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YYO OU UR R TTR RU US STTEED DS SO OU UR RC CEE O OFF P PH HA AR RM MA AC CYY IIN NFFO OR RM MAT ATIIO ON N MPS: Recognize pharmacists in transformative global health role MALAYSIA MALAYSIA •• NOVEMBER/DECEMBER NOVEMBER/DECEMBER 2020 2020 Malaysian pain undertreated compared to other countries Antibiotics may raise risk of appendicitis in children, teens BRACE CORONA advocates continuing ACEis/ARBs in mild-to-moderate COVID-19 IN COLLABORATION WITH MPS MEDICAL MEDICAL PROFESSIONAL PROFESSIONAL COPY COPY •• NOT NOT FOR FOR SALE SALE | YO U R T R U ST E D S O U R C E O F P H A R M A CY I N F O R M AT I O N CONTENTS NOVEMBER/DECEMBER ISSUE Publisher Yasunobu Sakai Country Vice President (Marketing Platform & Medcomms) Aundrey Yeoh Contributing Editors Malaysia: Saras Ramiya, Pank Jit Sin, Rachel Soon Singapore: Elvira Manzano, Roshini Claire Anthony, Pearl Toh, Audrey Abella Hong Kong: Christina Lau, Dr Joseph Delano Fule Robles Philippines: Stephen Padilla, Jairia Dela Cruz, Elaine Soliven 4 NATIONAL NEWS MPS: Recognize pharmacists in transformative global health role 5 Peripheral artery disease a disability risk for Malaysians 6 New kid on the block reduces influenza symptoms, severity 8 New endometriosis patient support website launched 9 Malaysian pain undertreated compared to other countries 10 More advocacy needed for regular BP monitoring Circulation Executive Pauline Hoe 12 FRONT PAGE BRACE CORONA advocates continuing ACEis/ARBs in mild-to-moderate COVID-19 Accounting Manager Christine Goh 6 Business Managers Kam Zhi Yan, Rathika Nagarajan, Sugalia Santhira, Xavier Wee, Krystle Lim Designer Razli Rahman Published by MIMS Medica Sdn Bhd 2nd Floor, West Wing, Quattro West, No.4, Lorong Persiaran Barat 46200 Petaling Jaya Selangor, Malaysia Email: [email protected] Tel: (603) 7623 8000 10 What ifi cofiofiavifiufi What ifi 2019 cofiofiavifiufi dififiafifi (COVID-19)? 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MIMS Pharmacist is a controlled circulation publication to pharmacists and members of allied professions in Malaysia. Editorial matter published herein has been prepared by professional editorial staff. Views expressed are not necessarily those of MIMS Medica. Although great effort has been made in compiling and checking the information given in this publication to ensure that it is accurate, the authors, the publisher and their servants or agents shall not be responsible or in any way liable for the continued currency of the information or for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise howsoever, or for any consequences arising therefrom; the publisher bears no responsibility or liability for patent ownership or patent legality of any medical product mentioned or featured, nor is it responsible for verifying the ownership or originality of the product which, therein infringes upon the intellectual property rights or other rights of any third party. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields. The information contained within should not be relied upon solely for final treatment decisions. ©2020 MIMS Medica. All rights reserved. No part of this publication may be reproduced in any language, stored in or introduced into a retrieval system, or transmitted, in any form or by any means (electronic, mechanical, photocopying, recording or otherwise), without the written consent of the copyright owner. Permission to reprint must be obtained from the publisher. Advertisements are subject to editorial acceptance and have no influence on editorial content or presentation. MIMS Medica does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature. 25 CALENDAR PP17931/12/2013(033147) ISSN 2076-5738 2 NOVEMBER/DECEMBER ISSUE MESSAGE FROM THE MIMS PHARMACIST TEAM FACING THE THIRD WAVE O Dear readers, ctober 2020 has seen the largest surge of COVID-19 cases in Malaysia so far, with over 800 new cases a day emergent throughout the country, primarily in Sabah. Healthcare workers from the Peninsula are being flown east to support their colleagues, who have been struggling with shortages in the wake of this third wave. Meanwhile, multiple districts in Selangor, Kedah, Penang, and Perak have been declared red zones. Conditional movement control orders (CMCOs) in the affected districts appear to be slowing down the rate of community infection, although once again the restrictions involved have negatively impacted many livelihoods. We appreciate that pharmacists like you continue to serve communities in this time despite the personal risks involved, and hope that once again the collective efforts of all Malaysians will help stem the tide. To keep you updated on ongoing developments in COVID-19 and other areas of research, the MIMS Pharmacist team continues to publish news and reviews both online and as a monthly digital magazine at the MIMS Specialty News – Pharmacy website. (https://specialty. mims.com/pharmacy) If you would like to receive monthly email updates whenever new MIMS Pharmacist issues are out, you can register an account for free at www.mims. com and select “Pharmacy” as your specialty of interest to do so. We also welcome your contributions in the form of news, stories and opinions at [email protected]. If you or your organization would be interested in business opportunities with MIMS Pharmacist, do contact our business team at [email protected]. Sincerely, The MIMS Pharmacist team Are you a frontliner feeling the effects of stress and burnout? Useful resources for pharmacists: Ministry of Health (MOH) Malaysia Facebook https://www.facebook.com/ kementeriankesihatanmalaysia World Health Organization COVID-19 Technical Guidance Hub https://www.who.int/emergencies/ diseases/novel-coronavirus-2019/ technical-guidance International Pharmaceutical Federation COVID-19 Information Hub https://www.fip.org/coronavirus Malaysian Pharmaceutical Society (MPS) COVID-19 Resources and Initiatives https://www.mps.org.my/newsmaster. cfm?&menuid=37&action=view& retrieveid=7819 You can dial in to a dedicated psychosocial support hotline run jointly by the MOH, Mercy Malaysia, and the Women’s Aid Organization at these numbers from 8 am to 5 pm daily: 3 • 011-6399 6482 • 011-6399 4236 • 03-2935 9935 NOVEMBER/DECEMBER ISSUE NATIONAL NEWS MPS: Recognize pharmacists in transformative global health role Rachel Soon P harmacists are key healthcare frontliners at the community level as well as part of the final line of defence against COVID-19 at hospitals, says Malaysian Pharmaceutical Society (MPS) president Amrahi Buang. “In Malaysia, the importance of pharmacists cannot be understated,” said Amrahi, in an MPS press statement marking World Pharmacists Day 2020. “Ever since the Movement Control Order (MCO) was enforced on 18 March, pharmacy services have been classified as an essential service … [since then,] pharmacists everywhere have been working hard to contain the coronavirus.” To commemorate the role of pharmacists in the COVID-19 pandemic, ‘Transforming Global Health’ was the theme selected by the International Pharmaceutical Federation (FIP) for this year’s World Pharmacists Day; the tenth annual celebration thereof. “This theme is very appropriate in the present scenario with all the challenges caused by the COVID-19 pandemic ever since it was first discovered in Wuhan, China at the end of December 2019,” said Amrahi. “Whether in the private or public sector, we have seen many innovative value-added pharmaceutical services for the rakyat.” Amrahi added that the pandemic had opened windows of opportunities for pharmacists to serve in new innovative ways, such as via digital platforms and telepharmacy, with the aid of innovative equipment and applications. He highlighted their active involvement in medical research, clinical trials, healthcare logistics, as well as the development of new, safe, and effective drugs and vaccines. “Academic pharmacists also play an important [role] in health transformation by producing quality pharmacy graduates and competent scientists [of] high calibre to fill the needs of the country and community,” said Amrahi. In an online message to the pharmacy community, FIP president Dominique Jordan said that the day was an opportunity to communicate how pharmacists are collaboratively “transforming the health in their communities through a variety of professional services such as advising on healthy living, vaccinating to prevent disease, and ensuring that medicines are used optimally.” [https://www.fip.org/news?news=newsitem&newsitem=343] We have seen many innovative valueadded pharmaceutical services for the rakyat. World Pharmacists Day is also a chance to let people know how “pharmaceutical scientists are transforming and prolonging lives by developing safe and effective medicines and vaccines, and pharmacy educators are transforming healthcare by ensuring that there are enough qualified and competent pharmacists and scientists to meet the growing needs of our societies,” Jordan added. Commenting on the FIP president’s statement, Amrahi added that pharmacists are also among the HCPs recognized as key players in achieving Sustainable Development Goals (SDGs) set by the United Nations. He emphasized the contributions of pharmacists in ensuring access to affordable and effective medications internationally, as well as expanding the use of technology as a care delivery medium. “Last but not least, to all 19,792 registered pharmacists in Malaysia, we wish all of you a happy World Pharmacists Day 2020,” said Amrahi in closing. 