Bolus Versus Continuous Nasogastric Feeds for Infants With Bronchiolitis: A Randomized Trial

BACKGROUND AND OBJECTIVES: Infants hospitalized with bronchiolitis are commenced on nasogastric feeding to maintain hydration. Feeding strategies vary according to physician or institution preference. The current study hypothesized that continuous nasogastric feeding would prolong length of stay (LOS) when compared to bolus feeding. METHODS: A randomized, parallel-group, superiority clinical trial was performed within an Australian children’s hospital throughout 2 bronchiolitis seasons from May 2018 to October 2019. Infants <12 months hospitalized with bronchiolitis and requiring supplemental nasogastric feeding were randomly assigned to continuous or bolus nasogastric regimens. LOS was the primary outcome. Secondary outcome measures included pulmonary aspirations and admissions to intensive care. RESULTS: The intention-to-treat analysis included 189 patients: 98 in the bolus nasogastric feeding group and 91 in the continuous group. There was no significant difference in LOS (median LOS of the bolus group was 54.25 hours [interquartile range 40.25–82] and 56 hours [interquartile range 38–78.75] in the continuous group). A higher proportion of admissions to intensive care was detected in the continuous group (28.57% [26 of 91] of the continuous group vs 11.22% [11 of 98] of the bolus group [P value 0.004]). There were no clinically significant pulmonary aspirations or statistically significant differences in vital signs between the groups within 6 hours of feed initiation. CONCLUSIONS: No significant difference in LOS was found between bolus and continuous nasogastric feeding strategies for infants hospitalized with bronchiolitis. The continuous feeding group had a higher proportion of intensive care admissions, and there were no aspiration events.

The Impact of the Time Interval Between Cycles on Pregnancy Outcome of Ovulation Induction Cycle Intrauterine Artificial Insemination

ObjectiveThe objective of this study was to estimate whether the time interval between two intrauterine inseminations (IUI) treatments needs to be extended by one menstrual cycle or more in patients undergoing successive cycles of ovulation stimulation, and whether this will have an impact on the clinical pregnancy rate (CPR).Study DesignRetrospective cohort study.Study siteThe study site was the reproductive medicine center of a teaching hospital.Patient(s)The subjects were women and their husbands who received two or more intrauterine insemination in our reproductive medicine center due to mild infertility in the period from January 2017 to December 2019. Patients were divided into 2 groups according to the number of days between the last menstrual day(LMD)and the previous IUI operation day(POD), continuous group (the time from the LMD to POD ≤ 34 days) and delayed group (the time from the LMD to POD ≥ 35 days). We excluded cycles with intervals of more than 180 days.In order to avoid the inclusion of multiple repeat cycles for the same couple, only the first two cycles of IUI treatment in the same couple were allowed to be included in this study. That is, when they failed the first IUI cycle, they were given a second IUI treatment.Intervention(s)No intervention.Main Outcome Measure(s)A total of 550 cycles met the inclusion criteria, and 374 (68.0%) cycles met the inclusion criteria for the continuous group,the remaining 176 (32.0%) cycles with at least one or more menstruations between two IUI cycles were included in the delayed group.The primary outcome measure was clinical pregnancy rate (CPR), with secondary outcomes including abortion rate. Differences in clinical pregnancy rate (CPR)、abortion rate were compared between the two groups.ResultThere was no significant difference between the continuous group and the delayed group in female age, male age, infertility duration, infertility type, female BMI, endometrial classification, endometrial thickness, semen volume before treatment, sperm density before treatment, percentage of forward motile sperm before treatment, sperm density after treatment, and percentage of forward motile sperm after treatment. There were no statistical differences between the delayed group vs continuous group regarding the clinical pregnancy rate (20.5 % vs 21.9 %) and abortion rate (27.8% vs 22.0%)（P>0.05）. The above factors were included for binary logistic regression analysis. It was found that the increase of endometrial thickness promoted the clinical pregnancy rate, which was statistically significant (OR=1.205, 95% CI 1.05-1.384,P=0.008). Compared with primary infertility, secondary infertility can promote the improvement of clinical pregnancy rate, which is statistically significant (OR=2.637,95%CI 1.313-5.298,P=0.006). The effect of time interval between IUI on clinical pregnancy was not statistically significant (OR=1.007,95% CI 0.513-1.974,P=0.985).ConclusionsOverall, prolonging the interval between two IUI did not significantly improve pregnancy outcomes. Unless there are clear clinical indications, it is not necessary to deliberately prolong the interval between two treatments.

