Male-factor infertility is involved in about half of all infertile couples who seek assisted reproduction treatment.1 The advent of in-vitro fertilisation (IVF) with intracytoplasmic sperm injection (ICSI) has allowed many men with severe male factor to have their own genetic child.2 The development of surgical sperm retrieval techniques by testicular sperm extraction (TESE) has extended the possibility of fatherhood to those with non-obstructive azoospermia (NOA).3

The reported sperm retrieval rate from TESE varies in different studies due to inclusion of different populations, but is generally quoted to be around 50%.4 Nevertheless TESE is invasive. In a recent retrospective cohort study by Vloeberghs et al,5 only one (14.3%) out of seven men undergoing IVF-TESE eventually became a biological father. Studies have also shown a high prevalence of chromosomal abnormalities and Y-microdeletion in infertile men with NOA or severe oligozoospermia.6 7 8 9 These genetic abnormalities can potentially be transmitted vertically resulting in a child with sex aneuploidies or boys with the same Y-microdeletion.10 Guidelines from the American Society for Reproductive Medicine, American Urological Association, Canadian Urological Association, and International Federation of Fertility Societies are unanimous in suggesting that all men with NOA due to testicular failure should be offered genetic testing to exclude chromosomal abnormalities and Y chromosome microdeletions, and that genetic counselling be offered if an abnormality is detected.11 12 13 14

There are currently no local data on the sperm retrieval and pregnancy rates in IVF-TESE cycles, especially with regard to the presence of genetic abnormalities. Such information is invaluable to couples in pretreatment counselling and could affect their decision about treatment options. In this study, we determined the sperm retrieval and pregnancy rates in infertile couples who underwent IVF-TESE for NOA.

The study was a retrospective analysis of couples who underwent the first IVF cycle and required TESE for NOA at Queen Mary Hospital, a university affiliated tertiary care hospital, from January 2001 to December 2013. They were identified from our assisted reproductive technique database. Ethics approval was obtained from the Institutional Review Board of the University of Hong Kong / Hospital Authority Hong Kong West Cluster, with the requirement of patient informed consent waived because of its retrospective nature.

Husbands who attended our subfertility clinic were requested to submit one semen sample to the andrology laboratory of our centre prior to the first consultation. If the first semen analysis was abnormal, they were asked to submit a second semen sample. Semen analysis was based on the criteria of the World Health Organization (1999, 2010).15 16 Those with azoospermia confirmed in two semen samples following centrifugation were referred to the male infertility clinic for further assessment by urologists. All patients had detailed urological and reproductive history, physical examination, and hormonal profile including morning serum testosterone, follicle-stimulating hormone (FSH), and luteinising hormone.17 Men with azoospermia deemed to be due to a non-obstructive cause, as suggested by raised FSH and small testes, were advised to check their karyotype and microdeletion of the Y chromosome. The detailed techniques for chromosome analysis and Y-microdeletion studies by polymerase chain reaction of DNA from peripheral blood have been previously described.6 9 18 Karyotyping was performed by analysis of banded metaphase chromosomes from cultured cells. At least 15 and 30 metaphases were analysed routinely and whenever an anomaly was suspected, respectively.6 Y-microdeletion was analysed using six Y chromosome specific sequence tagged site markers that corresponded to the AZFa (sY84, sY86), AZFb (sY127, sY132), and AZFc (SY254, sY255) regions.6 9 18 Information on karyotype and Y-microdeletion was obtained from the medical record of the patients, and cross-referenced with the database of the genetic screening for male subfertility at Tsan Yuk Hospital.

Men with NOA who wished to have their own genetic child would be advised to undergo TESE to retrieve sperms. The most common ovarian stimulation protocols used in our unit were the long gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist protocols. Details of the stimulation cycle have previously been described.19 Patients attended the clinic on day 2 of the treatment cycle. Transvaginal ultrasonography was performed to determine antral follicle count (AFC) and serum oestradiol level was checked. Ovarian stimulation was commenced if the serum oestradiol level was confirmed at basal level and there was no ovarian cyst. The gonadotropin dosage depended on the woman’s age, AFC, and previous ovarian response. Transvaginal ultrasound for follicular tracking was performed 7 days after the start of ovarian stimulation and every 1 to 3 days thereafter. Further dosage of gonadotropins was titrated depending on the ovarian response of the patient during follicular tracking. Human chorionic gonadotropin (hCG) was given to trigger final oocyte maturation when the mean diameter of the leading follicle was at least 18 mm and three or more follicles reached a mean diameter of at least 16 mm. Transvaginal ultrasound-guided oocyte retrieval was performed 34 to 36 hours later.

The urologist was responsible for performing TESE that was performed under general anaesthesia on the day of oocyte retrieval. In conventional TESE, the scrotal skin and tunica vaginalis were opened and the testis was exposed through an incision. Bilateral testicular biopsies from the upper, middle, and lower poles were performed. Microdissection TESE, which involved identification of spermatogenically active areas under high magnification for more targeted biopsies, was performed starting from 2010. The biopsied testicular tissue was minced mechanically with two microscope slides, and incubated for 1 hour to allow the sperms to swim out of the tissue. Enzymatic digestion of the testicular tissue was performed as described when no sperms were seen under microscope.20 The testicular sperms were isolated by mini-density gradient centrifugation. Sperms with high density at the bottom of the gradient as well as those in the interface between the gradients were collected in two aliquots of culture medium. Before ICSI, the embryologist searched the sperms first in the whole aliquot containing sperms of high density, and then in the aliquot containing sperms at the interface if no sperm was found in the first aliquot. Spare sperms were cryopreserved. Fertilisation was achieved by ICSI in patients with successful sperm retrieval. One or two embryos were replaced 2 days after retrieval. Luteal phase support was given with either two doses of hCG 1500 IU 5 days apart or vaginal progesterone for 2 weeks after embryo transfer. Patients were followed up with a urinary pregnancy test 16 days after embryo transfer and those with a positive pregnancy test had transvaginal ultrasound scan performed 10 to 14 days later and were referred for antenatal care at 8 to 10 weeks of gestation. Pregnancy outcome was monitored. Pregnancy was defined as a positive urinary pregnancy test. A clinical pregnancy was defined as a pregnancy with the presence of one or more intrauterine sac on transvaginal ultrasound. An ongoing pregnancy was defined as the presence of at least one fetal heart pulsation on ultrasound beyond 20 weeks. When no sperms were retrieved, the collected oocytes were either discarded, donated, or frozen if further treatment with donor sperm was considered.

Data analyses were performed by the Statistical Package for the Social Sciences (Windows version 20.0; SPSS Inc, Chicago [IL], US). Comparisons between the groups were made using the Fisher’s exact test, and P<0.05 was considered statistically significant.

Only information from the first cycle of IVF-TESE was included. Of 112 men who underwent TESE during the study period, 23 were excluded from analysis because of non-motile sperms in the ejaculate (n=3), ejaculatory dysfunction (n=4), and obstructive azoospermia and underwent TESE after failed microepididymal sperm aspiration (n=16). Therefore, 89 patients with NOA were included in the analysis.

The mean age of the men was 37.2 (standard deviation [SD], 6.2) years. Of the 85 patients with smoking history available, 59 (69.4%) were non-smokers and 26 (30.6%) were smokers. Genetic information was missing in nine men. Of 76 men with genetic information available, eight (10.5%) had karyotypic abnormality—six were sex chromosomal and two were autosomal, as shown in Table 1. The most common sex chromosomal abnormality was Klinefelter syndrome (3/6, 50%; 1 non-mosaic and 2 mosaic). The two men with autosomal chromosome abnormality were a ring chromosome 21 and a mosaic supernumerary marker chromosome. Of these 76 men, nine (11.8%) had microdeletion of the Y chromosome. The most common Y-microdeletion was AZFc microdeletion (6/9, 66.7%). Three men had both chromosomal abnormality and Y-microdeletion.

Of the 89 patients, sperms were successfully retrieved in 40 (44.9%). There was no statistically significant difference in the sperm retrieval rate in those with karyotype abnormalities and AFZc microdeletion compared with those without (Table 2). The same was true when those with sex chromosomal abnormality were compared with those having normal karyotype. Sperms were retrieved in the two patients with mosaic Klinefelter syndrome but not the one with non-mosaic Klinefelter syndrome. For those with Y-microdeletion, sperms were retrieved in 50% (3/6) with AZFc microdeletions, but no sperms were found in the men with AZFa+b+c and AZFb+c microdeletions. The men with AZFa+b+c and AZFb+c microdeletions all had co-existing sex chromosomal abnormalities (Table 1).

The mean age of the female partners was 37.2 (SD, 6.2) years. The median dosage of gonadotropins used was 1950 IU (interquartile range, 1650-2550 IU), duration of stimulation 12 days (11-14 days), peak oestradiol level 11 341 pmol/L (7859.5-19 260.5 pmol/L), and the number of metaphase II oocytes obtained was 8 (4-13). Pregnancy test was positive in 15/89 (16.9%) and the clinical pregnancy rate was 12/89 (13.5%). Among those with sperms found, pregnancy test was positive in 15/40 (37.5%) and the clinical pregnancy rate was 12/40 (30.0%). Clinical pregnancy rate per transfer was 12/35 (34.3%). Two patients had biochemical pregnancy and one had ectopic pregnancy. There were 10 live births—seven singletons and three pairs of twins. One patient underwent second-trimester medical termination of pregnancy for fetal alobar holoprosencephaly. One had an ongoing pregnancy at 12 weeks but was subsequently lost to follow-up. The ongoing pregnancy rate per cycle was 10/89 (11.2%). The clinical pregnancy rate was not statistically different between those who had karyotypic abnormalities (0/5, 0% vs 8/61, 13.1%; P=1.000) and Y-microdeletion (1/6, 16.7% vs 8/61, 13.1%; P=1.000) compared with those who did not. Among the five patients who did not have embryo transfer, two had failed fertilisation, two had no transferrable embryos, and one had no oocyte retrieved.

Ho et al17 highlighted the importance of male factor in infertility assessment and treatment in a recent case series in a local male infertility clinic. The incidence of azoospermia was reported to be up to 36.2%, of which 52.1% had a non-obstructive cause and would require TESE.17 With increasing awareness of male infertility, it is hoped that more men will seek professional help and share the burden in fertility treatment. Nevertheless, existing data available in the literature on outcomes of IVF-TESE are fragmentary5 and local data are still lacking.

Karyotypic abnormalities and Y-microdeletion have been associated with severe male factor infertility. Fu et al21 demonstrated high rates of chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men with azoospermia or severe oligozoospermia. In another local study from our centre, the prevalence of chromosomal abnormality and Y-microdeletion were up to 21.1% and 8.5%, respectively in the azoospermic group.6 The prevalence of sex chromosomal abnormality and Y-microdeletion in the present study was 6/76 (7.9%) and 9/76 (11.8%), respectively; the former was lower than that reported by our centre previously. This may be because we only included men who had TESE performed in the current study, and it is possible that some men, particularly those who were found to have genetic abnormality, did not further pursue assisted reproductive treatment considering the anticipated poor prognosis.

Testing for chromosomal abnormalities and Y-microdeletion are recommended as an essential part of the workup of men with NOA or severe oligospermia by the American Society for Reproductive Medicine,13 American Urological Association,12 Canadian Urological Association,11 and International Federation of Fertility Societies guidelines.14 In particular, microdeletion of the AZFa or AZFb regions were associated with poor prognosis of sperm retrieval and no sperms have been retrieved in these patients.22 Although our study did not show any statistically significant difference in the sperm retrieval rates in those with karyotype abnormalities and Y-microdeletion compared with those without, it should be noted that all patients who had sperms retrieved were having AZFc microdeletion consistent with existing reports, and those who had AZFabc and AZFbc did not have sperms retrieved. Nonetheless the three men with AZFabc and AZFbc microdeletions all had co-existing sex chromosomal abnormalities that may also have affected spermatogenesis. Men with AZFa or AZFb microdeletion are therefore often advised against TESE because of a very low chance of successful retrieval of mature spermatozoa. Given proper counselling, these patients may opt not to pursue further assisted reproductive techniques, and go directly for options including donor insemination or adoption. On the other hand, the majority of men with AZFc microdeletion have sperm available for use. In some studies, AZFc deletion was even associated with an increased likelihood of sperm retrieval.22 The sperm retrieval rate in men with Klinefelter syndrome via microdissection TESE has also been reported to be similar or even higher than in those with NOA and normal karyotype.23 24 25 In our experience, sperms were only found in the two patients with mosaic Klinefelter syndrome but not the one with non-mosaic Klinefelter syndrome. Previous studies showed that sperms are more likely to be retrieved in younger men with Klinefelter syndrome.26 27 In our study, the man with non-mosaic Klinefelter syndrome was 42 years old and might have passed the window of opportunity for successful sperm retrieval. The two patients with mosaic Klinefelter syndrome were 34 and 47 years old, respectively.

