Use of whole blood over plasma enhances the detection of dengue virus RNA: possible utility in dengue vaccine trials.

In the present study, the utility of viral RNA isolated from whole blood over plasma for detection of dengue virus (DENV) was investigated in 80 samples referred for serotyping by DENV serotype-specific one-step real-time RT-PCR. DENV RNA was detected in 71.25% of the whole blood samples compared to 46.25% in the corresponding plasma samples. In secondary infections, DENV RNA was detected in 83.3% of whole blood samples, while it was detected in 40.5% of plasma samples (P = 0.0001). Non-structural protein 1 (NS1) antigen was detected in only 54.8% of the secondary infections. The detection rate of DENV RNA in whole blood is higher than in plasma. We suggest that one-step real-time RT-PCR using RNA from whole blood combined with an NS1 ELISA should be the choice for dengue diagnosis in dengue vaccine trials.

Benefit of antenatal corticosteroids by year of birth among preterm infants in Canada during 2003-2017: a population-based cohort study.

OBJECTIVE: To evaluate the changes in the associations of antenatal corticosteroids (ACS) with neonatal mortality and severe neurological injury over time (2003-17). DESIGN: National, population-representative, retrospective cohort study. SETTING: Level III neonatal intensive care units participating in the Canadian Neonatal Network. POPULATION: All infants born at 230/7 -336/7 weeks of gestation (n = 43 456). METHODS: We estimated the associations between exposure to ACS and neonatal outcomes by year of birth. Year of birth was considered both continuously and categorically as three consecutive epochs. MAIN OUTCOME MEASURE: Neonatal mortality and severe neurological injury. RESULTS: The absolute rates of neonatal mortality and severe neurological injury decreased during the study period in both the ACS and No ACS groups. For infants born at 230/7 -306/7 weeks of gestation, ACS was associated with similar reductions in neonatal mortality across the three epochs (9.0% versus 18.1%, adjusted relative risk [aRR] 0.54, 95% CI 0.47-0.61 in 2003-09; 7.6% versus 19.6%, aRR 0.51, 95% CI 0.44-0.59 in 2010-13; and 7.3% versus 14.5%, aRR 0.56, 95% CI 0.46-0.68 in 2014-17) and in severe neurological injury (13.2% versus 25.8%, aRR 0.57, 95% CI 0.50-0.64 in 2003-09; 7.4% versus 17.4%, aRR 0.53, 95% CI 0.43-0.66 in 2010-14; and 7.2% versus 14.8%, aRR 0.59, 95% CI 0.48-0.74 in 2014-17). CONCLUSION: Despite the ongoing improvements in neonatal care of preterm infants, as reflected by the gradual decrease in the absolute rates of neonatal mortality and severe neurological injury, the association of ACS treatment with neonatal mortality and severe neurological injury among extremely preterm infants born at 23-30 weeks of gestation has remained stable throughout the study period of 15 years. TWEETABLE ABSTRACT: Despite the gradual decrease in the rates of neonatal mortality and severe neurological injury, antenatal corticosteroids remain an important intervention in the current era of neonatal care.

Serotype-specific differences in the laboratory parameters among hospitalized children with dengue and genetic diversity of dengue viruses circulating in Tamil Nadu, India during 2017.

In 2017, Tamil Nadu, a southern state, had the second highest number of dengue cases from India. In the present study, the serotype-specific differences in the clinical manifestations and laboratory parameters among hospitalized children with dengue were investigated and molecular characterization of the circulating dengue virus (DENV) serotypes during 2017 in Tamil Nadu was performed. Eighty children with dengue-like symptoms consecutively admitted to a tertiary care hospital and positive for DENV NS1 antigen were investigated for DENV serotype utilizing a real-time reverse transcriptase based polymerase chain reaction assay. Complete envelope (E) gene sequencing of the DENV strains was performed. Seventy samples were positive for serotyping (25 DENV-1, 17 DENV-2, six DENV-3, and 22 DENV-4). DENV-4 infections were associated with elevated levels of liver enzymes; Alanine aminotransferase (P = .021) and aspartate aminotransferase (P = .001). However, none of the serotype was associated with any specific clinical features and severe dengue. Asian and American/African genotypes of DENV-1 were cocirculating. The circulating genotype was cosmopolitan for DENV-2 with multiple lineages, genotype III for DENV-3 and genotype I for DENV-4. Unique mutations were present in the 2017 DENV-4 isolates. The present study suggests the association of DENV-4 with elevated liver enzymes in children hospitalized for dengue. Further, the study reports the genetic diversity of DENV circulating in Tamil Nadu during 2017. The study calls for continuous monitoring of the circulating serotypes and genotypes at regional level in India which might result in a region wise database useful in predicting future outbreaks.

