Translation of nonclinical to clinical safety findings for 27 biotherapeutics.

Human adverse drug reactions (ADRs), and in vivo nonclinical adverse and nonadverse findings, were identified in 27 biotherapeutic programs and placed into organ categories to determine translation. The sensitivity of detecting human ADRs was 30.8% with a positive predictive value (PPV) of 53.3% for nonclinical adverse findings; sensitivity increased to 67.3% and PPV fell to 35.0% when including nonadverse findings. Nonclinical findings were associated with a greater likelihood of a human ADR in that organ category, especially for adverse findings [positive likelihood ratio (LR+) >10 (lower 95% confidence interval [CI] of >5)]. The specificity and negative predictive value (NPV) were very high (>85%). A lack of nonclinical findings in an organ category was associated with a lower likelihood of a human ADR in that organ category. About 40-50% of human ADRs and nonclinical adverse findings, and about 30% of nonclinical nonadverse findings, were attributed to pharmacology. Slightly more than half of the human ADRs with a translating nonclinical finding had findings in animals that could be considered very similar. Overall, 38% of nonclinical findings translated to a human ADR at the organ category level. When nonclinical findings did not translate to humans, the cause was usually higher exposures or longer dosing in animals. All programs with human ADRs attributed to immunogenicity also had nonclinical adverse or nonadverse findings related to immunogenicity. Overall, nonclinical adverse and nonadverse findings were useful in predicting human ADRs, especially at an organ category level, and the majority of human ADRs were predicted by nonclinical toxicity studies.

Green synthesis of silver nanoparticles by using Allium sativum extract and evaluation of their electrical activities in bio-electrochemical cell.

An electrical application of green synthesized silver nanoparticles (Ag NPs) by developing a unique bio-electrochemical cell (BEC) has been addressed in the report. Here, garlic extract (GE) has been used as a reducing agent to synthesize Ag NPs, and as a bio-electrolyte solution of BEC. Ag NPs successfully formed into face-centered cubic structures with average crystallite and particle sizes of 8.49 nm and 20.85 nm, respectively, according to characterization techniques such as the UV-vis spectrophotometer, XRD, FTIR, and FESEM. A broad absorption peak at 410 nm in the UV-visible spectra indicated that GE played a vital role as a reducing agent in the transformation of Ag+ions to Ag NPs. After that four types of BEC were developed by varying the concentration of GE, CuSO4. 5H2O, and Ag NPs electrolyte solution. The open circuit voltage and short circuit current of all cells were examined with the time duration. Moreover, different external loads (1 Ω, 2 Ω, 5 Ω, and 6 Ω) were used to investigate the load voltage and load current of BEC. The results demonstrated that the use of Ag NPs on BEC played a significant role in increasing the electrical performance of BEC. The use of GE-mediated Ag NPs integrated the power, capacity, voltage efficiency, and energy efficiency of BEC by decreasing the internal resistance and voltage regulation. These noteworthy results can take a frontier forward to the development of nanotechnology for renewable and low-cost power production applications.

Elevated Plasma Matrix Metalloproteinase 8 Associates With Sputum Culture Positivity in Pulmonary Tuberculosis.

Current methods for tuberculosis treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during tuberculosis treatment as biomarkers. Plasma MMP-1, MMP-8, and MMP-10 concentrations significantly decreased during treatment. Plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture-positive relative to culture-negative participants, before (median, 4993 pg/mL [interquartile range, 2542-9188] vs 698 [218-4060] pg/mL, respectively; P = .004) and after (3650 [1214-3888] vs 720 [551-1321] pg/mL; P = .008) 6 months of tuberculosis treatment. Consequently, plasma MMP-8 is a potential biomarker to enhance tuberculosis treatment monitoring and screen for possible culture positivity.

Early cryoprecipitate transfusion versus standard care in severe postpartum haemorrhage: a pilot cluster-randomised trial.

