Refractory hypoxia and saturation gap in a COVID-19 patient.

Acquired methemoglobinemia, predominantly due to oxidizing medications occurs when heme iron in hemoglobin is oxidized from ferrous to ferric ion and binds oxygen irreversibly leading to functional anemia, cyanosis, and tissue hypoxia. We report a case of a 60-year-old man with multiple comorbidities who was diagnosed with coronavirus disease 2019 (COVID-19) and developed methemoglobinemia after consumption of prescribed supplements. He presented with dyspnea and cyanosis. An oxygen saturation gap with characteristic chocolate-brown arterial blood indicated methemoglobinemia. Outsourced methemoglobin (MetHb) was increased at 9.0%. Despite aggressive intervention, he succumbed to his illness. In this case, we discuss the pathophysiology of why some individuals, especially the elderly with COVID-19 are more susceptible to develop methemoglobinemia after possibly being exposed to oxidizing agents. Laboratory methods for assessing oxygen saturation, including pulse oximetry, arterial blood gas and co-oximetry are examined in relation to this case. The importance of considering a diagnosis of methemoglobinemia based on clinical and biochemical findings although MetHb assay or co-oximetry are not readily available is also emphasized.

Study protocol on risk factors for the diagnosis of gestational diabetes mellitus in different trimesters and their relation to maternal and neonatal outcomes (GDM-RIDMAN).

INTRODUCTION: Gestational diabetes mellitus (GDM) is often associated with adverse pregnancy outcomes. However, the association of risk factors with GDM diagnosis, maternal and neonatal health outcomes is less established when compared with women without GDM. We aim to examine the diagnostic accuracy of the conventional and novel risk factors for a GDM diagnosis and their impact on maternal and neonatal health outcomes. METHODS AND ANALYSIS: This retrospective cohort and nested case-control study at six public health clinics is based on medical records and questionnaire survey of women between 2 and 12 months postpartum. The estimated required sample size is 876 complete records (292 cases, 584 control, at a ratio of 1:2). Oral glucose tolerance test results will be used to identify glucose dysregulation, and maternal and neonatal outcomes include maternal weight gain, pre-eclampsia, polyhydramnios, mode of delivery, preterm or postdate birth, complications in labour, birth weight, gestational age at birth, Apgar score, congenital anomaly, congenital hypothyroidism, neonatal death or stillbirth, hypoglycaemia and hyperbilirubinaemia. Psychosocial measures include the WHO Quality of Life: brief, mother-infant bonding (14-item Postpartum Bonding Questionnaire and 19-item Maternal Postnatal Attachment Scale), anxiety (7-item Generalised Anxiety Disorder), depression (9-item Patient Health Questionnaire) and stress (Perceived Stress Scale symptoms) questionnaires. The comparative incidences of maternal and neonatal health outcomes, the comparative prevalence of the psychosocial outcomes between women with GDM and without GDM, specificity, sensitivity, positive and negative predictive values of the risk factors, separately and combined, will be reported. All GDM risk factors and outcomes will be modelled using multivariable regression analysis and the receiver operating characteristics curve will be reported. ETHICS AND DISSEMINATION: This study was approved by the Malaysia Research and Ethics Committee, Ministry of Health Malaysia. Informed consent will be obtained from all participants. Findings will be submitted for publications in scientific journals.

High-frequency repetitive transcranial magnetic stimulation at dorsolateral prefrontal cortex for migraine prevention: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex as a migraine prevention by conducting a systematic review and meta-analysis. BACKGROUND: The efficacy of high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex as preventive migraine treatment remains debatable. METHODS: PubMed, Scopus, CINAHL, CENTRAL, and BioMed Central databases were searched from their inception until December 2020. Randomised trials comparing high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex with sham for migraine prevention were included. The risk of bias was assessed using the Cochrane guidelines. Headache days, pain intensity, acute medication intake, and disability were extracted as study outcomes and the mean difference with a random-effects model was used to determine the effect size. RESULTS: Meta-analysis revealed that high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex significantly reduced acute medication intake (Mean Difference = 9.78, p = 0.02, 95%CI: 1.60, 17.96, p = 0.02) and functional disability (Mean Difference = 8.00, p < 0.05, 95%CI: 4.21, 11.79). However, no differences were found in headache days and pain intensity reduction, although there was a slight trend favouring high-frequency repetitive transcranial magnetic stimulation. CONCLUSION: High-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex may be effective in reducing acute medication intake and disability. However, more studies are needed to strengthen this preliminary evidence.

