Absolute Risk Difference Research Articles

Adverse outcomes and mortality in individuals with eating disorder-related electrolyte abnormalities in Ontario, Canada: a population-based cohort study

Individuals with eating disorders are at a higher risk of electrolyte abnormalities than the general population. We conducted the first representative cohort study assessing whether electrolyte abnormalities in people with eating disorders were associated with mortality and physical health outcomes. This was a retrospective population-based cohort study in Ontario including people aged 13 years or older with an eating disorder and an outpatient electrolyte measure within 1 year (between Jan 1, 2008 and June 30, 2019). An electrolyte abnormality was any of hypokalaemia, hyperkalaemia, hyponatraemia, hypernatraemia, hypomagnesaemia, hypophosphataemia, metabolic acidosis, or metabolic alkalosis. The primary outcome was all-cause mortality. Secondary outcomes were hospitalisation, a cardiac event, infection, acute or chronic kidney disease, fracture, and bowel obstruction. In additional analyses, we examined a younger cohort (<25 years old) and individuals with no previously diagnosed secondary outcome. We involved people with related lived or family experience in the study. 6163 patients with an eating disorder and an electrolyte measure within 1 year since diagnosis (mean age 26·8 years [SD 17·5]; 5456 [88·5%] female, 707 [11·5%] male; median follow-up 6·4 years [IQR 4-9]) were included. Ethnicity data were not available. The most common electrolyte abnormalities were hypokalaemia (994/1987 [50·0%]), hyponatraemia (752/1987 [37·8%]), and hypernatraemia (420/1987 [21·1%]). Overall, mortality occurred in 311/1987 (15·7%) of those with an electrolyte abnormality versus 234/4176 (5·6%) in those without (absolute risk difference 10·1%; adjusted hazard ratio 1·23 [95% CI 1·03-1·48]). Hospitalisation (1202/1987 [60·5%] vs 1979/4176 [47·4%]; 1·35 [1·25-1·46]), acute kidney injury (206/1987 [10·4%] vs 124/4176 [3%]; 1·91 [1·50-2·43]), chronic kidney disease (245/1987 [12·3%] vs 181/4176 [4·3%]; 1·44 [1·17-1·77]), bone fracture (140/1987 [7·0%] vs 167/4176 [4·0%]; 1·40 [1·10-1·78]), and bowel obstruction (72/1987 [3·6%] vs 57/4176 [1·4%]; 1·62 [1·12-2·35]) were associated with an electrolyte abnormality, but not infection or a cardiovascular event. Findings were consistent in young individuals (<25 years old) and those without secondary outcomes at baseline, by eating disorder type, and by sex. Electrolyte abnormalities are associated with death and poor physical health outcomes, supporting the importance of monitoring and possible interventions to prevent adverse outcomes. Findings also call for a refinement of the definition of severity of eating disorder and replication of these findings in other jurisdictions. None.

Predicting Individual Treatment Effects to Determine Duration of Dual Antiplatelet Therapy After Stent Implantation.

After coronary stent implantation, prolonged dual antiplatelet therapy (DAPT) increases bleeding risk, requiring personalization of DAPT duration. The aim of this study was to develop and validate a machine learning model to predict optimal DAPT duration after contemporary drug-eluting stent implantation in patients with coronary artery disease. The One-Month DAPT, RESET (Real Safety and Efficacy of 3-Month Dual Antiplatelet Therapy Following Endeavor Zotarolimus-Eluting Stent Implantation), and IVUS-XPL (Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesion) trials provided a derivation cohort (n=6568). Using the X-learner approach, an individualized DAPT score was developed to determine the therapeutic benefit of abbreviated (1-6 months) versus standard (12-month) DAPT using various predictors. The primary outcome was major bleeding; the secondary outcomes included 1-year major adverse cardiac and cerebrovascular events and 1-year net adverse clinical events. The risk reduction with abbreviated DAPT (3 months) in the individualized DAPT-determined higher predicted benefit group was validated in the TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus-Eluting Stent for Acute Coronary Syndrome) trial (n=3056), which enrolled patients with acute coronary syndrome treated with ticagrelor. The validation cohort comprised 1527 abbreviated and 1529 standard DAPT cases. Major bleeding occurred in 25 (1.7%) and 45 (3.0%) patients in the abbreviated and standard DAPT groups, respectively. The individualized DAPT score identified 2582 (84.5%) participants who would benefit from abbreviated DAPT, which was significantly associated with a lower major bleeding risk (absolute risk difference [ARD], 1.26 [95% CI, 0.15-2.36]) and net adverse clinical events (ARD, 1.59 [95% CI, 0.07-3.10]) but not major adverse cardiac and cerebrovascular events (ARD, 0.63 [95% CI, -0.34 to 1.61]), compared with standard DAPT in the higher predicted benefit group. Abbreviated DAPT had no significant difference in clinical outcomes of major bleeding (ARD, 1.49 [95% CI, -1.74 to 4.72]), net adverse clinical events (ARD, 2.57 [95% CI, -1.85 to 6.99]), or major adverse cardiac and cerebrovascular events (ARD, 1.54 [95% CI, -1.26 to 4.34]), compared with standard DAPT in the individualized DAPT-determined lower predicted benefit group. Machine learning using the X-learner approach identifies patients with acute coronary syndrome who may benefit from abbreviated DAPT after drug-eluting stent implantation, laying the groundwork for personalized antiplatelet therapy.

