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Provision and practice of specialist preterm labour clinics: a uk survey of practice

Provision and practice of specialist pretermlabour clinics: a UK survey of practice AN Sharp, Z Alfirevic Department of Women and Children's Health Research, University Department, Liverpool Women's Hospital, Liverpool, UKCorrespondence: Dr AN Sharp, Department of Women's and Children's Health Research, Liverpool Women's Hospital, Crown Street,Liverpool L8 7SS, UK. Email asharp@liv.ac.uk Accepted 1 October 2013. Published Online 3 December 2013.
Objective To identify the current status of specialist preterm prelabour rupture of membranes (95%), two large loop excisions labour (PTL) clinic provision and management within the UK.
of the transformation zone (95%) or cone biopsy (95%). Therewas significant heterogeneity in the indications for and method of Design Postal survey of clinical practice.
primary treatment for short cervix, with cervical cerclage used in 45% of units, progesterone in 18% of units and Arabin cervicalpessary in 5%. A further 23% used multiple treatment modalities Population All consultant-led obstetric units within the UK.
in combination.
Methods A questionnaire was sent by post to all 210 NHS Conclusions A significant heterogeneity in all topics surveyed consultant-led obstetric units within the UK. Units that had a suggests an urgent need for networking, more evidence-based specialist PTL clinic were asked to complete a further 20 questions guidelines and prospective comparative audits to ascertain the real defining their protocol for risk stratification and management.
impact of specialist PTL clinics on the reduction in preterm birth Main outcome measures Current practice in specialist preterm and its sequelae.
labour clinics.
Keywords Cerclage, cervix, preterm birth, specialist antenatal Results We have identified 23 specialist clinics; the most common clinic, transvaginal ultrasound.
indications for attendance were previous PTL (100%), preterm Please cite this paper as: Sharp AN, Alfirevic Z. Provision and practice of specialist preterm labour clinics: a UK survey of practice. BJOG2014;121:417–421.
sounded because of the recent controversies over intramus-cular 17a-hydroxyprogesterone caproate.12 Preterm birth affects up to 12.5% of all births1 and remains A lack of formal guidance from bodies such as the Royal a significant burden to healthcare services,2 with an esti- College of Obstetricians and Gynaecologists (RCOG) and mated health cost of more than £2.9 billion in the UK.3 the American College of Obstetricians and Gynecologists Over the last 10 years, the identification of women at high (ACOG) has hampered a clear approach to management.
risk of a preterm birth has been revolutionised by greater For example, RCOG suggests that high-risk women without recognition of the impact of risk factors, such as cervical a short cervix may be offered either serial sonographic surgery,4 and the increased use of transvaginal ultrasound assessment or expectant management, because of the high surveillance of cervical length during pregnancy.5 chance of delivery at >33 weeks in all high-risk groups.13 This advance in ultrasound detection of women at risk Although preventative treatment options are well defined, of preterm birth has occurred at a time when new treat- the indications for when to treat are still hotly debated, with ment options have been identified, to such an extent that cut-offs for cervical length of 25 mm14 or 15 mm15 and cen- we now appear to have several treatment options for short tile charts16 all being used. Further controversies exist over cervix, namely cervical cerclage,6,7 progesterone8,9 and the effectiveness of other management options, including Arabin cervical pessary,10 all of which appear, at least from fetal fibronectin testing,17 treatment of bacterial vaginosis,18 the limited comparative data currently available, to be vaginal pH testing,19 the use of vaginal probiotics,20 aspi- similarly efficacious.11 However, a note of caution must be rin21 and dietary advice, such as high oily fish intake.22 ª 2013 Royal College of Obstetricians and Gynaecologists The increasing complexity of management of these preg- One unit with a specialist PTL clinic provided informa- nancies has naturally led some units to develop dedicated tion about staffing and frequency, but failed to provide any preterm labour (PTL) clinics. This has occurred despite a information about their management policy, and was recent Cochrane review which states that there is a paucity of therefore excluded from the later analysis of clinic manage- evidence to support the benefits of a specialist PTL clinic.23 ment. One unit performed screening tests on both high- It is noteworthy that neither RCOG nor ACOG has and low-risk women, but was included in the analysis to made any recommendation on the use of specialist PTL demonstrate the range of clinical care offered. The staffing clinics. However, Whitworth et al.23 state that, despite a and skills mix is reported in Table 1.