This study provides important information on the prognosis for men with NOA. The sperm retrieval rate of 44.9% is very similar to a previous report at our centre where sperms were found in 12/26 (46.2%) of men.28 In that study, the pregnancy rate was 14.3% per cycle when spermatozoa were injected. Our study showed that the chance for a man with NOA undergoing TESE to father his own child is 13.5%, very similar to that of 13.4% reported by Vloeberghs et al.5 Indeed, Vloeberghs et al5 have only included men with normal karyotype and absence of Y-microdeletion, who were included in our study, and we only included men who underwent first cycle of IVF-TESE. The clinical pregnancy rate would have been higher if we also included men who underwent further attempts. Nonetheless, men were generally advised against further TESE after failure to retrieve sperms in the first attempt owing to the poor prognosis.

Another important issue is the potential for the genetic abnormality to be transmitted vertically via assisted reproductive technology. Couples wherein the male partner has Y-microdeletion should be counselled about the potential for inheritance of compromised fertility by male offspring and proper genetic counselling should be in place before embarking on IVF-TESE.

The practice of our centre was synchronous TESE on the day of oocyte retrieval. Several studies have shown comparable fertilisation and pregnancy rates when TESE is performed beforehand, either on the day before oocyte retrieval29 or even prior to initiation of controlled ovarian hyperstimulation.30 The merit of the latter approach is that women do not have to go through controlled ovarian stimulation if no sperms can be retrieved, and therefore can avoid the risks of ovarian hyperstimulation syndrome and the costs involved. The available cryopreservation-thawing procedure for sperms leads to sperm loss however, and there is still a possibility that the cycle will have to be cancelled if there are no viable sperms after thawing.

As 50% of couples undergo IVF-TESE in vain, with resulting psychological and financial implications, research into various factors that could predict successful sperm retrieval is important. Previous findings from our retrospective study did not suggest any significant differences in the age, history of mumps or orchitis/oligozoospermia, volume of both testes, serum FSH and testosterone levels in men with or without spermatozoa in IVF-TESE cycles.28 Indeed, no individual biochemical or hormonal marker has been found to reliably predict success in TESE.31 Although histopathology of testicular biopsy has been shown to predict TESE outcome, it is invasive and usually done at the time of TESE itself rather than beforehand in many patients, limiting its role as a predictive marker.31 The detection of Y chromosome microdeletion, especially AZFa and AZFb, was important to guide prognosis as discussed above. Ramasamy et al32 showed that high serum FSH level in men did not affect the success of microdissection TESE and should not be used to deny men the possibility to father a child with their own genetic material.14 Similarly, testicular size may represent poor spermatogenesis in general but does not consistently predict sperm retrieval rate.31 In a meta-analysis, serum inhibin B had a sensitivity of 0.65 and a specificity of 0.83 in prediction of successful TESE but it was still suboptimal as a single predictive criterion.33 Seminal anti-Müllerian hormone and inhibin B are secreted by the Sertoli cells into the seminiferous tubules and therefore in theory are more direct markers of spermatogenesis, but their predictive value for successful TESE was not confirmed in a prospective study of 139 men with NOA by Mitchell et al.34 A combination of factors have been shown to fare better, and authors have described the use of a predictive score involving the total testicular volume, FSH, and inhibin B to predict the sperm retrieval rate in NOA.35

There are several limitations to our study. The number of men who declined genetic testing or TESE was not known. These men may be those with anticipated poor prognosis such that our study has included those with ‘better’ prognosis and therefore a higher sperm retrieval rate. In addition, while some authors suggest that hormonal profile or testicular volume may have provided prognostic information,35 36 our information on hormonal profile of men was incomplete. Prior to TESE, FSH might have been checked up to 2 years because of the long waiting list for IVF, and therefore was not analysed in this study. Other important limitations are the small number of cases and retrospective nature of our study that precludes proper statistical analysis. When pregnancy outcome is analysed, it is essential to remember the other confounding variables of the female partner such as age and diagnostic category that limit the conclusions that can be drawn. Moreover, as the study spanned over 13 years, there have been changes such as surgical techniques. Men included in the earlier years underwent TESE while those more recently underwent microdissection TESE. Further studies looking into different prognostic factors to predict successful sperm retrieval are needed.

The sperm retrieval rate and clinical pregnancy rate per cycle in men undergoing IVF-ICSI-TESE in our unit were 44.9% and 13.5%, respectively. Karyotype and AZFc microdeletion abnormalities did not predict the success of sperm retrieval or clinical pregnancy rate in couples undergoing IVF-ICSI-TESE in the present case series, but are important in patient counselling. Consistent with existing literature, no sperms could be retrieved in individuals with AZFa and AZFb microdeletions.

We would like to thank Mr Tak-ming Cheung for data management, and the laboratory colleagues of Prenatal Diagnostic Laboratory at Tsan Yuk Hospital who have helped trace the karyotype and Y-microdeletion results.

All authors have disclosed no conflicts of interest.

1. Infertility diagnosis by age of patients receiving RT procedures (other than DI and AIH) in 2013. Council on Human Reproductive Technology. Available from: http://www.chrt.org.hk/english/publications/files/table17_2013.pdf. Accessed 6 Jul 2015.

2. Devroey P, Van Steirteghem A. A review of ten years experience of ICSI. Hum Reprod Update 2004;10:19-28. Crossref

3. Devroey P, Liu J, Nagy Z, et al. Pregnancies after testicular sperm extraction and intracytoplasmic sperm injection in non-obstructive azoospermia. Hum Reprod 1995;10:1457-60. Crossref

4. Donoso P, Tournaye H, Devroey P. Which is the best sperm retrieval technique for non-obstructive azoospermia? A systematic review. Hum Reprod Update 2007;13:539-49. Crossref

5. Vloeberghs V, Verheyen G, Haentjens P, Goossens A, Polyzos NP, Tournaye H. How successful is TESE-ICSI in couples with non-obstructive azoospermia? Hum Reprod 2015;30:1790-6. Crossref

6. Ng PP, Tang MH, Lau ET, et al. Chromosomal anomalies and Y-microdeletions among Chinese subfertile men in Hong Kong. Hong Kong Med J 2009;15:31-8.

7. Chiang HS, Wei HJ, Chen YT. Genetic screening for patients with azoospermia and severe oligo-asthenospermia. Int J Androl 2000;23 Suppl 2:20-5. Crossref

8. Chandley AC. Chromosome anomalies and Y chromosome microdeletions as causal factors in male infertility. Hum Reprod 1998;13 Suppl 1:45-50. Crossref

9. Tse JY, Yeung WS, Lau EY, Ng EH, So WW, Ho PC. Deletions within the azoospermia factor subregions of the Y chromosome in Hong Kong Chinese men with severe male-factor infertility: controlled clinical study. Hong Kong Med J 2000;6:143-6.

10. Lee SH, Ahn SY, Lee KW, Kwack K, Jun HS, Cha KY. Intracytoplasmic sperm injection may lead to vertical transmission, expansion, and de novo occurrence of Y-chromosome microdeletions in male fetuses. Fertil Steril 2006;85:1512-5. Crossref

11. Jarvi K, Lo K, Grober E, et al. The workup and management of azoospermic males. Can Urol Assoc J 2015;9:229-35. Crossref

12. Jarow J, Sigman M, Kolettis PN, et al. The evaluation of the azoospermic male: AUA Best Practice Statement (revised 7/22/11). US, Maryland: American Urological Association Education and Research, Inc; 2011.

13. Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Male Reproduction and Urology. Evaluation of the azoospermic male. Fertil Steril 2008;90(5 Suppl):S74-7. Crossref

14. Standards and Practice Committee. International Federation of Fertility Societies. Global standards of infertility care. Standard 17. Investigation and management of non-obstructive azoospermia. Recommendations for practice. June 2014.

15. World Health Organization. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4th ed. Cambridge: Cambridge University Press; 1999.

16. Cooper TG, Noonan E, von Eckardstein S, et al. World Health Organization reference values for human semen characteristics. Human Reprod Update 2010;16:231-45. Crossref

17. Ho KL, Tsu JH, Tam PC, Yiu MK. Disease spectrum and treatment patterns in a local male infertility clinic. Hong Kong Med J 2015;21:5-9.

18. Tse JY, Yeung WS, Ng EH, et al. A comparative study of Y chromosome microdeletions in infertile males from two Chinese populations. J Assist Reprod Genet 2002;19:376-83. Crossref

19. Li HW, Lee VC, Lau EY, Yeung WS, Ho PC, Ng EH. Role of baseline antral follicle count and anti-Mullerian hormone in prediction of cumulative live birth in the first in vitro fertilisation cycle: a retrospective cohort analysis. PLoS One 2013;8:e61095. Crossref

20. Crabbé E, Verheyen G, Silber S, et al. Enzymatic digestion of testicular tissue may rescue the intracytoplasmic sperm injection cycle in some patients with non-obstructive azoospermia. Hum Reprod 1998;13:2791-6. Crossref

21. Fu L, Xiong DK, Ding XP, et al. Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men. J Assist Reprod Genet 2012;29:521-7. Crossref

22. Stahl PJ, Masson P, Mielnik A, Marean MB, Schlegel PN, Paduch DA. A decade of experience emphasizes that testing for Y microdeletions is essential in American men with azoospermia and severe oligozoospermia. Fertil Steril 2010;94:1753-6. Crossref

23. Bakircioglu ME, Ulug U, Erden HF, et al. Klinefelter syndrome: does it confer a bad prognosis in treatment of nonobstructive azoospermia? Fertil Steril 2011;95:1696-9. Crossref

24. Sabbaghian M, Modarresi T, Hosseinifar H, et al. Comparison of sperm retrieval and intracytoplasmic sperm injection outcome in patients with and without Klinefelter syndrome. Urology 2014;83:107-10. Crossref

25. Ozveri H, Kayabasoglu F, Demirel C, Donmez E. Outcomes of micro-dissection TESE in patients with non-mosaic Klinefelter’s syndrome without hormonal treatment. Int J Fertil Steril 2015;8:421-8.

26. Rohayem J, Fricke R, Czeloth K, et al. Age and markers of Leydig cell function, but not of Sertoli cell function predict the success of sperm retrieval in adolescents and adults with Klinefelter’s syndrome. Andrology 2015;3:868-75. Crossref

27. Mehta A, Paduch DA. Klinefelter syndrome: an argument for early aggressive hormonal and fertility management. Fertil Steril 2012;98:274-83. Crossref

28. Ng HY, Lau YL, Yeung SB, So WK, Tam PC, Ho PC. Testicular sperm extraction and intracytoplasmic sperm injection in non-obstructive azoospermia. Chinese Med J (Engl) 2000;113:246-50.

29. Levran D, Ginath S, Farhi J, Nahum H, Glezerman M, Weissman A. Timing of testicular sperm retrieval procedures and in vitro fertilization–intracytoplasmic sperm injection outcome. Fertil Steril 2001;76:380-3. Crossref

30. Karacan M, Alwaeely F, Erkan S, et al. Outcome of intracytoplasmic sperm injection cycles with fresh testicular spermatozoa obtained on the day of or the day before oocyte collection and with cryopreserved testicular sperm in patients with azoospermia. Fertil Steril 2013;100:975-80. Crossref

31. Bernie AM, Ramasamy R, Schlegel PN. Predictive factors of successful microdissection testicular sperm extraction. Basic Clin Androl 2013;23:5. Crossref

32. Ramasamy R, Lin K, Gosden LV, Rosenwaks Z, Palermo GD, Schlegel PN. High serum FSH levels in men with nonobstructive azoospermia does not affect success of microdissection testicular sperm extraction. Fertil Steril 2009;92:590-3. Crossref

33. Toulis KA, Iliadou PK, Venetis CA, et al. Inhibin B and anti-Müllerian hormone as markers of persistent spermatogenesis in men with non-obstructive azoospermia: a meta-analysis of diagnostic accuracy studies. Hum Reprod Update 2010;16:713-24. Crossref

34. Mitchell V, Boitrelle F, Pigny P, et al. Seminal plasma levels of anti-Müllerian hormone and inhibin B are not predictive of testicular sperm retrieval in nonobstructive azoospermia: a study of 139 men. Fertil Steril 2010;94:2147-50. Crossref

35. Boitrelle F, Robin G, Marcelli F, et al. A predictive score for testicular sperm extraction quality and surgical ICSI outcome in non-obstructive azoospermia: a retrospective study. Hum Reprod 2011;26:3215-21. Crossref

36. Yang Q, Huang YP, Wang HX, et al. Follicle-stimulating hormone as a predictor for sperm retrieval rate in patients with nonobstructive azoospermia: a systematic review and meta-analysis. Asian J Androl 2015;17:281-4. Crossref

Hostile proximal infrarenal aortic neck is often considered one of the relative contra-indications for infrarenal endovascular aortic repair (EVAR), but large multicentre registries have shown that more EVARs have been performed worldwide beyond manufacturers’ indications.1 2 3 Data from the EUROSTAR Registry more than a decade ago looking at aneurysm morphology and procedural details of 2272 patients showed that perioperative type 1a endoleak was significantly associated with a larger angulated infrarenal neck with thrombus.4 Other morphological features included short aortic neck length, large sac diameter, severe angulation, and conical neck configuration.5 Endoleak is defined as the persistence of blood flow outside the lumen of an endovascular graft but within an aneurysm sac. Type 1a endoleak is a leak around the proximal graft attachment site. They are clinically important since they can lead to continual aneurysm enlargement and eventual rupture.6

Although the development of renal and mesenteric fenestration or branched stent graft technology to extend the landing zone more proximally may overcome type 1a endoleaks, these devices may not be ideal because of regulations, complexity, and manufacturing delays.7 In addition, contemporary published literature does not provide sufficiently strong evidence to warrant a change in treatment guidelines for juxtarenal or short-neck aneurysm.8

The use of a proximal giant Palmaz stent (Cordis Corp, Fremont [CA], US) is a well-recognised technique to manage a type 1a endoleak intra-operatively.9 10 11 12 A prophylactic Palmaz stent inserted for hostile neck has also been reported.13 14 15 The aim of this study was to report the effectiveness and safety of an intra-operative Palmaz stent for an immediate type 1a endoleak.