Association Between Mycobacterium tuberculosis Sensitization and Insulin Resistance Among US Adults Screened for Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) may be a long-term sequela of infection with Mycobacterium tuberculosis (Mtb) by mechanisms that remain to be fully explained. We evaluated the association between Mtb sensitization and T2DM and, via mediation analysis, the extent to which it is mediated by insulin resistance and/or β-cell failure. Adults were assessed for T2DM by fasting plasma glucose, 2-hour oral glucose tolerance testing, and hemoglobin A1c; β-cell dysfunction and insulin resistance by homoeostasis model assessment 2; and Mtb sensitization by tuberculin skin testing. Associations between Mtb sensitization and T2DM were modeled with probit regression and decomposed into indirect effects of β-cell dysfunction and insulin resistance. Analyses were adjusted for sociodemographic, behavioral, and clinical characteristics. We included 1843 adults. Individuals with Mtb sensitization were older than those without Mtb (median [IQR], 54 [39-64] vs 47 [33-62] years). As compared with being uninfected, Mtb sensitization was associated with T2DM (adjusted absolute risk difference, 9.34% [95% CI, 2.38%-15.0%]; P < .001) and increased insulin resistance (adjusted median difference, 0.16 [95% CI, .03-.29]; P = .014) but not β-cell dysfunction (adjusted median difference, -3.1 [95% CI, -10.4 to 4.3]; P = .42). In mediation analyses, insulin resistance mediated 18.3% (95% CI, 3.29%-36.0%; P = .020) of the total effect of the association between Mtb sensitization and T2DM. Definitive prospective studies examining incident T2DM following tuberculosis are warranted. Notwithstanding, our findings suggest that exposure to Mtb may be a novel risk factor for T2DM, likely driven by an increase in insulin resistance.

Simultaneous evaluation of the imprecision and inconsistency domains of GRADE can be performed using prediction intervals

ObjectivesTo explore the use of prediction interval (PI) for the simultaneous evaluation of the imprecision and inconsistency domains of Grading of Recommendations, Assessment, and Evaluation using stakeholder-provided decision thresholds. Study Design and SettingWe propose transforming the PI of a meta-analysis from a relative risk scale to an absolute risk difference using an appropriate baseline risk. The transformed PI is compared to stakeholder-provided thresholds on an absolute scale. We applied this approach to a large convenience sample of meta-analyses extracted from the Cochrane Database of Systematic Reviews and compared it against the traditional approach of rating imprecision and inconsistency separately using confidence intervals and statistical measures of heterogeneity, respectively. We used empirically derived thresholds following Grading of Recommendations, Assessment, and Evaluation guidance. ResultsThe convenience sample consisted of 2516 meta-analyses (median of 7 studies per meta-analysis; interquartile range: 5–11). The main analysis showed the percentage of meta-analyses in which both approaches had the same number of certainty levels rated down was 59%. The PI approach led to more levels of rating down (lower certainty) in 27% and to fewer levels of rating down (higher certainty) in 14%. Multiple sensitivity analyses using different thresholds showed similar results, but the PI approach had particularly increased width with a larger number of included studies and higher I2 values. ConclusionUsing the PI for simultaneous evaluation of imprecision and inconsistency seems feasible and logical but can lead to lower certainty ratings. The PI-based approach requires further testing in future systematic reviews and guidelines using context-specific thresholds and evidence-to-decision criteria. Plain Language SummaryThe prediction interval (PI) addresses both the imprecision and inconsistency domains of certainty. In this study, we applied this PI approach to simultaneously judge both domains and compared this to the traditional approach of making these separate judgments. The 2 approaches had moderate agreement. The PI-based approach requires further testing in future systematic reviews and guidelines using context-specific thresholds and evidence-to-decision criteria.

