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1.
Childs Nerv Syst ; 40(3): 873-880, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37979014

ABSTRACT

PURPOSE: This study examines long-term benefit on functional outcomes and quality of life after selective dorsal rhizotomy (SDR) in children with spastic diplegia in Hong Kong. METHOD: This is a case control study. Individuals with spastic diplegia who were at 6 to 12 years post-SDR were recruited. Age, gender, cognition, and Gross Motor Function Classification System level-matched individuals with spastic diplegia who had not undergone SDR were recruited as controls. Outcome measures included physical level, functional level, physiological level, and quality of life. All data were compared by independent t-test. RESULTS: Individuals post-SDR (n = 15) demonstrated a significantly better range of ankle dorsiflexion in knee extension by - 5.7 ± 10.9° than the control group (n = 12). No other significant differences were observed. CONCLUSION: SDR is a safe, one-off procedure and provides long-term reduction in spasticity with no major complications. With the heterogeneity, we did not demonstrate between-group differences in long-term functional outcomes.


Subject(s)
Cerebral Palsy , Rhizotomy , Child , Humans , Rhizotomy/methods , Retrospective Studies , Case-Control Studies , Cerebral Palsy/complications , Quality of Life , Muscle Spasticity/surgery , Muscle Spasticity/etiology , Treatment Outcome
2.
Plant Dis ; 108(6): 1762-1768, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38243181

ABSTRACT

Watermelon is affected by diseases such as Fusarium wilt, gummy stem blight, and root-knot nematode (RKN). Succinate dehydrogenase inhibitors (SDHIs) with potential fungicide and nematicide activity provide the opportunity to control multiple diseases with one compound. In this study, we aimed to determine the sensitivity of Meloidogyne incognita race 4 (MI4), Fusarium oxysporum f. sp. niveum (FON), and Stagonosporopsis citrulli (SCIT) to existing SDHIs: benzovindiflupyr, fluopyram, cyclobutrifluram, and pydiflumetofen. All SDHIs had fungicidal activity against 19 SCIT isolates in mycelial growth assays, but isolates were most sensitive to pydiflumetofen (median EC50 = 0.41 µg/ml). Most of the 50 FON isolates tested were sensitive to cyclobutrifluram for mycelial growth (median EC50 = 4.04 µg/ml) and conidial germination (median EC50 = 0.2 µg/ml) assays but were not sensitive to fluopyram. MI4 was most sensitive to cyclobutrifluram for egg hatch (mean EC50 = 0.0019 µg/ml) and J2 motility (mean EC50 = 1.16 µg/ml) assays but was not sensitive to pydiflumetofen. Significant positive correlations between the sensitivity of SCIT (mycelial growth) and FON (mycelial growth and conidial germination) for cyclobutrifluram and benzovindiflupyr (SCIT r = 0.88; FON r = 0.7; P < 0.0001) and cyclobutrifluram and pydiflumetofen (SCIT r = 0.83; FON r = 0.67 and 0.77; P < 0.0001) indicate a potential for cross-resistance between these SDHIs for these fungal pathogens. Overall, results suggest that cyclobutrifluram may be used for managing RKN, whereas it should be used judiciously for Fusarium wilt of watermelon and gummy stem blight due to the existence of insensitive isolates to the fungicide.


Subject(s)
Citrullus , Fungicides, Industrial , Fusarium , Plant Diseases , Succinate Dehydrogenase , Tylenchoidea , Fusarium/drug effects , Plant Diseases/parasitology , Plant Diseases/microbiology , Tylenchoidea/drug effects , Citrullus/microbiology , Citrullus/parasitology , Animals , Succinate Dehydrogenase/antagonists & inhibitors , Fungicides, Industrial/pharmacology , Enzyme Inhibitors/pharmacology , Antinematodal Agents/pharmacology
3.
Clin Radiol ; 78(10): 715-723, 2023 10.
Article in English | MEDLINE | ID: mdl-37453807

