Intensive Treatment Group Research Articles

Comparative Efficacy of Family-Mediated Intervention Versus Early Intensive Behavioral Intervention on Developmental Domains in Children with Autism Spectrum Disorder: A Randomized Controlled Trial

Background: Autism spectrum disorder is a neurodevelopmental disorder of childhood in which there is a deficit in social and communicative skill, and the child shows restricted and repetitive behavior. For children diagnosed with autism spectrum disorder, family-mediated intervention and early intensive behavioral intervention are considered standard of care. The study aimed to compare their efficacy on social skills and other developmental domains in our cultural context. Methods: This study was a parallel-arm, open-label, randomized active-controlled clinical trial. Fifty children diagnosed with autism spectrum disorder were randomly assigned to either the family-mediated intervention or early intensive behavioral intervention groups. Communication DEALL Developmental Checklist was applied at 0, 12, and 24 weeks. Results: The difference in the mean value of Communication DEALL Developmental Checklist at the end of 24 weeks from the initial value was significantly better in the family-mediated intervention as compared to the early intensive behavioral intervention group in social (mean difference = −16.8, 95% CI = −27.18, −6.49, p = .002) as well as fine motor, cognitive, and overall development. In other developmental domains of Communication DEALL Developmental Checklist, the family-mediated intervention group performed better in comparison to the early intensive behavioral intervention group at different time periods although not statistically significant. Conclusion: The results of the study indicated that, throughout the course of 24 weeks of treatment, autism spectrum disorder children in family-mediated intervention showed a distinct improvement in major developmental domains. Family-mediated intervention can be advocated for autism spectrum disorder children in our cultural context in view of improved functioning in major developmental domains in the background of our study findings.

Терапия расстройств пищевого поведения: от исследований к практике

<p>This digest reviews recent significant changes that can play a role in the treatment of eating disorders. It also contains proposals on improving the efficacy of treatment in general and investigation of the outcome of intensive treatment and psychodynamic group therapy for patients with eating disorders.</p>

Comparison of intensive treatment versus standard treatment in lowering blood pressure and its association with cognitive decline and dementia: a systematic review and meta-analysis

Abstract Background The ideal blood pressure target level for preventing cognitive decline or dementia in patients with systemic arterial hypertension (SAH) remains unclear. Purpose This study aims to investigate whether intensive blood pressure reduction compared to standard treatment is associated with a reduced risk of cognitive decline or dementia in adults with SAH. Methods PubMed, Scopus and Cochrane databases were searched for randomized clinical trials (RCTs) comparing intensive treatment versus standard treatment for blood pressure reduction in patients with SAH. A random-effects model was used for analyzing the results, which were presented as relative risk (RR) with a 95% confidence interval (CI). Heterogeneity was examined using the I² statistic. Statistical analysis was performed using R software version 4.2.3. Results A total of 5 RCTs and 46,658 patients were included, of whom 23,726 (50,85%) underwent intensive therapy for SAH treatment. The mean age of participants ranged from 62.8 to 80.9 years in the intensive treatment group while it ranged from 63.3 to 80.3 years in the standard treatment group. Occurrence of dementia or probable dementia was significantly lower in the intensive treatment group (3.8% vs. 4,3%; RR 0.88; 95% CI: 0.80 - 0.96; p= 0.0049; I²=0%). Dementia or Cognitive decline (16.4% vs. 18.8%; RR 0.87; 95% CI 0.83 - 0.90; p < 0.000001; I²=0%), and cognitive decline (13.2% vs. 15.2%; RR 0.88; 95% CI 0.80 - 0.98; p= 0.014; I²=53%) also tended towards the intensive treatment group. Additionally, no significant association was found in mortality (6.4% vs. 7.3%; RR 0.87; 95% CI 0.75 - 1.02; p= 0.09; I²=28%) and serious adverse effects (34.4% vs. 35.5%; RR 0.99; 95% CI 0.92 - 1.06; p=0.73; I²=63%). Conclusion Our study shows that intensive blood pressure treatment is associated with a fewer occurrence of dementia, probable dementia and cognitive decline in comparison to the standard blood pressure target.General Analysis

Association of different timepoint and threshold of time-in-target-range and MACEs: insight from the SPRINT study

