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Clinical Outcomes in Patients With Isolated or Combined Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State: A Retrospective, Hospital-Based Cohort Study

OBJECTIVE

Many patients with hyperglycemic crises present with combined features of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). The implications of concomitant acidosis and hyperosmolality are not well known. We investigated hospital outcomes in patients with isolated or combined hyperglycemic crises.

RESEARCH DESIGN AND METHODS

We analyzed admissions data listing DKA or HHS at two academic hospitals. We determined 1) the frequency distributions of HHS, DKA, and combined DKA-HHS (DKA criteria plus elevated effective osmolality); 2) the relationship of markers of severity of illness and clinical comorbidities with 30-day all-cause mortality; and 3) the relationship of hospital complications associated with insulin therapy (hypoglycemia and hypokalemia) with mortality.

RESULTS

There were 1,211 patients who had a first admission with confirmed hyperglycemic crises criteria, 465 (38%) who had isolated DKA, 421 (35%) who had isolated HHS, and 325 (27%) who had combined features of DKA-HHS. After adjustment for age, sex, BMI, race, and Charlson Comorbidity Index score, subjects with combined DKA-HHS had higher in-hospital mortality compared with subjects with isolated hyperglycemic crises (adjusted odds ratio [aOR] 2.7; 95% CI 1.4, 4.9; P = 0.0019). In all groups, hypoglycemia (<40 mg/dL) during treatment was associated with a 4.8-fold increase in mortality (aOR 4.8; 95% CI 1.4, 16.8). Hypokalemia ≤3.5 mEq/L was frequent (55%). Severe hypokalemia (≤2.5 mEq/L) was associated with increased inpatient mortality (aOR 4.9; 95% CI 1.3, 18.8; P = 0.02).

CONCLUSIONS

Combined DKA-HHS is associated with higher mortality compared with isolated DKA or HHS. Severe hypokalemia and severe hypoglycemia are associated with higher hospital mortality in patients with hyperglycemic crises.




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Redesigning Primary Care to Improve Diabetes Outcomes (the UNITED Study)

OBJECTIVE

The effective redesign of primary care delivery systems to improve diabetes care requires an understanding of which particular components of delivery consistently lead to better clinical outcomes. We identified associations between common systems of care management (SysCMs) and the frequency of meeting standardized performance targets for Optimal Diabetes Care (NQF#0729) in primary care practices.

RESEARCH DESIGN AND METHODS

A validated survey of 585 eligible family or general internal medicine practices seeing ≥30 adult patients with diabetes in or near Minnesota during 2017 evaluated the presence of 62 SysCMs. From 419 (72%) practices completing the survey, NQF#0729 was determined in 396 (95%) from electronic health records, including 215,842 patients with type 1 or type 2 diabetes.

RESULTS

Three SysCMs were associated with higher rates of meeting performance targets across all practices: 1) a systematic process for shared decision making with patients (P = 0.001), 2) checklists of tests or interventions needed for prevention or monitoring of diabetes (P = 0.002), and 3) physician reminders of guideline-based age-appropriate risk assessments due at the patient visit (P = 0.002). When all three were in place, an additional 10.8% of the population achieved recommended performance measures. In subgroup analysis, 15 additional SysCMs were associated with better care in particular types of practices.

CONCLUSIONS

Diabetes care outcomes are better in primary care settings that use a patient-centered approach to systematically engage patients in decision making, remind physicians of age-appropriate risk assessments, and provide checklists for recommended diabetes interventions. Practice size and location are important considerations when redesigning delivery systems to improve performance.




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Update on Cardiovascular Outcomes at 30 Years of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

John M. Lachin
Jan 1, 2014; 37:39-43
DCCT/EDIC 30th Anniversary Summary Findings




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Cardiovascular Outcomes Trials in Type 2 Diabetes: Where Do We Go From Here? Reflections From a Diabetes Care Editors Expert Forum

William T. Cefalu
Jan 1, 2018; 41:14-31
Diabetes Care Expert Forum




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Standardizing Clinically Meaningful Outcome Measures Beyond HbA1c for Type 1 Diabetes: A Consensus Report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endo

Gina Agiostratidou
Dec 1, 2017; 40:1622-1630
Continuous Glucose Monitoring and Risk of Hypoglycemia




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Intensive Diabetes Treatment and Cardiovascular Outcomes in Type 1 Diabetes: The DCCT/EDIC Study 30-Year Follow-up

The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group
May 1, 2016; 39:686-693
Cardiovascular Disease and Diabetes




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Can a Shift in Fuel Energetics Explain the Beneficial Cardiorenal Outcomes in the EMPA-REG OUTCOME Study? A Unifying Hypothesis

Sunder Mudaliar
Jul 1, 2016; 39:1115-1122
Diabetes Care Symposium




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Improvement in Outcomes of Clinical Islet Transplantation: 1999-2010