Effects of Mediterranean diet during pregnancy on the onset of overweight or obesity in the offspring: a randomized trial.

The PREMEDI study was designed to assess the efficacy of nutritional counseling aimed at promoting Mediterranean Diet (MD) during pregnancy on the incidence of overweight or obesity at 24 months in the offspring. PREMEDI was a parallel-arm randomized-controlled trial. 104 women in their first trimester of pregnancy were randomly assigned in a 1:1 ratio to standard obstetrical and gynecological care alone (CT) or with nutritional counseling promoting MD. Women enrolled in the MD arm were provided with 3 sessions of nutritional counseling (one session per trimester). The main outcome was the proportion of overweight or obesity among the offspring at the age of 24 months. Maternal MD-adherence and weight gain during pregnancy were also evaluated. Lastly, the evaluation of epigenetic modulation of metabolic pathways in the offspring was analyzed in cord blood. Five women in the MD arm and 2 in the CT arm were lost to follow-up, so a total of 97 completed the study. At 24 months, children of MD mothers were less likely to have overweight or obesity than those of the CT mothers (6% vs. 33%, absolute risk difference = -27%, 95% CI -41% to -12%, p < 0.001; number needed to treat 3, 95% CI 2 to 8, intention to treat analysis). A significantly higher increase of MD-adherence during the trial was observed in the MD arm compared to the CT arm. A similar body weight gain at the end of pregnancy was observed in the two arms. The mean (SD) methylation rate of the leptin gene in cord blood was 30.4 (1.02) % and 16.9 (2.99) % in the CT and MD mothers, respectively (p < 0.0001). MD during pregnancy could be an effective strategy for preventing pediatric overweight or obesity at 24 months. This effect involves, at least in part, an epigenetic modification of leptin expression.

Long-term risk of heart failure in adult cancer survivors: a systematic review and meta-analysis

BackgroundCancer survivors are at increased risk of heart failure (HF). While cardiotoxicity is commonly sought at the time of cancer chemotherapy, HF develops as a result of multiple ‘hits’ over...

Risk of Venous Thromboembolism After Total Knee Arthroplasty in Patients with Obstructive Sleep Apnea: Results from a National Cohort.

Obstructive sleep apnea (OSA) is a prevalent condition associated with many comorbidities. However, establishing the independent impact of OSA on specific health outcomes can be challenging without access to a substantial patient cohort. This study aimed to investigate whether a diagnosis of OSA was independently associated with venous thromboembolism (VTE) after total knee arthroplasty (TKA). In this retrospective cohort study, we interrogated the TriNetX Analytics Research Network, a large database comprising the billing claims and electronic health record-derived data of >117 million patients. Using Current Procedural Terminology (CPT) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, we identified US adult patients who underwent TKA between January 1, 2013 and January 1, 2023, with and without preexisting OSA (and ≥2 OSA occurrences overall). We then analyzed the 1-month postoperative incidence of VTE as a composite outcome of deep vein thrombosis (DVT) and pulmonary embolism (PE) incidence, as well as cerebrovascular accident (CVA), myocardial infarction (MI), and DVT and PE individually. Baseline demographic and comorbidity covariates were incorporated into a 1:1 propensity score-matched analysis to clarify the independent effect of OSA. During the 10-year study period, a total of 197,460 patients underwent TKA. Of these, 27,976 met the criteria for inclusion in the OSA cohort, while 150,830 had no documented history of OSA. In the initial analysis, OSA was significantly associated with the primary outcome (DVT/PE) as well as all secondary outcomes (CVA, MI, and individually with DVT and PE) at 1 month postsurgery. After generating propensity score matched cohorts, DVT/PE remained significantly associated with OSA, with an absolute risk difference of 0.7% (odds ratio [OR], 1.19, confidence interval [CI], 1.1-1.3, P < .001), as were the secondary outcomes of DVT (OR, 1.11, CI, 1.0-1.2, P = .030) and PE (OR, 1.41, CI, 1.2-1.6, P < .001). In this study encompassing a nationally representative sample of TKA patients, OSA was associated with increased incidence of VTE at 1 month postoperatively, an association that persisted after the generation of matched cohorts. While limitations related to the lack of patient-level data, disease severity, and therapy adherence should be acknowledged, our large sample size enabled us to factor many baseline characteristics into our analysis, reinforcing the association of these findings. Prospective work is needed on the impact of modulating factors such as anticoagulation regimen and positive airway pressure therapy on these outcomes.