There is a lack of evidence evaluating cryoprecipitate transfusion in severe postpartum haemorrhage. We performed a pilot cluster-randomised controlled trial to evaluate the feasibility of a trial on early cryoprecipitate delivery in severe postpartum haemorrhage. Pregnant women (>24 weeks gestation), actively bleeding within 24 h of delivery and who required at least one unit of red blood cells were eligible. Women declining transfusion in advance or with inherited clotting deficiencies were not eligible. Four UK hospitals were randomly allocated to deliver either the intervention (administration of two pools of cryoprecipitate within 90 min of first red blood cell unit requested plus standard care), or the control group treatment (standard care, where cryoprecipitate is administered later or not at all). The primary outcome was the proportion of women who received early cryoprecipitate (intervention) vs. standard care (control). Secondary outcomes included consent rates, acceptability of the intervention, safety outcomes and preliminary clinical outcome data to inform a definitive trial. Between March 2019 and January 2020, 199 participants were recruited; 19 refused consent, leaving 180 for analysis (110 in the intervention and 70 in the control group). Adherence to assigned treatment was 32% (95%CI 23-41%) in the intervention group vs. 81% (95%CI 70-90%) in the control group. The proportion of women receiving cryoprecipitate at any time-point was higher in the intervention (60%) vs. control (31%) groups; the former had fewer red blood cell transfusions at 24 h (mean difference -0.6 units, 95%CI -1.2 to 0); overall surgical procedures (odds ratio 0.6, 95%CI 0.3-1.1); and intensive care admissions (odds ratio 0.4, 95%CI 0.1-1.1). There was no increase in serious adverse or thrombotic events in the intervention group. Staff interviews showed that lack of awareness and uncertainty about study responsibilities contributed to lower adherence in the intervention group. We conclude that a full-scale trial may be feasible, provided that protocol revisions are put in place to establish clear lines of communication for ordering early cryoprecipitate in order to improve adherence. Preliminary clinical outcomes associated with cryoprecipitate administration are encouraging and merit further investigation.

New Parasitic Records of Aves: Phasianidae (Alectoris Chukar) in Malakand Division Northern, Pakistan.

More than 24,000 species of helminth parasitize wild birds worldwide, and this number is expanding as interest in wildlife parasitology increases. The objective of the current study was to update the baseline of helminthological surveys conducted on chukar partridges (Alectoris chukar) in northern Pakistan. After reviewing the available literature, a parasite-host association checklist was developed. Nematodes (53.8 %) were the most commonly reported parasite, followed by cestodes (15.3 %) and trematodes (15.3 %) respectively. Seventy (70) chukar partridge (Alectoris chukar) distributed across the Malakand division of northern Pakistan were screened for parasitosis during the period from October 2020 to the end of December 2021. Blood samples of all the specimens were screened for haemoprotozoa, the digestive tract was examined for protozoans and helminths. The examined birds were infected with nine different helminth parasite species identified as cestodes (4 species), trematodes (2 species) and 3 species of nematodes. 29 out of 70 birds were infected, with the male and female infection rates being 36 % and 52.1 %, respectively, with a total prevalence of 41.3 %. Among the infected birds 10 (34.4 %) contained cestodes, 2 (6.8 %) contained trematodes and 17 (58.6 %) contained nematodes. Of which Ascaridia galli and Capillaria phasianina recorded the highest prevalence (10 %). While Amoebotaenia cuneate, Choanotaenia infundibulum, Hypoderaeum conoideum, Lyperosomum longicauda recorded the least (1.4 %) respectively. Reporting of Raillietina echinobothrida, Amoebotaenia cuneate and Lyperosomum longicauda constitute new host records. A. cuneate is a new record in the parasitological list in the country. In terms of host's sexuality, the overall figures show no significant changes in infection indices.

Accuracy of imaging modalities for adnexal torsion: a systematic review and meta-analysis.