Franca B. Barton
Jul 1, 2012; 35:1436-1445
Diabetes Care Symposium




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CV Protection in the EMPA-REG OUTCOME Trial: A "Thrifty Substrate" Hypothesis

Ele Ferrannini
Jul 1, 2016; 39:1108-1114
Diabetes Care Symposium




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Cardiovascular Outcomes Trials in Type 2 Diabetes: Where Do We Go From Here? Reflections From a Diabetes Care Editors Expert Forum

William T. Cefalu
Jan 1, 2018; 41:14-31
Diabetes Care Expert Forum




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Diabetes Is Associated With Worse Long-term Outcomes in Young Adults After Myocardial Infarction: The Partners YOUNG-MI Registry

OBJECTIVE

We sought to determine the prevalence of diabetes and associated cardiovascular outcomes in a contemporary cohort of young individuals presenting with their first myocardial infarction (MI) at age ≤50 years.

RESEARCH DESIGN AND METHODS

We retrospectively analyzed records of patients presenting with a first type 1 MI at age ≤50 years from 2000 to 2016. Diabetes was defined as a hemoglobin A1c ≥6.5% (48 mmol/mol) or a documented diagnosis of or treatment for diabetes. Vital status was ascertained for all patients, and cause of death was adjudicated.

RESULTS

Among 2,097 young patients who had a type 1 MI (mean age 44.0 ± 5.1 years, 19.3% female, 73% white), diabetes was present in 416 (20%), of whom 172 (41%) were receiving insulin. Over a median follow-up of 11.2 years (interquartile range 7.3–14.2 years), diabetes was associated with a higher all-cause mortality (hazard ratio 2.30; P < 0.001) and cardiovascular mortality (2.68; P < 0.001). These associations persisted after adjusting for baseline covariates (all-cause mortality: 1.65; P = 0.008; cardiovascular mortality: 2.10; P = 0.004).

CONCLUSIONS

Diabetes was present in 20% of patients who presented with their first MI at age ≤50 years and was associated with worse long-term all-cause and cardiovascular mortality. These findings highlight the need for implementing more-aggressive therapies aimed at preventing future adverse cardiovascular events in this population.




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Renal and Cardiovascular Outcomes After Weight Loss From Gastric Bypass Surgery in Type 2 Diabetes: Cardiorenal Risk Reductions Exceed Atherosclerotic Benefits

OBJECTIVE

We examined detailed renal and cardiovascular (CV) outcomes after gastric bypass (GBP) surgery in people with obesity and type 2 diabetes mellitus (T2DM), across several renal function categories, in a nationwide cohort study.

RESEARCH DESIGN AND METHODS

We linked data from the National Diabetes Register and the Scandinavian Obesity Surgery Register with four national databases holding information on socioeconomic variables, medications, hospitalizations, and causes of death and matched 5,321 individuals with T2DM who had undergone GBP with 5,321 who had not (age 18–65 years, mean BMI >40 kg/m2, mean follow-up >4.5 years). The risks of postoperative outcomes were assessed with Cox regression models.

RESULTS

During the first years postsurgery, there were small reductions in creatinine and albuminuria and stable estimated glomerular filtration rate (eGFR) in the GBP group. The incidence rates of most outcomes relating to renal function, CV disease, and mortality were lower after GBP, being particularly marked for heart failure (hazard ratio [HR] 0.33 [95% CI 0.24, 0.46]) and CV mortality (HR 0.36 [(95% CI 0.22, 0.58]). The risk of a composite of severe renal disease or halved eGFR was 0.56 (95% CI 0.44, 0.71), whereas nonfatal CV risk was lowered less (HR 0.82 [95% CI 0.70, 0.97]) after GBP. Risks for key outcomes were generally lower after GBP in all eGFR strata, including in individuals with eGFR <30 mL/min/1.73 m2.

CONCLUSIONS

Our data suggest robust benefits for renal outcomes, heart failure, and CV mortality after GBP in individuals with obesity and T2DM. These results suggest that marked weight loss yields important benefits, particularly on the cardiorenal axis (including slowing progression to end-stage renal disease), whatever the baseline renal function status.




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The Effects of Intensive Glycemic Control on Clinical Outcomes Among Patients With Type 2 Diabetes With Different Levels of Cardiovascular Risk and Hemoglobin A1c in the ADVANCE Trial

OBJECTIVE

To study whether the effects of intensive glycemic control on major vascular outcomes (a composite of major macrovascular and major microvascular events), all-cause mortality, and severe hypoglycemia events differ among participants with different levels of 10-year risk of atherosclerotic cardiovascular disease (ASCVD) and hemoglobin A1c (HbA1c) at baseline.

RESEARCH DESIGN AND METHODS

We studied the effects of more intensive glycemic control in 11,071 patients with type 2 diabetes (T2D), without missing values, in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, using Cox models.

