Self-Care and Self-Management Among Adolescent T2DM Patients: A Review

Uncontrolled hyperglycaemia can lead to macro- and microvascular complications. Adolescents with T2DM develop similar complications as in adults, including cardiovascular disease, stroke, myocardial infarction, renal insufficiency, and chronic renal failure. Although regular medical follow-up is essential to avoid long-term complications, patients with diabetes mellitus need to perform holistic self-care activities such as opting for a healthy diet, physical activity, self-monitoring, and proper medication. To the best of our knowledge, only a limited number of studies have focused on self-care activities and self-management, including self-care practices, supportive networks, and self-care education programs in adolescent with T2DM. Some of the studies focused on the appreciation of self-care in adolescents with T2DM. This review aimed to analyse self-care and self-management among adolescents with T2DM, and discuss the impact of self-care and self-management on glycaemic control. The difficulties faced by adolescents in self-managing their disease are also highlighted. Such information is essential for healthcare providers in promoting self-care practices among adolescents with T2DM. A thorough search of the literature was performed using three databases: Medline, Google Scholar, and Scopus. The articles focused on self-care and self-management of adolescents patients with T2DM aged between 12 and 19 years old were included. Findings from this review reveal that healthy food adaptation, adequate physical activity, proper medication practices, and regular glucose monitoring are the most common self-care practices. Parental involvement and clinician encouragement also contribute toward the practice of self-care and self-management among the adolescents with T2DM. In conclusion, independent self-management regimens and supportive networks for appropriate administration are vital factors to enhance clinical outcomes of adolescents with T2DM

Safety and Effectiveness of Bivalirudin in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

Recent clinical trials have shown that while bivalirudin exhibits similar efficacy with heparin, it offers several advantages over heparin, such as a better safety profile. We aimed to evaluate the efficacy and safety of bivalirudin use during Percutaneous Coronary Intervention (PCI) in the treatment of angina and acute coronary syndrome (ACS). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, EMBASE, and Science Direct from January 1980 to January 2016. Randomized controlled trials (RCTs) comparing bivalirudin to heparin during the course of PCI in patients with angina or ACS were included. Outcome measures included all-cause mortality, myocardial infarction, revascularisation, stent thrombosis, stroke, and major bleeding. The selection, quality assessment, and data extraction of the included trials were done independently by four authors, and disagreements were resolved by consensus. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated. A total of 12 RCTs involving 44,088 subjects were included. Bivalirudin appeared to be non-superior compared to heparin in reducing all-cause mortality, myocardial infarction, revascularisation, and stroke. Bivalirudin appeared to be related to a higher risk of stent thrombosis when compared to heparin plus provisional use of a glycoprotein IIb/IIIa inhibitor (GPI) at day 30 (RR 1.94 [1.16, 3.24] p < 0.01). Overall, bivalirudin-based regimens present a lesser risk of major bleeding (RR 0.56 [0.44–0.71] p < 0.001), and Thrombolysis In Myocardial Infarction (TIMI) major bleeding (RR 0.56 [0.43–0.73]) compared with heparin-based regimens either with provisional or routine use of a GPI. However, the magnitude of TIMI major bleeding effect varied greatly (p < 0.001), depending on whether a GPI was provisionally used (RR 0.42 [0.34–0.52] p < 0.001) or routinely used (RR 0.60 [0.43 –0.83] p < 0.001), in the heparin arm. This meta-analysis demonstrated that bivalirudin is associated with a lower risk of major bleeding, but a higher risk of stent thrombosis compared to heparin

Genetic diversity of circumsporozoite protein in Plasmodium knowlesi isolates from Malaysian Borneo and Peninsular Malaysia

Understanding the genetic diversity of candidate genes for malaria vaccines such as circumsporozoite protein (csp) may enhance the development of vaccines for treating Plasmodium knowlesi. Hence, the aim of this study is to investigate the genetic diversity of non-repeat regions of csp in P. knowlesi from Malaysian Borneo and Peninsular Malaysia. A total of 46 csp genes were subjected to polymerase chain reaction amplification. The genes were obtained from P. knowlesi isolates collected from different divisions of Sabah, Malaysian Borneo, and Peninsular Malaysia. The targeted gene fragments were cloned into a commercial vector and sequenced, and a phylogenetic tree was constructed while incorporating 168 csp sequences retrieved from the GenBank database. The genetic diversity and natural evolution of the csp sequences were analysed using MEGA6 and DnaSP ver. 5.10.01. A genealogical network of the csp haplotypes was generated using NETWORK ver. 4.6.1.3. The phylogenetic analysis revealed indistinguishable clusters of P. knowlesi isolates across different geographic regions, including Malaysian Borneo and Peninsular Malaysia. Nucleotide analysis showed that the csp nonrepeat regions of zoonotic P. knowlesi isolates obtained in this study underwent purifying selection with population expansion, which was supported by extensive haplotype sharing observed between humans and macaques. Novel variations were observed in the C-terminal non-repeat region of csp. The csp non-repeat regions are relatively conserved and there is no distinct cluster of P. knowlesi isolates from Malaysian Borneo and Peninsular Malaysia. Distinctive variation data obtained in the C-terminal non-repeat region of csp could be beneficial for the design and development of vaccines to treat P. knowlesi

