Effectiveness of mHealth apps on adherence and symptoms to oral anticancer medications: a systematic review and meta-analysis.

PURPOSE: Despite the rapid expansion of mHealth apps, their adoption has not always been based on evidence of effectiveness on patient outcomes. This systematic review aimed to determine the effect of mHealth apps on adherence and symptom to oral anticancer medications (OAMs) and identify the app design that led to such effects. METHODS: Pubmed, Cochrane Central, PsycINFO, EMBASE, and WoS were searched from inception to April 2023. Randomised controlled trials (RCTs) that evaluated effects of mHealth apps on primary outcomes OAM adherence and symptom burden were included. Two reviewers independently assessed risk-of-bias using Cochrane Risk-of-Bias version 2 and extracted the data. Quality of evidence was assessed using GRADE. The protocol was registered in PROSPERO (CRD42023406024). RESULTS: Four RCTs involving 806 patients with cancer met the eligibility criteria. mHealth apps features included a combinations of symptom reporting, medication reminder, automated alert to care team, OAM and side effect information, one study implemented structured follow-up by a nurse. The intervention group showed no significant difference in OAM adherence (relative ratio 1.20; 95% CI 1.00 to 1.43), but significantly improved symptoms to OAMs with a lower standardised mean symptom burden score of 0.49 (SMD - 0.49; 95% CI - 0.93 to - 0.06), and a 25% lower risk of grade 3 or 4 toxicity (risk ratio 0.75; 95% CI 0.58 to 0.95) compared to usual care. CONCLUSION: These findings suggest a potential role for mHealth app in managing OAM side effect. Further research should explore the role of AI-guided algorithmic pathways on the interactive features of mHealth apps.

Acceptance of Electronic Labeling for Medicinal Product Information Among Malaysian Hospital Patients: Cross-Sectional Study.

BACKGROUND: While perceptions of electronic labeling (e-labeling) in developed countries have been generally positive, existing data primarily come from studies involving hospital pharmacists, community pharmacy customers who may not be frequent medication users, and individuals receiving COVID-19 vaccines. OBJECTIVE: This study aims to assess e-labeling acceptance, perceptions of its benefits, challenges with its implementation, and preferences among hospital ambulatory care patients in Malaysia. Additionally, the study investigates the factors influencing patients' acceptance of e-labeling. METHODS: A cross-sectional study using a 28-item questionnaire was conducted at the outpatient pharmacy department of a quaternary hospital in Kuala Lumpur, Malaysia, from May to June 2023. The questionnaire was developed based on a review of published literature related to e-labeling and was guided by the Unified Theory of Acceptance and Use of Technology, second version (UTAUT2). Patients aged 18 years and above were recruited using a stratified sampling method to ensure representative age-related medication usage. A mobile tablet was provided to patients for self-completion of the e-survey in their preferred language (English, Malay, or Mandarin). Categorical data on e-labeling acceptance, perceptions, and preferences were analyzed using descriptive statistics. Qualitative content analysis was performed to characterize participants' responses to open-ended questions. Univariate and multivariate binomial logistic regression analyses were conducted to identify predictors of e-labeling acceptance. RESULTS: Out of 462 patients approached, 387 (83.8%) participated in the survey, with 283 (73.1%) accepting e-labeling. Most participants perceived the electronic version of the package insert as beneficial, particularly for understanding their medication better through the choice of language (352/387, 91.0%). However, around half of the participants (197/387, 50.9%) expressed concerns about the potential risks of obtaining illegal medication information via e-labeling. Most participants (302/387, 78.0%) preferred to access electronic leaflets through government websites. However, 221/387 (57.1%) still wanted the option to request printed leaflets. Significant predictors of e-labeling acceptance included perceived benefits such as better understanding of medication (adjusted odds ratio [AOR] 8.02, 95% CI 2.80-22.97, P<.001), environmental protection (AOR 7.24, 95% CI 3.00-17.51, P<.001), and flexibility in information retrieval (AOR 2.66, 95% CI 1.11-6.35, P=.03). Conversely, being of Chinese ethnicity compared with Malay (AOR 0.28, 95% CI 0.13-0.60, P=.005) and perceived lack of self-efficacy in browsing electronic leaflets (AOR 0.25, 95% CI 0.11-0.56, P<.001) were associated with lower acceptance. CONCLUSIONS: The acceptance rate for e-labeling among hospital ambulatory care patients was moderately high and was significantly influenced by ethnicity as well as patients' perceived benefits and challenges related to its implementation. Future strategies to enhance e-labeling uptake should address patient concerns regarding the challenges of using the digital platform and emphasize the benefits of e-labeling.

