Timely intensification of glucose-lowering drugs in type 2 diabetes mellitus (T2DM) is essential to improve durability of glycaemic control and prevent diabetes-related complications.1 2 Progressive beta-cell failure is a hallmark in T2DM, especially in Asians in whom pancreatic beta-cell dysfunction and insulin resistance frequently coexist.3 4 In the Hong Kong Diabetes Register, 50% of patients with T2DM were treated with insulin after 10 years of disease.5 Despite a growing portfolio of glucose-lowering drugs in the last decade,6 only one third of patients with type 1 diabetes mellitus (T1DM) or T2DM achieved personalised glycaemic goals.7 Although increasing insulin dosages may improve glycaemic control, overzealous use of insulin can increase the risk of hypoglycaemia and weight gain.7 Weight gain leads not only to higher insulin dosages but also to increased blood pressure, which is a major cardiovascular risk factor and attenuates the benefits of glucose lowering.8

Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce blood glucose by inhibiting glucose reabsorption in the early proximal renal tubule and promote glucosuria. While the calorie loss can lead to weight reduction, the coupling of sodium and glucose transporters also leads to natriuresis which contribute to lowering blood pressure.3 9 10 Given its beneficial effects on multiple cardiovascular risk factors, there is a strong rationale for using this class of medications as an insulin-sparing agent.2 11

In this issue of Hong Kong Medical Journal, Tan et al12 provide practical guidance to help physicians recognise, monitor, and treat patients with SGLT2 inhibitors, in combination with insulin therapy. Compared with placebo, the addition of SGLT2 inhibitor to insulin therapy in patients with T1DM and T2DM reduced haemoglobin A1c by 0.4% to 0.7%, body weight by 0.2 to 3 kg, and total daily insulin dose by 0.2 to 13 units.12 Possible reasons for the low reported risk of hypoglycaemia with this combination therapy include: a compensatory increase in SGLT1-mediated glucose reabsorption in the distal part of proximal renal tubule; the upregulation of counterregulatory mechanisms including increase in glucagon and hepatic gluconeogenesis; and reduced glycaemic variability.9 12 13

In patients with T2DM with cardiovascularrenal complications and/or multiple risk factors, data from randomised controlled trials have confirmed the benefits of SGLT2 inhibitors in reducing major adverse cardiovascular events, hospitalisation for heart failure, all-cause death, and worsening renal function including end-stage renal disease over a median follow-up period of between 2.6 and 4 years.14 15 16 17 In addition to lowering blood glucose, blood pressure, and body weight, SGLT2 inhibitors may also increase blood haemoglobin with increased tissue oxygenation and decrease uric acid, a known cardiovascular risk factor.18

Another mechanism that may explain the cardiovascular-renal benefits of SGLT2 inhibitors is a metabolic switch, in part due to increase in glucagon, from glucose to free fatty acid oxidation with increased formation of ketone bodies as a more efficient energy source.10 In non-stressed situation, use of SGLT2 inhibitors can be associated with physiological ketosis but without acidosis. However, in the presence of metabolic stress such as surgical procedures and critical illnesses, especially in patients who are lean and those with reduced beta-cell reserves due to long disease duration as well as those who take ketogenic diet for weight reduction, overt/euglycaemic DKA may occur.

In order to minimise the risk of hypoglycaemia, Tan et al12 suggest down-titration of total daily insulin dose by 10% to 20%. Depending on the general state of the patients, treatment modifications should be individualised with reinforcement of sick-day management including increased frequency of monitoring of blood glucose and blood/urine ketone.11 Adequate communication between patients and physicians is particularly important during the perioperative or periprocedural periods where close adherence to treatment recommendations including temporary withdrawal of SGLT2 inhibitors is necessary. During these periods of major stress, increased release of counterregulatory hormones coupled with reduced beta-cell release, against a background of increased glucagon release, can markedly increase the risk of overt/euglycaemic DKA in patients treated with SGLT2 inhibitors. Ensuring adequate hydration, avoiding low carbohydrate diet, and ensuring adequate coverage of insulin are needed to avoid metabolic decompensation.11 12

Despite the high relative risk, the absolute incidence of urogenital infections associated with the use of SGLT2 inhibitors is low and usually well tolerated and self-limiting, at least in randomised controlled trial settings.12 However, the potential link between the use of SGLT2 inhibitors and Fournier gangrene, a progressive bacterial necrotising fasciitis of the perianal, perineal, and/or external genital areas is concerning.19 Despite its rare occurrence affecting less than 0.02% of hospitalisations in the US, these events are extremely devastating and distressing to patients and can be potentially fatal.19 In real-world settings where care is less well supervised, poor glycaemic control may persist even with the use of SGLT2 inhibitors, especially in patients with poor insulin reserve but not adequately replaced. Indeed, in patients who developed Fournier gangrene, as many as 70% had poor glycaemic control and/or obesity.19 In these patients, the glucosuric milieu induced by SGLT2 inhibitors in these anatomical sites with rich bacterial flora may increase the risk of Fournier gangrene.19 20