RESULTS

During 5 years’ follow-up, intensive glycemic control reduced major vascular events (hazard ratio [HR] 0.90 [95% CI 0.83–0.98]), with the major driver being a reduction in the development of macroalbuminuria. There was no evidence of differences in the effect, regardless of baseline ASCVD risk or HbA1c level (P for interaction = 0.29 and 0.94, respectively). Similarly, the beneficial effects of intensive glycemic control on all-cause mortality were not significantly different across baseline ASCVD risk (P = 0.15) or HbA1c levels (P = 0.87). The risks of severe hypoglycemic events were higher in the intensive glycemic control group compared with the standard glycemic control group (HR 1.85 [1.41–2.42]), with no significant heterogeneity across subgroups defined by ASCVD risk or HbA1c at baseline (P = 0.09 and 0.18, respectively).

CONCLUSIONS

The major benefits for patients with T2D in ADVANCE did not substantially differ across levels of baseline ASCVD risk and HbA1c.




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Continuous Glucose Monitoring in Pregnancy: Importance of Analysing Temporal Profiles to Understand Clinical Outcomes

OBJECTIVE

To determine if temporal glucose profiles differed between 1) women who were randomized to real-time continuous glucose monitoring (RT-CGM) or self-monitored blood glucose (SMBG), 2) women who used insulin pumps or multiple daily insulin injections (MDIs), and 3) women whose infants were born large for gestational age (LGA) or not, by assessing CGM data obtained from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT).

RESEARCH DESIGN AND METHODS

Standard summary metrics and functional data analysis (FDA) were applied to CGM data from the CONCEPTT trial (RT-CGM, n = 100; SMBG, n = 100) taken at baseline and at 24- and 34-weeks gestation. Multivariable regression analysis determined if temporal differences in 24-h glucose profiles occurred between comparators in each of the three groups.

RESULTS

FDA revealed that women using RT-CGM had significantly lower glucose (0.4–0.8 mmol/L [7–14 mg/dL]) for 7 h/day (0800 h–1200 h and 1600 h–1900 h) compared with those with SMBG. Women using pumps had significantly higher glucose (0.4–0.9 mmol/L [7–16 mg/dL]) for 12 h/day (0300 h to 0600 h, 1300 h to 1800 h, and 2030 h to 0030 h) at 24 weeks with no difference at 34 weeks compared with MDI. Women who had an LGA infant ran a significantly higher glucose by 0.4–0.7 mmol/L (7–13 mg/dL) for 4.5 h/day at baseline; by 0.4–0.9 mmol/L (7–16 mg/dL) for 16 h/day at 24 weeks; and by 0.4–0.7 mmol/L (7–13 mg/dL) for 14 h/day at 34 weeks.

CONCLUSIONS

FDA of temporal glucose profiles gives important information about differences in glucose control and its timing, which are undetectable by standard summary metrics. Women using RT-CGM were able to achieve better daytime glucose control, reducing fetal exposure to maternal glucose.




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Long-term Metabolic and Socioeducational Outcomes of Transient Neonatal Diabetes: A Longitudinal and Cross-sectional Study

OBJECTIVE

Transient neonatal diabetes mellitus (TNDM) occurs during the 1st year of life and remits during childhood. We investigated glucose metabolism and socioeducational outcomes in adults.

RESEARCH DESIGN AND METHODS

We included 27 participants with a history of TNDM currently with (n = 24) or without (n = 3) relapse of diabetes, and 16 non-TNDM relatives known to be carriers of causal genetic defects and currently with (n = 9) or without (n = 7) diabetes. Insulin sensitivity and secretion were assessed by hyperinsulinemic-euglycemic clamp and arginine-stimulation testing in a subset of 8 TNDM participants and 7 relatives carrying genetic abnormalities, with and without diabetes, compared with 17 unrelated control subjects without diabetes.

RESULTS

In TNDM participants, age at relapse correlated positively with age at puberty (P = 0.019). The mean insulin secretion rate and acute insulin response to arginine were significantly lower in TNDM and relatives of participants with diabetes than in control subjects (4.7 [3.6–5.9] vs. 13.4 [11.8–16.1] pmol/kg/min, P < 0.0001; and 84.4 [33.0–178.8] vs. 399.6 [222.9–514.9] µIU/mL, P = 0.0011), but were not different between participants without diabetes (12.7 [10.4–14.3] pmol/kg/min and 396.3 [303.3–559.3] µIU/mL, respectively) and control subjects. Socioeducational attainment was lower in TNDM participants than in the general population, regardless of diabetes duration.

CONCLUSIONS

Relapse of diabetes occurred earlier in TNDM participants compared with relatives and was associated with puberty. Both groups had decreased educational attainment, and those with diabetes had lower insulin secretion capacity; however, there was no difference in insulin resistance in adulthood. These forms of diabetes should be included in maturity-onset diabetes of the young testing panels, and relatives of TNDM patients should be screened for underlying defects, as they may be treated with drugs other than insulin.