A tumor-associated splice-isoform of MAP2K7 drives dedifferentiation in MBNL1-low cancers via JNK activation.

Master splicing regulator MBNL1 shapes large transcriptomic changes that drive cellular differentiation during development. Here we demonstrate that MBNL1 is a suppressor of tumor dedifferentiation. We surveyed MBNL1 expression in matched tumor/normal pairs across The Cancer Genome Atlas and found that MBNL1 was down-regulated in several common cancers. Down-regulation of MBNL1 predicted poor overall survival in breast, lung, and stomach adenocarcinomas and increased relapse and distant metastasis in triple-negative breast cancer. Down-regulation of MBNL1 led to increased tumorigenic and stem/progenitor-like properties in vitro and in vivo. A discrete set of alternative splicing events (ASEs) are shared between MBNL1-low cancers and embryonic stem cells including a MAP2K7∆exon2 splice variant that leads to increased stem/progenitor-like properties via JNK activation. Accordingly, JNK inhibition is capable of reversing MAP2K7∆exon2-driven tumor dedifferentiation in MBNL1-low cancer cells. Our work elucidates an alternative-splicing mechanism that drives tumor dedifferentiation and identifies biomarkers that predict enhanced susceptibility to JNK inhibition.

Vascular adhesion protein-1 (VAP-1) in vascular inflammatory diseases.

Vascular adhesion protein-1 (VAP-1) also known as amino oxidase copper containing 3 (AOC3) is a pro-inflammatory and versatile molecule with adhesive and enzymatic properties. VAP-1 is a primary amine oxidase belonging to the semicarbazide-sensitive amine oxidase (SSAO) family, which catalyzes the oxidation of primary amines leading to the production of ammonium, formaldehyde, methylglyoxal, and hydrogen peroxide. VAP-1 is mainly expressed by endothelial cells, smooth muscle cells, adipocytes and pericytes. It is involved in a repertoire of biological functions, e.g., immune cell extravasation, angiogenesis, and vascularization. Research into VAP-1 has intensified within the last decade on its role as a novel clinical biomarker and as a potential therapeutic target of vascular inflammatory disorders such as atherosclerosis, stroke, diabetes, neurovascular disorders (e.g., Alzheimer's Disease), hepatic disease (e.g., non-alcoholic steatohepatitis), and skin conditions (e.g., psoriasis). This is the most up-to-date and comprehensive review on VAP-1 focusing on the translational aspects of VAP-1. Compared to recent reviews, our review provides novel insights on VAP-1 and heart failure, stroke and frailty, diabetes, endometriosis, osteoarthritis, COVID-19, conjunctivitis associated systemic lupus erythematosus, hematopoietic stem cells, gliomas, treatment of colorectal cancer with a novel VAP-1 inhibitor (U-V269), promoting recovery of motor functions and habit learning with a novel VAP-1 inhibitor (PXS-4681A), and 68Ga-DOTA-Siglec-9, a labelled peptide of Siglec-9 (a VAP-1 ligand), which appears to be a safe PET tracer for inflammation in rheumatoid arthritis. Finally, we present the emerging role of VAP-1 in pregnancy as a gatekeeper of immune cells, which are critical for spiral arterial remodeling, the deficiency of which could lead to vascular disorders of pregnancy such as preeclampsia. Future research should prioritize clinical trials on VAP-1 small-molecule inhibitors and monoclonal antibodies, thus, maximizing the potential of VAP-1 targeted therapy as well as research into sVAP-1 as a clinical biomarker of diseases and its prognosis.

