripheral Blood Cells and Cognitive Status in the Amish

AbstractBackgroundMosaic loss of chromosome Y (mLOY) refers to acquired aneuploidy in a fraction of somatic cells. In aging men, has been suggested as a possible biomarker for increased risk of numerous diseases, including Alzheimer’s disease (AD). We investigated mLOY as a risk factor for AD in the Mid‐Western Amish, a founder population with homogeneous lifestyle, reducing the effect of confounding environmental factors.MethodThe median of the log R ratio (mLRRY) from SNP array data within the male‐specific region of chromosome Y was used to measure the degree of mLOY. A mLRRY value lower than the 99% confidence limit of the experimental distribution was scored to estimate the frequency of mLOY. The cognitive status was assigned via consensus review of cognitive examination results. Men in 3 age groups (65‐74, 75‐84, &gt;=85) were included. The linear mixed model with a polygenic component to account for relatedness and a transformation to address non‐normality was used to estimate familial correlations and heritability. A likelihood ratio test of association was performed with age at blood sampling and age of cognitive exam as covariates.ResultAfter extensive QC, 533 participants (mean age=75.42±6.17) were included and 39 (7.9%) had a detectable level of mLOY. mLOY frequency increased with age (p&lt;1.0x10‐6): 1.0% (65‐74; n=103), 8.4% (75‐84; n=334) and 14.3% (85+; n=96). Heritability of mLOY was 0.53 and the residual sibling correlation was 0.27 (n=201, p&lt;1.0x10‐2). A subset of 423 individuals were assigned to the cognitively impaired (n=134) or unimpaired (n=289) groups and mLOY was significantly higher in the cognitively impaired group (p&lt;0.0001). .ConclusionThe sibling correlation was significant for mLOY. We observed the same trend as reported in other European descent populations: mLOY increased with age and was more frequent in cognitively impaired individuals. The frequency of mLOY in Amish was lower than reported, overall and in each age stratum. Our results along with the lower prevalence of AD in Amish reinforces as a promising biomarker for the risk of AD.

Frequency of H.Pylori in Liver Cirrhosis Patients with Overt Hepatic Encephalopathy: A Cross-Sectional Study Design

Objective: The study aim is to evaluate the frequency of H. pylori in Liver cirrhosis patients with overt HE. Place and duration of study: This Study is conducted in the department of Pathology, Peshawar Institute of Medical Sciences (PIMS) Peshawar and The duration of study is from Ist April, 2022 till 30th September, 2022. Material and Method: Cross sectional study design having sample size of 140 individuals suffering from H.pylori infections also having a history of hepatic insufficiency.Non-probability sampling technique is used, Patients having age greater than 30 years of any sex but having an history of hepatic cirrhosis for the last 5-6 months, ultrasounds for overt Hepatic encephalopathy are included in this study design. Sample participants having different age strata, disease duration and child’s pugh classification are expressed in means and standard deviation with the help of SPSS. Results: Patients having helicobacter pylori infection in hepatic cirrohsis with overt hepatic encephalopathy are 44(31.4%) and 96 (68.4%) patients have not suffering from any simultaneous infection. There are 65(46.4%) males and 75(53.6% ) females, The mean duration of disease in our study is 4.89+ 1.5 years. Stratification with duration of disease in years in shown in table 1, having significant result with p-value of 0.000. Startified findings of CP is found to be insignificant with H.Pylori infection(p-value=0.500). Practical Implications: According to this study, H pylori infection should be promptly assessed in all patients with liver cirrhosis. The patients' chances of developing hepatic encephalopathy and bleeding chances as a result of the H pylori infection. It may be possible to lessen the severity of consequences such bleeding from esophageal varices, portal hypertensive gastropathy, and hepatic encephalopathy with the early identification and subsequent eradication of H pylori infection. Conclusion: The conclusive remarks of this study shows the prevalence of less frequency of Helicobacter pylori infections in Liver cirrhosis in the patients of Pakistan. But, among all of them Helicobacter Pylori causes prolongation in duration of liver cirrhosis. This study also highlights that as aged patients with liver cirrhosis having more cases of having helicobacter pylori infection. Keywords: Hepatic Encephalopathy, Child’s Pugh Classification,Helicobacter Pylori infection, Liver insufficiency

Inferring causal effects of homocysteine and B-vitamin concentrations on bone mineral density and fractures: Mendelian randomization analyses.