Comparative effectiveness of 6x R-CHOP21 versus 6x R-CHOP21 + 2 R for patients with advanced-stage diffuse large B-cell lymphoma

First-line treatment for advanced-stage diffuse large B-cell lymphoma (DLBCL) typically involves 6x R-CHOP21 or 6x R-CHOP21 with two additional rituximab administrations (6x R-CHOP21 + 2 R). In contemporary practice, this treatment choice might be guided by interim PET scan results. This nationwide, population-based study investigates the comparative effectiveness of these treatment regimens in an era where interim PET-guided treatment decisions were not standard practice. Utilizing the Netherlands Cancer Registry, we identified 1577 adult patients diagnosed with advanced-stage DLBCL between 2014–2018 who completed either 6x R-CHOP21 (43%) or 6x R-CHOP21 + 2 R (57%). We used propensity scores to assess differences in event-free survival (EFS) and overall survival (OS). At five years, EFS (hazard ratio of 6x R-CHOP21 + 2 R versus 6x R-CHOP21 [HR] = 0.89; 95% confidence interval [CI], 0.72–1.09) and OS (HR = 0.93; 95% CI, 0.73–1.18) were not significantly different between both regimens. In exploratory risk-stratified analysis according to the International Prognostic Index (IPI), high-IPI patients (i.e., scores of 4-5) benefit most from 6x R-CHOP21 + 2 R (5-year absolute risk difference of EFS = 16.8%; 95% CI, −0.4%−34.1% and OS = 12.1%; 95% CI, −5.4–29.6%). Collectively, this analysis reveals no significant differences on average in EFS and OS between the two treatments. However, the potential benefits for high-risk patients treated with 6x R-CHOP21 + 2 R underscore the need for future research.

Endometriosis and Long-Term Cardiovascular Risk: A Nationwide Danish study.

Endometriosis, a systemic gynecological disease affecting 10% of women in reproductive age, shares pathophysiological characteristics with cardiovascular disease. However, data on the relationship between endometriosis and cardiovascular outcomes are scarce, prompting this study to address the knowledge-gap. Using Danish nationwide registries, women diagnosed with endometriosis (1977-2021) were identified and matched with controls in a 1:4 ratio based on year of birth. The primary outcome was a composite of acute myocardial infarction and ischemic stroke. The secondary outcomes were arrhythmias, heart failure, and mortality. In total, 60,508 women with endometriosis and 242,032 matched controls were included (median age 37.3 years). Women with endometriosis were more comorbid and used more medications than controls. The incidence rates of the composite outcomes were 3.2 (95% confidence interval [CI] 3.2-3.3) and 2.7 (95% CI 2.7-2.8) per 1000 person-years among women with and without endometriosis, respectively. Women with endometriosis had a significantly higher associated rate of the composite outcome compared with controls (unadjusted hazard ratio [HR] 1.18 [95% CI 1.14-1.23], adjusted HR 1.15 [95% CI 1.11-1.20]). Likewise, women with endometriosis were also at significantly increased associated risk of arrhythmias (unadjusted HR 1.24 [95% CI 1.20-1.28], adjusted HR 1.21 [95% CI 1.17-1.25]) and heart failure (unadjusted HR 1.16 [95% CI 1.09-1.22], adjusted HR 1.11 [95% CI 1.05-1.18]) but at decreased risk of mortality (unadjusted HR 0.95 [95% CI 0.92-0.97], adjusted HR 0.93 [95% CI 0.91-0.96]). Women with endometriosis have a higher associated long-term risk of cardiovascular outcomes compared with controls. Despite subtle absolute risk-differences, the high prevalence of endometriosis underscores the importance of these findings.

Acoustic-based rule out of stable coronary artery disease: the FILTER-SCAD trial.

Overtesting of low-risk patients with suspect chronic coronary syndrome (CCS) is widespread. The acoustic-based coronary artery disease (CAD) score has superior rule-out capabilities when added to pre-test probability (PTP). FILTER-SCAD tested whether providing a CAD score and PTP to cardiologists was superior to PTP alone in limiting testing. At six Danish and Swedish outpatient clinics, patients with suspected new-onset CCS were randomised to either standard diagnostic examination (SDE) with PTP, or SDE plus CAD score, and cardiologists provided with corresponding recommended diagnostic flowcharts. The primary endpoint was cumulative number of diagnostic tests at one year and key safety endpoint major adverse cardiac events (MACE). In total 2008 patients (46% male, median age 63 years) were randomised from October 2019 to September 2022. When randomised to CAD score (n=1002), it was successfully measured in 94.5%. Overall, 13.5% had PTP ≤5%, and 39.5% had CAD score ≤20. Testing was deferred in 22% with no differences in diagnostic tests between groups (p for superiority =0.56). In the PTP ≤5% subgroup, the proportion with deferred testing increased from 28% to 52% (p<0.001). Overall MACE was 2.4 per 100 person-years. Non-inferiority regarding safety was established, absolute risk difference 0.4% (95% CI -1.85 to 1.06) (p for non-inferiority = 0.005). No differences were seen in angina-related health status or quality of life. The implementation strategy of providing cardiologists with a CAD score alongside SDE did not reduce testing overall but indicated a possible role in patients with low CCS likelihood. Further strategies are warranted to address resistance to modifying diagnostic pathways in this patient population.