Abstract Objective To evaluate the prognostic value of different timepoint and threshold of systolic blood pressure (SBP) Time in Target Rang (TTR) in Major Adverse Cardiovascular Events (MACEs). Method This is a post-hoc analysis of the SPIRNT (Systolic Blood Pressure Intervention Trial). Participants with complete record of BP values and no adverse events occurred in the initial 2-years follow-up were enrolled. Different SBP TTR indexes was calculated by different timepoint (3 month,12 month,24 month) and threshold (110-130mmHg;110-140mmHg;110-130mmHg for intensive treatment group and 120-140mmHg for standard treatment group) (Fig 1). The primary outcome was major adverse cardiovascular events (MACEs) occurred 2 years later, defined as the composite of myocardial infarction, stroke, heart failure and cardiovascular death. Results A total of 7134 participants in SPIRNT were enrolled in this study. Those SBP TTR indicators with independent predictive value of MACEs were selected by a multivariable COX model adjusted for traditional cardiovascular risk factors (Fig 2). SBP TTR calculated with 110-140mmHg window in 3 months (3month SBP TTR110-140) was considered to be the best predictor of MACEs occurred 2 years later among selected SBP TTR indexes according to c statistics and relative informativeness (Table1). The restricted cubic spline plot was used to evaluate the nonlinear trend of the TTR indicator. In addition, we obtain the cut-off value by looking for the point in the RCS curve with the largest slope change. 0.65 was considered to be the best truncation for 3month SBP TTR110-140(Fig 3). Patients with 3month TTR110-140 greater than 0.65 had 23.9% lower incidence of MACEs than patients with TTR less than or equal to 0.65 (HR 0.761[0.592-0978], P=0.033).(Table 2) In addition, for patients with early SBP control (3month SBP TTR110-140 >0.65), there was no significant difference in mean SBP between 110-130 mmHg and 130-140 mmHg (Fig4 Group1 Vs Group2). Lasso regression also suggests that TTR110-140 has more informatics advantages than TTR110-130 in cox model at different timepoints (Fig5). Conclusions 3month SBP TTR110-140 was considered to be the best predictor of MACEs occurred 2 years later in different SBP TTR indexes, which indicated the importance of early SBP control. This study also proposed 0.65 as the critical value of 3-month SBP TTR110-140 for prevention of the incident of MACEs. In the future, more cohort studies are needed to expend these findings.

Health-related quality of life among pediatric patients with acute lymphoblastic leukemia: An exploratory cross-sectional study.

Improved survival rates broadened the pediatric oncology focus to include health-related quality of life (HRQoL). This cross-sectional study aimed to examine HRQoL by treatment phase and disease risk level in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL), including those in early survivorship. A subset of data from a larger prospective cohort study was analyzed. Data were collected from 73 patients (73 parent reports and 28 self-reports). Parent proxy and self-report PROMIS measures assessed HRQoL across treatment phases (early intensive, maintenance, and off treatment) and disease risk groups (standard vs high). Analyses assessed the relationship between parent proxy and patient self-reports and the differences in HRQoL among treatment phases and risk groups. Parent proxy reports generally indicated worse fatigue, pain interference, and mobility compared with patient self-reports. Self-reports in the early intensive treatment group suggested worse depressive symptoms, fatigue, mobility, and upper extremity function compared with those in later phases. Parent proxy reports showed worse fatigue and depressive symptoms in early intensive treatment group relative to those in later phases. Patient self-reports in the maintenance group demonstrated the best peer relationships scores. Parent proxy reports in the high-risk group reported significantly higher depressive symptoms and fatigue compared with the standard-risk group. Differences in HRQoL suggest targets for further assessment and intervention. The early treatment and immediate post-survivorship periods may represent particularly critical time points. Longitudinal studies with larger and diverse samples should further explore HRQoL trajectories in this population.

Impact of Hypertension Duration on the Cardiovascular Benefit of Intensive Blood Pressure Control.

The optimal timing for initiating intensive systolic blood pressure (SBP) treatment remains unclear. While longer hypertension duration is positively associated with increased cardiovascular disease risk, it is unknown whether patients with prolonged hypertension can derive similar benefits from intensive SBP treatment. From the STEP trial (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients), 8442 participants with complete hypertension duration data were categorized by hypertension duration ≤5 years, 5 to 10 years, 10 to 15 years, and >15 years. The primary outcome was a composite of cardiovascular events. Hazard ratios were calculated using the Fine-Gray subdistribution hazard model. The incidences of the primary outcome increased significantly in patients with hypertension over 15 years than those <5 years in the standard SBP treatment group (adjusted hazard ratios, 1.68 [95% CI, 1.11-2.56]) but not in the intensive treatment group. Each 1-year increase in hypertension duration continuously increased the adjusted risk of major cardiovascular events by 4% (95% CI, 1.01-1.08) up to 20 years, plateauing at an adjusted hazard ratio of 2.27 (95% CI, 1.28-4.04). After intensive SBP treatment, the incidences of major cardiovascular events were similar across different hypertension duration groups, which were 2.22%, 1.69%, 3.02%, and 2.52%, respectively (P>0.05). Subgroup analyses indicated a potential sex difference in this relationship between hypertension duration and the primary outcome in the standard SBP treatment group (Pinteraction=0.05). Initiating intensive SBP treatment at any stage of hypertension duration could reduce cardiovascular disease risk to a comparable level. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03015311.