Clinical evaluation of an in-house-developed real-time RT-PCR assay for serotyping of dengue virus.

In the present study, an in-house-developed real-time RT-PCR (rRT-PCR) for serotyping of dengue virus (DENV) was evaluated for its performance, using 612 clinical samples. Compared to the composite reference standard, the in-house-developed rRT-PCR had an overall sensitivity of 97.5% and a specificity of 100%. The assay had a sensitivity of 100%, 95.6%. 96.9% and 100% for detecting DENV-1, DENV-2, DENV-3 and DENV-4, respectively. We recommend periodic evaluation of real-time RT-PCR assays for detecting DENV serotypes with a large number of samples and the use of at least two assays that target different regions of DENV genomes.

Involvement of dual serotypes during a severe dengue outbreak in Wadi area, Nagpur district, Maharashtra 2017.

BACKGROUND & OBJECTIVES: An outbreak of dengue-like illness was reported from Wadi area within the Nagpur Municipal Corporation during September-October 2017 with five deaths. Major symptoms reported were high fever (103-106 oF), acute joint pains, myalgia, drowsiness, breathlessness, etc. An investigation was conducted to confirm the etiological agent, its characterization and the vectors involved in the outbreak. METHODS: Serological analysis was conducted to detect dengue (DEN)/chikungunya IgM antibodies in 158 sera samples. Nested-PCR was carried out to serotype eight ELISA positive samples. Adult and larval mosquito collections were conducted in the affected areas to determine species composition and mosquito density. RESULTS: Dengue IgM antibodies were detected in 44 sera samples. Molecular typing revealed involvement of DEN-2 and DEN-3 serotypes. Dengue hemorrhagic fever symptoms were observed in two patients. Aedes aegypti breeding was found rampant with Breteu index and house index ranging from 23 to 70 and 17 to 56, respectively. Major breeding habitats encountered were, used tyres, cement tanks and refrigerator trays. INTERPRETATION & CONCLUSION: Clinical symptoms, detection of anti-DEN IgM antibodies in high number of samples and heavy breeding of Ae. aegypti confirmed it was a dengue outbreak.

A review of international clinical practice guidelines for the use of oxygen in the delivery room resuscitation of preterm infants.

AIM: To collate and assess international clinical practice guidelines (CPG) to determine current recommendations guiding oxygen management for respiratory stabilisation of preterm infants at delivery. METHODS: A search of public databases using the terms 'clinical practice guidelines', 'preterm', 'oxygen' and 'resuscitation' was made and complemented by direct query to consensus groups, resuscitation expert committees and clinicians. Data were extracted to include the three criteria for assessment: country of origin, gestation and initial FiO2 and target SpO2 for the first 10 minutes of life. RESULTS: A total of 45 CPGs were identified: 36 provided gestation specific recommendations (<28 to <37 weeks) while eight distinguished only between 'preterm' and 'term'. The most frequently recommended initial FiO2 were between 0.21 and 0.3 (n = 17). Most countries suggested altering FiO2 to meet SpO2 targets recommended by expert committees, However, specific five-minute SpO2 targets differed by up to 20% (70-90%) between guidelines. Five countries did not specify SpO2 targets. CONCLUSION: CPG recommendations for delivery room oxygen management of preterm infants vary greatly, particularly in regard to gestational ages, initial FiO2 and SpO2 targets and most acknowledge the lack of evidence behind these recommendations. Sufficiently large and well-designed randomised studies are needed to inform on this important practice.