Asymptomatic morphometric vertebral fractures and its associated factors: A cross-sectional study among adults in a selected urban area in Selangor, Malaysia.

OBJECTIVE: This study aimed to determine the prevalence of vertebral fractures (VF) in a selected urban population in Malaysia and to explore possible variables associated with VF in the study population. METHODS: A cross-sectional study involving community-living, healthy subjects aged between 45-90 years from the state of Selangor, Malaysia, were invited to attend a bone health check-up. Subjects with diseases known to affect bone metabolism or were on treatment for osteoporosis (OP) were excluded. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry (DXA). Lateral and antero-posterior view lumbar spine x-rays were performed and VF was determined by the semi-quantitative Genant method. RESULTS: A total of 386 subjects were studied. Asymptomatic morphometric VF were found in 44 (11.4%) subjects. T12 was the most common vertebrae to be fractured. The prevalence of VF was significantly higher in menopausal women (12.4%) compared to non-menopausal women, in those above the age of 60 (18.5%), in those of Chinese ethnicity (16.5%), in those with a low body fat percentage (17.1%) and among those with OP (27.0%). The mean (standard deviation) 25-hydroxyvitamin D [25(OH)D] levels were significantly higher in those with VF compared to those without VF, 67.64 (23.50) and 57.47 (21.71) nmol/L, respectively. However, after multiple regression analysis, age over 60 years and OP on DXA BMD measurement were the only significant associated factors for VF. CONCLUSION: Overall, 11.4% of a selected Malaysian urban population had asymptomatic morphometric VF. Age over 60 years and OP on DXA BMD measurement, but not 25(OH)D levels, were associated with VF.

High-frequency repetitive transcranial magnetic stimulation at dorsolateral prefrontal cortex for migraine prevention: A protocol for a systematic review of controlled trials.

BACKGROUND: Migraine may lead to a negative impact on the patients' quality of life with a subsequent substantial burden to society. Therapy options for treatment and prevention of migraine have progressed over the years and repetitive transcranial magnetic stimulation (rTMS) is one of the promising non-pharmacological options. It induces and alters electric current in the brain via repetitive non-invasive brain stimulation in high frequency. In migraine patients, two common stimulation sites are the M1 cortex and dorsolateral prefrontal cortex (DLPFC). The mechanism on how rTMS exerts therapeutic effects on migraine is not fully established, but the main postulation is that the neuromodulation via high-frequency rTMS (hf-rTMS) might inhibit pain perception. However, evidence from studies has been conflicting, thus the usefulness of hf-rTMS as migraine preventive treatment is still uncertain at this moment. METHODS: This is a systematic review protocol describing essential reporting items based on the PRISMA for systematic review protocols (PRISMA-P) (Registration number: CRD42020220636). We aim to review the effectiveness, tolerability, and safety of hf-rTMS at DLPFC in randomised controlled trials (RCTs) as migraine prophylactic treatment. We will search Scopus, Cumulative Index to Nursing and Allied Health Literature Plus, PubMed, Cochrane Central Register of Controlled Trials and Biomed Central for relevant articles from randomised controlled clinical trials that used hf-rTMS applied at DLPFC for the treatment of migraine. The risk of bias will be assessed using the version 2 "Risk of bias" tool from Cochrane Handbook for Systematic Reviews of Interventions Version 6.1. We will investigate the evidence on efficacy, tolerability and safety and we will compare the outcomes between the hf-rTMS intervention and sham groups. DISCUSSION: This systematic review will further determine the efficacy, safety, and tolerability of hf-rTMS applied at DLPFC for migraine prophylaxis. It will provide additional data for health practitioners and policymakers about the usefulness of hf-rTMS for migraine preventive treatment.

Effectiveness and tolerability of repetitive transcranial magnetic stimulation for preventive treatment of episodic migraine: a single-centre, randomised, double-blind, sham-controlled phase 2 trial (Magnet-EM).

