Worldwide, dementia is one of the major causes of disability and dependency among elderly populations. Globally, there are approximately 50 million people with dementia, and nearly 10 million new cases are diagnosed every year.1 The global costs and economic impacts of dementia to the society are huge—an amount equivalent to about 1 trillion dollars in 2019.2 China accounts for approximately 25% of the worldwide population of patients with dementia.3 The overall prevalence of dementia in Chinese people aged ≥60 years is 5.3% (95% confidence interval=4.3%-6.3%).4 Both the annual cost per person and the proportion of the national gross domestic product that dementia accounts for exceeds the global averages, imposing a substantial economic burden on China.5 In addition, other conditions that are common in elderly populations, such as frailty, hip fractures, and cancer6 7 8 9 may further compound the consequences of dementia.

In this issue of the Hong Kong Medical Journal, Lam and colleagues report findings with important implications for the assessment and diagnosis of dementia.10 They review recent approaches for its diagnosis and highlighted their applications in primary healthcare settings. They summarise the importance and definition of dementia, categorise the differential diagnosis of cognitive impairment, and explain the diagnostic approach, including the history and physical examination, cognitive assessment, laboratory tests, and neuroimaging. Most importantly, Lam et al10 provide background information and advice for healthcare professionals on how they should utilise recent approaches in diagnosing dementia in clinical practice. Recent studies have used standardised patients who were recruited from local communities and extensively trained to present the same set of standard symptoms to multiple providers to assess quality of clinical care in China, India, and Kenya. They have shown that the quality of primary care in low-and-middle-income countries was poor.11 12 13 14 15 16 Most cases were incorrectly diagnosed based on a very lenient definition, and simple medical conditions were improperly managed in the majority of cases. Antibiotics were usually inappropriately overprescribed, and it was less likely for primary care providers to refer patients to higher-level hospitals for specialist care when needed. Although the large “know-do gap”—the gap between healthcare providers’ knowledge and their performance in clinical practice—can explain part of the low quality, the lack of essential and updated knowledge to handle this medical condition is still one of the major reasons for substandard care.17 18 19 According to the National Institute for Health and Care Excellence guideline on dementia issued in 2018, primary care professionals are expanding their roles in the diagnosis and assessment of dementia, which highlights the need for updated education and training for healthcare professionals on dementia diagnosis and treatment.20

Lam et al10 provide background information for the diagnosis of dementia; however, there are caveats that require caution when we are using these methods. First, the costs of each type of diagnostic method should be considered. For example, neuroimaging can be very expensive and is not without hazard. It may not be suitable for extensive use in primary care. Second, the sensitivity and specificity of the tools should be explored to minimise misdiagnosis due to false positive or false negative results. Third, individuals with a high risk of cognitive impairment and dementia should also be identified. Patients with a profile of cardiovascular risk factors (ie, hypertension, diabetes, or dyslipidaemia) are more likely to have dementia.21 Diagnosis and screening may be more efficient if primary care professionals could recognise these patients earlier.

Not only should primary care providers be trained in management of dementia, but a national level project should be implemented to train specialists on dementia so as to enhance capacity to devise interventions in the community, such as establishment of more memory clinics. Training modules are suggested to be based on most recent research findings, including systematic reviews and meta-analysis. For instance, the 2018 National Institute on Aging–Alzheimer’s Association Research Framework could be adopted in the design of training materials.22 23 Moreover, the prevalence of dementia and updated clinical management guidelines in China should be incorporated. Recent studies in Hong Kong have also highlighted some novel findings that could be applicable for care of dementia.24 25 26 27 28 In addition to training professionals, building an appropriately structured partnership, which takes incentives for both primary care providers and specialists, the welfare of patients and caregivers, and the cost of government and society into consideration, is also a challenge for policymakers in redesigning healthcare policy. It is also essential to enhance public awareness so that dementia patients and their caregivers are encouraged to seek help from professional care facilities for reducing their physical and mental burden.5

All authors contributed to the concept or design, acquisition of data. analysis or interpretation of data, drafting of the article, and critical revision for important intellectual content. 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.

The authors have declared no conflict of interest.

The authors are supported by the 111 Project (Grant No. B16031).

1. World Health Organization. Global Action Plan on the Public Health Response to Dementia, 2017-2025. Geneva: World Health Organization; 2017.

