Abstract Background We have previously shown that an exclusively human milk-based diet is beneficial for extremely premature infants who are at risk for necrotizing enterocolitis (NEC). However, no significant difference in the other primary study endpoint, the length of time on total parenteral nutrition (TPN), was found. The current analysis re-evaluates these data from a different statistical perspective considering the probability or likelihood of needing TPN on any given day rather than the number of days on TPN. This study consisted of 207 premature infants randomized into three groups: one group receiving a control diet of human milk, formula and bovine-based fortifier (“control diet”), and the other two groups receiving only human milk and human milk-based fortifier starting at different times in the enteral feeding process (at feeding volumes of 40 or 100 mL/kg/day; “HM40” and “HM100”, respectively). The counting process Cox proportional hazards survival model was used to determine the likelihood of needing TPN in each group. Results The two groups on the completely human-based diet had an 11-14 % reduction in the likelihood of needing nutrition via TPN when compared to infants on the control diet (p = 0.0001 and p = 0.001, respectively for the HM40 and HM100 groups, respectively). This was even more pronounced if the initial period of TPN was excluded (p < 0.0001 for both the HM40 and HM100 groups). Conclusions A completely human milk-based diet significantly reduces the likelihood of TPN use for extremely premature infants when compared to a diet including cow-based products. This likelihood may be reduced even further when the human milk fortifier is initiated earlier in the feeding process. Trial registration This study was registered at http://www.clinicaltrials.gov reg. # NCT00506584

Objective

We studied the impact of continuing versus discontinuing pioglitazone on hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and weight when starting bedtime insulin in patients with poor glycemic control.

Methods

We retrospectively analyzed data from a 13-month randomized control trial on 77 patients with type 2 diabetes mellitus (DM), who despite maximum doses of three oral diabetes medications (metformin, sulfonylurea and pioglitazone) had HbA1C levels above 7.5%. Patients were randomized to either continuing or discontinuing pioglitazone in addition to starting and up-titrating bedtime insulin. HbA1C, FPG, and weight were assessed at baseline, 3months, 7months and 13months with the differences from baseline for the two groups compared at each of the three time points using the Wilcoxon rank sum test.

Results

We found that HbA1c was significantly lower at the 7-month (p=0.01) and 13-month time points (p=0.036), and FPG was significantly lower at all three time points in the group continuing pioglitazone compared with those discontinuing pioglitazone. Continuing pioglitazone resulted in a greater increase in weight at the 3-month (p=0.002), 7-month (p=0.0001) and 13-month (p=0.00003) time points. Patients with the lowest HbA1c (<8.2%) at baseline were more likely to benefit from continuing pioglitazone than those with higher baseline HbA1c. Patients who started insulin and discontinued pioglitazone had similar HbA1c, FPG and weight at the three time points as at baseline, suggesting that pioglitazone and bedtime insulin has similar glycemic effect in this population.

Conclusions

We conclude that in patients with uncontrolled type 2 DM, continuing pioglitazone while concurrently starting bedtime insulin within a 13-month period led to a significant decrease in both HbA1c and FPG levels compared with those who did not receive pioglitazone; however weight increased during this period.

Background

Microvascular blood flow (MBF) impairment in patients with lower extremity arterial disease (LEAD) is associated with more severe major adverse limb events (MALE). The contribution of ticagrelor, a P2Y12 antagonist and an adenosine enhancer, on blood viscosity (BV) and BV-dependent MBF in LEAD is unknown. The aim of the trial is to investigate the effects of ticagrelor on BV, and explore the association of BV-dependent MBF in participants with LEAD and type 2 diabetes (T2DM).

Methods

Randomized, double-blind, double-dummy, crossover trial design that compares treatment with aspirin 81 mg/ticagrelor placebo, aspirin 81 mg/ticagrelor 90 mg twice daily and aspirin placebo/ticagrelor 90 mg twice daily on high-shear (300 s^-1) and low-shear (5 s^-1) BV, and laser Doppler flowmetry (LDF) in the dorsum of the feet of participants with T2DM.

Results

We randomized 70 (45% female) participants aged (mean ± SD) 72 ± 9 years. The duration of LEAD was 12.3 ± 10.3 years, and 96.9% reported intermittent claudication symptoms. Use of statins was 93% (high-intensity 43%, moderate intensity 49%), renin-angiotensin-aldosterone system inhibitors (75%) and beta-blockers (61%). Treatment with ticagrelor with or without aspirin reduced high-shear BV by 5%, in both cases, while aspirin monotherapy increased high-shear BV by 3.4% (p < 0.0001). Ticagrelor with or without aspirin reduced low-shear BV by 14.2% and 13.9% respectively, while aspirin monotherapy increased low-shear BV by 9.3% (p < 0.0001). The combination of ticagrelor and aspirin increased MBF in the left foot compared to the other two treatments (p = 0.02), but not in the right foot (p = 0.25).

Conclusions

Ticagrelor should be considered in the treatment of microvascular disease in patients with LEAD and T2DM. Trial registration Registration number: NCT02325466, registration date: December 25, 2014.