Optimising the use of high-cost antifungal agents in clinical practice

Fungal infections are often associated with prolonged hospital stay and high mortality, and are costly to the healthcare system. The incidence of fungal infections has increased in tandem with the growing number of immunocompromised patients in recent years, underlining the need for novel antifungal agents. The 2000s were the most prolific decade for the development of antifungal drugs, with the introduction of newer triazoles (voriconazole, posaconazole) and echinocandins (caspofungin, micafungin, anidulafungin), providing a wider choice of treatment options. These newer antifungal agents, however, are much more expensive, and thus, significantly increase hospital drug expenditure. Relative health returns of these high-cost alternatives need to be determined given that healthcare services have limited resources. Accordingly, this thesis was geared towards deriving critical information to facilitate decision making by the healthcare providers in optimising the use of these high-cost antifungal agents for the prophylaxis and treatment of fungal infections. Three main areas were explored: voriconazole prophylaxis in lung transplant (LTx) recipients, cost-effective use of echinocandins in treating candidaemia and invasive candidiasis (IC) and the potential use of caspofungin eye drops for the treatment of fungal keratitis. Within the context of antifungal prophylaxis in lung transplantation, there is no consensus with respect to the choice of agent and strategy due to the paucity of data. An anonymous web-based survey was conducted to determine antifungal prophylactic practice in LTx centres world-wide. Findings from the survey indicated that voriconazole was the most commonly used agent for both universal and pre-emptive prophylaxis within the first six months post-LTx. A retrospective, single-centre, observational study was then undertaken to investigate the efficacy and safety of voriconazole pre-emptive prophylaxis in 62 LTx recipients. Six months after initiation of voriconazole prophylaxis, the majority (75.8%) had successful eradication of fungal colonisation; one patient developed proven fungal infection. Sixteen (25.8%) had died by 12 months after commencing prophylaxis, half due to Bronchiolitis Obliterans Syndrome. Chronic rejection within the 30 days prior to voriconazole prophylaxis was significantly associated with mortality at the 6-month and 12-month end-points. Ten patients (16.1%) had drug-related hepatotoxicity. The second focus was to determine the cost-effectiveness of echinocandins compared to other antifungal agents in treating candidaemia and IC. Accordingly, pharmacoeconomic comparisons between echinocandins (caspofungin, micafungin, anidulafungin), liposomal amphotericin B (LAmB) and fluconazole in the Australian setting were conducted. The comparisons employed decision analytical models based on treatment pathways derived from published randomised clinical trials, and utilised expert panels from Australia. Analyses were from a hospital perspective and cost inputs were obtained from the latest Australian resources. The robustness of the economic models was evaluated by sensitivity analyses. Hospitalisation was revealed as the major cost driver. Anidulafungin was a cost-effective option compared to fluconazole, with an incremental cost-effectiveness ratio of AU$22,003 per life-year saved. Micafungin was expected to have a total net cost-saving of AU$10,957 per patient over LAmB, whereas it was cost-equivalent to caspofungin, with variation in drug acquisition cost likely to be a critical factor. The final aim was to investigate the potential use of caspofungin eye drops as a novel strategy to treat fungal keratitis, with the intention of improving clinical outcomes and saving costs. The successful use of intrastromal and topical caspofungin 0.5% in combination with voriconazole in a case of refractory atypical Alternaria keratitis in a local institution was reported. The utility of caspofungin eye drops in fungal keratitis, however, remains limited, partly due to the lack of data on penetration into the human eye. A liquid chromatography/mass spectrometry assay was then developed and validated to determine the concentrations of caspofungin in human aqueous humour. An open-label study demonstrated that caspofungin 0.5% eye drops resulted in low penetration into the human eye in the absence of inflammation or corneal abrasion, but were generally well tolerated. The eye drops were shown to be stable for at least 28 days at 4 ± 1ºC, affording economical use in clinical practice. This thesis has explored a number of important aspects related to the optimal and cost-efficient use of high-cost antifungal agents. Significantly, the data will facilitate informed decision making by clinical practitioners and healthcare policy makers about the use of these high-cost antifungal agents