Filter life and safety of heparin-grafted membrane for continuous renal replacement therapy - A randomized controlled trial.

Polyethyleneimine-layered membrane with grafted heparin (oXiris) may improve filter life during continuous renal replacement therapy (CRRT) in addition to its immunoadsorptive capability, compared with that of conventional membrane. In this single center, prospective, open-label pilot study, we randomized critically ill patients with bleeding risk who underwent anticoagulation-free CRRT, to commence with oXiris or M150 filter with sequential crossover. We examined the filter life with each circuit and its effect on systemic coagulation parameters. We randomized 11 and nine patients to commence CRRT with oXiris and M150 respectively, with 19 oXiris and 20 M150 filter-circuits in all. Patient profiles in both arms were comparable for illness severity and comorbidities. Median filter lives for oXiris versus M150 circuits were 13 h versus 18 h (p = 0.10). Among 11 patients with paired crossover filters, filter lives for 14 oXiris-M150 circuit pairs were 13 h versus 16 h (p = 0.27), and corresponding transmembrane pressures increased to 111 mmHg versus 75 mmHg by 12 h (p = 0.02). Patients' coagulation parameters were comparable following both filter-circuits. CRRT with oXiris (vs. M150) was independently associated with shorter filter life, adjusted for prescribed dose, vascular access, and coagulopathy. Use of oXiris did not prolong filter life over conventional membrane with no evidence of systemic heparin exposure; significant membrane clogging is observed by 12 h with oXiris.

Acceptability of pharmacist-led interventions to resolve drug-related problems in patients with chronic myeloid leukaemia.

PURPOSE: Chronic myeloid leukaemia (CML) patients on long-term tyrosine kinase inhibitor (TKI) therapy are susceptible to drug-related problems (DRPs). This study aimed to evaluate the acceptability and outcomes of pharmacist-led interventions on DRPs encountered by CML patients. METHODS: This study included participants from the intervention arm of a randomised controlled trial which was conducted to evaluate the effects of pharmacist-led interventions on CML patients treated with TKIs. Participants were recruited and followed up in the haematology clinics of two hospitals in Malaysia from March 2017 to January 2019. A pharmacist identified DRPs and helped to resolve them. Patients were followed-up for six months, and their DRPs were assessed based on the Pharmaceutical Care Network Europe Classification for DRP v7.0. The identified DRPs, the pharmacist's interventions, and the acceptance and outcomes of the interventions were recorded. A Poisson multivariable regression model was used to analyse factors associated with the number of identified DRPs per participant. RESULTS: A total of 198 DRPs were identified from 65 CML patients. The median number of DRPs per participants was 3 (interquartile range: 2, 4). Most participants (97%) had at least one DRP, which included adverse drug events (45.5%), treatment ineffectiveness (31.5%) and patients' treatment concerns or dissatisfaction (23%). The 228 causes of DRPs identified comprised the following: lack of disease or treatment information, or outcome monitoring (47.8%), inappropriate drug use processes (23.2%), inappropriate patient behaviour (19.9%), suboptimal drug selection (6.1%), suboptimal dose selection (2.6%) and logistic issues in dispensing (0.4%). The number of concomitant medications was significantly associated with the number of DRPs (adjusted Odds Ratio: 1.100; 95% CI: 1.005, 1.205; p = 0.040). Overall, 233 interventions were made. These included providing patient education on disease states or TKI-related side effects (75.1%) and recommending appropriate instructions for taking medications (7.7%). Of the 233 interventions, 94.4% were accepted and 83.7% were implemented by the prescriber or patient. A total of 154 DRPs (77.3%) were resolved. CONCLUSIONS: The pharmacist-led interventions among CML patients managed to identify various DRPs, were well accepted by both TKI prescribers and patients, and had a high success rate of resolving the DRPs.

Correction to: Efficacy of a medication management service in improving adherence to tyrosine kinase inhibitors and clinical outcomes of patients with chronic myeloid leukaemia: a randomised controlled trial.