Inquiry and argumentation skill development work in conjunction

The argument and inquiry families of scientific thinking skills overlap. Yet they rarely are investigated together, with researchers instead focusing on one or the other. Here we hypothesize that inclusion of an additional intervention focused on inquiry will enhance the outcome of an established intervention known to be successful in developing argument skills, compared to the argument intervention alone. An Argument only (A) and an Argument and Inquiry (A&I) group of young adolescents participated in one or the other of these intensive intervention groups for four hours daily over a two-week period. Both groups made progress in argument skills as expected, but the A&I group showed greater gains in use of evidence to support claims, stronger forms of counterargument, and integrative however arguments that connect opposing claims to one another. The A&I group showed a particular advantage in reconciling contrasting claims, an epistemological understanding that lies at the core of scientific thinking. These findings suggest the value of conceptualizing argument skill development in a broader framework that includes an investigative component as well as the skill of coordinating claims and evidence that is fundamental to argument.

Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial

Uncertainty exists about whether lowering systolic blood pressure to less than 120 mm Hg is superior to that of less than 140 mm Hg, particularly in patients with diabetes and patients with previous stroke. In this open-label, blinded-outcome, randomised controlled trial, participants with high cardiovascular risk were enrolled from 116 hospitals or communities in China. We used minimised randomisation to assign participants to intensive treatment targeting standard office systolic blood pressure of less than 120 mm Hg or standard treatment targeting less than 140 mm Hg. The primary outcome was a composite of myocardial infarction, revascularisation, hospitalisation for heart failure, stroke, or death from cardiovascular causes, assessed by the intention-to-treat principle. This trial was registered with ClinicalTrials.gov, NCT04030234. Between Sept 17, 2019, and July 13, 2020, 11 255 participants (4359 with diabetes and 3022 with previous stroke) were assigned to intensive treatment (n=5624) or standard treatment (n=5631). Their mean age was 64·6 years (SD 7·1). The mean systolic blood pressure throughout the follow-up (except the first 3 months of titration) was 119·1 mm Hg (SD 11·1) in the intensive treatment group and 134·8 mm Hg (10·5) in the standard treatment group. During a median of 3·4 years of follow-up, the primary outcome event occurred in 547 (9·7%) participants in the intensive treatment group and 623 (11·1%) in the standard treatment group (hazard ratio [HR] 0·88, 95% CI 0·78-0·99; p=0·028). There was no heterogeneity of effects by diabetes status, duration of diabetes, or history of stroke. Serious adverse events of syncope occurred more frequently in the intensive treatment group (24 [0·4%] of 5624) than in standard treatment group (eight [0·1%] of 5631; HR 3·00, 95% CI 1·35-6·68). There was no significant between-group difference in the serious adverse events of hypotension, electrolyte abnormality, injurious fall, or acute kidney injury. For hypertensive patients at high cardiovascular risk, regardless of the status of diabetes or history of stroke, the treatment strategy of targeting systolic blood pressure of less than 120 mm Hg, as compared with that of less than 140 mm Hg, prevents major vascular events, with minor excess risk. The Ministry of Science and Technology of China and Fuwai Hospital. For the Mandarin translation of the abstract see Supplementary Materials section.

Association between longitudinal changes in body composition and the risk of kidney outcomes in participants with overweight/obesity and type 2 diabetes mellitus.