BACKGROUND: Adnexal torsion (AT), a serious gynaecological emergency, often presents with non-specific symptoms leading to delayed diagnosis. OBJECTIVE: To compare the test accuracy of ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) to diagnose AT. SEARCH STRATEGY: We searched EMBASE, MEDLINE and Cochrane CENTRAL until December 2019. SELECTION CRITERIA: Studies reporting on the accuracy of any imaging modality (Index Test) in female patients (paediatric and adult) suspected of AT compared with surgical diagnosis and/or standard clinical/radiological follow-up period until resolution of symptoms (Reference Standard). DATA COLLECTION AND ANALYSIS: We assessed study quality using QUADAS-2. We conducted test accuracy meta-analysis using a univariate model or a hierarchical model. MAIN RESULTS: We screened 3836 citations, included 18 studies (1654 women, 665 cases), and included 15 in the meta-analyses. Ultrasound pooled sensitivity (n = 12, 1187 women) was 0.79 (95% CI 0.63-0.92) and specificity was 0.76 (95% CI 0.54-0.93), with negative and positive likelihood ratios of 0.29 (95% CI 0.13-0.66) and 4.35 (95% CI 2.03-9.32), respectively. Using Doppler with ultrasound (n = 7, 845 women) yielded similar sensitivity (0.80, 95% CI 0.67-0.93) and specificity (0.88, 95% CI 0.72-1.00). For MRI (n = 3, 99 women), the pooled sensitivity was 0.81 (95% CI 0.63-0.91) and specificity was 0.91 (95% CI 0.80-0.96). A meta-analysis for CT was not possible with two case-control studies and one cohort study (n = 3, 232 women). Its sensitivity range was 0.74-0.95 and specificity was 0.80-0.90. CONCLUSIONS: Ultrasound has good performance as a first-line diagnostic test for suspected AT. Magnetic resonance imaging could offer improved specificity to investigate complex ovarian morphology, but more evidence is needed. TWEETABLE ABSTRACT: To investigate adnexal torsion, ultrasound is a good first-line diagnostic test with a pooled sensitivity of 0.79 and specificity of 0.76.

Virtual reality for acute pain in outpatient hysteroscopy: a randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of virtual reality as a distraction technique in the management of acute pain and anxiety during outpatient hysteroscopy. DESIGN: Parallel group, prospective randomised controlled trial. SETTING: UK University Hospital. METHODS: Forty consenting, eligible women were randomised to virtual reality intervention (immersive video content as a distraction method) or standard care during outpatient hysteroscopy from August to October 2018. MAIN OUTCOME MEASURES: Pain and anxiety outcomes were measured as a numeric rating score (scale 0-10). RESULTS: Compared with standard care, women with virtual reality intervention experienced less average pain (score 6.0 versus 3.7, mean difference 2.3, 95% CI 0.61-3.99, P = 0.009) and anxiety (score 5.45 versus 3.3, mean difference 2.15, 95% CI 0.38-3.92, P = 0.02). CONCLUSION: Virtual reality was effective in reducing pain and anxiety during outpatient hysteroscopy in a mixed-methods randomised control trial. Its wide potential role in ambulatory gynaecological procedures needs further evaluation. TWEETABLE ABSTRACT: Virtual reality can be used as a part of a multimodal strategy to reduce acute pain and anxiety in patients undergoing outpatient hysteroscopy.

Pravastatin for early-onset pre-eclampsia: a randomised, blinded, placebo-controlled trial.

