Absolute Incidence Research Articles

Elevated lipoprotein(a) as a predictor for coronary events in older men

Elevated circulating lipoprotein (a) [Lp(a)] is associated with an increased risk of first and recurrent cardiovascular events; however, the effect of baseline Lp(a) levels on long-term outcomes in an elderly population is not well understood. The current single-center prospective study evaluated the association of Lp(a) levels with incident acute coronary syndrome to identify populations at risk of future events. Lp(a) concentration was assessed in 755 individuals (mean age of 71.9 years) within the community and followed for up to 8 years (median time to event, 4.5 years; interquartile range, 2.5–6.5 years). Participants with clinically relevant high levels of Lp(a) (>50 mg/dl) had an increased absolute incidence rate of ASC of 2.00 (95% CI, 1.0041) over 8 years (P = 0.04). Moreover, Kaplan-Meier cumulative event analyses demonstrated the risk of ASC increased when compared with patients with low (<30 mg/dl) and elevated (30–50 mg/dl) levels of Lp(a) over 8 years (Gray’s test; P = 0.16). Within analyses adjusted for age and BMI, the hazard ratio was 2.04 (95% CI, 1.0–4.2; P = 0.05) in the high versus low Lp(a) groups. Overall, this study adds support for recent guidelines recommending a one-time measurement of Lp(a) levels in cardiovascular risk assessment to identify subpopulations at risk and underscores the potential utility of this marker even among older individuals at a time when potent Lp(a)-lowering agents are undergoing evaluation for clinical use.

Comparison of simulated outcomes between stool- and blood-based colorectal cancer screening tests.

10529 Background: The Centers for Medicare &amp; Medicaid Services (CMS) recommends covering blood-based biomarker tests with proposed minimum performance thresholds for colorectal cancer (CRC) screening test every 3 years for average-risk, asymptomatic Medicare beneficiaries ages 50–85 years. A blood-based test is a non-invasive screening method to detect CRC but is limited by low sensitivity to detect adenomas. Using the CRC-AIM microsimulation model, predicted life-years gained (LYG) and CRC incidence and mortality reduction were compared between a blood-based test meeting the CMS minimum thresholds and stool-based screening tests (fecal immunochemical test [FIT], fecal occult blood test [FOBT], and multitarget stool DNA [mt-sDNA]). Methods: Outcomes of blood- and stool-based tests were simulated for average-risk individuals free of diagnosed CRC at age 40 and screened between ages 45–75 years per USPSTF recommendations. Per CMS proposed criteria, CRC sensitivity and specificity for a blood-based test were set at 74% and 90%, respectively, and adenoma sensitivity was set at 10%. Published adenoma and CRC sensitivity and specificity were used for each stool test. For the primary analysis, adherence was assumed to be 100%. For secondary analysis, adherence was set at 30–70%, in 10% increments. Outcomes were per 1000 individuals. Results: At 100% adherence, LYG was 229 for a blood test and ≥305 for stool tests, corresponding to at least 25% lower LYG for a blood test relative to all stool tests (Table). Absolute CRC incidence and mortality reductions were at least 19% and 18% lower, respectively, for a blood test vs all stool tests. Secondary analysis indicates that at identical adherence rates that are less than 100%, a blood test had lower LYG vs all stool tests (Table). When the adherence of any test was 50%–70%, a blood test resulted in at least 20% lower LYG vs any stool test, and absolute reductions in CRC incidence and mortality were at least 9% and 10% lower, respectively, vs any stool test. Conclusions: This model suggests that if blood-based CRC screening tests do not sufficiently detect advanced adenomas, clinical outcomes will be inferior to stool-based testing due to lack of cancer prevention. Further discovery efforts to identify blood-based markers associated with both invasive and preinvasive neoplasia are needed to address this deficiency. [Table: see text]

Sequential Intrathecal Injection of Hyperbaric and Isobaric Bupivacaine in Orthogeriatric Lower Limb Surgery, a Prospective Randomized Study.

The hemodynamic consequences of sympathetic blockade under spinal anesthesia remains a major concern especially in elderly frail patients. The baricity of the injected solution remains the principal factor controlling the diffusion of spinal anesthetics and the resulting sympathetic blockade. In this study, the sequential administration of isobaric and hyperbaric bupivacaine (HB) is evaluated regarding the incidence of hypotension during orthogeriatric surgery. Fifty elderly patients (age ＞ 60), scheduled for lower limb orthopedic surgery were randomly divided into two groups. In group HIB (n = 25), sequential injection of two syringes, 1.5 mL of 0.5% HB with 15 μ of fentanyl was injected, followed immediately by 1.5 mL of 0.5% isobaric bupivacaine, and in group HB (n = 25), 3 mL of 0.5% HB mixed with 15 μ of fentanyl citrate (0.3 mL of fentanyl 50 μg/mL) were used for spinal anesthesia. No statistical difference was found between the two groups regarding patient demographics, comorbidities, or preoperative laboratory data. The absolute incidence of hypotension (16% vs. 44%, P = 0.03) was statistically lower in the HIB group than the HB group. Also, the total number of hypotensive episodes and the need for vasopressor medications were statistically lower in the HIB group than the HB group (P = 0.02 vs. P = 0.01). Our results show a better hemodynamic profile of the sequentially injected mixture with a lower incidence of intraoperative hypotension and subsequent lower vasopressor requirements.