Based on data from the US Food and Drug Administration Adverse Event Reporting System (FAERS), 55 patients who were treated with SGLT2 inhibitors developed Fournier gangrene during a 6-year period, compared with 19 patients treated with other glucose-lowering drugs.20 Physicians must emphasise the importance of good personal hygiene when using SGLT2 inhibitors, especially in those with poor glycaemic control.3 11 A high index of suspicion for the condition is required if patients complain of local pain disproportionate to findings on physical examination, especially in those with risk factors such as long-term glucocorticoid therapy, immunocompromised state, and chronic alcoholism.19 20 If diagnosed early, Fournier gangrene is treatable with withdrawal of SGLT2 inhibitors, fluid resuscitation, immediate broad-spectrum antibiotics, and urgent surgical debridement.19

Another safety concern associated with the use of SGLTs is lower extremity amputation (LEA).15 17 21 Using pharmacovigilance data from the US FAERS, canagliflozin, with or without concomitant insulin therapy, was associated with excess risk of LEA; no similar association was recorded for dapagliflozin or empagliflozin.22 In the Swedish and Norwegian national health registers, the relative risk of LEA increased by 2 times with the use of SGLT2 inhibitors compared with glucagon-like peptide 1 receptor agonists, irrespective of history of cardiovascular disease or amputation, although the overall event rate was low (2.7 vs 1.1 events per 1000 person-years).23 More studies are needed to clarify whether the risk of LEA is a class effect or drug-specific, as well as to reveal the underlying mechanisms, clinical profiles of patients, and settings of these clinical events. Examination of lower extremity including foot pulses is particularly important, especially in those with multiple risk factors, history of foot ulcers, and/or dehydrated (eg, high-dose diuretics) in whom SGLT2 inhibitors should be used with caution or avoided altogether.

In day-to-day practice, the key questions for patients and physicians are when and how to safely initiate SGLT2 inhibitors as adjunctive to insulin therapy. The clinical perspectives by Tan et al12 contextualises the patient profiles and provides practical tips to avoid adverse events. The large body of evidence supports the importance of periodic assessment of risk factors and complications and use of personalised data to stratify risk, educate/empower patients, and promote good patient-doctor communication to maximise benefits and minimise harms of SGLT2 inhibitors in the prevention of morbidities, hospitalisations, and premature death related to T2DM.24

All authors contributed to the concept or design, data interpretation, drafting of the article, and critical revision for important intellectual content. All authors contributed to the manuscript, approved the final version for publication, and take responsibility for its accuracy and integrity.

This work received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

JCN Chan is the Chief Executive Officer (on pro-bono basis) of Asia Diabetes Foundation, a charitable foundation established under The Chinese University of Hong Kong Foundation for developing the JADE Technology. She has received honoraria and travelling support for consultancy or giving lectures and her affiliated institutions have received research and educational grants from Amgen, Ascencia, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Eli-Lilly, GlaxoSmithKline, Medtronic, Merck Serono, Merck Sharp & Dohme, Novo Nordisk, Pfizer, and Sanofi. LL Lim has received honoraria and travelling support for giving lectures and her affiliated institutions have received research and educational grants from AstraZeneca, Boehringer Ingelheim, Merck Serono, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Procter & Gamble, Sanofi, and Servier.

1. Ray KK, Seshasai SR, Wijesuriya S, et al. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet 2009;373:1765-72. Crossref

2. Davies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018;41:2669-701. Crossref

3. Lim LL, Tan AT, Moses K, Rajadhyaksha V, Chan SP. Place of sodium-glucose cotransporter-2 inhibitors in East Asian subjects with type 2 diabetes mellitus: Insights into the management of Asian phenotype. J Diabetes Complications 2017;31:494-503. Crossref

4. Yabe D, Seino Y. Type 2 diabetes via β-cell dysfunction in east Asian people. Lancet Diabetes Endocrinol 2016;4:2-3. Crossref

5. Tong PC, Ko GT, So WY, et al. Use of anti-diabetic drugs and glycaemic control in type 2 diabetes—The Hong Kong Diabetes Registry. Diabetes Res Clin Pract 2008;82:346-52. Crossref

6. Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet 2017;389:2239-51. Crossref

7. Aschner P, Gagliardino JJ, Ilkova HM, et al. Nonachievement of glycemic target—results from the International Diabetes Management Practices Study (IDMPS). Diabetes 2018;67(Supplement 1):1030-P. Crossref

8. Genev NM, Lau IT, Willey KA, et al. Does insulin therapy have a hypertensive effect in type 2 diabetes? J Cardiovasc Pharmacol 1998;32:39-41. Crossref

9. Rieg T, Vallon V. Development of SGLT1 and SGLT2 inhibitors. Diabetologia 2018;61:2079-86. Crossref

10. Lytvyn Y, Bjornstad P, Udell JA, Lovshin JA, Cherney DZ. Sodium glucose cotransporter-2 inhibition in heart failure: Potential mechanisms, clinical applications, and summary of clinical trials. Circulation 2017;136:1643-58. Crossref

11. Deerochanawong C, Pheng CS, Matawaran BJ, et al. Use of SGLT-2 inhibitors in patients with type 2 diabetes mellitus and multiple cardiovascular risk factors: an Asian perspective and expert recommendations. Diabetes Obes Metab 2019 Jul 2. Epub ahead of print.