To assess the relationship of longitudinal changes in fat mass (FM), lean mass (LM) and waist circumference (WC) with incident kidney outcomes in people with overweight/obesity and type 2 diabetes mellitus (T2DM). A total of 3927 participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 from the Look AHEAD (Action for Health in Diabetes) trial were included. The primary outcome was kidney outcomes, defined as a decrease in eGFR of at least 40% from baseline at follow-up visit, or end-stage kidney disease. During a median follow-up of 8.0 years, 450 kidney outcomes were documented after the first 1 year. In the intensive lifestyle intervention (ILI) group, reductions in FM (per 10% decrease, adjusted hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.69-0.94) and WC (per 10% decrease, adjusted HR 0.72, 95% CI 0.59-0.88) from baseline to 1-year follow-up were significantly associated with a lower risk of kidney outcomes. The change in LM was not significantly associated with risk of kidney outcomes (per 10% decrease, adjusted HR 0.78, 95% CI 0.58-1.06). In the diabetes support and education group (control group), no significant association was found between changes in body composition and kidney outcomes. Similar results were observed for the 4-year changes in body composition. In this post hoc analysis of the Look AHEAD trial, longitudinal declines in FM and WC were associated with a lower risk of kidney outcomes in the ILI group in participants with overweight/obesity and T2DM.

Association of intensive blood pressure management with cardiovascular outcomes in patients using multiple classes of antihypertensive medications: a post-hoc analysis of the STEP Trial

High medication burden is associated with poor treatment effect and high risk of cardiovascular outcomes. This study aimed to investigate the association between the antihypertensive medication burden and cardiovascular outcomes in the STEP trial. This post-hoc analysis of the STEP trial enrolled 8511 participants, including 8041 with low burden and 470 with high burden. High antihypertensive medication burden was defined as being treated with ≥3 different classes of prescribed antihypertensive medications. The primary outcome was a composite of cardiovascular outcomes. Fine-Gray model was used in this study. Among all participants, high antihypertensive medication burden was associated with a higher risk of the primary outcome compared with low medication burden (HR, 1.52; 95% CI, 1.03–2.24), which was consistent in the standard group (HR, 1.95; 95% CI, 1.20–3.18) and the intensive group (HR, 1.10; 95% CI, 0.57–2.13; Pinteraction = 0.18). The beneficial effects of intensive systolic blood pressure (SBP) control on the primary outcome remained significant in the high burden group (HR, 0.42; 95% CI, 0.19–0.95) and the low burden group (HR, 0.79; 95% CI, 0.63–0.98; Pinteraction = 0.18). At 24 months, the percentage of participants achieving the target SBP was lower in the high medication burden group (risk ratio, 0.93; 95% CI, 0.89–0.98). In both standard and intensive treatment groups, participants with a high medication burden were harder to achieve the target SBP (Pinteraction = 0.65). High antihypertensive medication burden was associated with worse SBP control and a greater risk of cardiovascular events. Intensive SBP control showed cardiovascular benefits in both medication burden groups. Trial registration: STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.

Intensive Glycemic Management Is Associated With Reduced Retinal Structure Abnormalities on Ocular Coherence Tomography in the DCCT/EDIC Study.

To investigate quantitative and qualitative changes in retinal structure using optical coherence tomography (OCT) and their associations with systemic or other risk factors in individuals with type 1 diabetes (T1D). In the Epidemiology of Diabetes Interventions and Complications (EDIC) study, OCT images were obtained during study years 25-28 (2019-2022) in 937 participants; 54% and 46% were from the original intensive (INT) and conventional (CONV) glycemic management treatment groups, respectively. Average age for participants was 61 years old, diabetes duration 39 years, and HbA1c 7.6%. Participants originally in the CONV group were more likely to have disorganization of retinal inner layers (DRIL) (CONV 27.3% vs. INT 18.7%; P = 0.0003), intraretinal fluid (CONV 24.4% vs. INT 19.2%; P = 0.0222), and intraretinal cysts (CONV 20.8% vs. INT 16.6%; P = 0.0471). In multivariable models, sex, age, smoking, mean updated systolic blood pressure, and history of "clinically significant" macular edema (CSME) and of anti-VEGF treatment were independently associated with changes in central subfield thickness, while HbA1c, BMI, and history of CSME and of ocular surgery were associated with DRIL. Visual acuity (VA) decline was associated with significant thinning of all retinal subfields except for the central and inner nasal subfields. Early intensive glycemic management in T1D is associated with a decreased risk of DRIL. This important morphological abnormality was associated with a history of macular edema, a history of ocular surgery, and worse VA. This study reveals benefits of intensive glycemic management on the retina beyond features detected by fundus photographs and ophthalmoscopy.

Blood Pressure after Successful Endovascular Therapy: A Systematic Review and Meta-Analysis of Randomized Control Trials.