2. Wimo A, Guerchet M, Ali GC, et al. The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimers Dement 2017;13:1-7. Crossref

3. GBD 2016 Dementia Collaborators. Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019;18:88-106. Crossref

4. Wu YT, Ali GC, Guerchet M, et al. Prevalence of dementia in mainland China, Hong Kong and Taiwan: an updated systematic review and meta-analysis. Int J Epidemiol 2018;47:709-19. Crossref

5. Jia L, Quan M, Fu Y, et al. Dementia in China: epidemiology, clinical management, and research advances. Lancet Neurol 2019. pii: S1474-4422(19)30290-X. Crossref

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

7. 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

8. Leung KS, Yuen WF, Ngai WK, et al. How well are we managing fragility hip fractures? A narrative report on the review with the attempt to set up a Fragility Fracture Registry in Hong Kong. Hong Kong Med J 2017;23:264-71. Crossref

9. Lai CK, Igarashi A, Lau NM, Yu CT. Cancer screening for older people: to screen or not to screen. Hong Kong Med J 2017;23:503-16. Crossref

10. Lam K, Chan WS, Luk JK, Leung AY. Assessment and diagnosis of dementia: a review for primary healthcare professionals. Hong Kong Med J 2019;25:473-82. Crossref

11. Das J, Woskie L, Rajbhandari R, Abbasi K, Jha A. Rethinking assumptions about delivery of healthcare: implications for universal health coverage. BMJ 2018;361:k1716. Crossref

12. Sylvia S, Xue H, Zhou C, et al. Tuberculosis detection and the challenges of integrated care in rural China: A cross-sectional standardized patient study. PLoS Med 2017;14:e1002405. Crossref

13. Daniels B, Kwan A, Satyanarayana S, et al. Use of standardised patients to assess gender differences in quality of tuberculosis care in urban India: a two-city, cross-sectional study. Lancet Glob Health. 2019;7:e633-43. Crossref

14. Daniels B, Dolinger A, Bedoya G, et al. Use of standardised patients to assess quality of healthcare in Nairobi, Kenya: a pilot, cross-sectional study with international comparisons. BMJ Glob Health 2017;2:e000333. Crossref

15. Xue H, Hager J, An Q, et al. The quality of tuberculosis care in urban migrant clinics in China. Int J Environ Res Public Health 2018;15. pii:E2037. Crossref

16. Xue H, Shi Y, Huang L, et al. Diagnostic ability and inappropriate antibiotic prescriptions: a quasi-experimental study of primary care providers in rural China. J Antimicrob Chemother 2019;74:256-63. Crossref

17. Mohanan M, Vera-Hernández M, Das V, et al. The know-do gap in quality of health care for childhood diarrhea and pneumonia in rural India. JAMA Pediatr 2015;169:349-57. Crossref

18. Shi Y, Yi H, Zhou H, et al. The quality of primary care and correlates among grassroots providers in rural China: a cross-sectional standardised patient study. Lancet 2017;390:S16. Crossref

19. Xue H, Shi Y, Medina A. Who are rural China’s village clinicians? China Agric Econ Rev 2016;8:662-76. Crossref

20. Pink J, O’Brien J, Robinson L, Longson D; Guideline Committee. Dementia: assessment, management and support: summary of updated NICE guidance. BMJ 2018;361:k2438. Crossref

21. Gottesman RF, Albert MS, Alonso A, et al. Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort. JAMA Neurol 2017;74:1246-54. Crossref

22. Wei J, Hu Y, Zhang L, et al. Hearing impairment, mild cognitive impairment, and dementia: A meta-analysis of cohort studies. Dement Geriatr Cogn Dis Extra 2017;7:440-52. Crossref

23. Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement 2018;14:535-62. Crossref

24. 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

25. Tse MM, Kwan RY, Lau JL. Ageing in individuals with intellectual disability: issues and concerns in Hong Kong. Hong Kong Med J 2018;24:68-72. Crossref

26. Yee A, Tsui NB, Chang YN, et al. Alzheimer’s disease: insights for risk evaluation and prevention in the Chinese population and the need for a comprehensive programme in Hong Kong/China. Hong Kong Med J 2018;24:492-500. Crossref

27. Shea YF, Chu LW, Lee SC, Chan AO. The first case series of Chinese patients in Hong Kong with familial Alzheimer’s disease compared with those with biomarker-confirmed sporadic late-onset Alzheimer’s disease. Hong Kong Med J 2017;23:579-85. Crossref

28. 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

As the second leading cause of death worldwide, cancer has posed enormous burden to patients, their families, and the society as a whole. The shift from cancer treatment to prevention, with an emphasis on coordinated multisectoral actions, has become a global trend.

The Hong Kong Cancer Strategy 20191 recently released by the Hong Kong SAR Government is the first holistic plan to upscale cancer prevention and control in Hong Kong. Target outcomes of the seven aspects in the Strategy are expected to be achieved by 2025. The key strategies set for cancer prevention include reducing risk factors, providing population-based cancer screening based on evidence, seeking early detection and diagnosis, and strengthening primary healthcare services in Hong Kong. Globally, the UK has long been featured by its expanding role of primary care in cancer prevention.2 Meanwhile, primary care is also being promoted increasingly in mainland China,3 where a community-based longitudinal study is in progress. Patients’ adherence to healthy lifestyles is being followed up within the context of family doctor team–led activities to prevent long-term conditions that share common risk factors with cancer.