Optimising the use of high-cost antifungal agents in clinical practice

Fungal infections are often associated with prolonged hospital stay and high mortality, and are costly to the healthcare system. The incidence of fungal infections has increased in tandem with the growing number of immunocompromised patients in recent years, underlining the need for novel antifungal agents. The 2000s were the most prolific decade for the development of antifungal drugs, with the introduction of newer triazoles (voriconazole, posaconazole) and echinocandins (caspofungin, micafungin, anidulafungin), providing a wider choice of treatment options. These newer antifungal agents, however, are much more expensive, and thus, significantly increase hospital drug expenditure. Relative health returns of these high-cost alternatives need to be determined given that healthcare services have limited resources. Accordingly, this thesis was geared towards deriving critical information to facilitate decision making by the healthcare providers in optimising the use of these high-cost antifungal agents for the prophylaxis and treatment of fungal infections. Three main areas were explored: voriconazole prophylaxis in lung transplant (LTx) recipients, cost-effective use of echinocandins in treating candidaemia and invasive candidiasis (IC) and the potential use of caspofungin eye drops for the treatment of fungal keratitis. Within the context of antifungal prophylaxis in lung transplantation, there is no consensus with respect to the choice of agent and strategy due to the paucity of data. An anonymous web-based survey was conducted to determine antifungal prophylactic practice in LTx centres world-wide. Findings from the survey indicated that voriconazole was the most commonly used agent for both universal and pre-emptive prophylaxis within the first six months post-LTx. A retrospective, single-centre, observational study was then undertaken to investigate the efficacy and safety of voriconazole pre-emptive prophylaxis in 62 LTx recipients. Six months after initiation of voriconazole prophylaxis, the majority (75.8%) had successful eradication of fungal colonisation; one patient developed proven fungal infection. Sixteen (25.8%) had died by 12 months after commencing prophylaxis, half due to Bronchiolitis Obliterans Syndrome. Chronic rejection within the 30 days prior to voriconazole prophylaxis was significantly associated with mortality at the 6-month and 12-month end-points. Ten patients (16.1%) had drug-related hepatotoxicity. The second focus was to determine the cost-effectiveness of echinocandins compared to other antifungal agents in treating candidaemia and IC. Accordingly, pharmacoeconomic comparisons between echinocandins (caspofungin, micafungin, anidulafungin), liposomal amphotericin B (LAmB) and fluconazole in the Australian setting were conducted. The comparisons employed decision analytical models based on treatment pathways derived from published randomised clinical trials, and utilised expert panels from Australia. Analyses were from a hospital perspective and cost inputs were obtained from the latest Australian resources. The robustness of the economic models was evaluated by sensitivity analyses. Hospitalisation was revealed as the major cost driver. Anidulafungin was a cost-effective option compared to fluconazole, with an incremental cost-effectiveness ratio of AU$22,003 per life-year saved. Micafungin was expected to have a total net cost-saving of AU$10,957 per patient over LAmB, whereas it was cost-equivalent to caspofungin, with variation in drug acquisition cost likely to be a critical factor. The final aim was to investigate the potential use of caspofungin eye drops as a novel strategy to treat fungal keratitis, with the intention of improving clinical outcomes and saving costs. The successful use of intrastromal and topical caspofungin 0.5% in combination with voriconazole in a case of refractory atypical Alternaria keratitis in a local institution was reported. The utility of caspofungin eye drops in fungal keratitis, however, remains limited, partly due to the lack of data on penetration into the human eye. A liquid chromatography/mass spectrometry assay was then developed and validated to determine the concentrations of caspofungin in human aqueous humour. An open-label study demonstrated that caspofungin 0.5% eye drops resulted in low penetration into the human eye in the absence of inflammation or corneal abrasion, but were generally well tolerated. The eye drops were shown to be stable for at least 28 days at 4 ± 1ºC, affording economical use in clinical practice. This thesis has explored a number of important aspects related to the optimal and cost-efficient use of high-cost antifungal agents. Significantly, the data will facilitate informed decision making by clinical practitioners and healthcare policy makers about the use of these high-cost antifungal agents

Clinical utility of voriconazole eye drops in ophthalmic fungal keratitis

Daoud Al-Badriyeh, Chin Fen Neoh, Kay Stewart, David CM KongCentre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Victoria, AustraliaAbstract: Fungal keratitis is one of the major causes of ophthalmic mycosis and is difficult to treat. The range of common antifungal agents available for fungal keratitis remains inadequate and is generally associated with poor clinical outcomes. Voriconazole is a new generation triazole antifungal agent. Only marketed in systemic formulation and, with broad-spectrum activity and high intraocular penetration, voriconazole has demonstrated effectiveness against fungal keratitis. Systemic voriconazole, however, is not without side effects and is costly. Voriconazole eye drops have been prepared extemporaneously and used for the treatment of ophthalmic fungal keratitis. The current article sought to review the literature for evidence related to the effectiveness and safety of topical voriconazole and its corneal penetration into the aqueous humor of the eye. The voriconazole eye drops used are typically of 1% concentration, well tolerated by the eye, and are stable. Despite existing evidence to suggest that the eye drops are effective in the treatment of fungal keratitis, more studies are needed, especially in relation to using the eye drops as first-line and stand-alone treatment, preparation of higher concentrations, and optimal dosing frequency.Keywords: voriconazole, fungal keratitis, eye drops, corneal penetratio

