Risk Of Multiple Adverse Outcomes Research Articles

Management of systemic lupus erythematosus: a systematic literature review informing the 2023 update of the EULAR recommendations

ObjectivesTo analyse the new evidence (2018–2022) for the management of systemic lupus erythematosus (SLE) to inform the 2023 update of the European League Against Rheumatism (EULAR) recommendations.MethodsSystematic literature reviews were...

Glycemic Variability as a Predictor of Graft Failure Following Infrainguinal Bypass for Peripheral Arterial Disease: A Retrospective Cohort Study

BackgroundGlycaemic variability (GV), measured as the change in visit-to-visit glycated haemoglobin (HbA1c), increases the risk of multiple adverse outcomes. However, the impact of GV on graft patency following infra-inguinal bypass (IIB) is unknown. A retrospective cohort study was undertaken to assess the impact of GV on graft patency. MethodA 3-year single centre retrospective case notes analysis of all people undergoing IIB between 2017-2019. Rutherford stage, graft conduit, level of bypass, procedure details, baseline demographics, co-morbidities, and GV were assessed. Time to re-intervention, ipsilateral amputation or death were recorded to determine primary patency (PP). Results106 IIB outcomes were analysed: mean (±SD) age 68.0(9.2) years; 69(65.1%) male, 37(33.9%), 75(70.8%) had DM; 46(43.4.%) underwent elective procedures.GV>9.1% was associated with significantly lower median PP than GV<9.1%, 198 [97-753.5] vs. 713 [166.5-1044.5] days (p = 0.045).On univariate analysis, GV >9.1% vs <9.1% was significantly associated with PP (HR 1.85 [CI 1.091-3.136], p = 0.022). Bypass level was also a univariate predictor, with below knee bypasses (HR 2.31 [CI 1.164-4.564], p = 0.017), and tibial (HR 2.00 [CI 1.022-3.090], p <0.043) having lower PP than above knee bypasses. On multivariate adjustment, GV >9.1% and level of bypass remained independent predictors of primary patency, HR 1.96 (95% CI:1.12-3.42, p=0.018) and HR 2.54 (95%CI:1.24-5.22, p=0.011) respectively. ConclusionsGV is an independent predictor of primary patency following infra-inguinal bypass, thus optimising GV should be a therapeutic target.

Association of combined healthy lifestyle with risk of adverse outcomes in patients with prediabetes.

Prediabetes and lifestyle factors have been associated with the risks of multiple adverse outcomes, but the effect of a healthy lifestyle on prediabetes-related complications remains unknown. We aimed to investigate whether the risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) among individuals with prediabetes can be offset by a broad combination of healthy lifestyle factors. This prospective study used data from the UK Biobank cohort. An overall lifestyle score ranging from 0 to 6 was created with 1 point for each of the 6 healthy lifestyle factors: no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, no overweight or obese, and adequate sleep duration. T2DM, CVD, and CKD were ascertained during a median follow-up of 14years. Cox proportional hazard regression models were used to estimate the associations. Sensitivity analyses were performed to test the robustness of the results. We included 202,993 participants without T2DM, CVD, and CKD at baseline (mean age 55.5years [SD 8.1]; 54.7% were women). Among these participants, 6,745, 16,961, and 6,260 participants eventually developed T2DM, CVD, and CKD, respectively. Compared with the participants with normoglycaemia, those with prediabetes showed a higher risk of these adverse outcomes. In addition, those prediabetic participants with a lifestyle score of 0-1 had a significantly higher risk of T2DM (hazard ratio [HR] 16.73, 95% CI 14.24, 19.65), CVD (HR 1.96, 95% CI 1.74, 2.21), and CKD (HR 1.92, 95% CI 1.58, 2.34) compared with those with no prediabetes and a score of 5-6. Moreover, among the participants with prediabetes, the HRs for T2DM, CVD, and CKD comparing a lifestyle score of 5-6 versus 0-1 decreased to 0.43 (95% CI 0.36, 0.51), 0.52 (95% CI 0.44, 0.62), and 0.60 (95% CI 0.46, 0.79), respectively. Combined healthy lifestyle factors were associated with a significantly lower risk of multiple adverse outcomes, including T2DM, CVD, and CKD. This indicates that prioritising multifactorial approaches to behavioural lifestyle modification is crucial for preventing and postponing the development of complications related to prediabetes.

Association between late gadolinium enhancement and outcome in dilated cardiomyopathy: A meta-analysis.