To date, a substantial body of research evidence in primary prevention of cancer has confirmed that modifiable lifestyles such as tobacco consumption, alcohol use, poor diet, physical inactivity, and overweight and obesity are associated with cancers, such as colorectal, lung, breast, prostate, and liver cancer, that are prevalent locally and internationally. Infections, exposure to environmental and occupational carcinogens, and exposure to radiation are also important in cancer development. Public health education and health policies that encourage healthy (or discourage unhealthy) behavioural practices can greatly benefit the prevention of cancer. Evidence from the UK suggested that approximately 4 in 10 cancer cases could be prevented through behavioural changes alone.4 5 6 Furthermore, a widespread adoption of vaccination administration approach, such as universal vaccination against hepatitis B virus that has been part of the Hong Kong Childhood Immunisation Programme for 30 years, has shown to be safe and most cost-effective in reducing the incidence of liver cancer. Most recently, eligible female primary school students of suitable ages will be provided with human papillomavirus vaccination, starting from the 2019/20 school year, as evidence supports this vaccination strategy as effective in reducing the incidence of cervical cancer.

Of equal importance is the secondary prevention of cancer that aims to detect cancer at an early stage when treatment is more effective. Cancer screening and early detection is inevitably a multi-determined field with complexity illustrated by the overriding concern on whether screening does more good than harm to individuals and to society. Recommendations and controversies on the benefits and downsides of prevention and screening strategy have been brought to the public’s attention with regard to cervical cancer,7 colorectal cancer,8 and breast cancer.9 10 11 12 At present, the cervical screening programme and the colorectal cancer screening programme are the two territory-wide strategies regularised in Hong Kong based on current evidence.1 It is recommended that Hong Kong individuals aged 50 to 75 years with average risk for colorectal cancer should consult their physicians to consider either one of the three screening modalities (faecal occult blood test, sigmoidoscopy, or colonoscopy) at different screening intervals. This is consistent with UK policy, where asymptomatic individuals who are at average risk and aged ≥50 years are provided with flexible sigmoidoscopy and faecal occult blood test.2 On certain types of cancers such as breast cancer, most criticisms of the screening are related to unfavourable cost-effectiveness, false-positive (or false-negative) results, overdiagnosis, overtreatment, complications arising from subsequent invasive procedures, and psychological distress.9 Therefore, population-based mammography screening still requires more robust evidence to ascertain the screening appropriateness for asymptotic women at average risk. For prostate cancer, recent evidence of its incidence and mortality highlights the potential influence of cancer screening and diagnostic ascertainment on geographic variations.13 A local study conducted among Chinese patients with prostate cancer14 reported that patients who presented with cancer-related symptoms had more metastatic disease and poorer prognosis than asymptomatic individuals who were diagnosed by an opportunistic case-finding preventive approach. This implied the importance of screening methodology in secondary prevention of cancer.

In this issue of the Hong Kong Medical Journal, Cheng et al15 examined incidence and types of complications and associated predictive factors for transrectal ultrasound-guided (TRUS) biopsy in diagnosing suspected prostate cancer. In their retrospective cohort study, the authors demonstrated a satisfactorily low level of overall post-biopsy complications that required subsequent visits to emergency departments or hospital admissions. Their findings support the use of TRUS biopsy as a safe procedure for diagnosing suspected prostate cancer. Although these findings from Hong Kong may not be readily generalisable to Western populations, they are compatible with guidelines released by the British Association of Urological Surgeons and the British Association of Urological Nurses that support the use of TRUS biopsy in early detection given its widespread availability, affordability, and easy-to-learn procedure.16 The UK National Institute for Health and Care Excellence recommends that physicians should explain the risks and benefits to patients with adequate time for informed consideration.17 As suggested by Cheng et al,15 more evidence generated from a multicentre study in the wider Asian population would be valuable to offer a comprehensive picture of the magnitude of the complications.

A methodological highlight of Cheng et al’s study15 is the investigation performed on the basis of a territory-wide centralised electronic patient record system in Hong Kong. In the UK, electronic clinical decision support has been in use for adult cancer. Primary care clinical computers are integrated with diagnostic software, which can automatically search the records for relevant entries with an absolute cancer risk estimated.2 As advocated in The Hong Kong Cancer Strategy 2019, the application of big data analytics should be given a priority to examine clinical information for better management of cancer patients.