4 NOVEMBER/DECEMBER ISSUE NATIONAL NEWS Peripheral artery disease a disability risk for Malaysians number of lower limb amputees experience psychological adjustment problems.” “There is an urgent need to address the unmet needs and disease burden for patients suffering from PAD,” said Datuk Dr Zanariah Hussein, consultant endocrinologist at Hospital Putrajaya and Malaysian Endocrine and Metabolic Society (MEMS) president. “Early diagnosis is advisable, and this can be easily done using basic clinical examination and administered by general practitioners or nurses.” L-R: Dr Mhark Vincent Bautista, associate medical director, Bayer Malaysia; Prof Dato’ Dr Hanafiah Harunarashid; Prof Dr Wan Azman Wan Ahmad; and Datuk Dr Zanariah Hussein, during a panel discussion on peripheral artery disease in Malaysia. Rachel Soon M ore timely diagnosis and treatment for peripheral artery disease (PAD) can significantly reduce the need for late-stage amputations, say experts. According to Prof Dato’ Dr Hanafiah Harunarashid, managing director and consultant vascular surgeon, Hospital Canselor Tuanku Muhriz UKM, the increasing prevalence of PAD risk factors among Malaysians—eg, obesity, diabetes, smoking, high saturated fat intake, sedentary living, as well as ageing—could lead to increasing PAD rates among the general population. “More than 70% of the world’s new PAD cases between 2010 and 2015 came from Asia-Pacific countries,” said Hanafiah, adding that Asians seemed to be prone to PAD at a younger age, due to their artery size being narrower on average. [Lancet Glob Health 2019;7:e1020– e1030] Speaking at a recent media event in Kuala Lumpur on the development of rivaroxaban for PAD treatment, Hanafiah noted that PAD is commonly due to the development of atherosclerotic plaque in the legs, arms, neck or kidneys, causing the slow narrowing of blood flow in the area. This can eventually lead to complete blockage, resulting in critical limb ischaemia and gangrene. While lifestyle changes and pharmacological treatment can prevent or slow the onset of severe PAD by maintaining healthy arterial blood flow, many patients are initially asymptomatic, creating challenges for early intervention, said Hanafiah. He added that overlooking PAD has led to ‘avoidable problems’ in patients receiving treatment for gangrene but not for underlying PAD, often resulting in further upper limb atrophy during the patient’s recovery period. “It is not uncommon that patients with PAD need to undergo a lower limb amputation, with or without previous revascularization attempts,” said Hanafiah. “The impact of the amputation and disease goes beyond physical disability and financial burden for treatment … clinical reports have indicated that a significant 5 According to Prof Dr Wan Azman Wan Ahmad, senior consultant cardiologist at UM Specialist Centre (UMSC) and president of the National Heart Association of Malaysia (NHAM), the development of antithrombotic drugs such as rivaroxaban has improved the prognosis for patients with PAD. “Previously, our only options were anticoagulants such as warfarin which came with several logistics issues, such as a small therapeutic window, food interactions, and the need for frequent monitoring,” said Wan Azman. “Antiplatelets such as aspirin also showed only modest reductions as they did not affect fibrin production in the clotting process … however, dual-pathway inhibition with aspirin and rivaroxaban has shown effectiveness in improving PAD outcomes.” [N Engl J Med 2017;377:1319–1330; 2020;382:1994–2004] “On top of available treatments for PAD, patients are advised to adopt a healthy lifestyle and consult their HCPs for proper screening and diagnosis for prevention and early detection,” Wan Azman added. Hanafiah, Zanariah, and Wan Azman were speaking at a media event organized by Bayer Malaysia. NOVEMBER/DECEMBER ISSUE NATIONAL NEWS New kid on the block reduces influenza symptoms, severity Pank Jit Sin A new first-in-class therapeutic agent indicated for the treatment of acute, uncomplicated influenza in persons aged 12 years and above is now available in Malaysia. The new drug, baloxavir marboxil (Xofluza™, Roche), is taken as a single dose within 48 hours after the onset of influenza symptoms. When compared to placebo, baloxavir has been shown to significantly reduce the median time to alleviation of symptoms and median time to resolution of fever (p<0.001 for both). When compared to placebo and oseltamivir, baloxavir significantly reduced infectious viral load within a shorter duration. Furthermore, it has a favourable safety profile with side effects comparable to oseltamivir. [N Engl J Med 2018;379:913–923] Speaking at the virtual launch of the new drug, Dr Petrick @ Ramesh K. Periyasamy, head of infectious diseases unit, Hospital Canselor Tuanku Muhriz UKM, said one main challenge of physicians when diagnosing influenza is how it can be easily confused with other respiratory illnesses, such as the common cold, as they share similar milder symptoms such as cough, nasal discharge and sore throat. However, influenza is characterized by more severe systemic symptoms such as fever, muscle pain and general unwellness. It can cause a variety of complications ranging from sinus or ear infections to more severe complications such as pneumonia. Petrick said: “Symptoms of influenza include sudden onset of fever, cough (usually dry), headache, muscle and joint pain, sore throat and a runny nose. The symptoms usually start 24 to 48 hours L-R: Dr Petrick @ Ramesh K. Periyasamy and Dr Charles Li. after infection and lasts up to 8 days. Most adults are contagious 1 day before their symptoms start and remain contagious up to 7 days after becoming sick.” Dr Charles Li, medical and regulatory director, Roche Malaysia, said the new drug represents a new chapter in influenza treatment with it being convenient (thereby improving patient compliance) and efficacious. At the same time, Roche Malaysia has launched the ‘Axe The Flu’ campaign, targeting the public to increase awareness of influenza symptoms and severity. Li said: “Recognizing influenza symptoms early is key to effective treatment and prevention of the virus spreading. If patients see their doctors within 48 hours of symptom onset, one dose of baloxavir marboxil can significantly reduce the duration of influenza symptoms.” The treatment could be covered by medical insurance depending on the policy; patients are advised to check with their provider for confirmation of coverage. It is already available at hospitals, GP clinics and pharmacies. However, Li said patients may find it easier to access the treatment in the hospital setting for the time being. The expected price for a dose of baloxavir marboxil is around RM250. 6 About baloxavir marboxil The new therapeutic agent is a first-inclass antiviral with a novel mechanism of action. Unlike previous antiviral agents, baloxavir marboxil inhibits a subunit of viral polymerase and stops viral replication early in the disease cycle. This mechanism works on both A and B strains of influenza. The evidence for baloxavir marboxil came from the CAPSTONE-1* trial, a phase III multicentre, randomized, placebo-controlled study which looked at 1,436 participants aged 12 to 64 years who were diagnosed with symptomatic, uncomplicated influenza. Participants were randomly assigned to receive a single oral administration of 40 mg or 80 mg (40 mg if they weighed less than 80 kg and 80 mg if more than 80 kg) of baloxavir marboxil; placebo or 75 mg of oseltamivir twice daily for 5 days. Baloxavir marboxil met its primary endpoint of significantly reduced duration of influenza symptoms compared to placebo. It further demonstrated similar efficacy to oseltamivir in symptom duration and adverse events. * CAPSTONE-1: A Study of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir in Otherwise Healthy Patients With Influenza NOVEMBER/DECEMBER ISSUE INTRODUCING A NEW ONLINE MODULE ON GERD Stay safe and keep earning your CPD points online W NE Earn Your CPD Points Here Improving Blood Pressure Control with Combination Therapy Evidence shows that combination therapy is more effective at lowering blood pressure (BP) compared with increasing the dose of monotherapy. Single-pill fixed dose combinations provide better BP control by simplifying patients’ drug regimen, thereby improving treatment adherence. This module aims to educate healthcare providers on the use of combination therapy towards achieving BP goals in patients currently taking antihypertensive medication. MPS code: 0569 n to access S ca GERD is a condition wherein stomach acid rises and enters the oesophagus, often resulting in either manageable symptoms or long-term complications if left untreated. Epidemiological studies in Asia have shown an increasing prevalence of symptom-based GERD year after year. This module aims to educate healthcare providers on the use of proton pump inhibitors (PPIs) as an effective treatment in suppressing gastric acid secretion in patients with GERD. Compared to other methods of treatment, PPIs exhibit faster onset of action with tolerable safety profiles. n to access S ca Gastric acid control: The role of proton pump inhibitors in the treatment of gastroesophageal reflux disease (GERD) MPS code: 0136 an to registe Sc r The global prevalence of Alzheimer’s disease (AD) and its treatment costs are projected to increase tremendously, thus placing increasing pressure on developing countries’ healthcare systems. Pharmacists are well-positioned to assist clinicians in the provision of various care services to individuals living with AD. This module aims to provide an overview of the epidemiology and burden of disease, as well as the risk factors and prevention strategies for AD. In addition, it also discusses the role of pharmacists in AD management, while simultaneously reviewing current approaches to AD management. MY-CPD-140_MP_NOV2020 n to access S ca Alzheimer’s disease: Pharmacists’ role in the era of expanding scopes of practice MPS code: 0206 Start earning CPD points at Log in to register now www.mims-cpd.com.my www.mims-cpd.com.my For your convenience, you can monitor your CPD points earned via the website at anytime. Your personal My CPD Log can be printed or emailed. Enquiries: MIMS Medica Sdn Bhd (891450-U) 2nd Floor, West Wing, Quattro West No. 4, Lorong Persiaran Barat 46200 Petaling Jaya, Selangor, Malaysia. Tel: +603 7623 8000 Fax: +603 7623 8188 Email: [email protected] Website: www.mims.com NATIONAL NEWS New endometriosis patient support website launched Rachel Soon A new patient-centred website for Malaysians with endometriosis