In the progress of bone metabolism, homocysteine (Hcy) and B vitamins play substantial roles. However, the causal associations of homocysteine, B-vitamin concentrations with bone mineral density (BMD), and fractures remain unclear. Therefore, we employed a two-sample Mendelian randomization (MR) design to infer the causal effects of Hcy and B vitamins on BMD and fractures. We selected instrumental variables from large genome-wide association studies (GWASs). Specifically, the exposures mainly included Hcy (sample size: 44,147), vitamin B12 (sample size: 45,576), folate (sample size: 37,465), and vitamin B6 (sample size: 1,864). The outcome variables included total body BMD (sample size: 66,628), heel BMD (sample size: 142,487), femoral neck BMD (sample size: 32,735), lumbar spine BMD (sample size: 28,498), and forearm BMD (sample size: 8143). Additionally, the total body BMD in several age strata was also included. Furthermore, the fractures of the forearm, femoral neck, lumbar spine, heel corresponding with the BMD regions, and femoral neck and lumbar spine BMD in men and women, separately, were added as additional outcomes. Two-sample MR approaches were utilized in this study. Inverse variance weighting (IVW) was adopted as the main analysis. MR-PRESSO, MR-Egger, the weighted median estimate, and multivariable MR were performed as sensitivity methods. In the main analysis, Hcy concentrations have an inverse association with heel BMD (Beta = 0.046, 95% confidence interval (CI) -0.073 to -0.019, P = 9.59E-04) per SD unit. In addition, for one SD increase of vitamin B12, the total body BMD decreased 0.083 unit (95%CI -0.126 to -0.040, P = 1.65E-04). The trend was more obvious in age over 45 years (Beta = -0.135, 95%CI -0.203-0.067, P = 9.86E-05 for age 45-60; Beta = -0.074, 95%CI -0.141 to -0.007, P = 0.031 for age over 60 years). No association of B vitamins and Hcy levels with the risk of fractures and femoral neck and lumbar spine BMD in men and women was found in this study. Other sensitivity MR methods elucidated consistent results. Our findings indicated that there exist the inversely causal effects of Hcy and vitamin B12 on BMD in certain body sites and age strata. These give novel clues for intervening bone-related diseases in public health and nutrition.

Young MSM changed temporal HIV-1 epidemic pattern in Heilongjiang Province, China.

Human immunodeficiency virus type 1 (HIV-1) epidemic in China is featured by geographical diversity of epidemic patterns. Understanding the characteristics of regional HIV-1 epidemic allows carrying out targeted prevention and controlling measures. This seven-year cross-sectional study was conducted in Heilongjiang, one province of Northeast China, where newly diagnosed infection is fast increasing yearly, but temporal HIV-1 epidemic trend is largely unknown. Information of 1,006 newly diagnosed HIV-1-infected participants were collected before antiretroviral therapy during 2010-2016 in Heilongjiang province. HIV-1 genotype was identified based on the viral gag and env gene sequences. Recent infection was determined by Limiting-Antigen Avidity assays. Comparison analyses on the median ages, CD4 counts, proportions of stratified age groups and CD4 count groups, and rates of recent HIV-1 infection among different population and sampling times were performed to understand temporal HIV-1 epidemic features. Homosexual contact among men who have sex with men (MSM) was the main transmission route and CRF01_AE was the most dominant HIV-1 genotype. During 2010-2016, the HIV-1 epidemic showed three new changes: the median age continued to decline, the cases with a CD4 count more than 500 cells/μl (CD4hi cases) disproportionally expanded, and the recent HIV-1 infection rate steadily increased. MSM cases determined the temporal trend of HIV-1 epidemic here. Increase of young MSM cases (aged <30 years) made the main contribution to the younger age trend of MSM cases. These young MSM exhibited a higher median CD4 count, a higher proportion of CD4hi cases, and a higher rate of recent HIV-1 infection than cases aged 30 years and more. MSM infected by CRF01_AE virus mostly affected HIV-1 epidemic patterns among MSM population. Young MSM have become a new hotspot and vulnerable group for HIV-1 transmission in Heilongjiang Province, Northeast China. The rapid increase in the number of young MSM cases, mainly those with CRF01_AE infection, changed temporal HIV-1 epidemic pattern here. Measures for prevention and control of HIV-1 infection among this population are urgently needed in the future.

Diagnosis Code and Health Care Utilization Patterns Associated With Diagnostic Uncertainty.