OBJECTIVE: Women with pre-eclampsia have elevated circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1). Statins can reduce sFlt-1 from cultured cells and improve pregnancy outcome in animals with a pre-eclampsia-like syndrome. We investigated the effect of pravastatin on plasma sFlt-1 levels during pre-eclampsia. DESIGN: Blinded (clinician and participant), proof of principle, placebo-controlled trial. SETTING: Fifteen UK maternity units. POPULATION: We used a minimisation algorithm to assign 62 women with early-onset pre-eclampsia (24+0 -31+6  weeks of gestation) to receive pravastatin 40 mg daily (n = 30) or matched placebo (n = 32), from randomisation to childbirth. PRIMARY OUTCOME: Difference in mean plasma sFlt-1 levels over the first 3 days following randomisation. RESULTS: The difference in the mean maternal plasma sFlt-1 levels over the first 3 days after randomisation between the pravastatin (n = 27) and placebo (n = 29) groups was 292 pg/ml (95% CI -1175 to 592; P = 0.5), and over days 1-14 was 48 pg/ml (95% CI -1009 to 913; P = 0.9). Women who received pravastatin had a similar length of pregnancy following randomisation compared with those who received placebo (hazard ratio 0.84; 95% CI 0.50-1.40; P = 0.6). The median time from randomisation to childbirth was 9 days (interquartile range [IQR] 5-14 days) for the pravastatin group and 7 days (IQR 4-11 days) for the placebo group. There were three perinatal deaths in the placebo-treated group and no deaths or serious adverse events attributable to pravastatin. CONCLUSIONS: We found no evidence that pravastatin lowered maternal plasma sFlt-1 levels once early-onset pre-eclampsia had developed. Pravastatin appears to have no adverse perinatal effects. TWEETABLE ABSTRACT: Pravastatin does not improve maternal plasma sFlt-1 or placental growth factor levels following a diagnosis of early preterm pre-eclampsia #clinicaltrial finds.

Effects of oral probiotic supplements on vaginal microbiota during pregnancy: a randomised, double-blind, placebo-controlled trial with microbiome analysis.

OBJECTIVE: To determine the effects on the vaginal microbiota of an oral probiotic preparation administered from early pregnancy. DESIGN: Randomised, double blind, placebo-controlled trial. SETTING: Four maternity units in the UK. POPULATION: Women aged 16 years or older recruited at 9-14 weeks' gestation. METHODS: Participants were randomly allocated to receive oral capsules of probiotic containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 each at 2.5 × 109 colony-forming units (CFUs) or placebo once daily from recruitment until the end of pregnancy. MAIN OUTCOME MEASURE: Rates of bacterial vaginosis (BV, defined as Nugent score ≥7) at 18-20 weeks' gestation compared by logistic regression adjusted for possible confounders. RESULTS: The primary analysis included 78% (238/304) of participants who initially consented (probiotic group 123, placebo group 115). Of these participants, 95% (227/238) reported an intake of 93% or more of the required number of capsules. The rates of BV did not differ between groups at 18-20 weeks' gestation (15% (19/123) in the probiotic group vs. 9% (10/115) in the placebo group, adjusted odds ratio 1.82, 95% confidence interval 0.64-5.19). There were also no differences between the groups in the proportion of women colonised with the probiotic strains, Escherichia coli, group B streptococci or other vaginal microbiota. There were no differences in the alpha diversity or composition of the bacterial communities between or within the probiotic and placebo groups at 9-14 and 18-20 weeks' gestation. CONCLUSIONS: Oral probiotics taken from early pregnancy did not modify the vaginal microbiota. TWEETABLE ABSTRACT: The oral probiotic preparation used in this study does not prevent BV in pregnant women.

Breastfeeding avoidance following psychological intimate partner violence during pregnancy: a cohort study and multivariate analysis.

OBJECTIVE: To evaluate if the experience of psychological intimate partner violence (IPV) adversely affects breastfeeding rates. DESIGN: A cohort study. SETTING: Maternities in 15 public hospitals, drawn using cluster sampling of obstetric services in Andalusia, Spain. POPULATION: A total of 779 consecutive mothers receiving antenatal care including ultrasound and giving birth during February-June 2010. METHODS: Trained midwives gathered IPV data using the Index of Spouse Abuse validated in the Spanish language (score ranges: 0-100, higher scores reflect more severe IPV; cut-off: psychological IPV = 25). Sociodemographic data including lack of kin support, and obstetric and neonatal outcomes were collected. Multivariate logistic regression estimated adjusted odds ratios (aOR), with 95% confidence intervals (CI), of the relationship between psychological IPV and breastfeeding, controlling for sociodemographic characteristics and obstetric complications. MAIN OUTCOME MEASURE: Breastfeeding avoidance defined as lack of breastfeeding or pumping of breast milk to feed the new baby in the immediate post-partum period. RESULTS: Response rate was 92.2%. A total of 70% (n = 545) of women initiated breastfeeding. Psychological IPV, reported by 21.0% (n = 151), increased the odds of breastfeeding avoidance (aOR = 2.0; 95% CI = 1.2-3.3) adjusting for the presence of obstetric complications (aOR = 1.6; 95% CI = 1.0-2.4). CONCLUSIONS: Mothers with psychological IPV avoid breastfeeding. Clinicians should be aware of the risks to infant arising from this deficiency due to IPV in pregnancy. TWEETABLE ABSTRACT: Psychological intimate partner violence, reported by one in five mothers in this study, on average doubles the avoidance of breastfeeding.