ABSTRACT

Gadoxetic disodium (Primovist) is a hepatocyte-specific magnetic resonance imaging (MRI) contrast agent with increasing popularity with its unique dual dynamic and excretory properties in focal liver lesion detection and characterisation. In-depth knowledge of its diagnostic utility and pitfalls in hepatocellular carcinoma (HCC) and liver metastases is crucial in facilitating clinical management. The current article reviews the pearls and pitfalls in these aspects with highlights from the latest research evidence. Pearls for common usage of Primovist in HCC includes detection of precursor cancer lesions in cirrhotic patients. Hepatobiliary phase hypointensity precedes arterial phase hyperenhancement (APHE) in hepatocarcinogenesis. Hepatobiliary phase hypointense nodules without APHE can represent early or progressed hepatocellular carcinoma (HCC) and high-grade dysplastic nodules. In addition, Primovist is useful to differentiate HCC from pseudolesions. Pitfalls in diagnosing HCC include transient tachypnoea in the arterial phase, rare hepatobiliary phase hyperintense HCC, and decompensated liver cirrhosis compromising image quality. Primovist is currently the most sensitive technique in diagnosing liver metastases before curative hepatic resection. Other patterns of enhancement of liver metastases, "disappearing" liver metastases are important pitfalls. Radiologists should be aware of the diagnostic utility, limitations, and potential pitfalls for the common usage of hepatobiliary specific contrast agent in liver MRI.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Contrast Media , Sensitivity and Specificity , Gadolinium DTPA , Magnetic Resonance Imaging/methods , Retrospective Studies
4.
Clin Radiol ; 78(5): 323-332, 2023 05.
Article in English | MEDLINE | ID: mdl-36849280

ABSTRACT

Fat necrosis of the breast is a commonly encountered condition in daily practice. It is a benign pathology, but it can have variable manifestations and patterns that may sometimes mimic malignancy, depending on its stage of evolution and its underlying cause. This review demonstrates the wide spectrum of appearances of fat necrosis on mammography, digital breast tomosynthesis (DBT), ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and positron-emission tomography (PET). Sequential follow-up images are included in some cases to illustrate the temporal change of the findings. The typical location and distribution of fat necrosis from a comprehensive list of aetiologies are discussed. Improved knowledge of the multimodality imaging features of fat necrosis could enhance diagnostic accuracy and clinical management, thus avoiding unnecessary invasive investigations.


Subject(s)
Breast Neoplasms , Fat Necrosis , Humans , Female , Fat Necrosis/diagnostic imaging , Fat Necrosis/pathology , Breast/diagnostic imaging , Breast/pathology , Mammography/methods , Tomography, X-Ray Computed , Magnetic Resonance Imaging/methods , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology
5.
Skeletal Radiol ; 52(9): 1729-1738, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37043019

ABSTRACT

OBJECTIVES: Determine whether MR imaging findings or demographics predict surgical management in patients with first MTP joint injuries. MATERIALS AND METHODS: Retrospective study of 161 forefoot MRs for traumatic first MTP injury (M:F 92:69, mean age 33 ± 13 yrs.). Two radiologists reviewed imaging for ligamentous, osseous, and tendinous injuries. Ligaments and tendons were graded as 0:normal, 1:sprain or strain, 2:partial tear, 3:complete tear. Osseous injuries were classified as edema, fracture, or cartilage injury. Clinical data obtained included sex, age, injury acuity, sport participation, level of sport, and treatment. Imaging findings and demographic data were assessed to determine predictive factors for surgical management. Statistics included kappa, chi-squared, Fisher's exact, and logistic regression. RESULTS: Logistic regression (odds ratio [95% CI], p-value) showed that grade 2 or 3 injuries of the plantar ligamentous complex (2.87, [1.10, 7.48], p = 0.031), grade 2 or 3 injuries of the medial collateral ligament (3.24, [1.16, 9.08], p = 0.025), and participation in collegiate or professional sports (4.34 [1.64, 11.52], p = 0.003) were associated with an increased rate of surgical intervention. k = ligamentous injury (0.71-0.83), osseous trauma (0.88-0.95), and tendon injury (0.78). All other imaging findings and demographic factors were not significant predictors of surgery (p > 0.05). CONCLUSION: Participation in collegiate or professional sports and tears of the plantar ligamentous complex or medial collateral ligament predicted surgical management in patients with first MTP trauma.