lack of proven cost-effectiveness, specialist clinics are here All units invited women with a history of previous pre- to stay, a statement which mirrors the introduction of a term birth, although there was significant heterogeneity in variety of specialised antenatal clinics in other areas (mater- what gestation constituted a clinically significant previous nal medical disorders, multiple pregnancy).24 preterm birth (Table 2). Other indications for referral to a This survey aimed to identify current practice within the PTL clinic included previous preterm prelabour rupture of UK, given the variety of management options and lack of membranes (PPROM) (n = 20, 95%), uterine anomalies good quality of guidelines. We hoped that clarification of (n = 19, 90%), recurrent first trimester miscarriage (n = 1, the current provision would lead to the development of a 5%), recurrent second trimester miscarriage (n = 20, 95%) more standardised approach to care, at least within the and previous cervical surgery (n = 20, 95%). The signifi- context of a social care system.
cance given to cervical surgery also varied, with some con-sidering a single large loop excision of the transformation zone (LLETZ) as significant (n = 11, 52%), whereas othersinvited women with two (LLETZ) procedures (n = 20, The survey (Appendix S1) with a covering letter was mailed 95%) or a cone biopsy (n = 20, 95%). The timing of to each of the 210 NHS hospitals with a consultant obstet- appointments also varied significantly, with 11 (55%) clin- ric unit in the UK (England, Wales, Scotland, Northern ics seeing women at <12 weeks for their initial appoint- Ireland, Channel Islands and Isle of Man). The first round ment and all units seeing them before 20 weeks (Table 2).
of questionnaires was sent in November 2012 and this was Thirteen units (59%) initiated treatment with a cervical followed up by a second round in February 2013 to those length of <25 mm, whereas two units used a cut-off of units which had not responded to the initial invitation. If 15 mm (9%). A further four units (18%) used a variety of the unit did not have a specialist PTL clinic, the responder different cut-off measurements for treatment, and three was thanked for their time and no further questions were units (14%) used a cervical normogram (Table 3).
The most commonly used primary treatment for asymp- For those units with a specialist PTL clinic, further ques- tomatic women with ultrasound-detected short cervix was tions established the frequency of clinics, staffing and local cervical cerclage (n = 10, 45%). However, both vaginal protocols. Particular emphasis was placed on risk stratifica- progesterone pessaries (n = 4, 18%) and Arabin cervical tion and management options, including the use of trans- pessary (n = 1, 5%) were also used. Some units treated vaginal ultrasound, treatment options for a short cervix with multiple modalities (n = 5, 23%), which included a Finally, each unit was asked whether their clinical data wasregularly audited and made available for external scrutiny.
Table 1. Staffing and organisation of specialist preterm labourclinics Staffing of preterm labour clinic Of the initial 210 units identified, 12 responses were Lead clinician-university staff excluded as the unit no longer provided acute obstetrics, or Lead clinician-NHS staff had merged with other hospitals, leaving 198 hospitals for Designated midwife Cervical length assessment operator consideration. The survey was sent in two rounds in Obstetric consultant November 2012 and February 2013, achieving an overall Obstetric trainee response rate of 144/198 (73%).
Of the 144 responders, 48 units (33%) reported a deliv- Research/clinical fellow ery rate of >5000 per annum, 73 (51%) between 2500 and 5000, and 23 (16%) of <2500, with 19, three and one spe- cialist PTL clinic, respectively. All specialist PTL clinics *Two units did not answer this question.
were located within England.