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Screening and Treatment Outcomes in Adults and Children With Type 1 Diabetes and Asymptomatic Celiac Disease: The CD-DIET Study

OBJECTIVE

To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD.

RESEARCH DESIGN AND METHODS

Asymptomatic patients (8–45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA1c and continuous glucose monitoring over 12 months.

RESULTS

Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9–8.2%, N = 1,298] vs. 4.7% [95% CI 3.4–5.9%, N = 1,089], P = 0.035) with lower rates of prior CD screening (6.9% vs. 44.2%, P < 0.0001). Fifty-one participants were randomized to a GFD (N = 27) or GCD (N = 24). No HbA1c differences were seen between the groups (+0.14%, 1.5 mmol/mol; 95% CI –0.79 to 1.08; P = 0.76), although greater postprandial glucose increases (4-h +1.5 mmol/L; 95% CI 0.4–2.7; P = 0.014) emerged with a GFD.

CONCLUSIONS

CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.




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Using the BRAVO Risk Engine to Predict Cardiovascular Outcomes in Clinical Trials With Sodium-Glucose Transporter 2 Inhibitors

OBJECTIVE

This study evaluated the ability of the Building, Relating, Assessing, and Validating Outcomes (BRAVO) risk engine to accurately project cardiovascular outcomes in three major clinical trials—BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME), Canagliflozin Cardiovascular Assessment Study (CANVAS), and Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction (DECLARE-TIMI 58) trial—on sodium–glucose cotransporter 2 inhibitors (SGLT2is) to treat patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

Baseline data from the publications of the three trials were obtained and entered into the BRAVO model to predict cardiovascular outcomes. Projected benefits of reducing risk factors of interest (A1C, systolic blood pressure [SBP], LDL, or BMI) on cardiovascular events were evaluated, and simulated outcomes were compared with those observed in each trial.

RESULTS

BRAVO achieved the best prediction accuracy when simulating outcomes of the CANVAS and DECLARE-TIMI 58 trials. For the EMPA-REG OUTCOME trial, a mild bias was observed (~20%) in the prediction of mortality and angina. The effect of risk reduction on outcomes in treatment versus placebo groups predicted by the BRAVO model strongly correlated with the observed effect of risk reduction on the trial outcomes as published. Finally, the BRAVO engine revealed that most of the clinical benefits associated with SGLT2i treatment are through A1C control, although reductions in SBP and BMI explain a proportion of the observed decline in cardiovascular events.

CONCLUSIONS

The BRAVO risk engine was effective in predicting the benefits of SGLT2is on cardiovascular health through improvements in commonly measured risk factors, including A1C, SBP, and BMI. Since these benefits are individually small, the use of the complex, dynamic BRAVO model is ideal to explain the cardiovascular outcome trial results.




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microRNA-21/PDCD4 Proapoptotic Signaling From Circulating CD34+ Cells to Vascular Endothelial Cells: A Potential Contributor to Adverse Cardiovascular Outcomes in Patients With Critical Limb Ischemia

OBJECTIVE

In patients with type 2 diabetes (T2D) and critical limb ischemia (CLI), migration of circulating CD34+ cells predicted cardiovascular mortality at 18 months after revascularization. This study aimed to provide long-term validation and mechanistic understanding of the biomarker.

RESEARCH DESIGN AND METHODS

The association between CD34+ cell migration and cardiovascular mortality was reassessed at 6 years after revascularization. In a new series of T2D-CLI and control subjects, immuno-sorted bone marrow CD34+ cells were profiled for miRNA expression and assessed for apoptosis and angiogenesis activity. The differentially regulated miRNA-21 and its proapoptotic target, PDCD4, were titrated to verify their contribution in transferring damaging signals from CD34+ cells to endothelial cells.

RESULTS

Multivariable regression analysis confirmed that CD34+ cell migration forecasts long-term cardiovascular mortality. CD34+ cells from T2D-CLI patients were more apoptotic and less proangiogenic than control subjects and featured miRNA-21 downregulation, modulation of several long noncoding RNAs acting as miRNA-21 sponges, and upregulation of the miRNA-21 proapoptotic target PDCD4. Silencing miR-21 in control subject CD34+ cells phenocopied the T2D-CLI cell behavior. In coculture, T2D-CLI CD34+ cells imprinted naïve endothelial cells, increasing apoptosis, reducing network formation, and modulating the TUG1 sponge/miRNA-21/PDCD4 axis. Silencing PDCD4 or scavenging reactive oxygen species protected endothelial cells from the negative influence of T2D-CLI CD34+ cells.