has been launched by the Endometriosis Association of Malaysia (MyEndosis). Developed with the support of Bayer Co. (Malaysia) Sdn Bhd, the website (http://myendosis.org) provides information on disease symptoms, diagnosis, and treatment options, as well as patient testimonials and connection to peer support. “A lack of awareness of endometriosis and social taboos surrounding the disease are common factors associated with the delay in seeking treatment,” said MyEndosis founder and president Surita Mogan. “Many women live in silence and pain because they don’t know what is normal and what isn’t when it comes to menstrual health.” Speaking at its official launch, Surita said that the website was the first to be managed purely by patients and caregivers. Currently accessible in Bahasa Malaysia and English, the association aims to add Chinese and Vietnamese translations of site content in future. Imelda. “Although symptoms may vary in type and severity, the pain can be both physically and mentally exhausting, leaving patients feeling helpless and overwhelmed.” “The website will also be a catalyst for us to launch our MyEndosis National Survey in October 2020,” said Surita. “This survey will give us statistics from all states in Malaysia in order for us to push for acknowledgement from government ministries and agencies so we have a better healthcare plan to help patients financially and emotionally.” While there are no official statistics or large-scale studies on prevalence or the delays in diagnosis experienced in Malaysia, at least 2,500 individuals have joined MyEndosis’ Facebook support group since its inception in March 2014. Through a preliminary study of 30 women conducted in August 2020, MyEndosis also reported that a third of respondents endured symptoms for over 9 years before seeking treatment. Breaking the silence At the same event, consultant obstetrician and gynaecologist Dr Imelda Balchin highlighted that it can take up to 11 years for patients with pelvic pain to receive an endometriosis diagnosis. [Am J Obstet Gynecol 2019;220(4):354.e1–354.e12] “Endometriosis affects one-in-ten women during their reproductive years, yet not many are aware of what [it] entails and how it can be managed,” said Closing the treatment gap When asked about how GPs could support patients, consultant obstetrician and gynaecologist Dr Patricia Lim Su-Lyn said that it was important to listen to their history, particularly descriptions of debilitating period symptoms, and focus on their impact on quality of life. “Even if [gynaecologists] do not find any signs of endometriosis on ultrasound [scan] or raised CA-125* levels [in the patient], we may still empirically opt to treat the patient’s case as endometriosis to see if they benefit from any treatment,” said Lim. She added that GPs with the means to do so could conduct ultrasound scans to detect ovarian cysts or blood tests to check the patient’s CA125 levels. On the same topic, Imelda emphasized the use of accessible language and local culture in conversations about the disease, noting that while scientific terms such as ‘endometriosis’ itself could be obtuse for most people, colloquial names such as ‘senggugut’ were often more quickly understood by patients and their families. L-R: Dr Patricia Lim Su-Lyn, Dr Imelda Balchin and Surita Mogan, at the official launch of the MyEndosis website. * 8 CA-125: Cancer Antigen 125 NOVEMBER/DECEMBER ISSUE NATIONAL NEWS Malaysian pain undertreated compared to other countries Rachel Soon M any Malaysians choose to delay seeking treatment for pain and are less likely to do so than residents of other countries, according to a recent international consumer study. In a report from the Global Pain Index (GPI) 2020 study, over 85% of Malaysian respondents said they had experienced some form of pain in the last year, with the top five most common being headache (89%), tension headache (80%), muscle ache (77%), period pain (71%), and joint pain (70%). However, only 38% of respondents said they chose to seek treatment immediately for pain, with 56% preferring to wait hours (38%) or days to weeks (18%) before treating it. Six percent said they never treated their pain. Malaysian respondents were also less likely to medicate for pain compared to the global average in the study, with only 48% of respondents reported taking pain medication (vs 65% globally). In contrast, 74% reported preferring to rest or sleep to deal with pain issues. Thirty-one percent of Malaysian respondents said they avoided taking pain medication in general, with the commonest reasons cited including possible dependency (29%) and adverse effects (25%). The GPI 2020 study was conducted by Edelman Intelligence UK and commissioned by GlaxoSmithKline (GSK) Consumer Healthcare, with its results being announced at a virtual press event in September. Consisting of a 25-minute online survey, the study examined 19 countries with a representative sample of 1,000 respondents (across age, gender, and region) interviewed from each country. Improving health literacy around pain Speaking at the press event, Dr Gopinathan Raju, consultant anaesthetist and pain management specialist, noted that it was important for healthcare professionals to help educate patients and dispel myths regarding common overthe-counter pharmacological treatments for pain, such as those surrounding tolerance, adverse effects, drug-drug interactions, and special demographic groups. “Research has shown that long periods of unrelieved pain can lead to adverse psychological and physical complications,” added Shawn Roy, GSK Consumer Insight Lead, South East Asia and Taiwan. “In fact, the GPI 2020 showed 67% of Malaysians believed that pain decreases their quality of life.” Roy highlighted that delayed or untreated pain had negative impacts not only on individuals, but on broader socioeconomic areas. He noted that the Malaysian Employers Federation (MEF) Man-Days Lost and Absenteeism Survey 2019 estimated productivity losses of over 10.7 million man-days due to sick leave taken by workers between June 2018 and May 2019. [https://www. nst.com.my/news/nation/2019/11/ 542802/mef-107-million-man-days-lostsick-leave] According to Bryan Wong, general manager, GSK Consumer Healthcare Malaysia, the GPI 2020 results also showed a low level of health literacy among respondents comparable with the findings of the 2019 National Health and Morbidity Survey (NHMS 2019), which reported low health literacy among 35.1% of adults aged 18 years and above. “Given the data … it is very important to provide accessible and easy-to-digest health information with verified sources on the right channels to empower and improve the community’s health literacy,” said Wong. At the same event, GSK Consumer Healthcare Malaysia announced a collaboration with Watsons Malaysia on a health literacy campaign called ‘Know Your Medicine, Find the Right Relief’ to be conducted on social media, digital and broadcast platforms, and physical stores nationally. According to GSK representatives, it aims “to educate and increase Malaysians’ access to medicine knowledge which will help in [the] pain management journey and enable enhancement of the quality of life of the overall population.” 9 NOVEMBER/DECEMBER ISSUE NATIONAL NEWS More advocacy needed for regular BP monitoring Rachel Soon W ith rising rates of hypertension among younger populations, regular blood pressure (BP) monitoring should be encouraged in adults 18 years and older, says an expert. According to Dr Mohd Arifin Mohd Ali, president of the Malaysian Society of Hypertension (MSH), a lack of awareness on one’s BP status as well as the potential complications of uncontrolled hypertension could contribute to increased rates of stroke, heart attack, and kidney disease, particularly in those with a family history of hypertension. A recent consumer survey conducted by OMRON Healthcare found that 42% of 504 respondents felt that their BP was not serious or in need of regular monitoring, while 34% felt that checking their BP whenever they visited their doctor was sufficient. However, at least 85% had checked their BP at least once in the preceding year. In addition, the latest National Health and Morbidity Survey (NHMS) 2019 reported a 30.0% overall hypertension rate among Malaysian adults 18 years and older; a prevalence comparable to those reported in the NHMS 2015 (30.3%) and 2011 (32.6%). Of the 30.0%, 15.9% had known hypertension, while the remaining 14.1% had elevated BP not yet diagnosed as hypertension. being a contributing factor to hypertension. Previous NHMS data has tracked a concerning rise in the proportion of Malaysians considered obese, ranging from a mere 4.4% in 1996 to 14.0% in 2006, 17.7% in 2015, and 19.7% as of 2019. ... a lack of awareness on one’s BP status as well as the potential complications of uncontrolled hypertension could contribute to increased rates of stroke, heart attack, and kidney disease. Asked about the role of community healthcare workers (HCWs) such as general practitioners (GPs) and pharmacists in tackling hypertension—particularly patients with unknown hypertension— Arifin stressed public awareness first and foremost, pointing to the MSH’s efforts in providing up-to-date training on the topic for HCWs as well as in public forums. “This is where the media, GPs, and pharmacists must also be updated to current levels of knowledge about hypertension; they have a role to play in educating and explaining [the same] to their patients,” said Arifin. “Knowledge about obesity and weight control, fattening foods, control of blood sugar, diet, reducing salt intake, need for exercise and so on—must all be part of [this]. He added that in his own practice, he advised patients to be compliant and to ‘know their numbers’ (BP readings). He also advocated for the use of home BP monitoring devices by patients, with regular clinical follow-ups at 3-to-4 month intervals. As a public service to help identify those with at increased risk of developing hypertension, OMRON Healthcare has announced the release of an online self-checklist (https://hypertensionrisk. questionpro.com/) developed in collaboration with MSH to encourage the public to monitor their BP as well as seek medical advice on prevention and treatment of hypertension. “In my opinion, … we may consider [the NHMS 2019 findings] to be rather good as the [prevalence] rate has not increased, though the total [of people with hypertension] has increased,” said Arifin. However, he added that the growing prevalence of obesity among adults 18 years and above as reported in the NHMS was also concerning due to it 10 NOVEMBER/DECEMBER ISSUE KEEP UP WITH YOUR MEDICAL EDUCATION NEEDS Complete these online modules successfully and earn a total of 3 CPD points Earn Your CPD Points Here The prevalence of allergic rhinitis (AR) is on the rise; it affects approximately 40% of the population globally, with the highest rates observed in the Asia Pacific region. This module focuses on current practices in AR management among primary care practitioners and their familiarity with current guidelines. Additionally, it also explores the patient perspective of AR management. The Allergic Rhinitis Boot Camp | Part 2 Using patient profiles to guide antihistamine choice: An expert consensus an to registe Sc r Antihistamines are the mainstay of treatment for allergic rhinitis (AR), particularly in the primary care setting. However, selecting appropriate antihistamines may be a challenge owing to the wide range of antihistamines available. This module highlights the use of patient profiles to guide the choice of antihistamines in primary care based on expert consensus and recommendations. MY-CPD-143_MP_DEC2020 n to access S ca The Allergic Rhinitis Boot Camp | Part 1 Allergic rhinitis management and patient journey: Understanding the disease and current guidelines MPS code: 0181 MPS code: 0369 n to access S ca Hypertension (HTN) remains a challenging medical problem, affecting over 1 billion individuals worldwide. HTN is often called the “silent killer” because it typically has no symptoms. Suboptimal BP control puts a tremendous burden on the health and welfare of individuals and the population. This online CPD video provides an update on the evidence for managing HTN, while simultaneously highlighting the role of single-pill fixed-dose combination in promoting adherence to HTN treatment. n to access S ca Hypertension: Understanding the silent killer MPS code: 0436 Start earning CPD points at Log in to register now www.mims-cpd.com.my www.mims-cpd.com.my For your convenience, you can monitor your CPD points earned via the website at anytime. Your personal My CPD Log can be printed or emailed. Enquiries: MIMS Medica Sdn Bhd (891450-U) 2nd Floor, West Wing, Quattro West No. 4, Lorong Persiaran Barat 46200 Petaling Jaya, Selangor, Malaysia. Tel: +603 7623 8000 Fax: +603 7623 8188 Email: [email protected] Website: www.mims.com FRONT PAGE BRACE CORONA advocates continuing ACEis/ARBs in mild-to-moderate COVID-19 Roshini Claire Anthony P atients hospitalized with mild-to-moderate COVID-19 who are on angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for hypertension should continue these medications, according to primary results of the BRACE CORONA trial presented at ESC 2020. “In patients hospitalized with COVID-19, suspending ACE inhibitor/ ARB therapy for 30 days did not impact the number of days alive and out of hospital,” presented principal investigator Professor Renato Lopes from the Duke Clinical Research Institute, Durham, North Carolina, US. “Because these data indicate that there is no clinical benefit from routinely suspending these medications in hos- pitalized patients with mild-to-moderate COVID-19, they should be generally continued for those with an indication,” said Lopes. Participants in this multicentre, phase IV Brazil-based trial were 659 adults (mean age 55.7 years, 40.4% female, mean BMI 31.0 kg/m2) hospitalized with a confirmed diagnosis of COVID-19 and who were chronic users of ACE inhibitors/ARBs. They were randomized to either temporarily suspend their use of ACE inhibitors/ARBs for 30 days (n=334) or continue with their medications (n=325). Patients hospitalized for decompensated heart failure in the past year, those on sacubitril/valsartan or >3 antihypertensive medications, and those with haemodynamic instability in the first 24 hours until confirmation of COVID-19 diagnosis were excluded. 12 NOVEMBER/DECEMBER ISSUE FRONT PAGE About half the patient population was obese (52.2%) and 31.9% had diabetes, while few patients had heart failure or kidney disease (1.4% each). At hospital admission, patients were primarily on ARBs (83.3%) and 16.7% were on ACE inhibitors. Patients had a median 5-year duration of use of these drugs. Other medications included beta blockers (14.6%), calcium channel blockers (18.2%), and diuretics (31.1%). The most common presenting symptoms of COVID-19 were cough (70.3%), fever (69.5%), and dyspnoea (53.7%), with patients experiencing symptoms a median 6 days prior to admission. In the first 24 hours of admission, most patients had either mild (57.1%) or moderate (42.9%) COVID-19, with no incidence of severe COVID-19 (due to exclusion criteria). At 30 days, number of days alive and out of hospital was comparable between patients who suspended and continued ACE inhibitors/ARBs (mean 21.9 vs 22.9 days; mean difference -1.1 days; mean ratio, 0.95; p=0.09). [ESC 2020, Hot Line session] A similar proportion of patients who suspended or continued ACE inhibitors/ ARBs were alive and out of hospital at day 30 (91.8% vs 95.0%). The median number of days alive and out of hospital at 30 days was 25 days in both groups. Gianfranco Parati from the University of Milan-Bicocca and San Luca Hospital, Milan, Italy. [https://www.youtube.com/ watch?v=NqtjzX7iWZs, accessed 3 September 2020] “There has been conflicting observational evidence about the potential impact of ACE inhibitors/ARBs on patients with COVID-19,” noted Lopes. There has been conflicting observational evidence about the potential impact of ACE inhibitors/ARBs on patients with COVID-19. “On one hand, renin-angiotensin-aldosterone system (RAAS) inhibition is harmful. ACE inhibitors and ARBs could increase ACE-2 receptor expression and thus, enhance viral entry and binding leading to outcomes in patients with COVID-19,” said Lopes. [https://www. youtube.com/watch?v=z9GxFTBFdPQ, accessed 3 September 2020] “On the other hand, preliminary data hypothesize that RAAS inhibitors could benefit patients with COVID-19 by decreasing acute lung damage and preventing angiotensin-II-mediated pulmonary inflammation,” he said. “This is the first randomized data assessing the role of continuing vs stopping ACE inhibitors and ARBs in patients with COVID-19. Our findings constitute contemporary and high-quality randomized evidence to guide the care of patients with COVID-19,” Lopes said. Not the whole story Despite the positive results, issues remain, and analysing them may help clarify some of the findings, Parati pointed out. The trial included a relatively young population of patients with mild or moderate COVID-19. “By selecting [patients with] relatively mild or moderate [COVID-19], with such a low mortality rate, in my opinion, the [researchers] could not really solve the issue,” he said. There might also be differences in the outcomes between ACE inhibitors and ARBs. While the results are important because they were obtained from a randomized trial, they might “not be telling us the last words.” “It might be nice to consider the interaction between age, comorbidities, and these treatments. That might tell us more,” concluded Parati. There were nine deaths in each group during the trial. All-cause mortality at 30 days did not significantly differ between patients who suspended or continued their ACE inhibitors/ARBs (2.7% vs 2.8%; hazard ratio, 0.97, 95% confidence interval, 0.38–2.52; p=0.95). Implications of BRACE CORONA “COVID-19 has really changed our lives … and one of the issues raised is what to do with ARBs and ACE inhibitors because most patients are taking these [medications] because of cardiovascular disease,” said discussant Professor 13 NOVEMBER/DECEMBER ISSUE FROM ABROAD [COVID-19 UPDATES] Remdesivir improves recovery, reduces mortality of COVID-19 patients symptom duration, or disease severity. “However, among patients whose symptoms worsen and who require mechanical ventilation or ECMO on day 5 of the remdesivir course, continuing treatment through 10 days may be beneficial versus discontinuing it on day 5,” the researchers noted. For those with moderate COVID-19, a 5-day course compared with standard of care was associated with small reductions in mortality and serious AEs and a greater number of patients having clinical improvement at day 11. Notably, a 10-day course was not more effective than 5 days or standard of care. [JAMA 2020;324:1048–1057] Stephen Padilla A systematic review of randomized controlled trials (RCTs) has confirmed the potential of remdesivir in improving recovery and reducing serious adverse events (AEs), as well as mortality and time to clinical improvement, but not hospital length of stay, in coronavirus disease (COVID-19) patients. “For adults not receiving mechanical ventilation or extracorporeal membrane oxygenation (ECMO), a 5-day course of remdesivir may provide similar benefits to and fewer harms than a 10-day course,” the researchers said. English-language RCTs of remdesivir treatments for adults with suspected or confirmed COVID-19 were searched from several databases, tables of contents of journals, and US Food and Drug Administration and company websites from 1 January through 31 August 2020. A single reviewer abstracted data and assessed risk of bias, which were verified by a second reviewer. Certain- ty of evidence was evaluated using Grading of Recommendations Assessments, Development and Evaluation (GRADE) methods. Four RCTs met the eligibility criteria. Compared with placebo, remdesivir significantly improved recovery in adults with severe COVID-19 (absolute risk difference [ARD] range, 7–10%) and was associated