Patients with an infrarenal abdominal aortic aneurysm (AAA) who had undergone EVAR were retrospectively reviewed for the period 1 July 1999 to 30 September 2015. Data were extracted from prospectively collected computerised departmental database, supplemented by patient records. This study was done in accordance with the principles outlined in the Declaration of Helsinki. All patients had undergone a preoperative fine-cut computed tomographic (CT) scan and careful preoperative planning with a conclusion that EVAR was feasible. All our patients who underwent EVAR had preoperative three-dimensional aortic anatomy examined using the stationary TeraRecon Aquarius workstation (TeraRecon, San Mateo [CA], US) that rapidly manipulates all preoperative data sets in the Digital Imaging and Communications in Medicine, and examines the aortic morphology. These details would be difficult to appreciate on two-dimensional planar CT imaging, especially in those with inadequate short hostile neck. Those patients who were deemed unsuitable for infrarenal sealing would either undergo open repair or, more recently, fenestrated or adjunctive EVAR (such as chimney technique).

Cook Zenith (Cook Medical, Bloomington [IN], US), Medtronic Endurant (Medtronic Inc, Minneapolis [MN], US), and TriVascular Ovation (TriVascular Inc, Santa Rosa [CA], US) stent grafts were most commonly used. We sometimes extended the manufacturers’ indications of use to include difficult aortic necks. All operations were performed in our institution, a tertiary vascular referral centre, by experienced vascular specialists in a hybrid endovascular suite (Siemens Artis zee Multipurpose System; Siemens, Erlangen, Germany). Post-deployment balloon moldings with Coda balloon (Cook Medical, Bloomington [IN], US) and completion angiograms with power injection were performed in all patients.

In the event of proximal endoleak on completion angiogram, further balloon molding would be attempted. Persistent endoleak was managed with balloon expandable giant Palmaz stent P4014 (Cordis Corp). Our preference was for the Palmaz stent to be positioned at the infrarenal region over the fabric of the stent graft, so as not to jeopardise any future chance of proximal extension with a renal or mesenteric fenestrated cuff. They would be crimped on a Coda balloon (maximum inflated diameter, 40 mm) and railed through a stiff guidewire to the top neck.

Cause of proximal endoleak was usually hostile neck. We focused on aortic infrarenal neck anatomy where the Palmaz stent was placed and exerted its effect. All preoperative CT scans were analysed. Measurement was automatically calculated by computer software Aquarius iNtuition Client version 4.4 (TeraRecon Inc), after a median centre line path (MCLP) was drawn. We used definitions of neck measurement as defined by Filis et al16:

(1) Neck length is calculated between the point of MCLP at the orifice of the lower renal artery and MCLP at the start of the aneurysm.

(2) Neck diameter is measured on the orthogonal cross-section of the neck, from the outer wall to the outer wall. It is measured at the lower renal artery level, 1 cm and 2 cm below.

(3) Neck angle is the angle between the axis of the neck (straight line between the MCLP of the aorta at the level of the orifice of the lower renal artery and the MCLP of the aorta at the start of the aneurysm) and the axis of the lumen of the aneurysm (straight line between the MCLP at the start of the aneurysm and the MCLP at the end of the aneurysm).

(4) Neck morphology (Fig 1):
(a) Funnel shape is defined as 20% decrease in neck area between the level of the lower renal artery and 2 cm below.
(b) Conical shape is defined as 20% increase in neck area between the level of the renal artery and 2 cm below.
(c) Cylindrical shape is defined between the above two.
(d) Shape is undetermined if neck length is less than 2 cm.

Immediate radiological result following Palmaz stent placement was reported. Any procedural mortality or morbidity was recorded. Our departmental protocol recommends postoperative imaging, either CT scan or duplex scan, at 1 to 3 months, then every 6 months for the first 2 years, and annually thereafter. These were supplemented by X-ray to detect any stent fracture or migration. Any endoleak detected during follow-up was reported as well as any alteration in sac size. Follow-up was dated to the most recent objective imaging available.

During the study period 1 July 1999 to 30 September 2015, a total of 842 AAA surgeries were performed, of which 320 (38%) were open repair and 522 (62%) were endovascular repair (28 fenestrated/branched EVAR and 494 infrarenal EVAR). In a cohort of 494 patients with infrarenal EVAR, 12 (2.4%) received an intra-operative proximal Palmaz stent for type 1a endoleak that was noticed on completion angiogram. No patients received prophylactic Palmaz stent for difficult neck anatomy.

Patient demographics are summarised in Table 1. The median age was 84 (range, 58-95) years. All had undergone elective surgery for asymptomatic AAA. The median AAA size was 7.6 cm (range, 5.0-9.4 cm). Seven patients received a Cook Zenith stent graft, one patient a Cook Aorto-Uni-Iliac device, three had Metronic Endurant stent grafts, and one had TriVascular Ovation stent graft. The occurrence of type 1a endoleak was more common in recent years (Table 2).

Table 2 summarises the neck morphologies of our cohort. Morphological review of the pre-EVAR aneurysm neck showed five conical, one funnel, five cylindrical, and one undetermined short necks. The median neck angle was 61 degrees (range, 19-109 degrees). Use of the stent graft was outside of the manufacturer’s guidelines in six (50%) patients. Most patients had one or more features of hostile neck, rendering them at high risk of proximal endoleak.

All 12 patients had persistent proximal type 1a endoleak after stent graft placement with standard balloon molding. Placement of a giant Palmaz stent in the infrarenal position was technically successful in all cases, although one Palmaz stent was placed too low and lodged in one of the iliac limbs. Nonetheless, it served its function well in correcting the proximal endoleak (Figs 2 and 3). Immediate resolution of the endoleak was achieved in eight (67%); whilst four (33%) had improved but persistent leak at completion of the procedure.

After a median follow-up of 16 (range, 1-59) months, no patient had a type 1a endoleak on subsequent imaging, either CT scan or duplex ultrasound scan. All patients had at least one postoperative CT scan. Patient 2 had a type 1c endoleak from an embolised left internal iliac artery that was managed conservatively. Patients 9 and 11 had a type 2 endoleak, also managed conservatively. All had shrinkage of sac size. Sac size of the aneurysms decreased from a mean of 7.4 cm pre-EVAR to 7.3 cm, 6.9 cm, 7.1 cm, and 6.1 cm at 1 month, 6 months, 1 year, and 2 years post-EVAR, respectively (Fig 4). Routine X-ray surveillance did not reveal any Palmaz stent fracture or migration.

One patient required secondary endovascular re-intervention for occluded left iliac limb at day 10 postoperatively. It was due to a tortuous iliac system causing an acute bend to the stent graft limb. There was no other reported secondary intervention. Seven patients have since died (at 6, 9, 16, 16, 20, 24, and 59 postoperative months) from non-aneurysm–related causes. Five remain alive at the time of writing.

Hostile aortic neck anatomy often precludes endovascular treatment of AAA. It has been shown in large clinical cohorts that up to 42% of EVARs are performed outside the instructions for use for commercially available stent grafts.3 17 18 19 Multiple measures have been developed to include more of these difficult necks for endovascular treatment. Evolution of stent graft design including suprarenal fixation20 and renal and mesenteric fenestration21 are examples. Adjunctive neck measures, eg endostapling,22 23 proximal fibrin glue embolisation,24 open aortic neck banding,25 and proximal covered cuff extension10 may be used in cases of perioperative type 1a endoleak following EVAR. Endostapling and glue embolisation, though minimally invasive, are not always feasible and risk major aortic injury. Open aortic neck banding requires laparotomy. Proximal cuff extension is only feasible if there is an additional sealing zone to the most caudal renal artery. Since we routinely landed our stent graft at the level of the lowest renal artery, this technique was not usually practical. The simplest and most well-recognised manoeuvre remains placement of a proximal Palmaz stent.

The morphology of the infrarenal aortic neck is important in securing the proximal landing zone. Three-dimensional workstation planning has been considered useful by many26 27; for example, Sobocinski et al28 showed that it reduced the rate of type 1 endoleaks and Velazquez et al29 indicated that it decreased the rate of extra iliac extension. We emphasise the importance of proper pre-EVAR planning, as this is one of the obvious factors that may compromise long-term durability and outcome. The fact that half of stent graft usage in our series was outside the instructions for use and most patients had one or more hostile neck feature rendered them at high risk of proximal endoleak. Under these circumstances, a Palmaz stent should always be readily available during EVAR.

Multiple series have reported their experience in its successful use. Early study by Dias et al9 reported nine patients who received a Palmaz stent and in whom aneurysm remained excluded at a median follow-up of 13 months (range, 6-24 months). Rajani et al10 reported successful treatment of intra-operative type 1 endoleak with Palmaz stent in 27 patients who had no recurrence at follow-up, although length of follow-up was not mentioned. Arthurs et al11 reported no type 1 endoleak in 31 patients after a median follow-up of 53 months (interquartile range, 14-91 months). The Palmaz stent was effective across a variety of available devices with suprarenal fixation (eg Cook Zenith) or infrarenal fixation (eg Gore Excluder; WL Gore & Associates, Inc, Newark [DE], US). Our results are in agreement with these findings.

Other series have shown controversial results. Farley et al15 reported 18 cases of Palmaz stent placement. Technical placement failed in one patient, in whom attempts at passing the access sheath to the proximal landing zone resulted in proximal migration of the main body of the aortic stent graft. An attempt at passage of the balloon-mounted stent without sheath protection resulted in slippage of the stent from the balloon. The stent could not be retrieved and was deployed in the iliac limb. With a mean follow-up period of 254 days in the 17 successful Palmaz stent placements, one patient had unresolved type 1 endoleak. Malposition of the stent was not an unusual complication.30 31 Kim et al32 described a deployment technique to ensure accuracy. Palmaz stent was asymmetrically hand-crimped on an appropriately sized valvuloplasty balloon that assured the proximal aspect would deploy first.

Some series have advocated prophylactic Palmaz stent placement in hostile necks, including 15 patients reported by Cox et al.13 One (7%) patient had secondary endoleak with intervention after a mean follow-up of 12 months. Qu and Raithel14 reported 117 cases of difficult neck treated with unibody Powerlink device (Endologix Inc, Irvine [CA], US). In this series, 83 (72.8%) had proximal Palmaz stent as an adjunctive procedure. Proximal cuff extension was also used. The mean follow-up was 2.6 years (range, 4 months-5 years). Results were satisfactory with an overall re-intervention rate of 5.3%, and no device migration, conversion, or post-EVAR rupture.

Palmaz stents were routinely placed at an infrarenal position in our unit on the basis that future extension with a fenestrated cuff is possible. If a transrenal position is adopted, the strut of the Palmaz stent, which is a very tight space, may hinder catheterisation of renal or visceral arteries should a fenestrated cuff be inserted. This is not absolute, however. Oikonomou et al33 reported a case of post-treatment with Powerlink stent graft and transrenal Palmaz stent. Treatment of proximal endoleak at 3 years after operation was successful by means of a proximal fenestrated graft. Selective catheterisation of both renal arteries and dilation of the stent struts prior to stent graft repair ensured that it would be feasible to catheterise the renal arteries through the fenestrated cuff.

There are limitations to this study. The retrospective nature of our cohort may risk inaccurate information. The efficacy of the Palmaz stent in aneurysms with short infrarenal neck may not be tested, as the majority were considered straight for custom-made fenestrated or branched EVAR. In our limited experience, a Palmaz stent is a valuable tool to expand the boundary of endovascular treatment for AAA.