Effectiveness of progesterone, cerclage and pessary for preventing preterm birth in singleton pregnancies: a systematic review and network meta-analysis.

BACKGROUND: Preterm birth (PTB) is the leading cause of infant death, but it is unclear which intervention is best to prevent it. OBJECTIVES: To compare progesterone, cerclage and pessary, determine their relative effects and rank them. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL and Web of Science (to April 2016), without restrictions, and screened references of previous reviews. SELECTION CRITERIA: We included randomised trials of progesterone, cerclage or pessary for preventing PTB in women with singleton pregnancies at risk as defined by each study. DATA COLLECTION AND ANALYSIS: We extracted data by duplicate using a piloted form and performed Bayesian random-effects network meta-analyses and pairwise meta-analyses. We rated evidence quality using GRADE, ranked interventions using SUCRA and calculated numbers needed to treat (NNT). MAIN RESULTS: We included 36 trials (9425 women; 25 low risk of bias trials). Progesterone ranked first or second for most outcomes, reducing PTB < 34 weeks [odds ratio (OR) 0.44; 95% credible interval (CrI) 0.22-0.79; NNT 9; low quality], <37 weeks (OR 0.58; 95% CrI 0.41-0.79; NNT 9; moderate quality), and neonatal death (OR 0.50; 95% CrI 0.28-0.85; NNT 35; high quality), compared with control, in women overall at risk. We found similar results in the subgroup with previous PTB, but only a reduction of PTB < 34 weeks in women with a short cervix. Pessary showed inconsistent benefit and cerclage did not reduce PTB < 37 or <34 weeks. CONCLUSIONS: Progesterone was the best intervention for preventing PTB in singleton pregnancies at risk, reducing PTB < 34 weeks, <37 weeks, neonatal demise and other sequelae. TWEETABLE ABSTRACT: Progesterone was better than cerclage and pessary to prevent preterm birth, neonatal death and more in network meta-analysis.

Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis.

BACKGROUND: About half of twin pregnancies deliver preterm, and it is unclear whether any intervention reduces this risk. OBJECTIVES: To assess the evidence for the effectiveness of progesterone, cerclage, and pessary in twin pregnancies. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ISI Web of Science, without language restrictions, up to 25 January 2016. SELECTION CRITERIA: Randomised controlled trials of progesterone, cerclage, or pessary for preventing preterm birth in women with twin pregnancies, without symptoms of threatened preterm labour. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data using a piloted form. Study quality was appraised with the Cochrane Risk of Bias tool. We performed pairwise inverse variance random-effects meta-analyses. MAIN RESULTS: We included 23 trials (all but three were considered to have a low risk of bias) comprising 6626 women with twin pregnancies. None of the interventions significantly reduced the risk of preterm birth overall at <34 or <37 weeks of gestation, or neonatal death, our primary outcomes, compared to a control group. In women receiving vaginal progesterone, the relative risk (RR) of preterm birth <34 weeks of gestation was 0.82 (95% CI 0.64-1.05, seven studies, I2  36%), with a significant reduction in some key secondary outcomes, including very low birthweight (<1500 g, RR 0.71, 95% CI 0.52-0.98, four studies, I2  46%) and mechanical ventilation (RR 0.61, 95% CI 0.45-0.82, four studies, I2  22%). CONCLUSION: In twin gestations, although no overarching intervention was beneficial for the prevention of preterm birth and its sequelae, vaginal progesterone improved some important secondary outcomes. TWEETABLE ABSTRACT: Vaginal progesterone may be beneficial in twin pregnancies, but not 17-OHPC, cerclage, or pessary.

Seroprevalence of dengue in a rural and an urbanized village: A pilot study from rural western India.