Improvements in cancer detection and patient outcome, with reduced mortality, are the prime goal of cancer prevention. Emphasis on the individuals’ continuous engagement in their care should be placed across the cancer continuum with enhanced capacity and expertise support. Primary prevention remains the single most effective and efficient strategy in both clinical and community settings for many decades. Secondary prevention, despite holding the potential for reduced morbidity and mortality through concentrated efforts in screening and early detection, requires more cutting-edge science and high-quality data to ascertain the appropriateness at each risk stratum. The government should be proactive in developing structured cancer screening programmes, based on up-to-date and robust evidence confirming that the benefits outweigh risks and harms, and ensure adequate coverage for the target population. Cancer screening interventions that remain controversial should be subject to individualised consideration and undergo rigorous risk-benefit assessments before being recommended for implementation on a wider scale. Meanwhile, emphasis should be made on individual preferences and shared decision making with sufficient discussions that detail the benefits, uncertainties, and possible complications to patients, their families and carers.

The future of cancer prevention is challenging but promising. We look forward to a growing body of scientific work that can further advance the understanding of benefits and risks arising from emerging strategies and novel technologies in cancer prevention. Knowledge accumulated and transferred from evidence-based studies will ultimately help achieve the vision and mission of The Hong Kong Cancer Strategy 2019.

All authors contributed to the concept or design; acquisition of data; analysis or interpretation of data; drafting of the article; and critical revision for important intellectual content. 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.

The authors have declared no conflict of interest.

1. Hong Kong SAR Government. Hong Kong Cancer Strategy 2019 Summary Report. July 2019. Available from: https://www.fhb.gov.hk/download/press_and_publications/otherinfo/190700_hkcs/e_hkcs_summary.pdf. Accessed 14 Sep 2019.

2. Rubin G, Berendsen A, Crawford SM, et al. The expanding role of primary care in cancer control. Lancet Oncol 2015;16:1231-72. Crossref

3. Wang HH, Wang JJ, Wong SY, Wong MC, Mercer SW, Griffiths SM. The development of urban community health centres for strengthening primary care in China: a systematic literature review. Br Med Bull 2015;116:139-53. Crossref

4. Parkin DM, Boyd L, Walker LC. 16. The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Br J Cancer 2011;105 Suppl 2:S77-81. Crossref

5. Brown KF, Rumgay H, Dunlop C, et al. The fraction of cancer attributable to modifiable risk factors in England, Wales, Scotland, Northern Ireland, and the United Kingdom in 2015. Br J Cancer 2018;118:1130-41. Crossref

6. Cancer Research UK–Ludwig Cancer Research Nutrition and Cancer Prevention Collaborative Group. Current opportunities to catalyze research in nutrition and cancer prevention—an interdisciplinary perspective. BMC Med 2019;17:148. Crossref

7. Ting YH, Tse HY, Lam WC, Chan KS, Leung TY. The pattern of cervical smear abnormalities in marginalised women in Hong Kong. Hong Kong Med J 2017;23:28-34. Crossref

8. Lam TH, Wong KH, Chan KK, et al. Recommendations on prevention and screening for colorectal cancer in Hong Kong. Hong Kong Med J 2018;24:521-6. Crossref

9. Lam TH, Wong KH, Chan KK, et al. Recommendations on prevention and screening for breast cancer in Hong Kong. Hong Kong Med J 2018;24:298-306. Crossref

10. Sitt JC, Lui CY, Sinn LH, Fong JC. Understanding breast cancer screening—past, present, and future. Hong Kong Med J 2018;24:166-74. Crossref

11. Clift AK. Breast screening controversy and the ‘mammography wars’—two sides to every story. Hong Kong Med J 2018;24:320-1. Crossref

12. Lam TH. Population-based mammography screening programme should be rigorously evaluated. Hong Kong Med J 2018;24:428. Crossref

13. Wong MC, Goggins WB, Wang HH, et al. Global incidence and mortality for prostate cancer: analysis of temporal patterns and trends in 36 countries. Eur Urol 2016;70:862-74. Crossref

14. Chan SY, Ng CF, Lee KW, et al. Differences in cancer characteristics of Chinese patients with prostate cancer who present with different symptoms. Hong Kong Med J 2017;23:6-12. Crossref

15. Cheng KC, Lam WC, Chan HC, et al. Emergency attendances and hospitalisations for complications after transrectal ultrasound-guided prostate biopsies: a 5-year retrospective multicentre study. Hong Kong Med J 2019;25:349-55. Crossref

16. Greene D, Ali A, Kinsella N, Turner B. Transrectal ultrasound and prostatic biopsy: guidelines & recommendations for training. The British Association of Urological Surgeons/British Association of Urological Nurses; April 2015. Available from: https://www.baus.org.uk/professionals/baus_business/publications/76/transrectal_ultrasound_prostatic_biopsy.Accessed 14 Sep 2019.

17. NICE Guidance—Prostate cancer: diagnosis and management: NICE (2019) Prostate cancer: diagnosis and management. BJU Int 2019;124:9-26. Crossref

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

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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