Palmaz stent helps proximal sealing and fixation. In our experience, Palmaz stenting is effective and safe as a salvage treatment of immediate proximal endoleak during EVAR. We emphasise the importance of appropriate patient selection, pre-EVAR planning, and diligent follow-up.

All authors have disclosed no conflicts of interest.

1. Bachoo P, Verhoeven EL, Larzon T. Early outcome of endovascular aneurysm repair in challenging aortic neck morphology based on experience from the GREAT C3 registry. J Cardiovasc Surg (Torino) 2013;54:573-80.

2. Matsumoto T, Tanaka S, Okadome J, et al. Midterm outcomes of endovascular repair for abdominal aortic aneurysms with the on-label use compared with the off-label use of an endoprosthesis. Surg Today 2015;45:880-5. Crossref

3. Hoshina K, Hashimoto T, Kato M, Ohkubo N, Shigematsu K, Miyata T. Feasibility of endovascular abdominal aortic aneurysm repair outside of the instructions for use and morphological changes at 3 years after the procedure. Ann Vasc Dis 2014;7:34-9. Crossref

4. Buth J, Harris PL, van Marrewijk C, Fransen G. The significance and management of different types of endoleaks. Semin Vasc Surg 2003;16:95-102. Crossref

5. Stanley BM, Semmens JB, Mai Q, et al. Evaluation of patient selection guidelines for endoluminal AAA repair with the Zenith Stent-Graft: the Australasian experience. J Endovasc Ther 2001;8:457-64. Crossref

6. Fransen GA, Vallabhaneni SR Sr, van Marrewijk CJ, et al. Rupture of infra-renal aortic aneurysm after endovascular repair: a series from EUROSTAR registry. Eur J Vasc Endovasc Surg 2003;26:487-93. Crossref

7. Chuter T, Greenberg RK. Standardized off-the-shelf components for multibranched endovascular repair of thoracoabdominal aortic aneurysms. Perspect Vasc Surg Endovasc Ther 2011;23:195-201. Crossref

8. Ou J, Chan YC, Cheng SW. A systematic review of fenestrated endovascular repair for juxtarenal and short-neck aortic aneurysm: evidence so far. Ann Vasc Surg 2015;29:1680-8. Crossref

9. Dias NV, Resch T, Malina M, Lindblad B, Ivancev K. Intraoperative proximal endoleaks during AAA stent-graft repair: evaluation of risk factors and treatment with Palmaz stents. J Endovasc Ther 2001;8:268-73. Crossref

10. Rajani RR, Arthurs ZM, Srivastava SD, Lyden SP, Clair DG, Eagleton MJ. Repairing immediate proximal endoleaks during abdominal aortic aneurysm repair. J Vasc Surg 2011;53:1174-7. Crossref

11. Arthurs ZM, Lyden SP, Rajani RR, Eagleton MJ, Clair DG. Long-term outcomes of Palmaz stent placement for intraoperative type Ia endoleak during endovascular aneurysm repair. Ann Vasc Surg 2011;25:120-6. Crossref

12. Chung J, Corriere MA, Milner R, et al. Midterm results of adjunctive neck therapies performed during elective infrarenal aortic aneurysm repair. J Vasc Surg 2010;52:1435-41. Crossref

13. Cox DE, Jacobs DL, Motaganahalli RL, Wittgen CM, Peterson GJ. Outcomes of endovascular AAA repair in patients with hostile neck anatomy using adjunctive balloon-expandable stents. Vasc Endovascular Surg 2006;40:35-40. Crossref

14. Qu L, Raithel D. Experience with the Endologix Powerlink endograft in endovascular repair of abdominal aortic aneurysms with short and angulated necks. Perspect Vasc Surg Endovasc Ther 2008;20:158-66. Crossref

15. Farley SM, Rigberg D, Jimenez JC, Moore W, Quinones-Baldrich W. A retrospective review of Palmaz stenting of the aortic neck for endovascular aneurysm repair. Ann Vasc Surg 2011;25:735-9. Crossref

16. Filis KA, Arko FR, Rubin GD, Zarins CK. Three-dimensional CT evaluation for endovascular abdominal aortic aneurysm repair. Quantitative assessment of the infrarenal aortic neck. Acta Chir Belg 2003;103:81-6. Crossref

17. Walker J, Tucker LY, Goodney P, et al. Adherence to endovascular aortic aneurysm repair device instructions for use guidelines has no impact on outcomes. J Vasc Surg 2015;61:1151-9. Crossref

18. Igari K, Kudo T, Toyofuku T, Jibiki M, Inoue Y. Outcomes following endovascular abdominal aortic aneurysm repair both within and outside of the instructions for use. Ann Thorac Cardiovasc Surg 2014;20:61-6. Crossref

19. Lee JT, Ullery BW, Zarins CK, Olcott C 4th, Harris EJ Jr, Dalman RL. EVAR deployment in anatomically challenging necks outside the IFU. Eur J Vasc Endovasc Surg 2013;46:65-73. Crossref

20. Robbins M, Kritpracha B, Beebe HG, Criado FJ, Daoud Y, Comerota AJ. Suprarenal endograft fixation avoids adverse outcomes associated with aortic neck angulation. Ann Vasc Surg 2005;19:172-7. Crossref

21. Verhoeven EL, Vourliotakis G, Bos WT, et al. Fenestrated stent grafting for short-necked and juxtarenal abdominal aortic aneurysm: an 8-year single-centre experience. Eur J Vasc Endovasc Surg 2010;39:529-36. Crossref

22. Donas KP, Kafetzakis A, Umscheid T, Tessarek J, Torsello G. Vascular endostapling: new concept for endovascular fixation of aortic stent-grafts. J Endovasc Ther 2008;15:499-503. Crossref

23. Avci M, Vos JA, Kolvenbach RR, et al. The use of endoanchors in repair EVAR cases to improve proximal endograft fixation. J Cardiovasc Surg (Torino) 2012;53:419-26.

24. Feng JX, Lu QS, Jing ZP, et al. Fibrin glue embolization treating intra-operative type I endoleak of endovascular repair of abdominal aortic aneurysm: long-term result [in Chinese]. Zhonghua Wai Ke Za Zhi 2011;49:883-7.

25. Scarcello E, Serra R, Morrone F, Tarsitano S, Triggiani G, de Franciscis S. Aortic banding and endovascular aneurysm repair in a case of juxtarenal aortic aneurysm with unsuitable infrarenal neck. J Vasc Surg 2012;56:208-11. Crossref

26. Lee WA. Endovascular abdominal aortic aneurysm sizing and case planning using the TeraRecon Aquarius workstation. Vasc Endovascular Surg 2007;41:61-7. Crossref

27. Parker MV, O’Donnell SD, Chang AS, et al. What imaging studies are necessary for abdominal aortic endograft sizing? A prospective blinded study using conventional computed tomography, aortography, and three-dimensional computed tomography. J Vasc Surg 2005;41:199-205. Crossref

28. Sobocinski J, Chenorhokian H, Maurel B, et al. The benefits of EVAR planning using a 3D workstation. Eur J Vasc Endovasc Surg 2013;46:418-23. Crossref

29. Velazquez OC, Woo EY, Carpenter JP, Golden MA, Barker CF, Fairman RM. Decreased use of iliac extensions and reduced graft junctions with software-assisted centerline measurements in selection of endograft components for endovascular aneurysm repair. J Vasc Surg 2004;40:222-7. Crossref

30. Gabelmann A, Krämer SC, Tomczak R, Görich J. Percutaneous techniques for managing maldeployed or migrated stents. J Endovasc Ther 2001;8:291-302. Crossref

31. Slonim SM, Dake MD, Razavi MK, et al. Management of misplaced or migrated endovascular stents. J Vasc Interv Radiol 1999;10:851-9. Crossref

32. Kim JK, Noll RE Jr, Tonnessen BH, Sternbergh WC 3rd. A technique for increased accuracy in the placement of the “giant” Palmaz stent for treatment of type IA endoleak after endovascular abdominal aneurysm repair. J Vasc Surg 2008;48:755-7. Crossref

33. Oikonomou K, Botos B, Bracale UM, Verhoeven EL. Proximal type I endoleak after previous EVAR with Palmaz stents crossing the renal arteries: treatment using a fenestrated cuff. J Endovasc Ther 2012;19:672-6. Crossref

Silver-Russell syndrome (SRS) [OMIM 180860] is a clinically and genetically heterogeneous congenital imprinting disorder. It was first described in 1953 by Dr Henry Silver and his colleagues, who reported two children with short stature and congenital hemihypertrophy.1 In the following year, Dr Alexander Russell reported five similar cases with intrauterine dwarfism and craniofacial dysostosis.2 The term SRS has been used since 1970 to describe a constellation of features with intrauterine growth retardation without postnatal catch-up, distinct facial characteristics, relative macrocephaly, body asymmetry, and/or fifth finger clinodactyly.3 4 The prevalence of SRS was estimated to be 1 in 100 000,5 but was probably underestimated due to the diverse and variable clinical manifestations. The majority of SRS cases are sporadic, although occasional familial cases have been reported.

Two major molecular mechanisms have been implicated in SRS—maternal uniparental disomy of chromosome 7 (mUPD7)6 and loss of DNA methylation (LOM) of the imprinting control region 1 (ICR1) on the paternal allele of chromosome 11p15 region that regulates the IGF2/H19 locus.6 7 8 9 According to the studies, LOM of ICR1 and mUPD7 roughly account for 45% to 50% and 5% to 10% of SRS cases, respectively.6 7 8 9 Rare cytogenetic rearrangements have also been reported in 1% to 2% of cases.4 10 11 There remain 30% to 40% of SRS cases in which the molecular mechanisms remain elusive, however.

Owing to the wide spectrum of clinical presentations of SRS, there is considerable clinical overlap with other growth retardation syndromes. At present there is no consensus for the diagnostic criteria, so diagnosing SRS is challenging. Several scoring systems have been proposed to facilitate clinical diagnosis and to guide genetic testing.7 11 12 13 14 Based on the prevalence of different molecular mechanisms, methylation study of the 11p15 region is the recommended first-tier investigation for patients with suspected SRS, and mUPD7 analysis is the second tier.14

The comprehensive clinical spectrum and molecular study of SRS have not been reported in the Chinese population. Therefore, a retrospective review that aimed to summarise the clinical and genetic findings of all SRS patients in Hong Kong was conducted. The sensitivity and specificity of different scoring systems7 11 12 13 14 in identifying Hong Kong Chinese SRS patients have also been studied.

The Clinical Genetic Service (CGS), Department of Health and the clinical genetic clinic at Queen Mary Hospital (QMH), The University of Hong Kong, are the only two tertiary genetic referral centres that provide comprehensive genetic counselling, and diagnostic and laboratory service for the Hong Kong population. Patients with a clinical suspicion of growth failure due to genetic causes or possibly SRS were referred for assessment and genetic testing.

In this review, all records of patients with suspected SRS seen at the CGS or clinical genetic clinic of QMH between January 2010 and September 2015 were retrieved from the computer database system using the key words of “Silver Russell syndrome” and “failure to thrive and growth retardation”. The clinical and laboratory data of these patients were retrospectively analysed. Patients with alternative diagnoses after assessment and genetic investigation were excluded. This study was done in accordance with the principles outlined in the Declaration of Helsinki.

Currently, there is no universal consensus on the diagnostic criteria of SRS, but the Hitchins et al’s criteria15 are the most commonly used clinically. The diagnosis of SRS in this study was made when a patient fulfilled three major, or two major and two minor criteria.

Major criteria included (1) intrauterine growth retardation/small for gestational age (<10th percentile); (2) postnatal growth with height/length <3rd percentile; (3) normal head circumference (3rd-97th percentile); and (4) limb, body, and/or facial asymmetry.

Minor criteria included (1) short arm span with normal upper-to-lower segment ratio; (2) fifth finger clinodactyly; (3) triangular facies; and (4) frontal bossing/prominent forehead.

Investigation of the methylation status and copy number change of the H19 differentially methylated region (H19 DMR) and KvDMR1 at chromosome 11p15 region was done with methylation specific–multiplex ligation-dependent probe amplification (MS-MLPA) method, using SALSA MLPA ME030-B1 BWS/RSS kit (MRC-Holland, Amsterdam, The Netherlands). Following the manufacturer’s instructions, approximately 100 ng genomic DNA was first denatured and hybridised overnight with the probe mixture supplied with the kit. The samples were then split into two portions, treated either with ligase alone or with ligase and HhaI. Polymerase chain reactions (PCR) were then performed with the reagents and primers supplied in the kit. The PCR products were separated by capillary electrophoresis (model 3130xl; Applied Biosystems, Foster City [CA], US). The electropherograms were analysed using GeneScan software (Applied Biosystems, Foster City [CA], US), and the relative peak area was calculated using the Coffalyser version 9.4 software (MRC-Holland, Amsterdam, The Netherlands).

