The global increasing elderly population is placing a great burden on the financial and health systems of all countries. A major source of this burden is fragility fracture.1 In Hong Kong, around 6000 patients present each year with hip fracture, and current projections indicate that the numbers will double by 2050.2 3

Fragility fracture has long been a major source of the workload for orthopaedic departments in Hong Kong. Patients with hip, vertebral, or wrist fracture occupy a high percentage of orthopaedic beds in all public hospitals. Most hip fractures require either internal fixation or hip replacement to alleviate fracture pain and allow early ambulation.4 5 A decade ago, most hip fracture patients in Hong Kong would wait 5 to 6 days for surgery because health personnel—including orthopaedic surgeons, anaesthetists, and nurses—did not consider the condition to be important. Nonetheless such a delay is now known to increase in-patient and postoperative mortality and morbidity. The Blue Book of the British Orthopaedic Association 2007 stated that hip fractures should be operated on within 48 hours.2 In 2009, the Hospital Authority selected geriatric hip fracture as the first Key Performance Indicator for orthopaedics in Hong Kong.6 The aim was to confine preoperative stay to no more than 2 days for 70% of hip fracture patients. Prior to 2007 this figure was approximately 30%, but had improved to 62% by August 2008. The mean preoperative length of stay has now been reduced by 3.5 days, from the previous 6 days. By 2009, the hard work of all orthopaedic surgeons, geriatricians, and allied health colleagues had shortened the waiting time to 2 days in 70% of patients.6 Postoperative mortality and morbidity are also much reduced and, more importantly, the length of time the patient has fracture pain. These elderly now walk earlier and are discharged earlier. Thus their quality of life is improved and more hospital beds are available for other patients.

There are a few tests that help the orthopaedic surgeons to assess mortality risks of hip fracture patients. They are discussed in one of the articles in this issue, and improve communication between the doctor and patient’s family, as well as minimising any misunderstanding.7

In patients with vertebral fracture, treatment is mostly conservative although some suffer significant back pain and may be bedridden for a few months. Nonetheless with advances in technology patients who do not respond well to conservative treatment now benefit from vertebroplasty, which implies injection of bone cement into the fractured vertebra.8 Good pain relief is achieved in many patients postoperatively, enabling early rehabilitation.

Wrist fracture is a very common problem in the elderly after a fall. For a long time, treatment was focused on closed reduction and application of plaster-of-Paris (POP) although such plaster immobilisation resulted in stiffness and pressure sores. Patients often required a long period of physiotherapy to regain movement. Internal fixation was seldom performed because the failure rate with old implants was high. The development of new locking anatomical plates and bone substitute has greatly improved the success rate of surgery and these patients can now move their wrist much earlier following surgery and avoid the complications associated with POP immobilisation.

With increasing use of new surgical techniques and implants, the number of operative complications is expected to rise. The price of the implants is also considerably increased and management of complications is often difficult in these elderly patients. This may place increasing demands on hospital services and budget. Adequate training and supervision of junior doctors is required to ensure the job is done well.

Prevention is always better than treatment. Several osteoporotic drugs are widely used to help in the treatment and prevention of osteoporosis. Their use is usually long-term and they are not cheap, however.

Apart from osteoporosis, sarcopenia is another factor that causes fall of the elderly and is also discussed in this issue of the journal.9 Paying more attention to nutrition is very important in these elderly to build up muscle bulk. Many of these patients have medical co-morbidities so collaboration of geriatricians with orthopaedic surgeons is of utmost importance to ensure uninterrupted and well-coordinated pre- and post-operative care. All patients with fragility fracture after a fall should be offered a multidisciplinary service to prevent another fall. It is advisable for public hospitals to organise a team of staff that includes orthopaedic surgeons, geriatricians, allied health colleagues and nurses with special interest in this field to manage these patients with fragility fracture together.

Longevity is nothing to admire, rather we should pursue a better quality of life for our senior citizens. Looking after patients with fragility fracture well is a lot cheaper than looking after them badly. The Hong Kong SAR Government and community should invest more in the care of these patients. The rewards can be surprisingly high.