with a small reduction in mortality (ARD range, –4% to 1%) and a shorter time to recovery or clinical improvement. [Ann Intern Med 2020;doi:10.7326/M20-5752] Remdesivir, however, showed little to no effect on hospital length of stay. The antiviral agent also reduced serious AEs by a moderate amount (ARD range,–6% to –8%). Among hospitalized patients not requiring mechanical ventilation, a 5-day remdesivir course, compared with a 10day course, reduced mortality, increased recovery or clinical improvement by small to moderate amounts, shortened time to recovery, and lessened serious AEs. Recovery did not vary by age, sex, 14 “Our findings are generally in line with prior reviews, although none included the trial of remdesivir in patients with moderate COVID-19, and outcomes reported in prior reviews were limited,” the researchers said. [J Med Virol 2020;doi:10.1002/jmv. 26443; Eur J Clin Invest 2020:e13383; Virus Res 2020;288:198137; BMJ 2020; 370:m2980; www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management] “Our living review uses methods specifically derived for continual updating and is intended, in part, to inform the work of the American College of Physicians Scientific Medical Policy Committee,” they added. This systematic review was limited by low-certainty evidence with few published trials, including one preliminary report and two open-label trials. Trials also excluded pregnant women and adults with severe kidney or liver disease. “New evidence will be incorporated using living review methods and may alter these conclusions,” the researchers said. NOVEMBER/DECEMBER ISSUE FROM ABROAD [COVID-19 UPDATES] Sofosbuvir-daclatasvir: a role in COVID-19 management? Roshini Claire Anthony A small study conducted in Iran suggests a role for sofosbuvir-daclatasvir in the treatment of moderate-to-severe COVID-19. This open-label trial included 66 adult patients with moderate or severe COVID-19 who were admitted at one of four hospitals in Tehran, Iran. They were randomized 1:1 to receive the standardof-care (SoC)* regimen of hydroxychloroquine (200 mg twice/day) ± lopinavir/ ritonavir (250 mg twice/day) with or without a once-daily regimen of sofosbuvir (400 mg) plus daclatasvir (60 mg) for 14 days. Patient characteristics were as follows: sofosbuvir-daclatasvir group: median age 58 years, 61% male; SoC-only group: median age 62 years, 42% male. Fifty-two and 33% of patients in the sofosbuvir-daclatasvir and SoC groups, respectively, had diabetes, 36% and 33%, respectively, had hypertension, and 23% and 33%, respectively, were obese. A greater proportion of sofosbuvir-daclatasvir compared with SoC-only recipients achieved clinical recovery** within 14 days of treatment, though this was not significant (88% vs 67%; p=0.076). Time to clinical recovery was significantly shorter in the sofosbuvir-daclatasvir compared with the SoC-only group (median 6 vs 11 days; p=0.041). Duration of hospitalization was significantly shorter among patients who received sofosbuvir-daclatasvir compared with SoC only (mean 6 vs 8 days; p=0.029). The need for mechanical ventilation did not significantly differ between the sofosbuvir-daclatasvir and SoC-only groups (9% vs 21%; p=0.303). More patients in the SoC-only than sofosbuvir-daclatasvir group received lopinavir/ritonavir (64% vs 33%; p=0.026). “However, the outcomes in the treatment group were balanced across lopinavir/ritonavir administration,” said Hannah Wentzel, a public health student at Imperial College London, UK, who presented the results at the COVID-19 conference organized by the International AIDS Society. In addition, corticosteroid administration (36% and 24% of sofosbuvir-daclatasvir and SoC-only recipients, respectively) did not predict clinical recovery outcomes, she said. No adverse events were reported. There were three deaths in the sofos- buvir-daclatasvir group and five in the SoC-only group. The researchers also conducted a meta-analysis combining this trial and two others in Abadan and Sari, Iran, with a total of 176 patients. The trial in Abadan was not randomized and consecutive patients received hydroxychloroquine with either sofosbuvir-daclatasvir or lopinavir/ritonavir plus ribavirin***. In the Sari study, patients received either sofosbuvir-daclatasvir plus ribavirin or hydroxychloroquine ± lopinavir/ritonavir. In the pooled analysis, median age of patients was 57 and 61 years in the sofosbuvir-daclatasvir and control arms, respectively, and 52% and 42%, respectively, were male. Time to discharge from hospital was improved in the sofosbuvir-daclatasvir compared with the control arm (subhazard ratio, 2.03; p<0.001). Meta-analysis showed a reduction in mortality risk with sofosbuvir-daclatasvir vs SoC. “Other viral families share similar replication mechanisms to SARS-CoV-2. Therefore, existing nucleotide and nucleoside analogues are being investigated as potential COVID-19 therapies,” said Wentzel. “Sofosbuvir-daclatasvir is associated with faster discharge from hospital and improved survival in this combined analysis of three trials,” she added. However, limitations include the small sample size and lack of viral load data. The results will be confirmed in the larger, double-blind, placebo-controlled, randomized DISCOVER trial, results of which are anticipated in September, she said. * ** SoC at time of trial normalization of fever (<37.2°C [oral]), respiratory rate ≤24 per minute on room air, oxygen saturation ≥94% on room air for ≥24 hours *** change in SoC following change in national treatment guidelines 15 NOVEMBER/DECEMBER ISSUE FROM ABROAD [COVID-19 UPDATES] Corticosteroids do not avert mortality in severe, critical COVID-19 patients Stephen Padilla U se of systemic corticosteroids does not reduce in-hospital mortality for patients with severe or critical coronavirus disease (COVID-19), in stark contrast to observations from the RECOVERY clinical trial, according to a study in Wuhan, China. “Absence of the beneficial effect in our study in contrast to that was observed in the clinical trial may be due to biases in observational data, in particular confounding by indication bias, differences in clinical characteristics of patients, choice of corticosteroid used, or timing of initiation of treatment and duration of treatment,” the researchers said. A total of 1,514 severe and 249 critical hospitalized COVID-19 patients from two medical centres in Wuhan were included in this study. The researchers assessed the association of corticosteroid use with the risk of in-hospital mortality in severe and critical cases using multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (inverse-probability-of-treatment-weighting [IPTW] and propensity score matching [PSM]). Among hospitalized patients, 531 (35.1%) with severe and 159 (63.9%) with critical COVID-19 received corticosteroids. Compared to nonuse, use of systemic corticosteroid was not associated with reductions in in-hospital mortality in either severe (hazard ratio [HR], 1.77, 95% confidence interval [CI], 1.08–2.89; p=0.023) or critical cases (HR, 2.07, 95% CI, 1.08–3.98; p=0.028). [J Clin Endocrinol Metab 2020;105:dgaa627] Time-varying Cox analysis showed similar results. Furthermore, corticosteroid use in patients with severe COVID-19 at admission resulted in neither improved nor harmful outcome in either PSM or IPTW analysis. Findings for critical patients at admission were consistent in multivariable Cox model analysis. Several reasons explain why these results conflict with those from the RECOVERY trial, according to the researchers. First, the baseline conditions of patients were different between treated and untreated cases due to the retrospective and nonrandomized nature of the current study. Second, prednisone was used by most patients in this study as opposed to dexamethasone. Although both agents are glucocorticoids, dexamethasone is four to five times more potent than prednisone and >20 times more potent than naturally occurring hormone cortisol. [N Engl J Med 2005;353:1711–1723] Finally, durations and doses of corticosteroid therapy were different between the two studies. In the current analysis, dexamethasone 7.5 mg was initiated at the onset of severe illness for a median of 5 days. In the RECOVERY trial, dexamethasone 6 mg was administered for 7 days. “The rationale for corticosteroid use includes its potential role in suppressing inflammatory storm, reducing inflammatory exudation, and preventing multiple 16 organ injuries in acute respiratory failure,” the researchers said. “However, its multifaceted negative impacts on prognosis should not be overlooked.” In other recent studies, the viral load of SARS-CoV-2, the causative agent of COVID-19, significantly exacerbated the severity of the disease. Corticosteroids may suppress immunity and promote virus replication, further worsening prognosis. [Sci China Life Sci 2020;63:364374; BMJ 2014;348:g1721] “Our results showed that median lymphocyte count remained low during the use of systemic corticosteroids, which might lead to a higher risk of superinfections,” the researchers said. “Systemic corticosteroids could also induce hyperglycaemia, which was shown to be an independent risk factor for the prognosis of infection and critically ill patients.” [J Clin Endocrinol Metab 2015;100:4490–4497; Crit Care Med 2020;48:e115–e122; Diabetes Metab J 2013;37:385–390] Use of corticosteroids was also associated with complications in the elderly population. In the present cohort, the median age of severe and critical COVID-19 patients was 61.0 and 68.0 years, respectively. [Gastroenterology 2014;147:784–792.e9; Ann Intern Med 2004;141:764–770] NOVEMBER/DECEMBER ISSUE EMPOWERING HEALTHCARE COMMUNITIES FROM ABROAD [COVID-19 UPDATES] COVID-19 in hospitals: Toilets, staff, public areas show contamination Pearl Toh W ith much remains controversial regarding the possible transmission route of the SARS-CoV-2 virus, a study reveals yet another surprise worthy of caution in the hospital setting. The review presented during the ESCMID* Conference on Coronavirus Disease (ECCVID) showed high level