We studied mUPD7 with eight polymorphic microsatellite markers, three on 7p and five on 7q (D7S531, D7S507, D7S2552, D7S2429, D7S2504, D7S500, D7S2442, and D7S2465), using a standard protocol. Haplotype analysis was then performed. A diagnosis of mUPD7 required evidence of exclusive maternal inheritance at two or more informative markers.

Epidemiological data, physical characteristics, growth records, and molecular findings were then collected for analysis. Clinical photographs were taken during consultation (Fig 1). In order to delineate the (epi)genotype-phenotype correlation, we divided the patients according to their (epi)genotype, namely H19 LOM, mUPD7, mosaic maternal uniparental disomy of chromosome 11 (mUPD11), or SRS of unexplained origin. The SRS of unexplained origin was defined as negative for 11p15 region epimutation and mUPD7 study. For statistical calculation, Student’s t test was used for continuous variables and Fisher’s exact test for categorical variables. Two-tailed P values were also computed. Differences were considered to be statistically significant when P≤0.05.

Three clinical scoring systems were applied to all patients referred with suspected SRS and included Netchine et al score,7 Bartholdi et al score,12 and the Birmingham score.14 An overview of the three SRS scoring systems is summarised in Table 1. Using the Hitchins et al’s criteria15 as standard in this study, the sensitivity and specificity of these three scoring systems in identifying SRS were compared.

During the study period, 83 patients with suspected SRS were referred to both genetic clinics. After clinical assessment and investigations, 54 patients had an alternative diagnosis. The remaining 29 patients were clinically diagnosed with SRS using the Hitchins et al’s criteria.15 All were Chinese. One was a prenatal case with maternal H19 duplication. Since termination of pregnancy was performed at 23 weeks of gestation, it was excluded for downstream analysis. For the remaining 28 SRS patients, their age at the end of the study (September 2015) ranged from 2 years to 22 years 9 months, with a median of 9 years 4 months. The male-to-female ratio was 9:5. Sequential MS-MLPA study on chromosome 11p15 region and mUPD7 study were performed on all SRS patients. Among the 28 live-birth SRS patients, 35.7% (n=10) had H19 LOM, 21.4% (n=6) had mUPD7, 3.6% (n=1) had mosaic mUPD11, and 39.3% (n=11) were of SRS of unexplained origin. The clinical features of the SRS cohort are summarised in Table 2. The clinical features of some molecularly confirmed SRS patients in this study and one illustrative microsatellite electropherogram in mUPD7 analysis are shown in Figure 1.

In order to study the (epi)genotype-phenotype correlation among the H19 LOM and mUPD7 groups, the clinical features were compared. There was no significant difference among the two groups (data not shown). When comparing the 28 molecularly confirmed SRS and 54 SRS of unexplained origin patients, postnatal microcephaly (P=0.01) and café-au-lait spots (P=0.05) were more common among SRS of unexplained origin, while body asymmetry (P<0.01) and limb asymmetry (P<0.01) were more common among the molecularly confirmed group.

The performance of the three clinical scoring systems namely Netchine et al score,7 Bartholdi et al score,12 and Birmingham score14 in identifying SRS in our cohort was compared. The proportion of molecularly confirmed cases in those ‘likely SRS’ and ‘unlikely SRS’ based on the scoring system are summarised in Table 3. The sensitivity and specificity among different scoring systems for identifying SRS are summarised in Table 4.

Silver-Russell syndrome is a clinically and genetically heterogeneous disorder. This is the first comprehensive clinical and epigenetic study of SRS in Hong Kong. With sequential 11p15 epimutation analysis and mUPD7 study of SRS patients in this cohort, molecular confirmation was achieved in 60.7% of cases; H19 LOM and mUPD7 accounted for 35.7% and 21.4% of the cases, respectively. Although the proportion of H19 LOM–related SRS cases was similar to the western and Japanese populations,6 7 8 9 16 the proportion of mUPD7 in our cohort was significantly higher. Nonetheless, due to the small sample size, this observation might not reflect the true ethnic-specific epigenetic alteration in the Chinese population. Further studies are necessary to confirm this difference.

In previous studies of (epi)genotype-phenotype correlation4 7 12 17 18 19 20 in SRS, patients with mUPD7 had a milder phenotype but were more likely to have developmental delay. On the contrary, patients with H19 LOM appeared to have more typical SRS features such as characteristic facial profile and body asymmetry. Such a correlation could not be demonstrated in our cohort. When comparing the molecularly confirmed and SRS of unexplained origin groups, postnatal microcephaly and café-au-lait spots were more common in the group of SRS of unexplained origin, while body/limb asymmetry was more common in the molecularly confirmed group. This observation has also been reported in Japanese SRS patients.16 This might be due to the greater clinical and genetic heterogeneity in the molecularly negative SRS.

Although SRS has been extensively studied, there remains no universal consensus on the clinical diagnostic criteria. Hitchins et al’s criteria15 are currently the most commonly used. In order to facilitate the clinical diagnosis, several additional scoring systems have been proposed which include the Netchine et al,7 Bartholdi et al,12 and Birmingham scores.14 Each of them has its advantages and limitations. The major caveats of those scoring systems include relative subjectivity of clinical signs, and time-dependent and evolving clinical features. The heterogeneity of clinical manifestations also limits their application. In order to validate these scoring systems, several studies have been performed to evaluate their accuracy in predicting the molecular genetic testing result.14 21 We also evaluated the performance of these three scoring systems in this Chinese cohort. All three scoring systems are 100% specific in diagnosing SRS, but the sensitivity for Netchine et al score,7 Bartholdi et al score,12 and Birmingham score14 is 75%, 53.6%, and 71.4%, respectively when compared with Hitchins et al’s criteria.15 This suggests that Hitchins et al’s criteria15 remain the most sensitive diagnostic criteria for SRS when used clinically.

The management of SRS is challenging and requires multidisciplinary input. Growth hormone (GH) treatment is the current recommended therapy for children with small for gestational age without spontaneous catch-up growth and those with GH deficiency. In SRS, abnormalities in spontaneous GH secretion and subnormal responses to provocative GH stimulation have been well reported.20 The proposed mechanism is dysregulation of the growth factors and its major binding protein,4 particularly in the H19 LOM group. Besides, SRS patients are expected to have poor catch-up growth. Nonetheless, GH therapy is not a universal standard treatment for SRS. In Hong Kong, the indications for GH therapy under Hospital Authority guidelines do not include SRS22 without GH response abnormalities. In our cohort, only three patients who had a suboptimal GH provocative stimulation test are currently receiving GH treatment. The long-term outcome is not yet known.

Although tissue-specific epigenetic manifestation has been reported in SRS,23 mosaic genetic or epigenetic alteration is uncommon.24 We have one patient with mUPD11 confirmed by molecular testing with peripheral blood and buccal swab samples. Mosaicism should be considered when a patient has typical SRS phenotype but negative routine testing. Testing of other tissue should be pursued so as to provide an accurate molecular diagnosis that can guide subsequent genetic counselling and clinical management.

Finally, upon review of the literature, it is well known that gain of function of the CDKN1C gene25 and maternal UPD14 (Temple syndrome)26 27 can result in a phenotype mimicking SRS. There are also other syndromic growth retardation disorders with many overlapping clinical features with those of SRS, such as mulibrey nanism and 3-M syndrome.28 29 Therefore, with the latest understanding of the molecular pathogenetic mechanisms of SRS, together with evidence21 30 31 and results from this study, we propose the diagnostic algorithm for Chinese SRS patients as depicted in Figure 2. All clinically suspected SRS patients should be assessed by a clinical geneticist. Although the Netchine et al score,7 Bartholdi et al score,12 and Birmingham score14 are highly specific, they are less sensitive than the Hitchins et al’s criteria15 for diagnosing SRS in our Chinese cohort. Therefore, the Hitchins et al’s criteria15 should be used clinically to classify those suspected SRS patients into ‘likely’ or ‘unlikely’ SRS. For those ‘likely SRS’ patients, sequential 11p15 region methylation study and mUPD7 analysis should be performed because 11p15 region epigenetic alteration is more prevalent than mUPD7 in SRS. For those molecularly unconfirmed SRS, further testing for other SRS-like syndromes including Temple syndrome or CDKN1C-related disorder should be pursued if indicated.

This 5-year review is the first territory-wide study of Chinese SRS patients in Hong Kong. It showed that the clinical features and underlying epigenetic mechanisms of Chinese SRS are similar to those of other western populations. Early diagnosis and multidisciplinary management are important for managing SRS patients. Vigilant clinical suspicion with confirmation by molecular testing is essential. Based on the current evidence and performance evaluation of different clinical scoring systems, a comprehensive diagnostic algorithm is proposed. We hope that with an increase in understanding of the underlying pathophysiology and the (epi)genotype-phenotype correlation in Chinese SRS patients, the quality of medical care will be greatly improved in the near future.

We thank all the paediatricians and physicians who have referred their SRS patients to our service and QMH. We are also grateful to all the laboratory staff in CGS for their technical support. This work in HKU is supported by HKU small project funding and The Society for the Relief of Disabled Children in Hong Kong.

All authors have disclosed no conflicts of interest.

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9. Schönherr N, Meyer E, Eggermann K, Ranke MB, Wollmann HA, Eggermann T. (Epi)mutations in 11p15 significantly contribute to Silver-Russell syndrome: but are they generally involved in growth retardation? Eur J Med Genet 2006;49:414-8. Crossref

10. Azzi S, Abi Habib W, Netchine I. Beckwith-Wiedemann and Russell-Silver Syndromes: from new molecular insights to the comprehension of imprinting regulation. Curr Opin Endocrinol Diabetes Obes 2014;21:30-8. Crossref

11. Price SM, Stanhope R, Garrett C, Preece MA, Trembath RC. The spectrum of Silver-Russell syndrome: a clinical and molecular genetic study and new diagnostic criteria. J Med Genet 1999;36:837-42.

12. Bartholdi D, Krajewska-Walasek M, Ounap K, et al. Epigenetic mutations of the imprinted IGF2-H19 domain in Silver-Russell syndrome (SRS): results from a large cohort of patients with SRS and SRS-like phenotypes. J Med Genet 2009;46:192-7. Crossref

13. Eggermann T, Gonzalez D, Spengler S, Arslan-Kirchner M, Binder G, Schönherr N. Broad clinical spectrum in Silver-Russell syndrome and consequences for genetic testing in growth retardation. Pediatrics 2009;123:e929-31. Crossref

14. Dias RP, Nightingale P, Hardy C, et al. Comparison of the clinical scoring systems in Silver-Russell syndrome and development of modified diagnostic criteria to guide molecular genetic testing. J Med Genet 2013;50:635-9. Crossref

15. Hitchins MP, Stanier P, Preece MA, Moore GE. Silver-Russell syndrome: a dissection of the genetic aetiology and candidate chromosomal regions. J Med Genet 2001;38:810-9. Crossref

16. Fuke T, Mizuno S, Nagai T, et al. Molecular and clinical studies in 138 Japanese patients with Silver-Russell syndrome. PLoS One 2013;8:e60105. Crossref

17. Bliek J, Terhal P, van den Bogaard MJ, et al. Hypomethylation of the H19 gene causes not only Silver-Russell syndrome (SRS) but also isolated asymmetry or an SRS-like phenotype. Am J Hum Genet 2006;78:604-14. Crossref

18. Bruce S, Hannula-Jouppi K, Peltonen J, Kere J, Lipsanen-Nyman M. Clinically distinct epigenetic subgroups in Silver-Russell syndrome: the degree of H19 hypomethylation associates with phenotype severity and genital and skeletal anomalies. J Clin Endocrinol Metab 2009;94:579-87. Crossref

19. Kotzot D. Maternal uniparental disomy 7 and Silver-Russell syndrome—clinical update and comparison with other subgroups. Eur J Med Genet 2008;51:444-51. Crossref

20. Binder G, Seidel AK, Martin DD, et al. The endocrine phenotype in Silver-Russell syndrome is defined by the underlying epigenetic alteration. J Clin Endocrinol Metab 2008;93:1402-7. Crossref

21. Azzi S, Salem J, Thibaud N, et al. A prospective study validating a clinical scoring system and demonstrating phenotypical-genotypical correlations in Silver-Russell syndrome. J Med Genet 2015;52:446-53. Crossref

22. But WM, Huen KF, Lee CY, Lam YY, Tse WY, Yu CM. An update on the indications of growth hormone treatment under Hospital Authority in Hong Kong. Hong Kong J Paediatr 2012;17:208-16.