12. Tan K, Chow WS, Leung J, et al. Clinical considerations when adding a sodium-glucose co-transprter-2 inhibitor to insulin therapy in patients with diabetes mellitus. Hong Kong Med J 2019;25:312-9.

13. Rama Chandran S, Tay WL, Lye WK, et al. Beyond HbA1c: Comparing glycemic variability and glycemic indices in predicting hypoglycemia in type 1 and type 2 diabetes. Diabetes Technol Ther 2018;20:353-62. Crossref

14. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-28. Crossref

15. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017;377:644-57. Crossref

16. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019;380:347-57. Crossref

17. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019;380:2295-306. Crossref

18. Inzucchi SE, Zinman B, Fitchett D, et al. How does empagliflozin reduce cardiovascular mortality? Insights from a mediation analysis of the EMPA-REG OUTCOME trial. Diabetes Care 2018;41:356-63. Crossref

19. Hagedorn JC, Wessells H. A contemporary update on Fournier’s gangrene. Nat Rev Urol 2017;14:205-14. Crossref

20. Bersoff-Matcha SJ, Chamberlain C, Cao C, Kortepeter C, Chong WH. Fournier gangrene associated with sodium-glucose cotransporter-2 inhibitors: A review of spontaneous postmarketing cases. Ann Intern Med 2019 May 7. Epub ahead of print. Crossref

21. Ryan PB, Buse JB, Schuemie MJ, et al. Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: A real-world meta-analysis of 4 observational databases (OBSERVE-4D). Diabetes Obes Metab 2018;20:2585-97. Crossref

22. Fadini GP, Avogaro A. SGLT2 inhibitors and amputations in the US FDA Adverse Event Reporting System. Lancet Diabetes Endocrinol 2017;5:680-1. Crossref

23. Ueda P, Svanström H, Melbye M, et al. Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study. BMJ 2018;363:k4365. Crossref

24. Lim LL, Lau ES, Kong AP, et al. Aspects of multicomponent integrated care promote sustained improvement in surrogate clinical outcomes: A systematic review and meta-analysis. Diabetes Care 2018;41:1312-20. Crossref

The population of Hong Kong is ageing. The number of elderly persons aged ≥65 years is projected to increase from 0.85 million in 2005 to 1.68 million in 2024. Moreover, there will be a rapid increase in the old-old population aged ≥85 years, reaching 0.237 million in 2024.1 These elderly individuals face substantial healthcare-related problems, including dementia,2 3 4 fragility hip fractures,5 6 frailty,7 carriage of multi-drug resistant organisms in residential care homes for the elderly (RCHEs),8 and provision of end-of-life services.9 In 2017, there were 74 257 residents in RCHEs in Hong Kong, which is equivalent to 6% of the elderly population.2 Approximately one-third of these residential care places are non-private (subvented).10 With an increasing old-old population, the demand for RCHEs is expected to greatly increase. As elderly care is one of the most important government agendas, ageing in place should be given a higher priority.11 The Social Welfare Department is responsible for the issue of licences to all RCHEs and for regulating them through the Code of Practice.12 The quality standards in the Code of Practice focus mainly on the structure (eg, space, furniture, fire safety, equipment, and staff) and process of care (eg, record keeping, diet, nutrition, drug administration, urinary catheter care, feeding tubes and other nursing procedures, and infection control measures), but not outcomes (eg, mortality, morbidity, or hospital admissions) for their elderly residents. The infection control chapter in the Code of Practice was added after the 2003 SARS outbreak in Hong Kong. The aim was to improve infection control processes in RCHEs.

In the current issue of the Hong Kong Medical Journal, Wong et al13 report an audit study of the performance of infection control processes and procedures in RCHEs, in relation to the quality standards set by the Code of Practice, from 2005 to 2014. This is the first study of its kind in Hong Kong. The authors found that there has been an improvement over time in terms of residents-to-staff manpower ratio, proportion of RCHEs with isolation rooms/areas, health records of staff and visitors, and infection control skills and practice. However, the authors also found that non-private RCHEs often performed better than private RCHEs. For example, 93.0% of non-private RCHEs assigned nurses as Infection Control Officers (ICOs), whereas only 18.5% of private RCHEs followed this practice. In addition, 90.3% of non-private RCHEs provided isolation rooms/areas for infected residents, whereas only 73.3% of private RCHEs did so.

Some caution is recommended when considering these results. The authors assessed only two frontline care staff (the ICO and one care worker) per RCHE.13 Therefore, the results on the skills of infection control (ie, hand washing, donning and doffing of personal protective equipment, and using bleach solution for environmental disinfection) might not reflect the performance of the majority of the frontline care staff. A previous study by Chan et al14 reported that 46% of the staff in private RCHEs have a low education level. These care staff might perform less well than the ICOs. The authors also did not include data on the outcomes of infection control on elderly residents (ie, mortality, morbidity, hospitalisations). Among the different types of infections occurring in among elderly residents in RCHEs, influenza-like illnesses (including bacterial and viral infections) are the most common. In a study on 3857 residents in 46 RCHEs, the overall prevalence of all infections was 2.7%, and the most common infections were respiratory tract infection (1.3%).15 Hui et al16 reported an influenza-like illness–related mortality rate of 9.7% at 1 month or discharge from hospitals among elderly residents in RCHEs.