ª 2013 Royal College of Obstetricians and Gynaecologists Specialist preterm labour clinics in the UK (one unit) and vaginal progesterone with Arabin cervical Table 2. Indication for referral and general management structure pessary (one unit). If we include units that used multiple of specialist preterm labour (PTL) clinics therapies, primary treatment involved cervical cerclage in 14 units (64%), vaginal progesterone in seven units (31%), Arabin cervical pessary in two units (9%) and rectal and intramuscular progesterone in one unit (5%) each.
Thirteen units (59%) regularly assessed vaginal flora, seven units (32%) used fetal fibronectin and three units (14%) utilised the cervical stress test, whereas no units rou- tinely assessed vaginal acidity as part of their management strategy. If bacterial vaginosis was diagnosed, nine units (45%) treated with vaginal clindamycin, three units (15%) Uterine anomalies with oral clindamycin, seven units (35%) with metronida- zole and two units (10%) did not treat bacterial vaginosis An array of additional advice was given to women man- aged within specialist PTL clinics, which included restrict-ing physical activity (n = 10, 46%), avoidance of sexual intercourse (n = 9, 41%), stopping work (n = 6, 27%) and dietary advice (n = 6, 27%) (Table 4). However, eight units(36%) did not routinely give any additional advice.
After a diagnosis of short cervix, women were followed up within the specialist PTL clinic until 24 weeks (n = 1, Based on clinical 5%), 28 weeks (n = 9, 41%), 30 weeks (n = 1, 5%), 34 weeks (n = 8, 36%), 37 weeks or until delivery (n = 3, LLETZ, large loop excision of transformation zone; PPROM, pretermprelabour rupture of membranes.
Table 4. Other assessments and additional advice routinely *One unit excluded as perform screening test on all women.
conducted within specialist preterm labour clinics **One unit excluded as stated 37 weeks for initial appointment;one unit excluded as perform screening test on all women.
Table 3. Cervical length measurement deemed to be sufficiently significant to require primary treatment Cervical length at treatment Cervical stress test Fetal fibronectin Primary treatment choice None of the above Cervical cerclage Vaginal progesterone Arabin cervical pessary Multiple therapies* N = 20* (%) Gestational age N = 22 (%) Dependent on clinical picture *Two units used cervical cerclage and vaginal progesterone, oneunit used cervical cerclage and intramuscular progesterone, one unit Vaginal clindamycin used cervical cerclage and rectal progesterone, and one unit used vaginal progesterone and Arabin cervical pessary.
Oral metronidazole combination of cervical cerclage with vaginal progesterone bacterial vaginosis (two units), cervical cerclage with intramuscular progester-one (one unit), cervical cerclage with rectal progesterone *Two units did not respond to this question.
ª 2013 Royal College of Obstetricians and Gynaecologists 14%) (Table 4). Outcomes from women seen within the that there was even greater variation in other management specialist PTL clinic were routinely audited by 17 units strategies, such as vaginal flora or fetal fibronectin testing, (77%), but the information from only four units (18%) treatment of bacterial vaginosis or additional advice given was publicly available.
to high-risk women.
Strengths and limitationsAlthough the main focus of this survey was on specialist PTL clinics, clearly there are many other women who are This is the first time that a structured assessment of the managed in a similar way within the auspices of conven- current provision and management of women at risk of tional antenatal or fetal medicine clinics. Although this PTL has been performed within the UK. Perhaps, not sur- could have led to a less complete picture, we chose this prisingly, the majority of specialist PTL clinics were located approach as a pragmatic decision to achieve maximum within larger maternity units. This may reflect the larger clarity in response from dedicated specialist PTL clinics, number of high-risk women seen within these units, but which may be more likely to have a dedicated protocol.
also more clinicians with the expertise to establish and sup-port such a clinic. Thirty-one per cent of specialist PTL clinics are led by university staff, which may reflect the tra- This survey highlighted the significant degree of heteroge- ditional development of these clinics from a research focus.
neity in clinical practice with regard to the management of A high proportion of current clinics are led by an NHS cli- asymptomatic women at risk of preterm birth.
