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Lowy D.R.,U.S. National Cancer Institute | Herrero R.,The Detection Group | Hildesheim A.,U.S. National Cancer Institute | Cuzick J.,Cancer Research UK Research Institute | And 14 more authors.
The Lancet Oncology | Year: 2015

Although available human papillomavirus (HPV) vaccines have high efficacy against incident infection and disease caused by HPV types that they specifically target, new vaccine trials continue to be needed. The goals of these trials could include change of vaccine dose or route of administration (or both), development of second-generation vaccines, and the regional manufacture of biosimilar vaccines. We summarise present thinking about primary endpoints for HPV vaccine trials as developed at an experts workshop convened by the International Agency for Research on Cancer and the US National Cancer Institute in September, 2013. Efficacy trials that have led to licensure for cervical cancer prevention have used the disease endpoint of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). However, on the basis of experience from the trials and present knowledge of HPV infection, future efficacy trials for new vaccines can be safely streamlined by the use of persistent HPV infection, which occurs more frequently than CIN2+, and can be more reproducibly measured as a primary endpoint. Immunobridging trials can be sufficient to ascertain immunological non-inferiority for licensure for alternate dosing schedules, bridging to age 26 years or younger, and biosimilar vaccines, with post-licensure surveillance confirming effectiveness. These recommendations are intended to help stimulate continued vaccine development while ensuring appropriate assessment of safety and efficacy. © 2015 Elsevier Ltd.


Oliver C.,The Royal Womens Hospital | Watson H.,Papworth Hospital NHS Foundation Trust
Cochrane Database of Systematic Reviews | Year: 2016

Background: Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. This is an updated version of a previously published review. Objectives: To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality and to identify any adverse events associated with supplementation. Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Authors and persons interested in the subject of the review were contacted. Date of last search: 13 August 2013. Selection criteria: Randomised controlled trials in people with cystic fibrosis comparing omega-3 fatty acid supplements with placebo. Data collection and analysis: Two authors independently selected studies for inclusion, extracted data and assessed the risk of bias of the studies. Main results: The searches identified 15 studies; four studies with 91 participants (children and adults) were included; duration of studies ranged from six weeks to six months. Two studies were judged to be at low risk of bias based on adequate randomisation but this was unclear in the other two studies. Three of the studies adequately blinded patients, however, the risk of bias was unclear in all studies with regards to allocation concealment and selective reporting. Two studies compared omega-3 fatty acids to olive oil for six weeks. One study compared a liquid dietary supplement containing omega-3 fatty acids to one without for six months. One study compared omega-3 fatty acids and omega-6 fatty acids to a control (capsules with customised fatty acid blends) for three months. Only one short-term study (19 participants) comparing omega-3 to placebo reported a significant improvement in lung function and Shwachman score and a reduction in sputum volume in the omega-3 group. Another study (43 participants) demonstrated a significant increase in serum phospholipid essential fatty acid content and a significant drop in the n-6/n-3 fatty acid ratio following omega-3 fatty acid supplementation compared to control. The longer-term study (17 participants) demonstrated a significant increase in essential fatty acid content in neutrophil membranes and a significant decrease in the leukotriene B4 to leukotriene B5 ratio in participants taking omega-3 supplements compared to placebo. Authors' conclusions: This review found that regular omega-3 supplements may provide some benefits for people with cystic fibrosis with relatively few adverse effects, although evidence is insufficient to draw firm conclusions or recommend routine use of these supplements in people with cystic fibrosis. This review has highlighted the lack of data for many outcomes meaningful to people with or making treatment decisions about cystic fibrosis. A large, long-term, multicentre, randomised controlled study is needed to determine any significant therapeutic effect and to assess the influence of disease severity, dosage and duration of treatment. Future researchers should note the need for additional pancreatic enzymes. © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.


Said J.M.,The Royal Womens Hospital
Journal of pregnancy | Year: 2011

Fetal growth restriction is an important pregnancy complication that has major consequences for the fetus and neonate as well as an increased risk of long-term morbidity extending into adulthood. The precise aetiology of most cases of fetal growth restriction is unknown although placental thrombosis is a common feature in many of these cases. This paper will outline the potential role of proteoglycans in contributing to placental thrombosis and fetal growth restriction.


D'Arcy C.,The Royal Womens Hospital
Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society | Year: 2014

Congenital adrenal agenesis is an extremely rare condition wherein the adrenal glands fail to develop. The absence of adrenal tissue results in the complete absence of hormones produced in the adrenal cortex (cortisol, aldosterone) and medulla (catecholamines), and is not compatible with postnatal life without artificial hormone replacement therapy. To date, 9 cases of adrenal agenesis have been reported, many of which are associated with additional congenital anomalies. Most cases were not detected on antenatal imaging and were detected incidentally at postmortem examination. We present a case of adrenal agenesis, detected incidentally at postmortem examination after termination of pregnancy for suspected fetal hydrops, and review the heterogeneous phenotype of this condition with associated abnormalities and molecular genetics. This case reinforces the role of the perinatal autopsy to investigate cause of perinatal mortality, allowing correlation of pathology with antenatal imaging findings and clinical details.