Persistent high-risk opioid use in lymphoma survivors following treatment.

6585 Background: Opioid analgesia has an important role in treating cancer pain but can place survivors at risk for long-term adverse effects, including misuse, abuse, and overdose. While opioid use has been studied in surgical oncology patients, little is known about long-term use and outcomes for patients with hematologic malignancies who primarily receive non-surgical treatment. We evaluated the association between opioid use during lymphoma treatment and persistent high-risk opioid use. Methods: We conducted a retrospective cohort study using IBM Watson Health MarketScan Commercial Claims and Encounters Data from 2000-2019, containing claims for employer-sponsored privately insured individuals in the US. We identified opioid-naïve adults age 18-64 years at their first diagnosis of Hodgkin (HL) or Non-Hodgkin lymphoma (NHL) who had outpatient cancer therapy lasting 90-240 days (including ≥3 episodes of outpatient chemotherapy). Using outpatient pharmacy claims, we categorized each patient’s opioid exposure during cancer treatment to no exposure, moderate [1-7 days supply], or high [ &gt; 7 days supply]. Follow-up began 60 days after patients’ final cancer treatment and continued up to 365 days or until an outcome or censoring event. High-risk opioid use was defined as ≥120 days cumulative supply, ≥3 consecutive months of opioid prescriptions, or a prescription with ≥90 morphine milligram equivalents per day. We used time-to-event methods to estimate cumulative incidence and hazard ratios across exposure groups. Results: There were 4380 opioid-naïve lymphoma patients in the cohort. 42.5% had HL and 57.5% had NHL. Median age at diagnosis was 46 years (IQR 32-56) and median treatment duration was 147 days (IQR 112-166). 55.0% of patients were male. During cancer treatment, 42.8% of patients had no opioid exposure, 28.1% had moderate, and 29.1% had high. Among the no-opioid-exposure group, the 1-year cumulative incidence of high-risk opioid use was 1.7%. Compared to this no-exposure group, the hazard ratios for moderate and high exposure were 2.6 (95% CI 1.5-4.6) and 9.0 (95% CI 5.6-14.4), respectively, after adjustment for cancer treatment duration, age, cancer type, and calendar time. A sensitivity analysis comparing patients diagnosed 2000-2009 vs. 2010-2019 found that hazard ratios remained consistent between the two time periods; however, there was a decrease in the absolute incidence of high-risk opioid use by approximately half. Conclusions: In this cohort study of opioid-naïve lymphoma patients, higher opioid exposure during cancer treatment was associated with a higher likelihood for persistent high-risk opioid use in the year following cancer treatment. The absolute incidence of high-risk opioid use decreased over time and may be due to increased awareness of the opioid epidemic. Close clinical follow-up in the post-treatment period may be warranted for patients at high risk of adverse outcomes.

Impact of the SARS-CoV-2 Pandemic on the Prevalence and Incidence of Gastrointestinal Viruses in Children up to Five Years Old: a Retrospective Cohort Study.

ABSTRACTThe aim is determining the impact of non-pharmaceutical measures (NPIs) against SARS-CoV-2 in the incidence and prevalence of gastrointestinal viruses (GV) in children. Demographic, analytical, and clinical data of children from which samples were received at the Hospital Universitario La Paz (Madrid, Spain) and that had a gastrointestinal infection with a positive sample through multiplex-PCR for GV were collected. The time periods included were prepandemic (P1): March 14, 2019 to March 14, 2020 and pandemic (P2): March 15, 2020 to March 15, 2021. The global prevalence, relative incidence (RI, per 1,000 admissions) and absolute incidence (AI, per 100,000 population) of GV were compared for both time periods. The prevalence of GV versus SARS-CoV-2 was determined for P2. Seven-hundred and 50 out of 2,547 children analyzed in P1 and 106 out of 1,368 in P2 were positive by PCR for GV (46.3% decrease in P2). Prevalence and RI of GV declined in P2, except for the RI of rotavirus. Adenovirus showed the largest decreased of prevalence and RI (100%), followed by sapovirus. Astrovirus reduction was less pronounced (3.1% versus 0.4%). Norovirus was the most frequent virus in both time periods and its prevalence and RI also decreased in P2 (15.2% versus 4.7% and 3.40 versus 1.74, respectively). Rotavirus had the smallest decrease in prevalence (2.6% versus 2.5%), and its RI increased during P2 from 0.7 to 0.93. After removing the rotavirus vaccine strains from the analysis, the prevalence and RI decreased during P2 (2.1% to 0.7% and 0.5 to 0.3, respectively). The AI decreased during P2 in all GV, and the prevalence of SARS-CoV-2 and GV was inversely proportional over time. Prevalence and incidence of GV have decreased during the pandemic, probably due to the implementation of NPIs against this virus and the reduction of health care attention to infections other than COVID-19. The differences in the decrease of prevalence and incidence for each virus may be explained by differences in the transmission and the resistance in the environment. Prevalence and RI of rotavirus might be biased since the PCR used detects both the infecting and the vaccine strains.IMPORTANCE Our original article contains an analysis of the impact of the measures applied against SARS-CoV-2 on the prevalence and incidence of GV in children. The small number of studies published to date that analyze the impact of these measures individually on each of the GV makes our study of great interest at this time.