CONCLUSIONS

Migration of CD34+ cells predicts long-term cardiovascular mortality in T2D-CLI patients. An altered paracrine signaling conveys antiangiogenic and proapoptotic features from CD34+ cells to the endothelium. This damaging interaction may increase the risk for life-threatening complications.




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The Influence of Baseline Diastolic Blood Pressure on the Effects of Intensive Blood Pressure Lowering on Cardiovascular Outcomes and All-Cause Mortality in Type 2 Diabetes

OBJECTIVE

To examine whether low baseline diastolic blood pressure (DBP) modifies the effects of intensive systolic blood pressure (SBP) lowering on cardiovascular outcomes in type 2 diabetes mellitus (T2DM).

RESEARCH DESIGN AND METHODS

The Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP), a two-by-two factorial randomized controlled trial, examined effects of SBP (<120 vs. <140 mmHg) and glycemic (HbA1c <6% vs. 7.0–7.9% [<42 vs. 53–63 mmol/mol]) control on cardiovascular events in T2DM (N = 4,731). We examined whether effects of SBP control on cardiovascular composite were modified by baseline DBP and glycemic control.

RESULTS

Intensive SBP lowering decreased the risk of the cardiovascular composite (hazard ratio [HR] 0.76 [95% CI 0.59–0.98]) in the standard glycemic arm but not in the intensive glycemic arm (HR 1.06 [95% CI 0.81–1.40]). Spline regression models relating the effects of the intervention on the cardiovascular composite across the range of baseline DBP did not show evidence of effect modification by low baseline DBP for the cardiovascular composite in the standard or intensive glycemic arms. The relation between the effect of the intensive SBP intervention and baseline DBP was similar between glycemic arms for the cardiovascular composite three-way interaction (P = 0.83).

CONCLUSIONS

In persons with T2DM, intensive SBP lowering decreased the risk of cardiovascular composite end point irrespective of baseline DBP in the setting of standard glycemic control. Hence, low baseline DBP should not be an impediment to intensive SBP lowering in patients with T2DM treated with guidelines recommending standard glycemic control.




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Microvascular and Cardiovascular Outcomes According to Renal Function in Patients Treated With Once-Weekly Exenatide: Insights From the EXSCEL Trial

OBJECTIVE

To evaluate the impact of once-weekly exenatide (EQW) on microvascular and cardiovascular (CV) outcomes by baseline renal function in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).

RESEARCH DESIGN AND METHODS

Least squares mean difference (LSMD) in estimated glomerular filtration rate (eGFR) from baseline between the EQW and placebo groups was calculated for 13,844 participants. Cox regression models were used to estimate effects by group on incident macroalbuminuria, retinopathy, and major adverse CV events (MACE). Interval-censored time-to-event models estimated effects on renal composite 1 (40% eGFR decline, renal replacement, or renal death) and renal composite 2 (composite 1 variables plus macroalbuminuria).

RESULTS

EQW did not change eGFR significantly (LSMD 0.21 mL/min/1.73 m2 [95% CI –0.27 to 0.70]). Macroalbuminuria occurred in 2.2% of patients in the EQW group and in 2.5% of those in the placebo group (hazard ratio [HR] 0.87 [95% CI 0.70–1.07]). Neither renal composite was reduced with EQW in unadjusted analyses, but renal composite 2 was reduced after adjustment (HR 0.85 [95% CI 0.74–0.98]). Retinopathy rates did not differ by treatment group or in the HbA1c-lowering or prior retinopathy subgroups. CV outcomes in those with eGFR <60 mL/min/1.73 m2 did not differ by group. Those with eGFR ≥60 mL/min/1.73 m2 had nominal risk reductions for MACE, all-cause mortality, and CV death, but interactions by renal function group were significant for only stroke (HR 0.74 [95% CI 0.58–0.93]; P for interaction = 0.035) and CV death (HR 1.08 [95% CI 0.85–1.38]; P for interaction = 0.031).

CONCLUSIONS

EQW had no impact on unadjusted retinopathy or renal outcomes. CV risk was modestly reduced only in those with eGFR ≥60 mL/min/1.73 m2 in analyses unadjusted for multiplicity.




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A Study of Pregnancy and Birth Outcomes among African-Born Women Living in Utah

Resettled African refugee women may experience particularly acute complications during pregnancy, birth, and the child's early infancy. Yet health care-providers and policymakers may not be aware of the particular challenges that these women and their children face. This report, examining women giving birth in Utah over a seven-year period, compares perinatal complications of the African born and a segment of the U.S. born.




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Diabetes Self-Management in a Community Health Center: Improving Health Behaviors and Clinical Outcomes for Underserved Patients

Daren Anderson
Jan 1, 2008; 26:22-27
Bridges to Excellence




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An unexpected Outcome : The heel prick test.




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The community development programme : evaluation of participation and employment outcomes / Department of the Prime Minister and Cabinet.