of viral load in the air surrounding COVID-19 patients, toilets, as well as staff and public areas in hospitals. [ECCVID 2020, abstract 00757] Based on 17 papers included in the review, more than a quarter (27.5%) of the air sampled from enclosed hospital environment around COVID-19 patients tested positive for SARS-CoV-2 RNA, regardless of whether it was in the intense care unit (ICU; 27/97, 27.8%) or non-ICU settings (41/150, 27.3%). Of the 67 air samples collected less than 1 metre away from the patient, only one (1.5%) turned out positive SARSCoV-2. For air sampled at a distance of 1–5 metres away from the cases, 6% (4/67) were positive for SARS-CoV-2. This implies few infectivity of the air surrounding patients with COVID-19, according to Dr Gabriel Birgand, University Hospital Centre Nantes, France. However, in other areas within the hospitals such as patient toilets, the rate of positivity for SARS-CoV-2 was 23.8% of the 21 toilets tested, and hit as high as 34.1% (14/41) in public areas in hospital settings. Of note, the median SARS-CoV-2 RNA concentration in patient toilets was 10 times higher than the samples collected from the patients’ rooms. For staff areas and clinical sites, SARS-CoV-2 contamination was found in 15 of 121 samples (12.4%) and 20 of 221 samples (9.5%), respectively. As detection of SARS-CoV-2 RNA does not necessarily mean the virus is viable, the researchers also compared results of viral cultures from these areas. Among the 78 viral cultures performed, three showed viable SARSCoV-2 virus (4%)—with all of these sourced from enclosed patient environments in non-ICU settings (3/39, 7.7%). “In hospital, the air near COVID-19 patients is frequently contaminated with SARS-CoV-2 RNA, with however, poor proof of its infectivity—meaning we detected the viral RNA, but when trying to culture these samples, there was little evidence of viable virus,” pointed out Birgand. “High viral loads found in toilet/bathrooms, staff and public hallways means these areas require strong compliance with cleaning measures and personal protective equipment [PPE],” he added. As Birgand explained, these findings support the current recommendations 18 for PPE—that surgical facemask is efficient for preventing transmission from patient to healthcare workers in most settings, except in aerosol generating procedures whereby protection class respirators FFP2 are required. For the review study, Birgand and team identified 2,034 published literature on air contamination by COVID-19 in the hospital settings—of which, 17 met the eligibility criteria for inclusion. The contamination rate indicated by SARSCoV-2 viral RNA was compared across different hospital settings, clinical context, distance from patient, and air ventilation system. The study also corroborates what was observed previously in environmental sampling from three hospital rooms of COVID-19 patients in National Centre for Infectious Diseases, Singapore, which showed contamination in toilet bowls and air exhaust outlets. Samples taken after disinfection measures turned out negative, which highlights the importance of routine cleaning. [JAMA 2020;323:1610–1612] * ESCMID: European Society of Clinical Microbiology and Infectious Diseases NOVEMBER/DECEMBER ISSUE FROM ABROAD [COVID-19 UPDATES] Viral shedding from asymptomatic COVID-19 patients may be prolonged Pearl Toh N ot only do asymptomatic COVID-19 carriers have viral loads that are similar to symptomatic patients, they could remain asymptomatic for a prolonged period of median 24 days from diagnosis, reveals a study. Hence, viral shedding could also be prolonged in asymptomatic people— sparking concerns on potential transmissibility of asymptomatic infections. Among 303 patients (median age 25 years, 66.3% women) who tested positive for SARS-CoV-2 by RTPCR, about one-third (36.3%) were asymptomatic at diagnosis. [JAMA Intern Med 2020;doi:10.1001/jamainternmed.2020.3862] Of note, 84.6% of the asymptomatic patients remained so for a median of 24 days from diagnosis. Despite being asymptomatic, these patients carried similar viral loads as those who were symptomatic, as indicated by Ct values of RT-PCR tests. respectively, showed negative conversion at day 14. The corresponding negative conversion rates at day 21 were 75.2% and 69.9%, respectively. However, viral loads of asymptomatic patients tended to decline more slowly than symptomatic patients, with respect to the envelope (env) gene of SARSCoV-2 detected from lower respiratory tract specimens (β=−0.065; p=0.005 for time interaction). “It is important to note that detection of viral RNA does not equate infectious virus being present and transmissible,” cautioned the researchers. Meanwhile, the drop in other genetic segments encoding for viral nucleocapsid protein and RNA-dependent RNA polymerase were not significantly different between asymptomatic and symptomatic patients. The median time to negative conversion among asymptomatic patients was 17 days compared with 19.5 days in symptomatic patients (p=0.07). At 14 days, 33.7% and 29.6% of asymptomatic and symptomatic patients, Viral loads of asymptomatic patients tended to decline more slowly than symptomatic patients. Even so, the results do not support the notion that infected individuals without symptoms are less likely to spread or be cleared of the virus sooner than symptomatic patients. “An important implication of our findings is that there may be substantial under-reporting of infected patients using the current symptom-based surveillance and screening,” the researchers highlighted. “Many individuals with SARS-CoV-2 infection remained asymptomatic for a prolonged period ... [and thus,] viral molecular shedding was prolonged,” they noted. “Because transmission by asymptomatic patients with SARSCoV-2 may be a key factor in community spread, population-based surveillance and isolation of asymptomatic patients may be required.” As the study cohort involved young, healthy patients, the researchers said the findings should not be generalized to the whole population at large. Another limitation was that the role of molecular viral shedding in transmission from asymptomatic patients is also unknown. 19 NOVEMBER/DECEMBER ISSUE FROM ABROAD Pharmacist-led audit/feedback intervention improves medication safety Stephen Padilla T he pharmacist-led Safety Medication dASHboard (SMASH) intervention has resulted in reduced rates of potentially hazardous prescribing and inadequate blood-test monitoring in general practices during the first 24 weeks after initiation, a study has shown. The reduction is sustained at 12 months for prescribing but not for monitoring. “There were substantial differences in rates of potentially hazardous prescribing between practices prior to the intervention, and there was a marked reduction in the variation between practices over the 12-month follow-up period,” the researchers said. SMASH was implemented in 43 general practices covering a population of 235,595 people in Salford, UK, and included the following components: training of clinical pharmacists to deliver the intervention; a web-based dashboard providing actionable, patient-level feedback; and pharmacists reviewing individual at-risk patients and initiating remedial actions or advising general practitioners on doing so. The intervention was initiated between 18 April 2016 and 26 September 2017. The researchers used an interrupted time series analysis of rates (prevalence) of potentially hazardous prescribing and inadequate blood-test monitoring to compare observed postintervention rates to extrapolations from a 24-month preintervention trend. A total of 47,413 (mean age, 60 years; 48.7% males) individuals were registered to participating practices and had one or more risk factors for being exposed to hazardous prescribing or inadequate blood-test monitoring at the start of the intervention. Ninety-five percent of practices at baseline had rates of potentially hazardous prescribing (composite of 10 indicators) between 0.88% and 6.19%. The prevalence of potentially hazardous prescribing decreased by 27.9% (95% confidence interval [CI], 20.3%– 36.8%; p<0.001) and by 40.7% (95% CI, 29.1%–54.2%; p<0.001) at 24 weeks and at 12 months after intervention initiation, respectively. [PLoS Med 2020;17:e1003286] For inadequate blood-test monitoring (composite of two indicators), the rate reduction was 22.0% (95% CI, 0.2%– 50.7%; p=0.046) at 24 weeks and nonsignificant at 12 months (23.5%, 95% CI, –4.5% to 61.6%; p=0.127). The rates of potentially hazardous prescribing stood between 0.74% and 3.02% for 95% of practices after 12 months. Previous studies showed how general practice-based pharmacists improved integrated patient care and how they could deliver clinical interventions efficiently and in high volume. [Int J Pharm Pract 2018;26:501–506; Res Social 20 Adm Pharm 2018;14:228–240] “Our study demonstrates how these pharmacists can also play a key role in sustainably improving medication safety in general practice and reducing variation in potentially hazardous prescribing between practices,” the researchers said. “However, for this to be effective, it is imperative to have an underpinning ‘learning health systems’ capability for continuous data-driven self-study that promotes change and improvement,” they added. [Yearb Med Inform 2017;26:16–23] Such capability requires a digital infrastructure for continuous, patient-level feedback that allows practitioners to identify high-risk patients, access educational materials, and compare rates of high-risk prescribing and monitoring both between practices and within their practice over time, according to the researchers. The current study was limited by the nonrandomization of practices, leading to potential unmeasured confounding of the findings, they noted. NOVEMBER/DECEMBER ISSUE FROM ABROAD Antibiotics may raise risk of appendicitis in children, teens Jairia Dela Cruz K ids and teens exposed to antibiotics risk developing appendicitis, and this risk is dictated by the frequency of exposure, a study has shown. “At first sight, we observed