Incidence rates of dilated cardiomyopathy in adult first-degree relatives versus matched controls.

BackgroundThe incidence rates and importance of traditional risk factors in dilated cardiomyopathy among first-degree relatives are unknown.Methods and ResultsWe identified all probands with dilated cardiomyopathy (n = 13,714, mean age at diagnosis 63 years) from the Danish nationwide registries between 1994 and 2017. Incidence rates among first-degree relatives (n = 29,671, mean age 38 years) and for up to 10 age- and sex-matched controls were calculated. Totally 233 (0.8%) first-degree relatives and 285 (0.1%) controls developed dilated cardiomyopathy during a median follow-up of 8.2 (Q1-Q3 4.4–13.3) years. Incidence rates (per 100,000 person-years) were 86.4 (95% confidence interval 73.9–101.0) and 111.1 (79.4–128.7) for first-degree relatives aged < 50 and ≥ 50 years, respectively, versus 7.5 (6.4–8.9) and 19.7 (16.8–23.2) for controls. Atrial fibrillation, diabetes, ischemic heart disease, and hypertension were associated with increased risks of developing dilated cardiomyopathy both in first-degree relatives and controls. Population attributable fractions for the 4 risk factors were 27.7% for first-degree relatives and 37.3% for controls aged < 50 years, and 46.4% versus 58.4% for first-degree relatives and controls among people aged ≥ 50 years, respectively.ConclusionsThe absolute incidence rates of dilated cardiomyopathy in first-degree relatives to patients with dilated cardiomyopathy were low, but significantly higher than in matched controls and elevated by the presence of additional risk factors, especially atrial fibrillation. Additional investigations are warranted to assess whether aggressive treatment of risk factors translates into a reduction of dilated cardiomyopathy in first-degree relatives.

Burden and Trends of Acute Viral Hepatitis in Asia from 1990 to 2019.

Asia has a very high burden of acute hepatitis; thus, a comprehensive study of the current burden and long-term trends of acute hepatitis in Asia is needed. We aimed to assess the current status and trends from 1990 to 2019 of acute hepatitis burden in Asia, using the data from the Global Burden of Diseases Study 2019 (GBD 2019) results. Methods: We used the data from the GBD 2019. Absolute death, incidence, and disability adjusted life years (DALY) number and rate of acute hepatitis in Asia were derived from the database from 1990 to 2019. Age-standardized mortality, incidence and DALY rates (ASMR, ASIR and ASDR) were used to compare populations in different regions and times. The estimated annual percentage change (EAPC) in the rates quantified the trends of the acute hepatitis burden. Results: From 1990 to 2019, the ASMR and ASDR of acute hepatitis decreased significantly at different paces, with the largest decrease in acute hepatitis C and the smallest in acute hepatitis E. The ASIR of acute hepatitis decreased relatively slowly, by an average of 0.06% (95% CI, 0.05–0.08%) per year in acute hepatitis A, 0.91% (0.64–1.18%) per year in acute hepatitis C and 0.26% (0.24–0.28%) per year in acute hepatitis E; while the ASIR of acute hepatitis B decreased by an average of 1.95% (1.08–2.11) per year. From 1990 to 2019, the incidence rate of acute hepatitis A increased in most age groups (from the age of 5 to 70), with the 50–55 years group having the fastest increase by an average of 1.81% (95% CI, 1.67–1.95%) per year. In 2019, Afghanistan had the highest ASMR (10.44 per 100,000) and ASDR (357.85 per 100,000) of acute hepatitis, and the highest ASIR was in Mongolia (4703.14 per 100,000). Conclusions: In Asia, the burden of acute viral hepatitis was at a relatively high level, compared with the other four continents. International cooperation and multifaceted and multisectoral actions are needed for Asian countries to eliminate viral hepatitis and to contribute to the global elimination of viral hepatitis.