Subject(s)
Plantar Plate , Sports , Sprains and Strains , Tendon Injuries , Humans , Young Adult , Adult , Middle Aged , Retrospective Studies , Magnetic Resonance Imaging , Rupture
6.
Med J Malaysia ; 78(4): 429-436, 2023 07.
Article in English | MEDLINE | ID: mdl-37518908

ABSTRACT

INTRODUCTION: Most evidence about the management of cancer and hematological malignancy in pregnancy are derived from retrospective observational studies with a small sample size. Availability of sufficiently large data has enabled evidence-based decision-making in this clinical dilemma. MATERIALS AND METHODS: Retrospective study looking into patients diagnosed with acute leukemia or lymphoma in pregnancy from 1st January 2014 to 1st January 2020 in Ampang General Hospital including newly or previously diagnosed and relapsed disease RESULTS: 37 cases of acute leukemia or lymphoma in pregnancy occurred in 34 patients. Majority of acute leukemia or lymphoma in pregnancy diagnosed in 1st trimester or in the setting of previously established or relapsed disease was therapeutically terminated. Thirteen pregnancies treated with antenatal chemotherapy resulted in livebirths except one stillbirth. More adverse obstetric outcomes are observed in pregnancies that did not receive antenatal chemotherapy, but association did not reach statistical significance. There was no significant difference in fetal outcome between cohort with and without antenatal chemotherapy. No treatment related mortality was observed in pregnancies with antenatal chemotherapy. Overall survival for newly diagnosed acute leukemia in pregnancy is significantly better with antenatal chemotherapy versus no antenatal chemotherapy. CONCLUSION: Treatment with chemotherapy in 2nd trimester of pregnancy onwards appears to have tolerable risks with favorable obstetric and fetal outcome. Deferment of treatment for acute leukemia in pregnancy to after delivery may cause increased risk of maternal and fetal adverse outcome.


Subject(s)
Leukemia , Lymphoma , Pregnancy , Female , Humans , Retrospective Studies , Malaysia/epidemiology , Leukemia/diagnosis , Leukemia/drug therapy , Leukemia/epidemiology , Lymphoma/diagnosis , Lymphoma/drug therapy , Lymphoma/epidemiology , Prenatal Care , Acute Disease , Pregnancy Outcome
7.
N Engl J Med ; 380(5): 425-436, 2019 01 31.
Article in English | MEDLINE | ID: mdl-30699315

ABSTRACT

BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).


Subject(s)
Administration, Oral , Anti-Bacterial Agents/administration & dosage , Bone Diseases, Infectious/drug therapy , Joint Diseases/drug therapy , Administration, Intravenous , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacokinetics , Female , Humans , Intention to Treat Analysis , Male , Medication Adherence , Middle Aged , Treatment Outcome , Young Adult
8.
Ann Oncol ; 33(9): 939-949, 2022 09.
Article in English | MEDLINE | ID: mdl-35691590

ABSTRACT

BACKGROUND: Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data provided by whole-genome and transcriptome sequencing and analysis (WGTA) present an opportunity to align a much larger proportion of patients to therapies. PATIENTS AND METHODS: Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy number and mutation signatures, were combined with RNA-based data, including gene expression and fusions, to generate comprehensive WGTA profiles. A multidisciplinary molecular tumour board used WGTA profiles to identify and prioritize clinically actionable alterations and inform therapy. Patient responses to WGTA-informed therapies were collected. RESULTS: Clinically actionable targets were identified for 83% of patients, of which 37% of patients received WGTA-informed treatments. RNA expression data were particularly informative, contributing to 67% of WGTA-informed treatments; 25% of treatments were informed by RNA expression alone. Of a total 248 WGTA-informed treatments, 46% resulted in clinical benefit. RNA expression data were comparable to DNA-based mutation and copy number data in aligning to clinically beneficial treatments. Genome signatures also guided therapeutics including platinum, poly-ADP ribose polymerase inhibitors and immunotherapies. Patients accessed WGTA-informed treatments through clinical trials (19%), off-label use (35%) and as standard therapies (46%) including those which would not otherwise have been the next choice of therapy, demonstrating the utility of genomic information to direct use of chemotherapies as well as targeted therapies. CONCLUSIONS: Integrating RNA expression and genome data illuminated treatment options that resulted in 46% of treated patients experiencing positive clinical benefit, supporting the use of comprehensive WGTA profiling in clinical cancer care.