The Impact of the Time Interval Between Cycles on Pregnancy Outcome of Intrauterine Insemination

Objective: The objective of this study was to estimate whether the time interval between two intrauterine inseminations (IUI) treatments needs to be extended by one menstrual cycle or more, and whether this will have an impact on the clinical pregnancy rate (CPR).Study Design: Retrospective cohort study.Study site: The study site was the reproductive medicine center of a teaching hospital.Patient(s): The subjects were women and their husbands who received two or more intrauterine insemination in our reproductive medicine center due to mild infertility in the period from January 2014 to December 2020. Patients were divided into 2 groups according to the number of days between the last menstrual day(LMD)and the previous IUI operation day(POD), continuous group (the time from the LMD to POD ≤ 34 days) and delayed group (the time from the LMD to POD ≥ 35 days). If the previous cycle was a pregnancy or abortion cycle, the next cycle immediately adjacent to it was defined as a new cycle, and the days between the two cycles were not included in the study.Intervention(s):No intervention.Main Outcome Measure(s): A total of 1491 cycles were finally included in the study.990 cycles followed by the second IUI cycle after the previous failure,501 cycles at least one menstrual cycle was separated between two IUI treatments. The primary outcome measure was clinical pregnancy rate (CPR), with secondary outcomes including abortion rate and live birth rate. Differences in clinical pregnancy rate (CPR)、abortion rate and live birth rate were compared between the two groups.Result: No significant differences with regard to baseline demographic and the number of treatment cycles, the duration of infertility, the type of infertility, the mode of treatment, and the cause of infertility were observed between the two groups.There were no statistical differences between the delayed group vs continuous group regarding the clinical pregnancy rate(15.0% vs 13.7%), live birth rate(78.7% vs 74.3%), and abortion rate(17.3% vs 18.4%)（P＞0.05）.The above factors were included for binary logistic regression analysis. The observed difference in clinical pregnancy rate between the groups was not statistically significant after adjustment(OR = 1.101,95%CI 0.807-1.499, P=0.546）.The all cycles were divided into four groups based on female age. results showed that when the female's age was ≤ 25 years old, the pregnancy rate in the continuous group was 16.5%, which was significantly higher than that in the delayed group by 5.8% (difference 0.107, 95% CI 0.016-0.198, P = 0.055), approached, but did not reach, statistical significance. When the female was 30-35 years old, the pregnancy rate in the delayed group was 19.4%, which was significantly higher than 10.9% in the continuous group (difference 0.085, 95% CI 0.016-0.154, P = 0.011). The difference between the two groups was statistically significant. The all cycles were divided into three groups based on years of infertility. Our results show that when the number of years of infertility was≤2 years, the clinical pregnancy rate was 20.7% in the delayed group and 12.5% in the continuous group (difference 0.107, 95% CI 0.150-0.014, P = 0.013), statistical significance was maintained. Based on the number of treatment cycles, it is divided into 2 cycles, 3 cycles, and≥4 cycles. The results showed that when≥4 cycles, the pregnancy rate in the continuous group were 19.4%, which was significantly higher than 6.1% in the delayed group (difference 0.133, 95% CI 0.246-0.020, P = 0.038). Statistical significance was maintained at P < 0.05.Conclusions: Overall, prolonging the interval between two IUI did not significantly improve pregnancy outcomes. Yet, for different age stages, duration of infertility, and the number of treatment cycles, we suggest that more flexible treatment strategies can be tried to improve the clinical pregnancy rate.

Exploring Potential Benefits of Accumulated Multicomponent-Training in Non-Active Older Adults: From Physical Fitness to Mental Health