2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

Analysis of OFDI Industry Linkage Network Based on Grey Incidence: Taking the Jiangsu Manufacturing Industry as an Example

Based on the outward direct investment data of each manufacturing industry segment in Jiangsu Province from 2000 to 2020, this paper establishes a correlation network by constructing a grey incidence model with the average value of absolute grey incidence as the threshold. We further analyze the relationship between each manufacturing industry segment in Jiangsu Province in the process of outward direct investment from two perspectives, namely, point and surface. The study shows that from the perspective of each node, the correlation coefficient between equipment manufacturing and other industries is significantly higher, i.e., the influence of equipment manufacturing on other industries is significantly greater. Chemical raw materials and chemical products manufacturing, general equipment manufacturing, special equipment manufacturing, and transportation equipment manufacturing are the important nodes in the network. From the perspective of the network as a whole, the Jiangsu manufacturing OFDI affiliation network is not concentrated. Still, it has small-world characteristics, which are conducive to disseminating information. In contrast, the close nature of the industry has more commonalities, leading to it being more easily divided into the same module in the network block model analysis.

Subsequent Primary Cancer Risk Among 5-Year Survivors of Adolescent and Young Adult Cancers.

A comprehensive examination of the incidence and mortality of subsequent primary cancers (SPCs) among adolescent and young adult (AYA) cancer survivors in the United States is lacking. Cancer incidence and mortality among 170404 cancer survivors of 5 or more years who were aged 15-39 years at first primary cancer diagnosis during 1975-2013 in 9 Surveillance, Epidemiology, and End Results registries were compared with those in the general population using standardized incidence ratio (SIR), absolute excess incidence (AEI), standardized mortality ratio (SMR), and absolute excess mortality (AEM). During a mean follow-up of 14.6 years, 13420 SPC cases and 5008 SPC deaths occurred among survivors (excluding the same site as index cancer), corresponding to 25% higher incidence (95% confidence interval [CI] = 1.23 to 1.27, AEI = 10.8 per 10 000) and 84% higher mortality (95% CI = 1.79 to 1.89, AEM = 9.2 per 10 000) than that in the general population. Overall, SPC risk was statistically significantly higher for 20 of 29 index cancers for incidence and 26 for mortality, with the highest SIR among female Hodgkin lymphoma survivors (SIR = 3.05, 95% CI = 2.88 to 3.24, AEI = 73.0 per 10 000) and the highest SMR among small intestine cancer survivors (SMR = 6.97, 95% CI = 4.80 to 9.79, AEM = 64.1 per 10 000). Type-specific SPC risks varied substantially by index cancers; however, SPCs of the female breast, lung, and colorectum combined constituted 36% of all SPC cases and 39% of all SPC deaths, with lung cancer alone representing 11% and 24% of all cases and deaths, respectively. AYA cancer survivors are almost twice as likely to die from a new primary cancer as the general population, highlighting the need for primary care clinicians to prioritize cancer prevention and targeted surveillance strategies in these individuals.

Safety of proprotein convertase subtilisin/kexin 9 inhibitors: a systematic review and meta-analysis

ObjectiveTo determine the harms of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in people who need lipid-lowering therapy.MethodsThis systematic review included randomised controlled trials that compared PCSK9 inhibitors with placebo, standard...

Sequential Intrathecal Injection of Hyperbaric and Isobaric Bupivacaine in Orthogeriatric Lower Limb Surgery, a Prospective Randomized Study.

The hemodynamic consequences of sympathetic blockade under spinal anesthesia remains a major concern especially in elderly frail patients. The baricity of the injected solution remains the principal factor controlling the diffusion of spinal anesthetics and the resulting sympathetic blockade. In this study, the sequential administration of isobaric and hyperbaric bupivacaine (HB) is evaluated regarding the incidence of hypotension during orthogeriatric surgery.Fifty elderly patients (age ＞ 60), scheduled for lower limb orthopedic surgery were randomly divided into two groups. In group HIB (n = 25), sequential injection of two syringes, 1.5 mL of 0.5% HB with 15 μ of fentanyl was injected, followed immediately by 1.5 mL of 0.5% isobaric bupivacaine, and in group HB (n = 25), 3 mL of 0.5% HB mixed with 15 μ of fentanyl citrate (0.3 mL of fentanyl 50 μg/mL) were used for spinal anesthesia.No statistical difference was found between the two groups regarding patient demographics, comorbidities, or preoperative laboratory data. The absolute incidence of hypotension (16% vs. 44%, P = 0.03) was statistically lower in the HIB group than the HB group. Also, the total number of hypotensive episodes and the need for vasopressor medications were statistically lower in the HIB group than the HB group (P = 0.02 vs. P = 0.01).Our results show a better hemodynamic profile of the sequentially injected mixture with a lower incidence of intraoperative hypotension and subsequent lower vasopressor requirements.

