Pre-symptomatic targeted treatment of patent ductus arteriosus in preterm newborns: A systematic review and meta-analysis.

BACKGROUND: A clinically significant patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in premature newborns. Symptomatic PDAs are often treated with prostaglandin synthesis inhibitors (PSI), but controversy remains if PSIs should also be used to manage early, asymptomatic PDAs. OBJECTIVE: To systematically identify, critically appraise, and evaluate the efficacy and safety of pharmacological management of pre-symptomatic PDA in preterm newborns after confirmed patency by echocardiography. STUDY DESIGN: Systematic review and meta-analysis. SEARCH METHODS: We searched MEDLINE (Ovid), EMBASE (Ovid), Cochrane Central Register of Controlled Trials (Wiley), from date of inception to February 2017. Supplemental searching was performed in Scopus and Web of Science to identify additional relevant citations. We also searched conference proceedings, reference lists of relevant articles and the WHO International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We included only randomized controlled trials (RCTs) that compared the use of indomethacin or ibuprofen to placebo for treatment of pre-symptomatic PDA in preterm newborns (<32 weeks gestational age and <1500gms). DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials, assessed risk of bias and extracted trial-level data. Outcomes are reported as risk ratios from random-effects models. Absolute risk reduction (ARR) is additionally reported for significant outcomes.We included seven trials (466 newborns). Targeted medical treatment did not significantly reduce mortality rates (RR 0.85, 95% CI 0.50 to 1.43; ARR -2.38%, 95% CI -8.04% to 3.29%; I2 0% 6 studies; 442 newborns), but it did significantly reduce the overall incidence of developing symptomatic PDA (RR 0.39, 95% CI 0.21 to 0.73; ARR -34.3%, 95% CI -50.8% to -17.8%; I2 0%; 3 studies; 97 newborns) compared to placebo. Other efficacy or safety outcomes were not significantly different. CONCLUSIONS: Targeted medical treatment of pre-symptomatic PDA decreases the incidence of developing symptomatic PDA, but not neonatal mortality. Further studies are essential to confirm these results.

Intensive gestational glycemic management and childhood obesity: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Hyperglycemia in pregnancy is associated with increased risk of offspring childhood obesity. Treatment reduces macrosomia; however, it is unclear if this effect translates into a reduced risk of childhood obesity. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy and safety of intensive glycemic management in pregnancy in preventing childhood obesity. METHODS: We searched MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov up to February 2016 and conference abstracts from 2010 to 2015. Two reviewers independently identified randomized controlled trials evaluating intensive glycemic management interventions for hyperglycemia in pregnancy and included four of the 383 citations initially identified. Two reviewers independently extracted study data and evaluated internal validity of the studies using the Cochrane Collaboration's Risk of Bias tool. Data were pooled using random-effects models. Statistical heterogeneity was quantified using the I2 test. The primary outcome was age- and sex-adjusted childhood obesity. Secondary outcomes included childhood weight and waist circumference and maternal hypoglycemia during the trial (safety outcome). RESULTS: The four eligible trials (n=767 children) similarly used lifestyle and insulin to manage gestational hyperglycemia, but only two measured offspring obesity and waist circumference and could be pooled for these outcomes. We found no association between intensive gestational glucose management and childhood obesity at 7-10 years of age (relative risk 0.89, 95% confidence interval (CI) 0.65 to 1.22; two trials; n=568 children). Waist circumference also did not differ between treatment and control arms (mean difference, -2.68 cm; 95% CI, -8.17 to 2.81 cm; two trials; n=568 children). CONCLUSIONS: Intensive gestational glycemic management is not associated with reduced childhood obesity in offspring, but randomized data is scarce. Long-term follow-up of trials should be prioritized and comprehensive measures of childhood metabolic risk should be considered as outcomes in future trials.

Experimental infection of chickens by a flagellated motile strain of Salmonella enterica serovar Gallinarum biovar Gallinarum.