Retreatability of two hydraulic calcium silicate-based root canal sealers using rotary instrumentation with supplementary irrigant agitation protocols: a laboratory-based micro-computed tomographic analysis.

AIM: To investigate the retreatability of two calcium silicate-based materials (BioRoot RCS, Septodont, Saint-Maur-des-Fossés, France and GuttaFlow Bioseal, Colténe/Whaledent AG, Langenau, Germany) using rotary instrumentation combined with supplementary irrigant agitation techniques using extracted teeth in a laboratory setting. METHODOLOGY: The root canals of extracted single-rooted mandibular premolars were prepared to size 40, .04 taper and randomly divided into two experimental groups (n = 36) depending on the root filling material. Root canals were filled with gutta-percha and GuttaFlow Bioseal (GB, group 1) or BioRoot RCS (BR, group 2), scanned using a micro-CT scanner and stored in phosphate-buffered saline for 4 months. Removal of root filling was performed with rotary instruments, and specimens were randomly allocated to one of the subgroups for supplementary irrigant agitation (n = 12): subgroup A, syringe irrigation (control); subgroup B, Tornado Brush (M.I.B, Suresnes, France) and subgroup C, ultrasonically activated irrigation. Specimens were re-scanned with micro-CT to calculate the volume of remnant root filling material. Data were analysed statistically by two-way ANOVA and post hoc Tukey's tests (P = 0.05). RESULTS: Specimens filled with GuttaFlow Bioseal were associated with a significantly smaller volume of root filling remnants compared with BioRoot RCS (P < 0.05). There was no significant difference between the supplementary irrigant agitation subgroups in the removal of GB (P > 0.05). In group 2 (BioRoot RCS), subgroups B (Tornado Brush) and C (ultrasonically activated irrigation) were associated with a significantly smaller volume of root filling remnants compared with subgroup A (syringe irrigation) (P < 0.05). There was no significant difference between subgroups B and C (P > 0.05). CONCLUSIONS: Significantly smaller volumes of root filling remnants of GuttaFlow Bioseal, than BioRoot RCS, were present after their removal with rotary instruments and irrigation. Supplementary irrigant agitation techniques were associated with smaller volumes of remnants during the removal of BioRoot RCS but not that of GuttaFlow Bioseal.

Influence of apical preparation size and irrigation technique on root canal debridement: a histological analysis of round and oval root canals.

AIM: To examine the debridement of round and oval root canals prepared to two apical sizes with and without ultrasonically activated irrigation. METHODOLOGY: Mandibular premolars with round (n = 48) and oval (n = 48) root canals were pair-matched after microCT scanning and randomly divided into two experimental groups (n = 20): group 1, rotary NiTi to size 20, .04 taper; group 2, rotary NiTi to size 40, .04 taper. Specimens were subdivided into two subgroups (n = 10): subgroup A, syringe and needle (SNI); subgroup B, ultrasonically activated irrigation (UAI). Untreated canals (eight oval and eight round) served as controls. Specimens were processed for histological evaluation for measurement of the remaining pulp tissue and debris (RPT), and the perimeter percentage of root canal area untouched by the instruments (PRAU). Following assessment of normality, multiple-way anova models were used to study the effects of preparation size, irrigation technique and canal cross-sectional shape, and their interactions on the RPT and PRAU (α = 0.05). RESULTS: All experimental groups had significantly less RPT than the control (P < 0.05). Both the preparation size (20 vs. 40) and the irrigation technique (SNI vs. UAI) had a significant effect on RPT (P = 0.006 and P < 0.001, respectively). Groups irrigated with SNI always had significantly greater RPT than those irrigated with UAI, irrespective of the preparation size (P < 0.001). Canals prepared to size 20 had significantly greater RPT than those with size 40 in the SNI subgroup (P < 0.001), but there was no significant difference in the UAI subgroup (P = 0.481). CONCLUSIONS: Root canals prepared to a larger size (40) were cleaner than those prepared to a smaller size (20), when irrigation was performed with a syringe and needle. When the irrigant was ultrasonically activated, smaller preparations resulted in canals that were as clean as larger preparations. This finding was common to both round and oval canals of freshly extracted premolars with vital pulp tissue.