BACKGROUND: This is a phase II randomised, double-blind, sham-controlled trial to evaluate the effectiveness and tolerability of repetitive transcranial magnetic stimulation for preventive treatment of episodic migraine amongst migraine subjects. METHODS: Subjects age 18 to 60 years will undergo a baseline evaluation to establish the diagnosis of migraine based on the International Classification of Headache Disorder 3rd Edition (ICHD-3). Those who fulfil the ICHD-3 criteria for episodic migraine and compliant to the headache diary during a month run-in period will be enrolled. A total of 76 subjects will be randomised to receive either transcranial magnetic stimulation or sham stimulation for 5 sessions within 2 weeks duration. Follow-up sessions will be conducted monthly for three consecutive months. Prior to treatment, subjects will be required to fill up questionnaires and undergo few procedures such as electroencephalography, transcranial Doppler ultrasound and biochemical analysis for serum serotonin, serum calcitonin gene-related peptide and serum beta-endorphin. These procedures will be repeated at month 3 after receiving the last treatment. The primary outcome measure of this study is the difference in mean monthly migraine days at baseline and at months 1, 2 and 3 after treatment sessions. DISCUSSION: Following evidence from previous studies showing restoration of dorsolateral prefrontal cortex (DLPFC) activation to almost normal level, the rTMS intervention will target left DLPFC in this study. An intermediate duration of treatment sessions is selected for this study. It is set to five treatment sessions given within 2 weeks duration. TRIAL REGISTRATION: ClinicalTrials.gov NCT03556722 . Registered on 14 June 2018.

Different reference ranges affect the prevalence of osteoporosis and osteopenia in an urban adult Malaysian population.

OBJECTIVES: To determine the prevalence of osteopenia (OPe) and osteoporosis (OP) in an urban adult population in Malaysia, and to compare the change in the prevalence when using a Caucasian compared to an Asian reference range. METHODS: A cross-sectional random sample of the population aged between 45 and 90 years from the state of Selangor, Malaysia, was invited to attend a bone health check-up. Participants with diseases known to affect bone metabolism or who were on treatment for OP were excluded. Bone mineral density was measured using dual energy X-ray absorptiometry. Based on the World Health Organization definitions, the prevalence of OPe and OP was calculated using the Asian and Caucasian T-scores. RESULTS: A total of 342 subjects (222 females, 120 males), with a mean age of 59.68 (standard deviation: 8.89) years, who fulfilled the study criteria were assessed. Based on the Asian reference range, there were 140 (40.9%) subjects with OPe and 48 (14.0%) with OP. On applying the Caucasian reference range, there were 152 (44.4%) subjects with OPe and 79 (23.1%) with OP, with significant increases in males, females, and Chinese ethnic groups. Overall, 75 (21.9%) of subjects had a change in their diagnostic status. T-scores were consistently lower when the Caucasian reference range was used. CONCLUSIONS: In a healthy urban Malaysian population, the prevalence of OP is 14.0% and OPe is 40.9%. Application of a Caucasian reference range significantly increased the number of subjects with OP and may potentially lead to over-treatment.

A pilot study on the association between SLCO1B1 RS4363657 polymorphism and muscle adverse events in adults with newly diagnosed dyslipidaemia who were prescribed a statin: the Malaysian primary health care cohort.

Introduction: Statin, the first-line treatment for dyslipidaemia, may have suboptimal adherence due to its associated muscle adverse events. These data, however, remain limited. Aim: To determine the association of serum creatine kinase (CK) and SLCO1B1 rs4363657 polymorphism with statin-associated muscle adverse events (SAMAE) among dyslipidaemia participants. Methods: This was a prospective cohort study at government health clinics involving newly diagnosed adults with dyslipidaemia. SAMAE were recorded based on the patient's complaint after a month on statin. CK was taken at baseline and follow-up. Genetic profiling was performed for SLCO1B1 rs4363657 polymorphism. Results: Among 118 participants, majority were Malay (72%) males (61%) with a mean age of 49 ± 12.2 years old and prescribed lovastatin (61.9). There was a significant association between statin types (lovastatin and simvastatin) and SAMAE (p = 0.0327); no significant association noted between CK and SAMAE (p = 0.5637). The SLCO1B1 rs4363657 polymorphism was significantly associated SAMAE (p < 0.0001). Conclusions: In this first pilot study of a multiethnic Malaysian population, the incidence of SAMAE was 18.6%. SAMAE were significantly higher in subjects on lovastatin compared to simvastatin. SLCO1B1 rs4363657 polymorphism was a significant risk factor for SAMAE.

Effects of Different Types of Statins on Lipid Profile: A Perspective on Asians.