Further studies are recommended to evaluate the effect of infection control measures on the health outcomes of residents in RCHEs. Health outcomes including mortality, morbidity, hospitalizations should be included.

The author approved the final version for publication, and takes responsibility for its accuracy and integrity.

As an editor of the journal, LW Chu was not involved in the peer review process.

1. Census and Statistics Department, Hong Kong SAR Government. Available from: https://www.censtatd.gov.hk/hkstat/sub/sp150.jsp?tableID=002&ID=0&productType=8. Accessed 23 Feb 2019.

2. Luk JK, Chan FH, Hui E, Tse CY. The feeding paradox in advanced dementia: a local perspective. Hong Kong Med J 2017;23:306-10. Crossref

3. Shea YF, Chu LW, Lee SC. A descriptive study of Lewy body dementia with functional imaging support in a Chinese population: a preliminary study. Hong Kong Med J 2017;23:222-30. Crossref

4. Chu LW. Challenges in the diagnosis and management of dementia in Hong Kong. Hong Kong Med J 2017;23:218-9. Crossref

5. Liu SK, Ho AW, Wong SH. Early surgery for Hong Kong Chinese elderly patients with hip fracture reduces short-term and long-term mortality. Hong Kong Med J 2017;23:374-80. Crossref

6. Cheung, MY, Ho AW, Wong SH. Post-fracture care gap: a retrospective population-based analysis of Hong Kong from 2009 to 2012. Hong Kong Med J 2018;24:579-83. Crossref

7. Wong CW. Frailty assessment: clinical application in the hospital setting. Hong Kong Med J 2018;24:623-8. Crossref

8. Chen H, Au KM, Hsu KE, et al. Multidrug-resistant organism carriage among residents from residential care homes for the elderly in Hong Kong: a prevalence survey with stratified cluster sampling. Hong Kong Med J 2018;24:350-60. Crossref

9. Luk JK. End-of-life services for older people in residential care homes in Hong Kong. Hong Kong Med J 2018;24:63-7. Crossref

10. Social Welfare Department, Hong Kong SAR Government. Social Welfare Department Review 2015-16 & 2016-17. Available from: https://www.swd.gov.hk/storage/asset/section/1435/en/SWD_Review_Year_2015-16_and_2016-17-en.pdf. Accessed 23 Feb 2019.

11. Cheng CP. Elderly care as one of the important government policy agenda. Hong Kong Med J 2018;24:442-3. Crossref

12. Social Welfare Department (Licensing Office), Hong Kong SAR Government. Code of practice for residential care homes (elderly persons). Available from: https://www.swd.gov.hk/doc/LORCHE/CodeofPractice_E_201303_20150313R3.pdf. Accessed 23 Feb 2019.

13. Wong CY, Ng T, Li T. Infection control in residential care homes for the elderly in Hong Kong (2005-2014). Hong Kong Med J 2019;25:113-9. Crossref

14. Chan TC, Luk JK, Chu LW, Chan FH. Low education level of nursing home staff in Chinese nursing homes. J Am Med Dir Assoc 2013;14:849-50. Crossref

15. Choy CS, Chen H, Yau CS, Hsu EK, Chik NY, Wong AT. Prevalence of infections among residents of Residential Care Homes for the Elderly in Hong Kong. Hong Kong Med J 2016;22:347-55. Crossref

16. Hui DS, Woo J, Hui E, et al. Influenza-like illness in residential care homes: a study of the incidence, aetiological agents, natural history and health resource utilisation. Thorax 2008;63:690-7. Crossref

Clinical scores and risk factors for a prediction of patient outcomes are useful for improving patient care. Famous examples include the response evaluation criteria in solid tumours (RECIST) score for guidance of treatment and the Framingham Risk Score for risk assessment of cardiovascular and related diseases. One great potential of clinical scores is accelerating diagnosis and providing timely treatment. In the case of pregnant women with pre-eclampsia, the result of spot urine protein-to-creatinine ratio test is highly correlated with that of the usual diagnostic criteria—over 300 mg of protein in a 24-hour urine sample.1 This allows prompt response or follow-up in positive cases and increases management efficiency. In addition, simpler detection methods with similar accuracy can encourage more people to take a test or complement existing tests to reduce errors, as seen with non-invasive prenatal testing after its introduction in Hong Kong in 2011.2

Risk factors can also be used to estimate the risk of mortality. In a study of Chinese geriatric patients who had received hip fracture operations, Lau et al3 combined the Charlson Comorbidity Index with score weighting that reflects age to form the total Charlson comorbidity score of patients. The authors found this score to be significantly associated with 30-day and 1-year mortality risk in geriatric patients.3 With information like this available, patients and health care providers can make better informed decisions. Better information can reassure patients and their families, and relieve their usual fear and stress in response to the uncertainty of undergoing surgery with co-morbidities. In addition, practitioners can quickly identify higher-risk patients and take these risks into consideration when providing treatment and follow-ups. Furthermore, managers can utilise clinical scores to perform needs assessments and to plan for resource allocation. For example, a scale for predicting length of hospital stay after primary total knee replacement based on the risk factors was verified in Hong Kong in 2017,4 but its value reaches beyond just estimating the length of stay. The predictive factors also provide information on how the quality of health care can be improved if the factors are non-biological and controllable, such as urinary catheterisation in this case.