23. Azzi S, Blaise A, Steunou V, et al. Complex tissue-specific epigenotypes in Russell-Silver Syndrome associated with 11p15 ICR1 hypomethylation. Hum Mutat 2014;35:1211-20. Crossref

24. Bullman H, Lever M, Robinson DO, Mackay DJ, Holder SE, Wakeling EL. Mosaic maternal uniparental disomy of chromosome 11 in a patient with Silver-Russell syndrome. J Med Genet 2008;45:396-9. Crossref

25. Brioude F, Oliver-Petit I, Blaise A, et al. CDKN1C mutation affecting the PCNA-binding domain as a cause of familial Russell Silver syndrome. J Med Genet 2013;50:823-30. Crossref

26. Ioannides Y, Lokulo-Sodipe K, Mackay DJ, Davies JH, Temple IK. Temple syndrome: improving the recognition of an underdiagnosed chromosome 14 imprinting disorder: an analysis of 51 published cases. J Med Genet 2014;51:495-501. Crossref

27. Kagami M, Mizuno S, Matsubara K, et al. Epimutations of the IG-DMR and the MEG3-DMR at the 14q32.2 imprinted region in two patients with Silver-Russell Syndrome–compatible phenotype. Eur J Hum Genet 2015;23:1062-7. Crossref

28. Hämäläinen RH, Mowat D, Gabbett MT, O’brien TA, Kallijärvi J, Lehesjoki AE. Wilms’ tumor and novel TRIM37 mutations in an Australian patient with mulibrey nanism. Clin Genet 2006;70:473-9. Crossref

29. van der Wal G, Otten BJ, Brunner HG, van der Burgt I. 3-M syndrome: description of six new patients with review of the literature. Clin Dysmorphol 2001;10:241-52. Crossref

30. Scott RH, Douglas J, Baskcomb L, et al. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) robustly detects and distinguishes 11p15 abnormalities associated with overgrowth and growth retardation. J Med Genet 2008;45:106-13. Crossref

31. Spengler S, Begemann M, Ortiz Brüchle N, et al. Molecular karyotyping as a relevant diagnostic tool in children with growth retardation with Silver-Russell features. J Pediatr 2012;161:933-42. Crossref

Violence, which has been ever present throughout the history of humanity, is defined as a threat or application of possessed power or strength towards another person, self, a group, or a community in order to cause injury and/or loss.1 The World Health Organization defines violence as “physical assault, homicide, verbal assault, emotional, sexual or racial harassment”.2

Workplace violence is defined as “abuse or attacks by one or more people on an employee within the workplace”.3 The health care field, which encompasses a wide range of employees, is among those in which workplace violence is common.4 Violence in the health care field is defined as “risk to a health worker due to threatening behaviour, verbal threats, physical assault and sexual assault committed by patients, patient relatives, or any other person”.3

According to the 2002 Workplace Violence in the Health Sector report, 25% of all violent incidents occurred in the health care sector.5 A study conducted in the United States determined that the risk of being subjected to violence is 16 times higher in the health care sector relative to other service sectors.6 Within the health care field, the department that is most frequently exposed to violence is the emergency department (ED).3 7 8 9 In this context, verbal and physical attacks by dissatisfied patients and their relatives are at the forefront.10 11

In this study we aimed to determine the extent of violence towards ED employees, analyse the attitude of the staff exposed to violence, and propose possible solutions.

This cross-sectional study was conducted in the EDs of Şevket Yilmaz Training and Research Hospital and Sakarya University between 1 July and 15 August 2012. Employees of ED—including doctors, nurses, health care officials, Emergency Medical Technicians (EMT), secretaries, laboratory technicians, radiology technicians, and security and cleaning staff—were included in the study. The questionnaire was prepared in accordance with previous publications3 10 11 and distributed to participants. All study participants were provided with information regarding the objectives of the study and were given instructions for completing the form. Of the 437 ED employees working in the two hospitals, 323 (73.9%) agreed to participate in the study and returned a completed questionnaire.

In addition to demographic information, the questionnaire contained questions about the number of violent incidents to which the individual had been subjected to, the type of violence, and whether the subject reported the incident or the reason for not reporting. Additional questions concerned a description of the person(s) responsible for the violence, the estimated age of the person(s) responsible for the violence, and the severity of the violence. We also asked participants about their attitude following the violent incident and suggestions for reducing violence in the ED.

This study was conducted in accordance with the principles of the 2008 Helsinki Declaration. The data were analysed using the Statistical Package for the Social Sciences (Windows version 15.0; SPSS Inc, Chicago [IL], US). Both proportions and mean ± standard deviation were used to represent the results. The Student’s t test, Pearson’s Chi squared test, and the Monte Carlo Chi squared tests were used to evaluate observed differences between groups and a P value of <0.05 was considered to represent a statistically significant difference.

Among the 323 participants included in the study, 189 (58.5%) were male and 134 (41.5%) were female. The mean age of the male participants was 31.5 ± 6.5 years (range, 18-55 years) and that of the female participants was 32.0 ± 6.9 years (range, 20-52 years). There was no significant difference in the age distribution between the male and female participants (P=0.476).

When participants were asked if they had ever been exposed to verbal or physical violence in the workplace during the course of their career, 239 (74.0%) indicated that they had been subjected to one or the other, and 57 (17.6%) reported being subjected to both verbal and physical violence. Among the participants who were subjected to violence, 162 (67.8%) reported being the victim of more than five violent incidents (Table 1).

The frequency of exposure to violence and the frequency of exposure to more than five violent incidents were similar for both men and women (P=0.185 and 0.104, respectively). Nonetheless, 25.9% of men reported both verbal and physical violence compared with only 6.0% of women, suggesting that the incidence of verbal and physical violence against men was greater than that against women (P<0.001) [Table 1].

We investigated the frequency of exposure to violence and the reported incidence of violence among various occupation groups (Table 2). The prevalence of exposure to violence was the highest among health care officials, EMTs, doctors, and security staff (P<0.001). In addition, only 102 (42.7%) out of 239 participants reported these violent incidents. It is notable that although the rate of incident reporting was 100% among security staff, none of the laboratory technicians reported the violent incidents (P<0.001).

A total of 43 (31.4%) out of the 137 study participants who had been exposed to violence but had not reported the incident provided reasons (Table 3). The most common reason for not notifying the authorities was the perception that “no resolution will be reached”. Other important reasons included the heavy workload, not wanting to deal with the legal process, disregarding verbal attacks, understanding/sympathising with the emotions of patients and their relatives, fear of the threat from patients and their relatives, and not knowing how and where to report such incidents.

A total of 248 participants responded to a question regarding the identity of the person who was to blame for the violence in ED in general (not their own experiences). Accordingly, 65.3% (n=162) stated that the patient’s relatives were responsible, 27.0% (n=67) stated that both the patients and their relatives were responsible, and 5.2% (n=13) placed sole responsibility on the patients. Six (2.4%) participants stated that they had been subjected to violence from other health care professionals.

When we asked individuals to estimate the age of the person(s) causing the violence that they had experienced, respondents who were exposed to multiple violent incidents answered this question by selecting multiple options and a total of 405 answers were obtained. As shown in Table 4, the majority (71.4%) of people responsible for violent incidents were young patients and patient relatives between the ages of 18 and 39 years.

When participants who were exposed to violence were asked who caused the violent incident, three (1.3%) participants stated that they themselves were responsible, five (2.1%) indicated that both sides were responsible, and the remaining 231 (96.7%) held the attacker responsible.

Participants were asked “What do you think is the reason for the violence?”. A total of 181 (56.0%) participants responded to this question. Some participants indicated more than one reason and a total of 188 answers were obtained. The top 10 most common responses to this question are given in descending order of frequency in Table 5. The most common cause of violence was ignorance and lack of education of patients and their relatives (28.7%), followed by the impatient attitudes and demanding priorities (23.4%) and the heavy workload and prolonged waiting time (10.6%).

Participants were asked “How do you think violence against health care workers can be reduced?”. Some participants indicated more than one reason and a total of 509 answers were obtained. They considered the most important steps suggested to reduce violence against ED employees were the enactment of deterrent legislation (42.6%), increased security measures in hospitals (28.5%), and improved public education (16.7%) [Table 5].

Participants were asked about their attitude after experiencing violence. Some respondents gave more than one answer and a total of 498 answers were obtained. There were 27.1% of participants who did not enjoy working in their current profession, 25.7% wanted to work in non–health care field, and 21.5% did not want to work in the ED (Table 6).

A total of 96.3% (n=311) of participants answered “Yes” to the question “Do you think that the violence against health care workers has increased in recent years?” Moreover, 90.7% (n=293) of the participants answered “Yes” to the question “Do news reports regarding violence against health care workers affect you?”. Then, when participants were asked “How does the news affect you?”, 64.7% (n=209) reported that they were “sad”, 44.3% (n=143) said they were “angry”, and 18.9% (n=61) said they were “scared”.

When participants were asked “Are there sufficient security measures in your workplace?”, only 66 (20.4%) participants gave a positive response, while 257 (79.6%) responded negatively. Among the 41 participants working as security staff, 33 (80.5%) found the safety measures inadequate. Thus, both the security staff and the general employee population agreed that hospital security was inadequate.

Workplace violence is the most prevalent in the health care sector.4 The ED is the health care unit with the highest frequency of exposure to violence.3 7 8 9 According to several previous studies, the proportion of health care professionals who report prior exposure to violence in the workplace ranges from 45% to 67.6%.3 8 12 13 14 The rate of violence against ED employees (79%-99%), however, is higher than the average for the health care field.15 16 17

Emergency services are high-risk areas for patients and staff with regard to workplace violence18 19 20 21; 24-hour accessibility, a high-stress environment, and the apparent lack of trained security personnel are underlying factors.22 Workplace violence negatively affects the morale of health care workers and negatively affects the health and effectiveness of presentation.23 24 25 26

Our study was conducted among ED employees of two different hospitals. We investigated the rate of exposure to verbal or physical violence. Among the participants, 239 (74.0%) stated that they had been subjected to exposure to violence, and 57 (17.6%) reported having been exposed to both verbal and physical violence. A study in Turkey found that among ED employees, including nurses, in the İzmir province of Turkey, 98.5% of respondents had been subjected to verbal violence and 19.7% were exposed to physical violence.16 In another study conducted in Turkey, 88.6% of ED employees were subjected to verbal violence and 49.4% reported having been the victim of physical violence.17

In the present study, the rate of exposure to violence by profession was 95.7% among health care officials/EMTs, 90.7% among doctors, and 80.5% among security personnel. According to Ayrancı et al,3 exposure to violence was most common among practitioners (67.6%) and nurses (58.4%). In another study, Alçelik et al27 reported that nurses were exposed to violence 3 times more often than other health care professionals. In the present study, the frequency of exposure to violence among nurses was 62.7%, which is lower than that in other professional groups.

In the present study, the estimated age distribution of patients and patient relatives responsible for violent incidents showed that the majority (71.4%) were between 18 and 39 years of age. Other studies have reported that individuals prone to violence are generally younger than 30 years.28

Health care workers are often subjected to verbal and physical attacks from patients and their relatives who are dissatisfied with the services provided.10 11 In the present study, the most common cause of violence was the lack of education and ignorance of the patients and their relatives. Heavy workload was identified as another cause of workplace violence. Factors such as patient stress and anxiety regarding their condition, high expectations of the patients and their relatives, lack of effective institutional and legal arrangements aimed at preventing violence, and the failure to effectively document the extent of workplace violence contribute to the high frequency of violence.12 There are several factors that increase the risk of violence in health care institutions, including 24-hour service, long waiting time for patients, poor access to health care services, heavy workload, limited staff, inadequate employee training, and lack of security personnel.29 30

Previous studies conducted in Turkey revealed that 60% of ED employees who were exposed to violence did not report the incident. Among the reasons for not reporting was a lack of confidence in health care and executive leadership as well as the justice system.12 In the present study, the incident reporting rate was also low (42.7%) and the most important reason (34.9%) for not reporting was the perception that “no resolution will be reached”. Indeed, a study found that there were no repercussions for the attacker in 77% of instances.12 This suggests the perception that “no resolution will be reached” is a valid one.

A heavy workload consumes the energy of employees and reduces their ability to empathise with patients and tolerate violent situations. Sometimes verbal or physical conflicts may arise between a stressed patient who may be subject to long waiting times and exhausted and stressed health care workers. Training regarding communication with patients helps health care professionals to avoid these problems.31 Effective communication alone, however, is not sufficient and additional steps must be taken to reduce waiting time of patients. Previous studies have indicated that the most important reason for patient dissatisfaction in the ED is the waiting time.32 33 Yet, the most important reason for long waiting times is the heavy workload caused, in part, by the discourteous attitude of patients and their relatives. Studies have also shown that more than half of patients who present to the ED are not ‘emergency patients’.34 35 36 Further education regarding the definition of “emergency” and the practice of effective triage may reduce the heavy workload in the ED and associated violent incidents.