Revised Funding Information.

Efficacy of a medication management service in improving adherence to tyrosine kinase inhibitors and clinical outcomes of patients with chronic myeloid leukaemia: a randomised controlled trial.

PURPOSE: Suboptimal adherence to tyrosine kinase inhibitors (TKIs) contributes to poor clinical outcomes in chronic myeloid leukemia (CML). This randomised controlled trial (RCT) aimed to evaluate the impact of a medication management service (MMS) on adherence to TKIs and clinical outcomes. METHODS: A parallel RCT was conducted in two hospitals in Malaysia, where 129 CML patients were randomised to MMS or control (usual care) groups using a stratified 1:1 block randomisation method. The 6-month MMS included three face-to-face medication use reviews, CML and TKI-related education, two follow-up telephone conversations, a printed information booklet and two adherence aids. Medication adherence (primary outcome), molecular responses and health-related quality of life (HRQoL) scores were assessed at baseline, 6th and 12th month. Medication adherence and HRQoL were assessed using medication possession ratio and the European Organisation for Research and Treatment in Cancer questionnaire (EORTC_QLQ30_CML24) respectively. RESULTS: The MMS group (n = 65) showed significantly higher adherence to TKIs than the control group (n = 64) at 6th month (81.5% vs 56.3%; p = 0.002), but not at 12th month (72.6% vs 60.3%; p = 0.147). In addition, a significantly higher proportion of participants in the MMS group achieved major molecular response at 6th month (58.5% vs 35.9%; p = 0.010), but not at 12th month (66.2% vs 51.6%; p = 0.092). Significant deep molecular response was also obtained at 12th month (24.6% vs 10.9%; p = 0.042). Six out of 20 subscales of EORTC-QLQ30-CML24 were significantly better in the MMS group. CONCLUSIONS: The MMS improved CML patients' adherence to TKI as well as achieved better clinical outcomes. TRIAL REGISTRATION: Clinicaltrial.gov (ID: NCT03090477).

Metabolic inflexibility in women with polycystic ovary syndrome: a systematic review.

Polycystic ovary syndrome (PCOS) is a risk factor for dysglycemia, insulin resistance, and type 2 Diabetes Mellitus (T2DM). Inefficient energy oxidation, metabolic inflexibility, is a marker of blunted metabolism. We conducted a systematic review on metabolic inflexibility in women with PCOS. We searched MEDLINE, EMBASE and Cochrane central (inception-October 2018) for studies evaluating metabolic inflexibility and reporting on changes in Respiratory Quotient (ΔRQ). We extracted data and assessed quality using The Newcastle-Ottawa Scale. We included five prospective cohort studies (461 women). Three compared PCOS women to unaffected subjects, one to women with obesity or T2DM, and one to adolescent girls; all had medium quality. Three studies showed higher metabolic inflexibility in women with PCOS (ΔRQ range 0.05-0.098) compared to unaffected subjects. Women with PCOS had similar metabolic inflexibility compared to those with T2DM (ΔRQ 0.05 ± 0.03 vs 0.06 ± 0.04, p = .98) and obesity (p = .06). Inflexibility was higher in hyperandrogenemic women with PCOS (ΔRQ 0.091 ± 0.060 vs 0.120 ± 0.010, p = .014). ΔRQ was lower in PCOS women with insulin resistance vs those with normal insulin sensitivity (0.04 ± 0.02 vs. 0.07 ± 0.04, p = .007). In conclusion, women with polycystic ovary syndrome appear to have higher metabolic inflexibility associated with hyperandrogenemia and insulin resistance.

Effects of visfatin on brown adipose tissue energy regulation using T37i cells.

