The "synactive" theory of neurobehavioral development forms the basis of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP). Our objective was to assess the effectiveness ...of NIDCAP in improving outcomes in preterm infants.
Medline, CINAHL, Embase, PsychInfo, The Cochrane Library, Pediatric Academic Societies' Abstracts and Web of Science were searched in July 2010 and February 2012. The studies selected were randomized controlled trials testing the effectiveness of NIDCAP on medical and neurodevelopmental outcomes. The authors abstracted baseline characteristics of infants and outcomes. The risk of bias was assessed by using Cochrane criteria. RevMan 5.1 was used to synthesize data by the use of relative risk and risk difference for dichotomous outcomes and mean or standardized mean difference for continuous outcomes.
Eleven primary and 7 secondary studies enrolling 627 neonates were included, with 2 of high quality. The composite primary outcomes of death or major sensorineural disability at 18 months corrected age or later in childhood (3 trials, 302 children; relative risk 0.89 95% confidence interval 0.61 to 1.29) and survival free of disability at 18 months corrected age or later in childhood (2 trials, 192 infants; relative risk 0.97 95% confidence interval 0.69 to 1.35), were not significantly different between the NIDCAP and control groups. With the sensitivity analysis that excluded the 2 statistically heterogeneous outlying studies, there were no significant differences between groups for short-term medical outcomes.
This systematic review including 627 preterm infants did not find any evidence that NIDCAP improves long-term neurodevelopmental or short-term medical outcomes.
Colorectal cancer, the third most common cancer in the United States, has a natural history that usually encompasses several decades. Dietary components have been implicated in the etiology of ...colorectal cancer, perhaps through their effect on inflammation.
We examined the ability of the dietary inflammatory index (DII) to predict colorectal cancer in the Iowa Women's Health Study. The DII was computed based on dietary intake assessed by a 121-item food frequency questionnaire in this cohort of 34,703 women, ages 55 to 69 years, free of any self-reported prior malignancy at enrollment in 1986. Incident colorectal cancer cases were identified through linkage with the State Health Registry of Iowa (a Surveillance, Epidemiology, and End Results program member). Cox proportional hazards regression was used to estimate HRs. Through the end of 2010, 1,636 incident colorectal cancers were identified, including 1,329 colon and 325 rectal cancers.
Multivariable analysis, adjusting for body mass index, smoking status, pack-years of smoking, hormone replacement therapy, education, diabetes, and total energy intake, revealed positive associations between higher DII and colorectal cancer risk HR for DIIcontinuous: 1.07 per unit increase in DII (corresponding to 0.5 SD unit increase); 95% confidence interval (CI), 1.01-1.13; HR for DIIquintiles: Q5 vs. Q1 = 1.20; 95% CI, 1.01-1.43. HRs for DII were similar for colon cancer and rectal cancer, though not statistically significant for rectal cancer.
These results indicate that a proinflammatory diet, as indicated by higher DII scores, was associated with higher risk of developing colorectal cancer.
Proinflammatory diets are associated with increased risk of colorectal cancer.
Background
Newborn animal studies and pilot studies in humans suggest that mild hypothermia following peripartum hypoxia‐ischaemia in newborn infants may reduce neurological sequelae without adverse ...effects.
Objectives
To determine the effect of therapeutic hypothermia in encephalopathic asphyxiated newborn infants on mortality, long‐term neurodevelopmental disability and clinically important side effects.
Search methods
We used the standard search strategy of the Cochrane Neonatal Review Group as outlined in The Cochrane Library (Issue 2, 2007). Randomised controlled trials evaluating therapeutic hypothermia in term and late preterm newborns with hypoxic ischaemic encephalopathy were identified by searching the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2007, Issue 2), MEDLINE (1966 to June 2007), previous reviews including cross‐references, s, conferences, symposia proceedings, expert informants and journal handsearching. We updated this search in May 2012.
Selection criteria
We included randomised controlled trials comparing the use of therapeutic hypothermia with standard care in encephalopathic term or late preterm infants with evidence of peripartum asphyxia and without recognisable major congenital anomalies. The primary outcome measure was death or long‐term major neurodevelopmental disability. Other outcomes included adverse effects of cooling and 'early' indicators of neurodevelopmental outcome.
Data collection and analysis
Four review authors independently selected, assessed the quality of and extracted data from the included studies. Study authors were contacted for further information. Meta‐analyses were performed using risk ratios (RR) and risk differences (RD) for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals (CI).