There are limited data evaluating the optimum blood pressure (BP) goal post mechanical thrombectomy (MT) and its effect on outcomes of patients with large vessel occlusions (LVO). The objective of this study was to compare the efficacy and safety of intensive versus conventional BP control after reperfusion with MT via a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched PubMed and Embase to obtain articles related to BP control post MT through September 2023. The primary outcome was functional independence (modified Rankin Scale [mRS] 0-2) at 3 months, while secondary outcomes included excellent outcome (mRS 0-1), symptomatic intracranial hemorrhage (sICH), and mortality. Four RCTs with 1,566 patients (762 randomized into intensive BP control vs. 806 randomized into conventional BP control) were included. Analysis showed that there was a lower likelihood of functional independence (mRS 0-2: odds ratio [OR]: 0.68, 95% confidence interval [CI] 0.51-0.91, p = 0.009) in the more intensive treatment group compared with the conventional treatment group. There was no statistically significant difference in achieving excellent outcome (mRS0-1: OR: 0.82, 95% CI: 0.63-1.07; p = 0.15), risk of sICH or mortality. This systematic review and meta- analysis Indicates that in patients who achieved successful MT for acute ischemic stroke with LVO, intensive BP control was associated with a lower likelihood of functional independence at 3 months without significant difference in likelihood of achieving excellent outcome, sICH risk, or mortality. ANN NEUROL 2024;95:858-865.

Family members’ and friends’ reports after standard and intensive group treatment for social communication difficulties following acquired brain injury – a mixed method approach

ABSTRACT Objective To examine family members/friends’ perception of change following standard and intensive group interactive structured treatment (GIST) for persons with social communication difficulties (SCDs). Methods A parallel mixed methods design combining data from questionnaires, the Goal Attainment Scale, and interviews. Participants Forty-nine adult (>18 years) family members/friends (69.4% female) of persons with SCDs and acquired brain injury (ABI) (cohabitating partner, 53.1%; other relatives, 30.6%; friends, 16.3%). Intervention Standard GIST consisted of 12 weekly outpatient sessions (2.5 h). Intensive GIST consisted of 4 weeks of inpatient rehabilitation (2 × 3 days/week, 2 × 4 days/week). Both treatments included 3- and 6-month follow-ups. Main outcome measures Quantitative measures (n = 49) included the following informant reports: Latrobe Communication Questionnaire (LCQ), Social Communication Skills Questionnaire-Adapted (SCSQ-A), Behavior Rating Inventory for Executive Functions-Adult version (BRIEF-A), and Goal Attainment Scale. The qualitative measure (n=9) was an interview performed at 6-month follow-up. Results Converging results were found, suggesting a perceived positive change over time for both standard and intensive GIST, with no substantial differences reported between the treatments. Conclusions Family members/friends reported improved social communication skills of the persons with SCDs following standard and intensive GIST. However, the integration of data showed the complexity of assessing SCDs and the need for further investigation.

Abstract WP196: Blood Pressure After Endovascular Therapy: A Systematic Review and Metanalysis of Randomized Control Trials

Background and Objectives: There are limited data evaluating the optimum blood pressure (BP) goal post mechanical thrombectomy (MT) and its effect on outcomes of patients with large vessel occlusions (LVO). The objective of this study was to compare the efficacy and safety of intensive versus less intensive blood pressure control after reperfusion with MT via a systematic review and meta-analysis of randomized controlled trials (RCTs). Methods: We searched the PubMed, and Embase to obtain articles related to blood pressure control post MT through September, 2023. The primary outcome was functional independence (modified Rankin Scale [mRS] 0-2) at 3 months. Effect sizes were computed as odd ratio (OR) with random-effect or fixed-effect models. Results: Four Randomized Clinical Trials (RCTs) with 1566 patients (762 randomized into intensive blood pressure control vs. 806 randomized into loess intensive blood pressure control) were included. The RCT analysis showed that the likehood of functional independence was less in the more intensive treatment group compared with the less intensive treatment group functional independence (mRS 0-2: OR 0.66, 95% CI 0.54-0.89, P &lt; 0.001). There was no significant increasing the risk of symptomatic intracranial hemorrhage (sICH: OR 1.14, 95% CI: 0.77-1.69, P = 0.51), or mortality ( mortality 1.22, 95% CI: 0.90-1.66, P =0.19). Conclusion: This systematic review and meta-analysis indicate that in patients who achieved successful MT for acute ischemic stroke with LVO, intensive BP control was associated with lower likehood of functional independence at 3 months without significant difference in sICH or mortality risk. Results of upcoming RCTs may provide further insight.

