Systematic review of immunosuppressant guidelines in the COVID-19 pandemic.

AIMS: Individuals taking immunosuppressants are at increased susceptibility to viral infections in general. However, due to the novel nature of the COVID-19, there is a lack of evidence about the specific risks of the disease in this patient group. This systematic review aims to summarize the current international clinical guidelines to highlight areas where research is needed through critical appraisal of the evidence base of these guidelines. METHODS: We conducted a systematic review of clinical practice guidelines about the usage of immunosuppressants during the COVID-19 pandemic. Electronic databases including MEDLINE and the websites of relevant professional bodies were searched for English language guidelines that were published or updated between March 2020 and May 2020 in this area. We assessed the quality and consistency of guidelines. The evidence base underpinning these guidelines was critically appraised using GRADE criteria. RESULTS: Twenty-three guidelines were included. Most guidelines (n = 15, 65.2%) informed and updated evidence based on expert opinion. The methodological quality of the guidelines varied, ranging from 'very low' to 'moderate'. Guidelines consistently recommended that high-risk patients, including those who are taking high doses of steroids for more than a month, or a combination of two or more immunosuppressants, should be shielding during the outbreak. Most guidelines stated that steroids usage should not be stopped abruptly and advised on individualized risk-benefit analysis considering the risk of the effect of COVID-19 infection and the relapse of the autoimmune condition in patients. DISCUSSION: Clinical practice guidelines on taking immunosuppressants during the COVID-19 outbreak vary in quality. The level of evidence informing the available guidelines was generally low. Given the novel nature of COVID-19, the guidelines draw on existing knowledge and data, refer to the use of immunosuppressants and risks of serious infections of other aetiologies and have extrapolated these to form their evidence base.

An overview of prevalence, determinants and health outcomes of polypharmacy.

A high rate of polypharmacy is, in part, a consequence of the increasing proportion of multimorbidity in the ageing population worldwide. Our understanding of the potential harm of taking multiple medications in an older, multi-morbid population, who are likely to be on a polypharmacy regime, is limited. This is a narrative literature review that aims to appraise and summarise recent studies published about polypharmacy. We searched MEDLINE using the search terms polypharmacy (and its variations, e.g. multiple prescriptions, inappropriate drug use, etc.) in titles. Systematic reviews and original studies in English published between 2003 and 2018 were included. In this review, we provide current definitions of polypharmacy. We identify the determinants and prevalence of polypharmacy reported in different studies. Finally, we summarise some of the findings regarding the association between polypharmacy and health outcomes in older adults, with a focus on frailty, hospitalisation and mortality. Polypharmacy was most often defined in terms of the number of medications that are being taken by an individual at any given time. Our review showed that the prevalence of polypharmacy varied between 10% to as high as around 90% in different populations. Chronic conditions, demographics, socioeconomics and self-assessed health factors were independent predictors of polypharmacy. Polypharmacy was reported to be associated with various adverse outcomes after adjusting for health conditions. Optimising care for polypharmacy with valid, reliable measures, relevant to all patients, will improve the health outcomes of older adult population.

Aspirin moderates the association between cardiovascular risk, brain white matter hyperintensity total lesion volume and processing speed in normal ageing.

OBJECTIVES: Cardiovascular risk is associated with cognitive decline and this effect is attributed to brain pathology, including white matter hyperintensity (WMH) burden. Low-dose aspirin is frequently recommended for reducing vascular events. We investigated the effect of taking aspirin on the association between cardiovascular risk, WMH burden and cognitive function. STUDY DESIGN: The study sample was drawn from 318 dementia-free adults aged 67-71 years. Brain magnetic resonance imaging (MRI) scans were acquired from 239 participants. MAIN OUTCOME MEASURES: WMH total lesion volumes (TLV) were extracted using the automated lesion segmentation algorithm. We measured cardiovascular risk by calculating ASSIGN score. Cognitive ability was measured using a test of processing speed. We developed structural equation models to test our hypothesis. RESULTS: Sixty-eight participants (47.1 % male, mean age = 68.8 years) reported that they took aspirin. The demographic measures did not differ significantly by aspirin use. Among aspirin users, there was a strong negative association between WMH TLV and cognition (ß = -0.43, p-value < 0.001), while in non-users of aspirin the only significant predictor of poorer cognition was cardiovascular risk (ß = -0.17, p-value = 0.001). CONCLUSIONS: Aspirin use moderates the negative effect of WMH burden on cognition. Considering WMH burden in addition to cardiovascular risk could improve the prediction of cognitive decline in older adults with aspirin use.

The association between polypharmacy and late life deficits in cognitive, physical and emotional capability: a cohort study.

Background Polypharmacy is a growing health concern for older adults and is associated with poorer clinical outcome. Objective This study aim is to investigate the association between polypharmacy and impairment in cognitive, physical and emotional capability controlling for the confounding effect of co-morbidities. Setting The Aberdeen 1936 Birth Cohort from 1999 to 2004. Method Recruited were 498 dementia free participants around 64 years old and recruited into wave one. Linear regression and structural equation models were used. Models were adjusted for the effect of age, gender, childhood IQ, education and Body Mass Index. A triad of impairment was defined as a composite measure of impairment in cognitive, physical and emotional function. Main outcome measure The relationships between polypharmacy, co-morbidity and triad of impairment. Results The prevalence of polypharmacy was 12.3% in this relatively healthy sample. Polypharmacy was significantly associated with increased impairment in cognitive, physical and emotional ability (ß = 3.6, p = 0.003) after controlling for the effect of comorbidities and other confounding variables. As expected, higher childhood IQ and educational achievement had protective effects against impairment while higher comorbidity score and Body Mass Index were associated with increased impairment in this population. Conclusions The independent association of polypharmacy and reduced cognitive, physical and emotional capability makes this a promising target for predicting and potentially reducing the risk of impairment and associated healthcare costs in older adults. Longitudinal studies are required to investigate the underlying mechanisms for the observed relationships further.