The prognostic value of late gadolinium enhancement (LGE) derived from cardiovascular magnetic resonance (CMR) is well studied, and several new metrics of LGE have emerged. However, some controversies remain; therefore, further discussion is needed, and more precise risk stratification should be explored. To investigate the associations between the positivity, extent, location, and pattern of LGE and multiple outcomes in dilated cardiomyopathy (DCM). PubMed, Ovid MEDLINE, and Cochrane Library were searched for studies that investigated the prognostic value of LGE in patients with DCM. Pooled hazard ratios (HRs) and 95% confidence intervals were calculated to assess the role of LGE in the risk stratification of DCM. Nineteen studies involving 7330 patients with DCM were included in this meta-analysis and covered a wide spectrum of DCM, with a mean left ventricular ejection fraction between 21% and 50%. The meta-analysis revealed that the presence of LGE was associated with an increased risk of multiple adverse outcomes (all-cause mortality, HR: 2.14; arrhythmic events, HR: 5.12; and composite endpoints, HR: 2.38; all P < 0.001). Furthermore, every 1% increment in the extent of LGE was associated with an increased risk of all-cause mortality. Analysis of a subgroup revealed that the prognostic value varied based on different location and pattern of LGE. Additionally, we found that LGE was a stronger predictor of arrhythmic events in patients with greater left ventricular ejection fraction. LGE by CMR in patients with DCM exhibited a substantial value in predicting adverse outcomes, and the extent, location, and pattern of LGE could provide additional information for risk stratification.

Streptococcus pneumoniae associated hemolytic uremic syndrome in children.

Previous small-scale, single-center investigations of Streptococcus pneumoniae associated hemolytic uremic syndrome (SpHUS) have shown increased disease severity among SpHUS relative to non-SpHUS patients. Our study compares the impact of S. pneumoniae on patient outcomes between SpHUS cases and non-SpHUS controls using the national, multicenter retrospective Pediatric Health Information Systems (PHIS) Database. Children <18 years of age with a diagnosis of HUS were included. Univariate analyses and multivariable linear and logistic regressions were utilized to assess the impact of S. pneumoniae on mortality, length of stay (LOS), intensive care unit admission (ICU), and mechanical ventilation use. Models were adjusted for demographic and clinical characteristics, including cardiac, neurologic, pulmonary, gastrointestinal, immunologic and renal clinical complications. Of 3,952 index HUS hospitalizations, 231 (5.8%) were due to SpHUS. SpHUS patients had worse outcomes, including longer hospital stays, increased rate of ICU admission, and increased use of mechanical ventilation (p < 0.001 for all). There was a strong positive relationship between clinical complications and adverse outcomes. After adjusting for covariates, SpHUS was associated with an increase in hospital LOS by 3.47 days (p = 0.009) and overall ICU-LOS by 4.21 days (p < 0.001). SpHUS was also associated with increased likelihood of mechanical ventilation (OR: 3.08; p < 0.001), with no increase in ICU admission (p = 0.070) and in-hospital mortality (p = 0.3874). Our study highlights that SpHUS patients are at increased risk of multiple adverse outcomes likely due to the summative impact of pneumococcal infection and HUS as well as more frequent clinical complications.

1 Applying a dimensional framework to the study of developmental neurotoxicity

Objective:In recent decades, a large body of evidence has linked prenatal exposure to environmental neurotoxins to adverse intellectual, neurodevelopmental, and psychiatric outcomes in offspring. This evidence has clearly highlighted the widespread impact of neurotoxin exposure on the developing brain; however, it is unclear how and why these exposures alter brain development in a way that appears to increase risk for multiple, seemingly disparate outcomes.Participants and Methods:Shifting our focus from describing links between neurotoxin exposure and symptoms of offspring mental/cognitive problems considered categorically, to investigating how neurotoxins adversely affect domains of functioning known to cut across risk for multiple problems in offspring may be critical to answering these questions. This presentation will discuss how combining research in developmental neurotoxicology with novel systems that take dimensional approaches to understanding emotions, cognition, and behaviour (i.e., the NIHM Research Domain Criteria (RDoC)) may provide a fruitful future research direction for the field. The RDoC framework aims to understand neuropsychological outcomes (i.e., mental health, mental illness, IQ) across major domains of human emotion, cognition, behaviour, and social functioning, rather than within distinct diagnostic categories.Results:Using lead exposure as an example, this presentation will outline a framework for how researchers can use this dimensional approach to develop more specific hypotheses that can reveal how and why neurotoxin exposure increases risk for multiple adverse outcomes and elucidate the mechanisms that may underly these links.Conclusions:Additionally, given that adverse development within domains of functioning can be detected prior to the onset of full-blown diagnoses, this research could enable us to develop more precise, targeted prevention and risk reduction campaigns. Adopting a dimensional framework will provide a more complete picture of the overall impact of prenatal exposure to neurotoxins - critical for informing public health policy.