1. American Academy of Orthopaedic Surgeons. Position statement: Recommendations for enhancing the care of patients with fragility fractures. June 2003. Revised December 2009. Available from: http://www.aaos.org/CustomTemplates/Content.aspx?id=22324&ssopc=1. Accessed Dec 2015.

2. The care of patients with fragility fracture. British Orthopaedic Association. September 2007. Available from: http://www.fractures.com/pdf/BOA-BGS-Blue-Book.pdf. Accessed Dec 2015.

3. Man LP, Ho AW, Wong SH. Excess mortality for operated geriatric hip fracture in Hong Kong. Hong Kong Med J 2016;22:6-10. Crossref

4. Hip fracture: management. Clinical guideline. National Institute for Health and Care Excellence (NICE). 22 June 2011. Available from: http://www.nice.org.uk/guidance/cg124/resources/hip-fracture-management-35109449902789. Accessed Dec 2015.

5. Chan VW, Chan PK, Chiu KY, Yan CH, Ng FY. Why do Hong Kong patients need total hip arthroplasty? An analysis of 512 hips from 1998 to 2010. Hong Kong Med J 2016;22:11-5. Crossref

6. Report of the Chairman. COC in Orthopaedics and Traumatology. Hong Kong: Hospital Authority; 2009.

7. Lau TW, Fang C, Leung F. Assessment of postoperative short-term and long-term mortality risk in Chinese geriatric patients for hip fracture using the Charlson comorbidity score. Hong Kong Med J 2016;22:16-22. Crossref

8. Heini PF, Wälchli B, Berlemann U. Percutaneous transpedicular vertebroplasty with PMMA: operative technique and early results. A prospective study for the treatment of osteoporotic compression fractures. Eur Spine J 2000;9:445-50. Crossref

9. Ho AW, Lee MM, Chan EW, et al. Prevalence of pre-sarcopenia and sarcopenia in Hong Kong Chinese geriatric patients with hip fracture and its correlation with different factors. Hong Kong Med J 2016;22:23-9. Crossref

Since 2010, paracetamol has been the most common agent used in Hong Kong for deliberate self-harm by overdose and poisoning.1 It is readily available over-the-counter and is commonly prescribed by doctors. There are more than 900 registered pharmaceuticals that contain paracetamol in Hong Kong. Paracetamol overdose can result in delayed, sometimes life-threatening, liver injury and dose-dependent damage. N-acetylcysteine (NAC) is well known to be an effective antidote that can prevent liver injury if administered in time. The decision to give NAC can be facilitated by plotting the serum paracetamol concentration against time since ingestion on the Rumack-Matthew nomogram.2 Serum concentration above the treatment line on the nomogram indicates the need for NAC therapy.

There are three treatment lines on the Rumack-Matthew nomogram: 100-treatment line, 150-treatment line, and 200-treatment line. Currently, the 150-treatment line is commonly used in most parts of the world including the US, Australia, and New Zealand. The 150-treatment line is parallel to the original 200-treatment line but has been arbitrarily lowered by 25% to improve sensitivity. The Hong Kong Poison Information Centre also recommends the 150-treatment line and most clinicians in Hong Kong follow this recommendation. In the UK, the original 200-treatment line was used for normal-risk patients and the 100-treatment line reserved for high-risk patients. Over the years, cases of liver failure accumulated when patients were treated according to the 200-treatment line. Thus in 2012 the health department in the UK decided to abandon the two-level approach and apply one treatment line of 100 mg/L for all patients.3

In the article written by Chan et al,4 the 150-treatment line has been evaluated and identified a failure rate of 0.45%. All four index patients developed chemical hepatitis that responded to supportive treatment. The incidence of 150-treatment line failures in the US has been reported as 1% to 3% and thought to be predominantly due to inaccurate ingestion history.5 Looking closely at the four cases presented in Chan et al’s study,4 two of them presented late, and in most cases there was an apparent discrepancy between the dose taken and the achieved paracetamol level. Similar to the US experience, an inaccurate ingestion history might explain treatment-line failure for some of these cases. Further evidence from more robust studies is needed before a recommendation can be made to lower the treatment threshold to the UK standard.