Subject(s)
Neoplasms , Gene Expression Profiling , Genomics/methods , Humans , Mutation , Neoplasms/drug therapy , Neoplasms/genetics , Precision Medicine/methods , RNA , Transcriptome
9.
Clin Radiol ; 77(7): 503-513, 2022 07.
Article in English | MEDLINE | ID: mdl-35365295

ABSTRACT

Physiological and pathological processes arising from the breast and anterior chest wall may share similar clinical presentations because of the small volume of male breasts. Therefore, imaging is frequently required to localise and characterise the lesion and guide biopsy when radiological findings are equivocal or suspicious. Mammography or digital breast tomosynthesis (DBT) and ultrasound are the mainstays of breast imaging work-up. Other imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI) and positron-emission tomography (PET) can sometimes augment the investigation and aid treatment planning. This article reviews the key imaging features of a wide spectrum of benign and malignant conditions that involve the male breast and anterior chest wall across various age groups. Familiarisation with the salient radiological findings is essential for reaching an accurate diagnosis and optimising management.


Subject(s)
Breast Neoplasms , Thoracic Wall , Adolescent , Breast/diagnostic imaging , Breast/pathology , Breast Neoplasms/pathology , Child , Humans , Male , Mammography/methods , Radiographic Image Enhancement/methods , Thoracic Wall/diagnostic imaging , Tomography, X-Ray Computed/methods , Young Adult
10.
Med J Malaysia ; 77(2): 267-270, 2022 03.
Article in English | MEDLINE | ID: mdl-35338643

ABSTRACT

Acute or subacute transverse myelitis is a rare disease caused by inflammation of the spinal cord. The extensive differential diagnosis of this disease require physician to timely decide the necessary investigations and plan for effective treatment. We report a case of anomalous multifactorial transverse myelitis in a patient with human immunodeficiency virus (HIV) who responded well with multimodal therapy. The patient was given immunosuppressive agent and plasma exchange for the demyelinating disease as well as antibiotics for neurosyphilis, antiviral for cytomegalovirus (CMV) neurologic disease, and highly active antiretroviral therapy (HAART). Three months after his first presentation, patient showed full neurology recovery and suppressed HIV viral load.


Subject(s)
HIV Infections , Myelitis, Transverse , Antiviral Agents/therapeutic use , Cytomegalovirus , HIV , HIV Infections/complications , HIV Infections/drug therapy , Humans , Myelitis, Transverse/diagnosis , Myelitis, Transverse/drug therapy , Myelitis, Transverse/etiology
11.
Curr Psychol ; : 1-10, 2022 May 17.
Article in English | MEDLINE | ID: mdl-35600262

ABSTRACT

Restrictive COVID-19 measures can have significant mental health impacts, particularly on young people. How such measures may influence day-to-day momentary affect, nonetheless, remains to be explored. Experience sampling data were collected from 165 young people (aged 15-24) as part of a larger epidemiological youth mental health study in Hong Kong. We examined the impact of one of the most stringent COVID-19 measures - dine-in restrictions - on momentary positive and negative affect and current contexts and activities of these young people. The effects of a milder form of COVID-19 measure - school suspension - were separately examined. Multilevel analysis revealed that those in the dine-in ban group, compared to dining-as-usual, showed significantly reduced momentary positive affect (ß = -0.17, SE = 0.06, p = 0.003). Its effect remained significant even when accounting for baseline depressive and anxiety symptoms and socioeconomic status (ß = -0.15, SE = 0.05, p = 0.008). The effect of dine-in ban on reduced momentary positive affect was found specifically when participants were in indoor locations (e.g., home, office), alone, and engaged in passive leisure activities. This pattern was not observed when participants were at school or at other outdoor locations, with friends, or engaged in active leisure activities. No significant effect of school suspension on momentary affect was observed. More severe COVID-19 measures, such as dine-in ban, can have significant impacts on the momentary positive affect of young people. Certain contexts and activities may offer protection against the consequences of COVID-19 measures. The current findings may help to inform future designs of mental health interventions and public health policies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03183-y.