Voluntary private health insurance and management of frailty in European Health Systems: a longitudinal analysis

Abstract Frailty is a major health concern associated with aging. It is a state of multisystem physiological decline and inability to maintain homeostasis, gradually leading to an increased risk of multiple adverse outcomes, such as falls, hospitalizations, and death. The prevalence of frailty in community-dwelling older Europeans (65 years and older) varies between 5.8% and 27.3%; in addition, between 34.6% and 50.9% are classified as ‘pre-frail’. In the face of the rapid population ageing occurring in Western societies, frailty is set to reach epidemic proportions over the next few decades. Although most European health care system offer essential treatment free of charge, voluntary private health insurances (VPHI) are becoming more common. Their coverage can be complementary or supplementary including access, faster treatment, waiting list avoidance, and out-of-pocket refund. A growing body of evidence is showing that there is erosion of the universal health coverage in European Health Systems and accessing VPHI might impact quality of care, especially for complex conditions i.e. Frailty. Using European data from the 2013 to 2011 we will assess trends of VPHI in individuals 65 years and older and whether accessing VPHI impacts frailty management and quality of life for elderly Europeans who are frail. These findings will help assessing quality of frailty management in European Health Systems and identify possible inequalities in accessing health services.

8.Q. Workshop: Covid-19 and pandemic measures: reducing or reproducing social and health inequities among migrants?

Abstract The Covid-19 pandemic has exacerbated preexisting social and health inequalities across communities, states and regions; and it has entailed major disruptions in human mobilities. There is evidence that the Covid-19 pandemic has thus had particularly severe and unique impacts on migrants, their families, and communities. However, as yet, little is known about the magnitude of Covid-19 related health inequalities among different migrant categories, and, moreover, about the structures and mechanisms - including pandemic measures - that have generated these inequalities. This workshop will provide an up-to-date overview of the available evidence on Covid-19 related health inequalities and on the effects of pandemic measures among different migrant categories worldwide. It will then “zoom in” on particular categories of marginalized migrants to critically examine the role of pandemic measures in mitigating or reproducing social and health inequalities. To this end, we will deliver three short presentations: The first presentation comprises a meta-analysis and synthesis of the empirical evidence on inequalities in Covid-19 related health risks and impacts of lockdown measures among migrants, refugees and internally displaced persons globally. The second presentation will render the results of a systematic review of the unintended consequences of pandemic measures on refugees accommodated in camp-like settings worldwide. The third presentation will address the occupational health and safety of migrant workers employed in food supply chain industries in Germany, the Netherlands, and the USA. Both the presented studies and the workshop itself benefit from bringing together academic researchers, representatives of governmental agencies (such as the German public health agency, Robert Koch Institute), and representatives of local and international non-governmental organizations (such as the International Organization of Migration). This team diversity allows us to draw on different perspectives, resources, kinds of knowledge, and skill sets, including scientific rigor and a practice-oriented approach aiming at informing public health policymaking. Our workshop will provide a consolidated, evidence-informed picture of social and health inequalities related to the Covid-19 pandemic and pandemic measures faced by migrant populations. On this basis, we will discuss with workshop participants what lessons can be learned for future emergency preparedness. For instance, what were shortcomings in the inclusion and accommodation of different migrant populations in the response to the Covid-19 pandemic? What were good practices? What are barriers and facilitators to migrants’ inclusion and equitable social and health protection during crises? What are evidence gaps and future directions for research, advocacy and policymaking? Key messages • The Covid-19 pandemic has exacerbated and intersected with preexisting structural disadvantages among migrants, putting them at higher risk for multiple adverse outcomes. • We present consolidated evidence to inform future pandemic preparedness toward migrant-sensitive public health policies and the context-specific consideration of migrants’ health and social needs.

Discordances Between Creatinine- and Cystatin C–Based Estimated GFR and Adverse Clinical Outcomes in Routine Clinical Practice