Obtaining an accurate history from patients who deliberately self-harm is known to be difficult. Patients may be unwilling or unable to provide accurate information to the clinician. According to the author’s own experience in managing such patients, history taking must be done tactfully and sometimes repeatedly from different sources of information. An astute physician should make the decision to give NAC after analysing all the available evidence including the best-gathered history, the clinical presentation, and the remaining treatment-time window, together with the serum paracetamol level. Laboratory tests may help but can never replace clinical skill, clinical judgement, and experience in patient management.

Previously, the responsibility for managing such time-critical overdosed patients was often borne by interns and junior residents. The quality of care provided may not have been optimal. Over the past 10 years emergency physicians and trainees have received intensive training in the management of toxicology cases based on updated evidence and standards. In addition, groups of interested emergency physicians have formed toxicology teams to oversee and support the management of poisoning patients in individual hospitals. This model of care improves patient outcome and shortens the length of stay for medical treatment.6 7 Such improvements might explain the observed good outcome for Chan et al’s cohort4 of patients with paracetamol overdose.

1. Chan YC, Tse ML, Lau FL. Hong Kong Poison Information Centre: Annual Report 2013. Hong Kong J Emerg Med 2014;21:249-59.

2. Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics 1975;55:871-6.

3. Paracetamol overdose: new guidance on use of intravenous acetylcysteine. Commission of Human Medicine, United Kingdom. Available from: http://www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con178654.pdf. Accessed Aug 2015.

4. Chan ST, Chan CK, Tse ML. Paracetamol overdose in Hong Kong: is the 150-treatment line good enough to cover patients with paracetamol-induced liver injury? Hong Kong Med J 2015;21:389-93. Crossref

5. Rumack BH. Acetaminophen hepatotoxicity: the first 35 years. J Toxicol Clin Toxicol 2002;40:3-20. Crossref

6. Chung AH, Tsui SH, Tong HK. The impact of an emergency department toxicology team in the management of acute intoxication. Hong Kong J Emerg Med 2007;14:134-43.

7. Ko S, Chan HY, Ng F. The impact of Emergency Medicine Ward in acute intoxication management. Hong Kong J Emerg Med 2010;17:323-31.

Preimplantation genetic diagnosis (PGD) gives couples who are at risk of having a child with an inherited genetic disorder or chromosome abnormality, a chance to have an unaffected child without undergoing termination or miscarriage of an affected pregnancy. Embryos obtained from in-vitro fertilisation (IVF) with or without intracytoplasmic sperm injection are tested genetically prior to selective transfer of unaffected ones into the uterus. The physical and psychological complications of a termination or miscarriage, especially in repeated situations, should not be underestimated.

In PGD, DNA can be obtained by blastomere biopsy at the cleavage stage, trophectoderm cell biopsy when an embryo has developed to the blastocyst stage or biopsy of one or both polar bodies. Compared with cleavage stage biopsy, trophectoderm biopsy does not adversely impact the embryo, although vitrification and cryopreservation of the embryo may be required to allow time for genetic analysis.1 Although polar body biopsy is less invasive, it is less predictive of actual clinical outcome than direct embryo assessment.2

Genetic laboratories have developed their own protocols to perform different molecular tests on the limited amount of DNA obtained from biopsy. Traditionally, fluorescent in-situ hybridisation is used for cytogenetic diagnosis, and polymerase chain reaction for molecular diagnosis. New technologies, including array comparative genomic hybridisation (CGH) and single nucleotide polymorphism (SNP) microarrays, can improve diagnostic accuracy.3 4 The single-cell whole genome amplification (WGA) method allows subsequent mutation study, directly by minisequencing and/or indirectly by linkage analysis alongside the mutation test. It also allows simultaneous PGD for more than one indication.5

The indications for PGD are increasing. Common ones include single-gene disorders, X-linked diseases, and inherited chromosome abnormalities. Preimplantation genetic diagnosis of predisposition to inherited cancer such as breast cancer (BRCA mutation) is also emerging.6 Nonetheless, social sexing is prohibited in Hong Kong and Europe. Legislation and regulation of PGD also vary among different countries.