nician, which suggests migration of specialist clinics out of A means of addressing these issues could include the research environment and into standard clinical care. It nationalised audit of outcomes from specialist PTL clinics is also reassuring to note that the majority of units have a or the voluntary adoption of a universal protocol for the dedicated midwife available.
management of these high-risk women. We suggest that, The most striking feature of this survey is the significant with the continued expansion in specialist antenatal clinics variation in clinical management between units in almost of all types, it would be an opportune time to begin to col- all aspects of the current identification and management late the real-life outcomes from women managed within strategies used for women at high risk of preterm birth these clinics. We believe that such a national clinical out- within the UK.
come review will become increasingly important in the This lack of consensus is perhaps most clearly shown by context of revalidation,25 resource allocation and standar- the lack of uniformity in cervical length measurement dised outcome reporting.26 deemed to necessitate treatment. Although 59% of unitsused <25 mm, others used <15 mm, cervical centile chartsand various other cut-offs, making a comparison of out- comes for treated women between individual units virtuallyimpossible.
We have demonstrated the wide variation in the manage- The common use of cervical cerclage as a primary treat- ment of high-risk women with a short cervix within spe- ment for short cervix is interesting. It reflects the signifi- cialist PTL clinics in the UK. The new trend in favour of cant amount of literature on efficacy, with some claiming a specialised antenatal clinics appears to be here to stay, and limited effect,7,15 whereas others claiming more substantial PTL clinics are just another aspect of this continued benefits.6,14 It is possible that, as evidence for the efficacy growth. Nothwithstanding the need for an individualised and safety of vaginal progesterone and cervical pessaries approached in many cases, such variation in management continues to grow, they may become increasingly accepted strategies employed by these clinics remains of concern.
into clinical practice, particularly as they offer a less inva- Better collaboration between these specialist clinics would sive alternative with a similar efficacy to cervical cerclage.11 provide a real opportunity to generate practice-based evi- Of interest is the significant minority of units that use dence and improve the care offered to these high-risk therapies in combination to treat women with short cervix.
These units were approached to confirm that this was theiractual practice. Although the use of multiple treatment Disclosure of interests modalities may be efficacious, it is not currently supported The authors have no conflicts of interest to declare.
by the literature and makes any comparison of outcomesdifficult to interpret.
Contribution to authorship Given the variation in practice with cervical length mea- The idea for the survey was conceived by AS; both AS and surement and treatment for short cervix, it is unsurprising ZA wrote the manuscript.
ª 2013 Royal College of Obstetricians and Gynaecologists Specialist preterm labour clinics in the UK Details of ethics approval 10 Goya M, Pratcorona L, Merced C, Rodo C, Valle L, Romero A, et al.
Ethical approval was not required as no patient informa- Cervical pessary in pregnant women with a short cervix (PECEP): anopen-label randomised controlled trial. Lancet 2012;379:1800–6.
tion was involved.
11 Alfirevic Z, Owen JCarreras Moratonas E, Sharp AN, Szychowski JM, Goya M. Vaginal progesterone, cerclage or cervical pessary for preventing preterm birth in asymptomatic singleton pregnantwomen with a history of preterm birth and a sonographic short No funding was received for this work.
cervix. Ultrasound Obstet Gynecol 2013;41:146–51.
12 Silver R, Cunningham FG. Deus ex Makena. Obstet Gynecol The authors would like to thank all the medical staff who 13 RCOG. Cervical Cerclage, Green-top Guideline No. 60. London: took the time to complete the survey.
Royal College of Obstetricians and Gynaecologists, 2011. pp. 1–21.
14 Owen J, Hankins G, Iams JD, Berghella V, Sheffield JS, Perez-Delboy A, et al. Multicenter randomized trial of cerclage for preterm birth Supporting Information prevention in high-risk women with shortened midtrimester cervicallength. Am J Obstet Gynecol 2009;201:e1–8.