Abstract P149: Sex-Specific Blood Pressure Thresholds in Middle-Aged Adults: Results from the Atherosclerosis Risk in Communities (ARIC) Study

Background: Recent studies reported higher coronary heart disease (CHD) risk at lower blood pressure (BP) in females than males, implying a need for sex-specific hypertension (HTN) thresholds. Whether these observations apply to diagnosis thresholds and/or treatment targets remains unclear. Objectives: To determine whether CHD risk differs by BP levels between males and females according to HTN treatment status. Methods: The ARIC Study measured seated BP during Visit 1 (1987-1989), averaging the second and third of three measurements. HTN treatment was determined based on pill-bottle review. We excluded participants with a history of CHD, heart failure, or stroke. Incident CHD events were adjudicated. We examined 10-year CHD risk scores using the PREVENT risk estimator, CHD incidence rates (IR), and the hazard ratios (HR) of CHD events via the Pooled Estimating Equation, Poisson regression, and Cox proportional hazard models, controlling for CHD risk factors ( Table Footnote ). Results: Of 13,426 participants (56% female, mean age [54±5.7 years]), 25% were treated for HTN. Males in both groups had higher average 10-year CHD risk scores across SBP categories than females ( P comparing trends &lt;0.001) ( Table ). While IRs were lower among females in the untreated group, they did not differ significantly from males in treated participants ( P comparing trends &gt; 0.05). Notably, while similar in untreated populations, treated females may experience higher risk (HR) of incidence CHD events than treated males across all SBP categories. Conclusion: While there were differences in absolute and relative risk of CHD between males and females, we did not find consistent evidence that untreated males and females experience different risk of CHD risk by SBP threshold. These findings do not support a sex-specific threshold for hypertension diagnosis or treatment.

Drug-coated balloon angioplasty with rescue stenting versus intended stenting for the treatment of patients with de novo coronary artery lesions (REC-CAGEFREE I): an open-label, randomised, non-inferiority trial

The long-term impact of drug-coated balloon (DCB) angioplasty for the treatment of patients with de novo coronary artery lesions remains uncertain. We aimed to assess the non-inferiority of DCB angioplasty with rescue stenting to intended drug-eluting stent (DES) deployment for patients with de novo, non-complex coronary artery lesions. REC-CAGEFREE I was an open-label, randomised, non-inferiority trial conducted at 43 sites in China. After successful lesion pre-dilatation, patients aged 18 years or older with de novo, non-complex coronary artery disease (irrespective of target vessel diameter) and an indication for percutaneous coronary intervention were randomly assigned (1:1), via a web-based centralised system with block randomisation (block size of two, four, or six) and stratified by site, to paclitaxel-coated balloon angioplasty with the option of rescue stenting due to an unsatisfactory result (DCB group) or intended deployment of second-generation thin-strut sirolimus-eluting stents (DES group). The primary outcome was the device-oriented composite endpoint (DoCE; including cardiovascular death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularisation) assessed at 24 months in the intention-to-treat (ITT) population (ie, all participants randomly assigned to treatment). Non-inferiority was established if the upper limit of the one-sided 95% CI for the absolute risk difference was smaller than 2·68%. Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT04561739. It is closed to accrual and extended follow-up is ongoing. Between Feb 5, 2021, and May 1, 2022, 2272 patients were randomly assigned to the DCB group (1133 [50%]) or the DES group (1139 [50%]). Median age at the time of randomisation was 62 years (IQR 54-69), 1574 (69·3%) of 2272 were male, 698 (30·7%) were female, and all patients were of Chinese ethnicity. 106 (9·4%) of 1133 patients in the DCB group received rescue DES after unsatisfactory DCB angioplasty. As of data cutoff (May 1, 2024), median follow-up was 734 days (IQR 731-739). At 24 months, the DoCE occurred in 72 (6·4%) of 1133 patients in the DCB group and 38 (3·4%) of 1139 in the DES group, with a risk difference of 3·04% in the cumulative event rate (upper boundary of the one-sided 95% CI 4·52; pnon-inferiority=0·65; two-sided 95% CI 1·27-4·81; p=0·0008); the criterion for non-inferiority was not met. During intervention, no acute vessel closures occurred in the DCB group and one (0·1%) of 1139 patients in the DES group had acute vessel closure. Periprocedural myocardial infarction occurred in ten (0·9%) of 1133 patients in the DCB group and nine (0·8%) in the DES group. In patients with de novo, non-complex coronary artery disease, irrespective of vessel diameter, a strategy of DCB angioplasty with rescue stenting did not achieve non-inferiority compared with the intended DES implantation in terms of the DoCE at 2 years, which indicates that DES should remain the preferred treatment for this patient population. Xijing Hospital and Shenqi Medical. For the Chinese translation of the abstract see Supplementary Materials section.