Objective

Small for gestational age (SGA) preterm infants (PT) are at greatest risk for growth failure. Our objective was to assess the impact of an exclusive human milk diet (HUM) on growth velocities and neonatal morbidities from birth to discharge in a SGA population.

Study design

Multicenter, retrospective cohort study, subgroup analysis of SGA PT comparing a cow's milk diet (CMD) with HUM diet.

Results

At birth 420 PT were classified as SGA (197 CMD group, 223 HUM group). Demographics and anthropometric measurements were similar. HUM group PT showed improvement in length Z score at discharge (p = 0.024) and reduction in necrotizing enterocolitis (NEC) (p = 0.004).

Conclusion

SGA PT fed a HUM diet had significantly decreased incidence of NEC, surgical NEC, and late-onset sepsis. Due to concerns about growth in a HUM diet, it is reassuring SGA infants fed the HUM diet had similar growth to CMD diet with trends toward improvement.

Background

Stepped wedge designs have gained recognition as a method for rigorously assessing implementation of evidence-based quality improvement interventions (QIIs) across multiple healthcare sites. In theory, this design uses random assignment of sites to successive QII implementation start dates based on a timeline determined by evaluators. However, in practice, QII timing is often controlled more by site readiness. We propose an alternate version of the stepped wedge design that does not assume the randomized timing of implementation while retaining the method's analytic advantages and applying to a broader set of evaluations. To test the feasibility of a nonrandomized stepped wedge design, we developed simulated data on patient care experiences and on QII implementation that had the structures and features of the expected data from a planned QII. We then applied the design in anticipation of performing an actual QII evaluation.

Methods

We used simulated data on 108,000 patients to model nonrandomized stepped wedge results from QII implementation across nine primary care sites over 12 quarters. The outcome we simulated was change in a single self-administered question on access to care used by Veterans Health Administration (VA), based in the United States, as part of its quarterly patient ratings of quality of care. Our main predictors were QII exposure and time. Based on study hypotheses, we assigned values of 4 to 11 % for improvement in access when sites were first exposed to implementation and 1 to 3 % improvement in each ensuing time period thereafter when sites continued with implementation. We included site-level (practice size) and respondent-level (gender, race/ethnicity) characteristics that might account for nonrandomized timing in site implementation of the QII. We analyzed the resulting data as a repeated cross-sectional model using HLM 7 with a three-level hierarchical data structure and an ordinal outcome. Levels in the data structure included patient ratings, timing of adoption of the QII, and primary care site.

Results

We were able to demonstrate a statistically significant improvement in adoption of the QII, as postulated in our simulation. The linear time trend while sites were in the control state was not significant, also as expected in the real life scenario of the example QII.

Conclusions

We concluded that the nonrandomized stepped wedge design was feasible within the parameters of our planned QII with its data structure and content. Our statistical approach may be applicable to similar evaluations.

Abstract Background Infants who survive advanced necrotizing enterocolitis (NEC) at the time of birth are at increased risk of having poor long term physiological and neurodevelopmental growth. The economic implications of the long term morbidity in these children have not been studied to date. This paper compares the long term healthcare costs beyond the initial hospitalization period incurred by medical and surgical NEC survivors with that of matched controls without a diagnosis of NEC during birth hospitalization. Methods The longitudinal healthcare utilization claim files of infants born between January 2002 and December 2003 and enrolled in the Texas Medicaid fee-for-service program were used for this research. Propensity scoring was used to match infants diagnosed with NEC during birth hospitalization to infants without a diagnosis of NEC on the basis of gender, race, prematurity, extremely low birth weight status and presence of any major birth defects. The Medicaid paid all-inclusive healthcare costs for the period from 6 months to 3 years of age among children in the medical NEC, surgical NEC and matched control groups were evaluated descriptively, and in a generalized linear regression framework in order to model the impact of NEC over time and by birth weight. Results Two hundred fifty NEC survivors (73 with surgical NEC) and 2,909 matched controls were available for follow-up. Medical NEC infants incurred significantly higher healthcare costs than matched controls between 6–12 months of age (mean incremental cost = US$ 5,112 per infant). No significant difference in healthcare costs between medical NEC infants and matched controls was seen after 12 months. Surgical NEC survivors incurred healthcare costs that were consistently higher than that of matched controls through 36 months of age. The mean incremental healthcare costs of surgical NEC infants compared to matched controls between 6–12, 12–24 and 24–36 months of age were US$ 18,274, 14,067 (p < 0.01) and 8,501 (p = 0.06) per infant per six month period, respectively. These incremental costs were found to vary between sub-groups of infants born with birth weight < 1,000g versus ≥ 1,000g (p < 0.05). Conclusions The all-inclusive healthcare costs of surgical NEC survivors continued to be substantially higher than that of matched controls through the early childhood development period. These results can have important treatment and policy implications. Further research in this topic is needed.

Introduction

Few human studies have explored the mechanisms of smoking-induced insulin resistance. Aims: To prospectively examine the metabolic changes of smoking reduction.