Garland S.M.,The Royal Womens Hospital | Garland S.M.,University of Melbourne | Garland S.M.,Murdoch Childrens Research Institute
Gynecologic Oncology | Year: 2010

Sexually transmitted human papillomavirus (HPV) infection is very common in men and women. Oncogenic HPV is strongly associated with cancers and high-grade dysplasias of the anogenital tract, including the anus, penis, and also a proportion of oropharyngeal cancers. In reducing male disease burden, some consider screening and treatment for high-grade anal dysplasia (AIN) to prevent anal cancer in high-risk populations. Such strategies have wide implications for the workforce, and require more evidence for the optimal management of AIN. Male sexual behavior, with consequent HPV infection and disease contribute to considerable disease burden in females. Hence, inclusion of males in prophylactic HPV vaccination programs should prevent HPV-related disease in males as well as substantially reducing disease burden in females. Clinical trial data in males 16-26 years for the quadrivalent vaccine show it is well tolerated, induces a strong type-specific immunological response comparable to that of females, and reduced vaccine HPV-type-related genital infection, as well as disease. Cost-benefit analyses and mathematical modeling show that the most cost-effective strategy involves routine administration of this vaccine to 12-year-old females, with catch-up vaccination of 12- to 24-year-olds, with the most effective strategy in disease reduction including men and/or boys in the program. Such a vaccination strategy including 12-year-old boys is projected by 2050 to reduce HPV 16 infection by 88-94% in females and 68-82% in males, plus the aforementioned male HPV- related cancers by 22-27%. Therefore, inclusion of males in an HPV vaccination program is likely to have significant health and economic benefits over and above those observed from current female-only programs. However, comprehensive cost-benefit analyses are needed to determine the efficacy of these programs in the overall population. Such analyses will be crucial for the design, acceptance, and implementation of these vaccination programs into clinical practice globally. © 2010.


Schmolzer G.M.,The Royal Womens Hospital
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: A respiratory function monitor is routinely used in neonatal intensive care units to continuously measure and display airway pressures, tidal volume and leak during ventilation. During positive pressure ventilation in the delivery room, clinical signs are used to monitor the effectiveness of ventilation. The additional use of a respiratory function monitor during positive pressure ventilation in the delivery room might help to improve the effectiveness of ventilation. OBJECTIVES: To determine whether the use of a respiratory function monitor in addition to clinical assessment compared to clinical assessment alone in newborn infants resuscitated with positive pressure ventilation reduces mortality and morbidity. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2010), MEDLINE (January 1996 to March 2010), EMBASE (January 1980 to March 2010) and CINAHL (January 1982 to March 2010). Clinical trials registers and the abstracts of the Society for Pediatric Research and the European Society for Pediatric Research were searched from 2004 to 2009. No language restrictions were applied. SELECTION CRITERIA: We planned to include randomised and quasi-randomised controlled trials and cluster trials that compared the use of a respiratory function monitor in addition to clinical assessment, compared to clinical assessment alone, in newborn infants resuscitated with positive pressure ventilation. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated the search results against the selection criteria. Data extraction and risk of bias assessment were not performed because there were no studies that met our inclusion criteria. MAIN RESULTS: No studies were found meeting the criteria for inclusion in this review AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the efficacy and safety of a respiratory function monitor in addition to clinical assessment during positive pressure ventilation at neonatal resuscitation. Randomised clinical trials comparing positive pressure ventilation with and without a respiratory function monitor in addition to clinical assessment at neonatal resuscitation are warranted.


Oliver C.,The Royal Womens Hospital
The Cochrane database of systematic reviews | Year: 2013

Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality and to identify any adverse events associated with supplementation. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Authors and persons interested in the subject of the review were contacted.Date of last search: 08 July 2013. Randomised controlled trials in people with cystic fibrosis comparing omega-3 fatty acid supplements with placebo. Two authors independently selected studies for inclusion, extracted data and assessed the risk of bias of the studies. The searches identified 14 studies; four studies with 91 participants were included. Two studies were judged to be at low risk of bias based on adequate randomisation but this was unclear in the other two studies. Three of the studies adequately blinded patients, however, the risk of bias was unclear in all studies with regards to allocation concealment and selective reporting.Two studies compared omega-3 fatty acids to olive oil for six weeks. One study compared a liquid dietary supplement containing omega-3 fatty acids to one without for six months. One study compared omega-3 fatty acids and omega-6 fatty acids to a control (capsules with customised fatty acid blends) for three months. Only one short-term study (19 participants) comparing omega-3 to placebo reported a significant improvement in lung function and Shwachman score and a reduction in sputum volume in the omega-3 group. Another study (43 participants) demonstrated a significant increase in serum phospholipid essential fatty acid content and a significant drop in the n-6/n-3 fatty acid ratio following omega-3 fatty acid supplementation compared to control. The longer-term study (17 participants) demonstrated a significant increase in essential fatty acid content in neutrophil membranes and a significant decrease in the leukotriene B4 to leukotriene B5 ratio in participants taking omega-3 supplements compared to placebo. This review found that regular omega-3 supplements may provide some benefits for people with cystic fibrosis with relatively few adverse effects, although evidence is insufficient to draw firm conclusions or recommend routine use of these supplements in people with cystic fibrosis. This review has highlighted the lack of data for many outcomes meaningful to people with or making treatment decisions about cystic fibrosis. A large, long-term, multicentre, randomised controlled study is needed to determine any significant therapeutic effect and to assess the influence of disease severity, dosage and duration of treatment. Future researchers should note the need for additional pancreatic enzymes.