All-cause and cause-specific mortality risk and loss in life expectancy associated with incident type 2 diabetes onset age and duration.

Evidence on type 2 diabetes onset age and duration on mortality risk has been limited by short follow-up, inadequate control for confounding, missing repeated measurements, and inability to cover the full range of onset age, duration, and major causes of death. Moreover, scarce data dissect how type 2 diabetes onset age and duration shape life expectancy. We evaluate prospectively these topics based on 270,075 eligible participants in the Nurses' Health Studies and Health Professionals Follow-up Study, leveraging repeated measurements throughout up to 40 years of follow-up. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In fully adjusted analyses, incident early onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64-3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27-10.1), respiratory disease (3.43, 1.38-8.51), neurodegenerative disease (5.13, 2.09-12.6), and kidney disease (8.55, 1.98-36.9). The relative risk elevations declined dramatically with each higher decade of age at diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Longer disease duration was associated with generally higher relative and absolute risk of mortality. Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy.

Higher proceduralist stroke thrombectomy volume is associated with reduced inpatient mortality

BackgroundThe aim of this study was to determine the impact of endovascular thrombectomy (EVT) proceduralist volume on in-hospital mortality in acute ischemic stroke (AIS) patients.MethodsWe performed a retrospective cohort study...

Comparison of obinutuzumab and rituximab for treating primary membranous nephropathy.

This study compared the effectiveness and safety profiles of obinutuzumab and rituximab in the treatment of patients with primary membranous nephropathy. Patients with primary membranous nephropathy who had urine protein ≥ 3.5 g/24 hours and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 despite six months of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker and treatment with obinutuzumab or rituximab were included and matched by propensity score (ratio: 1:2) based on age, sex, urine protein, eGFR, and titers of Anti-Phospholipase A2 receptor (PLA2R) antibody. The primary outcome was defined as a combination of partial or complete remission at 12 months. Logistic regression models, Kaplan Meier curves, and absolute risk differences were employed to compare the therapeutic effectiveness and safety profiles of obinutuzumab and rituximab. Sixty-three patients with primary membranous nephropathy were included in the study, with 21 patients receiving obinutuzumab and 42 patients receiving rituximab. At 12 months, the primary outcome was achieved in 20 of 21 patients in the obinutuzumab group and 28 of 42 patients in the rituximab group (obinutuzumab vs. rituximab: 95% vs. 67%; odds ratio (OR): 10.00, 95% confidence intervals (CI):1.21-82.35, P=0.03). Moreover, patients in the obinutuzumab group acquired more complete remission (obinutuzumab vs. rituximab: 38% vs. 14%; OR: 3.69, 95% CI:1.08-12.68, P=0.04). In PLA2R-associated primary membranous nephropathy subgroup analyses, patients in obinutuzumab group sustained lower CD19 B cell counts (CD19 B cell counts: median (IQR) 0 (0-6) cells/ul vs. 20 (3-58) cells/ul, P=0.002) and were more prone to achieve immunological remission (defined as PLA2R antibody <2 RU/ml) at six months [obinutuzumab vs. rituximab: 92% (12 out of 13) vs. 64% (16 out of 25), P=0.06] than rituximab. Both treatment regimens were well tolerated. Our study demonstrated that obinutuzumab is associated with higher odds of clinical remission compared to rituximab at 12 months which may be due to higher immunological remission at six months with a similar safety profile in patients with primary membranous nephropathy.

Implementation of single high-dose liposomal amphotericin B based induction therapy for treatment of HIV-associated cryptococcal meningitis in Uganda: a comparative prospective cohort study.