One previous study reported that verbal and physical attacks by patients and their relatives are the most important factors contributing to stress among ED employees.37 Consistent exposure to high-stress conditions resulting from exposure to verbal and physical violence results in both physical and mental exhaustion. As a result, a situation known commonly as ‘burnout syndrome’ emerges.38 39 The burnout syndrome is defined as holding a negative view of current events, frequent despair, and lost productivity and motivation.40 Reluctance among physicians to work in the ED is one consequence of burnout syndrome.41 In the present study, among the participants who were subjected to violence, 21.5% indicated that they wanted to work in a department other than the ED, while 25.7% stated a desire to work outside the health care field. In a study conducted in Canada, 18% of participants who had been exposed to violence stated that they did not want to work in the ED, and 38% wanted to work outside the health care field.9 Others indicated that they had quitted their jobs because of workplace stress.9 In the present study, 10.4% of ED employees stated that they were afraid of patients and their relatives. In the same Canadian study, 73% of respondents stated that after experiencing violence they were afraid of patients.9 In our study, 96.3% of respondents thought that there had been an increase in violence against ED health care workers in recent years. Moreover, 79.6% of respondents stated that the safety measures in their institutions were insufficient. The participants in the present study suggested that the preparation of deterrent legislation, increased security measures, and efforts to better educate the general population regarding the appropriate use of ED resources will help to reduce violence against health care workers.

The study was carried out in only two hospitals in Turkey that may not be representative of all hospitals. In addition, participants could decide whether or not to answer all questions and some questionnaires were incomplete. The response rate was only 74% and this might give rise to self-selection bias, that is, those who did not respond may have had a higher (or lower) exposure to violence than those who responded. Hence, the various percentages reported in this paper might be over- or under-estimated.

The results of the current study as well as those of earlier studies indicate that the prevalence of violence against ED employees is high. Factors such as patient and stress of health care provider, prolonged waiting times due to overcrowding in the ED, negative attitude of discourteous patients and their relatives, insufficient security measures, and the lack of sufficiently dissuasive legal regulations may contribute to increased violence in the ED. These factors in turn increase stress among ED employees, reduce job satisfaction, and lower the quality of services provided. Measures to decrease the workload in the ED and shorten waiting time of patients, the adoption of legal policies that deter violent behaviour, and increased security measures in health care facilities should be reassessed. Steps should be taken to educate the public in order to reduce violence against health care workers.

All authors have disclosed no conflicts of interest.

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2. Violence and injury prevention. Available from: http://www.who.int/violence_injury_prevention/violence/activities/workplace/documents/en/index.html. Accessed Nov 2012.

3. Ayrancı Ü, Yenilmez Ç, Günay Y, Kaptanoğlu C. The frequency of being exposed to violence in the various health institutions and health profession groups. Anatol J Psychiatry 2002;3:147-54.

4. Wells J, Bowers L. How prevalent is violence towards nurses working in general hospitals in the UK? J Adv Nurs 2002;39:230-40. Crossref

5. Workplace violence in the health sector. Framework guidelines for addressing workplace violence in the health sector. Available from: http://www.ilo.org/wcmsp5/groups/public/---ed_dialogue/---sector/documents/publication/wcms_160912.pdf. Accessed Nov 2012.

6. Kingma M. Workplace violence in the health sector: a problem of epidemic proportion. Int Nurs Rev 2001;48:129-30. Crossref

7. Gülalp B, Karcıoğlu, Köseoğlu Z, Sari A. Dangers faced by emergency staff: experience in urban centers in southern Turkey. Ulus Travma Acil Cerrahi Derg 2009;15:239-42.

8. Lau J, Magarey J, McCutcheon H. Violence in the emergency department: a literature review. Aust Emerg Nurs J 2004;7:27-37. Crossref

9. Fernandes CM, Bouthillette F, Raboud JM, et al. Violence in the emergency department: a survey of health care workers. CMAJ 1999;161:1245-8.

10. Yanci H, Boz B, Demirkiran Ö, Kiliççioğlu B, Yağmur F. Medical personal subjected to the violence in emergency department—enquiry study. Turk J Emerg Med 2003;3:16-20.

11. Sucu G, Cebeci F, Karazeybek E. Violence by patient and relatives against emergency service personnel. Turk J Emerg Med 2007;7:156-62.

12. Çamci O, Kutlu Y. Determination of workplace violence toward health workers in Kocaeli. J Psychiatr Nurs 2011;2:9-16.

13. Stirling G, Higgins JE, Cooke MW. Violence in A&E departments: a systematic review of the literature. Accid Emerg Nurs 2001;9:77-85. Crossref

14. Sönmez M, Karaoğlu L, Egri M, Genç MF, Günes G, Pehlivan E. Prevalence of workplace violence against health staff in Malatya. Bitlis Eren Univ J Sci Technol 2013;3:26-31.

15. Stene J, Larson E, Levy M, Dohlman M. Workplace violence in the emergency department: giving staff the tools and support to report. Perm J 2015;19:e113-7. Crossref

16. Senuzun Ergün F, Karadakovan A. Violence towards nursing staff in emergency departments in one Turkish city. Int Nurs Rev 2005;52:154-60. Crossref

17. Boz B, Acar K, Ergin A, et al. Violence toward health care workers in emergency departments in Denizli, Turkey. Adv Ther 2006;23:364-9. Crossref

18. Joa TS, Morken T. Violence towards personnel in out-of-hours primary care: a cross-sectional study. Scand J Prim Health Care 2012;30:55-60. Crossref

19. Magnavita N, Heponiemi T. Violence towards health care workers in a Public Health Care Facility in Italy: a repeated cross-sectional study. BMC Health Serv Res 2012;12:108. Crossref

20. Arimatsu M, Wada K, Yoshikawa T, et al. An epidemiological study of work-related violence experienced by physicians who graduated from a medical school in Japan. J Occup Health 2008;50:357-61. Crossref

21. Taylor JL, Rew L. A systematic review of the literature: workplace violence in the emergency department. J Clin Nurs 2011;20:1072-85. Crossref

22. Gacki-Smith J, Juarez AM, Boyett L, Homeyer C, Robinson L, MacLean SL. Violence against nurses working in US emergency departments. J Nurs Adm 2009;39:340-9. Crossref

23. Kowalenko T, Gates D, Gillespie GL, Succop P, Mentzel TK. Prospective study of violence against ED workers. Am J Emerg Med 2013;31:197-205. Crossref

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28. Young GP. The agitated patient in the emergency department. Emerg Med Clin North Am 1987;5:765-81.

29. Stathopoulou HG. Violence and aggression towards health care professionals. Health Sci J 2007;2:1-7.

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31. Yardan T, Eden AO, Baydın A, Genç S, Gönüllü H. Communication with relatives of the patients in emergency department. Eurasian J Emerg Med 2008;7:9-13.

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35. Ersel M, Karcıoğlu Ö, Yanturali S, Yörüktümen A, Sever M, Tunç MA. Emergency Department utilization characteristics and evaluation for patient visit appropriateness from the patients’ and physicians’ point of view. Turk J Emerg Med 2006;6:25-35.

36. Aydin T, Aydın ŞA, Köksal Ö, Özdemir F, Kulaç S, Bulut M. Evaluation of features of patients attending the Emergency Department of Uludağ University Medicine Faculty Hospital and emergency department practices. Eurasian J Emerg Med 2010;9:163-8. Crossref

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Advances in medical management now enable children with developmental disabilities (DD) who may previously have died to live well into adulthood.1 Such disabilities are defined as any condition that is present before the age of 22 years and due to physical or cognitive impairment or a combination of both that significantly affects self-care, receptive and expressive language, mobility, learning, independent living, or the economic independence of the individual.2 The transition from adolescence to adulthood is a critical period for all young people.3 In a clinical context, adult transition is “the purposeful, planned movement of adolescents and young adults with chronic physical and medical conditions from child-centered to adult-oriented health-care systems”.4 In 2001, a consensus statement with guidelines was endorsed to ensure adolescents with DD, who depend on coordinated health care services, make a smooth transition to the adult health care system in order to receive the services that they need in developed countries such as the United States.5

Researchers have identified needs and factors necessary for the successful transition of adolescents with DD.6 7 From the adolescent’s perspective, barriers to success include their dependence on others, reduced treatment time and access to specialists in the adult health service, lack of information about transition, and lack of involvement in the decision-making process. Parents of adolescents with DD were reluctant or confused about changing responsibilities during the transition period. The majority of challenges came from the service systems and included unclear eligibility criteria and procedures, limited time and lack of carer training, fragmented adult health service provision, lack of communication between service providers, and inaccessibility to resources including information.6 7

Based on the 2015 census of ‘Persons with disabilities and chronic diseases in Hong Kong’ from the Hong Kong Census and Statistics Department, there were 22 100 (3.8%) people with disability (excluding cognitive impairment) aged between 15 and 29 years, ie who were transitioning from the paediatric to adult health service.8 According to the Hospital Authority, Hong Kong, all public hospitals, and specialist and general out-patient clinics are organised into seven hospital clusters based on geographical location.9 The Duchess of Kent Children’s Hospital (DKCH) is a tertiary centre that provides specialised services for children with orthopaedic problems, spinal deformities, cerebral palsy and neurodevelopmental disorders, and neurological and degenerative diseases. Unlike overseas health care, there is no children’s hospital in Hong Kong that provides an acute health service. All paediatric patients go to the same hospital as adult patients but are triaged into the paediatric section for management by both in-patient and out-patient services. The specialised out-patient clinic list under each hospital cluster varies. Children with DD might receive services from general paediatrics clinic, a cerebral palsy clinic, Down’s clinic, behavioural clinic, or paediatric neurology out-patient clinic. Once a child reaches the age of 18 years, they are referred to the adult section of the same hospital for continued care. They will be followed up in neurology or movement disorder clinics, where other patients with adult-onset neurological conditions or movement disorders, such as stroke, Parkinson’s disease, multiple sclerosis are followed up. There is no separate specialised clinic for complex child-onset DD.10

Although adult transition for adolescents with DD has been recognised as a crucial area in health care overseas, it is an under-developed service in Hong Kong.11 A local study found that there is a service gap in adult transition for young people with chronic medical conditions, such as asthma, diabetes, and epilepsy. Training and education are urgently required for both service providers and young people with chronic health conditions and their families.11 It is unclear if the challenges and barriers identified in overseas literature6 7 are applicable to Hong Kong, where the paediatric and adult health services, especially the medical services, are located in the same building. At present, no study has been conducted with adolescents with DD and their families in Hong Kong about the issues they face during clinical transition. As a start, in this pilot study, we aimed to explore the acceptance of clinical transition and identify the main barriers to successful clinical transition for adolescents with DD and their caregivers in Hong Kong.

A survey study was conducted on a convenience sample of adolescents and/or their caregivers, who were recruited from two special high schools (Hong Kong Red Cross John F Kennedy Centre [JFK] and Haven of Hope Sunnyside School [HOH]) in Hong Kong. Students from JFK have primarily physical and multiple disabilities including cerebral palsy or muscular dystrophy and those from HOH have severe cognitive impairment. Both schools provide rehabilitation services on site including physiotherapy, occupational therapy, speech therapy, nursing support, and family support via the school social workers. The medical out-patient services for the students fall under different hospital clusters, depending on where the students’ families live. The parents are responsible for taking their adolescent children for medical review. As there was no previous study on which basis to calculate the required sample size and as a pilot study, we aimed to recruit 10 adolescents and their parents/caregivers in each school.

The inclusion criteria of the adolescents were: (1) aged 16 to 19 years and (2) a diagnosis of DD. All participating adolescents and/or their parents or legal guardians gave written informed consent before the survey. For adolescents with severe cognitive impairment, consent was sought from their parents as proxy and only their parents participated in the survey. This pilot study was approved by the Human Subjects Ethics Sub-committee of the Hong Kong Polytechnic University.

A specific questionnaire was developed for this pilot study to collect information relative to: (1) demographic characteristics of the participants; (2) whether or not the study participants were aware of the transition and the information source(s); (3) if the study participants were willing to transition to the adult health service and the underlying reasons; (4) for those who had transitioned, if they were satisfied with the adult health service and the underlying reasons; and (5) the opinion of the study participants of the clinical transition service. As a pioneer pilot study, health service included both medical and rehabilitation services and the study aimed to explore the general issues faced by this group of adolescents and their families during clinical transition. Lastly, as we predicted that the competency level of the adolescents and their caregivers in managing their disabilities might influence their perception of clinical transition, information about their self-rated competency level was also collected. Questions in the latter part were based on information from the Adolescent Transition Care Assessment Tool and were designed to assist health care professionals to provide a better transition for adolescents with chronic illness.12 The whole survey was administered by interviewers for the study adolescents and/or their caregivers separately in Cantonese. All interviews were recorded for data analyses.

The survey comprised closed- and open-ended questions. The closed-ended questions were designed to require a dichotomous answer, ie ‘yes’ or ‘no’, or an answer from a set of choices. For example, when asked about the sources of information about clinical transition, the study participants could choose their answers from a list of professionals such as paediatricians, social workers, physiotherapists, and school teachers. The open-ended questions focused on the reasons for an earlier response. For example, when asked if they wished to move to the adult health service, the individual would first answer ‘yes’ or ‘no’, then give their reasons. For the questions about self-perceived competency level, study participants read a number of statements (8 for the adolescents and 14 for parents) and indicated how much they agreed with the statement using a Likert-scale from ‘strongly disagree’ to ‘strongly agree’.