BACKGROUND & OBJECTIVES: Dengue is highly prevalent in tropical and subtropical regions. The prevalence of dengue is influenced by number of factors, i.e. host, vector, virus and environmental conditions including urbanization and population density. A cross sectional study was undertaken to determine the seroprevalence of dengue in two selected villages that differed in the level of their urbanization and population density. METHODS: Two villages with demographically well-defined populations close to Pune, a metropolitan city of western India, were selected for the study. Age stratified serosurvey was carried out during February to May 2011 in the two villages-a rural village A, located 6 km from the national highway with a population density of 159/km2 ; and an urbanized village B, located along the highway with a population density of 779/km2 . Assuming a low seroposi- tivity of 10%, 702 serum samples were collected from village A. Sample size for village B was calculated on the basis of seropositivity obtained in village A, and 153 samples were collected. Serum samples were tested for the presence of dengue virus (DENV)-specific IgG. Simple proportional analyses were used to calculate and compare the seroprevalence. RESULTS: Of the 702 samples collected from village A, 42.8% were found positive for anti-DENV IgG. A significantly higher seropositivity for DENV (58.8%) was found in village B. In village A, there was an age dependent increase in seroprevalence; whereas, in village B, there was a steep increase from 17% positivity in 0-10 yr age group to 72% in the 11-20 yr age group. The seroprevalence was almost similar in the older age groups. INTERPRETATION & CONCLUSION: The observations suggested that prevalence of dengue is probably associated with urbanization and host population density. Areas that are in the process of urbanization needs to be monitored for prevalence of dengue and its vector, and appropriate vector control measures may be implemented.

Universal prophylaxis or preemptive strategy for cytomegalovirus disease after liver transplantation: a systematic review and meta-analysis.

We systematically reviewed and meta-analyze the efficacy of universal prophylaxis (UP) and preemptive (PE) strategies (using ganciclovir or valganciclovir) in preventing cytomegalovirus (CMV) disease (CMD) among liver transplant recipients (LTRs). We performed an electronic search of MEDLINE, EMBASE and the Cochrane Database till December 2013. Studies that assessed UP or PE for preventing CMD in LTRs were included. The risk of bias was assessed using the Newcastle-Ottawa scale. The primary outcome was CMD, secondary outcomes being acute cellular rejection (ACR), graft loss (GL) and mortality. Due to the heterogeneity of comparative studies, an indirect comparison was performed. Pooled incidence rates with 95% confidence interval (CI) are calculated for each outcome using a random-effects model. Thirty-two studies involving 2456 LTRs were included. The majority of the studies were of low risk of bias. Irrespective of donor/recipient CMV sero-status, CMD was 10% with UP (95% CI: 6-14; I(2) = 87%; 16 studies, n = 1581) and 7% with PE (95% CI: 3-10; I(2) = 84%; 16 studies, n = 875) (mean difference 2.6; 95% CI: -3.25 to 8.45, p = 0.34). Likewise, ACR and mortality were similar with the two strategies. However, GL was significantly lower in the UP group, regardless of donor/recipient sero-status. In indirect comparison, the incidence of CMD, ACR and mortality in LTRs were similar with two strategies. Trials comparing the two strategies directly are needed.

Association of combinations of interleukin-10 and pro-inflammatory cytokine gene polymorphisms with dengue hemorrhagic fever.