Diagnostic uncertainty is challenging to identify and study in clinical practice. This study compares differences in diagnosis code and health care utilization between a unique cohort of hospitalized children with uncertain diagnoses (UD) and matched controls. This case-control study was conducted at Cincinnati Children's Hospital Medical Center. Cases were defined as patients admitted to the pediatric hospital medicine service and having UDs during their hospitalization. Control patients were matched on age strata, biological sex, and time of year. Outcomes included type of diagnosis codes used (ie, disease- or nondisease-based) and change in code from admission to discharge. Differences in diagnosis codes were evaluated using conditional logistic regression. Health care utilization outcomes included hospital length of stay (LOS), hospital transfer, consulting service utilization, rapid response team activations, escalation to intensive care, and 30-day health care reutilization. Differences in health care utilization were assessed using bivariate statistics. Our final cohort included 240 UD cases and 911 matched controls. Compared with matched controls, UD cases were 8 times more likely to receive a nondisease-based diagnosis code (odds ratio [OR], 8.0; 95% confidence interval [CI], 5.7-11.2) and 2.5 times more likely to have a change in their primary International Classification of Disease, 10th revision, diagnosis code between admission and discharge (OR, 2.5; 95% CI, 1.9-3.4). UD cases had a longer average LOS and higher transfer rates to our main hospital campus, consulting service use, and 30-day readmission rates. Hospitalized children with UDs have meaningfully different patterns of diagnosis code use and increased health care utilization compared with matched controls.

Medical Cannabis Laws and Adolescent Alcohol Use Initiation.

The effects of medical cannabis laws (MCLs) on adolescent alcohol use remains unclear. Previous literature investigates alcohol consumption rather than alcohol initiation among adolescents, and does not examine the effect by sociodemographic characteristics and state-level dispensary status. We used population representative, state-level data to examine the relationship between MCLs and adolescent alcohol initiation. Data for this study were derived from the Youth Risk Behavior Survey (YRBS), a nationally representative, cross-sectional school-based survey administered by the Centers for Disease Control (CDC) in odd-numbered years from 1991 to 2015. We used a difference-in-difference model to assess pre and post effects of state MCL enactment on adolescent alcohol use initiation. Logistic regression analyses assessed associations between MCLs and varying ages of initiation. We further stratified our results by race/ethnicity, gender, and dispensary status. Results from adjusted logistic regression models showed higher odds of initiating alcohol among adolescents in states without MCLs when compared to adolescents in states with MCLs (OR 1.37, [95% CI = 1.29, 1.44]). This effect was consistent across age, race/ethnicity, and gender groups. Reductions in self-report of alcohol initiation were also consistently found in multiple age strata (9-10, 11-12, and 13-14), though this finding did not reach conventional levels of statistical detection in all race/ethnicities. Our findings support a substitutive effect, suggesting that adolescents in states with MCLs, as opposed to states without MCLs, may substitute cannabis for alcohol. Considering the evolving landscape of medical cannabis laws and the proliferation of state-level legalization laws, further research into the effects of such policies, such as adult-use cannabis laws, is warranted to further elucidate their effects on adolescent substance use.

Predicting visual outcomes after decompression of pituitary tumours based on stratified inner-retinal layer thickness and age.

The purpose of the study was to evaluate the potential role of stratified preoperative optical coherence tomography (OCT) measurements and age in predicting postoperative visual field (VF) improvement among adult patients with chiasmal compression due to pituitary tumours after decompression surgery. Postoperative visual outcomes were analysed using mean deviation of the VF test. Eyes were divided into three groups based on preoperative OCT parameters including peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness: groups 1, 2 and 3 with pRNFL thickness <65 μm, 65 μm or morebut <85 μm, and 85 μm or more, respectively. The GCIPL thickness was also divided into three groups based on values ranging from 55 to 77 μm. Each group was further categorized according to age: 20 years or older but younger than 40 years, 40 years or older but younger than 60, and 60 years or older. This study included 197 eyes of 197 patients with chiasmal compression due to pituitary tumours. No patient showed complete VF recovery in group 1 with a preoperative pRNFL thickness <65 μm or a GCIPL thickness <55 μm regardless of age. These groups showed the worst VF outcome (pRNFL, p = 0.0001; GCIPL, p < 0.0001). However, a significant recovery in VF (greater than 2dB) was observed in 45% of group 1 patients based on pRNFL thickness and in 61.54% of group 1 patients according to GCIPL thickness. In groups 2 and 3 with a preoperative pRNFL thickness of 65 μm or more and a GCIPL thickness of 55 μm or more, the rate of complete VF recovery decreased as subjects' ages increased. Group 3 with a preoperative pRNFL thicknessof 85 μm or more and a GCIPL thickness of 77 μm or more were 2.5-fold and 4.0-fold more likely to completely recover VF, respectively, compared with group 2. Stratified preoperative pRNFL and GCIPL thicknesses measured via OCT in different age categories are effective biomarkers for predicting visual functional outcomes.