Aneuploidy is the most common cause of repeated implantation failure and recurrent miscarriage. As such, preimplantation genetic screening (PGS), using similar technology to PGD, is offered to improve delivery rates in patients of advanced maternal age, and in those with repeated implantation failure, repeated miscarriages, and severe male factor infertility. Evidence that PGS can help improve delivery rates is conflicting, however.7 Whether PGS using array CGH or SNP microarrays can increase delivery rates requires further study.

In 2006, a tertiary centre in London reported their experience of 330 PGD cycles including 96 cycles for single-gene disorders and 62 cycles for X-linked disorders.8 In 62% of the cycles, there was at least one unaffected embryo available for transfer, resulting in 90 pregnancies, 68 clinical pregnancies, and 58 live births. The clinical pregnancy rate and live birth rate was 33% and 28% per cycle started, respectively.8 This result was similar to a clinical pregnancy rate of 30.2% per transfer reported by the European Society of Human Reproduction and Embryology PGD Consortium in 2014.9

In this issue, authors in a local tertiary centre reported their 6-year experience of 124 PGD cycles for monogenetic diseases in 76 couples using WGA and linkage analysis.10 The ongoing pregnancy rate was 28.2% per initiated cycle and 38.0% per fresh embryo transfer.10 These pregnancy rates were similar to those of PGD using frozen-thawed embryo transfer cycles and for IVF for routine infertility treatment. Approximately 19% of the cycles for PGD were cancelled after initiation of stimulation. Approximately 70% of PGD was performed for thalassaemia (α or β), and the remaining 30% for 19 other monogenetic diseases that included spinocerebellar ataxia type 3 and Huntington’s disease. No misdiagnosis was found in this small series according to the available data.10

In clinical practice, thalassaemia is the most common single-gene disorder in Hong Kong. When both parents are a β-thalassaemia carrier, there is a 25% risk of having a fetus affected by homozygous β-thalassaemia. Conventional prenatal diagnosis is an option but couples will face termination of pregnancy if an affected pregnancy is detected. For an unaffected pregnancy, human leukocyte antigen (HLA) typing can subsequently be performed but may not be compatible with a previously affected child. On the other hand, PGD allows at-risk couples the chance to have an unaffected child without undergoing termination or miscarriage of an affected pregnancy. In addition, PGD can be offered to at-risk couples even in the absence of a previously affected pregnancy. It can also allow selection of an unaffected and HLA-compatible embryo simultaneously before transfer into the uterus. This results in subsequent availability of HLA-matched cord blood at birth for transplant to an affected elder sibling.

In a local study of women at risk,11 in particular those with subfertility problems or with a child affected by major thalassaemia, PGD provided an acceptable alternative to conventional prenatal diagnosis. Couples also had a positive attitude to the use of PGD/HLA typing to reproduce a ‘saviour child’ to save an affected sibling.12 It is unknown, however, whether Hong Kong women at risk of other genetic disorders share this view.

Preimplantation genetic diagnosis requires close collaboration between different specialists including obstetricians, fertility specialists, IVF laboratory, and human geneticists. It needs intensive effort and expensive techniques, and is demanding for the patients. In Hong Kong, the high costs of PGD and IVF must be borne by the patient. It is important to inform patients about the success rate and potential risks of IVF and PGD, possible complications of ovarian hyperstimulation, and the risk of multiple pregnancy.

Because of the possibility of mosaicism related to blastomere or trophectoderm cell biopsy and the false-negative rate due to allelic dropout or contamination related to the limited amount of DNA obtained from PGD, prenatal diagnosis is still recommended after PGD. Prenatal diagnosis is made following an invasive test such as chorionic villus sampling or amniocentesis or, in suitable situations, by a non-invasive approach such as testing of cell-free fetal DNA in maternal plasma for chromosomal abnormalities or by serial ultrasound examinations to exclude haemoglobin Bart’s disease.