In 2022, the World Health Organization (WHO) recommended a single 10mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of HIV-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda. We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022-2023. We compared 10-week survival and CSF early fungicidal activity with the outcomes observed in the AMBITION-cm clinical trial conducted at the same sites. During 2022-2023, 179 adults were treated with the AMBITION-cm regimen via routine care and compared to the 171 adults randomized to the AMBITION-cm trial interventional arm in Uganda from 2018-2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%; 95%CI 61.6%-76.3%) and AMBITION-cm trial participants in the intervention arm (71.7%; 95%CI 65.2%-78.8%; absolute risk difference = -3.1%; 95%CI -13.1% to 6.9%; p=.61). Early fungicidal activity did not differ (0.42 vs 0.39 log10CFU/mL/day; p=.80) between groups. Among observational cohort participants discharged alive initially and for whom follow up data were available, the incidence of re-hospitalizations due to persistently elevated intracranial pressure was 2.8% (4/144). The AMBITION-cm regimen for cryptococcal meningitis resulted in similar outcomes as observed in the AMBITION-cm clinical trial when implemented in routine care. Intracranial pressure management during hospitalization and awareness after discharge are key components of optimizing outcomes.

Evaluation of Etomidate Use and Association with Mortality Compared with Ketamine Among Critically Ill Patients.

Uncertainty remains regarding the risks associated with single dose use of etomidate. To assess use of etomidate in critically ill patients and compare outcomes for patients who received etomidate versus ketamine. We assessed patients who received invasive mechanical ventilation (IMV), admitted to an ICU in the Premier Healthcare Database, 2008-2021. The exposure was receipt of etomidate on the day of IMV initiation and the main outcome was hospital mortality. Using multivariable regression we compared patients who received IMV within the first two days of hospitalization who received etomidate with propensity-score matched patients who received ketamine. We also assessed whether receipt of corticosteroids in the days after intubation modified the association between etomidate and mortality. Of 1,689,945 patients who received IMV, nearly half (738,855; 43.7%) received etomidate. Among those who received IMV in the first two days of hospitalization, we established 22,273 matched pairs given either etomidate or ketamine. In the primary analysis, receipt of etomidate was associated with greater hospital mortality relative to ketamine (21.6% vs 18.7%; absolute risk difference: 2.8%, 95% CI 2.1%, 3.6%; adjusted odds ratio: 1.28, 95% CI 1.21,1.34). This was consistent across subgroups and sensitivity analyses. We found no attenuation of the association with mortality with receipt of corticosteroids in the days following etomidate use. Use of etomidate on the day of IMV initiation is common and associated with a higher odds of hospital mortality compared with ketamine. This finding is independent of subsequent treatment with corticosteroids.

Hyperkalemia-Related RAASi Reduction and Estimated Number Needed to Treat to Avoid a First Hospitalization by Maintaining RAASi.

Renin-angiotensin-aldosterone system inhibitor (RAASi) therapy provides cardiorenal protection but is often down-titrated or discontinued following a hyperkalemia episode. This observational study describes the extent of hyperkalemia-related RAASi reduction in patients with chronic kidney disease (CKD) and/or heart failure (HF), and estimates the number needed to treat (NNT) to avoid a first hospitalization if RAASi had been maintained at the prior dose. Healthcare registers and claims data from Germany, Spain, Sweden, and the UK were used to identify non-dialysis patients with CKD and/or HF who had a hyperkalemia episode while on RAASi. Patients whose RAASi therapy was reduced (down-titrated/discontinued) after the hyperkalemia episode were propensity score (PS)-matched to those with maintained RAASi, and their risks of a hospitalization within 6 months were estimated using the Kaplan-Meier method. Based on the absolute difference in this 6-month risk, the NNT framework was applied to estimate the number of patients who needed to have maintained instead of reduced their RAASi to avoid a first hospitalization during this period. Overall, 40,059 patients from Germany, Spain, Sweden, and the UK were included. Presence of CKD at baseline was similar across countries (72%-92%), while HF was less common in Spain (18%) versus other countries (32%-71%). After the hyperkalemia episode, RAASi was reduced in 25%-57% of patients. Following PS matching, the 6-month risk of hospitalization was consistently higher in those with reduced versus maintained RAASi; the absolute risk difference ranged from 2.7% to 7.3%. Applying the NNT framework, these data suggest that a first hospitalization within 6 months could potentially have been avoided if 25 patients had maintained instead of reduced their RAASi. Our findings suggest a potential for avoiding a first hospitalization, even within a short time frame, by increasing adherence to guidelines to maintain instead of reduce RAASi after a hyperkalemia episode.