Main results
We included 11 randomised controlled trials in this updated review, comprising 1505 term and late preterm infants with moderate/severe encephalopathy and evidence of intrapartum asphyxia. Therapeutic hypothermia resulted in a statistically significant and clinically important reduction in the combined outcome of mortality or major neurodevelopmental disability to 18 months of age (typical RR 0.75 (95% CI 0.68 to 0.83); typical RD ‐0.15, 95% CI ‐0.20 to ‐0.10); number needed to treat for an additional beneficial outcome (NNTB) 7 (95% CI 5 to 10) (8 studies, 1344 infants). Cooling also resulted in statistically significant reductions in mortality (typical RR 0.75 (95% CI 0.64 to 0.88), typical RD ‐0.09 (95% CI ‐0.13 to ‐0.04); NNTB 11 (95% CI 8 to 25) (11 studies, 1468 infants) and in neurodevelopmental disability in survivors (typical RR 0.77 (95% CI 0.63 to 0.94), typical RD ‐0.13 (95% CI ‐0.19 to ‐0.07); NNTB 8 (95% CI 5 to 14) (8 studies, 917 infants). Some adverse effects of hypothermia included an increase sinus bradycardia and a significant increase in thrombocytopenia.
Authors' conclusions
There is evidence from the 11 randomised controlled trials included in this systematic review (N = 1505 infants) that therapeutic hypothermia is beneficial in term and late preterm newborns with hypoxic ischaemic encephalopathy. Cooling reduces mortality without increasing major disability in survivors. The benefits of cooling on survival and neurodevelopment outweigh the short‐term adverse effects. Hypothermia should be instituted in term and late preterm infants with moderate‐to‐severe hypoxic ischaemic encephalopathy if identified before six hours of age. Further trials to determine the appropriate techniques of cooling, including refinement of patient selection, duration of cooling and method of providing therapeutic hypothermia, will refine our understanding of this intervention.
First-generation EGFR tyrosine kinase inhibitors (EGFR TKI) provide significant clinical benefit in patients with advanced EGFR-mutant (EGFRm(+)) non-small cell lung cancer (NSCLC). Patients ...ultimately develop disease progression, often driven by acquisition of a second T790M EGFR TKI resistance mutation. AZD9291 is a novel oral, potent, and selective third-generation irreversible inhibitor of both EGFRm(+) sensitizing and T790M resistance mutants that spares wild-type EGFR. This mono-anilino-pyrimidine compound is structurally distinct from other third-generation EGFR TKIs and offers a pharmacologically differentiated profile from earlier generation EGFR TKIs. Preclinically, the drug potently inhibits signaling pathways and cellular growth in both EGFRm(+) and EGFRm(+)/T790M(+) mutant cell lines in vitro, with lower activity against wild-type EGFR lines, translating into profound and sustained tumor regression in EGFR-mutant tumor xenograft and transgenic models. The treatment of 2 patients with advanced EGFRm(+) T790M(+) NSCLC is described as proof of principle.
We report the development of a novel structurally distinct third-generation EGFR TKI, AZD9291, that irreversibly and selectively targets both sensitizing and resistant T790M(+) mutant EGFR while harboring less activity toward wild-type EGFR. AZD9291 is showing promising responses in a phase I trial even at the first-dose level, with first published clinical proof-of-principle validation being presented.