Further analysing the health outcomes of multiple treatment routines, clinical scores could be applied to estimate the health effect of a certain treatment and its alternatives for individual patients. This prediction power would be particularly valuable in complex conditions where differences in individual factors, such as pharmacokinetics, could play a significant role in affecting the outcome. For example, in a clinical trial in 2015, Mulvenna et al5 found no significant difference in survival or quality-adjusted life years among 538 patients who received optimal supportive care only or additional whole-brain radiation therapy, suggesting the presence of very heterogeneous tumour behaviour. In contrast, a study of frameless stereotactic radiosurgery found that prognostic scoring identified patients who would benefit more from the treatment.6 In the current development direction of personalised care, clinical scores could be used to enhance informed clinical decision making or as a transitional alternative for precision medicine.

A useful clinical prediction instrument not only helps improving patient care, but also reduces wasting health care resources owing to misdiagnosis. In the current issue of the Hong Kong Medical Journal, Cheung et al7 have validated and refined the existing Ottawa subarachnoid haemorrhage (SAH) rule to improve its sensitivity for SAH diagnosis. The results of that study indicate the sensitivity of Ottawa SAH rule can be increased to 100% by adding two more predictors—vomiting and SBP >160 mm Hg—while retaining a specificity of 13.1%. The authors conclude that unnecessary costs (ie, 11.8% of computed tomographic scans in this study population) can likely be reduced.

Some caution is warranted when interpreting the performance of a clinical prediction instrument, and therefore its usefulness. Missing values are a common limitation for developing a clinical prediction rule, as acknowledged by Cheung et al.7 Some patients might be positive for certain symptoms but be misclassified as negative due to missing values. Differential misclassification can cause the odds ratios of predictors (the symptoms) to be biased away from the null hypothesis, jeopardising the validity of symptoms found to be associated or not associated with a disease.8 Caution is also needed when applying performance metrics to a clinical prediction instrument. For example, ‘accuracy’ is a specific measure of ability of a predictive test in identifying cases from non-cases; one measure of accuracy involves dividing the sum of true positive and true negative results by the total population size. Using the study from Cheung et al7 as an example, the prediction accuracy of the original Ottawa SAH rule was 39% (ie, [47+148]/500) which is higher than that of the modified Ottawa SAH rule (ie, [50+59]/500=21.8%). Thus, assessing the prediction performance based on multiple metrics are essential for judging the usefulness of a prediction rule. Last but not least, a useful clinical prediction tool should be subject to external validation, ie, with independent cohorts and data that have not been used in the model development.9 This validation process is able to help examine the heterogeneousness of the model predictions, ie, whether it is reliable or accurate enough to be used in a wider population. Most proposed prediction models in the literature involve only internal validations; relatively few models have been through external validations, primarily because of a lack of data.10 Future development and evaluations of clinical scores and risk factors should take such factors into consideration, and proposed models should be followed up with external validation. Under this framework, we anticipate that research and development on clinical scores and risk factors will be more useful in real-world settings. This may have an positive effect on patient care and clinical outcomes, such as patient survival and quality of life.

As the statistical advisor of the Hong Kong Medical Journal, KC Chong was not involved in the peer review process of this article. Other authors have disclosed no conflicts of interest. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

SY Chan and KM Jia contributed to the concept of this article. KC Chong drafted the manuscript and provided critical revision for important intellectual content.

1. Cheung HC, Leung KY, Choi CH. Diagnostic accuracy of spot urine protein-to-creatinine ratio for proteinuria and its association with adverse pregnancy outcomes in Chinese pregnant patients with pre-eclampsia. Hong Kong Med J 2016;22:249-55. Crossref

2. Kou KO, Poon CF, Kwok SL, et al. Effect of non-invasive prenatal testing as a contingent approach on the indications for invasive prenatal diagnosis and prenatal detection rate of Down’s syndrome. Hong Kong Med J 2016;22:223-30. Crossref

3. 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

4. Lo CK, Lee QJ, Wong YC. Predictive factors for length of hospital stay following primary total knee replacement in a total joint replacement centre in Hong Kong. Hong Kong Med J 2017;23:435-40. Crossref

5. Mulvenna P, Nankivell M, Barton R, et al. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet 2016;388:2004-14. Crossref

6. Mok ST, Kam MK, Tsang WK, et al. Frameless stereotactic radiosurgery for brain metastases: a review of outcomes and prognostic scores evaluation. Hong Kong Med J 2017;23:599-608. Crossref

7. Cheung HY, Lui CT, Tsui KL. Validation and modification of the Ottawa subarachnoid haemorrhage rule in risk stratification of Asian Chinese patients with acute headache. Hong Kong Med J 2018;24:584-92. Crossref

8. Alexander LK, Lopes B, Ricchetti-Masterson K, Yeatts KB. Sources of Systematic Error or Bias: Information Bias. ERIC Notebook. 2nd ed. Chapel Hill (NC): The University of North Carolina at Chapel Hill; 2015.