Effect of Heavy Mass Ion (Gold) and Light Mass Ion (Boron) Irradiation on Microstructure of Tungsten.

The difference in the defect structures produced by different ion masses in a tungsten lattice is investigated using 80 MeV Au7+ ions and 10 MeV B3+ ions. The details of the defects produced by ions in recrystallized tungsten foil samples are studied using transmission electron microscopy. Dislocations of type b = 1/2[111] and [001] were observed in the analysis. While highly energetic gold ion produced small clusters of defects with very few dislocation lines, boron has produced large and sparse clusters with numerous dislocation lines. The difference in the defect structures could be due to the difference in separation between primary knock-on atoms produced by gold and boron ions.

Experience of care for Parkinson's disease in European countries: a survey by the European Parkinson's Disease Association.

BACKGROUND: Few studies report on the experience of care for patients with Parkinson's disease (PD) from their own point of view. METHODS: An analysis was carried out of a survey in 11 European countries on self-reported access to services and satisfaction with different aspects of care. RESULTS: In all, 1775 people with PD (PwP) participated with disease duration ranging from <1 to 42 years. When referred to a specialist most were seen within 3 months but medication reviews occurred every 3 months in only 10%, every 6 months in 37%, once a year in 40% and every 2 years or less frequently in 13%. Waiting times to therapists were usually ≥4 months. Satisfaction with care was highest for involvement of PwP in decisions (63% of respondents satisfied) and involvement of family/carer (62%) followed by communication with PwP (57%), information received (54%), frequency of treatment reviews (52%) and suitability of treatment for the individual condition and circumstances (52%), but lowest for availability and accessibility of treatment when needed (48%) and collaborations between healthcare professionals in delivering care (41% satisfied). The main factors associated with overall satisfaction scores with care were the overall satisfaction with initial consultation (r = 0.26, P < 0.0001), the sensitivity with which the diagnosis was communicated, the quantity of information provided (both r = 0.24, P < 0.0001) and the frequency of medication review (r = 0.17, P < 0.0001). CONCLUSION: More coordinated and responsive care, tailored to the individual, with regular and timely medication reviews and information provision, is likely to improve satisfaction with care in current healthcare pathways.

Inadequate safety reporting in pre-eclampsia trials: a systematic evaluation.

BACKGROUND: Randomised trials and their syntheses in meta-analyses offer a unique opportunity to assess the frequency and severity of adverse reactions. OBJECTIVE: To assess safety reporting in pre-eclampsia trials. SEARCH STRATEGY: Systematic search using bibliographic databases, including Cochrane Central Register of Controlled Trials, Embase, and MEDLINE, from inception to August 2017. SELECTION CRITERIA: Randomised trials evaluating anticonvulsant or antihypertensive medication for pre-eclampsia. DATA COLLECTION AND ANALYSIS: Descriptive statistics appraising the adequacy of adverse reaction and toxicity reporting. MAIN RESULTS: We included 60 randomised trials. Six trials (10%) were registered with the International Clinical Trials Registry Platform, two registry records referred to adverse reactions, stating 'safety and toleration' and 'possible side effects' would be collected. Twenty-six trials (43%) stated the frequency of withdrawals within each study arm, and five trials (8%) adequately reported these withdrawals. Adverse reactions were inconsistently reported across eligible trials: 24 (40%) reported no serious adverse reactions and 36 (60%) reported no mild adverse reactions. The methods of definition or measurement of adverse reactions were infrequently reported within published trial reports. CONCLUSIONS: Pre-eclampsia trials regularly omit critical information related to safety. Despite the paucity of reporting, randomised trials collect an enormous amount of safety data. Developing and implementing a minimum data set could help to improve safety reporting, permitting a more balanced assessment of interventions by considering the trade-off between the benefits and harms. FUNDING: National Institute for Health Research (DRF-2014-07-051), UK; Maternity Forum, Royal Society of Medicine, UK. TWEETABLE ABSTRACT: Developing @coreoutcomes could help to improve safety reporting in #preeclampsia trials. @NIHR_DC.