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National return to work strategy 2020-2030 : a national strategy to drive and leverage national action to improve return to work outcomes for workers with a work-related injury or illness / Safe Work Australia.




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NCCP: The likely medium- to long-term ecological outcomes of major carp population reductions final report / Nichols S.J., Gawne B., Richards R., Lintermans M. and Thompson R; prepared by the Institute for Applied Ecology, University of Canberra for Fishe




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Are Schools Prepared to Respond to Sex Abuse? Latest Probe Reveals Shortcomings

A federal investigation of Chicago's failures to respond to sexual violence in schools raises troubling questions for school districts nationwide.




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Scalar-on-function regression for predicting distal outcomes from intensively gathered longitudinal data: Interpretability for applied scientists

John J. Dziak, Donna L. Coffman, Matthew Reimherr, Justin Petrovich, Runze Li, Saul Shiffman, Mariya P. Shiyko.

Source: Statistics Surveys, Volume 13, 150--180.

Abstract:
Researchers are sometimes interested in predicting a distal or external outcome (such as smoking cessation at follow-up) from the trajectory of an intensively recorded longitudinal variable (such as urge to smoke). This can be done in a semiparametric way via scalar-on-function regression. However, the resulting fitted coefficient regression function requires special care for correct interpretation, as it represents the joint relationship of time points to the outcome, rather than a marginal or cross-sectional relationship. We provide practical guidelines, based on experience with scientific applications, for helping practitioners interpret their results and illustrate these ideas using data from a smoking cessation study.




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The Effect of Counterfactual Information on Outcome Value Coding in Medial Prefrontal and Cingulate Cortex: From an Absolute to a Relative Neural Code

Adaptive coding of stimuli is well documented in perception, where it supports efficient encoding over a broad range of possible percepts. Recently, a similar neural mechanism has been reported also in value-based decision, where it allows optimal encoding of vast ranges of values in PFC: neuronal response to value depends on the choice context (relative coding), rather than being invariant across contexts (absolute coding). Additionally, value learning is sensitive to the amount of feedback information: providing complete feedback (both obtained and forgone outcomes) instead of partial feedback (only obtained outcome) improves learning. However, it is unclear whether relative coding occurs in all PFC regions and how it is affected by feedback information. We systematically investigated univariate and multivariate feedback encoding in various mPFC regions and compared three modes of neural coding: absolute, partially-adaptive and fully-adaptive.

Twenty-eight human participants (both sexes) performed a learning task while undergoing fMRI scanning. On each trial, they chose between two symbols associated with a certain outcome. Then, the decision outcome was revealed. Notably, in one-half of the trials participants received partial feedback, whereas in the other half they got complete feedback. We used univariate and multivariate analysis to explore value encoding in different feedback conditions.

We found that both obtained and forgone outcomes were encoded in mPFC, but with opposite sign in its ventral and dorsal subdivisions. Moreover, we showed that increasing feedback information induced a switch from absolute to relative coding. Our results suggest that complete feedback information enhances context-dependent outcome encoding.

SIGNIFICANCE STATEMENT This study offers a systematic investigation of the effect of the amount of feedback information (partial vs complete) on univariate and multivariate outcome value encoding, within multiple regions in mPFC and cingulate cortex that are critical for value-based decisions and behavioral adaptation. Moreover, we provide the first comparison of three possible models of neural coding (i.e., absolute, partially-adaptive, and fully-adaptive coding) of value signal in these regions, by using commensurable measures of prediction accuracy. Taken together, our results help build a more comprehensive picture of how the human brain encodes and processes outcome value. In particular, our results suggest that simultaneous presentation of obtained and foregone outcomes promotes relative value representation.




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Influence of Birth Hospital on Outcomes of Ductal-Dependent Cardiac Lesions

It is not known whether birth at a pediatric cardiac specialty center or at a hospital with a higher neonatal level of care affects mortality for infants with ductal-dependent congenital heart disease.

For infants with ductal-dependent congenital heart disease, there is no difference in 90-day mortality for those born at specialty centers versus other centers in the state of Washington. (Read the full article)




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Mortality and Adverse Neurologic Outcomes Are Greater in Preterm Male Infants

Very low birth weight (VLBW) male neonates appear to have increased mortality. VLBW female neonates appear to have better long-term outcomes.

VLBW male neonates have increased mortality and poorer neurological outcome. This gender difference appears to disappear at weeks' gestation. (Read the full article)




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Early Intervention Improves Behavioral Outcomes for Preterm Infants: Randomized Controlled Trial

Prematurely born children have an increased prevalence of behavioral problems in the long term. Knowledge regarding the effects of early intervention programs is sparse, and more randomized controlled trials are warranted.