Cystatin C is recommended for measuring estimated glomerular filtration rate (eGFR) when estimates based on creatinine (eGFRcr) are not thought to be accurate enough for clinical decision making. While global adoption is slow, routine cystatin C testing in Sweden has been available for over a decade, providing real-world evidence about the magnitude of differences between eGFRcys and eGFRcr and their association with clinical outcomes. Observational study. 158,601 adults (48% women; mean age 62 years, eGFRcr 80, and eGFRcys 73mL/min/1.73/m2) undergoing testing for creatinine and cystatin C on the same day in connection with a health care encounter during 2010-2018 in Stockholm, Sweden. Percentage difference of eGFRcys minus eGFRcr (eGFRdiff). Kidney failure with replacement therapy (KFRT), acute kidney injury (AKI), atherosclerotic cardiovascular disease (ASCVD), heart failure, and death. Multivariable Cox proportional hazards regression. Discordances between eGFRcr and eGFRcys were common, with eGFRcys being lower than eGFRcr (negative eGFRdiff) in most cases (65%). Patients with larger negative eGFRdiff were older, more often female, with higher eGFRcr and albuminuria, and more comorbid conditions. Compared with patients with similar eGFRcys and eGFRcr, the lowest quartile (eGFRcys > 27% lower than eGFRcr) had the higher HR of all study outcomes: AKI, 2.6 (95% CI, 2.4-2.9); KFRT, 1.4 (95% CI, 1.2-1.6); ASCVD, 1.4 (95% CI, 1.3-1.5); heart failure, 2.0 (95% CI, 1.9-2.2); and all-cause death, 2.6 (95% CI, 2.5-2.7). Conversely, patients in the highest quartile (positive eGFRdiff) were at lower risk. Observational study, lack of information on indications for cystatin C testing. Cystatin C testing in routine care shows that many patients have a lower eGFRcys than eGFRcr, and these patients have a higher risk of multiple adverse outcomes. Clinicians require guidance when there are discrepancies between the estimated glomerular filtration rate based on creatinine (eGFRcr) and based on cystatin C (eGFRcys) in the same individual. Routine cystatin C testing in Sweden for over a decade permits exploration of how common and large these discrepancies are, and their associations with adverse clinical outcomes. In this observational study, we found that discordances between eGFRcys and eGFRcr are common, and 1 in 4 patients tested had an eGFRcys > 28% lower than their eGFRcr. We also show that an eGFRcys that is lower than the eGFRcr consistently identifies patients at higher risk of adverse outcomes, including cardiovascular events, kidney replacement therapy, acute kidney injury, and death.

0516 Biopsychosocial intervention using virtual multidisciplinary group with improved PAP adherence after 1 year post intervention

Abstract Introduction Prevalence of untreated sleep apnea among veterans is 22.2 %. Untreated patients are at risk for multiple adverse outcomes including chronic sleep deprivation, excessive day time sleepiness, chronic fatigue, depression, and cardiovascular complications including hypertension, coronary artery disease, cerebrovascular accidents, pulmonary hypertension as result of increased sympathetic activity during apnea episodes. Nonadherence to PAP therapy within the first week of treatment are up to 50 % of patients who use PAP device during the first week between 12-25 % discontinue by PAP use by year 3. Barriers to PAP use include physical problems with PAP hardware, knowledge gaps, and psychological issues. Methods Veterans from sleep medicine and sleep apnea clinics as well as multiple primary care clinics participated in the PAP adherence group following 6 weeks biopsychosocial model. The intervention included weekly synchronized video encounters of behavior sleep specialist, respiratory therapist and sleep clinic nurse with the targeted group of veterans with sleep apnea and poor PAP adherence. This approach has multiple benefits, including being patient centered, cost effective and efficient with ability to help veterans at various motivational levels, assist 6-10 veterans virtually in 6 one-hour group sessions and easy care coordination. Results A total of 21 veterans with sleep apnea participated in virtual multidisciplinary group to improve PAP adherence between September 2020 and January 2021. Patients PAP adherence before intervention, post intervention and 1year after intervention was evaluated. Percent of patients using PAP &amp;gt;2 hours before intervention was 5 %, immediately after intervention it increased to 20 %, and there was further increase up to 33% after 1 year post. Conclusion A structured multidisciplinary biopsychosocial intervention demonstrated statistically significant improvement in PAP adherence which persisted up till 1 year post intervention. In fact additional improvement of &amp;gt;2 hours of PAP usage was noted in this patient group suggesting possible long term benefit of psychosocial multidisciplinary intervention on PAP adherence. This study also demonstrated efficiency of utilization of virtual/telemedicine platform for psychosocial intervention and brief behavioral therapy. Support (if any)

O007 Glycaemic variability is a predictor of graft failure following infra-inguinal bypass for peripheral arterial disease (PAD). A retrospective cohort study