Cognitive, motor, behavioural and academic performances of children born preterm: a meta-analysis and systematic review involving 64 061 children.

BACKGROUND: Preterm birth may leave the brain vulnerable to dysfunction. Knowledge of future neurodevelopmental delay in children born with various degrees of prematurity is needed to inform practice and policy. OBJECTIVE: To quantify the long-term cognitive, motor, behavioural and academic performance of children born with different degrees of prematurity compared with term-born children. SEARCH STRATEGY: PubMed and Embase were searched from January 1980 to December 2016 without language restrictions. SELECTION CRITERIA: Observational studies that reported neurodevelopmental outcomes from 2 years of age in children born preterm compared with a term-born cohort. DATA COLLECTION AND ANALYSIS: We pooled individual estimates of standardised mean differences (SMD) and odds ratios (OR) with 95% confidence intervals using a random effects model. MAIN RESULTS: We included 74 studies (64 061 children). Preterm children had lower cognitive scores for FSIQ (SMD: -0.70; 95% CI: -0.73 to -0.66), PIQ (SMD: -0.67; 95% CI: -0.73 to -0.60) and VIQ (SMD: -0.53; 95% CI: -0.60 to -0.47). Lower scores for preterm children in motor skills, behaviour, reading, mathematics and spelling were observed at primary school age, and this persisted to secondary school age, except for mathematics. Gestational age at birth accounted for 38-48% of the observed IQ variance. ADHD was diagnosed twice as often in preterm children (OR: 1.6; 95% CI: 1.3-1.8), with a differential effect observed according to the severity of prematurity (I2 = 49.4%, P = 0.03). CONCLUSIONS: Prematurity of any degree affects the cognitive performance of children born preterm. The poor neurodevelopment persists at various ages of follow up. Parents, educators, healthcare professionals and policy makers need to take into account the additional academic, emotional and behavioural needs of these children. TWEETABLE ABSTRACT: Adverse effect of preterm birth on a child's neurodevelopment persists up to adulthood.

The effect of viscous soluble fiber on blood pressure: A systematic review and meta-analysis of randomized controlled trials.

AIMS: Dietary fiber intake, especially viscous soluble fiber, has been established as a means to reduce cardiometabolic risk factors. Whether this is true for blood pressure remains controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of viscous soluble fiber supplementation on blood pressure and quantify the effect of individual fibers. DATA SYNTHESIS: MEDLINE, Embase, and Cochrane databases were searched. We included RCTs of ≥4-weeks in duration assessing viscous fiber supplementation from five types: ß-glucan from oats and barley, guar gum, konjac, pectin and psyllium, on systolic blood pressure (SBP) and diastolic blood pressure (DBP). Study data were pooled using the generic inverse variance method with random effects models and expressed as mean differences (MD) with 95% confidence intervals (CIs). Twenty-two (N = 1430) and twenty-one RCTs (N = 1343) were included in the final analysis for SBP and DBP, respectively. Viscous fiber reduced SBP (MD = -1.59 mmHg [95% CI: -2.72,-0.46]) and DBP (MD = -0.39 mmHg [95% CI: -0.76,-0.01]) at a median dose of 8.7 g/day (1.45-30 g/day) over a median follow-up of 7-weeks. Substantial heterogeneity in SBP (I2 = 72%, P < 0.01) and DBP (I2 = 67%, P < 0.01) analysis occurred. Within the five fiber types, SBP reductions were observed only for supplementation using psyllium fiber (MD = -2.39 mmHg [95% CI: -4.62,-0.17]). CONCLUSION: Viscous soluble fiber has an overall lowering effect on SBP and DBP. Inclusion of viscous fiber to habitual diets may have additional value in reducing CVD risk via improvement in blood pressure. PROTOCOL REGISTRATION: ClinicalTrials.gov identifier-NCT02670967.