The role of brown adipose tissue (BAT) in pathological states of energy homeostasis and impaired adipocyte function, such as obesity has been a major area of research interest in recent years. Herein, we sought to determine the direct effects of adipokines, visfatin and leptin on BAT thermogenesis. The effects of mouse recombinant visfatin, nicotinamide mononucleotide (NMN) and leptin with or without FK866 were studied on differentiated T37i cells. Treated cells were analyzed for key genes and proteins regulating BAT [UCP-1, PRD1-BF1-RIZ1 homologous domain-containing 16 (PRDM-16), PPARgamma-coactivator-1alpha (PGC-1α) and receptor-interacting protein 140 (RIP-140)] using quantitative PCR and western blot analysis. Data is presented as mean P-values. Both visfatin and leptin had significant concentration dependent effects on thermogenesis in brown pre-adipocytes and at physiological levels, increased uncoupling protein-1 (UCP-1) levels in brown adipocytes. These effects of visfatin were similar to that of nicotinamide mononucleotide (NMN), further strengthening the enzymatic role of visfatin. We also showed that leptin induced UCP-1 mRNA expression and protein production appears to be mediated by visfatin. High concentrations of both visfatin and leptin led to a dramatic decrease in UCP-1 protein levels, supporting the notion that visfatin levels are raised in obesity and that obese people have reduced BAT activity, plausibly through a reduction in UCP-1 levels. Additionally, we found differential regulation of key brown adipogenic genes, specifically, PRD1-BF1-RIZ1 homologous domain-containing 16 (PRDM-16), PPARgamma-coactivator-1alpha (PGC-1α) and receptor-interacting protein 140 (RIP-140) by visfatin. Our observations provide novel insights in the potential actions of visfatin in BAT.

Electronic health records accurately predict renal replacement therapy in acute kidney injury.

BACKGROUND: Electronic health records (EHR) detect the onset of acute kidney injury (AKI) in hospitalized patients, and may identify those at highest risk of mortality and renal replacement therapy (RRT), for earlier targeted intervention. METHODS: Prospective observational study to derive prediction models for hospital mortality and RRT, in inpatients aged ≥18 years with AKI detected by EHR over 1 year in a tertiary institution, fulfilling modified KDIGO criterion based on serial serum creatinine (sCr) measures. RESULTS: We studied 3333 patients with AKI, of 77,873 unique patient admissions, giving an AKI incidence of 4%. KDIGO AKI stages at detection were 1(74%), 2(15%), 3(10%); corresponding peak AKI staging in hospital were 61, 20, 19%. 392 patients (12%) died, and 174 (5%) received RRT. Multivariate logistic regression identified AKI onset in ICU, haematological malignancy, higher delta sCr (sCr rise from AKI detection till peak), higher serum potassium and baseline eGFR, as independent predictors of both mortality and RRT. Additionally, older age, higher serum urea, pneumonia and intraabdominal infections, acute cardiac diseases, solid organ malignancy, cerebrovascular disease, current need for RRT and admission under a medical specialty predicted mortality. The AUROC for RRT prediction was 0.94, averaging 0.93 after 10-fold cross-validation. Corresponding AUROC for mortality prediction was 0.9 and 0.9 after validation. Decision tree analysis for RRT prediction achieved a balanced accuracy of 70.4%, and identified delta-sCr ≥ 148 µmol/L as the key factor that predicted RRT. CONCLUSION: Case fatality was high with significant renal deterioration following hospital-wide AKI. EHR clinical model was highly accurate for both RRT prediction and for mortality; allowing excellent risk-stratification with potential for real-time deployment.

Curcumin Combination Chemotherapy: The Implication and Efficacy in Cancer.

Many chemotherapeutic drugs have been used for the treatment of cancer, for instance, doxorubicin, irinotecan, 5-fluorouracil, cisplatin, and paclitaxel. However, the effectiveness of chemotherapy is limited in cancer therapy due to drug resistance, therapeutic selectivity, and undesirable side effects. The combination of therapies with natural compounds is likely to increase the effectiveness of drug treatment as well as reduce the adverse outcomes. Curcumin, a polyphenolic isolated from Curcuma longa, belongs to the rhizome of Zingiberaceae plants. Studies from in vitro and in vivo revealed that curcumin exerts many pharmacological activities with less toxic effects. The biological mechanisms underlying the anticancer activity of co-treatment curcumin and chemotherapy are complex and worth to discuss further. Therefore, this review aimed to address the molecular mechanisms of combined curcumin and chemotherapy in the treatment of cancer. The anticancer activity of combined nanoformulation of curcumin and chemotherapy was also discussed in this study. Taken together, a better understanding of the implication and underlying mechanisms of action of combined curcumin and chemotherapy may provide a useful approach to combat cancer diseases.