Abstract Introduction Many factors influence graft patency following infra-inguinal bypass (IIB). Glycaemic variability (GV) is associated with increased risk of multiple adverse outcomes. However, the impact of GV on outcomes following IIB is unknown. Methods A 3-year single centre retrospective case notes analysis of all people undergoing IIB between 2017–2019. Rutherford stage, graft conduit, bypass level, procedure details, baseline demographics, co-morbidities, mean HbA1c and GV (HbA1c SD) were assessed. Time to re-intervention, ipsilateral amputation or death were recorded to determine primary (PP). Results Were reported as hazard ratios (HR) following multivariate adjustment.193 IIB outcomes were analysed: mean (±SD) age 68.9(9.2) years; 135(69.9%) male. 156 (80.8%) had pre-operative HbA1c for analysis and 88(45.6%) had DM; 87(45.1%) were current smokers; 107(55.4%) underwent emergency procedures. Those without diabetes were more likely to smoke (P=0.011), but those with DM were more likely to have IHD (0.007), had higher Rutherford stage (p=0.0006), underwent more distal bypasses (p=0.004) and more emergency procedures (p=0.04). GV&amp;gt;9.1% was associated with significantly lower PP than GV&amp;lt;9.1%, 198 [105–377] vs. 713 [313-1287] days (p=0.02). Univariate predictors of PP included Rutherford stage 4 vs 3 (p=0.01), level of bypass, (p=0.0003), DM (p=0.04) and GV&amp;gt;9.1% (p=0.02). On multivariate adjustment, GV &amp;gt;9.1% and level of bypass remained independent predictors of primary patency, HR 1.96 (95% CI:1.12-3.42, p=0.018) and HR 2.54 (95%CI:1.24-5.22, p=0.038) respectively. Conclusion We have demonstrated GV and level of bypass as independent predictors of graft failure on multivariate analysis. Therefore, optimising GV should be a therapeutic target to improve outcomes.

Outcomes in patients with cardiometabolic disease who develop hyperkalemia while treated with a renin-angiotensin-aldosterone system inhibitor

Many patients with indications for renin-angiotensin-aldosterone system inhibitor (RAASi) therapy are not receiving these medications. Concern about hyperkalemia is thought to contribute to this lack of evidence-based therapy. A retrospective cohort study included adult patients in primary care practices affiliated with an integrated health care delivery system treated with RAASi between 2000 and 2019 for any of the following indications: (a) coronary artery disease (CAD); (b) heart failure (HF) with a left ventricle ejection fraction ≤ 40%; (c) diabetes mellitus (DM) with proteinuria; or (d) chronic kidney disease (CKD) with proteinuria. Relationship between hyperkalemia (K > 5.0 mEg/L) over the first 12 months of follow-up and a composite end point of cardiovascular events, renal dysfunction, and all-cause mortality was evaluated. Among 82,732 study patients, 7,727 (9.34%) developed hyperkalemia. Patients with hyperkalemia were older (69.0 vs 64.6) and more likely to have CAD (57.8 vs 53.7%), CKD (57.3 vs 51.1%), HF (19.3 vs 9.7%), and DM (45.3 vs 33.3%) (P < .001 for all). Five-year cumulative risk of the primary outcome was higher in patients who did (63.9%; 95% CI: 62.8%-65.1%) versus did not (37.2%; 95% CI: 36.8%-37.6%) develop hyperkalemia. Five-year cumulative risk of ED visit or hospitalization for hyperkalemia was 15.6% (14.7%-16.6%) for patients with versus 2.7% (95% CI: 2.6-2.9) for patients without hyperkalemia, rising to 25.9% (95% CI: 22.4-29.9) for patients with severe (K > 6.0 mEq/dL) hyperkalemia. Patients who experienced hyperkalemia were more likely (34.4%) than patients who did not (29.2%) to deintensify RAASi therapy (P < .001). Five-year cumulative risk of the primary outcome was higher in patients who lowered RAASi dose (50.4%; 95% CI: 48.5%-52.4%) or stopped RAASi therapy completely (49.3%; 95% CI: 48.5%-50.1%), compared to patients who continued RAASi therapy (36.1%; 95% CI: 25.7-36.5). Similar findings were observed in multivariable analyses and for individual components of the primary outcome. Hyperkalemia is a common complication of RAASi therapy and is associated with an increased risk of multiple adverse outcomes. Patients who have their RAASi medications deintensified after a hyperkalemic event have higher incidence of cardiovascular events, renal dysfunction and death.

How Do the Different Types of Maternal Diabetes during Pregnancy Influence Offspring Outcomes?