a higher risk of appendicitis among children exposed to antibiotics early in life, but after adjustment for the number of antibiotic courses, this apparent association disappeared,” according to investigators. “Therefore, our results suggest that it is not early exposure but rather repeated exposure that is important. To our knowledge, no previous study has examined antibiotic exposure and subsequent risk of developing appendicitis,” they added. Accordingly, a potential underlying mechanism explaining our results is reverse causality: some children might have been prescribed antibiotics to treat an undiagnosed appendicitis. The analysis included a paediatric cohort of 1,385,707 children aged 0–19 years, with 7,406,397 antibiotic prescriptions dispensed over a mean follow-up of 10.1 years. Most of the children (84.1%) received at least one prescription (mean, 4), with penicillin being the most prescribed antibiotic (80.0%). There were 11,861 cases of appendicitis documented, occurring at a mean age of 9.8 years. Poisson and logistic regression models showed that compared with nonexposure, receipt of at least one course of antibiotics conferred about a 70% increase in the risk of developing appendicitis (adjusted rate ratio [RR], 1.72, 95% confidence interval [CI], 1.61–1.85). [Aliment Pharmacol Ther 2020;doi:10.1111/apt.16084] Notably, the risk increased by 1.04fold (95% CI, 1.04–1.04) per antibiotic course, with the highest risk seen in children who had received at least seven courses of antibiotics (RR, 2.02, 95% CI, 1.87–2.18). “Antibiotics have extensive effects on the composition, diversity, and function of the gut microbiota, and some studies have shown bacterial dysbiosis in the appendix to be a potential risk factor in development of appendicitis,” the investigators noted. [Microbiology 2010;156:3216–3223; Nat Microbiol 2018;3:1255–1265; Nat Commun 2016;7:10410] However, they acknowledged that despite the dose-dependent associa- 21 tion between antibiotics and appendicitis risk, suggesting that the drugs may be causally involved, causality cannot be inferred from the current observational study. “Accordingly, a potential underlying mechanism explaining our results is reverse causality: some children might have been prescribed antibiotics to treat an undiagnosed appendicitis,” the investigators claimed. It is also possible that the use of antibiotics may have been overestimated because of the possibility of filled but unused prescriptions, they added. The investigators called for further research to establish the causal involvement of antibiotics in developing appendicitis or whether some children are more susceptible to bacterial infections, including appendicitis, and therefore have a high exposure to antibiotics. NOVEMBER/DECEMBER ISSUE FROM ABROAD Rheuma drug shows disease-modifying potential for T1D Audrey Abella F indings from the phase IIa T1GER study revealed the therapeutic potential of the monoclonal antibody golimumab for children and young adults with type 1 diabetes (T1D). “There are no approved disease-modifying therapies for T1D,” said Dr Teresa Quattrin from the Jacobs School of Medicine and Biomedical Sciences, University of Buffalo in New York, US, during her presentation of the initial results. “[As such,] there is a significant need for therapies that slow the progression of T1D autoimmunity and disease,” noted Dr Eric Felner from the Emory University School of Medicine in Atlanta, Georgia, US, in his poster presentation of the subgroup findings. Golimumab specifically targets TNFα*, a pro-inflammatory cytokine influencing T1D initiation and progression, and is approved for the treatment of rheumatic diseases**. The team sought to determine the role of golimumab in T1D. Eighty-four participants (mean age 14 years, 60% male) were randomized 2:1 to receive SC golimumab*** or placebo for 52 weeks. [EASD 2020, abstract 53] function and prevent possible complications in individuals with T1D. Although HbA1c was numerically lower with golimumab vs placebo, the difference was not significant (p=0.80). “As often observed in clinical trials, an initial decline in HbA1c was observed in both groups over the first 4 weeks. But over time, HbA1c appeared to be lower with golimumab vs placebo,” noted Quattrin. Increase in daily insulin use was lower with golimumab vs placebo (0.07 vs 0.24 U/kg; p=0.001), as was the absolute amount of insulin used (0.51 vs 0.69 U/kg). Also, more golimumab vs placebo recipients were using a daily insulin dose of <0.5 U/kg (n=21 vs 3) and ≤0.25 U/kg (n=7 vs 0). “[These suggest] that golimumab provides optimal glycaemic control with low insulin dose,” said Quattrin. At week 52, C-peptide area under the curve (AUC) after a 4h MMTT# was higher with golimumab vs placebo (mean, 0.64 vs 0.43 pmol/mL; p<0.001). “[The] C-peptide change … started at week 12 and persisted throughout the study,” said Quattrin. There were also more golimumab vs placebo recipients who had C-peptide increase or minimal loss (41% vs 11%), who were in partial remission (IDAA1c## remission score <9; 43% vs 7%), or both (29% vs 4%). “These suggest that golimumab may be arresting disease progression for a large subset of patients,” noted Quattrin. C-peptide is a widely used measure of pancreatic β cell function, with low levels suggesting diabetes-related complications. [Diabetes Ther 2017;8:475– 487; Diabetes Med 2015;32:1346–1353] Therefore, this finding underscores the potential of golimumab to preserve β cell The rates of serious adverse events (AEs; 2% vs 4%) and drug-related AEs (43% in each arm) were similar between the golimumab and the placebo arms. Treatment discontinuation rate owing to AEs was higher with golimumab vs placebo (4% vs 0%), as was the incidence 22 of hypoglycaemia reported at investigator’s discretion (23% vs 7%). In a subgroup of participants aged 6–17 years (n=68), golimumab use led to a significantly less change in C-peptide AUC (mean, 0.11 vs 0.55 pmol/mL; pnominal<0.0001), less increase in insulin use (0.06 vs 0.27 U/kg/day; pnominal =0.0004), lower absolute insulin use (0.53 vs 0.74 U/kg/day), and numerically lower hypoglycaemic event rates (42% vs 48%) vs placebo. [EASD 2020, abstract 631] “[Taken together, the findings] demonstrate the ability [of golimumab] to preserve endogenous insulin production, reduce exogenous insulin requirements, and improve clinical and metabolic parameters in children and young adults with newly diagnosed stage 3 T1D … These results support golimumab as a potential disease-modifying therapy for T1D,” said Quattrin. Further evaluation is warranted to validate the findings. * TNFα: tumour necrosis factor alpha ** Rheumatoid arthritis, nonradiographic axial spondyloarthritis, polyarticular juvenile idiopathic arthritis *** Induction doses (weeks 0 and 2): 60 and 100 mg/ m2 for participants weighing <45 kg and ≥45 kg, respectively; maintenance doses (week 4 and every 2 weeks thereafter): 30 and 50 mg/m2, respectively # 4h MMTT: 4-hour mixed-meal tolerance test ## IDAA1c: insulin dose-adjusted A1c NOVEMBER/DECEMBER ISSUE EMPOWERING HEALTHCARE COMMUNITIES Bringing your trusted source of pharmacy news into the future. Keep up with the latest in local and international news and views in our bi-monthly online magazine for the pharmacy community. Sign up for free at www.mims.com/malaysia for email updates, or download our digital issues at https://specialty.mims.com/pharmacy FROM ABROAD Cranberry juice a potential treatment for H pylori infection? Pearl Toh C onsuming cranberry juice twice daily for 8 weeks can help suppress Helicobacter pylori infection among Chinese adults, suggests a randomized study—thus opening the door to using cranberry juice as a complementary approach to H. pylori management. Despite the availability of effective treatment with triple or quadruple antibiotics, treatment failure still occurred in 10–30% of patients and increasing antibiotic resistance may pose a challenge. "The study findings reveal that cranberry juice may be a useful aid in H. pylori management in adults in a high-risk region of China with an endemic infection rate of over 50%,” said principal investigator Professor Pan Kai-Feng from Peking University Cancer Hospital & Institute, Beijing, China. “While not alternatives to antibiotics, effective complementary strategies, like cranberry, that can contribute to managing H. pylori infections without negative side effects are highly desirable,” he added. while 93.15% of the patients receiving placebo remained positive for H. pyloriinfection in the intention-to-treat population (p=0.021). Similar results were seen in the per-protocol analysis, whereby the infection rate was significantly lower in the high-dose group compared with the placebo group (80.0% vs 92.65%; p=0.012). On the other hand, lower doses of proanthocyanidin-containing cranberry juice did not have an effect on H. pyloriinfection. The proportion of patients who remained positive for H. pylori infection in the low- and medium-dose groups were similar as the placebo group (~92%–95%). Among the participants who were tested negative at 8 weeks, 75% of them remained free of infection when they were retested 45 days after the end of intervention. The beneficial effect of cranberry juice may be attributed to the active phenolic compound proanthocyanidin, which can prevent bacteria from adhering to the stomach lining, according to the researchers. “Cranberry proanthocyanidins do not appreciably degrade under the highly acidic conditions in the stomach, allowing them to maintain bioactivity,” explained Pan and co-authors. After 8 weeks, the high-dose intervention led to an almost 20% drop in H. pylori infection rate. In addition, the effects of powder formulation of proanthocyanidin were also tested. However, the powder form did not have significant effect on H. pylorisuppression. “In situations where antibiotic treatment of H. pylori is warranted but resistance to antibiotics is reducing H. pylori eradication rates, concurrent administration of cranberry might help improve treatment outcomes,” the