Additional Supporting Information may be found in the 15 To MS, Alfirevic Z, Heath VC, Cicero S, Cacho AM, Williamson PR, online version of this article: et al. Cervical cerclage for prevention of preterm delivery in womenwith Appendix S1. Survey of practice in preterm labour clinics in the UK. & 16 Salomon LJ, Diaz-Garcia C, Bernard JP, Ville Y. Reference range for cervical length throughout pregnancy: non-parametric LMS-basedmodel applied to a large sample. Ultrasound Obstet Gynecol 1 Ananth CV, Vintzileos AM. Epidemiology of preterm birth and its 17 Berghella V, Hayes E, Visintine J, Baxter JK. Fetal fibronectin testing clinical subtypes. J Matern Fetal Neonatal Med 2006;19:773–82.
for reducing the risk of preterm birth. Cochrane Database Syst Rev 2 Petrou S, Sach T, Davidson L. The long-term costs of preterm birth and low birth weight: results of a systematic review. Child Care 18 Brocklehurst P, Gordon A, Heatley E, Milan SJ. Antibiotics for Health Dev 2001;27:97–115.
treating bacterial vaginosis in pregnancy. Cochrane Database Syst 3 Mangham LJ, Petrou S, Doyle LW, Draper ES, Marlow N. The cost of preterm birth throughout childhood in England and Wales.
19 Hoyme UB, Huebner J. Prevention of preterm birth is possible by vaginal pH screening, early diagnosis of bacterial vaginosis or 4 Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendaville W, abnormal vaginal flora and treatment. Gynecol Obstet Invest Paraskevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and 20 Othman M, Alfirevic Z, Neilson JP. Probiotics for preventing preterm meta-analysis. Lancet 2006;367:489–98.
labour. Cochrane Database Syst Rev 2007;1:CD005941.
5 Celik E, To M, Gajewska K, Smith GC, Nicolaides KH. Cervical 21 Bujold E, Roberge S, Tapp S, Giguere Y. Opinion & Hypothesis; length and obstetric history predict spontaneous preterm birth: could early aspirin prophylaxis prevent against preterm birth? development and validation of a model to provide individualized risk J Matern Fetal Neonatal Med 2011;24:966–7.
assessment. Ultrasound Obstet Gynecol 2008;31:549–54.
22 Salvig JD, Lamont RF. Evidence regarding an effect of marine n-3 6 Berghella V, Rafael TJ, Szychowski JM, Rust OA, Owen J. Cerclage fatty acids on preterm birth: a systematic review and meta-analysis.
for short cervix on ultrasonography in women with singleton Acta Obstet Gynecol Scand 2011;90:825–38.
gestations and previous preterm birth: a meta-analysis. Obstet 23 Whitworth M, Quenby S, Cockerill RO, Dowswell T. Specialised antenatal clinics for women with a pregnancy at high risk of preterm 7 Alfirevic Z, Stampalija T, Roberts D, Jorgenseon AL. Cervical stitch birth (excluding multiple pregnancy) to improve maternal and infant (cerclage) for preventing preterm birth in singleton pregnancy.
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24 Dodd JM, Crowther CA. Specialised antenatal clinics for women 8 Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH. Progesterone with a multiple pregnancy for improving maternal and infant and the risk of preterm birth among women with a short cervix. N outcomes. Cochrane Database Syst Rev 2012;8:CD005300.
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25 General Medical Council. Effective Governance to Support Medical 9 Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad Revalidation. London: General Medical Council, 2013.