There are ethical concerns that arise with new technologies such as microarrays and WGA that generate more detailed and complex genetic information than previous conventional approaches, and make preconception carrier testing feasible.13 Genetic laboratories should report their results according to internationally accepted accreditation standards.14 Adequate pre-testing counselling is important.

With a multidisciplinary approach and advances in technology, PGD is a great opportunity for couples at risk. It allows them to have an unaffected child while avoiding the need to terminate an affected pregnancy, and makes HLA-matched cord blood available at birth for transplantation to a previously affected child. Nonetheless, the process is expensive, demanding for couples, not always successful, and not without risks. Couples at risk should be well informed about the two reproductive options, namely PGD and prenatal diagnosis, in pre-pregnancy counselling.

1. Zhang S, Tan K, Gong F, et al. Blastocysts can be rebiopsied for preimplantation genetic diagnosis and screening. Fertil Steril 2014;102:1641-5. Crossref

2. Salvaggio CN, Forman EJ, Garnsey HM, Treff NR, Scott RT Jr. Polar body based aneuploidy screening is poorly predictive of embryo ploidy and reproductive potential. J Assist Reprod Genet 2014;31:1221-6. Crossref

3. Rubio C, Rodrigo L, Mir P, et al. Use of array comparative genomic hybridization (array-CGH) for embryo assessment: clinical results. Fertil Steril 2013;99:1044-8. Crossref

4. Tobler KJ, Brezina PR, Benner AT, Du L, Xu X, Kearns WG. Two different microarray technologies for preimplantation genetic diagnosis and screening, due to reciprocal translocation imbalances, demonstrate equivalent euploidy and clinical pregnancy rates. J Assist Reprod Genet 2014;31:843-50. Crossref

5. Vendrell X, Bautista-Llácer R. A methodological overview on molecular preimplantation genetic diagnosis and screening: a genomic future? Syst Biol Reprod Med 2012;58:289-300. Crossref

6. Derks-Smeets IA, Gietel-Habets JJ, Tibben A, et al. Decision-making on preimplantation genetic diagnosis and prenatal diagnosis: a challenge for couples with hereditary breast and ovarian cancer. Hum Reprod 2014;29:1103-12. Crossref

7. Mastenbroek S, Twisk M, van der Veen F, Repping S. Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Hum Reprod Update 2011;17:454-66. Crossref

8. Grace J, El-Toukhy T, Scriven P, et al. Three hundred and thirty cycles of preimplantation genetic diagnosis for serious genetic disease: clinical considerations affecting outcome. BJOG 2006;113:1393-401. Crossref

9. Moutou C, Goossens V, Coonen E, et al. ESHRE PGD Consortium data collection XII: cycles from January to December 2009 with pregnancy follow-up to October 2010. Hum Reprod 2014;29:880-903. Crossref

10. Chow JF, Yeung WS, Lee VC, Lau EY, Ho PC, Ng EH. Experience of more than 100 preimplantation genetic diagnosis cycles for monogenetic diseases using whole-genome amplification and linkage analysis in a single centre. Hong Kong Med J 2015;21:299-303. Crossref

11. Hui PW, Lam YH, Chen M, et al. Attitude of at-risk subjects towards preimplantation genetic diagnosis of alpha- and beta-thalassaemias in Hong Kong. Prenat Diagn 2002;22:508-11. Crossref

12. Hui EC, Chan C, Liu A, Chow K. Attitudes of Chinese couples in Hong Kong regarding using preimplantation genetic diagnosis (PGD) and human leukocyte antigens (HLA) typing to conceive a ‘Saviour Child’. Prenat Diagn 2009;29:593-605. Crossref

13. Hens K, Dondorp W, Handyside AH, et al. Dynamics and ethics of comprehensive preimplantation genetic testing: a review of the challenges. Hum Reprod Update 2013;19:366-75. Crossref

14. Harper J, Geraedts J, Borry P, et al. Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. Hum Reprod 2014;29:1603-9. Crossref