Descriptive statistics—including mean, median, standard deviation, or quartiles—were used to analyse the responses to the closed-ended questions. Discussion of the open-ended questions was transcribed and summarised by five team members (CLC, KHF, KHWF, LKL, and TCLT). The content was analysed and themes were identified independently by two other team members (TWP and WLSC). These themes were discussed and a consensus reached by all team members.

Thirteen potential families were approached at the JFK via the physiotherapist of the school anticipating possible refusal by some. All the students and their parents agreed to participate, so all were included. Ten families were approached at the HOH via the social worker at the school but one parent declined the offer and no other family was interested in participating in the study. Since the students from HOH, who were cognitively impaired, were not able to be interviewed, only their parents/caregivers were interviewed. As a result, 22 parents (13 from the JFK and 9 from the HOH) and 13 adolescents (all from the JFK) were asked to complete the face-to-face survey. The demographic data of the participants are listed in Table 1. Cerebral palsy and cognitive impairment were the principal types of DD. All adolescents received rehabilitation from the Hospital Authority and/or from their special school. All the adolescents accessed between four and seven paediatric medical specialists (eg paediatrician, neurologist, orthopaedic surgeon) and rehabilitation services (eg physiotherapy, occupational therapy, speech therapy) indicating their complex needs. Over 90% of the JFK students were followed up at the DKCH that is within walking distance of the school (personal communication, Senior Physiotherapist at JFK).

Table 2 summarises the participant responses about clinical transition. The majority of the parents (77%) and adolescents (85%) knew that clinical transition to adult care would occur at 18 years of age. They were mainly informed by their paediatrician (50% of parents and 69% of adolescents). Most parents (77%) were reluctant to make this move. Ten parents stated that their adolescent child was already receiving care from the adult sector and over half of them (60%) were dissatisfied with the service. Four of the 13 adolescents clearly stated that they had transitioned to the adult health service during the survey and all of them were happy with the transition. Among those 17 families who knew that clinical transition to adult care would occur at 18 years of age, 10 adolescents were all over 18 years old, whereas those in another seven (41%) families were also over 18 years old and still receiving services from the paediatric sector at the time of the study.

When asked why they were not willing to the transition or why they were dissatisfied after the transition, the parent responses could be summed up as two main areas of concern: reluctance to change and dissatisfaction with the adult health services. Most parents (16/22, 73%) did not want to change their existing care circumstances. When asked why, some parents cited dissatisfaction with the adult health service or health system (for the latter, 13/22, 59% of parents). For example, parents found it difficult to attend the follow-up appointments using public transport. Although there was a free shuttle bus service for families who needed it, parents were frustrated by the limited service.

Some parents also wanted more flexible visiting hours in the adult hospital so that they could look after their adolescent children, especially those who were cognitively impaired. The parents worried about the quality of care for their children who were entirely dependent for their daily activities. They were also unhappy about the waiting time for medical appointments and stated that their children with DD had a short attention span and were unable to control their behaviour. Long waiting times in a crowded waiting area, which is commonly observed in the adult setting, could easily trigger their behavioural problems.

There was also dissatisfaction with the adult health service providers (13/22, 59% of parents). Parents often found that the adult medical staff demonstrated limited understanding and knowledge of their child’s clinical presentation and abilities, especially for those with severe cognitive impairment. The adult health service providers did not know how to communicate with the cognitively impaired adolescents and treated them as other normal adults.

There is no formal clinical transition service in Hong Kong but when asked, the majority of parents (21/22, 95%) and adolescents (11/13, 85%) stated that they would welcome such a service. About two thirds of the study parents and adolescents (23/35, 66%) would like the clinical transition service to support them during the clinical transition. About one third of the parents (7/22, 32%) believed that the service could act as a bridge linking the paediatric and adult health services, providing information about available services in the adult sector.

The Figure summarises the responses of adolescents for self-perceived competency in managing their disability, and Table 3 summarises the study parents’ responses. Most adolescents demonstrated understanding of instructions (11/13, 85%), confidence in communicating with the service providers about their condition (10/13, 77%), and understanding the importance of treatments for their condition (12/13, 92%) [Fig]. About half were confident in seeking help from different specialties according to their condition (6/13, 46%) and making medical decisions (7/13, 54%) [Fig]. Over half of the adolescents, however, lacked the confidence to attend routine medical visits on their own (8/13, 62%) and worried about the unfamiliar adult medical service (6/13, 46%) [Fig]. Most parents stated that they were familiar with their children’s medical conditions and treatments (20/22, 91%) and able to seek help from different medical specialties based on their child’s condition (14/22, 64%) [Table 3]. Only a minority of parents (1/22, 5%), however, believed that their children were capable of attending medical appointments on their own. Less than half of the parents believed that their children would be able to explain their medical condition (9/22, 41%) or make independent clinical decisions in the future (7/22, 32%). None of the parents of an adolescent with cognitive impairment believed that the child would ever be able to manage their own health.

The present pilot study aimed to determine how adolescents with DD and their parents in Hong Kong accept the clinical transition and identify the main barriers to successful transition. This was the first step to understanding the issues of this population group during clinical transition and to enable planning for the future. As far as we know, this study is the first to be conducted in Hong Kong for this population group. Overall, 22 parents and 13 adolescents were recruited from two special schools (one for primarily physically disabled children and the other for severe physically and/or cognitively impaired individuals), aiming to understand what was the acceptance level and barriers faced by these two vastly different groups with DD. The results were very similar between these two subgroups, indicating that the study parents had similar issues during clinical transition, regardless of the type of DD of their child. Hence, the results from these two subgroups were discussed as one group.

Most of the study participants were aware of the clinical transition necessary at the age of 18 years. Only 10 (45%) of the 22 families shifted to the adult health service, despite the fact that their adolescent child was close to or over 18 years old (Tables 1 and 2). The reasons for this delay were not thoroughly explored but it has been suggested that medical practitioners in the paediatric service felt that the adolescents were not ready for the transition so they continued to see them well into adulthood while the parents and the adolescents were reluctant to make the move.11 The latter appeared to be true because when asked, most study participants did not want to change and move to the adult health service. This contradicts the results of a previous local study of adolescents with chronic medical conditions, in which over 80% of the study participants (adolescents and parents) were willing to move to the adult health service.11 The difference is likely due to the complexity of the health conditions of the present cohort. Adolescents with DD usually have varying degrees of physical and/or cognitive impairment and so depend more on others for managing their health condition, making them and their carers more anxious about any change.6 7 For those with chronic medical conditions, the physical and cognitive abilities of the adolescent were unlikely affected and hence the adolescents could manage their condition more independently and more readily after the transition.13 This speculation was supported by the findings about self-perceived competency level. Most study adolescents, who had mainly physical disabilities, were not confident about attending a medical appointment alone because of their limited physical abilities (Fig). The reluctance for change may also be due to fear of the unknown and of not being well prepared.11 In Hong Kong, clinical transition is non-structured and unplanned.11 Parents are often informed just before the transition, leading to poor preparation and confusion. Early and continuous clinical transition from early adolescence can enable parents and adolescents with DD to be prepared and actively participate in the transition planning.7 14 Although the clinical transition service is not well-known in Hong Kong, the study participants had a positive attitude towards a clinical transition service to help them navigate the process by bridging the paediatric and adult health services. In addition, the study parents wished to have more information about available adult health services, eg rehabilitation services, wheelchair maintenance services, etc. More information about the unknown has been shown to reduce the reluctance of parents and adolescents to change and to further improve their confidence about moving to adult care.5 6 15 16

Another barrier was dissatisfaction with the health care system and service providers in the adult setting (Table 2), and is in line with present literature.7 Some parents found it difficult to arrange transport to the adult hospital for follow-up while most of the appointments were currently at the special school. More accessible public transport might help, especially in Hong Kong, where private vehicles are not a common option. Flexible visiting hours in the adult hospital that would enable parents to care for their dependent adolescent child may also reduce their dissatisfaction. Longer waiting times for medical appointments in the adult setting was frequently mentioned by the study parents. In the adult sector, patients with all kinds of neurological conditions, both child-onset and adult-onset, are reviewed in the same clinic. The number of patients attending the clinic is vastly increased compared with the paediatric setting. In addition, patients with adult-onset neurological conditions and their family may not understand the characteristics of DD. Stressed behaviour of an adolescent child with DD may be perceived by other families as impatience. In the paediatric clinic, where all clinic attendees were children or adolescents with DD and their parents, the waiting time was shorter. Families as well as clinic staff had a full understanding of DD and would be more tolerant. It is likely that this lack of support in the adult setting further discouraged the study parents to make the transition willingly. Changes to the existing health care system, such as a separate clinic for child-onset DD conditions, may be a possible small step to assist this group in making a smooth transition. Education about clinical transition for staff in both the paediatric and adult settings allows them to prepare the families in advance. Education about paediatric conditions and communication with adolescents with DD can also equip adult staff with confidence so they develop a strong rapport with the families.16

Interestingly, from the perspective of the adolescents, the four adolescents who had transitioned stated that they were happy with the adult health service. Two (50%) adolescents indicated that because the ‘new’ doctors did not know them well, they paid more attention to them and one adolescent did not give any reason to support his statement. It is likely that in the paediatric sector, these adolescents had been followed up from early childhood by the same medical staff who virtually watched them grow up. A change of scene and people in the adult sector is welcomed by these adolescents. In addition, they might welcome the idea that they have started to actively participate in the consultation as a ‘patient’, unlike in the paediatric sector, where the consultation was directed at their parents, not them.14

Parents of adolescents who had physical and/or cognitive impairment had a similar perception of their adolescent child, that they would never be able to attend a medical appointment alone, presumably because of their disability (responses to questions 9 to 10 in Table 3). None of the parents of a cognitively impaired adolescent child believed their child to be capable of explaining their medical condition to others or making an independent medical decision. On the contrary, parents of a physically disabled child thought that while it may not apply at present, their child would be able to make their own decisions in future (responses to questions 11 to 14 in Table 3). Nonetheless, there was a discrepancy in this perception between the study adolescents and parents (Fig and Table 3). Most adolescents believed they could explain their condition to others (question 2 in the Fig) and over half believed that they could make an independent medical decision at the time of the study (question 7 in the Fig). Further studies are needed to determine whether this discrepancy is due to confusion on the part of the parents because of changing responsibilities during the transition.13 While western literature emphasises the importance of active participation by adolescents during clinical transition,14 it would be interesting to see if this can be endorsed in a parent-dominant Chinese society such as Hong Kong, where cultural differences may influence attitudes towards clinical transition.17

We were unable to analyse other challenges identified in overseas literature, such as unclear eligibility criteria and procedures and limited time for clinical transition, because comparable data were not available for Hong Kong. In other developed countries, adolescents are shifted with the assistance of a clinical transition service based in the children’s hospital (if any) or by applying clinical guidelines for best service.18 In Hong Kong, adolescents are referred from the paediatric section to the adult section within the same hospital. Each hospital cluster may have different procedures for this ‘transition’ and there is no defined department within the hospital structure to assist adolescents and their families through this process. Nor do the families receive any advice about how to negotiate this process. A future in-depth study is recommended to understand the existing situation of clinical transition in different hospital clusters and determine how to establish a more formal approach among all the hospital clusters in Hong Kong to support this group of adolescents and their families during this confusing time.

There may have been a selection bias in the study sample as the families were approached by convenience through the school staff. Due to the small sample size, no statistical analysis was conducted to compare the subgroups of adolescents with physical and cognitive impairments. Although the sample size was small, the purpose of the present pilot study was not to generalise the findings to all adolescents with DD but to begin to understand the acceptance of clinical transition and the main barriers to success for adolescents with DD and their family in Hong Kong. The present results are also in line with the literature in this area.4 7 11 14 17 Future studies with a larger sample size and more in-depth qualitative data are required to verify the present results. The potential subjective bias of the results, especially for the open-ended questions, was another limitation but we attempted to minimise this through consensus agreement among the team.

In the present explorative study, close to half of the study families had a delayed clinical transition to the adult health service. Most study parents were reluctant for their adolescent children to shift to the adult health service due to unwillingness to change and dissatisfaction with the adult medical service. A structured and well-planned clinical transition was urged by the study participants to bridge the paediatric and adult health services and to provide support to the family. Further studies are required to analyse the needs and concerns of adolescents with DD and their families as well as the service providers in the adult medical setting to facilitate the future development of a clinical transition service in Hong Kong.

The authors would like to thank all the participating families from the Hong Kong Red Cross John F Kennedy Centre and Haven of Hope Sunnyside School.

All authors have disclosed no conflicts of interest.

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