Methods

Cigarette smokers (n = 22; ½-2 packs per day) were enrolled in a smoking reduction program (counseling plus bupropion × 8 weeks; Phase I) followed by monitoring only (no counseling or bupropion × 16 weeks; Phase II). We serially measured exhaled carbon monoxide (CO) and urine nicotine metabolites; fat distribution, and metabolic parameters by hyperinsulinemic clamps including hepatic glucose output (HGO) and indirect calorimetry, adjusted for total caloric intake and expenditure.

Results

CO and nicotine metabolite levels fell with smoking reduction during Phase I (all p < 0.05), without any further changes through Phase II. Central-to-peripheral fat ratio increased during Phase I, but then fell during Phase II (all p < 0.05). Over 24 weeks, basal HGO fell (p = 0.02); and falling CO and nicotine metabolite levels correlated inversely with changes in glucose oxidation, and directly with changes in weight (all p < 0.05).

Conclusions

Smoking reduction produced a transient worsening of central fat redistribution followed by a more significant improvement; along with other net beneficial metabolic effects.

Introduction

The rapid clearance of factor IX necessitates frequent intravenous administrations to achieve effective prophylaxis for patients with hemophilia B. Subcutaneous administration has historically been limited by low bioavailability and potency. Dalcinonacog alfa was developed using a rational design approach to be a subcutaneously administered, next-generation coagulation prophylactic factor IX therapy.

Aim

This study aimed to investigate the pharmacokinetic, pharmacodynamic, and safety profile of dalcinonacog alfa administered subcutaneously in hemophilia B dogs.

Methods

Two hemophilia B dogs received single-dose daily subcutaneous dalcinonacog alfa injections for six days. Factor IX antigen and activity, whole blood clotting time, and activated partial thromboplastin time were measured at various time points. Additionally, safety assessments for clinical adverse events and evaluations of laboratory test results were conducted.

Results

There was an increase in plasma factor IX antigen with daily subcutaneous dalcinonacog alfa. Bioavailability of subcutaneous dalcinonacog alfa was 10.3% in hemophilia B dogs. Daily subcutaneous dosing of dalcinonacog alfa demonstrated the effects of bioavailability, time to maximal concentration, and half-life by reaching a steady-state activity sufficient to correct severe hemophilia to normal, after four days.

Conclusion

The increased potency of dalcinonacog alfa facilitated the initiation and completion of the Phase 1/2 subcutaneous dosing study in individuals with hemophilia B.

Background: Prior studies have posited poor patient adherence to remote patient monitoring as the reason for observed lack of benefits. Introduction: The purpose of this study was to examine the relationship between average adherence to the daily use of home telehealth (HT) and emergency room (ER) visits in Veterans with heart failure. Materials and Methods: This was a retrospective study using administrative data of Veterans with heart failure enrolled in Veterans Affairs (VA) HT Program in the first half of 2014. Zero-inflated negative binomial regression was used to determine which predictors affect the probability of having an ER visit and the number of ER visits. Results: The final sample size was 3,449 with most being white and male. There were fewer ER visits after HT enrollment (mean ± standard deviation of 1.85 ± 2.8) compared with the year before (2.2 ± 3.4). Patient adherence was not significantly associated with ER visits. Age and being from a racial minority group (not white or black) and belonging to a large HT program were associated with having an ER visit. Being in poorer health was associated with higher expected count of ER visits. Discussion: Subgroups of patients (e.g., with depression, sicker, or from a racial minority group) may benefit from added interventions to decrease ER use. Conclusions: This study found that adherence was not associated with ER visits. Reasons other than adherence should be considered when looking at ER use in patients with heart failure enrolled in remote patient monitoring programs.

Background

The effect of incorporating mobile technology to support participants' lifestyle change and weight loss in medical group visits has not been well studied in a safety-net setting.

Rationale and design

Thus, the rationale of the current study was to examine the effect of text messaging in a medical group visit, and test the effect of two texting programs (12 weeks and 20 weeks), compared to those who did not receive text-messaging in the Preventing Obesity With Eating Right (POWER) group visit program. The primary outcome was weight loss.

Results

We found that those enrolled in the 20-week and 12-week texting programs attended more group visit sessions than those enrolled in the POWER group only (p < 0.001). Both POWER and POWER + 20-week texting groups had a significant reduction in weight at their final group visit compared to their baseline (POWER, 114 ± 27 kg vs. 112 ± 26 kg, p < 0.001; POWER + 20-week texting, 111 ± 28 kg vs. 109 ± 28 kg, p < 0.01), but not the 12-week texting group (114 ± 29 kg vs. 113 ± 29 kg, p = 0.22), with no differences between the groups. The number of group visits was correlated with a decrease in weight (r_s  = 0.12, p < 0.05).

Conclusion

In conclusion, text messaging programs led to more attendance in the medical group visits, but not greater weight loss or reduction in HbA1c than the POWER group obesity program alone. Further studies are needed to maximize the beneficial effects of texting programs in medical group visits in underserved minority populations.