Carotenoids: How Effective Are They to Prevent Age-Related Diseases?

Despite an increase in life expectancy that indicates positive human development, a new challenge is arising. Aging is positively associated with biological and cognitive degeneration, for instance cognitive decline, psychological impairment, and physical frailty. The elderly population is prone to oxidative stress due to the inefficiency of their endogenous antioxidant systems. As many studies showed an inverse relationship between carotenoids and age-related diseases (ARD) by reducing oxidative stress through interrupting the propagation of free radicals, carotenoid has been foreseen as a potential intervention for age-associated pathologies. Therefore, the role of carotenoids that counteract oxidative stress and promote healthy aging is worthy of further discussion. In this review, we discussed the underlying mechanisms of carotenoids involved in the prevention of ARD. Collectively, understanding the role of carotenoids in ARD would provide insights into a potential intervention that may affect the aging process, and subsequently promote healthy longevity.

Vitamin D and assisted reproductive treatment outcome: a systematic review and meta-analysis.

STUDY QUESTION: Is serum vitamin D associated with live birth rates in women undergoing ART? SUMMARY ANSWER: Women undergoing ART who are replete in vitamin D have a higher live birth rate than women who are vitamin D deficient or insufficient. WHAT IS KNOWN ALREADY: Vitamin D deficiency has been associated with an increased risk of abnormal pregnancy implantation as well as obstetric complications such as pre-eclampsia and fetal growth restriction. However, the effect of vitamin D on conception and early pregnancy outcomes in couples undergoing ART is poorly understood. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis of 11 published cohort studies (including 2700 women) investigating the association between vitamin D and ART outcomes. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Literature searches were conducted to retrieve studies which reported on the association between vitamin D and ART outcomes. Databases searched included MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL. Eleven studies matched the inclusion criteria. MAIN RESULTS AND THE ROLE OF CHANCE: Live birth was reported in seven of the included studies (including 2026 patients). Live birth was found to be more likely in women replete in vitamin D when compared to women with deficient or insufficient vitamin D status (OR 1.33 [1.08-1.65]). Five studies (including 1700 patients) found that women replete in vitamin D were more likely to achieve a positive pregnancy test than women deficient or insufficient in vitamin D (OR 1.34 ([1.04-1.73]). All 11 of the included studies (including 2700 patients) reported clinical pregnancy as an outcome. Clinical pregnancy was found to be more likely in women replete in vitamin D (OR 1.46 [1.05-2.02]). Six studies (including 1635 patients) reported miscarriage by vitamin D concentrations. There was no association found between miscarriage and vitamin D concentrations (OR 1.12 [0.81-1.54]. The included studies scored well on the Newcastle-Ottawa quality assessment scale. LIMITATIONS REASONS FOR CAUTION: Although strict inclusion criteria were used in the conduct of the systematic review, the included studies are heterogeneous in population characteristics and fertility treatment protocols. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this systematic review show that there is an association between vitamin D status and reproductive treatment outcomes achieved in women undergoing ART. Our results show that vitamin D deficiency and insufficiency could be important conditions to treat in women considering ARTs. A randomized controlled trial to investigate the benefits of vitamin D deficiency treatment should be considered to test this hypothesis. STUDY FUNDING/COMPETING INTERESTS: No external funding was either sought or obtained for this study. The authors have no competing interests to declare. REGISTRATION NUMBER: N/A.

Functional cardiac orexin receptors: role of orexin-B/orexin 2 receptor in myocardial protection.