12.
BMC Fam Pract ; 22(1): 153, 2021 07 19.
Article in English | MEDLINE | ID: mdl-34275453

ABSTRACT

BACKGROUND: This qualitative study is a sub-component of BETTER WISE, a comprehensive and structured approach that proactively addresses chronic disease prevention, screening, and cancer survivorship, including screening for poverty and addressing lifestyle risks for patients aged 40 to 65. Patients (n = 527) from 13 primary care clinics (urban, rural, and remote) in Alberta, Ontario, and Newfoundland & Labrador, Canada agreed to participate in the study and were invited to a one-hour prevention visit delivered by a Prevention Practitioner (PP) as part of BETTER WISE. We identified the key components of a BETTER WISE prevention visit based on patients' and primary care providers' perspectives. METHODS: Primary care providers (PPs, physicians and their staff) participated in 14 focus groups and 19 key informant interviews to share their perspectives on the BETTER WISE project. Of 527 patients who agreed to participate in the study and were invited for a BETTER WISE prevention visit with a PP, we received 356 patient feedback forms. We also collected field notes and memos and employed thematic analysis using a constant comparative method focusing on the BETTER WISE prevention visit. RESULTS: We identified four key themes related to a BETTER WISE prevention visit: 1) Creating a safe environment and building trust with patients: PPs provided sufficient time and a safe space for patients to share what was important to them, including their concerns related to poverty, alcohol consumption, and mental health, topics that were often not shared with physicians; 2) Providing personalized health education: PPs used the BETTER WISE tools to provide patients with a personalized overview of their health status and eligible screening; 3) Non-judgmental empowering of patients: Instead of directing patients on what to do, PPs evoked patients' preferences and helped them to set goals (if desired); and 4) Integrating care for patients: PPs clarified information from patients' charts and surveys with physicians and helped patients to navigate resources within and outside of the primary care team. CONCLUSIONS: The results of this study underscore the importance of personalized, trusting, non-judgmental, and integrated relationships between primary care providers and patients to effectively address chronic disease prevention, screening, and cancer survivorship as demonstrated by the BETTER WISE prevention visits. TRIAL REGISTRATION: This qualitative study is a sub-component of the BETTER WISE pragmatic, cRCT, trial registration ISRCTN21333761 (date of registration 19/12/2016).


Subject(s)
Mass Screening , Primary Health Care , Chronic Disease , Humans , Ontario , Qualitative Research
13.
Med J Malaysia ; 76(4): 510-517, 2021 07.
Article in English | MEDLINE | ID: mdl-34305112

ABSTRACT

BACKGROUND: Radioactive iodine 131I (RAI) therapy is one of the definitive treatments for paediatric differentiated thyroid cancer (DTC) initiated at nuclear medicine departments. In Malaysia, there is a need to identify the standardisation of treatment regimes to align with international standards. We aimed to evaluate the clinicopathological features and the patient response to RAI therapy among paediatric DTC cases at Hospital Kuala Lumpur (HKL), Malaysia. METHODS: A retrospective, longitudinal study was conducted among paediatric DTC patients treated with RAI in HKL and followed up between 2000-2016. Sixty-five patients were studied (mean period: 58.8±36 months). The clinicopathological data of the patients was recorded, and descriptive analysis was made. The association between categorical and continuous data with disease status was assessed using chi-square and Kruskal-Wallis tests, p-value <0.05 taken as statistically significant. RESULTS: Most patients were female (78.5%), and adolescents comprised 89.2%. Pre-pubertal age, those presenting with cervical nodal involvement, extra-thyroidal extension and lymphovascular invasion were significantly associated with distant metastases at presentation. There was no mortality reported during the follow-up period. Sixty per cent of patients achieved remission, while 40% had persistent disease. The persistent disease was significantly correlated with distant metastasis at presentation (p=0.025). CONCLUSIONS: Paediatric DTC manifests with a more extensive disease burden at presentation and requires multiple RAI doses. Despite this, it carries an excellent overall prognosis.


Subject(s)
Iodine Radioisotopes , Thyroid Neoplasms , Adolescent , Child , Female , Hospitals , Humans , Iodine Radioisotopes/therapeutic use , Longitudinal Studies , Malaysia , Male , Retrospective Studies , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/surgery , Thyroidectomy , Treatment Outcome
14.
Med J Malaysia ; 76(5): 685-690, 2021 09.
Article in English | MEDLINE | ID: mdl-34508375