The present study aimed to analyze the impact of a multicomponent training (MCT) program in a group of non-active older adults, comparing two different dose distributions. Twenty-four individuals, assigned to two groups, completed 15 weeks of MCT (2 days/week). The continuous group (CMCT; n = 14, 9 females; 71.07 ± 5.09 years) trained for 60 min/session in the morning. The accumulated group (AMCT; n = 10, 5 females; 72.70 ± 3.59 years) performed the same exercises, volume, and intensity, but the training was distributed twice per day (30 min in the morning; 30 more in the afternoon). Bonferroni post hoc comparisons revealed significant (p < 0.001) and similar large improvements in both groups in lower limb strength (five times sit-to-stand test: CMCT, 12.55 ± 2.83 vs. 9.44 ± 1.72 s; AMCT, 10.37 ± 2.35 vs. 7.46 ± 1.75 s). In addition, there were large gains in preferred walking speed and instrumental daily life activities, which were higher for CMCT and AMCT, respectively (in this order: 1.00 ± 0.18 vs. 1.44 ± 0.26 m/s and 1.09 ± 0.80 vs. 1.58 ± 0.18 m/s; 33.07 ± 2.88 vs. 36.57 ± 1.65 points and 32.80 ± 1.93 vs. 36.80 ± 0.92 points); improvements in cardiorespiratory fitness, now moderate for CMCT (474.14 ± 93.60 vs. 529.64 ± 82.76 m) and large for AMCT (515.10 ± 20.24 vs. 589.60 ± 40.38 m); and medium and similar enhancements in agility in both groups (TUG test: CMCT: 7.49 ± 1.11 vs. 6.77 ± 1.16 s; AMCT: 6.84 ± 1.01 vs. 6.18 ± 0.62 s). None of the protocols had an impact on the executive function, whereas health-related quality of life showed a trend to significance in the whole sample only (EQindex overall sample, p = 0.062; d = 0.48 CMCT; d = 0.34 AMCT). Regardless of the type of dose distribution, starting multicomponent training improves physical function in non-active older adults, but does not improve cognitive function at mid-term. Because both forms of MCT showed similar compliance, slightly positive differences in accumulated strategies may indicate some benefits related to breaking afternoon sedentary behaviors, which deserves further research in longer and larger interventions. The mixed nature of MCT suggests accumulative group interventions may be a promising approach to address sedentary aging.

Maintenance Therapy in First-Line Gastric and Gastroesophageal Junction Adenocarcinoma: A Retrospective Analysis

BackgroundFluoropyrimidine with platinum-based chemotherapy has become the standard of care for advanced gastric and gastroesophageal (GEJ) cancer. Trials in colon cancer show that induction chemotherapy followed by maintenance chemotherapy is an efficacious strategy to maximize clinical response while minimizing toxicity. The current retrospective study aims to evaluate the efficacy and tolerability of maintenance versus continuous treatment in advanced GEJ malignancy.MethodsA retrospective analysis of patients with metastatic gastric/GEJ adenocarcinoma treated with fluoropyrimidine and platinum chemotherapy between 2007-2017 was performed. Patients who achieved at least stable disease after initial induction treatment were included. After 16 weeks of induction chemotherapy, patients were categorized into the continuous group if induction chemotherapy was continued and the maintenance group if chemotherapy was switched to maintenance fluoropyrimidine monotherapy or observed off treatment. Endpoints were progression-free survival (PFS), overall survival (OS), and toxicities.ResultsIn total, 90 patients met the criteria, 48 received continuous therapy, and 42 received maintenance. Baseline characteristics were comparable. No difference in PFS (9.9 vs 8.4 months p = .28) or in OS (16.1 vs 21.3 months p = .75) was observed, including after controlling for the best response on induction therapy and other variables. In patients on continuous induction therapy, there was a higher prevalence of grade three neuropathy (42.6% vs 9.8% p = .001) and neutropenic fever (13% vs 0% p =.03).ConclusionsMaintenance therapy following induction fluoropyrimidine and platinum-based therapy is associated with an improved toxicity profile and appears to have comparable efficacy to continuous treatment in metastatic gastric/GEJ cancer.

Application of Scalar Type Operators to Decomposability

In this paper, we give some application of scalar type operators to Decomposibility. In particular, we show that if H is of (α, α + 1) type R and that it generates a strongly continuous group on a Banach space, then its resolvent is Decomposable hence scalar type.