Orexins/hypocretins exert cardiovascular effects which are centrally mediated. In the present study, we tested whether orexins and their receptors may also act in an autocrine/paracrine manner in the heart exerting direct effects. Quantitative reverse transcription-PCR (RT-PCR), immunohistochemical and Western blot analyses revealed that the rat heart expresses orexins and orexin receptors (OXR). In isolated rat cardiomyocytes, only orexin-B (OR-B) caused an increase in contractile shortening, independent of diastolic or systolic calcium levels. A specific orexin receptor-2 (OX2R) agonist ([Ala11, d-Leu15]-Orexin B) exerted similar effects as OR-B, whereas a specific orexin receptor-1 (OX1R) antagonist (SB-408124) did not alter the responsiveness of OR-B. Treatment of the same model with OR-B resulted in a dose-dependent increase in myosin light chain and troponin-I (TnI) phosphorylation. Following ischaemia/reperfusion in the isolated Langendorff perfused rat heart model, OR-B, but not OR-A, exerts a cardioprotective effect; mirrored in an in vivo model as well. Unlike OR-A, OR-B was also able to induce extracellular signal-regulated kinase (ERK) 1/2 (ERK1/2) and Akt phosphorylation in rat myocardial tissue and ERK1/2 phosphorylation in human heart samples. These findings were further corroborated in an in vivo rat model. In human subjects with heart failure, there is a significant negative correlation between the expression of OX2R and the severity of the disease clinical symptoms, as assessed by the New York Heart Association (NYHA) functional classification. Collectively, we provide evidence of a distinct orexin system in the heart that exerts a cardioprotective role via an OR-B/OX2R pathway.

Effects of osmotic dehydration treatment on volatile compound (Myristicin) content and antioxidants property of nutmeg (Myristica fragrans) pericarp.

The effects of osmotic dehydration (OD) treatment on volatile compound (myristicin) content and the antioxidant capacity of nutmeg (Myristica fragrans) were studied. Fresh nutmeg pericarps were treated with varying sugar concentrations (60, 70, 80%) with different soaking periods at ambient temperature. The OD-treated nutmeg extracts were analyzed for myristicin content via Gas Chromatography Flame Ionization Detector. The phenolic content and antioxidant capacity were analyzed using Follin-Ciocalteu and a free radical scavenging activity assay. The myristicin content was highest (1.69 mg/100 mg) at 80% sugar concentration after 3 h of soaking. Total phenolic content and free radical scavenging activity were highest at 3 h of 80% sugar solution treatment with values of 76.90% and 1.75 mg GAE/g, respectively. OD treatment at varying sugar concentration levels and durations affects the production of myristicin and antioxidant composition. Treatment of nutmeg with OD at 80% sugar concentration for 3 h is preferable, resulting in an acceptable level of myristicin and high antioxidants.

Adverse events in women and children who have received intrapartum antibiotic prophylaxis treatment: a systematic review.

BACKGROUND: Adverse events from intrapartum antibiotic prophylaxis (IAP) are poorly documented yet essential to inform clinical practice for neonatal group B Streptococcus (GBS) disease prevention. In this systematic review, we appraised and synthesised the evidence on the adverse events of IAP in the mother and/or her child. METHODS: We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane, and Science Citation Index from date of inception until October 16th 2016. Reference lists of included studies and relevant systematic reviews were hand-searched. We included primary studies in English that reported any adverse events from intrapartum antibiotics for any prophylactic purpose compared to controls. The search was not restricted to prophylaxis for GBS but excluded women with symptoms of infection or undergoing caesarean section. Two reviewers assessed the methodological quality of studies, using the Cochrane Risk of Bias tool, and the Risk of Bias Assessment Tool for Nonrandomised Studies. Results were synthesised narratively and displayed in text and tables. RESULTS: From 2364 unique records, 30 studies were included. Despite a wide range of adverse events reported in 17 observational studies and 13 randomised controlled trials (RCTs), the evidence was inconsistent and at high risk of bias. Only one RCT investigated the long-term effects of IAP reporting potentially serious outcomes such as cerebral palsy; however, it had limited applicability and unclear biological plausibility. Seven observational studies showed that IAP for maternal GBS colonisation alters the infant microbiome. However, study populations were not followed through to clinical outcomes, therefore clinical significance is unknown. There was also observational evidence for increased antimicrobial resistance, however studies were at high or unclear risk of bias. CONCLUSIONS: The evidence base to determine the frequency of adverse events from intrapartum antibiotic prophylaxis for neonatal GBS disease prevention is limited. As RCTs may not be possible, large, better quality, and longitudinal observational studies across countries with widespread IAP could fill this gap. TRIAL REGISTRATION: CRD42016037195 .