ABSTRACT

Over the past decade, 18F-Fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PETCT) has emerged as an important imaging modality in the management of lymphoma. Since the introduction of Deauville scoring system (2009) and the Lymphoma Response Assessment Criteria (2014), clinicians are now sharing a common language in the management of lymphoma. In Malaysia, nearly a third of PET-CT request is related to lymphoma imaging. Though there are extensive publications regarding these scoring systems and assessment criteria for lymphoma, there are hardly any literature on the reporting format for the 18F-FDG PET-CT in this disease. The variable reporting formats have on many occasions caused confusion not only to the referring clinicians but also to nuclear medicine physicians. Thus, a working committee comprising experienced nuclear medicine physicians and haematologists in Malaysia have agreed and made a joint recommendation on the standard reporting format for 18F-FDG PET-CT in Lymphoma. This recommendation will minimize inter-observer discrepancies in reporting, facilitate the understanding of the report of the referring clinicians as well as facilitate counseling between patients and clinicians in the management of the disease.


Subject(s)
Fluorodeoxyglucose F18 , Lymphoma , Consensus , Humans , Lymphoma/diagnostic imaging , Positron Emission Tomography Computed Tomography , Positron-Emission Tomography
15.
Med J Malaysia ; 76(2): 125-130, 2021 03.
Article in English | MEDLINE | ID: mdl-33742617

ABSTRACT

INTRODUCTION: The global pandemic of Corona Virus Disease 2019 (COVID-19) has led to the re-purposing of medications, such as hydroxychloroquine and lopinavir-ritonavir in the treatment of the earlier phase of COVID-19 before the recognized benefit of steroids and antiviral. We aim to explore the corrected QT (QTc) interval and 'torsadogenic' potential of hydroxychloroquine and lopinavir-ritonavir utilising a combination of smartphone electrocardiogram and 12-lead electrocardiogram monitoring. MATERIALS AND METHODS: Between 16-April-2020 to 30-April- 2020, patients with suspected or confirmed for COVID-19 indicated for in-patient treatment with hydroxychloroquine with or without lopinavir-ritonavir to the Sarawak General Hospital were monitored with KardiaMobile smartphone electrocardiogram (AliveCor®, Mountain View, CA) or standard 12-lead electrocardiogram. The baseline and serial QTc intervals were monitored till the last dose of medications or until the normalization of the QTc interval. RESULTS: Thirty patients were treated with hydroxychloroquine, and 20 (66.7%) patients received a combination of hydroxychloroquine and lopinavir-ritonavir therapy. The maximum QTc interval was significantly prolonged compared to baseline (434.6±28.2msec vs. 458.6±47.1msec, p=0.001). The maximum QTc interval (456.1±45.7msec vs. 464.6±45.2msec, p=0.635) and the delta QTc (32.6±38.5msec vs. 26.3±35.8msec, p=0.658) were not significantly different between patients on hydroxychloroquine or a combination of hydroxychloroquine and lopinavir-ritonavir. Five (16.7%) patients had QTc of 500msec or more. Four (13.3%) patients required discontinuation of hydroxychloroquine and 3 (10.0%) patients required discontinuation of lopinavirritonavir due to QTc prolongation. However, no torsade de pointes was observed. CONCLUSIONS: QTc monitoring using smartphone electrocardiogram was feasible in COVID-19 patients treated with hydroxychloroquine with or without lopinavir-ritonavir. The usage of hydroxychloroquine and lopinavir-ritonavir resulted in QTc prolongation, but no torsade de pointes or arrhythmogenic death was observed.


Subject(s)
COVID-19 Drug Treatment , Electrocardiography , Enzyme Inhibitors/therapeutic use , Hydroxychloroquine/therapeutic use , Long QT Syndrome/diagnosis , Smartphone , Adult , Aged , Antiviral Agents/therapeutic use , Drug Combinations , Female , Humans , Long QT Syndrome/chemically induced , Lopinavir/therapeutic use , Male , Middle Aged , Mobile Applications , Ritonavir/therapeutic use
16.
J Antimicrob Chemother ; 75(12): 3485-3490, 2020 12 01.
Article in English | MEDLINE | ID: mdl-32830242