Effectiveness of supplementary irrigant agitation with the Finisher GF Brush on the debridement of oval root canals instrumented with the Gentlefile or nickel titanium rotary instruments.

AIM: To examine the efficacy of a novel supplementary irrigant agitating brush (Finisher GF Brush, MedicNRG, Kibbutz Afikim, Israel) on the debridement of root canals prepared with a novel stainless steel rotary instrumentation system (Gentlefile; MedicNRG), or nickel titanium rotary instruments in oval root canals. METHODOLOGY: Mandibular premolars (n = 72) were selected and divided randomly into three experimental groups (n = 24) after microCT scanning: group 1, canal preparation to rotary NiTi size 20, .04 taper (R20); group 2, rotary NiTi to size 25, .04 taper (R25) and group 3, Gentlefile size 23, .04 taper (GF). Specimens were subdivided into two subgroups: subgroup A, syringe-and-needle irrigation (SNI); subgroup B, Finisher GF Brush (GB). Ten untreated canals served as controls. Specimens were processed for histological evaluation, and the remaining pulp tissue (RPT) was measured. Data were analysed using Mann-Whitney and Kruskal-Wallis tests (P = 0.05). RESULTS: All experimental groups had significantly less RPT than the control (P < 0.05). Group 3B (GF-GB) had significantly less RPT than groups 1B (R20-GB) and 2B (R25-GF; P < 0.05). When irrigated with SNI, there was no significant difference in the RPT between the three groups (P > 0.05). When instrumented with R20, there was no significant difference between SNI and GF (P < 0.05) whilst GB had significantly less RPT than SNI for R25 (P < 0.05). CONCLUSIONS: Supplementary irrigant agitation with the Finisher GF Brush improved the debridement of canals prepared with Gentlefile and size 25, .04 taper rotary NiTi. Root canal debridement did not significantly differ between the instruments when syringe irrigation was used.

Patellofemoral morphology and alignment: reference values and dose-response patterns for the relation to MRI features of patellofemoral osteoarthritis.

OBJECTIVE: We aimed to (1) determine reference values for trochlear morphology and patellofemoral (PF) alignment in adults without magnetic resonance imaging (MRI)-defined PF full thickness cartilage damage or knee pain; and (2) evaluate dose-response patterns for these measures with prevalent MRI-defined PF structural damage and/or knee pain. DESIGN: The Framingham Community Cohort is a population-based sample of ambulatory adults aged ≥50 years. We evaluated six morphology and alignment measures using MRI (n = 985), and reported reference values (mean ± 2SD) in a subsample without MRI-defined PF full thickness cartilage damage or knee pain (n = 563). With restricted cubic spline Poisson regression, we evaluated dose-response patterns of each of the six measures with prevalent MRI-defined PF structural damage or joint pain. Our primary outcome was full thickness cartilage damage. RESULTS: For dose-response curves, prevalence ratios (PR) increased monotonically for all measures except patellar tilt, which rose with both lateral and medial tilt. Associations were generally strongest in the lateral PF compartment. PR for the strongest predictors of full thickness cartilage damage reached clinical relevance (PR > 1.5) at sulcus angle (SA) ≥135.0°; patellar tilt angle at ≤1.0° and ≥15.0°; and bisect offset ≥57.0%. Lateral trochlear inclination (LTI) achieved PR > 1.5 at ≤23.0° for full thickness cartilage damage with pain. CONCLUSIONS: SA, patellar tilt, and bisect offset were most strongly associated with full thickness cartilage damage. LTI, patellar tilt and bisect offset had stronger associations with the addition of pain. These findings contribute to better identifying a subset of patients who may benefit from mechanically based interventions.