Pro-inflammatory and anti-inflammatory cytokines have been shown to play an important role in dengue disease pathogenesis. In the present study, to find out whether single nucleotide polymorphisms (SNPs) in the pro-inflammatory and anti-inflammatory cytokine genes are associated with dengue disease severity, SNPs in TNF, IFNG, IL1B, IL8, IL0, IL17A and IL17F genes were investigated using polymerase chain reaction based methods in 132 dengue (DEN) cases [87 dengue fever (DF), 45 dengue hemorrhagic fever (DHF) cases] and 108 apparently healthy controls (HC) from Pune, Maharashtra, western India. Under recessive genetic model (C/C vs. T/T+T/C), the TNF rs1799964 C/C genotype was significantly associated with DEN [P=0.014, OR with 95% CI 3.07 (1.18-7.98)]. Frequency of T/C genotype of IL17F rs763780 was significantly lower in DEN group as compared to HC [P=0.033, OR with 95% CI 0.43 (0.19-0.95)]. Under overdominant genetic model (A/T vs. A/A+T/T), IL8 rs4973 A/T genotype was negatively associated with DHF compared to HCs [p=0.029, OR with 95% CI 0.43 (0.20-0.93)]. Under overdominant genetic model, A/G genotype of IL10 rs1800871 was significantly negatively associated with DHF compared to DF cases [p=0.014, OR with 95% CI 0.35 (0.15-0.84)]. Significantly higher frequency of the combined genotype IL10 A/A-IFNG A/T and lower frequency of the combined genotypes IL10 A/G-IL1B A/A, IL10 A/G-IL8 A/T and IL10 A/G-IL17F T/T were observed in DHF cases compared to DF. The results suggest that heterozygous genotypes of IL8 rs4973 and IL10 rs1800871 are associated with reduced risk of DHF. Combinations of IL10 rs1800871 and pro-inflammatory cytokine genotypes influence the risk of DHF.

Polymorphisms in the retinoic acid-1 like-receptor family of genes and their association with clinical outcome of dengue virus infection.

Polymorphisms in the DDX58 and IFIH1 genes, which code for the retinoic acid inducible gene-1 protein and myeloid differentiation factor (MDA) 5, were investigated in 120 dengue (DEN) cases (88 dengue fever [DF] cases and 32 dengue hemorrhagic fever [DHF] cases) and 109 healthy controls (HCs) to investigate their association with dengue. The results revealed a lower carrier frequency of the DDX58 rs3205166 G allele in DEN than in HCs and a higher frequency of the DDX58 rs669260 T/C genotype in DHF than in DF cases (P = 0.043, OR with 95 % CI 3.358 [1.038-10.861]). This suggests that polymorphisms in DDX58 gene influence the clinical outcome of DENV infection.

Development of a multiplex real-time RT-PCR assay for simultaneous detection of dengue and chikungunya viruses.

Dengue and chikungunya viruses co-circulate and cause infections that start with similar symptoms but progress to radically different outcomes. Therefore, an early diagnostic test that can differentiate between the two is needed. A single-step multiplex real-time RT-PCR assay was developed that can simultaneously detect and quantitate RNA of all dengue virus (DENV) serotypes and chikungunya virus (CHIKV). The sensitivity was 100 % for DENV and 95.8 % for CHIKV, whilst the specificity was 100 % for both viruses when compared with conventional RT-PCR. The detection limit ranged from 1 to 50 plaque-forming units. The assay was successfully used for differential diagnosis of dengue and chikungunya in Pune, where the viruses co-circulate.

Profile of killer cell immunoglobulin-like receptor and its human leucocyte antigen ligands in dengue-infected patients from Western India.

Killer cell immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells (NKs). Qualitative and quantitative differences in the type and the number of KIRs expressed on NK cells affect its activation which would influence the outcome of the disease. In this study, 114 hospitalized cases of dengue [82 dengue fever (DF) and 32 dengue haemorrhagic fever (DHF) cases] and 104 healthy controls (HC) without no known history of hospitalization for dengue-like illness were investigated for their KIR gene profile to find out the association of KIR genes with dengue disease severity. KIR gene profile was investigated using duplex sequence-specific priming polymerase chain reaction-based typing system. The results revealed a higher frequency of KIR3DL1 gene [P = 0.0225; odds ratio (OR) 4.1 95% confidence interval (CI) 1.1-14.8] and lower frequency of KIR3DS1/3DS1 genotype [P = 0.0225; OR 0.24 95% CI (0.068-0.88)] in DF cases compared to HC. Immunoglobulin-like receptor gene frequencies were not different between DHF and DF or HC. The results suggest that KIR3DL1/KIR3DS1 locus might be associated with the risk of developing DF.

How often are late preterm births the result of non-evidence based practices: analysis from a retrospective cohort study at two tertiary referral centres in a nationalised healthcare system.