Long-term efficacy and safety of sapropterin in patients who initiated sapropterin at < 4 years of age with phenylketonuria: results of the 3-year extension of the SPARK open-label, multicentre, randomised phase IIIb trial

Background During the initial 26-week SPARK (Safety Paediatric efficAcy phaRmacokinetic with Kuvan®) study, addition of sapropterin dihydrochloride (Kuvan®; a synthetic formulation of the natural cofactor for phenylalanine hydroxylase, tetrahydrobiopterin; BH4), to a phenylalanine (Phe)-restricted diet, led to a significant improvement in Phe tolerance versus a Phe-restricted diet alone in patients aged 0–4 years with BH4-responsive phenylketonuria (PKU) or mild hyperphenylalaninaemia (HPA). Based on these results, the approved indication for sapropterin in Europe was expanded to include patients < 4 years of age. Herein, we present results of the SPARK extension study (NCT01376908), evaluating the long-term safety, dietary Phe tolerance, blood Phe concentrations and neurodevelopmental outcomes in patients < 4 years of age at randomisation, over an additional 36 months of treatment with sapropterin. Results All 51 patients who completed the 26-week SPARK study period entered the extension period. Patients who were previously treated with a Phe-restricted diet only (‘sapropterin extension’ group; n = 26), were initiated on sapropterin at 10 mg/kg/day, which could be increased up to 20 mg/kg/day. Patients previously treated with sapropterin plus Phe-restricted diet, remained on this regimen in the extension period (‘sapropterin continuous’ group; n = 25). Dietary Phe tolerance increased significantly at the end of the study versus baseline (week 0), by 38.7 mg/kg/day in the ‘sapropterin continuous’ group (95% CI 28.9, 48.6; p < 0.0001). In the ‘sapropterin extension’ group, a less pronounced effect was observed, with significant differences versus baseline (week 27) only observed between months 9 and 21; dietary Phe tolerance at the end of study increased by 5.5 mg/kg/day versus baseline (95% CI − 2.8, 13.8; p = 0.1929). Patients in both groups had normal neuromotor development and growth parameters. Conclusions Long-term treatment with sapropterin plus a Phe-restricted diet in patients who initiated sapropterin at < 4 years of age with BH4-responsive PKU or mild HPA maintained improvements in dietary Phe tolerance over 3.5 years. These results continue to support the favourable risk/benefit profile for sapropterin in paediatric patients (< 4 years of age) with BH4-responsive PKU. Frequent monitoring of blood Phe levels and careful titration of dietary Phe intake to ensure adequate levels of protein intake is necessary to optimise the benefits of sapropterin treatment. Trial registration ClinicalTrials.gov, NCT01376908. Registered 17 June 2011, https://clinicaltrials.gov/ct2/show/NCT01376908.

Effects of Prenatal Exposure to Alcohol and Smoking on Fetal Heart Rate and Movement Regulation

Negative associations of prenatal tobacco and alcohol exposure (PTE and PAE) on birth outcomes and childhood development have been well documented, but less is known about underlying mechanisms. A possible pathway for the adverse fetal outcomes associated with PTE and PAE is the alteration of fetal autonomic nervous system development. This study assessed PTE and PAE effects on measures of fetal autonomic regulation, as quantified by heart rate (HR), heart rate variability (SD-HR), movement, and HR-movement coupling in a population of fetuses at ≥ 34 weeks gestational age. Participants are a subset of the Safe Passage Study, a prospective cohort study that enrolled pregnant women from clinical sites in Cape Town, South Africa, and the Northern Plains region, United States. PAE was defined by six levels: no alcohol, low quit early, high quit early, low continuous, moderate continuous, and high continuous; while PTE by 4 levels: no smoking, quit early, low continuous, and moderate/high continuous. Linear regression analyses of autonomic measures were employed controlling for fetal sex, gestational age at assessment, site, maternal education, household crowding, and depression. Analyses were also stratified by sleep state (1F and 2F) and site (South Africa, N = 4025, Northern Plains, N = 2466). The final sample included 6491 maternal-fetal-dyad assessed in the third trimester [35.21 ± 1.26 (mean ± SD) weeks gestation]. PTE was associated with a decrease in mean HR in state 2F, in a dose dependent fashion, only for fetuses of mothers who continued smoking after the first trimester. In state 1F, there was a significant increase in mean HR in fetuses whose mother quit during the first trimester. This effect was driven by the Norther Plains cohort. PTE was also associated with a significant reduction in fetal movement in the most highly exposed group. In South Africa a significant increase in mean HR both for the high quit early and the high continuous group was observed. In conclusion, this investigation addresses a critical knowledge gap regarding the relationship between PTE and PAE and fetal autonomic regulation. We believe these results can contribute to elucidating mechanisms underlying risk for adverse outcomes.