Management of rheumatoid arthritis in clinical practice using treat-to-target strategy: Where do we stand in the multi-ethnic Malaysia population?

To evaluate the achievement of treat-to-target (T2T) strategy in rheumatoid arthritis (RA) and identify factors associated with failed treatment target in a public rheumatology center. A cross-sectional study was conducted from June 2015 to February 2016. RA patients with disease duration greater than 2 years and under T2T for over a year were invited to the study. Demographic, clinical data, disease activity score of 28 joints (DAS28), and clinical disease activity index (CDAI) were collected in a single routine clinic visit. Treatment target was defined as DAS28 <3.2 or CDAI ≤10. Retrospective chart review was performed to determine reasons of failed treatment target. A total of 371 patients were recruited and 87.1% were female. Mean age and duration of RA were 53.5 years (SD 10.3) and 9.1 years (SD 6.6), respectively. Ethnic distribution was 49% Chinese, 27% Malay, and 24% Indian. T2T was achieved in 81.7% of the cohort. Non-Chinese ethnicity, positive rheumatoid factor, and treatment with three disease modifying anti-rheumatic drugs (DMARDs) were associated with failed treatment target. After controlling for covariates, Malay ethnicity (OR 2.96; 95% CI 1.47-5.96) and treatment with three DMARDs (OR 2.14; 95% CI 1.06-4.35) were associated with failed treatment target. There was no association between age, gender, duration of RA, BMI, smoking status, anti-citrulinated cyclic peptide, and achievement of T2T. The most common reasons of failed treatment target were inability to escalate DMARDs due to side effects (18.8%), lack of biologics fund (15.6%), and persistent disease despite optimum treatment (14.1%). T2T was successfully implemented. Malay patients need aggressive treatment adaptation to achieve optimal outcome.

Real-world clinical experience of biological disease modifying anti-rheumatic drugs in Malaysia rheumatoid arthritis patients.

The effect of biologic disease modifying anti-rheumatic drugs (bDMARDs) in treating rheumatoid arthritis (RA) in real-world clinical practice remains unknown in Southeast Asia. We aimed to assess the efficacy and safety of bDMARDs among Malaysian RA patients treated in routine clinical practice. A retrospective medical chart review of RA patients from 11 government hospitals were conducted from January 2003 to January 2014. A standardized questionnaire was used to abstract patient's demographic, clinical and treatment data. Level of disease activity was measured by DAS28 collected at baseline, 3, 6 and 12 months. Three hundred and one patients were available for analysis, mean age 41 (SD, 10.8) years, mean RA duration 12.3 (SD, 6.9) years and 98% had history of two or more conventional-synthetic DMARDs. There were 467 bDMARD courses prescribed with mean bDMARDs duration use of 12.9 months (SD 14.7). Tumour necrosis factor alpha inhibitors were the most common prescribed bDMARDs (77.1%), followed by Tocilizumab (14.6%) and Rituximab (8.4%). We observed significant improvement in mean DAS28 values from baseline to 3, 6 and 12 months (p < 0.001). Overall, 16.9% achieved DAS28 remission at 6 months. A third (35.6%) of patients reported adverse events, three commonest being infections (46.5%), allergy (22.9%) and laboratory abnormalities (12.9%). 3.7% of our patients had tuberculosis. Biologic DMARDs were effective in treating RA in real-world practice in Malaysia, despite a lower remission rate compared to developed countries. Except for higher rates of tuberculosis, the AEs were similar to the published reports.