An Interprofessional Collaboration between Medicine and Pharmacy Schools: Designing and Evaluating a Teaching Program on Practical Prescribing.

OBJECTIVE: Medical students need proper education in drug prescription. The aim of the present study is to introduce a course that improves the students' prescribing skills and also promotes an interprofessional collaboration between medicine and pharmacy schools. METHODS: This study was done in a skill laboratory at the pharmacotherapy department of Tehran University of Medical Sciences, Tehran, Iran. The course was an 18-h interactive workshop in 3 days under the supervision of clinical pharmacists. A total of 18 medical students participated in these classes before their internship. Before and after each class, they were given tests and paired t-test was done to compare the marks. FINDINGS: A total of 18 medical students participated in this study. The results showed that the knowledge of the students on pharmacotherapy, drug information, and prescribing skills has been significantly improved at the end of the course. CONCLUSION: Using clinical pharmacists to the present pharmacotherapy course could be an effective model for medical students to obtain better prescribing skills.

A Review of Frailty Syndrome and Its Physical, Cognitive and Emotional Domains in the Elderly.

BACKGROUND: Frailty, a very important complication of increasing age, is a well-recognised concept although it has not been accurately measured in the clinical setting. The aim of this literature review is to summarise commonly used frailty screening tools, and to describe how new measurement methods have been developed recently. METHODS: Several frailty measurement tools including the most cited and newly developed scales have been described in this review. We searched the MEDLINE using the search terms; "frailty score, scale, tool, instrument, index, phenotype" and then summarised selected tools for physical, cognitive, emotional and co-morbidity domains. RESULTS: The most cited frailty measurement methods developed from 1999 to 2005 are primarily criteria for physical frailty (e.g., frailty phenotype). More recently developed tools (e.g., triad of impairment and multidimensional frailty score) consider cognitive and emotional domains in addition to physical deficit in measuring frailty. Co-morbidity has also been considered as a domain of frailty in several measurement tools. CONCLUSION: Although frailty tools have traditionally assessed physical capability, cognitive and emotional impairment often co-exist in older adults and may have shared origins. Therefore, newer tools which provide a composite measure of frailty may be more relevant for future use.

Effects of cyclosporine A on the hepatobiliary disposition and hepatic uptake of etoposide in an isolated perfused rat liver model.

PURPOSE: A recirculating isolated perfused rat liver model was used to investigate the hepatobiliary disposition of etoposide and the effects of cyclosporine A (CyA) on the pattern of drug disposition in the bile and uptake in the liver. METHODS: The portal vein, bile duct, and superior vena cava were cannulated in four groups of rats. The perfusions were conducted in the control group, which only received 10 µg/ml etoposide, and the tested groups which received etoposide and CyA in 0.4, 2, and 10 mg/kg doses. Perfusate and bile samples were collected up to 180 min. RESULTS: The determination of etoposide in the samples and homogenized liver by the high-performance liquid chromatography method showed that the administration of CyA led to significant changes in the hepatic excretion (E h), hepatic clearance (CL h), and half-life (T 1/2) of etoposide in the CyA 2 and 10 mg/kg treatment groups but not in 0.4 mg/kg group. The volume of the bile decreased to 64 and 45 % and biliary clearance (CL b) of etoposide reduced by 73 and 82 % in 0.4 and 2 mg/kg CyA group, respectively, when compared with the control group. CONCLUSIONS: These results demonstrated the dose-dependant non-specific inhibitory effects of CyA on p-glycoproteins, multidrug resistance protein 2, bile salt export pump, and organic anion-transporting polypeptide, the drug transporters responsible for etoposide hepatobiliary disposition, hepatic uptake, and bile formation in rat.

Additive anticonvulsant effects of agmatine and lithium chloride on pentylenetetrazole-induced clonic seizure in mice: involvement of α2-adrenoceptor.

After 60 years, lithium is still the mainstay in the treatment of mood disorders and widely used in clinic. In addition to its mood stabilizer effects, lithium also shows some anticonvulsant properties. Similar to lithium, agmatine also plays a protective role in the CNS against seizures and has been reported to enhance the effect of different antiepileptic agents. Moreover, both agmatine and lithium have modulatory effects on α(2)-adrenoceptors. So, we designed this study: 1) to investigate whether agmatine and lithium show an additive effect against clonic seizures induced by pentylenetetrazole; 2) to assess whether this additive effect is mediated through the α(2)-adrenoceptor or not. In our study, acute administration of a single effective dose of lithium chloride (30 mg/kg, i.p.) increased the seizure threshold. Pre-treatment with low and, per se, non-effective doses of agmatine (1 and 3mg/kg) potentiated a sub-effective dose of lithium (10mg/kg). Interestingly, the anticonvulsant effects of these effective combinations of lithium and agmatine were prevented by pre-treatment with low and non-effective doses of yohimbine [α(2)-adrenoceptor antagonist] (0.1 and 0.5mg/kg). On the other hand, clonidine [α(2)-adrenoceptor agonist] augmented the anticonvulsant effect of a sub-effective combination of lithium (5mg/kg i.p.) and agmatine (1mg/kg) at relatively low doses (0.1 and 0.25mg/kg). In summary, our findings demonstrate that agmatine and lithium chloride exhibit additive anticonvulsant properties which seem to be mediated through α(2)-adrenoceptor.