Salmonella enterica subsp. enterica serovar Gallinarum biovar Gallinarum (SG) causes fowl typhoid (FT), a septicaemic disease which can result in high mortality in poultry flocks. The absence of flagella in SG is thought to favour systemic invasion, since bacterial recognition via Toll-like receptor (TLR)-5 does not take place during the early stages of FT. In the present study, chicks susceptible to FT were inoculated with a wild type SG (SG) or its flagellated motile derivative (SG Fla(+)). In experiment 1, mortality and clinical signs were assessed, whereas in experiment 2, gross pathology, histopathology, systemic invasion and immune responses were evaluated. SG Fla(+) infection resulted in later development of clinical signs, lower mortality, lower bacterial numbers in the liver and spleen, and less severe pathological changes compared to SG. The CD8(+) T lymphocyte population was higher in the livers of chicks infected with SG at 4 days post-inoculation (dpi). Chicks infected with SG had increased expression of interleukin (IL)-6 mRNA in the caecal tonsil at 1 dpi and increased expression of IL-18 mRNA in the spleen at 4 dpi. In contrast, the CD4(+) T lymphocyte population was higher at 6 dpi in the livers of birds infected with SG Fla(+). Therefore, flagella appeared to modulate the chicken immune response towards a CD4(+) T profile, resulting in more efficient bacterial clearance from systemic sites and milder infection.

Systematic review and meta-analysis of interventions for depression and anxiety in persons with multiple sclerosis.

BACKGROUND: Depression and anxiety are common in persons with multiple sclerosis (MS), and adversely affect fatigue, medication adherence, and quality of life. Though effective treatments for depression and anxiety exist in the general population, their applicability in the MS population has not been definitively established. OBJECTIVE: To determine the overall effect of psychological and pharmacological treatments for depression or anxiety in persons with MS. METHODS: We searched the Medline, EMBASE, PsycINFO, PsycARTICLES Full Text, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and Scopus databases using systematic review methodology from database inception until March 25, 2015. Two independent reviewers screened abstracts, extracted data, and assessed risk of bias and strength of evidence. We included controlled clinical trials reporting on the effect of pharmacological or psychological interventions for depression or anxiety in a sample of persons with MS. We calculated standardized mean differences (SMD) and pooled using random effects meta-analysis. RESULTS: Of 1753 abstracts screened, 21 articles reporting on 13 unique clinical trials met the inclusion criteria. Depression severity improved in nine psychological trials of depression treatment (N=307; SMD: -0.45 (95%CI: -0.74, -0.16)). The severity of depression also improved in three pharmacological trials of depression treatment (SMD: -0.63 (N=165; 95%CI: -1.07, -0.20)). For anxiety, only a single trial examined psychological therapy for injection phobia and reported no statistically significant improvement. CONCLUSION: Pharmacological and psychological treatments for depression were effective in reducing depressive symptoms in MS. The data are insufficient to determine the effectiveness of treatments for anxiety.

Comparative analysis of virulence genes, antibiotic resistance and gyrB-based phylogeny of motile Aeromonas species isolates from Nile tilapia and domestic fowl.

UNLABELLED: The nucleotide sequence analysis of the gyrB gene indicated that the fish Aeromonas spp. isolates could be identified as Aeromonas hydrophila and Aeromonas veronii biovar sobria, whereas chicken Aeromonas spp. isolates identified as Aeromonas caviae. PCR data revealed the presence of Lip, Ser, Aer, ACT and CAI genes in fish Aer. hydrophila isolates, ACT, CAI and Aer genes in fish Aer. veronii bv sobria isolates and Ser and CAI genes in chicken Aer. caviae isolates. All chicken isolates showed variable resistance against all 12 tested antibiotic discs except for cefotaxime, nitrofurantoin, chloramphenicol and ciprofloxacin, only one isolate showed resistance to chloramphenicol and ciprofloxacin. Fish Aeromonads were sensitive to all tested antibiotic discs except amoxicillin, ampicillin-sulbactam and streptomycin. SIGNIFICANCE AND IMPACT OF THE STUDY: Many integrated fish farms depend on the application of poultry droppings/litter which served as a direct feed for the fish and also acted as pond fertilizers. The application of untreated poultry manure exerts an additional pressure on the microbial world of the fish's environment. Aeromonas species are one of the common bacteria that infect both fish and chicken. The aim of this study was to compare the phenotypic traits and genetic relatedness of aeromonads isolated from two diverse hosts (terrestrial and aquatic), and to investigate if untreated manure possibly enhances Aeromonas dissemination among cohabitant fish with special reference to virulence genes and antibiotic resistant traits.