Background/Aim of the study: Exposure to maternal diabetes is considered one of the most common in utero insults that can result in an increased risk of complications later in life with a permanent effect on offspring health. In this study, we aim to assess the level of risk associated with each type of maternal diabetes on obesity, glucose intolerance, cardiovascular diseases (CVD), and neurodevelopmental disorders in offspring. Methods: We conducted a systematic review of the literature utilizing PubMed for studies published between January 2007 and March 2022. Our search included human cohorts and case control studies following offspring exposed at least to two different types of maternal diabetes clearly identified during pregnancy. Collected outcomes included prevalence, incidence, odds ratio, hazard ratio and risk ratio. Results: Among 3579 published studies, 19 cohorts were eligible for inclusion in our review. The risks for overweight, obesity, type 2 diabetes (T2D), glucose intolerance, metabolic syndrome, and CVD were increased for all types of maternal diabetes during pregnancy. The risk of overweight or obesity in infancy and in young adults was similar between gestational diabetes mellitus (GDM) and type 1 diabetes (T1D). The risk for T2D or abnormal glucose tolerance was double for offspring from GDM mothers compared to offspring from T1D mothers. In contrast, the risk for T1D in offspring at any age until young adulthood was increased when mothers had T1D compared to GDM and T2D. The risk for CVD was similar for all types of maternal diabetes, but more significant results were seen in the occurrence of heart failure and hypertension among offspring from T2D mothers. The risk of autism spectrum disorders and attention deficit/hyperactivity disorders was mainly increased after in utero exposure to preexisting T1D, followed by T2D. Conclusions: Offspring of diabetic mothers are at increased risk for multiple adverse outcomes with the highest risk detected among offspring from T2D mothers. Future work warrants large multiethnic prospective cohort studies that aim to identify the risks associated with each type of maternal diabetes separately.

Prospective Field Validation of the START:AV in a Dutch Secure Youth Care Sample.

The Short-Term Assessment of Risk and Treatability: Adolescent Version (START:AV) is a risk assessment instrument for adolescents that estimates the risk of multiple adverse outcomes. Prior research into its predictive validity is limited to a handful of studies conducted with the START:AV pilot version and often by the instrument's developers. The present study examines the START:AV's field validity in a secure youth care sample in the Netherlands. Using a prospective design, we investigated whether the total scores, lifetime history, and the final risk judgments of 106 START:AVs predicted inpatient incidents during a 4-month follow-up. Final risk judgments and lifetime history predicted multiple adverse outcomes, including physical aggression, institutional violations, substance use, self-injury, and victimization. The predictive validity of the total scores was significant only for physical aggression and institutional violations. Hence, the short-term predictive validity of the START:AV for inpatient incidents in a residential youth care setting was partially demonstrated and the START:AV final risk judgments can be used to guide treatment planning and decision-making regarding furlough or discharge in this setting.

Age- and Gender-Specific Prevalence of Frailty and Its Outcomes in the Longevous Population: The Chinese Longitudinal Healthy Longevity Study.

Background: Frailty is an epidemic age-related syndrome addressing heavy burden to the healthcare system. Subject to the rarity, age-, and gender-specific prevalence of frailty and its prognosis among the longevous population remains under-investigated.Methods: Based on the Chinese Longitudinal Healthy Longevity Study (CLHLS, 2008–2018), individuals aged ≥ 65 years having complete data of frailty were recruited. Modified Fried criteria (exhaustion, shrink, weakness, low mobility, and inactivity) were adopted to define pre-frailty (1–2 domains) and frailty (≥3 domains), respectively. The association between pre-frailty/frailty and adverse outcomes (frequent hospitalization, limited physical performance, cognitive decline, multimorbidity, and dependence) was analyzed using logistic regression models. The association between pre-frailty/frailty and mortality was analyzed using Cox proportional hazards models. Age- and gender-stratified analyses were performed.Results: Totally, 13,859 participants aged 85.8 ± 11.1 years, including 2,056 centenarians, were recruited. The overall prevalence of pre-frailty and frailty were 54.1 and 26.3%, respectively. Only 5.0% of centenarians were non-frailty whereas 59.9% of the young-old (65–79 years) showed pre-frailty. Both pre-frailty and frailty were associated with the increased risk of multiple adverse outcomes, such as incident limited physical performance, cognitive decline and dependence, respectively (P < 0.05). Frail males were more vulnerable to the risk of mortality (hazard ratio [HR] = 2.3, 95% confidence interval [CI], 2.1–2.6) compared with frail females (HR = 1.9, 95%CI, 1.7–2.1). The strongest association between frailty and mortality was observed among the young-old (HR = 3.6, 95%CI, 2.8–4.5). Exhaustion was the most common domain among patients with pre-frailty (74.8%) or frailty (83.2%), followed by shrink (32.3%) in pre-frailty and low mobility (83.0%) in frailty. Inactivity among females aged 65–79 years showed the strongest association with the risk of mortality (HR = 3.50, 95%CI, 2.52–4.87).Conclusion: A huge gap exists between longer life and healthy aging in China. According to the age- and gender-specific prevalence and prognosis of frailty, the strategy of frailty prevention and intervention should be further individualized.