Knowledge on Alzheimer's Disease among Public Hospitals and Health Clinics Pharmacists in the State of Selangor, Malaysia

The prevalence of Alzheimer's disease (AD) has increased with the fast growing of aging population, thereby posing great challenges to provision of care for AD patients. Pharmacists play a vital role in the management of AD; this includes recognizing early symptoms of AD, providing medication counseling to AD patients and their caretakers, and identifying potential adverse drug reactions. A comprehensive understanding of the disease progression, as well as the pharmacological therapy, is essential to provide effective care to AD patients. The level of knowledge about AD among the pharmacists, however, remains unknown. Hence, this study aimed to assess the knowledge on AD among the pharmacists in public hospitals and health clinics and its correlates. A clear picture of the characteristics associated with different levels of knowledge could facilitate the targeted re-training of pharmacists. The 30-item validated Alzheimer disease knowledge scale (ADKS) tool was pilot-tested and used in this cross-sectional study. All pharmacists, from nine public hospitals and seven public health clinics in the State of Selangor, Malaysia, were invited to participate in this cross-sectional survey. The ADKS score was computed and compared across demographics characteristics. A total of 445 pharmacists responded to the survey. These pharmacists had a moderate overall score in ADKS; nevertheless, high scores were recorded in the domains of treatment management and care giving. No difference in AD knowledge was found among pharmacists worked in public hospitals and health clinics, except for the domain of care giving (p = 0.033). Ethnicity and age group were independent predictors of ADKS score in the current study. The pharmacists in the current study had moderate AD knowledge. On-going education and training programme on AD, in particular the domains other than treatment management and care giving, should be provided to the pharmacists to ensure delivery of quality care to AD patients

Effect of Standardized Warfarin Treatment Protocol on Anticoagulant Effect: Comparison of a Warfarin Medication Therapy Adherence Clinic with Usual Medical Care

Objective: To evaluate the impact of pharmacist-led warfarin management and standardized treatment protocol.Methods: A retrospective cohort study was carried out in a cardiology referral hospital located in central Kuala Lumpur, Malaysia, from 2009 to 2014. The inclusion criteria were: adult patients who were diagnosed and treated for atrial fibrillation (AF) with warfarin, attended the warfarin medication therapy adherence clinic (WMTAC) for at least 12 weeks, and with at least four international normalized ratio (INR) readings. The electronic medical records were reviewed for demographics, type of AF, warfarin dose, INRs, adverse events, co-morbidities, and drug–drug interactions. The outcome measures included the mean time to therapeutic INR, the mean percentage of time in therapeutic range (TTR), bleeding events, and common drug interactions.Results: Out of 473 patients, 151 patients fulfilled the inclusion criteria. The findings revealed that there were significant associations between the usual medical care (UMC) group and pharmacist-led WMTAC in terms of TTR (p = 0.01) and INR (p = 0.02) levels. A positive impact of pharmacists’ involvement in the WMTAC clinic was where the “pharmacist’s recommendation accepted” (p = 0.01) and “expanded therapeutic INR range” (p = 0.04) were statistically significantly higher in the WMTAC group.Conclusion: There was a significant positive association between the pharmacist-led WMTAC and anticoagulation effect (therapeutic TTR, INR). The identified findings revealed that expanded role of pharmacist in pharmacist-managed warfarin therapy is beneficial to optimize the warfarin therapy. This study also highlighted the critical roles that pharmacists can actively play to ensure optimal anticoagulation pharmaceutical care.Key messages:What is already known on this subject?• Pharmacist-managed warfarin therapy is beneficial for optimizing warfarin therapy. In such therapy, recommendations such as dose adjustment and safer alternative drugs (given drug–drug interactions and/or food–drug interactions) are made.• The active involvement of pharmacists in warfarin adherence clinics could significantly improve adherence.• However, the warfarin treatment outcomes from UMC, pharmacist-and-physician-led care and pharmacist-led care have not been studied.• The impact of the implementation of the standardized protocol for the warfarin adherence clinic has not been assessed.What this study adds?• INR levels among UMC group and WMTAC group were significantly different.• Though the TTR level for the WMTAC group was not significantly different than the UMC group, it was higher and close to the targeted 60% level.• The identified findings show that pharmacists’ focus on intervention for missed doses, adherence and dose adjustment provide positive impact on patients’ warfarin therapy