Wong K.S.,The Royal Womens Hospital
The Cochrane database of systematic reviews | Year: 2013

Red blood cell alloimmunization in pregnancy can lead to fetal anaemia with potentially disastrous consequences. Traditional management involves the use of intrauterine transfusion, which is associated with significant procedure-related risks. An alternative treatment that has been trialled is the use of immunoglobulin administered intravenously to the mother. The objective of this review was to assess the efficacy and safety of the use of intravenous immunoglobulin antenatally to women with severe fetal red blood cell alloimmunization. We searched the Cochrane Pregnancy and Childbirth Group trials register (19 December 2012), and reference lists of articles. Randomized trials assessing the antenatal use of intravenous immunoglobulin administered at any dose, frequency or duration with a control group (using any other, or no treatment) in the management of fetal red blood cell alloimmunization. Two review authors independently assessed the available evidence. There are no included studies. No information is available from randomized trials to indicate whether the antenatal use of intravenous immunoglobulin is effective in the management of fetal red blood cell alloimmunization. Several case series suggest a beneficial role in delaying the onset of fetal anaemia requiring invasive intrauterine transfusion.


Rio I.,The Royal Womens Hospital
Australian Family Physician | Year: 2010

Background: The time before a woman has confirmed her pregnancy is an important time for both the woman and her unborn baby's wellbeing. With the period of organogenesis largely occurring between the third and eighth week of development, early pregnancy is a time when a woman may have problems related to the pregnancy itself, or where diseases have a higher risk of morbidity in the woman or the fetus. Yet, the woman and her doctor, may be unaware of the pregnancy. Objective: This article outlines presenting complaints where a doctor should specifically explore the possibility of early pregnancy in a woman in her reproductive years, as pregnancy may have an impact on the management, and ultimately the wellbeing, of both the woman and the fetus. Discussion: Identification and appropriate management of the coexisting pregnancy and presenting condition allows the general practitioner to provide the most appropriate care in this clinical situation.


Dawson J.A.,The Royal Womens Hospital
Cochrane database of systematic reviews (Online) | Year: 2012

Many small, sick and premature infants are unable to coordinate sucking, swallowing and breathing, and therefore, require gavage feeding. In gavage feeding, milk feeds are delivered through a tube passed via the nose or mouth into the stomach. Intermittent bolus milk feeds may be administered using a syringe to gently push milk into the infant's stomach (push feed). Alternatively, milk can be poured into a syringe attached to the tube and allowed to drip in by gravity (gravity feed). To determine whether the use of push compared with gravity gavage feeding results in a more rapid establishment of full gavage feeds without increasing adverse events in preterm or low birth weight, infants who require intermittent bolus gavage feeding. We searched the following electronic databases to locate randomised controlled or quasi-randomised trials: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2012, Issue 5), MEDLINE (from 1966 to May 2012), EMBASE (from 1980 to May 2012), and CINAHL (from 1982 to May 2012). We used the standard search strategy of the Cochrane Neonatal Review Group. Randomised or quasi-randomised controlled trials comparing push versus gravity intermittent gavage tube feeding in premature or low birth weight, or both, infants. We assessed the methodology of trials regarding blinding of randomisation and outcome measurement. We evaluated treatment effect with a fixed-effect model using risk ratio (RR), relative risk reduction, risk difference (RD) and number needed to treat (NNT) for categorical data; and using mean, standard deviation and weighted mean difference (WMD) for continuous data. We analysed outcomes measured as count data, for example frequency of apnoea, bradycardia and episodes of pulse oximeter oxygen (SpO(2)) desaturation, by comparing rates of events and the rate ratio. We evaluated heterogeneity to help determine the suitability of pooling results. Only one small cross-over trial met the criteria for inclusion in this review and therefore meta-analysis for any of the treatment outcomes was not performed. Symon 1994 reported a trend towards a higher respiratory rate at 10 to 30 minutes following push gavage feeding and no statistical difference in the time taken to give the feeds regardless of the method used. There was one small cross-over study that was included in this review. There is insufficient evidence to recommend either method of gavage feeding. A randomised trial is needed to evaluate the benefits and harms of push versus gravity bolus tube feeding in preterm infants. Infants should be stratified by gestational age at birth (above and below 32 weeks) or birth weight (above and below 1500 grams) and respiratory support (ventilated versus non-ventilated) and the sample size should be of sufficient size to evaluate the primary outcomes outlined in this review (time to establish full tube feeds and feeding intolerance).

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