A modified version of the Mother-Infant Transaction Program showed beneficial effects on behavioral outcomes reported by both parents of preterm infants with birth weights of <2000 g at a corrected age of 5 years. (Read the full article)




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Intellectual, Behavioral, and Social Outcomes of Accidental Traumatic Brain Injury in Early Childhood

Traumatic brain injury in school-aged children is associated with intellectual, behavioral, and social deficits. Research into outcomes of children injured before 3 years of age is limited despite data suggesting a high incidence of injury in this age group.

Results show that a moderate to severe traumatic brain injury before 3 years of age is associated with lowered cognitive function. Furthermore, this study highlights the link between social disadvantage and poor outcomes after traumatic brain injury in early childhood. (Read the full article)




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Perioperative Methylprednisolone and Outcome in Neonates Undergoing Heart Surgery

Recent studies have called into question the benefit of perioperative corticosteroids in children undergoing heart surgery, but have been limited by small sample size, the lack of placebo control, and the grouping of various steroid regimens together in analysis.

We evaluated outcomes across methylprednisolone regimens versus no steroids in a large cohort of neonates and found no mortality or length-of-stay benefit associated with any regimen, and a higher risk of infection in certain subgroups. (Read the full article)




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Intrapartum Temperature Elevation, Epidural Use, and Adverse Outcome in Term Infants

Previous observational studies and randomized trials have reported an association between the use of epidural analgesia for pain relief in labor and intrapartum maternal fever. Studies have also reported an increase in adverse neonatal outcomes with intrapartum maternal fever.

Among low-risk women receiving epidural analgesia, intrapartum maternal temperature >99.5°F was associated with adverse neonatal outcomes, with the rate of adverse outcomes increasing directly with maximum maternal temperature. Without temperature elevation, epidural use was not associated with adverse neonatal outcomes. (Read the full article)




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Stability of Cognitive Outcome From 2 to 5 Years of Age in Very Low Birth Weight Children

Very preterm children are at risk for developmental problems and, therefore, a systematic follow-up is important. However, the relevance of early follow-up of cognitive development has been questioned because of the divergent data on the prognostic value of early measures.

Good stability of cognitive development was found between the ages of 2 and 5 years. Well-conducted assessment of cognitive development in infancy is both reliable to anticipate later development and clinically valuable to identify those children who need developmental support. (Read the full article)




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Sleep-Disordered Breathing in a Population-Based Cohort: Behavioral Outcomes at 4 and 7 Years

Sleep-disordered breathing is associated with neurobehavioral morbidity in children. Prior related research has generally been cross-sectional or short (ie, 1–2 years) follow-up studies of a single symptom (ie, snoring, obstructive sleep apnea, mouth breathing), with limited control for confounders.

Sleep-disordered breathing was assessed as a trajectory of combined symptoms from 6 months to 69 months, in more than 11 000 children. Sleep-disordered breathing was associated with 40% and 60% more behavioral difficulties at 4 and 7 years, respectively. (Read the full article)




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Parental Psychological Well-Being and Behavioral Outcome of Very Low Birth Weight Infants at 3 Years

Preterm infants are at increased risk of behavioral problems, which has been associated with maternal distress. Paternal psychological well-being is less studied. Parents’ concerns may affect their perceptions or attitudes and have negative effects on the behavior of the child.

Parents report more behavior problems in VLBW children at age 3 if they themselves have had symptoms of depression, parenting stress, or weak sense of coherence. Also, the paternal psychological well-being contributes to the behavioral development of a preterm child. (Read the full article)




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The Outcome of ELBW Infants Treated With NCPAP and InSurE in a Resource-Limited Institution

The survival of extremely low birth weight infants in resource-limited situations is dismal due to limited neonatal intensive care facilities. Nasal continuous positive airway pressure resulted in an increased survival of these infants, but many still require back-up ventilation.

Nasal continuous positive airway pressure and intubation, surfactant, and extubation practiced in a neonatal high care ward with limited resources and limited back-up ventilatory facilities can improve the survival of extremely low birth weight infants. (Read the full article)




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Reference Ranges for Lymphocyte Counts of Neonates: Associations Between Abnormal Counts and Outcomes

High or low lymphocyte counts at birth have been reported as a marker for subsequent intraventricular hemorrhage, retinopathy of prematurity, and periventricular leukomalacia. However, this conclusion is questionable because reference ranges for lymphocyte counts have not been constructed by using large numbers of neonates.

This study provides reference ranges for lymphocytes of neonates. A high count at birth is associated with early onset sepsis and IVH and a low count with early onset sepsis, IVH, and retinopathy of prematurity. Among neonates with birth asphyxia, a low count identifies a high risk for death. (Read the full article)




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Qualitative Brain MRI at Term and Cognitive Outcomes at 9 Years After Very Preterm Birth

Cross-sectional studies have demonstrated associations between the white matter injury and cognitive impairment in very preterm born children. Longitudinal studies confirmed the relationships between cerebral MRI at term and neurodevelopmental outcomes at up to 2 years old.