ABSTRACT

BACKGROUND: The incidence of antimicrobial-resistant Neisseria gonorrhoeae (GC) is rising in Canada; however, antimicrobial resistance (AMR) surveillance data are unavailable for infections diagnosed directly from clinical specimens by nucleic acid amplification tests (NAATs), representing over 80% of diagnoses. We developed a set of 10 improved molecular assays for surveillance of GC-AMR and prediction of susceptibilities in NAAT specimens. METHODS: Multiplex real-time PCR (RT-PCR) assays were developed to detect SNPs associated with cephalosporin (ponA, porB, mtrR -35delA, penA A311V, penA A501, N513Y, G545S), ciprofloxacin (gyrA S91, parC D86/S87/S88) and azithromycin [23S (A2059G, C2611T), mtrR meningitidis-like promoter] resistance. The assays were validated on 127 gonococcal isolates, 51 non-gonococcal isolates and 50 NAATs with matched culture isolates. SNPs determined from the assay were compared with SNPs determined from in silico analysis of WGS data. MICs were determined for culture isolates using the agar dilution method. RESULTS: SNP analysis of the 50 NAAT specimens had 96% agreement with the matched culture RT-PCR analysis. When compared with MICs, presence of penA A311V or penA A501 and two or more other SNPs correlated with decreased susceptibility and presence of three or more other SNPs correlated with intermediate susceptibility to cephalosporins; presence of any associated SNP correlated with ciprofloxacin or azithromycin resistance. NAAT-AMR predictions correlated with matched-culture cephalosporin, ciprofloxacin and azithromycin MICs at 94%, 100% and 98%, respectively. CONCLUSIONS: We expanded molecular tests for N. gonorrhoeae AMR prediction by adding new loci and multiplexing reactions to improve surveillance where culture isolates are unavailable.


Subject(s)
Gonorrhea , Neisseria gonorrhoeae , Anti-Bacterial Agents/pharmacology , Azithromycin/pharmacology , Canada , Cephalosporins/pharmacology , Ciprofloxacin/pharmacology , Drug Resistance, Bacterial , Humans , Microbial Sensitivity Tests , Neisseria gonorrhoeae/genetics , Real-Time Polymerase Chain Reaction
17.
Hum Reprod ; 35(12): 2715-2724, 2020 12 01.
Article in English | MEDLINE | ID: mdl-33252677

ABSTRACT

STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgment and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand and Maurice and Phyllis Paykel Trust. G.D.A. reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. A.W.H. reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research and Wellbeing of Women and consultancy fees from AbbVie, Ferring, Nordic Pharma and Roche Diagnostics. M.L.H. reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. N.P.J. reports research sponsorship from AbbVie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics and Vifor Pharma. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from AbbVie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. E.H.Y.N. reports research sponsorship from Merck. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring and retains a financial interest in NexHand. J.S. reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring and being a clinical subeditor of Human Fertility. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Infertility , State Medicine , Consensus , Female , Humans , Infertility/therapy , Male , New Zealand , Ovulation Induction
18.
Philos Trans A Math Phys Eng Sci ; 378(2168): 20190201, 2020 Apr 03.
Article in English | MEDLINE | ID: mdl-32063172

ABSTRACT

This paper presents a novel interdisciplinary and catchment-based approach for exploring urban flood resilience. Our research identified and developed a diverse set of adaptation measures for Elwood, a suburb in Melbourne, Australia, that is vulnerable to pluvial and coastal flooding. We drew on methods from social science, urban design and environmental engineering to gain integrated insights into the opportunities for Elwood to increase its flood resilience and urban liveability. Results showed that an appropriate balance of social, infrastructural and urban design responses would be required to retreat from, accommodate and protect against flood risk. These would also deliver broader benefits such as securing water supplies through harvested stormwater and mitigating extreme heat through greener landscapes. Our interdisciplinary approach demonstrated the value of (i) engaging with the community to understand their concerns, aspirations and adaptation ideas, (ii) exploring design measures that densify and use urban forms in ways that implement adaptation measures while responding to local context, (iii) adopting modelling techniques to test the performance, robustness and economic viability of possible adaptation solutions, and (iv) innovating governance arrangements and principles needed to improve flood resilience in the Elster Creek catchment. Our research also provided valuable insight on how to operationalize interdisciplinary work in practice, highlighting the importance of sharing an impact agenda, taking a place-based approach, developing a common conceptual framework, and fostering a constructive team culture. This article is part of the theme issue 'Urban flood resilience'.