FC077: Cystatin C Testing Improves Risk Stratification Associated with Chronic Kidney Disease Without Adopting Age-Adapted Diagnostic Thresholds: A UK Biobank Study

Abstract BACKGROUND AND AIMS Age-adapted thresholds of estimated glomerular filtration rate (eGFR) have been proposed for the diagnosis of chronic kidney disease (CKD) [1] to acknowledge decline in kidney function with increasing age [2]. Proponents of age-adapted thresholds suggest that subjects over the age of 65 with eGFR 45–59 mL/min/1.73 m2 and without albuminuria appear to be at low risk of adverse outcomes [1]; however, the risks associated with CKD extend beyond kidney failure [3]. We evaluated whether cystatin C testing (eGFRcys) could improve risk stratification in CKD without adopting age-adapted thresholds. METHOD Data were from participants in the UK Biobank cohort with eGFR based on serum creatinine (eGFRcr) ≥45 mL/min/1.73 m2 and without albuminuria. Participants with a history of cardiovascular disease or kidney failure at baseline were excluded. CKD status was initially categorized by eGFRcr, then concordance of eGFRcys &amp;lt; 60 mL/min/1.73 m2 was determined. Multivariable-adjusted Cox proportional hazards models evaluated associations of CKD status with death, myocardial infarction (MI), stroke and kidney failure. Analyses were stratified by age: older (65–73 years) and younger (&amp;lt;65 years) participants. RESULTS Among 76 629 older and 351 773 younger participants, followed over median 11.5 (IQR 10.8–12.2) years, there were 24 251 deaths, 6983 MI, 4081 strokes and 209 kidney failure events. Of 2016 older participants with eGFRcr 45–59 mL/min/1.73 m2 37% had eGFRcys &amp;gt; 60 mL/min/1.73 m2. Furthermore, eGFRcr alone did not detect 6278 (8%) of older participants with eGFRcys &amp;lt; 60 mL/min/1.73 m2. In cross-sectional analyses, the median baseline eGFR was lower at higher age for all equations: this was most pronounced for eGFRcys (Figure 1). CKD by eGFRcys only or with both markers experienced higher absolute incidence of MI, stroke and mortality compared to those without CKD by either marker (Figure 2). Compared to those without CKD, older participants with concordant eGFRcr and eGFRcys &amp;lt; 60mL/min/1.73 m2 had elevated adjusted risks of death (HR 1.8, 1.6–2.0), MI (HR 1.9, 1.5–2.4), stroke (HR 1.7, 1.2–2.3) and kidney failure (HR 4.2, 1.2–14.1). Findings were similar in younger participants with concordant eGFRcr and eGFRcys &amp;lt; 60 mL/min/1.73 m2 for death (HR 2.2, 1.9–2.6) and stroke (HR 2.1, 1.4–3.2), though not MI (HR 1.2, 0.8–1.8). When CKD was not confirmed by eGFRcys, eGFRcr 45–59 mL/min/1.73 m2 was not associated with increased hazards of death (HR 1.1, 0.9–1.4), MI (HR 1.1, 0.7–1.7) or stroke (HR 1.1, 0.7–1.9) in older participants, nor in younger participants for the same outcomes: death (HR 1.1, 0.8–1.3), MI (HR 1.2, 0.8–1.9) and stroke (HR 0.8, 0.4–1.6). CONCLUSION Among persons with CKD, cardiovascular disease and mortality are important risks that should be considered when determining CKD status. CKD categorization by eGFRcr alone includes a large proportion of individuals who have similar risks to persons without CKD. eGFRcys detects a substantial number of high-risk individuals not identified to have CKD by eGFRcr. In the absence of cystatin C testing, lower, age-adapted thresholds for diagnosis of CKD may inadequately detect the broader risks associated with kidney disease in older people.

FC077: Cystatin C Testing Improves Risk Stratification Associated with Chronic Kidney Disease Without Adopting Age-Adapted Diagnostic Thresholds: A UK Biobank Study