CONTEXT: The present review aimed at reviewing the effects of different statins on lipid profile, particularly in Asians. EVIDENCE ACQUISITION: PubMed searches were conducted using the keywords 'statin, effect, and lipid profile' from database inception through March 2016. In this review, 718 articles were retrieved from the primary search. After reviewing the titles, abstracts, and full texts, we found that 59 studies met our inclusion criteria. These also included subsequent reference searches of retrieved articles. RESULTS: CURVES study compared the effect on lipid profile between atorvastatin and other statins. This study demonstrated that low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) were reduced more with atorvastatin compared to simvastatin, pravastatin, lovastatin, and fluvastatin. However, simvastatin provided a greater elevation of high-density lipoprotein cholesterol (HDL-C) compared to atorvastatin. The STELLAR trial was based on dose-to-dose comparisons between atorvastatin and rosuvastatin efficacy in reducing LDL-C. Te present study also revealed that as the doses of rosuvastatin, simvastatin, and pravastatin increased, HDL-C also increased, with rosuvastatin having the greatest effect. However, HDL-C levels decreased as the dose of atorvastatin increased. The DISCOVERY study involving the Asian population revealed that the percentage of patients achieving the European goals for LDL-C and TC at 12 weeks was higher in rosuvastatin group compared to atorvastatin group. CONCLUSIONS: The effects of statins on lipid profile are dose dependent. Most studies showed that rosuvastatin has the best effect on lipid profile. Prescribing lower doses of statins in Asians seems necessary.

Trends in post osteoporotic hip fracture care from 2010 to 2014 in a private hospital in Malaysia.

OBJECTIVE: Following an osteoporotic fracture, pharmacological treatment is recommended to increase bone mineral density and prevent future fractures. However, the rate of starting treatment after an osteoporotic hip fracture remains low. The objective of this study was to survey the treatment rate following a low-trauma hip fracture at a tertiary private hospital in Malaysia over a period of 5 years. METHODS: The computerised hospital discharge records were searched using the terms "hip," "femur," "femoral," "trochanteric," "fracture," or "total hip replacement" for all patients over the age of 50, admitted between 2010 and 2014. The medical charts were obtained and manually searched for demographic data and treatment information. Hip operations done for non-low-trauma-related fracture and arthritis were excluded. RESULTS: Three hundred seventy patients over the age of 50 years were admitted with a hip fracture, of which 258 (69.7%) were low trauma, presumed osteoporotic, hip fractures. The median age was 79.0 years (interquartile range [IQR], 12.0). Following a hip fracture, 36.8% (95 of 258) of the patients received treatment, but out of these, 24.2% (23 of 95) were on calcium/vitamin D only. The median duration of treatment was 1 month (IQR, 2.5). In 2010, 56.7% of the patients received treatment, significantly more than subsequent years 2011-2014, where approximately only 30% received treatment. CONCLUSIONS: Following a low-trauma hip fracture, approximately 72% of patients were not started on active antiosteoporosis therapy. Of those who were, the median duration of treatment was 1 month. This represents a missed opportunity for the prevention of future fractures.

Pre-transplantation serum ferritin as a prognostic marker in allogeneic haemopoietic stem cell transplant patients in a tertiary care hospital in Malaysia.

BACKGROUND: The principal cause of iron overload in patients with haematological malignancies is recurrent red cell transfusions for anaemia. The serum ferritin level reflects the iron burden in the body, in the absence of inflammation or liver disease. In Malaysia, data are lacking on the association between pre-transplant serum ferritin levels and outcome after allogeneic haemopoietic stem cell transplant. METHODS: We did a cross-sectional study using retrospective data of 106 post-allogeneic haemopoietic stem cell transplant patients (HLA-matched sibling) with haematological malignancies at Hospital Ampang to determine the relationship between pre-transplant serum ferritin levels and post-transplant outcome, post-transplant complications and survival time. Patients were divided into two groups according to the iron status: serum ferritin level >1000 µg/L (iron overload) and <1000 µg/L. RESULTS: The median age for patients was 30.5 (18-58) years. The median pre-transplantation serum ferritin level and the prevalence of pre-transplantation iron overload were 2423 (408.2-7664) µg/L and 87.5%, respectively. No significant association was found between iron status and demographic factors, type of haematological malignancy and post-transplant complications. Although insignificant, patients with iron overload had a shorter survival time (36 months) compared to those with no iron overload (40 months). There was also no significant association between the iron status and post-transplant outcome. Significant post-transplant complications associated with post-transplant outcome were the need for total parenteral nutrition (TPN) (p=0.014) and chronic graft-versus-host disease (GVHD) (p=0.008). Similarly, significant associations were found between age group (p=0.003), TPN (p=0.035) and chronic GVHD (p=0.012) with survival time using Kaplan-Meir analysis. However, after Cox regression, only age group was found to be significantly associated with survival time (p=0.014). CONCLUSION: Serum ferritin is an acute phase reactant and its levels increase in the presence of tissue necrosis and inflammation. Both these events occur in haematological malignancies. Although serum ferritin level is a non-invasive, relatively cost-effective, widely available and practical indicator of iron status, it is not specific to iron overload. Therefore, a true association between the serum ferritin level and iron burden is problematic in patients with haematological malignancies.