9. Moons KG, Kengne AP, Grobbee DE, et al. Risk prediction models: II. External validation, model updating, and impact assessment. Heart 2012;98:691-8. Crossref

10. Riley RD, Ensor J, Snell KI, et al. External validation of clinical prediction models using big datasets from e-health records or IPD meta-analysis: opportunities and challenges. BMJ 2016;353:i3140. Crossref

Clinical practice guidelines (CPGs) are considered as one of the most influential and effective tools for the promotion of evidence-based medicine.1 The use of guidelines in clinical practice may lead to a reduction in practice discrepancy and release the tension between health care cost and quality. In homogeneous populations, CPGs are most useful; for example, in the case of recommendations for preventive vaccination in children. In this issue, Chua et al2 summarise the updates and the recommendations on vaccination in egg-allergic patients.

The aim of creating CPGs is to have consensus based on consistent and thorough review of the literature. With specific content where the evidence is inconclusive and there is variation in clinical practice, CPGs are most effective. Quality of care can be improved by reducing the variation in clinical practice and adherence to standards of good care. With increasing recognition of the shortcomings of health care systems, CPGs have become widely advocated as a means of summarising and encouraging compliance with evidence-based medicine. Clinical practice guidelines can be used in a wide range of conditions to provide the best possible care.3 4 5 6 7 8 9 10 11

Despite their popularity, it remains controversial that whether CPGs lead directly to improvements in clinical practice. Moreover, CPGs tend not to be widely used in clinical practice.12 Problems associated with the usability of CPGs include inaccessibility of the guidance at the point of care, long lifecycle of CPG development, inapplicability to local settings, and lack of active user involvement.13 Most guidelines are based on results of trials which usually study homogenous populations. In clinical practice, patients are inhomogeneous. To limit confounding factors, randomised controlled trials usually aim to answer a very specific question in a clearly defined population. However, in clinical practice, patients are rarely identical to the study populations. While some CPGs are oversimplified and lack patient-specific guidance, others may end up being too ambiguous with the intent to allow flexibility for clinicians to decide the management that is most suitable for their patients.14 15

To overcome these drawbacks of CPGs, involvement of active or local users and refinement of CPGs according to local circumstances is necessary. In the paper by Chua et al,2 we can see the involvement of various professional and clinicians at different levels of experience. Hopefully, this can provide suitable recommendations to local clinicians and paediatricians.

Guidelines are directed at the disease, not at a particular patient. They should not supersede individualised medicine. Clinical practice should be directed by a combination of clinical experiences, evidenced-based guidelines, and the peculiarities of individual patients.

The author has disclosed no conflicts of interest.

1. Wolff M, Bower DJ, Marbella AM, Casanova JE. US family physicians’ experiences with practice guidelines. Fam Med 1998;30:117-21.

2. Chua GT, Li PH, Ho MH, et al. Hong Kong Institute of Allergy and Hong Kong Society for Paediatric Immunology Allergy & Infectious Diseases joint consensus statement 2018 on vaccination in egg-allergic patients. Hong Kong Med J 2018;24:527-31. Crossref

3. Chan AW, Chan JK, Tam AY, Leung TF, Lee TH. Guidelines for allergy prevention in Hong Kong. Hong Kong Med J 2016;22:279-85. Crossref

4. Cheung CW, Chan TC, Chen PP, et al. Opioid therapy for chronic non-cancer pain: guidelines for Hong Kong. Hong Kong Med J 2016;22:496-505. Crossref

5. Gangwani RA, Lian JX, McGhee SM, Wong D, Li KK. Diabetic retinopathy screening: global and local perspective. Hong Kong Med J 2016;22:486-95. Crossref

6. Fung EL, Fung BB; Subcommittee on the Consensus Statement of the Hong Kong Epilepsy S. Review and update of the Hong Kong Epilepsy Guideline on status epilepticus. Hong Kong Med J 2017;23:67-73. Crossref

7. Fong JK, Chan EL, Leung H, et al. An update of the Hong Kong Epilepsy Guideline: consensus statement on the use of antiepileptic drugs in Hong Kong. Hong Kong Med J 2017;23:74-88. Crossref

8. Cheung BM, Cheng CH, Lau CP, et al. 2016 Consensus statement on prevention of atherosclerotic cardiovascular disease in the Hong Kong population. Hong Kong Med J 2017;23:191-201. Crossref

9. Wong CW, Lee JS, Tam KF, et al. Diabetes in older people: position statement of The Hong Kong Geriatrics Society and the Hong Kong Society of Endocrinology, Metabolism and Reproduction. Hong Kong Med J 2017;23:524-33. Crossref

10. Wu JC, Chan AO, Chan YW, et al. The current treatment landscape of irritable bowel syndrome in adults in Hong Kong: consensus statements. Hong Kong Med J 2017;23:641-7. Crossref

11. Cheung TT, Kwok PC, Chan S, et al. Hong Kong Consensus Statements for the Management of Unresectable Hepatocellular Carcinoma. Liver Cancer 2018;7:40-54. Crossref

12. Geleris P, Boudoulas H. Problems related to the application of guidelines in clinical practice: a critical analysis. Hellenic J Cardiol 2011;52:97-102.