Summary Background Infants of women with diabetes in pregnancy are at increased risk of hypoglycaemia, admission to a neonatal intensive care unit (NICU), and not being exclusively breastfed. Many ...clinicians encourage women with diabetes in pregnancy to express and store breastmilk in late pregnancy, yet no evidence exists for this practice. We aimed to determine the safety and efficacy of antenatal expressing in women with diabetes in pregnancy. Methods We did a multicentre, two-group, unblinded, randomised controlled trial in six hospitals in Victoria, Australia. We recruited women with pre-existing or gestational diabetes in a singleton pregnancy from 34 to 37 weeks' gestation and randomly assigned them (1:1) to either expressing breastmilk twice per day from 36 weeks' gestation (antenatal expressing) or standard care (usual midwifery and obstetric care, supplemented by support from a diabetes educator). Randomisation was done with a computerised random number generator in blocks of size two and four, and was stratified by site, parity, and diabetes type. Investigators were masked to block size but masking of caregivers was not possible. The primary outcome was the proportion of infants admitted to the NICU. We did the analyses by intention to treat; the data were obtained and analysed masked to group allocation. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000217909. Findings Between June 6, 2011, and Oct 29, 2015, we recruited and randomly assigned 635 women: 319 to antenatal expressing and 316 to standard care. Three were not included in the primary analysis (one withdrawal from the standard care group, and one post-randomisation exclusion and one withdrawal from the antenatal expressing group). The proportion of infants admitted to the NICU did not differ between groups (46 15% of 317 assigned to antenatal expressing vs 44 14% of 315 assigned to standard care; adjusted relative risk 1·06, 95% CI 0·66 to 1·46). In the antenatal expressing group, the most common serious adverse event for infants was admission to the NICU for respiratory support (for three <1% of 317. In the standard care group, the most common serious adverse event for infants was moderate to severe encephalopathy with or without seizures (for three <1% of 315). Interpretation There is no harm in advising women with diabetes in pregnancy at low risk of complications to express breastmilk from 36 weeks' gestation. Funding Australian National Health and Medical Research Council.
Late-onset sepsis frequently complicates prematurity, contributing to morbidity and mortality. Probiotics may reduce mortality and necrotizing enterocolitis (NEC) in preterm infants, with unclear ...effect on late-onset sepsis. This study aimed to determine the effect of administering a specific combination of probiotics to very preterm infants on culture-proven late-onset sepsis.
A prospective multicenter, double-blinded, placebo-controlled, randomized trial compared daily administration of a probiotic combination (Bifidobacterium infantis, Streptococcus thermophilus, and Bifidobacterium lactis, containing 1 × 10(9) total organisms) with placebo (maltodextrin) in infants born before 32 completed weeks' gestation weighing <1500 g. The primary outcome was at least 1 episode of definite late-onset sepsis.
Between October 2007 and November 2011, 1099 very preterm infants from Australia and New Zealand were randomized. Rates of definite late-onset sepsis (16.2%), NEC of Bell stage 2 or more (4.4%), and mortality (5.1%) were low in controls, with high breast milk feeding rates (96.9%). No significant difference in definite late-onset sepsis or all-cause mortality was found, but this probiotic combination reduced NEC of Bell stage 2 or more (2.0% versus 4.4%; relative risk 0.46, 95% confidence interval 0.23 to 0.93, P = .03; number needed to treat 43, 95% confidence interval 23 to 333).
The probiotics B infantis, S thermophilus, and B lactis significantly reduced NEC of Bell stage 2 or more in very preterm infants, but not definite late-onset sepsis or mortality. Treatment with this combination of probiotics appears to be safe.
Purpose
Chronic diseases such as cancer and cardiovascular disease (CVD) are well-established causes of disability and premature deaths. Dietary components that are known to affect chronic ...inflammation have been implicated in the etiology and prognosis of these chronic diseases. We examined the ability of the dietary inflammatory index (DII) to predict overall, cancer and CVD mortality in the Iowa Women’s Health study.
Methods
The DII was computed from baseline dietary intake assessed in this cohort of 37,525 women, who were aged 55–69 years when enrolled starting in 1986. During the follow-up period, through December 31, 2010, in a total of 17,793 deaths, 5044 cancer- and 6528 CVD-related deaths were identified through mortality record linkage. Cox proportional hazards regression was used to estimate hazard ratios (HR) with DII expressed both as a continuous variable and as quartiles.
Results
Comparing subjects in DII Quartile 4 versus Quartile 1, modest positive associations were noted for all-cause mortality (HR
Q4vsQ1
1.07; 95 % CI 1.01–1.13;
p-
trend = 0.006), digestive cancer mortality (HR
Q4vsQ1
1.19; 95 % CI 1.00–1.43;
p-
trend = 0.05), CVD mortality (HR
Q4vsQ1
1.09; 95 % CI 1.01–1.18;
p-
trend = 0.08), non-cancer/non-CVD/non-acute mortality (HR
Q4vsQ1
1.09; 95 % CI 1.00–1.19;
p-
trend = 0.19), coronary heart disease (CHD) mortality (HR
Q4vsQ1
1.17; 95 % CI 1.05–1.30;
p-
trend = 0.001) and chronic obstructive pulmonary disease (COPD) mortality (HR
Q4vsQ1
1.43; 95 % CI 1.18–1.75;
p-
trend = 0.0006). No substantial associations were observed for mortality from stroke, Alzheimer’s disease or unspecified dementia.