OBJECTIVE: To determine the proportion, characteristics, and predictors of late preterm birth (LPTB) in relation to evidence-based (EB) and non-evidence based (NEB) indications. DESIGN: Retrospective cohort study. SETTING: Two Canadian tertiary referral centres. POPULATION: All live singleton LPTBs over 1 year from 2010 to 2011, excluding major congenital anomalies. METHODS: Indications for LPTB were classified a priori as EB (i.e. based on practice guidelines or on evidence from randomised controlled trials) or NEB. Data were abstracted from maternal antenatal and labour records. Univariate analyses were completed using Fischer's exact, Pearson's chi-square, or analysis of variance (anova) F-tests. Logistic regression included gestation at birth, delivery provider, previous stillbirth, previous caesarean section, corticosteroid administration, and previous preterm birth as predictors for NEB LPTB. MAIN OUTCOME MEASURES: The proportion, characteristics, and predictors of women with NEB versus EB LPTBs. RESULTS: Of 524 LPTBs, 25.2% (n = 132) were NEB. Logistic regression revealed that NEB LPTBs were less likely if patients were delivered by their own doctor or their doctor's practice partner (OR 0.53, 95% CI 0.34-0.83). However, NEB LPTBs were more likely in women who had experienced a previous stillbirth (OR 2.57, 95% CI 1.20-5.49). CONCLUSIONS: Approximately one-quarter of LPTBs are NEB. Further research is needed to see if a review of the indications for LPTB, and subsequent reduction in NEB LPTBs, translates into improved neonatal outcomes and cost savings.

Factors associated with the development of cardiac allograft vasculopathy--a systematic review of observational studies.

Cardiac allograft vasculopathy (CAV) is a significant factor impacting outcomes after heart transplant. We performed a systematic review of risk factors for the development of CAV. A search of electronic databases was performed. The eligibility criteria included cohort and case-control studies with more than 50 adult patients submitted to a heart transplant. The outcome should be CAV diagnosed by angiography and/or intravascular ultrasound (IVUS). Two reviewers performed study selection, data abstraction, and quality assessment. Of 2514 citations, 66 articles were included--46 had 200 participants or less; 61 were single-center; and 44 were retrospective cohorts. The most used definition of CAV using angiography was the detection of any degree of abnormality (21 studies of 58). In studies using IVUS, an intimal thickness ≥0.5 mm was the most used definition (five of eight studies). Quality assessment revealed an inadequate description of patient selection, attrition, and accounting of potential confounders. Donor age, recipient age, recipient gender, etiology of heart failure, ischemic time, human leukocyte antigen matching, cytomegalovirus, lipid profile, and rejection episodes were the most studied factors. Our review indicates that the current evidence is not consistent across different studies. The definite contribution of risk factors for the development of CAV is still to be determined.

Development and evaluation of the clinimetric properties of the Medication-Related Osteonecrosis of the Jaw Quality of Life Questionnaire (MRONJ-QoL).

The purpose of this study was to develop a self-administered questionnaire (MRONJ-QoL) to assess the quality of life (QoL) of patients with medication-related osteonecrosis of the jaw (MRONJ). A prospective study was performed to develop and evaluate the questionnaire. The MRONJ-QoL was formulated through a review of the literature and interviews of experts and patients. Following development, it was administered to 60 patients with a diagnosis of MRONJ. The sensibility of the questionnaire was assessed by evaluating feasibility (via interviews of patients), face validity (via interviews of patients and experts), and content validity (via evaluation of internal consistency, floor/ceiling effects, and factor analysis). Reliability was evaluated by measuring intra-rater reliability. Construct validity of the questionnaire was evaluated by both cross-sectional and longitudinal comparisons, including comparing scores of the MRONJ-QoL to disease resolution at 6 months. The final MRONJ-QoL questionnaire consisted of 14 questions, demonstrating high internal consistency (Cronbach's alpha of 0.85) and good reliability (weighted kappa score of 0.65). At the 6-month follow-up, disease resolution was found to be significantly associated with improved MRONJ-QoL scores, suggesting validity of the questionnaire (P < 0.01). Therefore, this is a sensible, reliable, and valid questionnaire for evaluating the QoL of patients with MRONJ.