Abstract BACKGROUND AND AIMS Age-adapted thresholds of estimated glomerular filtration rate (eGFR) have been proposed for the diagnosis of chronic kidney disease (CKD) [1] to acknowledge decline in kidney function with increasing age [2]. Proponents of age-adapted thresholds suggest that subjects over the age of 65 with eGFR 45–59 mL/min/1.73 m2 and without albuminuria appear to be at low risk of adverse outcomes [1]; however, the risks associated with CKD extend beyond kidney failure [3]. We evaluated whether cystatin C testing (eGFRcys) could improve risk stratification in CKD without adopting age-adapted thresholds. METHOD Data were from participants in the UK Biobank cohort with eGFR based on serum creatinine (eGFRcr) ≥45 mL/min/1.73 m2 and without albuminuria. Participants with a history of cardiovascular disease or kidney failure at baseline were excluded. CKD status was initially categorized by eGFRcr, then concordance of eGFRcys &amp;lt; 60 mL/min/1.73 m2 was determined. Multivariable-adjusted Cox proportional hazards models evaluated associations of CKD status with death, myocardial infarction (MI), stroke and kidney failure. Analyses were stratified by age: older (65–73 years) and younger (&amp;lt;65 years) participants. RESULTS Among 76 629 older and 351 773 younger participants, followed over median 11.5 (IQR 10.8–12.2) years, there were 24 251 deaths, 6983 MI, 4081 strokes and 209 kidney failure events. Of 2016 older participants with eGFRcr 45–59 mL/min/1.73 m2 37% had eGFRcys &amp;gt; 60 mL/min/1.73 m2. Furthermore, eGFRcr alone did not detect 6278 (8%) of older participants with eGFRcys &amp;lt; 60 mL/min/1.73 m2. In cross-sectional analyses, the median baseline eGFR was lower at higher age for all equations: this was most pronounced for eGFRcys (Figure 1). CKD by eGFRcys only or with both markers experienced higher absolute incidence of MI, stroke and mortality compared to those without CKD by either marker (Figure 2). Compared to those without CKD, older participants with concordant eGFRcr and eGFRcys &amp;lt; 60mL/min/1.73 m2 had elevated adjusted risks of death (HR 1.8, 1.6–2.0), MI (HR 1.9, 1.5–2.4), stroke (HR 1.7, 1.2–2.3) and kidney failure (HR 4.2, 1.2–14.1). Findings were similar in younger participants with concordant eGFRcr and eGFRcys &amp;lt; 60 mL/min/1.73 m2 for death (HR 2.2, 1.9–2.6) and stroke (HR 2.1, 1.4–3.2), though not MI (HR 1.2, 0.8–1.8). When CKD was not confirmed by eGFRcys, eGFRcr 45–59 mL/min/1.73 m2 was not associated with increased hazards of death (HR 1.1, 0.9–1.4), MI (HR 1.1, 0.7–1.7) or stroke (HR 1.1, 0.7–1.9) in older participants, nor in younger participants for the same outcomes: death (HR 1.1, 0.8–1.3), MI (HR 1.2, 0.8–1.9) and stroke (HR 0.8, 0.4–1.6). CONCLUSION Among persons with CKD, cardiovascular disease and mortality are important risks that should be considered when determining CKD status. CKD categorization by eGFRcr alone includes a large proportion of individuals who have similar risks to persons without CKD. eGFRcys detects a substantial number of high-risk individuals not identified to have CKD by eGFRcr. In the absence of cystatin C testing, lower, age-adapted thresholds for diagnosis of CKD may inadequately detect the broader risks associated with kidney disease in older people.

Molecular subtyping reveals uniqueness of prognosis in breast ductal carcinoma in situ patients with lumpectomy

BackgroundWe aimed to analyse the discrepancy in clinical features and prognosis between molecular subtypes in primary ductal carcinoma in situ (DCIS) patients with lumpectomy. MethodsPrimary DCIS patients were identified from the Surveillance, Epidemiology, and End Results registries database from 2010 to 2017. Based on immunohistochemistry markers of hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2), enrolled DCIS cases were divided into four molecular subtypes, HR-HER2-, HR-HER2+, HR + HER2+, and HR + HER2-. Clinical features and prognosis were compared between molecular subtypes. Radiotherapy (RT) effects on prognosis were also analysed in each molecular subtype. ResultsA total of 5,628 DCIS cases were retrospectively enrolled in this study. HR-HER2-, HR-HER2+, HR+HER2+, and HR+HER2- are 299 (5.3%), 498 (8.8%), 1,086 (19.3%), and 3,745 (66.5%), respectively. HR + HER2- cases have smaller tumor size (72.6%, P < 0.001) and lower grade (23.5%, P < 0.001). Comedo necrosis is more frequent in HR-HER2- (24.4%, P < 0.001) and HR-HER2+ DCIS cases (24.3%, P < 0.001). In univariate analyses, HR-HER2+ cases have significantly higher ipsilateral breast event (IBE) recurrence than HR+HER2- cases (P = 0.010). HR-HER2- cases show higher disease-specific mortality than HR+HER2+ cases (P = 0.021). In high-risk DCIS cases, RT reduces the absolute 5-year IBE incidence by 1.3%, 0.7%, 1.9%, and 2.6%, respectively in HR-HER2-, HR-HER2+, HR+HER2+, and HR+HER2- cases, respectively. ConclusionIn this population-based study, DCIS cases have diverse clinical and prognostic features for different molecular subtypes. Adjusting treatment strategies according to DCIS molecular subtypes is worth advancing.