Abstract 149: Different Response to Blood Pressure Reduction in Lobar and Deep Intracerebral Hemorrhage

Background: Blood pressure (BP) reduction is associated with better neuroimaging and clinical outcomes in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH). Because this evidence comes from studies that overwhelmingly enrolled deep hemorrhages, the impact of BP reduction in patients with lobar ICH remains understudied. Methods: We re-analyzed data from the pivotal Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 (ATACH-2) study. We included all patients with available neuroimaging data. Participants were randomized to either intensive (systolic BP target 110-139 mmHg) or standard (systolic BP target 140-179 mmHg) acute BP lowering. The main outcome measures were hematoma expansion &gt; 6 mL in the first 24 hours (HE), poor functional outcome (3-month mRS 4-6) and renal adverse events (RAE) until day 7 or hospital discharge. We fitted multivariable logistic regression models to test for association between the intervention and our outcomes of interest. Covariates included sex, age, race and ethnicity, and baseline ICH volume. Results: Among 1,000 patients enrolled in ATACH-2, 875 (87.5%) with complete data were included (88.9% deep hemorrhages and 11.1% lobar hemorrhages). The baseline characteristics of the intensive and standard treatment groups remained balanced as in the original study (all comparisons p &gt;0.05). Multivariable logistic regression showed that intensive BP reduction decreased the risk of HE (OR 0.60, 95%CI 0.39-0.90; p=0.02) and increased the risk of RAE (OR 2.53, 95%CI 1.40-4.77; p=0.003) in patients with deep, but not lobar ICH (HE, OR: 0.89; 95% CI= 0.31 - 2.52; p=0.83 and RAE, OR: 0.46; 95% CI= 0.04 - 5.10; p=0.53). Intensive BP reduction was not associated with improved mRS in either deep (OR: 0.96; 95 % CI= 0.68 - 1.37; p= 0.82) nor lobar (OR: 0.66; 95% CI= 0.16 - 2.42; p= 0.54) ICH. Conclusion: The impact of intensive blood pressure lowering differs in deep and lobar ICH. These results emphasize the need for a better understanding about biologic differences in ICH, which may have therapeutic implications.

Effects of intensive glycemic control on microvascular outcomes in type 2 diabetes mellitus are modified by long-term HbA1c variability: A post hoc analysis of the ACCORD trial

AimsTo assess the impact of long-term visit-to-visit variability in HbA1c on microvascular outcomes in type 2 diabetes mellitus (T2DM), and its influence on the effects of intensive glycemic control. MethodsIncluded were participants with T2DM enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) who had at least three measurements of HbA1c prior to new-onset microvascular outcomes, namely nephropathy, retinopathy and neuropathy. Variability in HbA1c was defined as the coefficient of variation (CV) across HbA1c measurements obtained from enrollment to the transition from intensive to standard glycemic therapy. ResultsDuring a median of 22,005, 23,121, and 13,080 person-years of follow-up, 2,905 nephropathy, 2,655 retinopathy, and 1,974 neuropathy cases were recorded, respectively. Median CV (IQR) was 7.91 % (5.66 %-10.76 %) in the standard treatment group and 9.79 % (7.32 %-13.35 %) in the intensive treatment group. In the standard treatment group, lower HbA1c-CV (the first versus the second quartile) was associated with a higher risk of all microvascular outcomes, while higher HbA1c-CV (the fourth quartile) was associated with a higher risk of nephropathy only. In the intensive treatment group, only higher HbA1c-CV was associated with a higher risk of developing the microvascular outcomes. Intensive therapy reduced all microvascular outcomes among individuals with lower HbA1c-CV, but increased the risk among those with the highest HbA1c-CV (all P values for interaction < 0.0001). For example, hazard ratios (95 % CI) of retinopathy comparing intensive with standard treatments were 0.65 (0.56–0.75), 0.84 (0.71–0.98), 0.97 (0.82–1.14) and 1.28 (1.08–1.53) across the lowest to the highest quartiles of HbA1c variability. ConclusionsThe effects of intensive glycemic control on microvascular outcomes in T2DM appear to be modified by the variability of HbA1c during the treatment process, suggesting the significance of dynamic monitoring of HbA1c levels and timely adjustments to the therapeutic strategy among individuals with a high HbA1c variability.

Remnant cholesterol and intensive blood pressure control in older patients with hypertension: a post hoc analysis of the STEP randomized trial†.