Bacterial endotoxin-induced maternal inflammation leads to fetal intestinal injury and affects microbial colonization in the neonatal period

Background Intraamniotic infection is associated with an increased risk of multiple adverse outcomes in offspring, especially neonatal necrotizing enterocolitis (NEC), which is one of the serious gastrointestinal diseases in neonates. However, the underlying mechanism remains undefined. We hypothesize that bacterial endotoxin-induced maternal inflammation causes intestinal injury in offspring, thereby affecting the composition of the intestinal microbiome. Methods Pregnant Sprague Dawley rats were received intraperitoneal injections with 700 μg/kg lipopolysaccharide (LPS, which was the same as bacterial endotoxin) or saline at 15 days of gestation. Pups were allowed to deliver naturally and euthanized at days 0, 3 and 7 after birth. Intestinal tissue and feces samples from offspring were collected to evaluate the effects of maternal inflammation on intestinal flora colonization and intestinal mucosal development. Results Significant intestinal injury of the offspring induced by prenatal LPS exposure was observed on day 0 and 3 after birth. In addition, prenatal LPS exposure also induced significant changes in the intestinal microbiome of the offspring with a significant increase in Proteobacteria (Escherichia-Shigella) and a decrease in Firmicutes at 7 days after birth. Conclusions Thus, our findings suggest that LPS-induced maternal inflammation induces intestinal injury in offspring and subsequently leads to NEC-like changes in the composition of the intestinal microbiome.

Examining the Effects of Postmastectomy Radiation Therapy in Prepectoral Versus Subpectoral Autologous Breast Reconstruction.

Postmastectomy radiation therapy (PMRT) is known to increase the risk of multiple adverse outcomes after breast reconstruction. In the context of delayed-immediate autologous breast reconstruction, PMRT is typically conducted after placement of subpectoral (SP) tissue expanders. With the re-emergence of prepectoral (PP) reconstruction, there are little data assessing the outcomes of PP reconstruction in breasts receiving PMRT. We compared postoperative outcomes of PMRT patients undergoing delayed-immediate, autologous breast reconstruction with placement of tissue expanders in either the PP or SP plane. A retrospective chart review was conducted on all consecutive patients who underwent delayed-immediate autologous breast reconstruction and received PMRT at either the Stanford University or the Johns Hopkins University Hospitals between January 2009 and December 2018. Demographics, comorbidities, perioperative information, and oncologic data were collected for all patients. Complications were collected and analyzed after stage 1 surgery, between 30 days of stage 1 and up to stage 2 surgery, and after stage 2 surgery. Multivariable regressions were used to determine predictors of 1 or more complications. A total of 71 patients (73 breasts) were included. Prepectoral reconstruction comprised of 52.2% of the cohort, and the remaining 47.8% were SP reconstructions. Demographics and comorbidities were similar between groups, except for premastectomy radiation, which was more prevalent in the PP cohort (P = 0.010). Complications were similar between cohorts after stage 1 surgery (P = 0.420), between stages 1 and 2 (P = 0.100), and after stage 2 (P = 0.570). There were higher rates of skin necrosis in the SP cohort between stages 1 and 2 (PP: 2.6%, SP: 20%, P = 0.004). Multivariable analysis revealed body mass index to be the only predictor of complication (P = 0.041). The mean number of revisionary surgeries was higher in the SP cohort (PP: 0.8 vs SP: 1.9, P = 0.002). The mean follow-up was 385.5 days and similar between groups (P = 0.870). Rates of overall complication were similar between PP and SP expander placement. However, in SP reconstructions, skin necrosis was significantly higher between stages 1 and 2. The patients in the SP cohort also underwent a greater number of revisionary surgeries, although overall rates of pursuing any revisionary surgery were similar between groups.

Psychiatric disorders and risk for multiple adverse outcomes: a national prospective study.