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ª 2013 Royal College of Obstetricians and Gynaecologists

Source: http://www.ptbnetwork.co.uk/app/download/809785/Sharp+and+Alfirevic+2014.pdf

Dr_bieger_neurostress-guide-juli.2009-kurz201

PD Dr med WP Bieger NeuroStress Guide EINLEITUNG Der vorliegende NeuroScience-Guide ist als Anleitung für Patienten, Ärzte und Therapeuten gedacht. Er soll einen Einblick in die Funktionsweise des Neuroendokriniums und in die Grundlagen neuroendokriner Funktionsstörungen und deren Behandlung vermitteln. Die von uns entwickelte „NeuroStress"-Diagnostik wird vorgestellt und physiologische Behandlungsformen besprochen. Schon lange gibt es hochwirksame Substanzen für die natürliche Behandlung psychoneurovegetativer Störungen, die allerdings durch die Entwicklung der modernen Psychopharmaka verdrängt wurden. Die unbefriedigenden Ergebnisse der Antidepressiva haben die traditionellen Behandlungskonzepte jedoch wieder ins Bewusstsein gerückt. Unser aktuelles ganzheitliches diagnostisch-therapeutisches Konzept greift die bewährten Verfahren auf und verbindet sie mit innovativen Diagnose- und Behandlungsformen aus den USA. Eingangsüberlegungen: 1. Die Zahl neurovegetativer Störungen und psychischer Krankheiten nimmt weltweit stark zu. Damit auch die Nachfrage nach neuen diagnostischen Möglichkeiten und effzienten, gut verträglichen Behandlungen. Seit Jahren steigt die Zahl psychischer Störungen in den westlichen Industrieländern. Man geht davon aus, dass bis zu 60% der Krankheitsfälle in der täglichen ärztlichen Praxis psychischer Natur sind bzw. eng mit psychischen Belastungen verbunden sind. Schon heute entfallen viele Krankheitstage auf psychische Störungen, ihre Zahl nimmt ständig zu, während die Gesamtzahl krankheitsbedingter Fehltage seit Jahren zurückgeht. Besonders gravierend ist die Zunahme der Depressionen. Während Herz-Kreislauferkrankungen, Herzinfarkt, sogar die häufigsten Krebserkrankungen (Lungen-, Brust- und Prostatakrebs) seit einigen Jahren abnehmende Tendenz zeigen, nimmt der Anteil von Depressionen ständig zu. Die WHO geht in einem ihrer jüngsten Gesundheitsberichte (2006) davon aus, dass bereits in den nächsten 5-10 Jahren Depressionen die zweithäufigste medizinische Krankheitsursache überhaupt sein werden. 2. Psychopharmaka werden heute in enormem Maße eingesetzt, sie sind mit >65 Mrd € die umsatzstärkste pharmazeutische Präparategruppe. Ihre Wirksamkeit, vor allem die der Antidepressiva, ist jedoch begrenzt. Die Nebenwirkungen sind zahlreich und zum Teil lebensbedrohlich. Immer wieder werden Zweifel am Aussagewert von Psychopharmakastudien geäußert, die Publikation von klinischen Studien mit Antidepressiva erfolgt offensichtlich nach willkürlichen Kriterien (NEJM, 2008). In einer kürzlichen Metaanalyse wurde die fehende Wirksamkeit von Antidepressiva bei leichten bis mittelschweren Depressionen konstatiert (PloS Medicine, 2008). Nur bei schweren Depressionen findet sich ein Vorteil von Antidepressiva gegenüber Placebos. 3. Die Neurobiologie psychischer Störungen wird seit Jahren intensiv untersucht, neue Untersuchungsverfahren wie MRT, PET, SPECT, Immunologie oder Molekulargenetik haben das Verständnis der zentralen Prozesse enorm verbessert. Neue Diagnose- und Behandlungsverfahren können daher stärker auf Wissen und weniger auf Zufallsbeobachtungen wie bisher basiert werden. STRESS Als eines der zentralen Geschehen gilt chronischer Stress, der vielfach zu bleibenden psychovegetativen Störungen führt. Ein kürzlich erschienenes Buch des Bonner Psychiaters Prof. Benkert (2006) hat den Begriff der „StressDepression" geprägt und damit „Stress" als ganz wesentlichen Grund für psychische Störungen einschließlich Depressionen in den Mittelpunkt

Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug binding site

Contents lists available at Molecular Immunology Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug binding site Katarzyna B. Handing , Ivan G. Shabalin , Karol Szlachta , Karolina A. Majorek , a Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908-0736, USA b New York Structural Genomics Research Consortium (NYSGRC), USA