Emerging evidence shows a close relationship between remnant cholesterol (RC) and hypertension. However, it is unknown whether RC is associated with the effects of intensive systolic blood pressure (SBP) lowering on cardiovascular outcomes. We performed a post hoc analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Participants were randomly allocated to intensive (110 to <130 mmHg) or standard (130 to <150 mmHg) treatment groups. The effects of intensive SBP lowering on the primary composite outcome (stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, or cardiovascular death), the components thereof, and all-cause mortality were analysed by the tertile of baseline RC (lowest, middle, and highest). We followed 8206 patients for 3.33 years (median). The adjusted hazard ratios (HRs) [95% confidence interval (CI)] for the primary outcome were 1.06 (0.73-1.56), 0.58 (0.38-0.87), and 0.67 (0.46-0.96) in the lowest, middle, and highest RC tertiles, respectively (P for interaction = 0.11). However, significant heterogeneity in the treatment effects was observed when comparing the upper two tertiles with the lowest tertile (P for interaction = 0.033). For all-cause mortality, the adjusted HRs (95% CI) were 2.48 (1.30-4.73), 1.37 (0.71-2.65), and 0.42 (0.22-0.80) in the lowest, middle, and highest RC tertiles, respectively (P for interaction <0.0001). Baseline RC concentrations were associated with the effects of intensive SBP lowering on the primary composite cardiovascular outcome and all-cause mortality in hypertensive patients. These results are hypothesis-generating and merit further study. STEP ClinicalTrials.gov number: NCT03015311.

TP53-Mutated Acute Myeloid Leukemia Patients Treated with Intensive Therapies Have Superior Outcomes: A Single Institution, Retrospective Study

Background: Mutations in TP53, found in 5-20% of acute myeloid leukemia (AML), confer poor prognosis and are associated with high rates of therapy resistance, high relapse rates, and dismal overall survival (OS). Recent advances have provided a variety of options for up-front AML therapy including a liposomal preparation of standard-of-care chemotherapy (CPX-351) and venetoclax-based combinations. Due to known poor outcomes with intensive chemotherapy, many providers are favoring less intense strategies for patients with TP53 mutant AML, but these approaches have not been directly compared for this patient subgroup. Strategies for treating TP53 mutant AML are highly heterogeneous and optimal treatment strategies have not been defined in this setting. We performed a retrospective study to compare the clinical outcomes of TP53 mutant AML patients treated at our center. Methods: The study was a single-center, retrospective cohort analysis conducted at the University of Minnesota. Adult patients (age ≥18 years) with the diagnosis of AML or myeloid sarcoma between January 1, 2014 and July 31, 2022 who have next-generation sequencing panel confirming a pathogenic TP53 mutation and received front-line therapy for AML at our center were included in this study. Kaplan-Meier analysis was used to estimate the probabilities of OS, defined as the date of treatment initiation to the date of death from any cause or last follow-up. Results: Our study includes 88 patients with TP53 mutant AML with available clinical data in an AML registry at our institution. Baseline demographic and clinical characteristics are summarized in Table 1. The median age at diagnosis was 67 years (range 28-87) with male predominance (65.9%). Among this, 15/88 patients (17.1%) had therapy-related AML and 40/88 patients (45.5%) had secondary AML. The median bone marrow blast percentage at diagnosis was 31% and peripheral blast percentage was 9%. The majority of patients have high variant allelic frequency (VAF, 71.9% with VAF &amp;gt; 0.4 for patients with available VAF data) and ASXL1 was the most frequent co-mutation identified followed by KRAS and NRAS. Treatment regimens were classified as intensive or nonintensive. Intensive treatment regimens included infusional cytarabine with either daunorubicin or idarubicin (7+3), liposomal cytarabine and daunorubicin (CPX-351), and mitoxantrone, etoposide and cytarabine (MEC). Nonintensive regimens included hypomethylating agents (decitabine or azacitidine) with or without venetoclax and clofarabine with low-dose subcutaneous cytarabine. A total of 66 patients were included in the survival analysis. There was no significant difference in OS between patients aged &amp;lt; 65 years and ≥ 65 years at diagnosis (2-year OS, 11% versus 5%, P=0.76). Superior 2-year OS was observed in patients who received front-line intensive (n = 31) versus nonintensive (n = 35) induction chemotherapy (2-year OS, 13% versus 3%, P=0.01, Figure 1). Patients who received intensive therapy for any line of treatment also demonstrated superior OS compared to those who never received intensive therapy (2-year OS, 12% versus 3%, P=0.02). The rate of achieving complete remission (CR) was higher in patients who received intensive treatment compared to non-intensive therapy in the first-line (51.6% versus 25.7%, P=0.03). Rate of CR at any time was also higher for patients who received intensive treatment for any line of treatment (50% versus 18.2%, P&amp;lt;0.01). Among the intensive first-line treatment group, 7+3 (n = 18) showed superior OS relative to CPX-351 (n = 12) (2-year OS, 22% versus 0%, P=0.03) although there was no significant difference in CR rate (55.6% versus 50%, P=0.77). Furthermore, significant survival benefit was shown in patients who underwent allogeneic hematopoietic cell transplantation compared to patients who had not (2-year OS, 21% versus 4%, P&amp;lt;0.01]). Conclusions: In our cohort, TP53 mutant AML patients treated with intensive chemotherapy and transplant have superior outcomes to those who do not. Since this was a retrospective study, we cannot rule out the possibility that these results are confounded by providers favoring more intensive therapies for fitter patients. However, these data imply that TP53 mutant patients may benefit from more intensive therapy and suggests that future work to define optimal therapy regimens in this patient population may incorporate intensive strategies.