Factors associated with antibiotic administration delay among preterm infants with late-onset bloodstream infection.

Early antibiotic administration is an important modifiable factor in reducing mortality from late-onset bloodstream infections in preterm infants. In a cohort study including 142 infants with non-coagulase negative staphylococcus bloodstream infection at two tertiary neonatal intensive care units, we identified typical practice-related factors that may be targeted to prevent delays in antibiotic administration. Collection of cerebrospinal fluid or urine sample before administering antibiotics, a longer time taken to site a peripheral intravenous catheter among those without pre-existing access, and a longer time taken to administer fluid boluses were associated with a longer than median time to antibiotic administration.

Variability in the diagnostic and management practices of post-hemorrhagic ventricular dilatation in very preterm infants across Canadian centers and comparison with European practices.

OBJECTIVES: To investigate the variability in diagnostic and therapeutic approaches to posthemorrhagic ventricular dilatation (PHVD) among Canadian neonatal centers, and secondary exploration of differences in approaches between Canadian and European practices. METHODS: We conducted a survey among Canadian tertiary neonatal centers on their local practices for managing very preterm infants with PHVD. The survey covered questions on the diagnostic criteria, timing and type of interventions and resources utilization (transfer to neurosurgical sites and neurodevelopmental follow-up). In a secondary exploration, Canadian responses were compared with responses to the same survey from European centers. RESULTS: 23/30 Canadian centers (77%) completed the survey. There was no consensus among Canadian centers on the criteria used for diagnosing PHVD or to initiate intervention. The therapeutic interventions also vary, both for temporizing procedures or permanent shunting. Compared to European practices, the Canadian approach relied less on the sole use of ultrasound criteria for diagnosing PHVD (43 vs 94%, p < 0.0001) or timing intervention (26 vs 63%, p = 0.007). Majority of European centers intervened early in the development of PHVD based on ultrasound parameters, whereas Canadian centers intervened based on clinical hydrocephalus, with fewer centers performing serial lumbar punctures prior to neurosurgical procedures (40 vs 81%, p = 0.003). CONCLUSION: Considerable variability exists in diagnosis and management of PHVD in preterm infants among Canadian tertiary centers and between Canadian and European practices. Given the potential implications of the inter-center practice variability on the short- and long-term outcomes of preterm infants with PHVD, efforts towards evidence-based Canada-wide practice standardization are underway.

Fruit and vegetable intake and bone health in women aged 45 years and over: a systematic review.

UNLABELLED: High fruit and vegetable intake may be associated with improved bone status among women aged ≥ 45 years. This is the first systematic review that specifically assessed this association and identified research gaps. The benefits of fruit and vegetables (F&V) on bone health remain unclear. Further studies are needed. INTRODUCTION: F&V have several components that are beneficial to bones. Some studies report that high F&V intake is associated with improved bone status in middle aged and aged women; however, findings are inconsistent. The objective was to systematically review observational and interventional studies that investigated the effects of F&V intake on incidence of osteoporotic fractures, bone mineral density (BMD), and bone turnover markers (BTM) in women aged ≥ 45 years and to identify potential research gaps. METHODS: Electronic databases were searched, and peer-reviewed manuscripts published in English, with F&V intake as a main dietary exposure, were included. Data selection, extraction, and evaluation of risk of bias were performed independently by two reviewers. RESULTS: Eight studies were included. One cohort study reported cross-sectional as well as longitudinal data. There was significant between-study heterogeneity in design, definition, and amount of F&V intake, outcomes, analyses, and reporting of results. Two studies had low, two had moderate, and four had high risk of bias. Among reports with low or moderate risk of bias, two cross-sectional analyses reported positive associations between F&V intake and BMD of the forearm, lumbar spine, or total hip, whereas one randomized controlled trial and two prospective cohort analyses reported no effects. One trial reported no associations between F&V and BTM. CONCLUSIONS: Based on limited evidence, the benefits of F&V on bone health remain unclear for women aged ≥ 45 years. Further studies with low risk of bias are needed.