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In an extensively referenced and incisive article, Prof Gilberto Leung lays out the controversial issue of medical manslaughter.1 In English law, the associated legal offence is termed gross negligence manslaughter (GNM). Doctors can be charged and convicted of this offence when a duty of care is breached, with grossly negligent acts or omissions causing patient death. Prosecution of doctors for GNM is rare but on the rise in the UK, and doctors have expressed concerns about the impact such investigations and prosecutions have on staff morale and health services.2

The law with respect to GNM was clarified in the 1994 Adomako case,3 in which the anaesthetist in charge of a patient during an eye operation failed to notice the disconnection of an oxygen pipe for 6 minutes, and the patient died as a result. The jury in this case was directed to “to consider whether that breach of duty should be characterised as gross negligence and therefore as a crime”. What then constitutes ‘gross’ negligence? The guidance provided by Lord Mackay was that the jury should judge how far the defendant’s conduct departed from the standard of care, and the conduct should be ‘so bad’ as to amount to a criminal act. In her award-winning law reform essay, Katherine Wright4 considered the problem of uncertainty regarding the legal test for gross negligence in some detail. She noted that even prosecutors themselves had difficulty articulating their interpretation of gross negligence, and that a solid prosecution policy for this serious charge is lacking. The decision whether or not to prosecute may not be arbitrary but does seem particularly reliant on the prosecutor’s own moral frame or even gut feelings.4

The field of GNM law appears to be oblivious to the field of patient safety improvement, where ‘blame-free culture’ is the paradigm. Jeremy Hunt, the UK Health Secretary, delivered a passion-filled speech titled “From a blame culture to a learning culture” in his address at the Global Safety Summit in March 2016.5 In the speech, he quoted a 1990 case of ‘a bright 24-year-old medical school graduate’ who started his first job in medicine as a pre-registration house officer, and in his first month of duty, he wrongly injected a highly toxic chemotherapy drug to a patient’s spine. The 16-year-old patient died, and the medical house officer and another colleague were prosecuted for medical manslaughter and given suspended jail sentences. The conviction was eventually overturned by the Court of Appeal.

Hunt4 regretted that “…the real crime was missed: as the legal process rumbled on, exactly the same error was made in another National Health Service (NHS) hospital and another patient died because our system was more interested in blaming than learning”. He went on to say, “The blame culture doesn’t just create fear [among] doctors. It causes heartbreak for patients and their families…” Blocked by fear of blame, defensive health care workers shut grieving families out when unexpected patient death occurs.5 Hunt insisted that a blame-free environment promotes learning and openness and that prosecuting such medical mistakes as criminal offences does not help.5

How do we reconcile the observation that, on the one hand, the UK Health Secretary made such a passionate plea for a non-punitive approach, and on the other hand, that investigations and prosecutions for GNM are on the rise? Is the UK of split mind?

Winding the clock back by two decades may help us see how the pendulum has been swinging between the blame-free paradigm and hard legal sanctions. The story might have begun in the US. In November 1999, the Institute of Medicine (now the US Academy of Medicine) issued a groundbreaking report To Err is Human: Building a Safer Health System.6 With this, the US and the rest of the world embarked on a decade-long pursuit of a patient safety agenda. No-blame or blame-free culture became buzzwords throughout the decade.7 8

The premises of this patient safety movement can be simply stated: first, medical errors are common and cause many patient injuries and even deaths; second, most medical errors are caused by underlying unsafe practices, work processes, and poor systems. This is not to say that human factors are not important, but the common notion of bad physicians being the root cause of bad care appeared unfounded in the vast majority of cases. To build safety systems in health care, it is essential to encourage openness in incident reporting and root cause analysis. Lessons will not be learned if the root causes cannot be discussed openly without fear of retribution.

Perhaps the pendulum swung again in 2010 with the NHS Mid Staffordshire Trust tragedy. ‘Tragedy’ is a euphemism for a fairly large scandal, which revealed hundreds of patients having died needlessly as the result of substandard care and staff failings at two hospitals in Mid Staffordshire between January 2005 and March 2009. A public inquiry led by Robert Francis QC produced the Francis Report,9 in which 290 recommendations for improvement were made.

The Francis report was not enough to weather the political storm. In 2013, the UK Prime Minister commissioned Professor Donald Berwick from the US to study Mid Staffordshire’s various accounts and the recommendations of the Francis report to distil lessons to be learned by the UK Government. Berwick, the co-founder of the Institute of Healthcare Improvement and chair of the National Advisory Council of the Agency for Healthcare Research and Quality, is a fervent champion of health care quality and safety. The Berwick report released in October 2013 indicated a complete systems failure during the Mid Staffordshire Trust tragedy.10 It recommended a broad culture change in the NHS: “The way out is through learning, curiosity, commitment, and empathy rather than anger, fear and blame”.10

Berwick’s non-punitive and encouraging approach was hailed by some as having completely dismissed “the nonsense of criminal sanctions in healthcare”.11 This overlooked the part of the report that called for effective regulations to be strong, focused, and detailed, as well as a recommendation “to build a hierarchy of regulatory responses, including making new criminal sanctions” (Recommendation 10, Section VIII).10 The argument was that existent criminal sanctions (including GNM) are not wide enough in scope, and therefore that the UK Government should introduce new sanctions “in cases where healthcare workers or organisations are unequivocally guilty of willful or reckless neglect or mistreatment of patients”. The Berwick report drew on parallels with existing laws that protect mentally incapacitated and mentally ill people under institutional care.