researchers suggested. The double-blind trial randomized 522 adults (mean age 47.24 years, 44.40% male) who were tested positive for H. pylori to receive any one of three doses (low, medium, high) of proanthocyanidin-standardized cranberry juice or placebo for 8 weeks. Proanthocyanidin is the active phenolic compound found in cranberry. H. pylori infection was tested using 13C-urea breath testing. [J Gastroenterol Hepatol 2020;doi:10.1111/jgh.15212] After 8 weeks, the high-dose intervention (juice containing 88 mg proanthocyanidin) led to an almost 20% drop in H. pylori infection rate to 82.43%, 24 NOVEMBER/DECEMBER ISSUE FROM ABROAD Turmeric extract may help relieve pain in knee OA Pearl Toh T urmeric extract supplements can help reduce knee pain associated with knee osteoarthritis, although there are no changes in knee effusion-synovitis or cartilage composition, a study suggests. “[So far, there is] no approved disease-modifying drugs currently are available to treat osteoarthritis,” said the researchers. The current treatment strategies such as NSAID and acetaminophen not only produce low to moderate effect on easing pain and do not slow structural progression, they are also associated with multiple side effects, they pointed out. Multicentre trials with larger sample sizes are needed to assess the clinical significance of these findings. In the double-blind, single-centre study, 70 participants (mean age 62 years) with symptomatic knee osteoarthritis and effusion-synovitis on ultrasonography were randomized 1:1 to receive two capsules containing turmeric extract 1,000 mg daily or a matching placebo for 12 weeks. [Ann Intern Med 2020;doi:10.7326/M20-0990] After 12 weeks, turmeric extract led to significant improvement in the primary outcome of knee pain assessed on a visual analogue scale (VAS) compared with placebo (mean, -23.8 vs -14.6 mm; difference, -9.1 mm; p=0.039). Knee pain assessed by WOMAC* was also significantly improved in the turmeric group vs the placebo group (mean -84.2 mm vs -37.0 mm; difference, -47.2 mm; p=0.006). However, there were no significant changes in the coprimary outcome of effusion-synovitis volume between the two groups (difference, 3.2 mL; p=0.075). T2 relaxation time of the lateral femoral cartilage on MRI was also comparable among patients who received turmeric extract vs placebo (difference, -0.4 ms; p=0.30). “The effect on pain was only moderate; however, it was achieved without any effect on knee structural measures assessed by MRI,” observed the researchers. Post hoc analyses revealed that pain reductions were reported in patients who had a lower effusion-synovitis volume at baseline but not in those with a higher volume. “[This] is an important hypothesis-generating finding. A possible explanation is that participants with a higher effusion-synovitis volume may have more severe disease,” said the researchers. * “[In addition,] we did not find any difference in the number of reported adverse events between groups, indicating that [turmeric extract] was safe and modestly effective in treating osteoarthritis in this short-term study,” they added. Adverse events (AEs) occurred at comparable rates in the two groups, with 39% of patients receiving turmeric extract and 53% of those on placebo experiencing at least one AE of any grade (p=0.16). Two of the AEs in the turmeric group and five in the placebo group were considered to be possibly related to treatment. One limitation of the study was the relatively short duration spanning just 12 weeks, which might not be sufficient to detect structural changes. As the treatment effect on pain had yet to plateau at the end of the study, the researchers believed that treatment effect may be greater with longer duration. “Multicentre trials with larger sample sizes are needed to assess the clinical significance of these findings,” they suggested. WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index 25 NOVEMBER/DECEMBER ISSUE FROM ABROAD New evidence backs safety of low-dose aspirin in women attempting pregnancy Jairia Dela Cruz D aily use of low-dose aspirin (LDA) among women of reproductive age appears to have no harmful effect on menstrual cycle length and hormone patterns, as shown in a study. Given the potential uses of daily LDA in women—including reducing the risks of stroke and cardiovascular disease, colon cancer, and obstetrical complications such as pre-eclampsia, foetal growth restriction, pregnancy loss, and preterm birth—the present data reassure those wanting to get pregnant that “LDA is unlikely to adversely affect their menstrual cycles,” according to investigators. “LDA may have further benefits in human reproduction by improving uterine and ovarian blood flow, enhancing embryo implantation and placental invasion, and sustaining early pregnancy. Indeed, we previously observed in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial that preconception LDA [use] in women with a single recent pregnancy loss was associated with higher rate of live birth compared with placebo,” they added. [J Clin Endocrinol Metab 2017;102:86– 92; Lancet 2014;384:29–36] In the current study, the investigators performed a secondary analysis of the EAGeR trial, which included 915 women (mean age, 29 years; mean body mass index, 26 kg/m2) with regular periods who had been randomized to receive 81mg aspirin (n=452) or placebo (n=463) daily in addition to 400 mg folic acid. Participants were followed for six menstrual cycles or through pregnancy. There were no significant between-group differences observed in menstrual cycle length and follicular and luteal phases. LDA did not confer a greater risk of having a short (relative risk [RR], 1.02) or long follicular phase length (RR, 1.01), short (RR, 1.02) or long cycle length (RR, 0.97), and short (RR, 1.23) or long luteal phase length (RR, 1.03). [Fertil Steril 2020;doi:10.1016/j.fertnstert.2020.06.022] Furthermore, hormone levels during the first two cycles were similar in the LDA and placebo groups. “Our results are consistent with one study evaluating serum hormone concentrations that also found no association between over-the-counter aspirin taken for one or two menstrual cycles and E2, luteal progesterone, follicle-stimulating hormone, and luteinizing hormone,” the investigators noted. [Gynecol Obstet Invest 1985;19:32–37; Hum Reprod 2015;30:1714–1723] Meanwhile, the discrepancies in menstrual cycle length seen in several other studies are likely related to differences in aspirin dose and duration of use, they added. [Contraception 1984;29:181–188; J Clin Endocrinol Metab 2017;102:86–92; Gynecol Obstet Invest 1985;19:32–37] In an editorial piece, Dr Jennifer Eaton, of the Women and Infants 26 Hospital and Warren Alpert Medical School of Brown University, Rhode Island, US, said that the study is strengthened by its randomized, placebo-controlled design and its large study population, and the findings may be used to counsel women on the use of LDA. [Fertil Steril 2020;doi:10.1016/j. fertnstert.2020.08.018] Eaton emphasized that normal cycle parameters and hormone levels do not necessarily mean normal fertility. Therefore, couples who fail to conceive based on the duration of unprotected intercourse should still undergo the standard fertility evaluation. “Finally, women who present with cycle irregularity while taking LDA should be evaluated to determine the aetiology. Despite biologic plausibility, the hypothetical impact of LDA on menstrual cyclicity is not supported by the data presented in this well-designed study,” she added. Eaton also pointed out some important limitations to the study. Among these are the inclusion of only normally cycling women, which limits data extrapolation to women with short or long cycles, and the use of urinary samples rather than serum samples, which could have influenced the results. NOVEMBER/DECEMBER ISSUE EVENT CALENDAR NOVEMBER APRIL 2021 APRIL 2021 FRIDAY–SUNDAY FRIDAY–SUNDAY SUNDAY–TUESDAY 27-29 Malaysian Society of Gastroenterology and Hepatology Annual Scientific Meeting (Virtual GUT 2020) Location: Virtual Conference Tel: 03 8996 0700 / 1700 / 2700 Fax: 03 8996 4700 Email: [email protected] Website: www.msgh.org.my 2-4 National Heart Association of Malaysia Congress 2021 (NHAM Congress 2021) Location: Kuala Lumpur Convention Centre Info: NHAM Congress Secretariat Tel: 03 7931 2131 Website: www.nham-conference.com 4-6 Asia-Oceania Conference on Obesity and Malaysian Association for the Study of Obesity Scientific Conference (AOCO-MASO 2021) Location: Hotel Istana, Kuala Lumpur Info: Conference Secretariat Tel: 03 9769 2471 Email: [email protected] Website: www.aocomaso2021.com APRIL 2021 JULY–AUGUST 2021 AUGUST 2021 TUESDAY–SATURDAY THURSDAY–SUNDAY TUESDAY–THURSDAY 6-10 Federation of Asian Pharmaceutical Associations (FAPA) Congress 2020 Location: KL Convention Centre Info: FAPA Secretariat URL: www.facebook.com/FAPA2020 AUGUST 2021 19-22 THURSDAY–SUNDAY Asia Pacific Digestive Week (APDW) 2021 Location: Kuala Lumpur Convention Centre Info: Malaysian Society of Gastroenterology & Hepatology (MSGH) Email: [email protected] URL: www.apdwkl2021.org 29-1 11th Malaysian Endocrine & Metabolic Society (MEMS) Annual Congress (MAC 11) Location: TBC Info: Congress Secretariat Tel: (03) 7931 2856 Email: [email protected] URL: www.memsmac.org TBC MPS Northern Region Pharmacists Convention (NRPC) 2020 & MPSKP Annual General Meeting Location: AIMST University, Kedah Info: Malaysian Pharmaceutical Society Kedah/Perlis Area (MPSKP) URL: facebook.com/MPSKPArea 17-19 Asian Symposium on Medicinal Plants and Spices (ASOMPS) XVII Location: Zenith Hotel, Putrajaya Info: Malaysian Natural Products Society (Prof Dr Faridah Abas) Email: [email protected] URL: asompsxvii.org TBC 11th National Pharmacy R&D Conference 2020 Location: TBC Info: Pharmaceutical Research & Development Branch, Pharmacy Policy & Strategic Planning Division, Ministry of Health (MOH) URL: research.pharmacy.gov.my/ rndconf2020 To notify us of any events of interest to pharmacists, please submit details to [email protected]. 28 NOVEMBER/DECEMBER ISSUE