Incidence and Mortality of Post-Polypectomy Colorectal Cancer in Patients with Low-Risk Adenomas: A Systematic Review and Meta-Analysis of Observational Studies

Introduction: The long-term risks of post-polypectomy colorectal cancer (CRC) incidence and mortality among patients with low-risk adenomas (LRAs) are unclear. This study aimed to perform a systematic review and meta-analysis of the risk of CRC incidence and mortality following LRAs removal. Methods: We searched the PubMed, Embase, and Cochrane library for studies that reported the risk of metachronous CRC incidence and mortality after colonoscopy. The primary outcome was the risk of CRC incidence and mortality in patients with LRAs. Random-effects models were used to calculate the pooled risk ratio (RR) with a 95% confidence interval (CI). Results: Thirteen observational studies with 1,750,305 patients (45.4% male; follow-up: 4.5–16.5 years) were included. A meta-analysis of seven studies showed a higher CRC incidence in patients with LRAs than those without adenomas (per 10,000 person-years: 5.2 vs. 3.9; RR 1.25 [95% CI 1.05–1.49], I² = 0%). However, the CRC-related death rate was not significantly different between the two groups (RR 1.13 [95% CI 0.75–1.69], I² = 0%). When compared with the general population, the meta-analysis showed a significantly lower risk of CRC incidence in patients with LRAs (RR 0.59 [95% CI 0.45–0.77], I² = 0%), and another three studies, which could not be pooled, showed a reduction in the risk of CRC-related death in the LRAs group. Conclusions: Patients with LRAs have a small but higher risk of post-polypectomy CRC incidence than patients without adenomas. The marginally higher absolute incidence seemed insufficient for more intensive surveillance colonoscopy, but the significant difference suggested different follow-up strategies between patients with LRAs and those without adenomas.

Cardiac Events in Childhood Cancer Survivors Treated with Anthracyclines: The Value of Previous Myocardial Strain Measurement.

In echocardiographic surveillance of anthracycline-treated childhood cancer survivors (CCS), left ventricular ejection fraction (LVEF) has insufficient prognostic value for future cardiac events, whereas longitudinal strain may be more sensitive. We describe the long-term incidence of cardiac events in CCS after previous measurement of LVEF and myocardial strain. Echocardiography, including four-chamber view longitudinal strain (4CH-LS), of 116 anthracycline-treated CCS was obtained between 2005–2009 (index echocardiography). Follow-up was obtained at the late-effects clinic. Primary outcome was occurrence of cardiac events, defined as either symptomatic heart failure, life-threatening arrhythmias, LVEF < 40% or cardiac death, in CCS with normal versus abnormal index 4CH-LS. LVEF from subsequent echocardiograms was obtained to evaluate its natural course as a secondary outcome. After index echocardiography (median 13.1 years since childhood cancer diagnosis), our study added a median follow-up of 11.3 years (median last clinical contact 23.6 years since diagnosis). Only three CCS developed a cardiac event (6.2, 6.4 and 6.7 years after index echocardiography), resulting in a ten-year cumulative incidence of 2.7% (95%CI 0.9–8.2). All three CCS had a clearly reduced index 4CH-LS and relevant cardiovascular risk factors, whereas their index LVEFs were around the lower limit of normal. Index LVEF correlated with index 4CH-LS but mean long-term natural course of LVEF was comparable for CCS with abnormal versus normal index 4CH-LS. Absolute 10-year cumulative incidence of cardiac events in anthracycline-treated CCS during long-term follow-up was low. Sensitive echocardiographic measurements, such as 4CH-LS may be useful to tailor surveillance frequency in a selected group of CCS without cardiovascular disease.

Decreased Risk of Anxiety in Diabetic Patients Receiving Glucagon-like Peptide-1 Receptor Agonist: A Nationwide, Population-Based Cohort Study

Background: Previous findings on using Glucagon-like peptide-1 receptor agonist (GLP1-RA) as an antidepressant were conflicting, lacking large-scale studies. We used population-based data to investigate depression and anxiety risk in diabetic patients receiving the medication. Methods: From claims records of the National Health Insurance Research Database (NHIRD) of Taiwan, we identified cohorts of 10,690 GLP1-RA users and 42,766 propensity score-matched patients without GLP1-RA use from patients with diabetes mellitus (DM) diagnosed in 2011–2017, matched by age, gender, index year, occupation, urbanization, comorbidities, and medications. Incidence, hazard ratios (HR) and 95% confidence interval (CI) of depression and/or anxiety were estimated by the end of 2017. Results: The overall combined incidence of anxiety and/or depression was lower in GLP1-RA users than in non-users (6.80 versus 9.36 per 1,000 person-years), with an adjusted HR adjusted hazard ratio (aHR) of 0.8 (95% CI: 0.67–0.95) after controlling for covariates. The absolute incidence reduction was greater in anxiety (2.13 per 1,000 person-years) than in depression (0.41 per 1,000 person-years). The treatment effectiveness was significant for women. Patients taking GLP1-RA for longer than 180 days had the incidence of anxiety reduced to 2.93 per 1,000 person-years, with an aHR of 0.41 (95%CI: 0.27–0.61), compared to non-users. Dulaglutide could significantly decrease risks of both anxiety and depression. Conclusion: Patients with DM receiving GLP1-RA therapy have a greater reduction of the risk of anxiety than that of depression. Our findings strengthen previous research that advocated possible anti-depressant or anxiolytic effects of GLP1-RA and may lead to improved treatment adherence among patients with DM.