Authors of the Berwick report were conscious of the apparent contradiction of this recommendation on new criminal sanctions with the celebrative ‘blame free’ learning culture advocated in the rest of the report. The report emphasised that supporting NHS staff and hospitals in learning from errors and holding them criminally accountable are not mutually exclusive approaches. This assertion that we can have the best of both worlds (being blame-free and imposing criminal sanctions as a deterrent at the same time) seems neither self-evident nor evidence-based.

Would criminalising health care professionals for wilful neglect improve patient safety? The UK Government has yet to make a decision on this particular recommendation in the Berwick report. The issue has been debated: one proponent has argued that criminal sanctions have worked in public health law. An example is the success of making seatbelt wearing legally compulsory, which has effectively saved many lives.12 However, the example of seatbelt wearing is a poor one: modern health care is extremely complex, and risk mitigation in medical practice is dissimilar from the single requirement of seatbelt buckling.

Medical manslaughter is a difficult subject, and we should be mindful that protection of doctors is not primarily at stake. Insisting on a totally blame-free culture may be idealistic and can be mistaken for not accepting responsibility when medical harm occurs. Even if we accept that medical errors, including fatal medical incidents, are often caused by a mix of systemic and human factors, doctors and management should be accountable for the parts for which they are responsible. Accordingly, accountability and ‘just culture’ have been proposed.13 14 Prosecution for medical manslaughter may be justified in extreme cases of recklessness and blatant violation of standards of care. The difficulty lies in drawing a line between simple negligence due to fleeting lapses of attention under overworked conditions and gross negligence that is truly reckless. As discussed by Leung,1 gross negligence is not a clearly defined legal concept.1 We need a sustainable health care system that cherishes positive efforts to learn and improve care and is just to the public and fair to professionals. Open discussion is the way forward.

The author has disclosed no conflicts of interest. The author had full access to all data, contributed to the paper, approved the final version for publication, and takes responsibility for its accuracy and integrity.

1. Leung GK. Medical manslaughter in Hong Kong—how, why, and why not. Hong Kong Med J 2018;24:384-90. Crossref

2. Medico-Legal Committee. The British Medical Association. Medical and gross negligence manslaughter. Available from: https://www.bma.org.uk/collective-voice/committees/medico-legal-committee/medical-manslaughter. Accessed 14 May 2018.

3. R v Adomako [1995] 1 AC 171.

4. Wright K. When clinical becomes criminal: reforming medical manslaughter. Law Reform Essay. Bar Council of UK. Available from: https://www.barcouncil.org.uk/media/627460/_35__law_reform_essay.pdf. Accessed 18 May 2018.

5. Hunt J. From a blame culture to a learning culture. Mar 2016. Available from: https://www.gov.uk/government/speeches/from-a-blame-culture-to-a-learning-culture. Accessed 18 May 2018.

6. US Institute of Medicine Committee on Quality of Health Care in America. In: Kohn LT, Corrigan JM, Donaldson MS, editors. To Err is Human: Building a Safer Health System. Washington, US: National Academies Press; 2000.

7. Lilleyman J. A blame-free culture in the NHS: quixotic notion or achievable ambition? Perfusion 2005;20:233. Crossref

8. Elmqvist KO, Rigaudy MT, Vink JP. Creating a no-blame culture through medical education: a UK perspective. J Multidiscip Healthc 2016;9:345-6. Crossref

9. UK Government. Report of the Mid Staffordshire NHS Foundation Trust public inquiry. Feb 2013. Available from: https://www.gov.uk/government/publications/report-of-the-mid-staffordshire-nhs-foundation-trust-public-inquiry. Accessed 13 Mar 2017.

10. Department of Health and Social Care, UK Government. Berwick review into patient safety: recommendations to improve patient safety in the NHS in England. 6 Aug 2013. Available from: https://www.gov.uk/government/publications/berwick-review-into-patient-safety. Accessed 18 May 2018.

11. Berwick report highlights nonsense of criminal sanctions in healthcare. Aug 2013. Available from: https://www.pharmaceutical-journal.com/news-and-analysis/berwick-report-highlights-nonsense-of-criminal-sanctions-in-healthcare/11124155.article. Accessed 21 May 2018.

12. Bibby J, Tomkins C. Would criminalising healthcare professionals for wilful neglect improve patient care? BMJ 2014;348:g133. Crossref

13. Walton M. Creating a “no blame” culture: have we got the balance right? BMJ 2004;13:163-4. CrossRef

14. Wachter RM, Pronovost PJ. Balancing “no blame” with accountability in patient safety. N Engl J Med 2009;361:1401-6. Crossref