Early immune dynamics following infection with Salmonella enterica serovars Enteritidis, Infantis, Pullorum and Gallinarum: cytokine and chemokine gene expression profile and cellular changes of chicken cecal tonsils.

Salmonella enterica subspecies enterica infection remains a serious problem in a wide range of animals and in man. Poultry-derived food is the main source of human infection with the non-host-adapted serovars while fowl typhoid and pullorum disease are important diseases of poultry. We have assessed cecal colonization and immune responses of newly hatched and older chickens to Salmonella serotypes Enteritidis, Infantis, Gallinarum and Pullorum. S. Enteritidis and S. Infantis colonized the ceca more efficiently than S. Gallinarum and S. Pullorum. Salmonella infection was also associated with increased staining for B-lymphocytes and macrophages in the cecal tonsils of infected birds. S. Enteritidis infection in newly hatched birds stimulated the expression of CXCLi1 and CXCLi2 chemokines in the cecal tonsils, while S. Gallinarum up-regulated the expression of LITAF. In older chickens, S. Enteritidis infection resulted in a significantly higher expression of CXCLi2, iNOS, LITAF and IL-10 while S. Pullorum appeared to down-regulate CXCLi1 expression in the cecal tonsils. Data from spleens showed either no expression or down-regulation of the tested genes.

Characterisation and objective monitoring of balance disorders following head trauma, using videonystagmography.

OBJECTIVE: To characterise balance disorders occurring after head trauma, using videonystagmography, and to test the efficiency of videonystagmography as a diagnostic and monitoring tool. METHOD: Prospective, cohort analysis of 126 head trauma patients managed with vestibular evaluation, monitoring and treatment, in a tertiary referral centre. Analytical parameters included: head injury severity; balance disorder type, severity and time of onset; and patient recovery and outcome. RESULTS: Head trauma was minor in 31.7 per cent, mild in 36.6 per cent, moderate in 19 per cent and severe in 12.7 per cent. Balance disorder symptoms included vertigo in 42.9 per cent, unsteadiness in 15.9 per cent, dizziness in 9.5 per cent and none in 31.7 per cent. Videonystagmographic balance disorder diagnosis type was peripheral vestibular in 23.8 per cent, central in 7.9 per cent, mixed in 12.7 per cent, benign paroxysmal positional vertigo in 4.8 per cent and no findings in 50.8 per cent. Balance disorder was immediate in 47.6 per cent (this included all moderate and severe trauma cases). Benign paroxysmal positional vertigo developed within the first week in two-thirds of cases. More severe trauma cases had longer recovery times. Peripheral, mixed and central balance disorders recovered within the first three months. Early rehabilitation of acute balance disorders led to early recovery regardless of diagnosis. CONCLUSION: Videonystagmography enables precise, simple, cost-effective monitoring of balance disorders after head trauma, and improves care and outcomes.

The application of quantitative methods for identifying and exploring the presence of bias in systematic reviews: PDE-5 inhibitors for erectile dysfunction.

A systematic review of PDE-5 inhibitors for erectile dysfunction was performed to evaluate the utility of quantitative methods for identifying and exploring the influence of bias and study quality on pooled outcomes from meta-analyses. We included 123 randomized controlled trials (RCTs). Methodological quality was poorly reported. All three drugs appeared highly effective. Indirect adjusted analyses showed no differences between the three drugs. Funnel plots and statistical tests showed no evidence of small-study effects for sildenafil whereas there was evidence of such bias for tadalafil and vardenafil. Adjustment for missing studies using trim and fill techniques did not alter the pooled estimates substantially. The exclusion of previous sildenafil nonresponders was associated with larger treatment effects for tadalafil. This investigation was hampered by poor reporting of methodological quality, a low number of studies, heterogeneity and large effect sizes. Despite such limitations, a comprehensive assessment of biases should be a routine in systematic reviews.

Gonadotrophin-releasing hormone antagonists for assisted conception: a Cochrane review.