Incorporating Individual-Level Treatment Effects and Outcome Preferences Into Personalized Blood Pressure Target Recommendations.

There are no shared decision-making frameworks for selecting blood pressure (BP) targets for individuals with hypertension. This study addressed whether results from the SPRINT (Systolic Blood Pressure Intervention Trial) could be tailored to individuals using predicted risks and simulated preferences. Among 8202 SPRINT participants, Cox models were developed and internally validated to predict each individual's absolute difference in risk from intensive versus standard BP lowering for cardiovascular events, cognitive impairment, death, and serious adverse events (AEs). Individual treatment effects were combined using simulated preference weights into a net benefit, which represents a weighted sum of risk differences across outcomes. Net benefits were compared among those above versus below the median AE risk. In simulations for which cardiovascular, cognitive, and death events had much greater weight than the AEs of BP lowering, the median net benefit was 3.3 percentage points (interquartile range [IQR], 2.0-5.7), and 100% of participants had a net benefit favoring intensive BP lowering. When simulating benefits and harms to have similar weights, the median net benefit was 0.8 percentage points (IQR, 0.2-2.2), and 87% had a positive net benefit. Compared with participants at lower risk of AEs from BP lowering, those at higher risk had a greater net benefit from intensive BP lowering despite experiencing more AEs (P<0.001 in both simulations). Most SPRINT participants had a predicted net benefit that favored intensive BP lowering, but the degree of net benefit varied considerably. Tailoring BP targets using each patient's risks and preferences may provide more refined BP target recommendations.

Naloxone and Patient Outcomes in Out-of-Hospital Cardiac Arrests in California

The incidence of opioid-associated out-of-hospital cardiac arrest (OA-OHCA) has grown from less than 1% of OHCA in 2000 to between 7% and 14% of OHCA in recent years; American Heart Association (AHA) protocols suggest that emergency medical service (EMS) clinicians consider naloxone in OA-OHCA. However, it is unknown whether naloxone improves survival in these patients or in patients with undifferentiated OHCA. To evaluate the association of naloxone with clinical outcomes in patients with undifferentiated OHCA. Retrospective cohort study of EMS-treated patients aged 18 or older who received EMS treatment for nontraumatic OHCA in 3 Northern California counties between 2015 and 2023. Data were analyzed using propensity score-based models from February to April 2024. EMS administration of naloxone. The primary outcome was survival to hospital discharge; the secondary outcome was sustained return of spontaneous circulation (ROSC). Covariates included patient and cardiac arrest characteristics (eg, age, sex, nonshockable rhythm, any comorbidity, unwitnessed arrest, and EMS agency) and EMS clinician determination of OHCA cause as presumed drug-related. Among 8195 patients (median [IQR] age, 65 [51-78] years; 5540 male [67.6%]; 1304 Asian, Native Hawaiian, or Pacific Islander [15.9%]; 1119 Black [13.7%]; 2538 White [31.0%]) with OHCA treated by 5 EMS agencies from 2015 to 2023, 715 (8.7%) were believed by treating clinicians to have drug-related OHCA. Naloxone was administered to 1165 patients (14.2%) and was associated with increased ROSC using both nearest neighbor propensity matching (absolute risk difference [ARD], 15.2%; 95% CI, 9.9%-20.6%) and inverse propensity-weighted regression adjustment (ARD, 11.8%; 95% CI, 7.3%-16.4%). Naloxone was also associated with increased survival to hospital discharge using both nearest neighbor propensity matching (ARD, 6.2%; 95% CI, 2.3%-10.0%) and inverse propensity-weighted regression adjustment (ARD, 3.9%; 95% CI, 1.1%-6.7%). The number needed to treat with naloxone was 9 for ROSC and 26 for survival to hospital discharge. In a regression model that assessed effect modification between naloxone and presumed drug-related OHCA, naloxone was associated with improved survival to hospital discharge in both the presumed drug-related OHCA (odds ratio [OR], 2.48; 95% CI, 1.34-4.58) and non-drug-related OHCA groups (OR, 1.35; 95% CI, 1.04-1.77). In this retrospective cohort study, naloxone administration as part of EMS management of OHCA was associated with increased rates of ROSC and increased survival to hospital discharge when evaluated using propensity score-based models. Given the lack of clinical practice data on the efficacy of naloxone in OA-OHCA and OHCA in general, these findings support further evaluation of naloxone as part of cardiac arrest care.