Conclusion
These results indicate that a pro-inflammatory diet, as evidenced by higher DII scores, may be associated with total mortality as well as mortality from digestive cancer, CVD, CHD and COPD.
Summary Effective resuscitation of the newborn infant has the potential to save many lives around the world and reduce disabilities in children who survive peripartum asphyxia. In this Series paper, ...we highlight some of the important advances in the understanding of how best to resuscitate newborn infants, which includes monitoring techniques to guide resuscitative efforts, increasing awareness of the adverse effects of hyperoxia, delayed umbilical cord clamping, the avoidance of routine endotracheal intubation for extremely preterm infants, and therapeutic hypothermia for hypoxic–ischaemic encephalopathy. Despite the challenges of performing high-quality clinical research in the delivery room, researchers continue to refine and advance our knowledge of effective resuscitation of newborn infants through scientific experiments and clinical trials.
The ProPrems trial, a multi-center, double-blind, placebo-controlled randomized trial, previously reported a 54% reduction in necrotizing enterocolitis (NEC) of Bell stage 2 or more from 4.4 to 2.0% ...in 1099 infants born before 32 completed weeks' gestation and weighing < 1500 g, receiving probiotic supplementation (with Bifidobacterium longum subsp. infantis BB-02, Streptococcus thermophilus TH-4 and Bifidobacterium animalis subsp. lactis BB-12). This sub-study investigated the effect of probiotic supplementation on the gut microbiota in a cohort of very preterm infants in ProPrems.
Bifidobacterium was found in higher abundance in infants who received the probiotics (AOR 17.22; 95% CI, 3.49-84.99, p < 0.001) as compared to the placebo group, and Enterococcus was reduced in infants receiving the probiotic during the supplementation period (AOR 0.27; 95% CI, 0.09-0.82, p = 0.02).
Probiotic supplementation with BB-02, TH-4 and BB-12 from soon after birth increased the abundance of Bifidobacterium in the gut microbiota of very preterm infants. Increased abundance of Bifidobacterium soon after birth may be associated with reducing the risk of NEC in very preterm infants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Probiotic supplementation to mothers and/or their term‐born infants has been suggested to prevent allergic disease, in particular eczema; however, no studies have investigated probiotics ...for prevention of allergic diseases in very preterm infants. We evaluated the effect of a postnatal probiotic combination on development of allergic diseases in very preterm infants.
Methods
This sub‐study was an a priori secondary outcome of the ProPrems multi‐center, double‐blind, placebo‐controlled randomized trial (ANZCTR:12607000144415). ProPrems randomized 1099 very preterm infants to receive a probiotic combination or placebo from soon after birth until discharge from hospital or term corrected age (CA), whichever was earlier. Allergic disease (eczema, atopic eczema, food allergy, wheeze, atopic sensitization) was assessed in a subgroup of ProPrems infants (n = 281) as close to 12 months CA as possible by questionnaire, clinical examination, and skin prick tests to common allergens.
Results
There was no difference in eczema incidence between the probiotic and placebo groups (3530% of 118 infants vs 3727% of 137 infants, respectively, absolute difference 2.65%, 95% CI −8.45 to 13.75). Similarly, the incidence of atopic eczema (65% of 118 vs 32% of 137), food allergy (43% of 124 vs 21% of 154), wheeze (3931% of 127 vs 4529% of 154), and atopic sensitization (1413% of 106 vs 1311% of 123) were similar between the probiotic and placebo groups.
Conclusion
This study found no effect of postnatal administration of a probiotic combination on the incidence of allergic diseases or atopic sensitization in the first 2 years of life in children born very preterm. Evidence that probiotics are effective for prevention of allergic disease in premature infants remains lacking; adequately powered randomized controlled trials evaluating probiotic supplementation for allergy prevention in very preterm infants are needed.
We evaluated the effect of postnatal probiotic supplementation on the development of allergic diseases and atopic sensitization in very preterm infants. We found no difference in the incidence of allergic diseases or atopic sensitization between the probiotic and placebo groups. Although current guidelines recommend probiotics for prevention of allergic diseases in high‐risk infants, our findings demonstrate that there is insufficient evidence to determine whether the guideline recommendations are applicable to very preterm infants.
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