Gonadotrophin-releasing hormone (GnRH) antagonists suppress gonadotrophin secretion resulting in dramatic reduction in treatment cycle duration. Assuming comparable clinical outcomes, these benefits may justify changing the standard long GnRH agonist protocol to GnRH antagonist regimens. To evaluate the evidence, databases (e.g. Cochrane Library, MEDLINE, EMBASE) were electronically searched, hand searches were performed, and manufacturers in the field were contacted. Twenty-seven randomized controlled trials (RCT) fulfilled inclusion criteria for comparison of GnRH antagonist with long GnRH agonist protocol. Clinical pregnancy rate and ongoing pregnancy/live-birth rate were significantly lower in the antagonist group (P = 0.009; OR = 0.83, 95% CI 0.72-0.95 and P = 0.02; OR = 0.82, 95% CI 0.68-0.97 respectively). Conversely, incidence of severe OHSS was significantly reduced with the antagonist protocol (P = 0.01; OR = 0.60, 95% CI 0.40-0.88), and interventions to prevent OHSS were administered more frequently in the agonist group (P = 0.03; OR = 0.43, 95% CI 0.20-0.92). Concluding, GnRH antagonist protocols are short, simple, with good clinical outcomes and significant reduction in severe OHSS incidence and gonadotrophin amount; however, the lower pregnancy rate compared with the GnRH agonist long protocol necessitates counselling subfertile couples before recommending change from GnRH agonist to antagonist.

Ultrasound versus 'clinical touch' for catheter guidance during embryo transfer in women.

BACKGROUND: Many women undergoing an Assisted Reproductive Technology (ART) cycle will not achieve a live birth. Failure at the embryo transfer stage may be due to poor embryo quality, lack of uterine receptivity, or the transfer technique itself. Numerous methods, including the use of ultrasound guidance for proper catheter placement in the endometrial cavity, have been suggested as a means of improving the technique of embryo transfer. This review evaluates the effectiveness of ultrasound (UGET) in comparison with 'clinical touch' embryo transfer (CTET) the traditional method of embryo transfer. OBJECTIVES: :To determine whether ultrasound guidance influences treatment outcomes in women undergoing embryo transfer (ET) during assisted reproductive technology (ART) cycles. SEARCH STRATEGY: All electronic databases were searched on 20 th August 2006. We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched August 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2006), MEDLINE (1970-2006), EMBASE (1985-2006), BIO Extracts (1980-2006). Relevant conference proceedings were also hand searched (ASRM, ESHRE and FIGO). SELECTION CRITERIA: Only randomised controlled trials were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed eligibility and quality of trials and extracted data from those selected. MAIN RESULTS: Thirteen out of fifteen identified studies were eligible for analysis. No study reported live births, however, personal communication resulted in data relating to this outcome being obtained in two of the studies. Six studies reported on ongoing pregnancies. The live birth/ ongoing pregnancies per woman randomised associated with UGET (452/1376) was significantly higher than for clinical touch (353/1338) OR 1.40, 95%CI 1.18 to 1.66, P<0.0001). This means, for example, that for a population of women with a 25% chance of pregnancy using clinical touch this would be increased to 32% (28% to 46%) by using UGET. There were no statistically significant differences in the incidence of adverse events between the two comparison groups with the exception of blood on the catheter. AUTHORS' CONCLUSIONS: The studies are limited by their quality with only one of the thirteen studies reporting details of both computerised randomisation techniques and adequate allocation concealment. Ultrasound guidance does appear to improve the chances of live/ongoing and clinical pregnancies compared with clinical touch methods. The quality of future studies should be improved with adequate reporting of randomisation, allocation concealment, and power calculations. The primary outcome measure of future studies should be the reporting of live births per woman randomised.

Levonorgestrel-releasing intrauterine device (LNG-IUD) for symptomatic endometriosis following surgery.