Abstract WP200: Dementia Risk Following Ischemic Stroke: A Systematic Review And Meta-analysis Of Factors Collected At Time Of Stroke Diagnosis

Introduction: Delineating predictors of dementia among ischemic stroke survivors is critical to reduce dementia burden and to improve quality of life in this population. Methods: A Metaanalysis compliant with Preferred Reporting Items for Systematic Reviews and Metaanalysis was conducted. Analysis included absolute risk, incidence rates and patient level predictors (demographics, CVD history,TIA, stroke location, disability, chronic brain changes and stroke mechanism). Additional predictors included study setting, method of dementia diagnosis and inclusion of patients with recurrent or first ever stroke. A random effects meta-analysis was undertaken. Results: 4,325 studies were screened and a total of 21 studies were included in metaanalysis, representing 55183 patients with ischemic stroke, with average age of 70 years (range 65-80 years) and average followup of 29 months. Overall rate of dementia after ischemic stroke was 13.0 per 1000 py (95% CI 6.0, 36.0). Incidence rates were eight times higher in hospital based studies (17.0, CI 8.0, 36.0) compared to registry-based studies (1.8, CI 0.8, 4.0). Absolute dementia risk after stroke was 20% at 5 year, 30 at 15 years and 48 at 25 years of follow-up. There was 33 difference in dementia incidence in the later study periods (2007-2009) compared to (1996-2006). Statistically significant predictors of dementia after ischemic stroke included female gender (OR 1.2, CI 1.1-1.4), hypertension (1.4 CI 1.1-2.0), diabetes mellitus (1.6 CI 1.3-2.1), atrial fibrillation (1.9 CI 1.2-3.0), previous stroke (2.0 CI 1.6-2.6), presence of stroke lesion in dominant hemisphere (2.4 CI 1.3-4.5), brain stem (0.5, CI 0.3-0.9) frontal lobe (3.7 CI 1.2-12.0), aphasia (7.9, CI 2.4-26.0), dysphasia (5.8 CI 3.0-11.3), gait impairment (1.7, CI 1.1-2.7), white matter hyperintensities (3.2 CI 2.0-5.3), medial temporal lobe atrophy (3.9 CI 1.9-8.3) and transient ischemic attack as the predisposing aetiology for ischemic stroke (0.44 CI 0.22-0.88). Conclusions: Factors routinely collected at time of admission are key in monitoring patients at highest risk of progression to dementia after acute ischemic stroke, in particular stroke location and presence of stroke related disability.

Proximal humerus fractures: epidemiology and trends in surgical management of hospital-admitted patients in Portugal.

BackgroundProximal humerus fractures (PHFs) are frequent and associated with significant health care burden. National epidemiological data are limited. Our objective is to characterize the Portuguese population admitted with PHFs and analyze therapeutic management, the impact of associated lesions, and mortality rate.MethodsThis was a retrospective, observational study of admissions from mainland public hospitals (2000-2015), with primary or secondary diagnosis of PHFs. Incomplete records, pathologic lesions, malunion/nonunion, and hardware removal were excluded. Age, gender, admission date, hospitalization period, associated injuries, treatment, and mortality were recorded.ResultsA total of 19,290 patients were included. Through the analyzed period, an increase in the absolute number and incidence of PHFs was observed. The mean age at diagnosis was 62.6 ± 21.0 years old (57% elderly; 63.5% female). The mean length of stay was 10.0 ± 14.1 days, higher in patients submitted to arthroplasty (P < .001) and in those with associated fractures (25%; P < .001). A total of 14,482 patients were operated, most frequently with open reduction and internal fixation (28%). The inpatient mortality rate was 3.2%, significantly higher in patients with associated fractures (odds 2.77 for lower limb vs. upper limb).ConclusionThere is a trend toward an increase in surgical management of PHFs. The relative proportion of open reduction and internal fixation and arthroplasty (particularly reverse arthroplasty) increased, probably reflecting biomechanical implant properties, fracture pattern, and demand for better functionality. Associated fractures are an important comorbidity, associated with increased mortality and length of stay.