19.
Sex Health ; 17(2): 121-128, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32119814

ABSTRACT

Background Gay and other men who have sex with men of Asian background (GAM) have been identified as a key population in efforts to eradicate HIV in New South Wales. The aims of the present study were to evaluate current levels of engagement with HIV and sexually transmissible infection (STI) testing services, assess knowledge of pre- and post-exposure prophylaxis and to identify factors associated with service engagement in this group. METHODS: A survey of 604 GAM residing in Sydney and Melbourne was undertaken. RESULTS: The data identified that a significant proportion of non-HIV-positive men (i.e. HIV-negative men and men whose HIV status was unknown) surveyed (n = 567; 93.9%) had engaged in frequent HIV testing and comprehensive STI testing in the 12 months prior to the survey (n = 180; 31.7%). There were significant differences (P < 0.05) in sexual practices at the bivariate level between those who reported frequent and comprehensive HIV/STI testing and those who did not. Those who tested regularly were substantially more sexually active, were more likely to have multiple partners (P = 0.001) and were more likely to engage in condomless anal intercourse with both casual (P < 0.001) and regular (P = 0.002) partners. Those who engaged with testing initiatives were more likely to discuss HIV status with both regular (P = 0.008) and casual (P < 0.001) partners, and identified more reasons to test than their counterparts (P < 0.001). The data also highlighted key service venues, with gay men most likely to have used public sexual health clinics (46.9%) as their most recent testing venue. CONCLUSIONS: The data demonstrate an association between high levels of male-to-male sexual activity and engagement in frequent and comprehensive HIV and STI testing. This likely derives from both self-perceived notions of risk and current reliance on established gay community organisations to convey information around testing. Increasing engagement with testing initiatives beyond GAM who self-identify as being at high HIV and STI risk will require the use of novel routes by which to disseminate this information.


Subject(s)
HIV Infections/diagnosis , HIV Infections/prevention & control , HIV Testing/statistics & numerical data , Health Knowledge, Attitudes, Practice , Sexual and Gender Minorities , Sexually Transmitted Diseases/prevention & control , Adolescent , Adult , Aged , Asian People/ethnology , Australia/epidemiology , Australia/ethnology , Facilities and Services Utilization/statistics & numerical data , Homosexuality, Male/ethnology , Humans , Male , Mass Screening/statistics & numerical data , Middle Aged , Sexual Behavior , Sexual Partners , Young Adult
20.
Hong Kong Med J ; 26(6): 500-509, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33303700

ABSTRACT

INTRODUCTION: A magnetic seed marker system (Magseed, Endomagnetics, Cambridge, United Kingdom) is used as a localisation method for non-palpable breast lesions in the United States, Europe, and Hong Kong. It overcomes many limitations of conventional techniques and allows scheduling flexibility. We sought to evaluate its efficacy and safety in the Chinese population. METHODS: We retrospectively reviewed all Chinese women who underwent magnetic seed marker-guided breast lesion excision from June 2019 to February 2020 at a single institution. Placement success (final target-to-seed distance <10 mm) was evaluated by imaging on the day of surgery. Specimen radiographs and pathology reports were reviewed for magnetic seed markers and target removal. Margin clearance and re-excision rates were analysed. RESULTS: Twenty two magnetic seed markers were placed in 21 patients under sonographic or stereotactic guidance to localise 21 target lesions. One target lesion required two magnetic seed markers for bracketing. There was no migration of nine markers placed 6 to 56 days before the day of surgery. Placement success was achieved in 20 (90.9%) cases. Mean final target-to-seed distance was 3.1 mm. Two out of 21 (9.5%) lesions required alternative localisation due to marker migration ≥10 mm, while 19 (90.5%) lesions underwent successful magnetic seed marker-guided excision. Three of these 19 lesions (15.8%) were excised with therapeutic intent, one of which (33%) required re-excision due to a close margin. All 22 magnetic seed markers were successfully removed. No complications were reported. CONCLUSION: Magnetic seed markers demonstrated safety and efficacy in Chinese women for breast lesion localisation and excision.


Subject(s)
Breast Neoplasms/diagnosis , Early Detection of Cancer/methods , Magnetometry/methods , Adult , Aged , China , Early Detection of Cancer/instrumentation , Female , Humans , Magnetic Phenomena , Magnetometry/instrumentation , Magnets , Mammography , Middle Aged , Pilot Projects , Retrospective Studies
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