Caracterización de la gravedad del intento de suicidio en adolescentes hospitalizados en un hospital público de Chile.

Adolescent suicide has increased in the Americas. In Chile, at-tempted suicide in adolescents is a public health problem that needs an urgent solution. A quantitative, comparative and retrospective study was conducted to provide the hospital with intervention strategies and articulation with the territorial mental health network. The sociodemographic and clinical aspects of 96 records of adolescents hospitalized for attempted suicide between Janu-ary 2017 and December 2018 were reviewed, compared, and related. Two study groups were formed: Group I, 14 adolescents previously hospitalized in the Intensive Treatment Unit and Group II, 82 adolescents who did not require this unit. Gender, age, education, history of sexual abuse, diagnoses of mental disorders, co-morbidities, previous mental health consultations, and caregivers with mental disorders were studied. Descriptive statistics and odds ratios were used. In group I, with 92% male adolescents, severe depression was observed in 57% of cases, and 100% of its members suffered sexual abuse; in group II, with 91% female adolescents, 79% moderate depression was found, 85.3% ab-normal personality development and 70% of its members suffered sexual abuse. Sexual abuse explained the highest percentage of the variance (29%). It is con-cluded that the hospital must consider the distinctive characteristics of the study groups and coordinate with the territorial network of mental health the continuity of care in its interventions.

Intensive blood pressure control on arterial stiffness among older patients with hypertension.

Arterial stiffening increases with age and blood pressure and is associated with cardiovascular disease (CVD), but the relationship between blood pressure lowering and arterial stiffening is still uncertain, especially in older people. This study aimed to evaluate the effect of intensive blood pressure treatment on the progression of arterial stiffness and risk of CVD in older patients with hypertension. The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial was a multicenter, randomized, controlled trial performed at 42 clinical centers throughout China, and 8511 patients aged 60-80 years with essential hypertension were enrolled and randomly assigned to systolic blood pressure (SBP) target of 110 mmHg to <130 mmHg (intensive treatment) or 130 mmHg to <150 mmHg (standard treatment). Patients underwent repeated examinations of the brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) at baseline, and the arterial stiffness was evaluated at the 3-year follow-up. A total of 5339 patients who had twice repeated measurements were included in this study. Changes in arterial stiffness between the intensive and standard treatment groups were analyzed using a multivariate linear regression model. The Cox proportional hazard regression model was used to evaluate the effect of intensive treatment on primary CVD outcomes. The changes in baPWV were 61.5 cm/s (95% confidence interval [CI]: 49.8-73.2 cm/s) in the intensive treatment group and 98.4 cm/s (95% CI: 86.7-110.1 cm/s) in the standard treatment group ( P <0.001). Intensive treatment significantly delayed the progression of arterial stiffness, with an annual change of 23.1 cm·s -1 ·year -1vs. 36.7 cm·s -1 ·year -1 of baPWV in the intensive and standard treatment groups, respectively. During a median follow-up period of 3.36 years, primary CVD outcomes occurred in 77 (2.9%) patients in the intensive treatment group compared with 93 (3.5%) in the standard treatment group. Intensive treatment resulted in a significantly lower CVD risk in patients aged 70-80 years or with SBP <140 mmHg. Intensive blood pressure control with an SBP target of 110 mmHg to <130 mmHg could delay the progression of arterial stiffness and reduce the risk of CVD in older patients with hypertension. http://www.clinicaltrials.gov ; No. NCT03015311.