BACKGROUND: Various options exist for treating endometriosis, including ovarian suppression therapy, surgical treatment or a combination of these strategies. Surgical treatment of endometriosis sets out to remove visible areas of endometriosis and restore anatomy by division of adhesions. The aim of medical therapy is to inhibit growth of endometriotic implants by suppression of ovarian steroids and induction of a hypo-estrogenic state. Postoperative treatment with a hormone-releasing intrauterine system, using levonorgestrel (LNG-IUS), has been suggested. OBJECTIVES: To determine if postoperative use of an LNG-IUS in women with endometriosis improves pain symptoms associated with menstruation and reduces recurrence compared with treatment with surgery only, placebo or systemic hormones. SEARCH STRATEGY: The following databases were searched: (1) Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials; (2) Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 1); (3) MEDLINE (1966 to January 2006) and EMBASE (1980 to January 2006); (4) National Research Register (NRR). (5) The citation lists of relevant publications, review articles, abstracts of scientific meetings and included studies were also searched. SELECTION CRITERIA: Trials were included if they compared women undergoing any type of surgical treatment for endometriosis with uterine preservation then randomized to LNG-IUS insertion within two to three months versus no treatment, placebo (inert IUD) or systemic treatment. Diagnostic laparoscopy alone was excluded. DATA COLLECTION AND ANALYSIS: Two review authors (AM Abou-Setta and HG Al-Inany) independently selected studies for inclusion and extracted data. Statistical analysis was performed in accordance with the statistical guidelines developed by the Cochrane Menstrual Disorders and Subfertility Group. Data extracted from the trials was analyzed on an intention-to-treat basis. For binary data, the overall common odds ratio (OR) (that is, the odds of having clinical symptoms) and the risk difference with 95% confidence interval (CI) were calculated using the Mantel-Haenszel fixed-effect method. MAIN RESULTS: In one small randomized controlled trial (RCT) there was a statistically significant reduction in the recurrence of painful periods in the LNG-IUS group compared with the control group receiving a gonadotrophin-releasing hormone (GnRH) agonist (OR 0.14, 95% CI = 0.02 to 0.75). The proportion of women who were satisfied with their treatment was higher in the LNG-IUS group than in the control group but this difference did not reach statistical difference (OR 3.00, 0.79 to 11.44). AUTHORS' CONCLUSIONS: One small study has shown that postoperative use of the LNG-IUS reduces the recurrence of painful periods in women who have had surgery for endometriosis. There is a need for further well-designed RCTs of this approach.

Gonadotrophin-releasing hormone antagonists for assisted conception.

BACKGROUND: Gonadotrophin-releasing hormone antagonists produce immediate suppression of gonadotrophin secretion, hence, they can be given after starting gonadotrophin administration. This has resulted in dramatic reduction in the duration of treatment cycle. Two different regimes have been described. The multiple-dose protocol involves the administration of 0.25 mg cetrorelix (or ganirelix) daily from day six to seven of stimulation, or when the leading follicle is 14 to15 mm, until human chorionic gonadotrophin (HCG) administration and the single-dose protocol involves the single administration of 3 mg cetrorelix on day seven to eight of stimulation. Assuming comparable clinical outcome, these benefits would justify a change from the standard long protocol of GnRH agonists to the new GnRH antagonist regimens. OBJECTIVES: To evaluate the evidence regarding the efficacy of gonadotrophin-releasing hormone (GnRH) antagonists with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception. SEARCH STRATEGY: We searched Cochrane Menstrual Disorders and Subfertility Group's Specialised Register, MEDLINE and EMBASE databases from 1987 to February 2006, and handsearched bibliographies of relevant publications and reviews, and abstracts of scientific meetings. We also contacted manufacturers in the field. SELECTION CRITERIA: Randomized controlled studies comparing different protocols of GnRH antagonists with GnRH agonists in assisted conception cycles were included in this review. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. If relevant data were missing or unclear, the authors have been consulted MAIN RESULTS: Twenty seven RCTs comparing the GnRH antagonist to the long protocol of GnRH agonist fulfilled the inclusion criteria. Clinical pregnancy rate was significantly lower in the antagonist group. (OR = 0.84, 95% CI = 0.72 - 0.97). The ongoing pregnancy/ live-birth rate showed the same significant lower pregnancy in the antagonist group (P = 0.03; OR 0.82, 95% CI 0.69 to 0.98).However, there was statistically significant reduction in incidence of severe OHSS with antagonist protocol. The relative risk ratio was (P = 0.01; RR 0.61, 95% CI 0.42 to 0.89). In addition, interventions to prevent OHSS (e.g. coasting, cycle cancellation) were administered more frequently in the agonist group (P = 0.03; OR 0.44, 95% CI 0.21 to 0.93). AUTHORS' CONCLUSIONS: GnRH antagonist protocol is a short and simple protocol with good clinical outcome with significant reduction in incidence of severe ovarian hyperstimulation syndrome and amount of gonadotrophins but the lower pregnancy rate compared to the GnRH agonist long protocol necessitates counseling subfertile couples before recommending change from GnRH agonist to antagonist..