White matter injury (but not gray matter injury) on term MRI predicted cognitive impairments of very preterm born infants at 9 years old. Qualitative assessment of white matter signal intensities showed limited predictive values of cognitive impairments. (Read the full article)




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Child and Adult Outcomes of Chronic Child Maltreatment

We lack prospective studies documenting "dosage effects" of chronic child maltreatment for both subsequent adolescent and adult outcomes. It is unknown whether effects are linear, shelving, or exponential, and we lack data across domains of outcomes.

Chronic child maltreatment reports are a robust indicator of future negative health and behavioral outcomes. There is a dose-response relationship between chronicity and outcomes in adolescence, but this is attenuated in adulthood once adverse child outcomes are controlled. (Read the full article)




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Developmental Outcome at 6.5 Years After Acidosis in Term Newborns: A Population-Based Study

Conflicting results exist concerning long-term outcome in healthy infants with metabolic acidosis at birth.

Neonates who appear well after perinatal metabolic acidosis do not have an increased risk of neurologic or behavioral problems in need of referral actions or pedagogic arrangements at the age of 6.5 years. (Read the full article)




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Infant Outcomes After Maternal Antiretroviral Exposure in Resource-Limited Settings

Information on infant safety after exposure to maternal antiretroviral regimens during pregnancy in international clinical trials is lacking. As antiretroviral drugs are released to populations in resource-limited settings through clinical trials, it becomes critical to collect pediatric outcome data.

The study demonstrates the feasibility of reporting infant outcomes following adult antiretroviral trials in developing countries, provides HIV-free infant survival and prospective growth data in association with maternal parameters, and details morbidity, mortality, and genetic defects following maternal antiretroviral exposure. (Read the full article)




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Transient Neonatal Hypocalcemia: Presentation and Outcomes

Late-onset hypocalcemia is common in neonates, often presents with seizures or tetany, and is often attributed to transient hypoparathyroidism.

Late-onset hypocalcemia in neonates is often a sign of coexisting vitamin D deficiency and hypomagnesemia and is readily managed with therapy of limited duration, and neonates presenting with tetany or seizures due to hypocalcemia are unlikely to benefit from neuroimaging studies. (Read the full article)




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Approach to Infants Born at 22 to 24 Weeks' Gestation: Relationship to Outcomes of More-Mature Infants

Although morbidity-free survival for preterm infants has remained constant in US NICUs when assessed collectively, morbidity-free survival differs among centers. Center-specific practices before, at, or after delivery might affect outcomes of the most premature infants.

Our findings suggest that the approach taken to infants at the limits of viability is associated with outcomes of more-mature infants. Identifying centers with higher survival and lower morbidity might lead to identification of key practices to improve morbidity-free survival. (Read the full article)




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Long-term Outcomes of Group B Streptococcal Meningitis

Group B Streptococcus (GBS) is a common cause of meningitis in young infants. Studies from the 1980s revealed that GBS meningitis resulted in substantial mortality and reported that survivors of the infection had a high likelihood of adverse neurodevelopmental outcome.

Contemporary long-term outcomes for children surviving GBS meningitis reveal that 56% are functioning normally. The remainder sustained mild-to-moderate (25%) or severe (19%) neurodevelopmental impairment, highlighting the need for GBS prevention and for ongoing developmental follow-up for GBS meningitis survivors. (Read the full article)




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RCT of a Mentoring and Skills Group Program: Placement and Permanency Outcomes for Foster Youth

Children in foster care are at elevated risk for adverse outcomes. Placement instability and failure to achieve timely permanence exacerbate that risk. A handful of studies have found that parent-management training is effective in promoting placement stability and timely permanence.

Unlike parent-management training, youth focused interventions have not been systematically evaluated for their impact on placement and permanency outcomes. A mentoring and skills group intervention for preadolescents in foster care demonstrated better placement and permanency outcomes, especially for high-risk subgroups. (Read the full article)




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Outcome Trajectories in Extremely Preterm Infants

Death or neurodevelopmental impairment in extremely premature neonates can be predicted at birth by considering gender, antenatal steroids, multiple birth, birth weight, and gestational age.

Prediction of death or neurodevelopmental impairment in extremely premature infants is improved by using information available later during the clinical course. The importance of birth weight declines, whereas that of respiratory illness severity increases with advancing postnatal age. (Read the full article)




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Costs and Infant Outcomes After Implementation of a Care Process Model for Febrile Infants

Febrile infants in the first 90 days may have life-threatening serious bacterial infection. Well-appearing febrile infants with serious bacterial infections cannot be distinguished from those without by examination alone. Variation in care resulting in both undertreatment and overtreatment is common.

The systemwide implementation of an evidence-based care process model for the care of febrile infants in Intermountain Healthcare was associated with increased delivery of evidence-based care, improved infant outcomes, and lower costs. This model adopted nationally can improve value. (Read the full article)