Most psychiatric disorders, when examined individually, are associated with a broad range of adverse outcomes. However, psychiatric disorders often co-occur and their co-occurrence is well explained by a limited number of transdiagnostic factors. Yet it remains unclear whether the risk of these adverse outcomes is due to specific psychiatric disorders, specific dimensions of psychopathology (i.e., internalizing and externalizing dimensions), a general psychopathology factor or a combination of these explanations. In a large nationally representative prospective survey, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), we used structural equation modeling to examine the shared and specific effects of common Axis I and Axis II disorders on the risk of ten adverse outcomes (unemployment; financial crisis; low income; poorer general health; worse mental and physical health; legal problems; divorce; problems with a neighbor, friend or relative; and violence) in the general adult population. Effects of psychiatric disorders were exerted mostly through a general psychopathology factor representing the shared effect across all disorders, independent of sociodemographic characteristics and the presence of the adverse outcomes at baseline. Violence and legal problems were further associated with the externalizing factor, but there were no independent associations of the internalizing factor or any individual psychiatric disorders with any of the adverse outcomes. Our findings reveal that associations between psychiatric disorders and adverse outcomes occur through broad psychological dimensions. Understanding the biological and psychological mechanisms underlying these dimensions should yield key intervention targets to decrease the individual suffering and societal burden associated with common psychiatric disorders.

A cross-lagged panel analysis of children's sleep, attention, and mood in a prenatally stressed cohort: The QF2011 Queensland flood study

BackgroundIt is well recognized that childhood sleep, attention and mood problems increase risk for multiple adverse outcomes across the life-span; therefore, understanding factors, such as prenatal maternal stress, that underlie these types of childhood problems is critical for developing interventions that may optimize longer-term functioning. Our goal was to determine the association between disaster-related stress in pregnancy and young children's sleep, attention, and anxious/depressed symptoms. MethodsSoon after a major flood in Australia in 2011, we assessed various aspects of disaster-related prenatal maternal stress (PNMS) in women who had been pregnant at the time. Mothers rated several domains of their children's development with the Child Behavior Checklist (CBCL) at ages 2½ (n = 134) and 4 years (n = 118). ResultsThe primary finding was that more severe objective flood-related hardship in pregnancy predicted higher sleep problem scores at 2½ years, and that a negative maternal cognitive appraisal of the flood predicted lower attention problem scores at 2½ years. A cross-lagged panel analysis examined the association between children's sleep, attention, and anxious/depressed symptoms within and across ages. Results showed that these problems were likely to co-occur at each age, and that they were stable from 2½ to 4 years. Additionally, anxious/depressed scores at age 2½ predicted sleep problem scores at 4 years, all else being equal. LimitationsLimitations of the study include a relatively small sample size and the children's outcome data relied on maternal report using the CBCL, rather than independent observation of the children's functioning, which may have introduced reporter bias. ConclusionsThese findings highlight the importance of early intervention for these childhood problems to optimize long-term mental health, particularly under conditions of prenatal stress.

Impact of Chronic Medical Conditions on Academics of Children in the Child Welfare System

Objective: Children in the Child Welfare System (CWS) are at high risk for multiple adverse outcomes. Since involvement in CWS and having a chronic medical condition are both risk factors for poor academic achievement, a logical view is that the combination is additive, increasing the odds of poor performance. However, several factors may complicate such an association. This study explores negative and positive factors that could affect academic achievement in children in CWS with chronic medical conditions.Method: In a secondary data analysis of a nationally representative, longitudinal sample of children in CWS (N = 5,501), subjects were divided into three groups based on chronic medical condition: High Prevalence, Low Severity (HPLS; asthma, eczema, allergy, diabetes), Other (OTH; all other chronic conditions, including those with primary central nervous system involvement), and NONE (children with no chronic condition). Using weighted analyses, hierarchical logistic regression models addressed factors associated with academic achievement. Predictor variables included chronic condition group, sex, income level, case substantiation, home placement, and school engagement. Intelligence quotient was a covariate. Outcome variables were strong performances for reading and math, defined by standard score ≥85.Results: In TOTAL group, 80% had strong reading; more in HPLS (85%) vs. NONE (79%) and OTH (80%), adjusted F = 433, p < 0.001. In TOTAL group, 67% had strong math; more in NONE (68%) and HPLS (68%) vs. OTH (60%), adjusted F = 1,278, p < 0.001. Models predicting to strong reading and math achievement were significant, R2 = 0.51, p < 0.001 and R2 = 0.43, p < 0.001, respectively. HPLS had increased odds of strong reading achievement (aOR 1.3, 95% CI 1.3–1.4); both HPLS and OTH had lower odds of strong math achievement (aOR 0.87 and 0.76), p < 0.001, respectively. Male sex had lower odds of strong reading (aOR 0.44) and math achievement (aOR 0.62); positive school engagement had higher odds of strong reading (aOR 1.18) and math achievement (aOR 2.04), all p < 0.001.Conclusion: If true, our findings challenge the general belief that chronic illness can only be associated with negative outcomes and that cumulative adversities are simply additive in terms of risk. Increased contact with the medical system may provide an opportunity for improving reading achievement for children in CWS and promoting positive school engagement.